Ijcp nov 2015

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Volume 26, Number 6

November 2015, Pages 501–600

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IJCP Group of Publications Dr Sanjiv Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor Dr Deepak Chopra Chief Editorial Advisor

Dr KK Aggarwal Group Editor-in-Chief IJCP Group and eMedinewS Dr Veena Aggarwal MD, Group Executive Editor

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma, Dr Kamala Selvaraj Cardiology Dr Praveen Chandra, Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty ENT Dr Jasveer Singh Dr Chanchal Pal Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dr Rajiv Khosla Dermatology Dr Hasmukh J Shroff Dr Pasricha Dr Koushik Lahiri Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan Dr Vineet Suri Journal of Applied Medicine & Surgery Dr SM Rajendran, Dr Jayakar Thomas Orthopedics Dr J Maheshwari

Anand Gopal Bhatnagar Editorial Anchor Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

This journal is indexed in IndMED (http://indmed.nic.in) and full-text of articles are included in medIND databases (http://mednic.in) hosted by National Informatics Centre, New Delhi.

Volume 26, Number 6, November 2015 FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

506 Child Sexual Abuse: An Epidemic

KK Aggarwal

AMERICAN FAMILY PHYSICIAN

507 Nutrition Myths and Healthy Dietary Advice in Clinical Practice

Lenard I. Lesser, Mary Carol Mazza, Sean C. Lucan

512 Practice Guidelines 514 Photo Quiz CARDIOLOGY

516 Correlation of Retinopathy and TMT Positivity in Patients of Diabetes Mellitus

S Gupta, PK Baghel, H Gupta, S Lakhtakiya, MK Jain, Dharmendra Jain

COMMUNITY MEDICINE

522 A Study of Effect of Oral Iron Therapy on Cognitive Function in Iron-deficient Adolescent Girls

Priyanka Mandve, Vijay M Motghare

DENTISTRY

528 Clinical Efficacy of Bioactive Glass-containing Dentifrice: A 3-month Controlled Study

Meera H Gohil, Sharmila Verma, Geeta Singh Bhaduria

DERMATOLOGY

533 Erythroderma Secondary to Herbal Medicine

KH Basavaraj, Archana Meka

537 Netherton Syndrome: A Report of Two Cases

BK Brar, Neerja Puri, BB Mahajan, Gurmet Sethi

DRUGS

540 Nimesulide-induced Angioedema: A Case Report

Tushar B Nishandar, Anand S Kale, Harshal N Pise, Swapnil P Chube

GASTROENTEROLOGY

543 Revisiting Antacids: Co-therapy with Proton Pump Inhibitors in Gastroesophageal Reflux Disease

Philip Abraham

HEMATOLOGY

548 Thrombocytosis: Reactionary versus Primary?

Nandini Swamy, Chaitra G, Prashanth, Siva Subramaniyam, Vivek Tirlapur

INTERNAL MEDICINE

554 Poncet Disease: A Case Report of Polyarthropathy

Debaprasad Chakrabarti, Abhijit Datta, Amrit Kr Bhattacharyya

NEUROLOGY

Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E - 219, Greater Kailash, Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com

556 Isaacs’ Syndrome (Neuromyotonia): A Case Report

Ibraheem Khan, GN Saxena, Swati Srivastava, Surendra Yadav, Kamlesh Sharma

OBSTETRICS AND GYNECOLOGY

558 A Randomized Comparative Study of Intramuscular Camylofin Dihydrochloride and Intravenous Drotaverine Hydrochloride on Cervical Dilatation in Labor

Printed at New Edge Communications Pvt. Ltd., New Delhi E-mail: edgecommunication@gmail.com

Copyright 2015 IJCP Publications Ltd. All rights reserved.

Rajani Uday, Binu P

564 A Rare Case of Primary Ovarian Ectopic Pregnancy After Interval Tubal Ligation

The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

Tamal Kumar Mandal, Pratima Gorain, Debjani Deb, Kanak Lata

567 Resveratrol in Gynecology

Alka Gahlot

572 A 28 Weeks Pregnancy with Huge Ovarian Cyst: A Rare Case Report

Editorial Policies The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article.

Monica Verma, Laxmi Maru, Devyani Tiwari

PEDIATRICS

574 Role of Zinc in Growth and Immunity in Children

Shweta Pathak

PSYCHIATRY

577 An Atypical Presentation of Obsessive Compulsive Disorder with Repeated Somersaults

Nitisha Verma, Shilpa Adarkar, Deoraj Sinha, Ravindra M Kamath

MEDILAW

580 Laws Applicable on a Quack

KK Aggarwal

MEDICOFINANCE

585 Benefits of Estate Planning

Note: Indian Journal of Clinical Practice does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue.

AROUND THE GLOBE

587 Rozat Update 592 News and Views LIGHTER READING

595 Lighter Side of Medicine

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FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF

Prof. Dr KK Aggarwal

Group Editor-in-Chief IJCP Group and eMedinewS

Child Sexual Abuse: An Epidemic QUOTES FROM A DELHI HIGH COURT CASE The court termed child sexual abuse as an "epidemic".

Court: “Not only parents, but even trial courts dealing with such cases, should create an atmosphere where the victims can depose truthfully against "sexual perpetrators".

Justice PS Teji: "Children who have suffered sexual abuse at the hands of the sexual perpetrators do not only suffer from physical pain but are also subjected to mental and emotional trauma. The results of child sex abuse are severe and far reaching".

"Child sexual abuse is one of the most pervasive social problems faced by our society. Its impact is profound because of the sheer frequency with which it occurs and because of the trauma brought to the lives of the children who have experienced this crime. Child sexual abuse is an epidemic."

The trial court should "ensure the examination of the child witness by giving due protection to him and bringing the child out of the pressure".

"The parents of such victims have even a greater role to play in helping and aiding the child in overcoming the trauma".

SOME FACTS ÂÂ

A study conducted by Aram Foundation, an NGO working for child rights, has found that about 29% of students studying in 71 schools and 56 colleges in Coimbatore, Erode, Salem, Tirupur and Dharmapuri had suffered sexual abuse.

ÂÂ

As per a study conducted by Tulir CPHCSA in 2006, in which more than 2,211 school-going children in Chennai were interviewed, child sexual abuse prevalence rate was 42%.

ÂÂ

Another study conducted in 2007 backed by the Government of India, in which 1,25,000 children were interviewed in 13 states, more than half (53%) said that they had been subjected to one or more forms of sexual abuse.

ÂÂ

Eight cases of sex crimes against children have been registered every day in the last 2 years. About 6,816 police cases were registered from November, 2012—when the Protection of Children against Sexual Offences Act (POCSO)—came into force up to March, 2015. The highest number of FIRs has been registered in Rajasthan followed by Maharashtra, Uttar Pradesh, Madhya Pradesh and Kerala according to data available with the National Commission for Protection of Child Rights (NCPCR). The number of convictions is only 166 that is, 2.4% of the total cases registered while in 389 cases accused were acquitted.

Source: Times of India

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AMERICAN FAMILY PHYSICIAN

Nutrition Myths and Healthy Dietary Advice in Clinical Practice LENARD I. LESSER, MARY CAROL MAZZA, SEAN C. LUCAN

ABSTRACT Healthy dietary intake is important for the maintenance of general health and wellness, the prevention of chronic ill­ness, the optimization of life expectancy, and the clinical management of virtually all disease states. Dietary myths (i.e., concepts about nutrition that are poorly supported or contradicted by scientific evidence) may stand in the way of healthy dietary intake. Dietary myths exist about micronutrients, macronutrients, non-nutrients, and food energy. Representative myths of each type include that patients need to focus on consuming enough calcium to ensure bone health, dietary fat leads to obesity and is detrimental to vascular health, all fiber (whether naturally occurring or artificially added) is beneficial, and food calories translate to pounds of body weight through a linear relationship and simple arithmetic. A common theme for dietary myths is a reductionist view of diet that emphasizes selected food constituents as opposed to whole foods. Healthy dietary advice takes a more holistic view; consistent evidence sup­ports recommendations to limit the consumption of ultraprocessed foods and to eat whole or minimally processed foods, generally in a form that is as close to what occurs in nature as possible. Family physicians can help dispel myths for patients and give sound nutritional advice by focusing on actual foods and broader dietary patterns.

Keywords: Life expectancy, dietary myths, healthy dietary advice, minimally processed foods

W

hat an individual eats is important for the mainte­nance of general health and wellness and the management of virtually all disease states. Healthy diets are associated with reductions in morbidity and premature mortality.1 However, much of the dietary information presented as fact is actually myth (i.e., concepts poorly supported or contradicted by the scientific evidence).

There are dietary myths about micronutrients (vitamins and minerals), macronutrients (carbohydrates, proteins, and fats), non-nutrients (components of food not currently recognized as essential for growth or maintenance), and food energy (the stored capacity to do work that is often measured in calories). This article will discuss selected common myths in each of these areas.

LENARD I. LESSER, MD, MSHS, is an assistant research physician at the Palo Alto (Calif.) Medical Foundation Research Institute.

MARY CAROL MAZZA, PhD, AM, is a postdoctoral fellow at the Stanford (Calif.)

Clinical Excellence Research Center and the Palo Alto Medical Foundation Research Institute.

SEAN C. LUCAN, MD, MPH, MS, is an assistant professor at Albert Einstein College of Medicine Montefiore Medical Center in Bronx, NY. Source: Adapted from Am Fam Physician. 2015;91(9):634-638.

DIETARY MYTHS

Patients Need to Focus on Consuming Enough Calcium for Bone Health Encouraging calcium consumption for opti­ mal bone health and osteoporosis preven­tion is a routine part of many clinical visits, especially for female patients.

Nonetheless, the role of calcium in strengthening bones is unclear. Americans have among the highest calcium intake in the world, but also one of the highest rates of osteoporosis.2 A Cochrane review found that trials of calcium supplementation in children had minimal, if any, effect on bone mineral density.3 Another Cochrane review includ­ ing postmenopausal women and older men found that calcium supplements, even with concomitant vitamin D supplementation, had only small effects on fracture prevention; the number needed to treat (NNT) to prevent one hip fracture was approximately 1,000 for those living in the community and about 111 for nursing home residents.4 Although the U.S. Preventive Services Task Force does not make a stand-alone recom­ mendation on calcium, it concludes that the evidence is insufficient to recommend vita­min D supplementation, with or without calcium, to prevent fractures in noninstitutionalized women or men.5

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AMERICAN FAMILY PHYSICIAN The small chance of benefit with supplemental calcium may be outweighed by the increased risks of adverse effects, particularly kidney stones and cardiovascular events, even in dosages as low as 500 mg daily.6,7 Whereas a meta-analysis including older persons showed that the NNT with calcium supplementation to prevent one fracture was 302, the number needed to harm (number needed to cause one major car­diovascular event) was 178.8 Other meta-analyses did not find a statistically signifi­cant increase in cardiovascular risk with calcium supple­mentation,9 but suggested that it may actually increase the risk of hip fracture.10 Patients should be informed about the lack of evidence to support calcium supplements for bone health and the possibility of harm with supplementation (e.g., through pills or unnaturally fortified foods).

Calcium is also found in whole foods, such as dairy.

Although consuming dairy foods does not have clear benefits for bone health,3,11,12 it does not seem to pose risks for kidney stones or cardiovascular events as with artificial forms of calcium supplementation.6,8

Dietary Fat Leads to Obesity and is Detrimental to Vascular Health Macronutrients are the components of food that supply energy. Because fat is the macronutrient with the high­est number of calories per gram, there are concerns that consuming fat will lead to higher calorie intake and obesity. Dietary guidelines have recommended reducing fat intake,13,14 and physicians often recommend a low-fat diet. However, some high-fat foods may have beneficial effects, such as greater satiety subsequently leading to lower food intake overall.15,16 Studies have demonstrated that consuming higher-calorie fatty foods and higher-fat diets may produce and sustain as much or more weight loss than lower-fat diets.17-20 Some dietary guidelines specifically recommend replacing saturated fats with unsaturated fats to improve vascular health. The rationale is that consuming satu­rated fats raises levels of total and lowdensity lipopro­ tein cholesterol, whereas consuming unsaturated fats generally lowers these levels.21 Regardless of potential changes in disease-oriented lipid parameters, evidence is mounting that saturated fats may not be a primary driver of cardiometabolic disease or mortality.22-28 A Cochrane review found no effects on cardiovascular or all-cause mortality with reduction of saturated fat or with substi­tuting other fats for saturated fat. Although there was the suggestion

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of a small reduction in cardiovascular events in trials with dietary fat modification (maintaining total fat intake but with higher proportions of polyunsatu­rated and monounsaturated fats), effects became statis­tically nonsignificant when the review authors excluded biased studies (i.e., those having systematic differences between intervention and control groups, other than dietary-fat differences).29 It is important to note that patients do not eat isolated types of fat; they eat foods that contain mixes of fats, as well as other components such as proteins, carbohy­drates, micronutrients, and fiber. Some foods contain­ing saturated fats may be harmful, whereas others may be benign or even beneficial. For instance, consum­ing ultraprocessed foods high in saturated fats (e.g., preserved meats) has been associated with significant increases in cardiovascular and all-cause mortality,26 whereas consuming whole foods high in saturated fats (e.g., dairy products) has been inversely associated with incident cardiovascular disease27 and cardiometabolic risk factors such as type 2 diabetes mellitus and obe­sity.22,28 Reducing saturated fat in the diet may not lead to lower cardiovascular risk, especially if what replaces this fat is ultraprocessed (refined) carbohydrates.30

All Types of Fiber are Beneficial Fiber, a nondigestible food constituent, is not known to be essential for body growth and maintenance, but may be important for general health. The Institute of Medi­cine recommends a daily fiber intake of 25 g for adult women and 38 g for adult men.31 Not all kinds of fiber are equally beneficial, however.

Dietary fibers are a natural part of whole plant foods (e.g., fruits, vegetables, nuts, grains, seeds). Dietary fibers have soluble and insoluble forms, both of which may be beneficial. Increased intake of dietary fiber may help prevent cardiovascular disease, diabetes, constipa­tion, and gastrointestinal and breast cancers.32-37 By contrast, functional fibers are components of ultra­ processed foods. Functional fibers include polydextrose, inulin, resistant starch, chitosan, and indigestible dextrins. These substances are isolated or created in laboratories and then injected into ultraprocessed food items to increase their fiber content.31 The U.S. Food and Drug Adminis­tration defines any edible product with 2.5 g of fiber per serving as a “good” fiber source38; it does not distinguish natural dietary fibers from added functional fibers. In an effort to meet dietary fiber goals, persons often consume functional fibers in the form of

AMERICAN FAMILY PHYSICIAN high-fiber ultra­processed foods. Although evidence is lacking to show that functional fibers are beneficial,31 there is evidence that consuming functional fibers can lead to gastroin­ testinal distress and malabsorption of other nutrients.31 Physicians should steer patients toward whole foods that are naturally high in dietary fiber (e.g., fruits, vegetables, whole grains, nuts), for which there is good evidence of health benefits,39-41 and away from ultraprocessed prod­ucts with added functional fibers.31

3,500 Calories Translates to 1 Lb of Body Weight Patients who want to lose weight may ask their physicians how many fewer calories they need to eat or how many more they need to burn to lose weight.

The prevailing belief is that a net deficit of 3,500 calories (i.e., 3,500 calories burned in excess of calories ingested) will yield a body weight reduction of 1 lb (0.45 kg). This “3,500 calorie rule” is oversimplified and does not take into account the dynamic, nonlinear response of body weight to sustained changes in calorie balance.42 When individuals lose weight, compensatory mechanisms work to prevent further weight loss and promote regain.43,44 The 3,500 calorie rule would predict that an individ­ual underconsuming 100 net calories per day would lose more than 50 lb (22.7 kg) over five years. More accurate weight loss estimates, which take into account dynamic and compensatory changes, would predict a decrease

of only about 10 lb.43 Therefore, relying on the 3,500 calorie assumption may create false expectations for patients and set them up for failure and disappointment.

A better rule of thumb for adults is that a maintained deficit of 100 calories per day without any other changes will lead to an eventual weight loss of about 10 lb; it will take about one year to achieve 50% and about three years to achieve 95% of the total weight loss.45 Physi­cians who want to help patients predict weight loss can use the National Institutes of Health’s body weight simulator, which is available at http://www.niddk.nih. gov/research-funding/at-niddk/labs-branches/LBM/ integrative-physiology-section/body-weight-simulator/ Pages/body-weight-simulator.aspx. Recommendations to avoid processed foods and consume whole foods might help patients meet their overall caloric goals.

HEALTHY DIETARY ADVICE The selected myths described in this article are charac­ terized by dietary reductionism, which emphasizes food constituents instead of foods in their entirety. Although much nutritional science is based on evaluating the ben­efits or harms of food constituents such as micronutri­ents, macronutrients, non-nutrients, and energy, patients eat foods, not food constituents.46 If patients consume ultraprocessed foods that are altered, for instance, to add calcium and fiber and to remove saturated fat and calo­ ries, they will not necessarily be healthier, as the myths discussed in this

Table 1. Examples of Ultraprocessed Foods and Whole Food Alternatives Ultraprocessed foods*

Selected reductionist concerns

Whole food alternatives†

Candies, cookies, and other confections (even low-fat, low-calorie versions)

Refined sugars, unhealthy fats, few vitamins and minerals, little fiber

Fresh or dried unsweetened whole fruits

Chips, pretzels, and other refined snacks, even if low fat

Refined carbohydrates, few vitamins and minerals, little fiber

Nuts and seeds

Cold cuts, hot dogs, other preserved meats; vegetarian “meats” or products made from isolated vegetable protein

Saturated fats, high calorie density, and/or refined carbohydrate fillers

Whole soy (e.g., tofu, tempeh), beans, wild-caught fish, pastured meats or eggs, or wild game

White breads and refined bakery products (with or without added supplemental constituents such as fiber or calcium)

Refined carbohydrates, few vitamins and minerals, little fiber

100% whole-grain or sprouted/flourless breads and bakery products

White rice

Refined carbohydrates, few vitamins and minerals, little fiber

Brown rice

Note: The theme for healthy eating focuses on foods, not food constituents: limit ultraprocessed foods and eat more whole foods (or minimally processed foods), generally in a form that is as close to what occurs in nature as possible (e.g., organic plants and wild-caught or pastured animals raised on their natural diets). The healthiest food comes from farms, not factories or factory farms. *Highly altered foods from industrial processing plants, with various components removed and/or added (including colors, flavors, conditioners, stabilizers, and preservatives beyond the scope of this article). †Minimally

manipulated foods from living botanical plants (or, based on individual preferences, the animals that eat them) with limited removal or addition of components.

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AMERICAN FAMILY PHYSICIAN article suggest. There have been no long-term headto-head studies to guide clinicians in recommending specific whole foods over others to patients. However, various diets (e.g., low-carbohydrate, low-fat, lowglycemic, Mediterranean, mixed/balanced, Paleolithic) have been shown to improve weight; surrogate end points; or chronic dis­ ease incidence, prevalence, or severity in various trials and cohort studies.1,47,48 None of these diet plans have been shown to be superior to the others, and they all share common features and a consistent theme: limit ultraprocessed foods and eat whole foods (or minimally processed foods), generally in a form that is as close to what occurs in nature as possible.1 Within this theme for healthy eating, there is room for variation, such as the inclusion or exclusion of meats, other animal products, or certain grains.

Although many believe that whole or minimally pro­cessed foods are expensive, studies have shown that healthy whole foods can be cheaper than ultraprocessed foods.49-51 Table 1 provides examples of ultraprocessed foods and whole food alternatives. Family physicians can help their patients achieve healthy dietary changes using the simple advice to eat more whole foods and avoid ultraprocessed foods, advice highly consistent with the 2015 Dietary Guidelines Advisory Committee recommendations.52 REFERENCES 1. Katz DL, Meller S. Can we say what diet is best for health?

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33. Yao B, Fang H, Xu W, et al. Dietary fiber intake and risk of type 2 diabe­tes. Eur J Epidemiol. 2014;29(2):79-88.

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2012;18(48):7378-7383.

36. Aune D, Chan DS, Greenwood DC, et al. Dietary fiber and breast cancer risk. Ann Oncol. 2012;23(6):1394-1402.

37. Dahm CC, Keogh RH, Spencer EA, et al. Dietary fiber and colorectal cancer risk. J Natl Cancer Inst. 2010;102(9): 614-626.

39. Bellavia A, Larsson SC, Bottai M, Wolk A, Orsini N. Fruit and vegetable con­sumption and all-cause mortality. Am J Clin Nutr. 2013;98(2):454-459.

40. Jacobs DR, Pereira MA, Meyer KA, Kushi LH. Fiber from whole grains, but not refined grains, is inversely associated with all-cause mortal­ity in older women: the Iowa Women’s Health Study. J Am Coll Nutr. 2000;19(suppl 3): 326S-330S. 41. Bao Y, Han J, Hu FB, et al. Association of nut consumption with total and cause-specific mortality. N Engl J Med. 2013;369(21):2001-2011.

42. Thomas DM, Martin CK, Lettieri S, et al. Can a weight loss of one pound a week be achieved with a 3500-kcal deficit?

Commentary on a com­monly accepted rule. Int J Obes (Lond). 2013;37(12):1611-1613.

43. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure result­ing from altered body weight. N Engl J Med. 1995;332(10):621-628.

44. Hall KD, Hammond RA, Rahmandad H. Dynamic interplay among homeostatic, hedonic, and cognitive feedback circuits regulating body weight. Am J Public Health. 2014;104(7):1169-1175.

45. Hall KD, Sacks G, Chandramohan D, et al. Quantification of the effect of energy imbalance on bodyweight. Lancet.

2011;378(9793):826-837.

46. Lucan SC. Patients eat food, not food categories or constituents. Am Fam Physician. 2011;83(2):107-108.

47. Fung TT, Chiuve SE, McCullough ML, Rexrode KM, Logroscino G, Hu FB. Adherence to a DASH-style diet and risk of coronary heart disease and stroke in women [published correction appears in Arch Intern Med. 2008;168(12):1276]. Arch Intern Med. 2008;168(7):713-720.

48. Shai I, Schwarzfuchs D, Henkin Y, et al.; Dietary Intervention Randomized Controlled Trial (DIRECT) Group. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet [published correction appears in N Engl J Med. 2009;361(27):2681]. N Engl J Med. 2008;359(3):229-241.

49. Reed J. How Much Do Americans Pay for Fruits and Vegetables? Wash­ington, DC: USDA Economic Research Serv.; 2004.

50. Katz DL, Doughty K, Njike V, et al. A cost comparison of more and less nutritious food choices in US supermarkets.

Public Health Nutr. 2011;14(9):1693-1699.

51. McDermott AJ, Stephens MB. Cost of eating: whole foods versus con­venience foods in a low-income model. Fam Med. 2010;42(4):280-284.

52.

38. Hiza H, Fungwe T, Bente L. Trends in Dietary Fiber in the U.S. Food Sup­ply. Alexandria, Va.: U.S. Dept. of Agriculture; 2007.

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Scientific report of the 2015 Dietary Guidelines Advisory Committee. Office of Disease Prevention and Health Promotion. http://health.gov/ dietaryguidelines/2015scientific-report/. Accessed March 9, 2015.

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Practice Guidelines ACP PROVIDES GUIDANCE ON NONSURGICAL TREATMENT OF URINARY INCONTINENCE IN WOMEN

evidence indicating improvement in symptoms.

Additionally, no associated harms were apparent with this intervention.

The prevalence of urinary incontinence (UI) ranges from 25% in females 14 to 21 years of age to 75% in women 75 years and older, although it may actually be higher than reported because some evidence has shown that one-half or more of women with UI do not tell their physicians about symptoms. There is an increased risk of UI with preg­nancy and with pelvic floor trauma from delivering vaginally, as well as in women who are menopausal or obese; who have a uri­ nary tract infection, functional or cognitive impairment, chronic cough, or constipation; or who have had a hysterectomy.

Bladder Training

There are two categories of UI: stress, which is caused when the urethral sphincter does not work because of intra-abdominal pressure, and urgency, which is associated with the urgent need to urinate. Stress UI can cause urine to leak when laughing, coughing, or sneezing. Mixed UI is stress and urgency UI combined.

The American College of Physicians (ACP) has provided recommendations for nonsurgical treatment of UI in women. Treatment of UI is aimed at achieving, or at least improving, symptoms. It is deemed effective if it reduces the number of episodes by at least one-half.

Nonpharmacologic Therapy Nonpharmacologic therapy options for UI, which have been shown to be effective and have a lower risk of adverse effects, include lifestyle changes (weight loss and physical activity), bladder training, pelvic floor mus­cle training (PFMT), continence services, vaginal cones, and medical devices. There have not been enough data to compare vari­ous types of nonpharmacologic therapies or to compare nonpharmacologic with pharma­cologic therapies.

Lifestyle Changes In women with UI who are obese, weight loss and exercise are recommended, with moderate-quality

Source: Adapted from Am Fam Physician. 2015;91(11):801-802.

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Bladder training, which is behavioral treat­ ment that entails having women lengthen the time between urinating, is recommended in women with urgency UI, with low-quality evidence indicating improvement vs. no treatment.

Pelvic Floor Muscle Training Based on high-quality evidence, PFMT con­ sisting of educating women on the voluntary contraction of pelvic floor muscles should be first-line treatment for stress UI, and PFMT combined with bladder training is recom­mended for mixed UI. Studies have shown that, compared with no treatment, PFMT improved continence rates and quality of life in women with stress UI. It also was shown to have an effectiveness greater than five times that of no treatment for improving stress UI. Additionally, PFMT can be combined with biofeedback from vaginal electromyography, which allows patients to see when they are contracting their pelvic floor muscles cor­rectly; this also has been shown to improve stress UI. In women with mixed UI, PFMT plus bladder training led to continence and improved UI more often than no treatment.

Continence Services Continence services enlist the assistance of health care professionals who have knowledge and experience in diagnosing and managing UI; however, studies have shown that, compared with no treatment, it provided no statistically significant improvement in continence or UI. Vaginal Cones, Medical Devices, and Other Treatments Data are insufficient to make a conclusion about the effectiveness, compared with no treatment, of vaginal cones, pessaries, or intravaginal and intraurethral devices for treating stress UI, or of programs for behavioral changes, diets supplemented with soy, or acupuncture for mixed UI.

AMERICAN FAMILY PHYSICIAN Pharmacologic Treatment

Urgency UI

Systemic pharmacologic therapy is not recommended in women with stress UI; however, based on high-quality evidence, it is recommended in women with urgency UI in whom bladder training has failed. Decisions regard­ing medication should be based on tolerability, adverse effects, ease of use, and cost.

Antimuscarinics. Based on high-quality evidence and in comparison with placebo, darifenacin, fes­oterodine, and tolterodine improved UI; darifenacin improved quality of life; and oxybutynin, solifenacin, tolterodine, and trospium attained continence more often. Additionally, fesoterodine improved UI more than tolterodine.

Although it has some effec­tiveness, it should be noted that pharmacologic therapy has adverse effects, with evidence indicating that women may discontinue therapy as a result. Medication options include antimuscarinics, beta3-adrenoceptor agonists, duloxetine, and estrogen.

Data are insuf­fi cient to conclude which medications are most effective and safe.

Based on moderate-quality evidence and in compari­son with placebo, fesoterodine attained continence more often, and oxybutynin and propiverine (not available in the United States) improved UI. Additionally, fesotero­ dine attained continence more often than tolterodine.

Stress UI There are not enough data on topical estrogen prepara­tions regarding the effectiveness for treating stress UI; however, vaginal estrogen appears to improve continence and UI. Compared with placebo, transdermal formula­tions made stress UI worse and estradiol implants did not provide improvement.

Estrogen tablets and ovules improved UI compared with placebo, with tablets also increasing continence.

Intravaginal estriol combined with PFMT was more effective for attaining continence compared with estriol monotherapy, based on low-quality evidence. Highquality evidence showed that there was no statistically significant improvement in UI with duloxetine vs. placebo; however, based on low-quality evidence, it was shown to improve quality of life in women without severe UI or overactive bladder.

Beta3-adrenoceptor Agonists. Based on moderate-quality evidence and in comparison with placebo, mirabegron improved UI and attained continence more often.

Other. There are not enough data to make conclusions about the effectiveness of resiniferatoxin or nimodipine as UI therapy.

Adverse Effects Among the different classes of medication, adverse effects tended to be similar. Common adverse effects of anti­muscarinics were dry mouth, constipation, and blurred vision. In addition, tolterodine also increased the likeli­ hood that a patient would experience hallucinations. With regard to beta3-adrenoceptor agonists, patients taking mirabegron experienced more nasopharyngitis and gastrointestinal problems than those taking placebo. Although pharmacologic therapy can improve UI, and possibly can provide complete continence, patients may stop treatment because of adverse effects.

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Photo Quiz DIFFUSE, BRIGHT-RED RASH WITH DESQUAMATION AND SCALING IN AN ADULT A 59-year-old man presented with fever, chills, and a pruritic rash that had general­ ized peeling and underlying redness. The rash began one month prior as small pap­ules on his arms and then spread across his entire body, including his palms and soles. He also had pain in his hands. The rash did not improve after treatment with a topical medium-potency steroid, but subsequently responded to a course of oral prednisone.

His medical history was significant for hyper­tension and hyperlipidemia. He was taking hydrochlorothiazide and rosuvastatin. He did not have any sick contacts and was not using any new soap, lotion, or detergent.

On physical examination, he was ill appearing and febrile. His heart rate was 120 beats per minute, and his blood pressure was 90/50 mm Hg. The skin rash (Figure 1) con­sisted of diffuse pustules on an erythema­ tous background and involved more than 85% of his body surface area, including his head, trunk, and upper and lower extremi­ties. There was a thick scale, including on the palms and soles (Figure 2). Bacterial and viral culture results were negative.

Figure 1.

Question Based on the patient’s history and physical examination findings, which one of the fol­lowing is the most likely diagnosis?

A. Acute generalized exanthematous pustulosis.

B. Allergic contact dermatitis.

C. Erythrodermic psoriasis.

D. Pityriasis rubra pilaris.

Source: Adapted from Am Fam Physician. 2015;91(11):791-792.

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Figure 2.

SEE THE FOLLOWING PAGE FOR DISCUSSION.

AMERICAN FAMILY PHYSICIAN DISCUSSION

Summary Table

The answer is C: erythrodermic psoria­sis. Characteristic features include a dif­fuse, bright-red rash and desquamation with superficial scaling and often exudation. This is unlike plaque psoriasis, a common variant of psoriasis, which has thick, adherent white scales. The average age of onset is 50 years.1 The erythrodermic form is considered the most active psoriatic process with increased proliferation. This results in a loss of kerati­ nocyte maturation and abnormal keratino­ cytes that are loosely bound and more easily shed. In this patient, a skin biopsy showed dermal lymphohistiocytic inflammation with occasional eosinophils.

Condition

Characteristics

Acute generalized exanthematous pustulosis

Sterile, nonfollicular, small pustules on erythematous and edematous skin; associated with a medication exposure

Allergic contact dermatitis

Erythematous, pruritic vesicles and bullae with scaling and relatively welldemarcated borders on exposed skin, typically along the hands, face, and neck

Erythrodermic psoriasis

Diffuse, bright-red rash, and desquamation with superficial scaling and often exudation

Pityriasis rubra pilaris

Erythematous with salmon-colored plaques; redorange, palmoplantar, keratotic follicular papules and islands of well-demarcated sparing on the trunk

Patients with erythrodermic psoriasis can have excessive heat loss from generalized vasodilation of cutaneous vessels, leading to shivering and hypothermia.

Vasodilation can lead to loss of protein and extremity edema.2 Patients with this condition also have signs of systemic illness, including generalized pruri­ tus, fever, chills, dehydration, and lymphade­ nopathy.1 Erythrodermic psoriasis usually arises from pustular psoriasis but can be triggered by sunburn, human immunodefi­ciency virus infection, systemic infections, malignancies (mainly lymphomas), and even chronic plaque psoriasis.3 It can also arise after the withdrawal of systemic steroids.1,3 Treatment occurs in the intensive care unit and includes fluid and electrolyte manage­ ment, and treatment for sepsis.2 Acute generalized exanthematous pustu­losis is a rare, drug-induced eruption that is characterized by the sudden appearance of dozens of sterile, nonfollicular, small pustules on erythematous and edematous skin.4 It most commonly occurs with the use of antibiotics (penicillins and macrolides), calcium channel blockers, and antimalari­als. Fever and neutrophilia are present, and sometimes there is mild nonerosive muco­ sal involvement. One-third of patients have peripheral eosinophilia.4 Within a few days of stopping the causative drug, pustules spontaneously disappear.

The desquamation and reaction fully resolve within 15 days.4 Allergic contact dermatitis manifests as erythematous vesicles and bullae with scaling and relatively welldemarcated borders on exposed skin, typically along the hands, face, and neck, although any area can be affected. Pruritus is the most common symptom.5 Pityriasis rubra pilaris is an inflammatory condition of

uncertain etiology. The rash is typically erythematous with salmon-colored plaques. It is clinically distinguished from plaque psoriasis by the presence of red-orange, palmoplantar, keratotic follicular papules and islands of well-demarcated sparing on the trunk.6 Autoimmune diseases, infections, or malignancies are possible triggers.

REFERENCES 1. Hulmani M, Nandakishore B, Bhat MR, et al. Clinicoetiological study of 30 erythroderma cases from ter­ tiary center in South India. Indian Dermatol Online J. 2014;5(1):25-29.

2. Varman KM, Namias N, Schulman CI, Pizano LR. Acute generalized pustular psoriasis, von Zumbusch type, treated in the burn unit. A review of clinical features and new therapeutics. Burns. 2014;40(4):e35-e39.

3. Borges-Costa J, Silva R, Gonçalves L, Filipe P, Soares de Almeida L, Marques Gomes M. Clinical and labora­ tory features in acute generalized pustular psoriasis: a retrospective study of 34 patients. Am J Clin Dermatol.

2011;12(4):271-276.

4. Vassallo C, Derlino F, Brazzelli V, D’Ospina RD, Borroni G. Acute generalized exanthematous pustulosis: report of five cases and systematic review of clinical and histopathological findings. G Ital Dermatol Venereol.

2014;149(3):281-290.

5. Usatine RP, Riojas M. Diagnosis and manage­ment of contact dermatitis. Am Fam Physician. 2010;82(3):249-255.

6. Klein A, Landthaler M, Karrer S. Pityriasis rubra pilaris: a review of diagnosis and treatment. Am J Clin Dermatol.

2010;11(3):157-170.

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CARDIOLOGY

Correlation of Retinopathy and TMT Positivity in Patients of Diabetes Mellitus S GUPTA*, PK BAGHEL*, H GUPTA*, S LAKHTAKIYA*, MK JAIN*, DHARMENDRA JAIN†

ABSTRACT Background: Prevalence of diabetes is rapidly rising all over the globe at an alarming rate. It proceeds unnoticed ravaging the body. Although complications of diabetes do not occur at the onset of disease but due to delay in diagnosis, they are commonly seen at the time of diagnosis. Objective: We sought to determine the incidence of coronary artery disease (CAD) in patients of diabetes mellitus with retinopathy on the basis of treadmill test (TMT). Material and methods: Study was carried out on 75 patients of diabetes mellitus with retinopathy and normal resting electrocardiography in the Dept. of Medicine, SS Medical College and Associated SGM Hospital, Rewa, Madhya Pradesh over a period of 15 months from May 2012 to July 2013. TMT and optic fundus examination was done in all these 75 patients to find out possible correlation if any between severity of retinopathy and CAD. Results: Among 75 patients, 57 had nonproliferative diabetic retinopathy (NPDR) and 18 had proliferative diabetic retinopathy (PDR). Among NPDR patients, mean systolic blood pressure (SBP)/diastolic blood pressure (DBP) was 144 ± 2.5/89 ± 1.3 mmHg, mean age of presentation was 56.5 ± 4.0 years, mean duration of diabetes was 11.2 ± 2.1 years, mean glycosylated hemoglobin (HbA1C) was 9.1 ± 1.2, mean serum cholesterol level was 186 ± 51.1 mg/dL, mean serum triglyceride level was 181 ± 4.8 mg/dL, while among PDR patients mean SBP/DBP was 148 ± 3.2/93 ± 4.1 mmHg, mean age was 55.8 ± 6.0 years, mean duration of diabetes was 12.2 ± 1.6 years, mean HbA1C 10.2 ± 1.3 years, mean serum cholesterol level was 190 ± 4.8 mg/dL, mean serum triglyceride level was 208 ± 12.1 mg/dL. Out of these 75 patients, 25 were TMT positive. Among patients having NPDR (26.31%) were TMT positive, while among PDR patients (55.56%) were TMT positive. The results were statistically significant.

Among TMT positive patients, 88.0% had nephropathy. The results were statistically significant (p = 0.02). Conclusion: All patients with type 2 diabetes mellitus who have diabetic retinopathy and presence of cardiovascular risk factors such as arterial hypertension, nonspecific chest pain or dyslipidemia, should undergo detailed cardiologic assessment. Retinopathy can thus be included as an indication for doing TMT in diabetics for detection of asymptomatic CAD.

Keywords: Coronary artery disease, diabetes mellitus, retinopathy, treadmill test, electrocardiography

D

iabetes mellitus is accepted as a worldwide epidemic with an estimated increase in prevalence from 2.8% in 2000 to 4.4% by 2030.1 Diabetes mellitus is a vascular disease with many microvascular manifestations such as retinopathy and macrovascular complications like coronary artery disease (CAD). Large number of diabetics with retinopathy may have unidentified CAD. Even though the prevalence of microvascular complications of diabetes like retinopathy and nephropathy are

*Dept. of Medicine SSMC and SGMH, Rewa, Madhya Pradesh †Assistant Professor Dept. of Cardiology, IMS, BHU, Varanasi, Uttar Pradesh Address for correspondence Dr Dharmendra Jain Assistant Professor Dept. of Cardiology, IMS, BHU, Varanasi, Uttar Pradesh E-mail: djaincard@gmail.com

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comparatively lower in Indians, the prevalence of premature CAD is much higher in Indians compared to other ethnic groups.2 The purpose of this study was to analyze association of diabetic retinopathy and different presentations of cardiovascular disease (CVD).3 Diabetic retinopathy may be an independent risk marker for CVD.4 MATERIAL AND METHODS This was a cross-sectional observational study carried out in 75 diabetic patients with retinopathy.

All diabetic patients who were >25 years of age, had retinopathy of any duration and normal resting electrocardiography (ECG) were included in the study while patients who had symptoms of typical angina or chest pain, abnormal resting ECG or known cases of inherited cardiac disorders, valvular heart disease, heart failure or arrhythmia were excluded from the study. All patients of type 2 diabetes

CARDIOLOGY mellitus (T2DM) were selected without any bias for sex, severity, habitat and educational status. Each was carefully examined for various complications related to diabetes and was investigated. Blood pressure was measured in the ideal condition and average of two readings of blood pressure on two subsequent visits of patient. Hypertension was diagnosed according to JNC-7 criteria5 (systolic blood pressure [SBP] >140 mmHg and diastolic blood pressure [DBP] >90 mmHg or those who were taking antihypertensive medication).

Physical examination was done which included anthropometric measurements (weight in kg, height in cm and waist circumference in cm) and calculation of body mass index (BMI) in kg/m2. Height without shoes was recorded in cm and weight without shoes was recorded in kg using beam balance. BMI was calculated as BMI – wt in kg/ht in m2 (kg/m2).

Waist and hip girth were measured with the subject standing using fiberglass tape. The waist was defined on the smallest girth between costal margin and iliac crest and hip as the circumference at the level of greater trochanter. Waist-hip ratio of >90 cm in males and >80 cm in females was considered as criteria for obesity. All measurements were taken in the presence of two observers. Blood sample for lipid profile was taken after an overnight fast. Dyslipidemia was defined if patient had total cholesterol (>200 mg/dL), serum triglyceride (>150 mg/dL), serum high-density lipoprotein (HDL) (<40 mg/dL) in males (<50 mg/dL) in females and serum low-density lipoprotein (LDL) (>100 mg/dL).6 Retinopathy was diagnosed after fundus examination (direct ophthalmoscopy), which was performed by an experienced ophthalmologist under mydriasis of both eyes by tropicamide eye drops. Nephropathy was diagnosed on the basis of microalbuminuria (30300 mg/day) positive on two occasions in 6 months or urine albumin-creatinine ratio (>30 µg/mg). Twelve lead ECG was done.

RESULTS Correlation between blood pressure, age, duration of diabetes, glycosylated hemoglobin (HbA1C) and serum triglyceride level with retinopathy; correlation between blood pressure, age, duration of diabetes, HbA1C and serum triglyceride level with TMT; correlation of complications of diabetes with retinopathy and TMT; and correlation between retinopathy and TMT positivity are summarized in Tables 1-4.

Table 1. Correlation Between Blood Pressure, Age, Duration of Diabetes, HbA1C and Serum Triglyceride Level with Retinopathy NPDR PDR P value Variables (n = 57) (n = 18) Mean age 56.5 ± 4.0 55.8 ± 6.0 0.003 (in years) Mean duration of 11.2 ± 2.1 12.2 ± 1.6 0.012 diabetes (in years) 144 ± 2.5/ 148 ± 3.2/ 0.299 Mean SBP/DBP (mmHg) 89 ± 1.3 93 ± 4.1 9.1 ± 1.2 10.8 ± 1.3 0.003 Mean HbA1C Mean serum 181 ± 4.8 208 ± 12.1 0.007 triglyceride (mg/dL)

Table 2. Correlation Between Blood Pressure, Age, Duration of Diabetes, HbA1C and Serum Triglyceride Level with TMT Variables

Treadmill test

P value

Positive

Negative

Mean age (in years)

57.6 ± 5.3

56.4 ± 8.3

0.001

Mean duration of diabetes (in years)

12.8 ± 2.4

8.4 ± 3.2

0.001

Mean SBP/DBP (mmHg)

148 ± 2.6/ 90 ± 1.11

146 ± 3.2/ 90 ± 4.1

0.001

Mean HbA1C

8.8 ± 2.1

7.1 ± 1.3

0.001

206 ± 21.6

180 ± 12.8

0.056

Mean serum triglyceride (mg/dL)

Statistical Analysis Statistical analysis was done. Quantitative variables were described as mean ± 1 SD (standard deviation) unless otherwise indicated. Qualitative variables were described by % and compared using Chi-square test.

P value <0.05 was considered significant. Standard multistage maximal exercise (treadmill test [TMT]) was done on a motorized treadmill according to Bruce protocol. Informed consent was taken, prior approval from ethical committee was taken.

Table 3. Correlation of Complications of Diabetes with Retinopathy and TMT Complication

NPDR (n = 57)

PDR (n = 18)

TMT positive (n = 25)

Nephropathy (n = 62)

89.5% (n = 51)

61.1% (n = 11)

88.0% (n = 22)

Hypertension (n = 55)

77.2% (n = 44)

61.1% (n = 11)

80.0% (n = 20)

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CARDIOLOGY Table 4. Correlation Between Retinopathy and TMT Positivity Variable

Treadmill test Positive (n = 25)

Negative (n = 50)

NPDR (n = 57)

26.3% (n = 15)

73.7% (n = 42)

PDR (n = 18)

55.6% (n = 10)

44.4% (n = 8)

P value

0.045

DISCUSSION Complications of diabetes have been thought to occur late in the course of the disease. However, type 2 diabetes is an insidious illness with a long preclinical asymptomatic phase. Patients may be exposed to the ill effects of asymptomatic hyperglycemia for many years before clinical diagnosis of diabetes is made.

In the present study, majority of patients (92.0%) with retinopathy were >40 years. Mean age of patients with nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) was 56.5 ± 4 years and 55.8 ± 6 years, respectively which was comparable with studies by Juutilainen et al 2007,7 Niazi et al 20108 and Cheung et al 2007.9 Mean age of TMT positive patients was 57.6 ± 5.3 years and for TMT negative patients was 54.6 ± 8.3 years. Similar observations were found in studies by Agarwal et al 2008,10 Hernandez et al 201111 and Farood et al 2008.12 In the present study, there was significant relationship between age and retinopathy.

In the present study, among hypertensives 77.2% had NPDR and 61.1% had PDR. Mean SBP/DBP was 144 ± 2.5/89 ± 1.3, 148 ± 3.2/93 ± 4.1 in patients with NPDR and PDR, which were similar to studies by Demerdash et al 2012,13 Cheung et al 20079 and Juutilainen et al 2007.7 Eight percent of hypertensives were TMT positive.

The results were statistically significant. Agarwal et al 200810 found in his study that among TMT positive patients 90.9% and among TMT negative patients 83.3% were hypertensive. Farood et al 200812 in his study found average SBP and DBP of 134 ± 15 mmHg and 80 ± 6 mmHg, respectively in TMT negative patients and 137 ± 15 mmHg and 80 ± 8 mmHg in TMT positive patients. Hypertension is considered a significant risk factor for CAD. Significant correlation was found between blood pressure and silent CAD. In the present study of 75 patients with retinopathy, 85.3% patients were having diabetes

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for >10-year duration of which 25% had PDR and 75.0% had NPDR. The results were statistically significant. Mean duration of diabetes was 11.1 ± 2.1 years for NPDR and 12.2 ± 1.6 years for PDR. These results were comparable to studies by Demerdash et al 2012,13 Almeida et al 201114 and Niazi et al 20108 who also found that patients with severe diabetic retinopathy have a longer duration of diabetes. Pradeepa et al 200815 in CURES study found similar relationship. About 35.9% were TMT positive and results were statistically significant.

Mean duration of diabetes was 12.8 ± 2.4 years for TMT positive patients and 8.4 ± 3.2 years for TMT negative patients which was similar to study by Premlatha et al 1998,16 Farood et al 200812 and Hernandez et al 2011.11 It may be considered that this occurs due to longer duration of diabetes and poor glycemic control, which may cause loss of normal endothelial function and associated hypertension, dyslipidemia and endothelial dysfunction also contributed for higher number of patients with silent myocardial ischemia.

In the present study as the HbA1C levels increased the severity of retinopathy also increased. Majority of patients with retinopathy (96.0%) were having HbA1C levels >7 and the results were statistically significant. Mean HbA1C level was 9.1 ± 1.2 for NPDR and 10.2 ± 1.3 for PDR. These results were similar to study by Demerdash et al 2012.13 Mohan et al CUPES-14 200317 and Wahab et al 2008.18 Abdollahi et al 200619 also found statistically significant correlation between HbA1C and retinopathy. About 34.7% were TMT positive. The mean HbA1C in the present study was 8.8 ± 2.1 for TMT positive patients.

Janand-Delenne et al20 also reported that mean HbA1C in their patient was 9.4 ± 1.5 for patients with silent CAD. As compared to western counterparts mean HbA1C was high in present study. Mean age, duration of diabetes and HbA1C was higher in patients who were TMT positive and having PDR, which reflects poor glycemic control and detection of diabetes at late stages.

In present study, 28.0% were having serum triglyceride <150 mg/dL of which 52.3% had NPDR and 47.7% had PDR. Of 72.0% patients with serum triglyceride >150 mg/ dL, 85.2% had NPDR. The results were statistically significant. Mean serum triglyceride level was 208 ± 12.1 in PDR group and 181 ± 4.8 in NPDR. These results were comparable with the study by Demerdash et al 2012.13 In patients with serum triglyceride (<150 mg/dL), 14.3% were TMT positive while among patients with

CARDIOLOGY triglyceride >150 mg/dL, 40.7% were TMT positive.

Agarwal et al 2008,10 in his study also found high cholesterol (>200 mg/dL), high LDL (>140 mg/dL), low HDL (<40 mg/dL) and high triglyceride (>150 mg/dL) had a prevalence of 40.9%, 27.3%, 45.5%, 59.1% in CAD group, respectively as compared to non-CAD group who had prevalence of 29.6%, 9.3%, 38.9%, 55.6%, respectively.

Higher serum triglyceride levels in TMT positive patients indicates dyslipidemia is an important risk factor for CAD. In the present study, 89.5% patients, of NPDR and 61.1% of PDR had nephropathy. The results were statistically significant. Demerdash et al 2012,13 found significant correlation between urine albumin excretion and PDR and NPDR (p = 0.006). Among TMT positive patients 88.0% had nephropathy. Individuals with diabetic nephropathy commonly have diabetic retinopathy.

Nephropathy was higher in NPDR group in this study which might be due to more number of patients in NPDR group, but overall a significant correlation was present between retinopathy and nephropathy in our study.

Nephropathy is also an important risk factor for CAD but requires drawing blood sample, measurement of urine albumin and is expensive and time consuming as compared to fundoscopic examination which is a simple, bedside noninvasive test for subjecting patients for TMT. Out of 75 patients, 42.7% had some form of addiction in the form of tobacco, alcohol or both among these addicted patients 56.0% were TMT positive while among non-addicts 38.0% were TMT positive. The results were statistically significant (p = 0.003).

CONCLUSION In the present study, it was found that diabetic patients with retinopathy and who were positive on exercise stress testing had diabetes of long duration, were of higher age, had high serum triglyceride level, high HbA1C level and other associated complications of diabetes like nephropathy. No significant correlation was found with gender, serum cholesterol level, type of treatment and BMI. There was correlation between diabetic retinopathy and CAD in diabetics. It is advised that all diabetics should undergo repeated fundus examination and if retinopathy is present, then patients should be subjected to TMT to detect CAD. Ophthalmological examination in patients with diabetic retinopathy is a simple bed side, noninvasive test and has prognostic value for

the assessment of risk of ischemic heart disease.

Retinopathy can thus be included in indications for doing TMT in diabetics to detect CAD. REFERENCES 1. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047-53.

2. Mohan V, Sandeep S, Deepa R, Shah B, Varghese C. Epidemiology of type 2 diabetes: Indian scenario. Indian J Med Res. 2007;125(3):217-30.

3. Magri CJ, Fava S. The diabetic eye: a window to the heart & vascular system. J Diabetes Metab. 2012;S3:008.

4. Gimeno-Orna JA, Faure-Nogueras E, Castro-Alonso FJ, Boned-Juliani B. Ability of retinopathy to predict cardiovascular disease in patients with type 2 diabetes mellitus. Am J Cardiol. 2009;103(10):1364-7.

5. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-7). Prevention, Detection, Evaluation and Treatment of High Blood Pressure. National Heart, Lung and Blood Institute. Bethesda; 2004.

6. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-97.

7. Juutilainen A, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Retinopathy predicts cardiovascular mortality in type 2 diabetic men and women. Diabetes Care. 2007;30(2):292-9.

8. Muhammad Khizar Niazi, Arshad Akram, Muhammad Afzal Naz, Salahuddin Awan. Duration of diabetes as a significant risk factor for retinopathy. Pak J Opthalmol.

2010;26(4):182-6.

9. Cheung N, Wang JJ, Klein R, Couper DJ, Sharrett AR, Wong TY. Diabetic retinopathy and the risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Diabetes Care. 2007;30(7):1742-6.

10. Agarwal AK, Singla S, Singla S, Singla R, Lal A, Wardhan H, et al. Prevalence of coronary risk factors in type 2 diabetics without manifestations of overt coronary heart disease. J Assoc Physicians India. 2009;57:135-42.

11. Hernández C, Candell-Riera J, Ciudin A, Francisco G, Aguadé-Bruix S, Simó R. Prevalence and risk factors accounting for true silent myocardial ischemia: a pilot case-control study comparing type 2 diabetic with nondiabetic control subjects. Cardiovasc Diabetol. 2011;10:9.

12. Farood A, Masomi M. Risk factors for silent myocardial ischaemia in type II diabetic patients. Iranian Heart J. 2008;9(2):37-42.

13. Demerdash FE, Refaie W, Allakany R, Tantawy S, Dawood E. Diabetic retinopathy: a predictor of coronary artery disease. Egyptian Heart J. 2012;64(2):63-8.

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CARDIOLOGY 14. Almeida FK, Esteves JF, Gross JL, Biavatti K, Rodrigues TC. Severe forms of retinopathy predict the presence of subclinical atherosclerosis in type 1 diabetes subjects. Arq Bras Cardiol. 2011;97(4):346-9 15. Pradeepa R, Anitha B, Mohan V, Ganesan A, Rema M. Risk factors for diabetic retinopathy in a South Indian Type 2 diabetic population - the Chennai Urban Rural Epidemiology Study (CURES) Eye Study 4. Diabet Med. 2008;25(5):536-42.

16. Premalatha G, Anirudhan B, Mohan V, Sastry NG. Treadmill (Cardiac stress) test in the diagnosis of ischaemic heart disease in NIDDM patients: usefulness and safety. Int J Diab Develop Countr. 1995;15:3-6.

with special reference to family history, obesity and lifestyle factors - the Chennai Urban Population Study (CUPS 14). J Assoc Physicians India. 2003;51:771-7.

18. Wahab S, Mahmood N, Shaikh Z, Kazmi WH. Frequency of retinopathy in newly diagnosed type 2 diabetes patients. J Pak Med Assoc. 2008;58(10):557-61.

19. Abdollahi A, Malekmadani MH, Mansoori MR, Bostak A, Abbaszadeh MR, Mirshahi A. Prevalence of diabetic retinopathy in patients with newly diagnosed type II diabetes mellitus. Acta Medica Iranica. 2006;44(6):415-9.

20. Janand-Delenne B, Savin B, Habib G, Bory M, Vague P, Lassmann-Vague V. Silent myocardial ischemia in patients with diabetes: who to screen. Diabetes Care.

17. Mohan V, Shanthirani CS, Deepa R. Glucose intolerance 1999;22(9):1396-400. (diabetes and IGT) in a selected South Indian population ■■■■

Obese Kids as Young as 8 Show Signs of Heart Disease Some obese children as young as eight show significant signs of heart disease, according to research presented at the recently concluded American Heart Association’s Scientific Sessions in Orlando, Florida. Researchers compared 20 obese children and teenagers to 20 normal weight peers, and found that 40% of the obese children were considered at high-risk for heart disease because of thickened heart muscle which can interfere with the muscle’s pumping ability. Overall, obesity was linked to 27% more muscle mass in the left ventricle of their hearts and 12% thicker heart muscles - both signs of heart disease. Researchers warn that heart problems in youth may lead to even more severe disease in adulthood, and a higher likelihood of dying prematurely…

(ET Healthworld – AFP)

Hypertension, Respiratory Issues Among Major Health Problems in India One of the largest and first-of-its kind studies to assess ‘What Ails India’ has found that fever is the most common reason that leads patients to visit doctors. The study, based on analyses of 5,54,146 ailments reported in 2,04,912 patients’ visits has also revealed that hypertension is the most common diagnosis reported by physicians in India. This apart, respiratory problems are another major reason for visits to doctors. Other findings were that not all the sick visit a doctor, which means the burden of sick people in India is much higher. More males visited a doctor than females and this difference was greater in the pediatric age group, suggesting gender bias. Only 8% of the patients who visited a doctor were aged over 65, suggesting that old people do not visit a doctor as much as they should.… (The Indian Express)

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COMMUNITY MEDICINE

A Study of Effect of Oral Iron Therapy on Cognitive Function in Iron-deficient Adolescent Girls PRIYANKA MANDVE*, VIJAY M MOTGHARE†

ABSTRACT Aims and objectives: To study the effects of oral iron therapy on cognitive functions in iron-deficient adolescent girls. Material and methods: This study was carried out at a tertiary care teaching hospital in India. In this double-blind randomized placebocontrolled clinical trial, 50 iron-deficient adolescent school girls in the age group of 13-18 years fulfilling the criteria were selected.

After obtaining written consent, half received iron tablets and the half received placebo for 8 weeks. Hemoglobin and cognitive score was noted pre- and post-treatment. The statistical analysis was done using student t-test. Results: Baseline parameters were similar in iron and placebo-treated groups. At the end of 8 weeks, iron-treated group showed significant improvement in intelligence score and total cognitive function score (p < 0.05), other parameters showed improving trends although, not statistically significant. However, there was no significant improvement in the individual cognitive functions except attention concentration, which showed significant decrease (p < 0.05) in the placebo-treated group. Marked improvement in hemoglobin percentage (p < 0.001) was found in iron-treated group where as no such rise was observed in placebo-treated group. Conclusion: Iron supplementation improved hemoglobin as well as cognitive function in iron-deficient adolescent girls.

Keywords: Iron supplementation, hemoglobin, cognitive function, iron-deficient adolescent girls

I

ron deficiency anemia (IDA) is the most common nutritional deficiency in the world. The World Health Organization (WHO) estimates that worldwide, there are 2 billion individuals with anemia and up to 5 billion are iron-deficient.1

IDA is a systemic condition, which has many nonhematological consequences in addition to hematological ones. It impairs physical endurance, work capacity, infant growth and development and depresses immune function.

IDA is microcytic hypochromic anemia and the commonest cause of anemia in India. It is currently the most widespread micronutrient deficiency worldwide. Micronutrient deficiency is rightly referred as ‘Hidden hunger’, and is determining as well as the aggravating factor of health status and quality-of-life.2 Because of their greater physiologic requirements, combined with increased losses and poor dietary intake, those at highest risk of developing iron deficiency and IDA are infants, children and women of reproductive age, causing significant morbidity and mortality.

The risk of deficiency occurs during the time of rapid growth and nutritional demand especially age 6-24 months, adolescence and pregnancy. Adolescent girls and young women are still at high-risk of IDA because of increased iron demand during puberty, menstrual blood loss and limited dietary intake.

*Assistant Professor Dept. of Obstetrics and Gynecology, SVNGMC, Yavatmal, Maharashtra †Professor and Head Dept. of Pharmacology, SRTRGMCH, Ambejogai, Maharashtra Address for correspondence Dr Priyanka Mandve C/o: Mr Shivkumar Mandve Bilanpura, Achalpur, Amaravati - 444 806, Maharashtra E-mail: priyankamandve@yahoo.com

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Animal study models have revealed many mechanisms by which iron deficiency may affect cognition and these changes include change in brain iron content, distribution and neurotransmitter function.3 Decreased brain iron stores may impair the activity of iron-dependant enzymes necessary for synthesis, function and degradation of neurotransmitters such as dopamine, serotonin and noradrenaline.4,5 The body iron stores such as central nervous system (CNS) iron decreases, even before the red blood corpuscles production is affected by iron deficiency.

The changes in cognition and behavior may be independent of hemoglobin concentration e.g., Pica, is well-known manifestation of iron deficiency in which

COMMUNITY MEDICINE individual recovers soon after start of iron therapy.6,7 In addition, people who received iron for IDA commonly report improved memory, attention, mood and energy, before any improvement in hemoglobin indices are appearant.8

adolescent girls. It was reported that there is no difference in measurement of attention between the two groups, whereas the girls who received iron, showed improvement in assessment of recall, verbal learning and memory.

A number of observational studies have found that children who experience anemia early in life continued to demonstrate lower academic performances during their school age years, even after anemia has been corrected.9

Therefore, the present study was carried out to study effects of oral iron supplementation on attention, memory, learning and psychomotor functions in irondeficient state in the adolescent girls.

Hurtado (1999) examined the records of children who enrolled in special Supplemental Nutrition Program for women, infant and children before age of 5 years.10 Those who were anemic were more likely to experience academic problems at 10 years of age, compared to the children who were nonanemic at enrollment.

Concurrent iron status is also related to academic performances, as demonstrated in an investigation using data from 5,398 children aged 6-16 years from the National Health and Nutrition Examination Survey (NHANES) III survey in the United States.11 Halterman et al 2001, reported children with iron deficiency with and without anemia had lower score than children with normal iron status. These findings suggested that iron deficiency, even without anemia may place children at risk for cognitive delay.11 A Cochrane review in 2001 focused on randomized placebo-controlled clinical trials that had been conducted to examine the impact of iron therapy on development of children under the age of 3 years with iron deficiency.12 Among the five trials of short-term treatment, involving 180 children, iron therapy resulted in no difference on the childrenâ&#x20AC;&#x2122;s mental and motor performances.13 There were two trials on long-term therapy (over 30 days) involving 160 children. One study tested children 2 months after iron therapy was over and found no difference in the performance. The other study, conducted in Indonesia found that 4 months iron treatment produced an improvement in both mental and motor scores.14 The prevalence of iron deficiency in adolescent girls range from 9% to 40% depending on population studied and criteria used to define iron deficiency.

Ballin et al3 reported decreased lassitude, improved mood and ability to concentrate after iron administration. Bruner et al9 carried out cross-sectional placebo-controlled study on nonanemic iron-deficient

MATERIAL AND METHODS This study was carried out at a tertiary care teaching hospital in India. In this double-blind randomized placebo-controlled clinical trial, 50 iron-deficient adolescent school girls in the age group of 13-18 years having IDA (hemoglobin 8-10 gm%), without hemolytic or megaloblastic anemia, severe infection, neurological deficit were selected from a small high school near the medical center.

After obtaining written consent, 25 subjects received iron in the form of tablets (tablet ferrous sulfate 650 mg twice-daily) and another 25 subjects received identical placebo for 8 weeks. No other treatment was permitted during the trial period. The hemoglobin percentage (by autoanalyzer) and cognitive score was noted pre- and post-treatment.

Subject compliance with medication was assessed by asking subjects in nonjudgmental manner. A regular follow-up of the patients was done, by personally visiting the school every week.

The subjects had been enquired about any side effects in terms of nausea, vomiting, epigastric pain and passing of gray-colored stool. At the end of 8th week, hemoglobin and cognitive functions were tested using the same methods. A statistical analysis was done using student t-test.

RESULTS Out of 50 adolescent girls included in the study, one girl from placebo group and one girl from iron group could not complete the study and therefore there were 24 girls in each group. As shown in Table 1, maximum (64%) girls were in the age group of 14-15 years.

Tables 2 and 3 show that there was improvement in signs and symptoms in iron-treated group than placebo-treated group.

Table 4 and Figure 1 suggest that there was no significant improvement in individual cognitive functions in placebo-treated group except in attention

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COMMUNITY MEDICINE concentration, which showed significant decrease (p < 0.05). Table 4 and Figure 2 show significant improvement in intelligence score (p < 0.05) in irontreated group. Also other parameters show improving trends although not statistically significant.

hemoglobin percentage (p < 0.001). There is no such effect in placebo-treated group. The side effects in the iron-treated groups are summarized in Table 6. There were no side effects found in placebo-treated group.

Table 4 and Figure 3 imply that there was statistically significant improvement in total cognitive function score in iron-treated group (p < 0.05), whereas placebo group did not have significant effect.

Pre

Post

12 10 8 Score

It is clear from Table 5 and Figure 4 that iron consumption caused statistically significant rise in

6 4

Table 1. Age-wise Distribution of Subjects Age in years

2

No. of subjects (n = 50)

Percentage (%)

13-14

16

32

14-15

32

64

15-16

02

4

0

MB

AC

DR

VRD

VR

RC

IC

Figure 1. Comparison of cognitive function scores pre- and post-placebo therapy.

Table 2. Comparison of Signs and Symptoms Pre- and Post-iron Therapy Signs and symptoms

Pre-drug

Percentage (%)

Post-drug

Percentage (%)

Easy fatigability

24

100

10

41.66

Irritation

19

79.16

11

45.83

Palpitation

20

83.33

09

37.50

Percentage (%)

Post-drug

Percentage (%)

Table 3. Comparison of Signs and Symptoms Pre- and Post-placebo Therapy Signs and symptoms

Pre-drug

Easy fatigability

21

87.5

18

75

Irritation

08

33.33

08

33.33

Palpitation

21

87.5

18

75

Table 4. Comparison of Cognitive Function Scores Pre- and Post-iron and Placebo Therapy Tests

Placebo

Iron

Pre

Post

Pre

Post

MB

5.542 ± 1.141

5.5 ± 1.142

4.958 ± 1.967

5 ± 1.351

AC

11.29 ± 2.032

10 ± 2.396*

10 ± 2.265

10.08 ± 2.205

DR

8.5 ± 1.251

8.792 ± 1.02

8.458 ± 1.141

8.75 ± 1.073

VRD

7.958 ± 2.095

7.917 ± 2.32

7.417 ± 2.603

7.75 ± 2.723

VR

10.21 ± 3.092

11.17 ± 2.496

9.875 ± 3.288

10.75 ± 2.754

RC

9.542 ± 0.931

9.792 ± 0.4142

9.333 ± 1.049

9.542 ± 0.7211

IC

8.625 ± 3.987

9.125 ± 4.377

7.125 ± 3.627

9.25 ± 3.639*

Total

62.08 ± 7.667

61.42 ± 7.518

57.08 ± 8.256

61.5 ± 6.928*

*p < 0.05 MB = Mental balance; AC = Attention concentration; DR = Delayed recall; VRD = Visual recall of dissimilar pairs; VR = Visual retention; RC = Recognition; IC = Intelligence.

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COMMUNITY MEDICINE

Pre

Table 5. Comparison of Mean Hemoglobin Percentage Pre- and Post-iron and Placebo Therapy

Post

12

Placebo

10

Score

8 6 4

MB

AC

DR

VRD

VR

RC

IC

Figure 2. Comparison of cognitive function scores pre- and post-iron therapy.

Total score

Post

Pre

Post

24

24

24

24

Mean hemoglobin (%)

10.05 ± 0.5122

10.14 ± 0.7086

9.053 ± 0.9993

11.96 ± 0.7323**

Table 6. Side Effects in Iron-treated Group Side effects

No. of subjects

Percentage (%)

Black discoloration of stools

24

100 41.66

Abdominal discomfort

10

63

Nausea, vomiting

18

75

62

Constipation

2

8.33

No side effects

4

16.67

61 60 59

(No side effects were found in placebo-treated group).

58 57

work performance and exercise tolerance and impaired cognitive function.

56 55 54

Pre-test (Placebo)

Post-test (Placebo)

Pre-test (Iron)

Post-test (Iron)

Figure 3. Comparison of total values of cognitive functions in placebo- and iron-treated groups.

16

4 2 1

Although, the causative mechanism by which iron deficiency may alter brain functions has not been thoroughly defined, various theories have been proposed.9 It is reported that iron has multiple roles in neurotransmitter systems and may affect behavior through its effect on dopamine metabolism. Dopamine clearance has strong effects on attention, perception, memory, motivation and motor control.

The animal models show that iron deficiency is associated with changes in neurotransmitter synthesis, uptake and degradation, protein synthesis, oxidation, reduction and the electron transport.

8 Mean Hb (%)

Pre No. of subjects

**p < 0.001

2 0

Iron

Pre-Hb (Placebo)

Post-Hb (Placebo)

Pre-Hb (Iron)

Post-Hb (Iron)

Figure 4. Comparison of mean hemoglobin in both groups.

Another probable mechanism may be iron-induced increase in mean hemoglobin, leading to improve oxygen carrying capacity and improved brain function in general. The risk of deficiency occurs during the time of rapid growth and nutritional demand especially at the age of 6-24 months, adolescence and during pregnancy.

DISCUSSION

Therefore, the present study was carried out to understand the possible relation of cognitive functions in iron-deficient subjects after iron therapy.

Iron-deficient anemia is a highly prevalent nutritional disorder. It is a systemic condition, which has many nonhematological manifestations such as impaired immunity, decreased resistance to infection, lowered

As per Cochrane database, six trials, including 225 children with IDA, examined the effects of iron therapy on measures of psychomotor development and cognitive function within 30 days of commencement

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COMMUNITY MEDICINE of therapy. It was found that there is no convincing evidence that iron treatment of young children with IDA has an effect on psychomotor development or cognitive function within 30 days after commencement of therapy. The effect of long-term treatment remains unclear.12 Bruner et al found that in nonanemic irondeficient adolescent girls, iron supplementation improved verbal learning and memory.9 There are some reports which document the relation between iron status and cognition in premenopausal women.15-21 Iron status is a significant factor in cognitive performance in women of reproductive age. The severity of anemia primarily affects processing speed, and severity of iron deficiency affects accuracy of cognitive function over a broad range of tasks. Thus, the effects of iron deficiency on cognition are just not limited to the developing brain.22 Findings of present study are in contrast to Fordy and Benton,23 who found no correlation between low iron status and psychomotor functioning; this might be due to subtle effect of iron deficiency on cognitive function.

Greig et al, in the systematic meta-analyses found that there is a significant improvement in Arithmetic scores after treatment (p < 0.01), but no effect on Digit Symbol, Digit Span or Block Design. While an improvement in cognition after iron treatment was seen in seven out of 10 studies, the available evidence is limited by the poor study quality and heterogeneity across the studies.

Additional high-quality studies using consistent measures are warranted.24 One study25 showed an association between ferritin concentration and ECG asymmetry and another study26 observed change in urinary catecholamine in iron-deficient infants, which return to normal after iron treatment. Thus association between iron status and cognition is complex and further research in this direction is needed.

CONCLUSION The baseline parameters were similar in placebo and iron group at the beginning of trial. After iron treatment, individual cognitive score did not show statistically significant improvement except in case of intelligence, which showed statistically significant improvement.

After 8 weeks of iron therapy, total cognitive score as well as hemoglobin percentage improved significantly.

Placebo treatment neither showed any increment in hemoglobin percentage nor any improvement in

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individual or total cognitive function score. Therefore, it can be concluded that in the present study iron supplementation improved hemoglobin as well as cognitive function in iron-deficient adolescent girls.

REFERENCES 1. World Health Organization. The Prevalence of Anaemia in Women: A Tabulation of Available Information, 2nd Maternal Health and Safe Motherhood Programme.

WHO/MCH/MSM/92.2., Geneva, Switzerland: World Health Organization, 1992.

2. Bichile SK, Kumar V. Persistent iron deficiency anemia.

J Assoc Physicians India. 2002;50:617-8.

3. Ballin A, Berar M, Rubinstein U, Kleter Y, Hershkovitz A, Meytes D. Iron state in female adolescents. Am J Dis Child. 1992;146(7):803-5.

4. Ronald H. Disorders of iron metabolism and iron deficiency. In: Brittenham GM (Ed.). Haematology: Basic Principle and Practice, 2nd Edition. 472-522.

5. Dallman PR. Iron deficiency: does it matter? J Intern Med. 1989;226(5):367-72.

6. Fairbank V, Beutler E. Iron deficiency. In: Beutler E (Ed.).

Williams Haematology. 5th Edition, New York: McGrawHill; 1995: pp. 495.

7. Pollitt E, Leibel RL. Iron deficiency and behavior. J Pediatr.

1976;88(3):372-81.

8. Yehuda S, Youdim MB. Brain iron: a lesson from animal models. Am J Clin Nutr. 1989;50(3 Suppl):618-25; discussion 625-9.

9. Bruner AB, Joffe A, Duggan AK, Casella JF, Brandt J. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet. 1996;348(9033):992-6.

10. Hurtado EK, Claussen AH, Scott KG. Early childhood anemia and mild or moderate mental retardation. Am J Clin Nutr. 1999;69(1):115-9.

11. Halterman JS, Kaczorowski JM, Aligne CA, Auinger P, Szilagyi PG. Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States. Pediatrics. 2001;107(6):1381-6.

12. Black MM. Micronutrient deficiencies and cognitive functioning. J Nutr. 2003;133(11 Suppl 2):3927S-3931S. 13. Aukett MA, Parks YA, Scott PH, Wharton BA. Treatment with iron increases weight gain and psychomotor development. Arch Dis Child. 1986;61(9):849-57.

14. Idjradinata P, Pollitt E. Reversal of developmental delays in iron-deficient anaemic infants treated with iron. Lancet.

1993;341(8836):1-4.

15. Groner JA, Holtzman NA, Charney E, Mellits ED. A randomized trial of oral iron on tests of short-term memory and attention span in young pregnant women.

J Adolesc Health Care. 1986;7(1):44-8.

COMMUNITY MEDICINE 16. Kretsch MJ, Fong AK, Green MW, Johnson HL. Cognitive function, iron status, and hemoglobin concentration in obese dieting women. Eur J Clin Nutr. 1998;52(7):512-8.

17. Foley D, Hay DA, Mitchell RJ. Specific cognitive effects of mild iron deficiency and associations with blood polymorphisms in young adults. Ann Hum Biol.

1986;13(5):417-25.

18. McMahon LP, Mason K, Skinner SL, Burge CM, Grigg LE, Becker GJ. Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure. Nephrol Dial Transplant. 2000;15(9):1425-30.

19. Stivelman JC. Benefits of anaemia treatment on cognitive function. Nephrol Dial Transplant. 2000;15 Suppl 3:29-35.

20. Temple RM, Langan SJ, Deary IJ, Winney RJ. Recombinant erythropoietin improves cognitive function in chronic haemodialysis patients. Nephrol Dial Transplant.

1992;7(3):240-5.

maintained on chronic ambulatory peritoneal dialysis.

Nephrol Dial Transplant. 1995;10(9):1733-8.

22. Murray-Kolb LE, Beard JL. Iron treatment normalizes cognitive functioning in young women. Am J Clin Nutr.

2007;85(3):778-87.

23. Fordy J, Benton D. Does low iron status influence psychological functioning? J Hum Netr Diet. 1994;7: 127-33.

24. Greig AJ, Patterson AJ, Collins CE, Chalmers KA. Iron deficiency, cognition, mental health and fatigue in women of childbearing age: a systematic review. J Nutr Sci. 2013;2:e14.

25. Tucker DM, Sandstead HH, Swenson RA, Sawler BG, Penland JG. Longitudinal study of brain function and depletion of iron stores in individual subjects. Physiol Behav. 1982;29(4):737-40.

26. Voorhess ML, Stuart MJ, Stockman JA, Oski FA. Iron deficiency anemia and increased urinary norepinephrine 21. Temple RM, Deary IJ, Winney RJ. Recombinant excretion. J Pediatr. 1975;86(4):542-7. erythropoietin improves cognitive function in patients ■■■■

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Guidelines on Health Keep your blood cholesterol less than 160 mg%. Even 1% reduction in cholesterol reduces the chances of heart attack by 2%.

Uncontrolled diabetes and blood pressure can precipitate a heart attack. Keep these under check.

Eat less, walk more.

Regular exercise is good for health. The best exercise is ‘walking’, which is a brisker than brisk walking.

Soya products are good for health. These should form an essential ingredient of the diet.

Fruits are better than juices.

Brown rice is better than polished rice and jaggery is better than white sugar.

Eat high fiber diet.

Driving and drinking do not go together.

Pregnant women must not drink. It harms the baby in the womb.

Get your health check-up done at least once in a year.

Salt intake should be restricted.

Avoid APC where A stands for achar, P for papad and C for chutney.

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DENTISTRY

Clinical Efficacy of Bioactive Glass-containing Dentifrice: A 3-month Controlled Study MEERA H GOHIL*, SHARMILA VERMA†, GEETA SINGH BHADURIA‡

ABSTRACT Objective: To evaluate the antigingivitis and anti-plaque effects of a dentifrice-containing bioactive glass compared with a placebo control dentifrice in 12 weeks. Study design: It was a randomized, double-blinded, controlled clinical study. Twenty patients took part in the study and were matched for plaque index (PI), bleeding index (BI), gingival index (GI). The subjects received a supragingival scaling to remove all plaque, calculus and extrinsic stain and instructed to brush with their assigned dentifrice and toothbrush. The PI and BI & GI were determined at the baseline and at 12 weeks. The data were analyzed using a repeated-measures ANOVA conducted on the two dependent measures to compare the effect between two groups. Results: The PI, BI and GI were significantly reduced, respectively, over the 12 weeks period in the test group. There was a reduction in plaque growth. There was no difference of the PI and GI over the 12-week period in the control group. Conclusion: This study demonstrated that a dentifrice containing bioactive glass significantly improves oral health as measured by a reduction in bleeding and reduction in supragingival plaque compared with a control dentifrice over the 3 months study period.

Keywords: Gingivitis, bioactive glass, anti-plaque

D

ental plaque is the main etiologic factor of periodontal disease. Gingivitis is the earliest form of periodontal disease. Maintenance of gingival health is critical in preventing gingivitis and its progression into periodontal disease. Periodontal diseases are chronic infectious diseases of periodontal tissues. Plaque-induced gingivitis is one of the most common forms of periodontal disease.1

One of the primary causative factors in the development of gingivitis is inadequately controlled supragingival plaque. The two most important prevalent diseases of periodontium are plaque-induced gingivitis, a reversible condition and chronic periodontitis, an irreversible condition that can lead to tooth loss. Best approach to manage periodontal disease is prevention

*BDS and PG Student Dept. of Periodontics †Professor and Head Dept. of Periodontics ‡Senior Lecturer KM Shah Dental College and Hospital Sumandeep Vidhyapeeth University, Vadodara, Gujarat Address for correspondence Dr Meera H Gohil M-9, Doctors Quarters, Dhanvantari Campus Jail Road, Vadodara - 390 001, Gujarat E-mail: meeragohil5040@gmail.com

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Indian Journal of Clinical Practice, Vol. 26, No. 6, November 2015

followed by early detection and treatment. Plaqueinduced gingivitis can be prevented with good oral hygiene. This includes regular tooth brushing and flossing of teeth and periodic professional cleaning to prevent build-up of plaque and calculus.

Tooth brushing with dentifrices is the most widely used method of home dental care for prevention of periodontal diseases. Owing to the established relationship between bacteria, plaque and gingivitis, a major focus in the treatment of gingivitis in recent years has been the development and use of various antimicrobial therapies.2,3 Bioactive glasses have been used in bone and tissue regeneration for over 15 years.4,5 Recently antimicrobial properties inherently, in these materials have been described.6 One of their compositions has recently been formulated into a dentifrice and has demonstrated strong antimicrobial behavior in vitro.7 While the exact mechanisms of the antimicrobial activity have not yet been fully established, it is likely that the high rate of ionic release and local changes in oral pH seem to play a major role.

This clinical study was designed to evaluate the efficacy of bioactive glass-containing agent and triclosancontaining toothpaste for reducing gingivitis.

DENTISTRY MATERIAL AND METHODS The study was a randomized, double-blind clinical study, comparing bioactive glass-containing agent and triclosan-containing dentifrice for reducing gingivitis.

The protocol for the study was reviewed and approved by the Ethical Committee of Sumandeep Vidhyapeeth University. All volunteers provided written informed consent for participation in the study. Twenty volunteers took part in study. The inclusion criteria required patients between 18 to 65 years of age, in good general health, with chronic generalized gingivitis, with a minimum of 20 natural permanent teeth. Exclusion criteria included patients who received antibiotics or anti-inflammatory therapy within 6 months of the baseline examination or were on long-term antibiotic or anti-inflammatory therapy, patients who had periodontal pockets, no deep dental caries and restored teeth, pregnant or lactating women and patients with removable dentures (partial or full). Period of study was 3 months.

The Silness and Loe 1967 plaque index (PI) was used in this study. An average plaque score was calculated for each patient by summing the individual plaque scores for each tooth and dividing by the total number of sites scored for each subject. Gingival index (GI) (Loe and Silness 1967) and Modified Sulcular bleeding index (MSBI) was calculated for all teeth of each subject by summing the individual BI scores and dividing that sum by the number of sites graded for each subject.

These measurements were conducted at baseline and at 3 months recall visits.

Scaling was done and after that patient was provided by the tooth paste. Test group paste-containing bioactive glass and control group paste-containing triclosan.

In order to avoid bias on the part of the investigator and the patients, a control, double-blind, randomized study was used, where neither the scorer of the pain who examined the patients nor the patient himself was aware of the solutionâ&#x20AC;&#x2122;s name. Both selected paste was placed in bottles and coded with letters A and B by person who was not associated with the present clinical study.

RESULTS Once the project was over, paste was decoded. A total of 20 patients were took part in the study, 10 in case group and 10 in control group. Group A (Test group) was given dentifrices having bioactive glass-containing agent and Group B was given dentifrices having triclosan-containing agents. The demographic data for the patients shown in Table 1.

At degree of freedom 9, calculated t value of Group A is 7.87, which is much higher than table value of t at 0.001 that is 4.78. Change in GI in Group A by chance is <0.001, p < 0.0001. So, difference observed in Group A in GI is highly significant. Difference observed in Group B in GI is not significant (Table 2 and Fig. 1).

At degree of freedom 9, calculated t value of Group A is 6.34, which is much higher than table value of t at 0.001 that is 4.78. Change in PI in Group A by chance is <0.001, p < 0.0001. So, difference observed in Group A in PI is highly significant. Difference observed in Group B in PI is not significant (Table 3 and Fig. 2).

Table 1. Demographic Data Group A (n = 10)

Group B (n = 10)

Female

4

2

Male

6

8

23.1 years

25 years

Age (mean)

Table 2. Effects on Gingival Index at Two Time Periods (Mean and T value) Group A

Group B

2.57

1.91

12th week

1.11

1.14

Mean difference

1.46

0.77

T value

7.87

0.000

1st week

3 2.5

Baseline

1.91

2 1.5

12th week

2.57

1.41

1.11

1 0.5 0

Group B

Group A

Figure 1. Effects on gingival index at baseline and after 12 weeks.

Table 3. Effects on Plaque Index at Two Time Periods (Mean and T value) Group A

Group B

1st week

2.02

1.91

12th week

1.19

1.14

Mean difference

0.83

0.77

T value

6.34

0.000

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DENTISTRY Baseline

3

12th week

2.5 2.02

2 1.5

1.91 1.19

1.14

1 0.5 0

Group B

Group A

Figure 2. Effects on plaque index at baseline and after 12 weeks.

Table 4. Effects on Bleeding Index at Two Time Periods (Mean and T value) Group A

Group B

1st week

2.64

1.90

12th week

1.25

1.17

Mean difference

1.39

0.73

T value

2.53

0.000

Baseline

3 2.5

12th week

2.64 1.90

2 1.5

1.25

1.17

1 0.5 0

Group A

Group B

Figure 3. Effects on bleeding index at baseline and after 12 weeks.

At degree of freedom 9, calculated t value of Group A is 6.34, which is much higher than table value of t at 0.05 that is 2.26. Change in BI in Group A by chance is <0.05, p < 0.05. So, difference observed in Group A in BI is highly significant. Difference observed in Group B in BI is not significant (Table 4 and Fig. 3).

DISCUSSION The purpose of this clinical study was to evaluate the effect of a new bioactive glass-containing dentifrice on the gingival health of an adult population with moderate gingivitis. The material was incorporated into a nonaqueous dentifrice formulation without fluoride and contained 5% by weight of the bioactive

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glass. Mechanical control of dental plaque has been clearly shown to retard the advance of gingivitis and periodontal disease.8 Axelsson and Lindhe8 reported that noncompliant patients exhibited signs of recurrent disease processes. Owing to the inconsistency of simple mechanical control of plaque accumulation, a number of chemotherapeutic agents have been incorporated into home use products to control plaque and gingivitis.

These agents have generally been incorporated into either mouthrinses or toothpastes. The main action of these agents has been focused on their antimicrobial action. There have been a number of active ingredients incorporated into various dentifrices. Triclosan/copolymer dentifrices with or without zinc citrate have been studied extensively for their antiplaque and antigingivitis effectiveness.

More recently, Archila et al9 compared a stabilized stannous fluoride/sodium hexametaphosphate dentifrice with a triclosan-containing dentifrice as a control and found that the experimental group had statistically significantly less gingivitis and less bleeding than the control group. Mankodi et al10 published work on a 6-month clinical trial with a stabilized 0.454% stannous fluoride/sodium hexametaphosphate dentifrice and showed a 21.7% reduction in gingivitis, 57.1% reduction in GBI and 6.9% less plaque versus a fluoride dentifrice.

Tricolsan is a phenolic agent comprised of bisphenol and a nonionic germicide.11 Lindhe et al12 reported on the results of a 6-month clinical trial comparing a triclosan/ co-polymer dentifrice with a fluoride-containing dentifrice and found that the triclosan group had more plaque reduction and resolution of gingivitis than the regular fluoride dentifrice group. Studies including long-term clinical trials,13 short-term experimental gingivitis models14 and short-term randomized clinical studies15 have demonstrated significant reductions in plaque and gingivitis from about 20% to as high as 60%.

Although bioactive glasses have been used in bone regenerative surgeries for over 15 years, it is only recently that the inherent antimicrobial properties of these materials have been studied. Stoor et al,6 first published results of exposure of planktonic organisms known to be involved in the progression of gingivitis and periodontitis to particulate bioactive glass compositions. In these studies, it was found that exposure of a 40% solution of bioactive glass to the cultures for 10 minutes resulted in a 3 log reduction in Actinobacillus actinomycetemcomitans and total loss of viability of the organism with a 60 minutes exposure.

DENTISTRY Similar results were found in Porphyromonas gingivalis.

Actinomyces naeslundii lost total viability in a 10 minutes exposure to the bioactive glass as did Streptococcus mutans. Allan et al16 using particulates of bioactive glass with a size range from 300 to 500 mm, showed an antibacterial effect against S. mutans, Streptococcus sanguis, P. gingivalis, Fusobacterium nucleatum, A. actinomycetemcomitans and Prevotella intermedia with a 1-hour exposure to the particulates. The percentage kill ranged from 51% against S. mutans to 100% kill of P. intermedia. Allan ascribed much of the effect of the bacterial kill to an increase in pH of the bioactive glass in solution, although it appears that the release of large quantities of calcium from the bioactive glass might also play a role in the observed behavior towards the microbes.

The results of the current study demonstrated a significant reduction in gingivitis in a relatively short period of time. There were no adverse events reported with the use of the material. Further clinical studies are required to determine the long-term effectiveness of this new compound.

REFERENCES

bioactive glass in the treatment of periodontal osseous defects in humans. J Periodontol. 1998;69(9):1027-35.

6. Stoor P, Söderling E, Salonen JI. Antibacterial effects of a bioactive glass paste on oral microorganisms. Acta Odontol Scand. 1998;56(3):161-5.

7. Greenspan DC, Clark A, LaTorre GP. In vitro antimicrobial properties of a bioactive glass (NovaMin) containing dentifrice. J Dent Res. 2004;83:1586.

8. Axelsson P, Lindhe J. The significance of maintenance care in the treatment of periodontal disease. J Clin Periodontol. 1981;8(4):281-94.

9. Archila L, Bartizek RD, Winston JL, Biesbrock AR, McClanahan SF, He T. The comparative efficacy of stabilized stannous fluoride/sodium hexametaphosphate dentifrice and sodium fluoride/triclosan/copolymer dentifrice for the control of gingivitis: a 6-month randomized clinical study.

J Periodontol. 2004;75(12):1592-9.

10. Mankodi S, Bartizek RD, Winston JL, Biesbrock AR, McClanahan SF, He T. Anti-gingivitis efficacy of a stabilized 0.454% stannous fluoride/sodium hexametaphosphate dentifrice. J Clin Periodontol. 2005;32(1):75-80.

11. DeVizio W, Davies R. Rationale for the daily use of a dentifrice containing triclosan in the maintenance of oral health. Compend Contin Educ Dent. 2004;25(7 Suppl 1): 54-7.

1. AAP Position Paper. Parameter on plaque-induced gingivitis. J Periodontol. 2000;71:851-2.

12. Lindhe J, Rosling B, Socransky SS, Volpe AR. The effect of a triclosan-containing dentifrice on established plaque and gingivitis. J Clin Periodontol. 1993;20(5):327-34.

2. Clavero J, Baca P, Junco P, González MP. Effects of 0.2% chlorhexidine spray applied once or twice daily on plaque accumulation and gingival inflammation in a geriatric population. J Clin Periodontol. 2003;30(9):773-7.

13. Rosling B, Dahlén G, Volpe A, Furuichi Y, Ramberg P, Lindhe J. Effect of triclosan on the subgingival microbiota of periodontitis-susceptible subjects. J Clin Periodontol.

1997;24(12):881-7.

3. Santos S, Herrera D, López E, O’Connor A, González I, Sanz M. A randomized clinical trial on the short-term clinical and microbiological effects of the adjunctive use of a 0.05% chlorhexidine mouth rinse for patients in supportive periodontal care. J Clin Periodontol.

2004;31(1):45-51.

14. Nogueira-Filho GR, Toledo S, Cury JA. Effect of 3 dentifrices containing triclosan and various additives.

An experimental gingivitis study. J Clin Periodontol.

2000;27(7):494-8.

4. Wilson J, Clark AE, Hall M, Hench LL. Tissue response to Bioglass endosseous ridge maintenance implants. J Oral Implantol. 1993;19(4):295-302.

15. Volpe AR, Petrone ME, Prencipe M, DeVizio W. The efficacy of a dentifrice with caries, plaque, gingivitis, tooth whitening and oral malodor benefits. J Clin Dent.

2002;13(2):55-8.

16. Allan I, Newman H, Wilson M. Antibacterial activity 5. Lovelace TB, Mellonig JT, Meffert RM, Jones AA, of particulate bioglass against supra- and subgingival Nummikoski PV, Cochran DL. Clinical evaluation of bacteria. Biomaterials. 2001;22(12):1683-7.

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DERMATOLOGY

Erythroderma Secondary to Herbal Medicine KH BASAVARAJ*, ARCHANA MEKA*

ABSTRACT Erythroderma is a definitive term that refers to a scaling erythematous dermatitis involving 90% or more of the cutaneous surface.

Exfoliative dermatitis is characterized by erythema and scaling involving the skinâ&#x20AC;&#x2122;s surface and often obscures the primary lesions that are important clues to understanding the evolution of the disease. Clinicians are challenged to find the cause of exfoliative dermatitis by eliciting the history of illness prior to erythema and scaling, by probing with biopsies and by performing blood studies. Erythroderma is a potentially fatal dermatologic emergency that is often mistaken for infection. Indeed, the fact that it is difficult to diagnose is the main contributor to its significant mortality rate, as treatment is readily available.

We present a case of a 46-year-old man who was incorrectly diagnosed and treated for months. We review the etiologies, initial work-up and management of this disease. In our case, the patient was ill, had lost 10.4 kg and developed systemic inflammatory response syndrome. Without proper treatment he was at risk of developing full-blown sepsis. Although, there are many causes of erythroderma, prompt initial treatment directed at the underlying etiology typically results in a rapid remission.

Keywords: Erythematous dermatitis, exfoliative dermatitis, primary lesions, dermatologic emergency

E

rythroderma or exfoliative dermatitis is an erythematous, scaly dermatitis involving most, if not all, of the skin. This generalized scaling eruption of the skin is drug-induced, idiopathic or secondary to underlying cutaneous or systemic disease.

Appreciation for this condition requires an understanding of the skinâ&#x20AC;&#x2122;s normal epithelial layer. Normal epidermis has a continual turnover of epithelial cells. Cell division occurs near the basal layer. As cells move toward the periphery, they become well keratinized. This process requires approximately 10-12 days. Cells subsequently remain in the stratum corneum for another 12-14 days prior to being sloughed off. In exfoliative dermatitis, the mitotic rate in the basal layer increases and overall transit time decreases; therefore, more cells are lost from the surface. The mechanism responsible for this is not known, although an immunologic basis has been suggested.

Exfoliative dermatitis may occur in response to drug therapy, systemic disease or an idiopathic entity. As many as 40% of cases involve pre-existing cutaneous disease. Approximately 10% of cases are the result of drug reactions. As many as 40% are caused by underlying systemic disease. The remaining cases are

*Dept. of Dermatology, Venerelogy and Leprosy JSS Medical College, JSS University, Mysore, Karnataka

idiopathic. Histopathologic patterns observed for druginduced and idiopathic causes of exfoliative dermatitis are nonspecific. Biopsy findings in individuals with pre-existing cutaneous or systemic disease during an exfoliative stage may reveal, inconsistently, the underlying skin lesion or pathology. Through multiplebiopsy histologic analysis, the diagnosis may be confirmed in as many as 45% of patients.

There is a paucity of information on erythroderma in India. The growing increase in use of herbal medicines, the HIV epidemic, hospital visits in advanced disease stages and limited investigational resources in Third World environments â&#x20AC;&#x201C; all exacerbate the life-threatening nature of this condition. With increasing use of herbal and nonherbal medicines, more individuals are at risk of contracting erythroderma.

CASE REPORT A 46-year-old male presented with diffuse scaly lesions all over the body since 1 week. He presented with redness of skin for 5 days and fever for 2 days.

Patient initially presented with flat, whitish scaly lesions over the chest and scalp 1 week before admission. Two days later, lesions progressed in their distribution to involve the entire chest, abdomen and back. The lesions gradually spread to involve the arms, and lastly legs over the next few days (Figs. 1-6). The patient was a known case of psoriasis since 14 years with seasonal exacerbations.

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Figure 1. Scaly lesions over soles.

Figure 2. Exacerbation of scaly lesions over soles.

Figure 3. Scaly lesions over palms and soles.

Figure 4. Exacerbation of the lesions over palms and soles.

Redness of skin initially involved the trunk, which progressed to the arms and legs the following day.

Patient developed fever 2 days prior to admission, which was predominant in the evenings. He had no history of associated chills, rigors, diarrhea, vomiting or headache. One day prior to the onset of lesions, he received treatment in the form of herbal oil massage and oral medication. Following which, there was sudden exacerbation of skin lesions all over the body.

He was febrile and pale with pedal edema. Cutaneous examination revealed diffuse erythema, edema with loosely adherent scales distributed all over the body.

These lesions were diffuse in distributed all over the body sparing periorbital and nasal area of face.

Erythematous scaly papules and plaques were seen over soles. Sparse hair with multiple scaly plaques

were noted over scalp. Pitting of nails was observed on the second and the third fingers of the right hand.

Investigations revealed normal blood counts with altered A:G ratio (2.41). Liver enzymes (AST and ALP) were increased. Urine examination was normal. Skin biopsy results were nonspecific.

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Patient was started on intravenous antibiotics, antihistamines, saline compresses, topical corticosteroids and advised to take high protein diet (two egg whites, three glasses of milk, three cups of curd-distributed over the day, vegetable preparations, salads including sprouts, thick dal with rice for lunch and dinner, and sprouts, pulses and dry fruits as morning and evening snacks). Patient was afebrile 2 days following treatment and lesions regressed significantly by the fifth day of admission.

DERMATOLOGY ÂÂ

Maintain skin moisture with wet wraps, other types of wet dressings, emollients and mild topical steroids

ÂÂ

Antibiotics if secondary infection is present

ÂÂ

Antihistamines for severe itch.

If a cause can be identified then specific treatment should be started e.g., topical steroids for atopic dermatitis; acitretin or methotrexate for psoriasis.

Figure 5. Scaly lesions over trunk and upper limbs.

Figure 6. Scaly lesions over back.

Prognosis of erythroderma depends on the underlying disease process. If the cause can be removed or corrected then prognosis is generally very good.

If erythroderma is the result of a generalized spread of a primary skin disorder such as psoriasis or dermatitis, it usually clears with appropriate treatment of the skin disease but may recur at any time. The course of idiopathic erythroderma is unpredictable. It may persist for a long time with periods of acute exacerbation.

Patients presenting acutely with exfoliative dermatitis often require admission for inpatient management because their total body functions (including intake and output) can require monitoring. Hospital admission should be seriously considered in pediatric patients who present with erythroderma and fever because this presentation is a predictor of hypotension and even toxic shock syndrome. The principle of management is to maintain skin moisture, avoid scratching, avoid precipitating factors, apply topical steroids, and treat the underlying cause and complications.

Exfoliative dermatitis commonly resists therapy until the underlying disease is treated (e.g., phototherapy, systemic medications in psoriasis). Outcome is unpredictable in idiopathic exfoliative dermatitis.

The course is marked by multiple exacerbations, and prolonged glucocorticoid therapy often is needed. ÂÂ

Discontinue all unnecessary medications. Carefully monitor and control fluid intake, since patients can dehydrate or go into cardiac failure; monitor body temperature, since patients may become hypothermic.

ÂÂ

Apply tap water-wet dressings (made from heavy mesh gauze); change every 2-3 hours.

Apply intermediate-strength topical steroids (e.g., triamcinolone cream 0.025-0.5%) beneath wet dressings. Suggest a tepid bath (may be comforting) once or more daily between dressing changes. Reduce frequency of dressings and gradually introduce emollients between dressing applications as exfoliative dermatitis improves.

DISCUSSION The underlying cause of erythroderma should be established if possible. Skin biopsies may or may not be helpful. Erythroderma is a serious disease and most patients require hospitalization to restore fluid and electrolyte balance, circulatory status and body temperature.

The following general measures apply: ÂÂ

Discontinue all unnecessary medications

ÂÂ

Monitor fluid balance and body temperature

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DERMATOLOGY ÂÂ

Institute systemic antibiotics if signs of secondary infection are observed. Antihistamines help reduce pruritus and provide needed sedation.

ÂÂ

Systemic steroids may be helpful in some cases but should be avoided in suspected cases of psoriasis and staphylococcal scalded skin syndrome.

ÂÂ

Increased capillary permeability occasionally is severe enough to justify plasma infusion.

ÂÂ

Pre-existing malnutrition may become more marked and require nutritional intervention in older patients.

Ensure adequate nutrition with emphasis on protein intake, since exfoliative dermatitis patients lose a lot of protein through excessive desquamation and show a tendency toward hypoalbuminemia. Alter diet as necessary if ingestion of a certain food group is suspected as the etiology of exfoliative dermatitis.

CONCLUSION Erythroderma is a complex disorder whose prognosis depends on the etiologic cause. Virtually all cases of drug-induced erythroderma recover completely with prompt initial management and removal of the offending drug. However, erythroderma can often be clinically mistaken for other presentations, such as an infection, leading to higher mortality rates especially in

the very young and elderly. The attending emergency physician should always consider a broad differential diagnosis when assessing a patient with possible erythroderma. Individualized treatment based on the underlying etiologic cause should be combined with supportive skin care to ensure optimal outcomes.

In summary, erythroderma is one of the true dermatologic medical emergencies. Importantly, treatments must be evaluated based on acuity of disease and patient’s comorbidities.

SUGGESTED READING 1. Kimgai-Asadi A, Freedberg IM. Exfoliative dermatitis. In: Freedberg IM, Eisen AZ, Wolff K, et al (Eds.). Fitzpatrick’s Dermatology in General Medicine. 6th Edition, New York: McGraw-Hill; 2003:pp.436-41.

2. Busia K. Medical provision in Africa. Phyother Res. 2005;19:919-23.

3. Ferrante P, Delbue S, Mancuso R. The manifestation of AIDS in Africa: An epidemiological overview.

J Neurovirol. 2005;11:50-7.

4. Rym BM, Mourad M, Bechir Z, Dalenda E, Faika C, Iadh AM, et al. Erythroderma in adults: a report of 80 cases. Int J Dermatol. 2005;44:731-5.

5. Hulmani M, Nandakishore B, Bhat MR, Sukumar D, Martis J, Kamath G, et al. Clinico-etiological study of 30 erythroderma cases from tertiary center in South India.

Indian Dermatol Online J. 2014;5:25-9.

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Traditional Disease-related Factors Predict CV Risk in Psoriatic Arthritis Thirty Percent with PsA have a CV Event by Age 80 Both traditional cardiovascular (CV) risk factors and elevated disease activity explain the increased incidence of CV events in patients with psoriatic arthritis (PsA), Canadian researchers have found.

In their cohort analysis with 35 years of follow-up, predictors of major CV events were hypertension, diabetes, and the number of dactylitic digits, prompting the authors to conclude that “the risk of developing CV events was explained in part by traditional CV risk factors; however, the level of disease activity and the extent of systemic inflammation were independent predictors of CV events.”

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DERMATOLOGY

Netherton Syndrome: A Report of Two Cases BK BRAR*, NEERJA PURI†, BB MAHAJAN‡, GURMET SETHI#

ABSTRACT Nethertons syndrome is a rare autosomal recessive disease associated with variable expressions: Congenital ichthyosiform erythroderma, ichthyosis linearis circumflex, specific hair shaft defects (trichorrhexis invaginata) and atopic diathesis. We report a case of two brothers- one 3-year-old and the younger one aged 8 months presenting with an ichthyosiform eruption with generalized, polycyclic erythematous plaques with fine double-edged scaling. Repeated microscopy of the scalp hair revealed typical trichorrhexis invaginata.

Keywords: Nethertons syndrome, autosomal recessive disease, ichthyosiform eruption, polycyclic erythematous plaques, trichorrhexis invaginata

N

etherton syndrome is a rare and severe autosomal recessive disorder1 characterized by congenital ichthyosis, a specific hair shaft defect (trichorrhexis invaginata) and atopic manifestations. Infants with this syndrome often fail to thrive; life-threatening complications result in high postnatal mortality. At birth, infants exhibit generalized erythroderma2 and scaling, which may persist into childhood or may change to ichthyosis linearis circumflexa,3 consisting of migratory erythematous and scaling plaques with a double-edged scale. Scaly hair is sparse and brittle and examination by microscopy indicates that the hair has nodes (trichorrhexis invaginata or ‘bamboo hair’)4 resulting from the invagination of the distal part of the hair shaft to its proximal part. Expression of trichorrhexis invaginata is delayed and may be variable. As a result, the diagnosis of Netherton syndrome in early childhood is difficult and the first tentative diagnosis may mistake Netherton syndrome for other congenital ichthyosiform erythrodermas. Atopic manifestations are present in most instances of Netherton syndrome, including eczematous rashes, asthma, angioedema, hay fever, urticaria, high immunoglobulin E (IgE) levels in the

*Assistant Professor †Registrar ‡Associate Professor and Head Dept. of Dermatology #Professor and Head, Dept. of Pediatrics GGS Medical College and Hospital, Faridkot, Punjab Address for correspondence

Dr Neerja Puri C/o: Asha Puri H. No. 626, Urban Estate, Dugri Road, Ludhiana - 141 002, Punjab E-mail: neerajaashu@rediffmail.com

serum and hypereosinophilia, all nonspecific features.

Failure to thrive in infancy is frequent; the prognosis is poor, because infants experience hypernatremic dehydration5,6 and recurrent infections. A number of associated findings have also been reported, including severe enteropathy with villous atrophy, renal failure, aminoaciduria7 and growth retardation.

CASE REPORTS

Case 1 We report a case of 3-year-old male child of first birth order, who presented with multiple itchy erythematous scaly plaques on the scalp, face, axilla (Fig. 1) and flexor aspects of lower limbs since 3 years.

The history of the patient dated back to 3 years when the patient was delivered by a full-term normal vaginal delivery. Neither the parents of the boy nor the close relatives had any atopic manifestation or skin disease. Eight days after birth, patient developed itchy, erythematous papular lesions on the thighs, which gradually increased in number and extended on to the face, ears, axilla and upper limbs and evolved into plaques in a period of 2 weeks, which gradually progressed to erythroderma and scaling. The milestones of the child were delayed (Fig. 2). Soon a bilateral recurrent otitis media appeared presenting as discharge from both the ears. The whole skin gradually appeared erythrodermic with extensive scaling. The child also showed palmoplantar keratoderma (Fig. 3).

Because of the poor weight gain and recurrent otitis media, an immunodeficiency was suspected. Although immunoglobulins were in the normal range, there were slightly elevated specific IgE against egg white

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DERMATOLOGY

Figure 3. Palmoplantar keratoderma in a 3-year-old child.

Figure 1. Erythematous scaly lesions with hyperkeratosis in the axilla.

Figure 4. Photomicrograph showing thick granular layer with psoriasiform epidermal hyperplasia (H&E stain 100x).

Case 2

Figure 2. Stunted growth in a 3-year-old male child.

and against cow milk. History of frequent chest infections was present. Scalp examination revealed diffuse, scaling, brittle hair. Skin biopsy of the child revealed the following findings (Fig. 4). Confluent parakeratosis with thick granular layer and epidermal hyperplasia was noted. Granular layer was prominent.

Psoriasiform epidermal hyperplasia was noted. Sparse lymphohistiocytic infiltrate was present.

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Indian Journal of Clinical Practice, Vol. 26, No. 6, November 2015

The second case report is of an 8-month-old male child of second birth order. The child had scaly erythroderma at birth. The boy was a product of full term normal vaginal delivery. The whole skin gradually appeared erythrodermic with extensive scaling (Fig. 5) and a hypernatremic dehydration developed as well. The patient was treated with different locally applied steroids, a hypoallergenic diet, parenteral rehydration and antibiotics. As the results of the treatment were not encouraging, the mother decided to take the boy home.

During the subsequent follow-up of the child at the age of 18 months, there were numerous partly confluent gyrate lesions with double scaling on the skin of the entire body. Lichenification of the flexural areas, which is a symptom of atopic dermatitis also became evident.

Total IgE levels were elevated and allergy to house mite and grass pollen was found. The light microscopy of the hair of the child revealed trichorrhexis invaginata.

DISCUSSION Netherton syndrome is a rare autosomal recessive genodermatosis8 with erythroderma along with

DERMATOLOGY feeding difficulties and childhood infections. There is currently no cure for the disorder, but the symptoms may be relieved. In the neonatal period, the body’s salt and water balance needs to be monitored as the child may be dehydrated from the loss of water through the thin skin or from diarrhea and vomiting. The skin should be lubricated several times every day with a cream containing petroleum jelly and paraffin. Other therapies include topical steroids, tars, PUVA and oral vitamin A derivatives with moderate and temporary effects.11 Figure 5. Close-up view of trunk and thighs in an 8-monthold child.

hypernatremic dehydration and failure to thrive during the first months of life. The specificity of clinical and histopathological features is low in neonates so that it usually takes a long period before the final diagnosis is established. In the second year of life in patients with Netherton syndrome, erythroderma slowly disappears and migratory gyrate lesions with double edged scaling become evident. In patients with Netherton syndrome, atopy is usually manifested as angioedema, allergic, arthous urticaria and elevated IgE.9 Hair shaft abnormalities10 on patients’ scalp are manifested as trichorrhexis invaginata, pili torti and/or trichorrhexis nodosa. But the identification of these hair shaft abnormalities can be difficult because not all hairs show the particular finding, termed ‘bamboo’ nodes.

In some cases, sparsity of hair makes the examination deficient. However, all the hair is not necessarily affected and the characteristic swollen nodes may be absent at birth. It is therefore advisable to examine hair from different parts of the head and to repeat the examination from time to time during the first few months of the infant’s life. Histologically, combined characteristics of both psoriasis and atopic dermatitis are expressed in patients with Netherton syndrome, which makes a correct diagnosis difficult. Patients with Netherton syndrome may suffer from gastrointestinal involvement, which could be the reason for a dystrophy and poor weight gain in early childhood of our patient.

Netherton syndrome is an extremely rare condition, and for a long time it was often misdiagnosed owing to lack of knowledge and experience in the medical fraternity. In the past, children with the syndrome were mistakenly diagnosed with acrodermatitis enteropathica (Zinc deficiency) or erythrodermic eczema. Children with Netherton syndrome often have low growth velocity and gain weight slowly.

Their final stature is often below average. Both short stature and low weight may be a consequence of early

CONCLUSION To conclude, the early diagnosis of Netherton syndrome is usually difficult due to erythroderma in the first months of life, which later slowly disappears and lesions typical of ichthyosis linearis circumflexa become evident. The cases are extremely rare and hence under reported.

REFERENCES 1. Judge MR, Morgan G, Harper JI. A clinical and immunological study of Netherton’s syndrome.

Br J Dermatol. 1994;131(5):615-21.

2. Comèl M. Ichtyosis linearis circumflexa. Dermatologica.

1949;98:122-36.

3. Hausser I, Anton-Lamprecht I. Severe congenital generalized exfoliative erythroderma in newborns and infants: a possible sign of Netherton syndrome. Pediatr Dermatol. 1996;13:183-99.

4. Netherton EW. A unique case of trichorrhexis invaginata ‘bamboo hair.’ Arch Dermatol. 1958;78:483-7.

5. DeWolf K, Ferster A, Sass U, André J, Stene JJ. Netherton’s syndrome: a severe neonatal disease. A case report.

Dermatology. 1996;192(4):400-2.

6. Pradeaux L, Olives JP, Bonafé JL, Le Tallec C, Pigeon P, Ghisolfi J. Digestive and nutritional manifestation of Netherton's syndrome. Arch Fr Pediatr. 1991;48(2):95-8.

7. Caputo R, Vanutti P, Bertani E. Intermittent aminoaciduria have been observed in some patients. Arch Dermatol.

1984;120:220-2.

8. Plautin P, Delaire P, Guillet MH, Labouche F, Guillet G. Netherton syndrome, current aspects. A propose of 9 cases. Ann Dermatol Venereol. 1991;118(8):525-30.

9. Smith DL, Smith JG, Womg SW, deShazo RD. Netherton’s syndrome: a syndrome of elevated IgE and characteristic skin and hair findings. J Allergy Clin Immunol.

1995;95:116-23.

10. Stevanovic DV. Multiple defects of the hair shaft in Netherton’s disease. Br J Dermatol. 1969;81:851-57.

11. Kansky A, Podrumac B, Prelog I. Hereditary ichthyosis.

Pathogenesis and possibilities of treatment. ACTA Dermatoven APA. 1997;6:47-54.

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DRUGS

Nimesulide-induced Angioedema: A Case Report TUSHAR B NISHANDAR*, ANAND S KALE†, HARSHAL N PISE‡, SWAPNIL P CHUBE*

ABSTRACT Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed group of drugs for variety of indications. However, their use is associated with many potential adverse drug reactions. The detailed information of these reactions is necessary to decrease the morbidity and mortality associated with these reactions. Angioedema is the end result of deep dermal, subcutaneous and/or mucosal swelling, and is potentially a life-threatening condition in cases where the pharynx or larynx is involved. Drug-induced angioedema has been reported to occur in response to a wide range of drugs and vaccines.

Early recognition and discontinuation of responsible drug should be done. Here, we report a case of a patient who developed angioedema as a result of tablet nimesulide ingested for headache. Patient recovered gradually with stoppage of drug. According to Naranjo’s adverse drug reaction probability scale, the association of angioedema due to nimesulide in this case was possible.

Keywords: Adverse drug reaction, drug-induced angioedema, nimesulide

N

imesulide is a widely used nonsteroidal antiinflammatory drug (NSAID) available in oral and topical preparations. Chemical name 4-NItro-2-phenoxyMEthaneSULfonanilIDE serves basis for generic name of this molecule as ‘Nimesulide’.

Nimesulide belongs to sulfonanilides which is a unique chemical category within NSAIDs.1 Nimesulide is used as anti-inflammatory, analgesic and antipyretic.

It acts by inhibiting cyclooxygenase 2 (COX-2) preferentially. By inhibiting cytokines it produces antipyretic effect. Anti-inflammatory effect is produced because of inhibition of histamine, leukotriene B4 (LTB4) release, chemotaxis, nitric oxide (NO) production and reactive oxygen species (ROS) production. By above said both mechanisms, it acts as an analgesic.1 Common adverse drug reactions (ADRs) reported with oral nimesulide are like gastrointestinal (epigastralgia, heartburn, nausea, loose motions), dermatological (rash, pruritus), puffiness of face/eyelids and central (somnolence, dizziness). It also can cause severe ADR

*Junior Resident †Professor and Head ‡Assistant Professor Dept. of Pharmacology SRTR Govt. Medical College, Ambajogai, Beed, Maharashtra Address for correspondence Dr Tushar B Nishandar Junior Resident Dept. of Pharmacology SRTR Govt. Medical College, Ambajogai, Beed - 431 517, Maharashtra E-mail: nishandar9696@gmail.com

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like fulminant hepatic failure.2 Here, we report a case of angioedema caused by oral preparation of nimesulide, a commonly used analgesic in India.

CASE REPORT A 17-year-old female patient reported to casualty department with complaints of facial swelling (Fig. 1).

Facial swelling started from lips and spread all over the face gradually. There was mucosal involvement of lips and it was associated with itching. On detailed inquiry, patient gave history of headache since last 2 days. For same indication, she was prescribed tablet nimesulide by private general practitioner.

Following ingestion of prescribed tablet, patient developed facial swelling. There was no history of similar complaints in the past. Also, there was no history of any allergic disorder, any food or drug allergy. Patient was not on any other medication. Examination revealed blood pressure - 120/80 mmHg, pulse rate - 78/min, respiratory rate - 20/min. Systemic examination, otherwise, did not reveal any other significant finding.

Laboratory investigations were within normal limits.

Considering all the findings, patient was diagnosed as a case of drug-induced angioedema and managed accordingly. Nimesulide was stopped immediately and patient was treated with steroids, antihistaminic following which patient recovered in 4 days. Patient was discharged and follow-up visits were unremarkable.

In above said case, as per The Naranjo Algorithm or Adverse Drug Reaction Probability Scale score is 4,

DRUGS and mucous membrane (1.7%), itching/rash/urticaria (1.50%), renal (0.3%), puffiness of face/eyelids (0.70%).

Out of these most of the adverse effects subsided after stopping the drug. Very few required hospitalization.9 The only reliable test for NSAID sensitivity is oral challenge, as immunoglobulin E (IgE) detections, such as measurements of specific IgE antibody and skin tests cannot identify NSAID intolerance via a nonallergic mechanism. However, it is not performed routinely because of ethical issues.4

Figure 1. Nimesulide-induced angioedema.

suggesting it is a possible ADR. As per Modified Hartwig-Siegel Severity Scale of ADR, this reaction is classified as severe. As per Modified Schumock and Thorntonâ&#x20AC;&#x2122;s Preventability Scale of ADR, above said ADR is not preventable.3 DISCUSSION Adverse drug reactions to prescribed medicines are an inevitable part of drug therapy. Angioedema is a rare, life-threatening ADR, which is characterized by sudden-onset edematous swelling of the skin, mucus membrane and/or subcutaneous tissues. Angioedema can be caused by many factors like medication hypersensitivity, food allergy, infection, common allergens like animal stings, environmental factors, malignancy and hereditary conditions.

However, in many cases, the precise cause of the angioedema remains unknown. Drugs causing angioedema include angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), estrogen, penicillin, NSAIDs like aspirin and ibuprofen.

The prevalence of aspirin and other NSAIDs induced angioedema in the average population is 0.3-0.9%.4,5 The mechanism for NSAID-induced angioedema is hypothesized to involve the shunting of arachidonic acid metabolites from the cyclooxygenase pathway to the lipoxygenase pathway, such that leukotriene production is increased.6,7 Leukotrienes are known to cause vasodilation and edema.6,8 The adverse effect profile of nimesulide in Indian population in children was similar to that reported for all age groups. The adverse effects reported in 4,097 case report forms were gastrointestinal (3.1%), vomiting (1.34%), diarrhea (0.40%), nausea (0.17%), skin

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Nimesulide has been banned in many countries including United States, United Kingdom because of dangerous side effects like fulminant hepatic failure, angioedema. However, in India, due to paucity of data, the drug is rampantly used. Recently, in 2011, India also has banned use of nimesulide in patients with age less than 12 years.10 Drugs and other chemicals that are thought to have caused the angioedema must be used with caution. If there is a strong indication, use a drug from a different chemical class in the lowest dose possible and for lowest possible duration. Particular care is needed in cases with history of similar drug reaction in past.11 Treating physician should be cautious while prescribing nimesulide because of its potential to cause drug reactions. As angioedema is a life-threatening condition, there is a need to create awareness among practitioners to report all the ADRs to the Adverse Drug Reactions Monitoring Centers.

REFERENCES 1. Rainsford KD; Members of the Consensus Report Group on Nimesulide. Nimesulide - a multifactorial approach to inflammation and pain: scientific and clinical consensus. Curr Med Res Opin. 2006;22(6):1161-70.

2. Tripathi KD. Nonsteroidal anti-inflammatory drugs and antipyretic-analgesics. In: Tripathi M (Ed.). Essentials of Medical Pharmacology, 7th Edition, New Delhi: Jaypee Brothers Medical Publishers (P) Ltd., 2013. pp.192-209.

3. Mrugank BP, Hareesha RP. Prospective observational, non-randomized, parallel sequence study for assessment of adverse drug reactions due to chemotherapeutic treatment in different types of cancer patients. IJPSR. 2013;4(1):386-91.

4. Kidon MI, Kang LW, Chin CW, Hoon LS, See Y, Goh A, et al. Early presentation with angioedema and urticaria in cross-reactive hypersensitivity to nonsteroidal antiinflammatory drugs among young, Asian, atopic children.

Pediatrics. 2005;116(5):e675-80.

5. Inomata N. Recent advances in drug-induced angioedema. Allergol Int. 2012;61(4):545-57.

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GASTROENTEROLOGY

Revisiting Antacids: Co-therapy with Proton Pump Inhibitors in Gastroesophageal Reflux Disease PHILIP ABRAHAM

ABSTRACT Proton pump inhibitors (PPIs) are the most effective therapy for the management of gastroesophageal reflux disease (GERD).

However, because of the pathophysiological changes in GERD and the pharmacological limitations of PPIs, many patients do not get complete relief on PPI therapy, and often add to or modify their treatment. There is thus a need to improve on GERD management. Antacids provide quick relief against acid-related symptoms. Hence, they can be an effective adjuvant therapy for patients with GERD. A new algorithm has specified the role of antacids and antacid-alginate at different levels of GERD management.

Keywords: Proton pump inhibitors, gastroesophageal reflux disease, antacids, adjuvant therapy

G

astroesophageal reflux disease (GERD) is a multifactorial disorder in which reflux of gastric contents into the esophagus is associated with delayed esophageal clearance1 and esophageal dysmotility.2 It is a common condition in clinical practice3 and presents with typical (heartburn, regurgitation) and atypical (epigastric pain, noncardiac chest pain, respiratory or ear, nose and throat problems) symptoms.4 Symptoms of GERD affect approximately 20% of the population on a weekly basis;5 the prevalence in various Indian studies is reported at between 8% and 19%.6 The Indian Society of Gastroenterology Task Force reported that 7.6% of the Indian population have significant GERD symptoms.7 Symptoms of GERD may persist indefinitely.8 Severe GERD can result in significant impairment in quality-of-life,3 and cause complications such as severe esophagitis, Barrettâ&#x20AC;&#x2122;s esophagus and adenocarcinoma.

The treatment of GERD typically involves a combination of dietary/lifestyle modifications, and use of antacids, histamine 2 receptor antagonists (H2RA) and/or proton

Consultant Division of Gastroenterology PD Hinduja Hospital, Mahim, Mumbai, Maharashtra Address for correspondence Dr Philip Abraham Room No. 1104, Clinic Building, PD Hinduja Hospital Mahim, Mumbai - 400 016, Maharashtra E-mail: dr_pabraham@hindujahospital.com

pump inhibitors (PPIs).9 Patients with mild symptoms usually do not visit a physician.5 PROTON PUMP INHIBITORS: MOST EFFECTIVE TREATMENT FOR GERD PPI therapy is the most effective medical treatment for GERD.10 These drugs suppress gastric acid secretion by inhibiting the H+-K+ adenosine triphosphatase (ATPase) pump responsible for acid production. The blockage of gastric acid production with PPIs is regardless of the stimulus. PPIs produce greater and longer acid suppression compared to other therapies,11 and are considered the mainstay of antisecretory therapy for daytime and night-time GERD.12 CHALLENGES IN THE MANAGEMENT OF GERD Despite remarkable rates of symptom relief and healing with PPIs in GERD, many challenges still exist.13 Response to PPIs is not always adequate, compelling many patients to take twice-daily PPI and often add other medications.13

Reasons for Inadequate Response to PPI Therapy Variations in the efficacy of PPIs may be seen between individuals14 and also in the same individual between different PPIs.15 The reasons for failure of PPI therapy16 are shown in Table 1.

Nocturnal Acid Breakthrough Nocturnal acid breakthrough (NAB) is defined as gastric acid pH below 4 for at least 60 consecutive

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GASTROENTEROLOGY Table 1. Reasons for Inadequate Response to PPI Therapy yy Differences in pharmacokinetics of PPIs (e.g., absorption, bioavailability, half-life, metabolism) yy Formulation of PPIs (e.g., delay in onset of action due to enteric coating) yy Time of dosing and association with meal yy Noncompliance to therapy yy Nocturnal acid breakthrough

minutes during overnight period in patients on PPIs.16 Acid breakthrough symptoms usually occur in the evening after dinner and at night.10 NAB may contribute to the development of erosive esophagitis17 because of persistent acid injury to the esophagus.18 Up to 79% of patients with GERD experience nocturnal symptoms.13 According to one survey, in 48% of subjects upper gastrointestinal symptoms led to awakening from sleep, and sleep interruption was reported on an average of twice a week.10 Nocturnal acid reflux has a greater adverse impact on quality-of-life as compared to daytime symptoms19 because of multiple sleeprelated disorders.

NAB is more likely to cause erosive esophagitis than daytime reflux because of physiological changes during sleep. In the recumbent position and during nighttime, salivary secretion is decreased and as a result acid neutralization is also decreased. The frequency of swallowing is less compared to daytime and the effect of gravity is lost; hence, acid clearance from the esophagus is impaired.12,20 PPIs provide the most efficacious acid control during the daytime; however, there is recovery of some acid secretion during sleep.12 PPIs fail to normalize intraesophageal pH in some patients,21 and may not adequately control intragastric acidity during the night in a significant proportion of subjects.22 Breakthrough symptoms are commonly reported with PPI therapy,5,23 including with omeprazole,24 lansoprazole24 and esomeprazole.25 Many studies have evaluated therapeutic regimens for controlling NAB, including double-dose PPI therapy and single- or double-dose PPI therapy combined with an H2RA.11 In one study, 100% of participants reported NAB with a single morning PPI dose.10 As many as 70% of patients with GERD receiving twice-daily PPI therapy report NAB.26 In a survey, 400 adults receiving PPIs were interviewed regarding their medication usage patterns and perceived acid breakthrough symptoms.

Despite the high compliance to PPI regimens, 46% of

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daily PPI users experienced breakthrough symptoms.

Of the latter, only 34% reported extreme satisfaction with their PPI. Forty-five percent of PPI users were using antacids to supplement their PPI therapy approximately once every third day. Antacids were the most common (87%) agents used for acid breakthrough symptoms. Patients often used additional medications after dinner or at night.10 Thus, gastric acid breakthrough seems to be the norm rather than exception in patients on PPIs.27 Dissatisfaction with PPI therapy13 and continuing symptoms might lead a large number of patients to take additional medications,5 indicating a scope for improvement in the management of GERD. It appears that antacids can be a useful co-therapy for the management of GERD symptoms because of the quick and sufficient relief they provide.28

Acid Pocket The presence of a postprandial acid pocket just below the lower esophageal sphincter was described by Fletcher and colleagues in 2001.29 The acid pocket appears about 10 to 15 minutes after a meal, and may contribute to the reflux of acid into the esophagus.30 In GERD patients, upward migration of acid, especially in the supine position, leads to histological changes in the mucosa. Hence, the acid pocket is a good target for GERD treatment.31 ANTACIDS AS THERAPY FOR ACID-PEPTIC DISORDERS Almost two-thirds of patients have been reported to add some treatment to PPI therapy for acid breakthrough symptoms, without the knowledge of their physicians.10 This may be because the GERD prescription therapy provides only partial relief, and because patients seek faster symptom relief compared to their prescription therapy.5 Antacids act by partial neutralization of gastric hydrochloric acid and inhibition of the proteolytic enzyme pepsin.3 They can increase the local pH and provide relief from the acid pocket.4 Antacids are shown to be effective in the treatment of infrequent postprandial symptoms.32 They provide quick symptom relief compared to other treatments;4 however, the duration of action is short (i.e., 1-3 hours). Antacid therapy has multiple benefits for GERD treatment (Table 2).

Antacids like calcium carbonate and magnesium and aluminum salts are available in different formulations and combinations.3 They have been reported to be

GASTROENTEROLOGY commonly used by PPI users to treat acid breakthrough symptoms.10 Many GERD patients self-medicate with these over-the-counter (OTC) drugs.11 They are commonly used for the management of mild-tomoderate intermittent symptoms of GERD. If intragastric pH is maintained above 4, formation of pepsin from pepsinogen can be decreased;15 sufficient neutralization of gastric acid also reduces release of pepsin and gastrin. Gastrin-associated feedback mechanisms result in increased lower esophageal sphincter tone (Fig. 1).

REVISED ALGORITHM FOR TREATMENT OF GERD The revised algorithm4 for treatment of GERD has specified a more prominent role for antacids at all levels of treatment. Antacids have been recommended both as stand-alone and in combination with other acidsuppressive therapies.4 This algorithm is divided into three levels (i.e., self care, primary care and secondary care) (Fig. 2). ÂÂ

Self care: During self care, OTC therapy in the form of antacids or alginate-antacids, H2RA and lowdose PPI (readily available in some countries) are recommended as monotherapy. Speed of action is an important parameter during self care. Antacids or alginate-antacids can provide quickest relief of symptoms.

ÂÂ

Primary care: Combination therapy may be more beneficial than monotherapy. PPI, or a combination of alginate-antacid and acid suppressive therapy, can be administered.

ÂÂ

Secondary care: PPI plus or minus adjuvant therapy has also been recommended at secondary care for the management of nonerosive reflux disease/GERD (LA grades* AB or CD) and Barrett’s esophagus.

Table 2. Benefits of Antacid Therapy in Acid-peptic Disorders yy Rapid symptom relief4 yy Binding to bile acids yy Increase in lower esophageal sphincter tone yy Release of prostaglandins with cytoprotective effect yy Benefit in Helicobacter pylori infection33 yy Effectiveness in gas/bloating/dyspepsia: Dimethicone, an antifoaming agent often combined with antacids, reduces acid reflux and acts as an antiflatulent

Reduction in gastrin yyGastric pH >4

yyReduced pepsin and gastrin release

yyIncrease in LES tone

Sufficient gastric acid neutralization

Gastrin associated feedback mechanism

Figure 1. Improved LES tone with antacids.

LES = Lower esophageal sphincter.

Self care Episodic symptoms

Primary care Presumably GERD

OTC therapy (Antacids, alginate-antacids, H2RA, PPI)

Optimize OTC and/or PPI ± adjuvant therapy* (4-8 weeks)

BID PPI ± adjuvant therapy* (4 weeks, in case of failure)

*Los Angeles GERD grades: A: >1 mucosal break <5 mm, which does not extend between tops of two mucosal folds; B: >1 mucosal break >5 mm, which does not extend between tops of two mucosal folds; C: >1 mucosal break, which is continuous between tops of >2 mucosal folds but involves <75% of esophageal circumference; D: >1 mucosal break, which involves >75% of circumference.34

Thus, antacids are useful at self care and also useful at primary and secondary care levels as adjuvant therapy.

Antacids should be used on ‘as needed’ basis instead of continuous use because of the absence of long-term Secondary care Presumably GERD

NERD/GERD AB PPI ± adjuvant therapy* (4-8 weeks)

GERD CD PPI ± adjuvant therapy* (8 weeks)

Berrett’s longterm PPI ± adjuvant therapy*

*Antacids or alginate-antacids.

Therapy is based on severity of diseases: NERD/GERD AB, GERD CD and Barrett’s esophagus.

Figure 2. Antacid or antacid-alginate in algorithm for management of GERD.4 GERD = Gastroesophageal reflux disease; OTC = Over-the-counter; H2RA = Histamine 2 receptor antagonist; PPI = Proton pump inhibitor; NERD = Nonerosive reflux disease; BID = Twice-daily.

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GASTROENTEROLOGY safety data. In addition to quick relief from symptoms, the possibility of “as required” intake is another advantage of antacids.4 CONCLUSION Gastroesophageal reflux disease is a common entity in routine clinical practice. Although PPIs are the most effective acid-suppressing therapy for GERD, many patients do not achieve effective symptom relief.

Contributing factors for nocturnal acid breakthrough include the physiological changes during sleep or recumbent position and the pharmacological limitations of PPI therapy. In order to reduce the adverse effects of breakthrough symptoms, supplementing a PPI with an antacid preparation might be a useful strategy.

Physicians can play a proactive role and reassure patients regarding the safety of appropriate use of adjuvant products with PPI therapy.

Acknowledgment The author wishes to thank Dr Varsha Khatry and Dr Sanjay Shroff for their help in preparing the manuscript.

REFERENCES 1. Smout AJ. Pathophysiology of gastro-oesophageal reflux disease. Minerva Gastroenterol Dietol. 2003;49(4):243-60.

2. Yi ZH, Feng L, Wen MY, Liu JR, Yang L. Association between acid reflux and esophageal dysmotility in patients with gastroesophageal reflux disease. Sichuan Da Xue Xue Bao Yi Xue Ban. 2014;45(3):480-3.

3. Banks M. The modern investigation and management of gastro-oesophageal reflux disease (GORD). Clin Med. 2009;9(6):600-4.

4. Tytgat GN, McColl K, Tack J, Holtmann G, Hunt RH, Malfertheiner P, et al. New algorithm for the treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2008;27(3):249-56.

5. Jones R, Armstrong D, Malfertheiner P, Ducrotté P. Does the treatment of gastroesophageal reflux disease (GERD) meet patients’ needs? A survey-based study. Curr Med Res Opin. 2006;22(4):657-62.

6. Gaddam S, Sharma P. Shedding light on the epidemiology of gastroesophageal reflux disease in India - a big step forward. Indian J Gastroenterol. 2011;30(3):105-7.

7. Bhatia SJ, Reddy DN, Ghoshal UC, Jayanthi V, Abraham P, Choudhuri G, et al. Epidemiology and symptom profile of gastroesophageal reflux in the Indian population: report of the Indian Society of Gastroenterology Task Force.

Indian J Gastroenterol. 2011;30(3):118-27.

8. Dorval E, Rey JF, Soufflet C, Halling K, Barthélemy P. Perspectives on gastroesophageal reflux disease in primary care: the REFLEX study of patient-physician agreement. BMC Gastroenterol. 2011;11:25.

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9. Chapman DB, Rees CJ, Lippert D, Sataloff RT, Wright SC Jr. Adverse effects of long-term proton pump inhibitor use: a review for the otolaryngologist. J Voice. 2011;25(2):236-40.

10. Robinson M, Shaw K. Proton pump inhibitor attitudes and usage: a patient survey. P&T. 2002;27:202-6.

11. Maton PN. Profile and assessment of GERD pharmacotherapy. Cleve Clin J Med. 2003;70 Suppl 5:S51-70.

12. Katz PO. Nocturnal reflux: Assessing and addressing the problem. Pract Gastroenterol. 2005:30-9.

13. Scarpignato C, Hunt RH. Proton pump inhibitors: the beginning of the end or the end of the beginning? Curr Opin Pharmacol. 2008;8(6):677-84.

14. Katz PO, Hatlebakk JG, Castell DO. Gastric acidity and acid breakthrough with twice-daily omeprazole or lansoprazole. Aliment Pharmacol Ther. 2000;14(6):709-14.

15. James VE. Update on the medical management of GERD. Gastroenterology and Endoscopy News. Special Edition 2006;4:9-12.

16. Krznaric Z, Ljubas Kelecic D, Rustemovic N, Vranesic Bender D, Ostojic R, Markos P, et al. Pharmaceutical principles of acid inhibitors: unmet needs. Dig Dis. 2011;29(5):469-75.

17. Orr WC, Allen ML, Robinson M. The pattern of nocturnal and diurnal esophageal acid exposure in the pathogenesis of erosive mucosal damage. Am J Gastroenterol.

1994;89(4):509-12.

18. Harmon RC, Peura D. Management of patients with nocturnal GERD. Gastroenterology and Endoscopy News. 2008 April;18-20.

19. Farup C, Kleinman L, Sloan S, Ganoczy D, Chee E, Lee C, et al. The impact of nocturnal symptoms associated with gastroesophageal reflux disease on health-related quality of life. Arch Intern Med. 2001;161(1):45-52.

20. Tutuian R, Castell DO. Nocturnal acid breakthrough approach to management. MedGenMed. 2004;6(4):11.

21. Milkes D, Gerson LB, Triadafilopoulos G. Complete elimination of reflux symptoms does not guarantee normalization of intraesophageal and intragastric pH in patients with gastroesophageal reflux disease (GERD).

Am J Gastroenterol. 2004;99(6):991-6.

22. Tutuian R, Katz PO, Castell DO. Nocturnal acid breakthrough: pH, drugs and bugs. Eur J Gastroenterol Hepatol. 2004;16(5):441-3.

23. Fouad YM, Katz PO, Castell DO. Oesophageal motility defects associated with nocturnal gastro-oesophageal reflux on proton pump inhibitors. Aliment Pharmacol Ther. 1999;13(11):1467-71.

24. Peghini PL, Katz PO, Bracy NA, Castell DO. Nocturnal recovery of gastric acid secretion with twice-daily dosing of proton pump inhibitors. Am J Gastroenterol.

1998;93(5):763-7.

25. Hammer J, Schmidt B. Effect of splitting the dose of esomeprazole on gastric acidity and nocturnal acid breakthrough. Aliment Pharmacol Ther. 2004;19(10):1105-10.

GASTROENTEROLOGY 26. Katz PO, Anderson C, Khoury R, Castell DO. Gastrooesophageal reflux associated with nocturnal gastric acid breakthrough on proton pump inhibitors. Aliment Pharmacol Ther. 1998;12(12):1231-4.

27. Nzeako UC, Murray JA. An evaluation of the clinical implications of acid breakthrough in patients on proton pump inhibitor therapy. Aliment Pharmacol Ther.

2002;16(7):1309-16.

28. Wang YK, Hsu WH, Wang SS, Lu CY, Kuo FC, Su YC, et al. Current pharmacological management of gastroesophageal reflux disease. Gastroenterol Res Pract.

2013;2013:983653.

30. Boeckxstaens G. The relationship between the acid pocket and GERD. Gastroenterol Hepatol (N Y). 2013;9(9):595-6.

31. Kahrilas PJ, McColl K, Fox M, O’Rourke L, Sifrim D, Smout AJ, et al. The acid pocket: a target for treatment in reflux disease? Am J Gastroenterol. 2013;108(7):1058-64.

32. Tran T, Lowry AM, El-Serag HB. Meta-analysis: the efficacy of over-the-counter gastro-oesophageal reflux disease therapies. Aliment Pharmacol Ther. 2007;25(2):143-53.

33. Berstad K, Weberg R, Berstad A. Is there a place for antacids in the treatment of Helicobacter pylori infection?

Scand J Gastroenterol. 1992;27(12):1006-10.

34.

29. Fletcher J, Wirz A, Young J, Vallance R, McColl KE. Unbuffered highly acidic gastric juice exists at the gastroesophageal junction after a meal. Gastroenterology.

2001;121(4):775-83.

■■■■

Standards of Practice Committee, Lichtenstein DR, Cash BD, Davila R, Baron TH, Adler DG, Anderson MA, et al.

Role of endoscopy in the management of GERD. Gastrointest Endosc. 2007;66(2):219-24.

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HEMATOLOGY

Thrombocytosis: Reactionary versus Primary?

NANDINI SWAMY*, CHAITRA G†, PRASHANTH‡, SIVA SUBRAMANIYAM†, VIVEK TIRLAPUR†

ABSTRACT Essential thrombocytosis is one of the acquired myeloproliferative disorder which is characterized by a persistent elevation in platelet count and has a tendency to undergo thrombosis and hemorrhage. Acute ischemic stroke is one of the presenting features of essential thrombocytosis. We present a case of a 63-year-old female patient who presented with tubercular meningitis, recurrent ischemic stroke and thrombocytosis. Initially thought to be reactionary thrombocytosis, on re-evaluation of the cause, patient was found to have essential thrombocytosis.

Keywords: Primary thrombocytosis, reactive thrombocytosis, ischemic stroke, infection

CASE REPORT A 63-year-old female reported to our hospital emergency department with history of fever, altered sensorium and headache of 15 days duration. Patient had no significant past history. On examination, patient was disoriented with presence of neck stiffness and a blood pressure (BP) of 160/100 mmHg was recorded.

A clinical diagnosis of meningitis was made and a lumbar puncture was performed for confirmation of the same. Cerebrospinal fluid (CSF) analysis showed sugar - 45 mg/dL, protein - 318.7 mg/dL, cells - 165, 93% lymphocytes, elevated adenosine deaminase (ADA).

Routine blood investigations were as follows: Hemoglobin (Hb) - 10.0 g/dL, platelet count - 6.6 lakh/ mm3, total count - 19,600 cells/mm3, differential count P85E7Mix8, erythrocyte sedimentation rate - 5 mm/hour, negative for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus screening.

corticosteroids - dexamethasone and antihypertensivesamlodipine. Two days after admission, patient developed two episodes of generalized tonic-clonic seizures and left upper and lower limb weakness.

Computed tomography (CT) brain was done, which showed a right temporoparietal lobe infarct, attributed as a part of tubercular vasculitis (Fig. 1).

ATT - rifampicin, isoniazid, ethambutol, pyrazinamide and streptomycin; dexamethasone were tapered, antiepileptics-phenytoin, aspirin with physiotherapy was continued. Patient improved symptomatically.

Repeat investigations showed persistently elevated platelets and total counts. The same was attributed

Chest X-ray - normal. Electrocardiography (ECG) and 2D echo revealed no abnormality. A diagnosis of tubercular meningitis was made and patient was started on antitubercular therapy (ATT) - rifampicin, isoniazid, ethambutol, pyrazinamide and streptomycin;

*Senior Specialist †Postgraduate ‡Assistant Professor Dept. of Medicine, ESIC-PGIMSR, Bangalore, Karnataka Address for correspondence Dr Chaitra G Postgraduate, Dept. of Medicine, ESIC-PGIMSR, Bangalore, Karnataka

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Figure 1. CT brain showing right temporoparietal lobe infarct.

HEMATOLOGY to the presence of infection - tuberculosis and use of corticosteroids. Patient was advised regular reevaluation but was lost to follow-up.

One year later, patient returned to the emergency department with worsening of weakness of the left upper limb since 1 month with no history of fever, headache or seizures. She had completed ATT regimen at a primary health center. BP - 160/90 mmHg with power of 2/5 in the left upper limb. Hb - 11.1 g/dL, platelet count - 14.25 lakh/mm3, total count - 21,010 cells/mm3.

Peripheral smear showed no atypical cells. CT brain showed subacute infarct in right temporoparietal lobe with gliotic changes.

Blood culture and sensitivity, urine culture and sensitivity, chest X-ray ruled out any source of infection. Repeat CSF examination was normal.

Bone marrow examination was done to evaluate the cause for thrombocytosis and leukocytosis. Bone marrow aspiration revealed normoblastic erythroid maturation and megakaryocytic hyperplasia with large mononuclear megakaryocytes. Jak2 mutation analysis was found to be positive. A diagnosis of essential thrombocytosis was made and patient was started on hydroxyurea. Patient follow-up awaited.

DISCUSSION Platelet count greater than 4.5 lakh/mm3 is known as thrombocytosis and cause may be primary or secondary.1 Few causes of reactive (secondary) thrombocytosis are iron deficiency; chronic infections like tuberculosis, osteomyelitis; paraneoplastic process in Hodgkin’s disease, bronchial carcinoma; chronic inflammatory conditions like Crohn’s disease, polyarteritis nodosa, sarcoidosis; post-splenectomy, chronic blood loss; after administration of cytotoxic drugs, corticosteroids, physiological stress.

Essential thrombocytosis is one of the acquired myeloproliferative disorder, which is characterized by a persistent elevation in platelet and has a tendency to undergo thrombosis and hemorrhage. Increased platelet count is due to an expansion of megakaryocytic lineage. The annual incidence rates for essential thrombocytosis are 0.59-2.53/1,00,000. The prevalence is found to be around 30/1,00,000.1 The increased incidence has been attributed to increased diagnosis of essential thrombocytosis more frequently today than in the past.1,2 The median age of presentation is between 65 and 70 years, with incidence being two times higher in females compared to males.3

Around one-third of patients have no symptoms at time of diagnosis. Erythromelalgia is the most common symptom. The risk of thrombosis is greater in patients with essential thrombocytosis, and in patients older than 60, it is 15.1% per patient per year.4 Thus, acute ischemic stroke is usually a presenting feature.5 Thrombosis can involve cerebrovascular, coronary or peripheral arterial circulation.6 The 2008 World Health Organization (WHO) Diagnostic Criteria is used to make diagnosis of essential thrombocytosis - all the four criteria should be fulfilled.7 ÂÂ

Platelet count ≥450 × 109/L.

ÂÂ

Megakaryocyte proliferation with large and mature morphology.

ÂÂ

Not meeting WHO criteria for chronic myelogenous leukemia, polycythemia vera, primary myelofibrosis, myelodysplastic syndromes or other myeloid neoplasm.

ÂÂ

Demonstration of JAK2V617F or other clonal marker or no evidence of reactive thrombocytosis.

Hence for diagnosis of essential thrombocytosis reactive thrombocytosis and other chronic myeloid disorders be excluded.8 Most patients with essential thrombocythemia have a normal life expectancy without associated disease-related complications.9,10 Our patient presented with thrombocytosis, leukocytosis with ischemic symptoms on a background of tubercular meningitis. Thrombocytosis was diagnosed as reactionary thrombocytosis and infection was treated.

But the patient was lost to follow-up, platelet and total count were hence not repeated after treatment of the infection. When patient presented with second episode of infarction with elevated platelet count, a diagnosis of essential thrombocytosis was sought and confirmed. In severe thrombocytosis, so-called pseudohyperkalemia is often observed which was present in our patient.

CONCLUSION Platelets are involved actively in antimicrobial host defense such as inflammation and tissue repair apart from their role in hemostasis.11 Hence, patients of essential thrombocytosis can be susceptible to infections due to defective platelets and be misdiagnosed to have reactionary thrombocytosis. A high-degree of suspicion and thorough evaluation, regular follow-up of any case of thrombocytosis is required.

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HEMATOLOGY REFERENCES 1. Griesshammer M, Bangerter M, Sauer T, Wennauer R, Bergmann L, Heimpel H. Aetiology and clinical significance of thrombocytosis: analysis of 732 patients with an elevated platelet count. J Intern Med. 1999;245(3):295-300.

2. Johansson P. Epidemiology of the myeloproliferative disorders polycythemia vera and essential thrombocythemia. Semin Thromb Hemost. 2006;32(3):171-3.

3. Jensen MK, de Nully Brown P, Nielsen OJ, Hasselbalch HC. Incidence, clinical features and outcome of essential thrombocythaemia in a well defined geographical area.

Eur J Haematol. 2000;65(2):132-9.

4. Griesshammer M, Heimpel H, Pearson TC. Essential thrombocythemia and pregnancy. Leuk Lymphoma.

1996;22 Suppl 1:57-63.

6. Hart RG, Kanter MC. Hematologic disorders and ischemic stroke. A selective review. Stroke. 1990;21(8):1111-21.

7. Imbert M, Pierre R, Thiele J, Vardiman JW, Brunning RD, Flandrin G. Essential thrombocythaemia. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (Eds.). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2001. pp. 39-41.

8. Brière JB. Essential thrombocythemia. Orphanet J Rare Dis. 2007;2:3.

9. Harrison CN. Current trends in essential thrombocythaemia. Br J Haematol. 2002;117(4):796-808.

10. Passamonti F, Rumi E, Pungolino E, Malabarba L, Bertazzoni P, Valentini M, et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med. 2004;117(10):755-61.

5. Elliott MA, Tefferi A. Thrombosis and haemorrhage in 11. Klinger MH, Jelkmann W. Role of blood platelets in polycythaemia vera and essential thrombocythaemia. Br infection and inflammation. J Interferon Cytokine Res. 2002;22(9):913-22.

J Haematol. 2005;128(3):275-90.

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Iron Supplementation - When Less is Really More Anemia is often the result of an iron deficiency. In such cases the patients, who are typically female, will be prescribed iron supplements to be taken daily. In cases of severe deficiency, the dosage is increased to several tablets a day. A new study recently published in the medical journal Blood reveals that it may be difficult for the body to absorb iron in quantities that are necessary and desirable when the supplement doses are administered in 24-hour intervals.

FDA Approves Adynovate for Hemophilia A The US Food and Drug Administration (FDA) has approved Adynovate, a new recombinant PEGylated antihemophilic factor for children aged 12 years or older and adults with hemophilia A. The factor VIII therapy, manufactured by Baxalta US, Inc, is approved both as needed treatment and for prophylaxis. Adynovate contains full-length coagulation factor VIII molecules linked to other molecules, known as polyethylene glycol (PEGylated), which should make it last longer in the blood than unmodified antihemophilic factor, said the FDA, in a news release.

...Cont’d from page 542

6. Rudy E. Update - Drug induced angioedema without urticaria, ADR focus. Drug Therapy Topics. 2004;33(6): 33-7.

9. Srishyla MV, Sireesha K, Bhaduri J, et al. Letter to the editor. Indian Pediatr. 2002;39:310-1.

7. Greaves M, Lawlor F. Angioedema: manifestations and management. J Am Acad Dermatol. 1991;25(1 Pt 2):15561; discussion 161-5.

10. Central Drug Standard Control Organisation (Internet).

New Delhi, CDSCO 2014. Available from: http://cdsconic. in/writereaddata/drugsbannednthedcountry.pdf.

Accessed on 19th March, 2015.

8. Agostoni A, Cicardi M. Drug-induced angioedema without urticaria. Drug Saf. 2001;24(8):599-606.

11. Settipane GA. Aspirin sensitivity and allergy. Biomed Pharmacother. 1988;42(8):493-8.

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INTERNAL MEDICINE

Poncet Disease: A Case Report of Polyarthropathy DEBAPRASAD CHAKRABARTI*, ABHIJIT DATTA†, AMRIT KR BHATTACHARYYA‡

ABSTRACT Tuberculous rheumatism (Poncet’s disease), is a sterile reactive arthritis that can emerge during any stage of acute tuberculosis.

It is characterized by nondestructive parainfective polyarthropathy in patients with active visceral or disseminated tuberculosis.

There is striking absence of direct mycobacterial invasion of the joint but is due to an immunological reaction to tuberculoprotein.

Here we report a case of Poncet’s disease with atypical feature.

Keywords: Tuberculosis, arthritis, antitubercular chemotherapy

T

uberculous rheumatism also known as Poncet’s disease is a rare syndrome described in 1897 by Poncet.1 It is characterized by nondestructive parainfective polyarthropathy in patients with active visceral or disseminated tuberculosis (TB). There is striking absence of direct mycobacterial invasion of the joint but is due to an immunological reaction to tuberculoprotein. The symptoms resolve completely with antitubercular chemotherapy.1,2 CASE REPORT A 28 years unmarried female presented with chief complaints of pain and swelling in both wrist, right knee and right ankle joints for last 2½ months. A week later, she also noticed painful swelling of left ankle joint. It was associated with mild restriction of joint movement and morning stiffness. The symptoms used to improve temporarily with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, only to recur again. She also complained of low-grade fever in the evening hours and hair fall since last 2 months. There was no history of significant weight loss or anorexia, cough or conjunctivitis. She denied

*Associate Professor, Dept. of Medicine, Tripura Medical College and Dr BRAM Teaching Hospital, Agartala, Tripura †Associate Professor, Dept. of Pathology, Agartala Govt. Medical College and GB Pant Hospital, Agartala, Tripura ‡Professor and Head, Dept. of Medicine, Tripura Medical College and Dr BRAM Teaching Hospital, Agartala, Tripura Address for correspondence Dr Debaprasad Chakrabarti Associate Professor, Dept. of Medicine Tripura Medical College and Dr BRAM Teaching Hospital Doctors Qtr. E/1, Hapania, Agartala, Tripura (West) - 799 014 E-mail: drdebaprasad2007@rediffmail.com

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any history of oral ulcer, photosensitivity, dry eyes or any urinary and bowel trouble.

On Examination She was thinly built with mild pallor. Few discrete nontender lymph nodes of 2 × 2 cm diameter were palpable on left side of neck. There was no other lymphadenopathy elsewhere. Respiratory and cardiac examination was unremarkable. No organomegaly could be detected. Musculoskeletal examination revealed both wrist, right knee and left ankle, tender and swollen.

On Evaluation She had anemia (hemoglobin [Hb] - 9.1 g/dL) and mild leukocytosis TLC - 11,300, DLC - P85,L12,M1,E1,B0 with erythrocyte sedimentation rate (ESR) of 54 mm/hour.

Peripheral smear showed normocytic normochromic picture. Blood sugar, creatinine and liver function test (LFT) was normal. She had positive C-reactive protein (CRP) - 42 mg/L, but rheumatoid factor, anti-cyclic citrullinated peptide, antistreptolysin O titer, human immunodeficiency virus (HIV) and hepatitis B surface antigen (HBsAg) were negative. She was then subjected for antinuclear antibody (ANA), which was strongly positive. Positive ANA prompted us to do anti-ds-DNA and Smith (Sm) antibody, which turned negative. Fine needle aspiration cytology (FNAC) from cervical nodes revealed caseating granuloma (Fig. 1) suggestive of TB. X-rays of chest and joints and ultrasonography (USG) of abdomen were normal.

Based on the clinical profile and investigations, a diagnosis of tubercular lymphadenitis with reactive polyarthritis i.e., Poncet’s disease was made. She was put on anti-TB drugs and NSAID was added for

INTERNAL MEDICINE

Figure 1. Caseating granuloma of lymph node.

10 days as supportive measures. Over next 2 weeks, she noticed remarkable improvement and was symptomfree by 6 months. There was no recurrence of rheumatic symptoms on follow-up.

DISCUSSION Poncet’s disease is characterized by a sterile reactive polyarthritis that occurs during acute TB infection in which no mycobacterial involvement can be found or other known cause of polyarthritis can be detected.1,2 Although it has been described as polyarthritis, a review of literature reveals Poncet’s disease to be more often pauciarticular, symmetrical arthritis of large joints.2 It is a different entity from tubercular arthritis, which is monoarticular and caused by direct tubercular infection of the joint.3 The association of TB and rheumatologic diseases has been well-recognized. Franco Paredes et al have established four different categories.4 ÂÂ

Direct musculoskeletal Mycobacterium tuberculosis osteomyelitis.

involvement by such as arthritis,

ÂÂ

Reactive immune phenomena such as reactive arthritis.

ÂÂ

M. tuberculosis as an infective pathogen particularly with the use of newer biological agents.

ÂÂ

ATT-induced rheumatologic syndromes viz. druginduced lupus.

The etiopathogenesis of this disease is still controversial, the more accepted hypothesis include molecular mimicry and thermal shock protein.4 Novaes et al5 have proposed the following diagnostic criteria for Poncet’s disease: ÂÂ

Evidence of active extra-articular TB

ÂÂ

Rheumatic symptoms in more than one joint

ÂÂ

Absence of personal or family antecedents

ÂÂ

Lack of axial or sacroiliac impairment

ÂÂ

Complete remission with ATT and no permanent sequelae

ÂÂ

Exclusion of other rheumatic diseases

ÂÂ

Non-specific lab finding.

Thus active TB complicated by reactive arthritis remains essentially a diagnosis of exclusion. In our patient, evidence of active TB lymphadenitis together with polyarthritis and resolution of symptoms with ATT allowed us to make the diagnosis of Poncet’s disease secure. However, the diagnosis was confounded by the presence of strongly positive ANA. This is in contrast to the study by Malaviya et al6 who mentioned negative autoimmune markers in Poncet’s disease. It is worth mentioning here that mycobacterial infection can induce the development of autoantibodies and a positive ANA does not by itself indicate the presence of autoimmune disease.7 Physicians should be aware of Poncet’s disease, a rare complication associated with a common disease to prevent delay and initiation of appropriate treatment.

Hence, active TB should be strongly considered in the differential diagnosis of patients with fever with polyarthritis of unknown cause. Further this case will sensitize the physicians about the presence of autoantibodies in patients of TB. REFERENCES 1. Bloxham CA, Addy DP. Poncet’s disease: para-infective tuberculous polyarthropathy. Br Med J. 1978;1(6127):1590.

2. Bhargava AD, Malviya AN, Kumar A. Tuberculous rheumatism (Poncet’s disease) - a case series. Ind J Tub. 1998;45:215-9.

3. Dall L, Long L, Stanford J. Poncet’s disease: tuberculous rheumatism. Rev Infect Dis. 1989;11(1):105-7.

4. Schweitzer LC, Lipnharski F, Prezzi SH. Poncet’s arthritis: case report. Rev Bras Reumatol. 2011;51(4):388-90, 393.

5. Novaes GS, Kalil G, Borreli FE. Criterios de diagnostico da doenca de poncet. Rev Bras Reumatol. 1992;32(1)20-6.

6. Malaviya AN, Kotwal PP. Arthritis associated with tuberculosis. Best Pract Res Clin Rheumatol.

2003;17(2):319-43.

7. Elkayam O, Caspi D, Lidgi M, Segal R. Auto-antibody profiles in patients with active pulmonary tuberculosis.

Int J Tuberc Lung Dis. 2007;11(3):306-10.

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NEUROLOGY

Isaacs’ Syndrome (Neuromyotonia): A Case Report IBRAHEEM KHAN*, GN SAXENA†, SWATI SRIVASTAVA*,#, SURENDRA YADAV#, KAMLESH SHARMA#

ABSTRACT Acquired neuromyotonia (Isaacs’ syndrome) is a rare disorder of peripheral nerves with spontaneous and continuous muscle fiber activity leading to cramps, myokymia and fasciculations. Here an 18 years boy presented with chief complaint of inability to relax his hand voluntarily from 1 year and progressive stiffening of both upper limbs followed by both lower limbs in 9 months and had sweating in palms, soles and axilla over last 4-5 months. He was unable to perform his routine activities.

Physical examination revealed a muscular man with excessive sweating, stiff posture and all muscles were in a state of persistent contraction, no sensory involvement but deep tendon reflexes were increased in upper limbs with bilateral flexor plantar response. Electromyography revealed abnormal spontaneous activity in form of continuous motor activity with very high firing rate (= 70-75 Hz). Serology for antibodies against VGKC is not available in our institution. On the basis of clinical data and investigations reports diagnosis of neuromyotonia was made. Treatment with carbamazepine resulted in substantial improvement in stiffness, gait difficulties and sweating within 7 days.

Keywords: Acquired neuromyotonia, peripheral nerves, electromyography, carbamazepine

A

cquired neuromyotonia (Isaacs’ syndrome) is a rare disorder of peripheral nerves with spontaneous and continuous muscle fiber activity leading to cramps, myokymia and fasciculations.1 The association to hematologic malignancies such as thymoma, plasmacytoma, Hodgkin’s lymphoma and bronchogenic carcinoma paraneoplastic has been reported.2 This is related to the autoimmune mechanism where the autoantibodies are usually detected against the voltage-gated potassium channels (VGKCs).3 Another etiology is nonimmunologic mechanism from chemical intoxication including mercury, 2,4-dichlorophenoxyacetic acid, dichlorophenyl-dichloroethylene and oxaliplatin. Here we report a case of neuromyotonia.

CASE REPORT An 18 years boy presented with chief complaint of inability to relax his hand voluntarily from 1 year and

*Assistant Professor †Ex-Professor *,#Associate Professor #Residents Dept. of Medicine, SMS Medical College, Jaipur, Rajasthan Address for correspondence Dr Ibraheem Khan Samraya, Weir, Bharatpur - 321 408, Rajasthan E-mail: imedicine2008@gmail.com

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progressive stiffening of both upper limbs followed by both lower limbs in 9 months and had sweating in palms, soles and axilla over last 4-5 months. The stiffness was painless. It was so severe that he could not write properly. Riding bicycle and motor cycle was not possible due to inability to release the hand clutch.

He could not participate in any activity. Defecation and micturition were normal. His muscle mass particularly abdominal and arms increased substantially. Three months before admission, he had involuntary continuous contraction of muscles of arms and thigh.

All symptoms persisted day and night even when sleeping. He had no past medical history. There was no use of toxic substances or medications. There is no family history of these symptoms.

Physical examination revealed an afebrile muscular man with excessive sweating. His vital signs were: pulse rate (86/min), blood pressure (110/70 mmHg) and respiratory rate (16/min).

Neurological examination revealed stiff posture and all muscles were in a state of persistent contraction (Fig. 1).

His muscles were hypertrophied and power was normal. Sensory examination was normal but deep tendon reflexes were increased in upper limbs with bilateral flexor plantar response. Thyroid gland and lymph nodes were not palpable. Abdominal wall was hypertrophied with no palpable organomegaly. There was no evidence of any systemic disease. Complete blood count, erythrocyte sedimentation rate and other

NEUROLOGY pseudomyotonia, fasciculation and stiffness of trunk and limbs and hyperhidrosis.1 Central nervous system features are seen in 25% of cases of neuromyotonia and these include mood change, sleep disorders, hallucinations and personality changes.4

Figure 1. Contracture and stiffness in neuromyotonic muscular man with polydactyl.

Figure 2. Dramatic response in stiffness and contracture with carbamazepine after 7 days therapy.

blood investigations including serum electrolyte levels were normal. Lactate dehydrogenase was 718 KU and creatine kinase was 526. Magnetic resonance imaging brain and cervical spine was normal. Computerized tomography of chest and abdomen showed no mediastinal mass and other abnormalities. Thyroid function tests were normal. Cerebrospinal fluid examinations was normal. Electromyography (EMG) revealed abnormal spontaneous activity in form of continuous motor activity with very high firing rate (= 70-75 Hz). Serology for antibodies against VGKC is not available in our institution. On the basis of clinical data and investigation reports, diagnosis of neuromyotonia was made. Treatment with carbamazepine 200 mg/ day in three divided doses was started. There was a substantial improvement in stiffness, gait difficulties and sweating within 7 days (Fig. 2).

DISCUSSION Isaacs’ syndrome is a rare syndrome, only few cases have been reported in India. The diagnosis of Isaacs’ syndrome is based on clinical features and EMG findings. The cardinal features consists of myokymia,

EMG features of neuromyotonia are spontaneous motor unit discharges, which are thought to originate from the distal parts of the nerves. Typical findings are myokymic doublet, triplet, multiplet and positive sharp waves motor discharges, the former being the more common.4 Our patient had elevated creatine kinase levels and this has been reported in 50% cases of neuromyotonia.4 The major differential diagnoses of neuromyotonia are stiff man syndrome (in which the discharges disappear in sleep) and motor neurone disease, in which neuromyotonic discharges can be seen early on in the course.5 Our patient does not appear to have any of the above features. Treatment for neuromyotonia is with membrane stabilizing agents like phenytoin, carbamazepine, sodium valproate and lamotrigine may be used singly or in combination.5 So, we used a membrane stabilizing agent tablet carbamazepine 200 mg/day in three divided doses. Dramatic response occurred within 7 days. Contracture of all four limbs disappeared and patient could performing his routine activities (Fig. 2).

Other treatment options are immunosuppression with prednisolone and azathioprine or plasma exchange may be considered if these are unsuccessful.6 Immunoglobulin therapy; however, seems not to be helpful.5 REFERENCES 1. Lahrmann H, Albrecht G, Drlicek M, Oberndorfer S, Urbanits S, Wanschitz J, et al. Acquired neuromyotonia and peripheral neuropathy in a patient with Hodgkin’s disease. Muscle Nerve. 2001;24(6):834-8.

2. Auger RG. AAEM minimonograph #44: diseases associated with excess motor unit activity. Muscle Nerve.

1994;17(11):1250-63.

3. Sinha S, Newsom-Davis J, Mills K, Byrne N, Lang B, Vincent A. Autoimmune aetiology for acquired neuromyotonia (Isaacs’ syndrome). Lancet. 1991;338(8759):75-7.

4. Hart IK, Maddison P, Newsom-Davis J, Vincent A, Mills KR. Phenotypic variants of autoimmune peripheral nerve hyperexcitability. Brain. 2002;125(Pt 8):1887-95.

5. Maddison P. Neuromyotonia.

2006;117(10):2118-27.

Clin

Neurophysiol.

6. Skeie GO, Apostolski S, Evoli A, Gilhus NE, Hart IK, Harms L, et al. Guidelines for the treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol. 2006;13(7):691-9.

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OBSTETRICS AND GYNECOLOGY

A Randomized Comparative Study of Intramuscular Camylofin Dihydrochloride and Intravenous Drotaverine Hydrochloride on Cervical Dilatation in Labor RAJANI UDAY*, BINU P†

ABSTRACT Background: Both maternal and perinatal morbidity are greatly affected by the duration of labor. Uterine activity and the rate of cervical dilatation are the principal factors that determine the duration of labor. However, despite good uterine contractions, cervical dilatation may be impeded due to the inhibitory impulses in the form of spasm, thus resulting in prolonged labor.

Objectives: The purpose of the current study was to compare the effectiveness of intravenous drotaverine hydrochloride and intramuscular camylofin dihydrochloride on the following variables: Rate of cervical dilatation; duration of active phase of first stage of labor; mode of delivery and total duration of labor. The study also investigated the effectiveness of the above drugs in shortening the duration of labor and their potential adverse reactions on the mother and fetus. Methods: One hundred twentysix women in active labor were segregated into two groups consisting of 63 patients each. Group I received intramuscular camylofin dihydrochloride and Group II received intravenous drotaverine hydrochloride. The drugs were compared for their effectiveness in cervical dilatation. Results: Duration of active phase of labor was 332.54 ± 59.93 minutes in Group I and 356.78 ± 68.93 minutes in Group II. Although the mean duration of active phase of first stage of labor was shorter in Group I (332.54 minutes) as compared to Group II (356.78 minutes), it was not statistically significant. Mean cervical dilatation rate was significantly more in Group I (1.78 cm/hour) than Group II (1.61 cm/hour). Mean induction delivery interval was longer in Group II (228.38 minutes) than in Group I (207.96 minutes). The lengths of the second stage (39.49 ± 11.21 in Group I, 36.78 ± 10.9 in Group II) and third stage (5.39 ± 1.58 in Group I, 6.02 ± 2.01 in Group II) were statistically similar in both the groups. Conclusion: It was concluded that the duration of active phase of labor was shorter in camylofin group than drotaverine group, but it was statistically insignificant. The rate of cervical dilatation was more in camylofin group than drotaverine group, which is statistically significant. Induction delivery interval was significantly longer in drotaverine group than in camylofin group. No major maternal or fetal side effects were observed. Intramuscular camylofin dihydrochloride appeared to be more effective than intravenous drotaverine hydrochloride for cervical dilatation.

Keywords: Camylofin dihydrochloride, drotaverine hydrochloride, cervical dilatation

L

abor is an important and memorable event in a woman’s life.1 A painless and short labor is every mother’s desire and an obstetrician’s aim.

Progressive cervical dilatation and progressive descent of the presenting part determine the progress of labor.1 Cervical dilatation is the outcome of all the driving forces of uterine contraction acting against tissue resistance and significantly determines the duration of labor. Failure of the cervix to dilate in labor may lead to prolonged labor.1 The hazards of prolonged labor have long been recognized for both the mother and

*Professor, Dept. of Obstetrics and Gynecology MS Ramaiah Medical College, Bangalore, Karnataka †Dept. of Obstetrics and Gynecology Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka

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the fetus. While the mother faces a risk of obstructed labor, ketosis and infection, the fetus is exposed to the risks of infection, birth asphyxia and excessive cranial moulding.2 Labor is said to be prolonged if its duration exceeds 18 hours. In multiparous women, the labor is considered as prolonged if it exceeds 12 hours. This generally refers to prolongation of the first stage of labor associated with slow dilatation of the cervix. The second stage may be randomly defined as prolonged after 2 hours in primigravidae and 1 hour in multigravidae.3 The commonest causes of prolonged labor include: inadequate contractions, resistance by bony pelvis or soft tissues, and abnormal position and presentation.

Prolonged labor is managed with intravenous fluids; analgesics; prophylactic antibiotics - whenever there is

OBSTETRICS AND GYNECOLOGY membrane rupture more than 12 hours, repeated per vaginum (PV)’s in case of pyrexia and tachycardia and assessment of contractions, PV examination for cervical dilatation, descent and position of presenting part, malpresentation and abnormal pelvic architecture, use of partogram, augmentation by oxytocin and artificial rupture of membranes. Specific treatment involves use of oxytocin, artificial rupture of membranes and cesarean section if indicated, in the first stage and instrumental delivery or cesarean section if indicated, in the second stage.3,4

epidural analgesia or sedatives was compared with drotaverine group receiving the same.

Exclusion criteria were: ÂÂ

Pre-eclampsia

ÂÂ

Eclampsia

ÂÂ

Antepartum hemorrhage

ÂÂ

Any obstetric complications: Cephalopelvic disproportion, abnormal presentations and twin pregnancy.

ÂÂ

Medical disorders: Renal and hepatic dysfunction, cardiac disease and obstructive airway disease

ÂÂ

Known hypersensitivity to drug

ÂÂ

Patient in latent phase of labor.

AIMS The present study aimed to compare and evaluate the rate of cervical dilatation from onset of active labor to full cervical dilatation in patients randomized to receive intramuscular camylofin dihydrochloride and intravenous drotaverine hydrochloride.

OBJECTIVES ÂÂ

ÂÂ

ÂÂ

To compare the effectiveness of intravenous drotaverine hydrochloride and intramuscular camylofin dihydrochloride on: zz

Rate of cervical dilatation

zz

Duration of active phase of first stage of labor

zz

Mode of delivery

zz

Total duration of labor.

Patients qualifying for the study were assigned groups by simple random table. Two groups consisting of 63 patients each were formed. Group I was randomized to receive drotaverine 40 mg (one vial) intravenously; second injection was repeated after 2 hours. Group II received camylofin 25 mg (one vial) intramuscularly, single injection. Few cases were given second injection after 2 hours.

Maternal and fetal status was evaluated clinically in reference to the following points: ÂÂ

Patient’s name, husband’s name, age, address

ÂÂ

Registration number, date and time of admission

To find out the efficacy of the above drugs in shortening the duration of labor.

ÂÂ

Occupation of the patient

ÂÂ

Period of gestation

To study the adverse drug reactions on the mother and fetus.

ÂÂ

Duration of labor pains/history of leak or bleeding PV

ÂÂ

The time of induction in case of induced labor

ÂÂ

Menstrual and marital history

ÂÂ

General physical examination

ÂÂ

Systemic examination

ÂÂ

Per abdomen examination: To determine height of the uterus, number and duration of contractions, to assess the liquor clinically, to assess the number of fetal pole palpable per abdomen.

METHODS The study was conducted in MS Ramaiah Hospital, Bangalore from October 2010 to 2012 on a random population of pregnant females.

Inclusion criteria were: ÂÂ

Primigravidae

ÂÂ

Age 18-35 years

ÂÂ

Cervical dilatation >3 cm

ÂÂ

Vertex presentation

ÂÂ

Singleton full-term gestation (37-40 weeks)

ÂÂ

Intact fetal membranes

ÂÂ

Spontaneous and induced labor

ÂÂ

The effect of epidural analgesia and sedatives on cervical dilatation was controlled by matching the two groups i.e., camylofin group receiving

Patients were encouraged to keep their bladder empty.

Any side effects were noted and treated accordingly.

After the delivery of the placenta, cervix and the vagina were inspected to rule out any trauma to the cervix.

The study methodology stated that if at any point in the study, there appeared an indication for maternal or fetal health being jeopardized, the investigational drug would be stopped and adjunctive measures to affect

Indian Journal of Clinical Practice, Vol. 26, No. 6, November 2015

559

OBSTETRICS AND GYNECOLOGY delivery would be carried out immediately and the patient would be excluded from the study.

The primary endpoint of the study was delivery of baby. Following parameters were monitored in every patient: ÂÂ

Progress of labor using a partogram: Frequency and duration of uterine contractions were evaluated clinically by abdominal palpation every 30 minutes; cervical effacement and dilatation were monitored every 2 hours by PV examination; station and position of presenting part were noted.

PV examination was done earlier if: Rupture of membranes occurred, patient started bearing down, significant changes in fetal heart sound (FHS) were found or meconium-stained liquor was observed.

ÂÂ

Maternal well-being was assessed by pulse rate; blood pressure; any side effects like nausea, vomiting, palpitations, tachycardia, dryness of mouth, flushing, headache, hypotension, nausea, vomiting, pain at injection site were noted and treated accordingly.

ÂÂ

Fetal well-being was assessed by checking fetal heart rate; color of amniotic fluid and Apgar score at 1 and 5 minutes.

The effectiveness of intravenous drotaverine hydrochloride and intramuscular camylofin dihydrochloride was compared on the following grounds: ÂÂ

Total duration of active phase of first stage of labor

ÂÂ

Rate of cervical dilatation

ÂÂ

Total duration of labor

ÂÂ

Mode of delivery

ÂÂ

Any complication in the third stage

ÂÂ

Neonatal condition at birth.

Routine investigations included hemoglobin (Hb), blood grouping, Rhesus (Rh) factor, urine (albumin and sugar) and blood sugar. Ultrasonography (USG) and other investigations were done as required.

Data obtained was compiled and analyzed regarding comparative efficacy, safety and acceptability of the two methods involved.

Statistical Analysis Descriptive and inferential statistical analyses were conducted in the present study. Results on continuous measurements were presented on mean + SD (minmax) and results on categorical measurements were

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presented in number (%). Significance was assessed at 5% level of significance. Student t-test (two-tailed, independent) was used to find the significance of study parameters on continuous scale between two groups on metric parameters. Chi-square/Fisher exact test helped to determine the significance of study parameters on categorical scale between two or more groups.

OBSERVATIONS AND RESULTS The study assessed the incidence of lower segment cesarean section (LSCS) in the two groups with 63 subjects each, which was found to be comparable in both the groups. Therefore, in order to avoid confusion in calculation of the duration of active phase, second and third stage of labor, rate of cervical dilatation, injection delivery interval and the number of injections required, patients who had LSCS were excluded from these statistics. The difference in the age groups in two groups was not statistically significant (p value of 0.422). Most patients were 21-25 years of age (49.2% in camylofin group and 61.9% in drotaverine group, respectively) (Table 1).

The distribution of booked/unbooked patients was statistically similar in the two groups with p = 1.000.

Nearly 93.6% patients were booked in each group.

About 17.5% in the camylofin group and 4.8% in the drotaverine group were between 37 and 38 weeks of gestation. Nearly 27.0% in camylofin group and 42.8% in drotaverine group were between 38 and 39 weeks. About 55.5% in camylofin group and 52.4% in drotaverine group were between 39 and 40 weeks of gestation. Period of gestation was statistically significant in the two groups (p = 0.032). All the patients in both the groups belonged to 37-40 weeks of gestation (Fig. 1).

Distribution of spontaneous labor and induced labor was statistically similar in the two groups with p = 0.849.

About 66.7% in camylofin group and 68.3% in drotaverine group had spontaneous labor, while 33.3% in camylofin group and 31.7% in drotaverine group had induced labor (Fig. 2).

Oxytocin acceleration was statistically similar in both the groups of patients with p = 1.000.

About 90.5% in both the groups had oxytocin acceleration. Mean duration of active phase of first stage of labor was shorter in camylofin group (332.54 minutes) as compared to the drotaverine group (356.78 minutes); however, the difference was not statistically significant (p = 0.142). Mean duration of second stage of labor was 39.49 minutes in camylofin group versus 36.78 minutes in drotaverine group; again a statistically insignificant difference with p value of 0.185. Mean

OBSTETRICS AND GYNECOLOGY Table 1. Age Distribution of Patients Age (years)

Camylofin

Drotaverine

No.

%

No.

%

15-20

13

21-25

31

20.6

9

14.3

49.2

39

61.9

26-30

19

30.2

15

23.8

Total

63

100.0

63

100.0

Mean ± SD

23.67 ± 2.94

100

23.25 ± 2.76

Camylofin

90

Drotaverine

Percentage (%)

80 70 60

55.5

50 40 30

27 17.5

20 10 0

52.4

42.8

4.8 37-38 weeks

38-39 weeks Period of gestation

39-40 weeks

Figure 1. Period of gestation in study groups.

Induced

Percentage (%)

80

Mean cervical dilatation rate was significantly more in camylofin group (1.78 cm/hour) as compared to the drotaverine group (1.61 cm/hour) with p = 0.002.

Table 3 summarizes the rate of cervical dilation in study subjects. About 94.9% patients in camylofin group delivered after one injection; 5% required two injections. However, 91.5% of the patients in drotaverine group required two injections, and only 8.4% delivered after one injection (Fig. 3). Thus, significantly more number of injections were required for patients given drotaverine (p ≤ 0.001). The incidence of side effects are statistically similar in the two groups (p = 1.000). About 8.4% patients in each group developed side effects. One patient developed nausea, two patients developed vomiting and two patients developed dryness of mouth in camylofin group.

Nausea, vomiting, headache, hypotension and fetal tachycardia were observed in one patient, respectively in the drotaverine group. Of note, mean induction

Not induced

100 90

duration of third stage of labor was 5.39 minutes in camylofin group and 6.02 minutes in drotaverine group but not statistically significant with p value of 0.062. The mean of total duration of labor was shorter in camylofin group (378.94 minutes) than in drotaverine group (394.75 minutes); not statistically significant (p = 0.207) (Table 2).

Table 3. Rate of Cervical Dilation in Centimeter/Hour 33.3

Cx rate (cm/hour)

31.7

Camylofin No.

%

No.

%

1-1.5

12

20.3

22

37.2

1.5-2.0

33

55.9

31

52.5

70 60 50

67.7

68.3

40

Drotaverine

>2.0

14

23.7

6

10.1

20

Total

59

100.0

59

100.0

10

Mean ± SD

1.78 ± 0.31

30

0

Camylofin

1.61 ± 0.28

Drotaverine

Figure 2. Distribution of spontaneous and induced labor in study groups.

100 90

Camylofin

94.9

Drotaverine 91.5

Variables (minutes)

Camylofin

Drotaverine

P value

Stage 1 labor (active phase)

332.54 ± 59.63

356.78 ± 68.93

0.142

Stage 2 labor

39.49 ± 11.21

36.78 ± 10.9

0.185

Stage 3 labor

5.39 ± 1.58

6.02 ± 2.01

0.062+

378.94 ± 63.22

394.75 ± 71.87

0.207

Total labor

Percentage (%)

80

Table 2. Comparison of Duration of Stage 1, 2, 3 and Total Labor Among Patients Studied

70 60 50 40 30 20

8.4

10 0

1

5 No. of required

2

Figure 3. Percentage of patients requiring 1 or 2 injections.

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Rate of cervical dilatation was statistically similar in camylofin group irrespective of whether they received epidural or not (p = 0.406). Rate of cervical dilatation was statistically similar in drotaverine group irrespective of whether they received epidural or not (p = 0.307).

Rate of cervical dilatation in camylofin group was more than drotaverine group irrespective of whether they received epidural (p = 0.058) or not (p = 0.010) (Table 5).

Table 4. Induction Delivery Interval in Minutes IDI (minutes)

Camylofin

Drotaverine

No.

%

No.

%

<200

27

45.7

18

30.5

200-300

26

44.0

32

54.2

>300

6

10.1

9

15.2

Total

59

100.0

59

100.0

Mean ± SD

207.96 ± 53.90

228.38 ± 55.68

IDI: Induction delivery interval.

Present

Nil

Percentage (%)

22

27.1

80 70 60 50 40 30 20 10 0

Camylofin

Epidural

Drotaverine

Figure 4. Percentage of patients receiving epidural.

90 80

6.3

Normal 6.3 6

17.5

70 60 50 40 30 20 10 0

Camylofin

Mode of delivery

Drotaverine

Figure 5. Mode of delivery in the study groups.

Table 6. Comparison of Apgar Score of Neonates in Two Groups Variables

Camylofin

Drotaverine

P value

Apgar 1 (mean)

6.38 ± 0.705

6.43 ± 0.730

0.438

Apgar 5 (mean)

8.30 ± 0.585

8.35 ± 0.570

0.350

About 17.5% in camylofin group had instrumental delivery, compared to 6% in drotaverine group (not statistically significant; p = 0.424). Nearly 6.3% of patients in both groups had LSCS (two patients for nonprogression of labor and two patients for fetal distress in both groups, respectively) (Fig. 5).

DISCUSSION

Table 5. Comparison of Rate of Cervical Dilatation According to Presence/Absence of Epidural in Study Patients Rate of cervical dilatation

Camylofin

Drotaverine

P value

No epidural

1.80 ± 0.33

1.63 ± 0.29

0.010

Epidural

1.72 ± 0.25

1.53 ± 0.28

0.058

P value

0.406

0.307

-

562

100

Instrumental

About 4% of patients in both groups experienced third stage complication (p = 1.00). In camylofin group, atonic postpartum hemorrhage (PPH) and vaginal tear were seen in two patients each. In drotaverine group, two patients had atonic PPH, one had third-degree perineal tear and one had cervical tear. Mean blood loss was statistically similar in the two groups (camylofin 257.62 ± 100.3; drotaverine 253.17 ± 98.34; p = 0.804).

Mean Apgar at 1 and 5 minutes was statistically similar in both groups (Table 6). Mean birth weight was also statistically similar in the two groups with p = 0.428 (camylofin 2.85 ± 0.306 kg vs drotaverine 2.89 ± 0.347).

100 90

LSCS

Percentage (%)

delivery interval was significantly more in drotaverine group (228.38 minutes) as compared to the camylofin group (207.96 minutes) with p = 0.045 (Table 4).

Number of patients who received epidural was similar in both groups with p = 0.385 (27.1% camylofin; 22.0% drotaverine; Fig. 4).

Indian Journal of Clinical Practice, Vol. 26, No. 6, November 2015

Both the groups were comparable with respect to the distribution of age of patients. The mean age in this study population was comparable to other studies, such as those by Sharma et al, Warke et al and Singh et al.1,2,5 The range of age of the patients in the present study was also comparable to the range taken in various other studies. Maximum number of patients belonged to the age group of 21-25 years in this study. This was comparable to several studies where maximum

OBSTETRICS AND GYNECOLOGY patients belonged to the age group of 20-25 years.

About 55.5% subjects in Group I and 52.4% in Group II were in 39-40 weeks of gestation. All the patients in both the groups belonged to 37-40 weeks of gestation period. In the study by Sharma et al,1 mean period of gestation was 38.8, 38.9 and 38.6 in drotaverine group, valethamate group and control group, respectively.

In the study by Warke et al,2 the average gestational age was 39.1 weeks and 38.4 weeks in the camylofin and control group, respectively. In the study by Singh et al,5 mean gestational period was 39.36 in drotaverine group and 39.17 in the control group. The range of period of gestation of the patients in present study was comparable to the range taken in various other studies.

In present study, the mean duration of active phase of labor was shorter in camylofin group (332.54 minutes) than in drotaverine group (356.78 minutes); however, the difference was not statistically significant with p value of 0.142. Singh et al5 noted in their study that the mean duration of active phase of labor was shorter in drotaverine group (265.44 minutes) than placebo group (312.32 minutes). Similarly, Sharma et al1 demonstrated that the mean duration of active phase of labor was shorter in drotaverine group (194 minutes) than valethamate bromide group (220.7 minutes).

Warke et al2 demonstrated that the mean duration of active phase of labor was shorter in camylofin group (3 hours, 35 minutes) than placebo group (5 hours, 34 minutes). While there are no studies on comparison between camylofin and drotaverine for cervical dilatation, individual studies on the two agents are available. However, the result of present study was not comparable with other studies, as the mean duration of active phase of labor in drotaverine group in other studies was between 2.7 and 4.4 hours and the present study demonstrated it to be 5.9 hours. The mean duration of active phase of labor in camylofin group in other studies was 3-5 hours, but in the present study it was 5.5 hours.

Nearly 94.9% patients in camylofin group delivered after one injection, whereas only 8.4% in drotaverine group delivered after one injection. In a study by Sharma et al,1 66% of patients in drotaverine group delivered with two injections. Warke et al2 gave camylofin injection as intramuscular single dose to all patients in their study group. Thus, the present study was comparable with respect to the number of injections required in both groups. In the present study, mean cervical dilatation rate was significantly more in camylofin group (1.78 cm/hour) than drotaverine group (1.61 cm/hour). Mean cervical dilatation rates are comparable in the present study and in the study by Warke et al2 for the camylofin group. However, the dilatation rates in the present

study and other such studies are not comparable for drotaverine. The mode of delivery in the present study was comparable to that in other studies. The incidence of third stage complications in this study was similar to that in other studies. The present study revealed that both the drugs were free from fetal side effects and appeared to decrease perinatal mortality and morbidity by decreasing the duration of labor.

CONCLUSION The following conclusions were drawn from this study: ÂÂ

The duration of active phase of labor was shorter in camylofin group than drotaverine group, but it was not statistically significant (332.54 minutes vs 356.78 minutes; p = 0.142).

ÂÂ

Rate of cervical dilatation was more in camylofin group than drotaverine group, which was statistically significant (1.78 cm/hour vs 1.61 cm/ hour; p = 0.002).

ÂÂ

Induction delivery interval was significantly more in drotaverine group than in camylofin group (228.38 minutes vs 207.96 minutes; p = 0.045).

ÂÂ

No major maternal or fetal side effects were observed.

Therefore, in modern obstetrics, no woman should be made to suffer in pain and agony of labor. Drugs which hasten labor should be embraced by both obstetrician and the laboring mother. The two drugs studied were effective in shortening the duration of labor.

Intramuscular camylofin dihydrochloride was more efficacious than intravenous drotaverine hydrochloride in shortening the duration of labor.

REFERENCES 1. Sharma JB, Pundir P, Kumar A, Murthy NS. Drotaverine hydrochloride vs. valethamate bromide in acceleration of labor. Int J Gynaecol Obstet. 2001;74(3):255-60.

2. Warke HS, Chauhan AR, Raut VS, Ingle KM. The efficacy of camylofin dihydrochloride in acceleration of labor.

A randomized double blind trial. Bombay Hospital Journal. [online] Available from http://www.bhj.org.in/ journal/2003_4503_july/theefficacy_420.htm [Accessed May 7 2015].

3. Percival R, Holland, Brews. Normal labour. In: Daftary SN, Chakravarti S (Eds.). Manual of Obstetrics, 5th Edition. New Delhi: India, B.I. Churchill Livingstone; 1993. pp. 325-8.

4. Cunningham FG, Mac Donald PC, Gant NF, Leveno KJ, Gilstrap LC, Nankins GDV, et al. Dystocia abnormalities of the expulsive forces. Williams Obstetrics, 23rd Edition.

Appleton and Large; 1997.pp. 415-32.

5.

Singh KC, Jain P, Goel N, Saxena A. Drotaverine hydrochloride for augmentation of labor. Int J Gynecol Obstet India.

2004;84(1):17-22.

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A Rare Case of Primary Ovarian Ectopic Pregnancy After Interval Tubal Ligation TAMAL KUMAR MANDAL*, PRATIMA GORAIN†, DEBJANI DEB‡, KANAK LATA#

ABSTRACT We report a case of a woman presenting with symptoms of ruptured ectopic pregnancy. She had a history of tubal ligation done 3 years back. Exploratory laparotomy was done and a diagnosis of ruptured ovarian ectopic pregnancy was made.

Keywords: Ovarian ectopic pregnancy, interval tubal ligation

E

ctopic tubal gestation following tubal ligation accounts for 12% of all ectopic pregnancies.1 Ovarian ectopic gestation is very rare (0.5%)2 and there are very few reports of ovarian ectopic pregnancy following tubal ligation. We report a case of primary ovarian ectopic pregnancy, which occurred 3 years after bilateral tubal ligation.

CASE REPORT A 29-year-old lady P2+0 presented to our emergency in the Dept. of Obstetrics and Gynecology of Bankura Sammilani College and Hospital, Bankura with the chief complaint of lower abdominal pain and vomiting for 3 days.

On admission, she was alert, conscious, cooperative and apparently hemodynamically stable. Her blood pressure (BP) was 110/76 mmHg, pulse rate 80/min, temperature normal, with moderate amount of pallor.

Her menstrual cycle was regular. There was no history of missed period. She had history of two vaginal deliveries. Last childbirth was 5 years back and bilateral tubal ligation was done 3 years back.

*RMO cum Clinical Tutor †Associate Professor ‡Assistant Professor #Postgraduate Trainee Dept. of Obstetrics and Gynecology Bankura Sammilani Medical College and Hospital, Bankura, West Bengal Address for correspondence Dr Tamal Kumar Mandal C/o: Bhim Bhabani Mandal North Pratapbagan, Sarani No. 5, Bankura - 722 101, West Bengal E-mail: tamal.cool2011@gmail.com

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Indian Journal of Clinical Practice, Vol. 26, No. 6, November 2015

On per abdominal examination, abdomen was tensed with tenderness in right iliac fossa. Per vaginal examination showed bulky uterus with parous os, tenderness in right fornix with an adnexal mass.

Cervical motion tenderness was seen positive. No active bleeding per vagina was seen.

Urine for pregnancy test was positive. Before operation hemoglobin level was 7.8 gm%. Urgent ultrasonography report revealed right-sided tuboovarian mass 4.6 × 4.2 cm in size. Free fluid in abdomen + extending up to hepatorenal pouch. Uterine cavity was empty.

A diagnosis of ruptured ectopic pregnancy was made.

The patient was prepared for urgent exploratory laparotomy and sent to operation theater immediately.

Simultaneously resuscitation was going on to correct the shock. Under general anesthesia abdomen was opened. After opening abdomen, hemoperitoneum (approximately 500 mL) detected. Uterus was bulky.

A right-sided hemorrhagic blackish irregular nodular mass 5 × 4 × 4 cm was seen embedded within the right ovary and connected to the uterus by the uteroovarian ligament. Both the tubes including the fimbrial ends with ostia were intact with previous ligation sites. Leftsided ovary was healthy (Fig. 1).

Right-sided salpingo-oophorectomy was done and hemostasis was secured. Religation of left-sided fallopian tube was done. Abdomen was closed in layers after peritoneal wash and taking count of the instruments and the mops. Specimen of right-sided ovary with parts of both the fallopian tubes was sent for histopathological examination. Postoperative period was uneventful. Two units of whole blood were transfused. Patient was discharged in satisfactory condition after stitch removal.

OBSTETRICS AND GYNECOLOGY

Figure 1. Right-sided ovarian ectopic. Both the fallopian tubes including the fimbrial ends with ostia are intact with previous ligation sites. Left-sided ovary is healthy.

Figure 2. Histopathological section of ovary showing chorionic villi.

Histological Examination Histological examination of the ovary showed chorionic villi embedded in the ovarian parenchymal tissue with surrounding hemorrhage, consistent with ovarian ectopic gestation (Fig. 2). The fallopian tubes were edematous and congested, the lumens were filled with fresh blood and there was no evidence of gestational tissue. So, the features were suggestive of ovarian ectopic gestation.

DISCUSSION Ectopic gestation after tubal ligation occurs due to recanalization of the fallopian tube or formation of a tuboperitoneal fistula. Spermatozoa may pass through the ligation site, but the fertilized ovum fails to go through, so implantation occurs in the distal tubal segment.3,4 Ovarian pregnancy, as such, is very rare (0.5%)2 with a reported incidence of 1/7,000-1/40,000 pregnancies,5,6 while it is generally seen in cases following intrauterine contraceptive device (IUCD) insertion. Because IUCDs protect the endometrium and to a lesser extent, the proximal oviducts from implantation, it was expected that when IUCDs were introduced, future reports of

extrauterine pregnancies might show an increased rate of ovarian involvement. Data from the Cooperative Statistical Program of the Population Council show that 1 of every 9 ectopic pregnancies among IUCD users is an ovarian pregnancy.2 So far, only a few cases of ovarian pregnancy following tubal ligation have been reported as per the literature survey. A case

by Wittich in 20047 was reported where an ovarian ectopic pregnancy occurred following postpartum tubal ligation as the tubes were edematous, friable and congested, which resulted in incomplete occlusion of tubes. But, in our case, ovarian ectopic pregnancy occurring following interval tubal ligation without any history of amenorrhea, is, in fact, quite rare.

The embedding may occur intrafollicular or extrafollicular. Only 15% of cases of ovarian pregnancy are intrafollicular in origin.2 In an intrafollicular ovarian pregnancy, the second stage of meiosis, ovum capacitation and fertilization each occur within the follicle. In an intrafollicular pregnancy, a wellpreserved corpus luteum can be identified in the wall of the gestational sac. Four other “criteria presented by Spiegelberg” for identifying an intrafollicular pregnancy are: 1) that the tube, including the fimbria ovarica, is intact and is clearly separate from the ovary; 2) that the gestational sac definitely occupies the normal position of the ovary; 3) that the sac is connected to the uterus by the uteroovarian ligament and 4) that ovarian tissue is unquestionably demonstrated in the wall of the sac.

Early diagnosis of an ovarian pregnancy, of all the diagnoses relating to extrauterine gestations, is perhaps the most difficult. The classic presentation of pain and uterine bleeding with the finding of an adnexal mass is present in only 14% of patients with ectopic pregnancy.2 Even when present, these classic signs and symptoms are not entirely specific for ectopic pregnancy. Persistent pelvic pain alone is the most frequent clinical manifestation of an ovarian gestation.

Although an adnexal mass is palpable in as many as 60% of ovarian pregnancies,2 the mass is frequently confused with a leaking corpus luteum hematoma.

Incomplete spontaneous abortion with a leaking corpus luteum hematoma mimics an ovarian pregnancy.

All of the test criteria used for diagnosing a tubal pregnancy are helpful in diagnosing a primary ovarian pregnancy. Critical evaluation of all of the diagnostic studies, particularly the highly sensitive and rapid β-hCG (human chorionic gonadotropin) immunoassay and transvaginal ultrasonography, is necessary in making the diagnosis. When the β-hCG is positive, ultrasonography shows no intrauterine gestational

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OBSTETRICS AND GYNECOLOGY sac and free fluid exists in the peritoneal cavity; a laparoscopy, as a diagnostic tool, should be performed to confirm or refute a diagnosis of suspected ovarian pregnancy if the condition of the patient permits.

The highly sensitive β-hCG immunoassay can confirm the presence of a gestational process, but the β-hCG level does not help to precisely locate the gestation.

A tubal pregnancy can easily be ruled out with laparoscopy, but an ovarian pregnancy is sometimes difficult to differentiate from a leaking corpus luteum hematoma by gross appearance. Ultrasonography can be helpful, but only in advanced ovarian pregnancy will the ultrasound image show a discrete gestational sac, therefore confirming an ovarian pregnancy.

with typical or atypical signs and symptoms of ectopic gestation following history of amenorrhea or even without any history of amenorrhea.

The benefits derived from the early diagnosis of an ectopic pregnancy include the potential use of medical and conservative surgical procedures that optimize future fertility and conservation of the ovary in case of ovarian ectopic pregnancy. Early diagnosis may also preclude ectopic pregnancy rupture and therefore result in lower patient morbidity and mortality. Women undergoing tubal ligation should be educated about its possibility, so that early interventions can be taken to minimize complications.

A safe approach is to proceed with localized surgical resection of the bleeding mass with conservation of the ovary, if possible. Only rarely is the hemorrhage so profuse that oophorectomy is required to control bleeding. Even if the last trophoblastic villus cannot be removed in the ovarian resection, the ovary should be preserved. Any remaining trophoblastic tissue will usually degenerate rapidly or respond to postoperative methotrexate therapy and therefore should produce no long-standing clinical problem.2 In our case, rightsided salpingo-oophorectomy was done as there was hemorrhage from the mass and most of the ovarian tissue was damaged. Serum β-hCG level became normal after 2 weeks in postoperative period.

REFERENCES

CONCLUSION

6. Salas Valien JS, Reyero Alvarez MP, González Morán MA, García Merayo M, Nieves Díez C. Ectopic ovarian pregnancy. An Med Interna. 1995;12(4):192-4.

We would like to emphasize the fact that, though ectopic tubal or ovarian gestation are rare after tubal ligation, the clinician has to consider this possibility when the patient with history of tubal ligation comes

1. Chakravarti S, Shardlow J. Tubal pregnancy after sterilization. Br J Obstet Gynaecol. 1975;82(1):58-60.

2. In: Rock JA, Jones HW III. Te Linde’s Operative Gynecology., 10th Edition. Lippincott: Williams & Wilkins 2008. pp. 817-8.

3. Davis MR. Recurrent ectopic pregnancy after tubal sterilization. Obstet Gynecol. 1986;68(3 Suppl):44S-45S. 4. Stock RJ, Nelson KJ. Ectopic pregnancy subsequent to sterilization: histologic evaluation and clinical implications. Fertil Steril. 1984;42(2):211-5.

5. Itoh H, Ishihara A, Koita H, Hatakeyama K, Seguchi T, Akiyama Y, et al. Ovarian pregnancy: report of four cases and review of the literature. Pathol Int. 2003;53(11):806-9.

7. Wittich AC. Primary ovarian pregnancy after postpartum bilateral tubal ligation: a case report. J Reprod Med. 2004;49(9):759-61.

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OBSTETRICS AND GYNECOLOGY

Resveratrol in Gynecology ALKA GAHLOT

ABSTRACT Resveratrol, the naturally occurring polyphenolic compound characterized by antioxidative, anti-inflammatory and apoptotic properties, appears to contribute substantially to cardioprotection and cancer prevention. Resveratrol is being extensively studied for its anti-angiogenic, antioxidant, anti-inflammatory properties in gynecology. In experimental rats resveratrol has been seen to suppresses inflammatory responses in endometrial stromal cells. Resveratrol alone is a potential agent for the treatment of endometriosis and may be an alternative to luprolide acetate. Since, resveratrol has been shown to have a potent growth-inhibitory effect against various human cancer cells as well as in in vivo preclinical cancer models. Its use in prevention and treatment of ovarian cancer with serious consideration. Also resveratrol has a role to play in ovarian development and oocyte apoptosis.

Keywords: Resveratrol, antioxidant, cardioprotection, antidiabetic

R

esveratrol is a naturally occurring powerful antioxidant. It is produced by some plants to protect them from the environmental stresses.

It is abundantly found in red grape skin, Japanese knotweed (Polygonum cuspidatum), peanuts, blueberries and some other berries. Resveratrol has been hypothesized to be responsible for low rates of heart disease in the French population compared to other populations, in spite of the fact that they have many risk factors including a high fat diet, smoking and consumption of high amounts of coffee. All of these are known contributors of high cholesterol, high blood pressure, stroke and heart attacks. In theory, this benefit in the French population is due to the consumption of moderate amounts of red wine, which is a rich source of resveratrol.

The first mention of resveratrol was in a Japanese article in 1939 by Michio Takaoka, who isolated it from the poisonous, but medicinal, Veratrum album, variety grandiflorum.1 The name presumably comes from the fact that it is a resorcinol derivative coming from a Veratrum species.2 In 2003, D Sinclair from Harvard Medical School reported in “Nature” that

Associate Professor Dept. of Obstetrics and Gynecology Mahatma Gandhi University of Medical Sciences and Technology, Jaipur, Rajasthan Address for correspondence Dr Alka Gahlot 170, Heera Nagar, DCM, Ajmer Road, Jaipur - 302 021, Rajasthan E-mail: dralkagahlot@gmail.com, alkagahlot23@gmail.com

resveratrol activated sirtuins (SIRT) in yeast cells. While pharmacological effects of resveratrol did not turn out to be commercially viable, their discovery lead to efforts to develop other types of SIRT genes’ activators.

PHARMACOKINETICS While 70% of orally administered resveratrol is absorbed, its oral bioavailability is approximately 0.5% due to extensive hepatic glucuronidation and sulfation.3 Only trace amounts (below 5 ng/mL) of unchanged resveratrol could be detected in the blood after 25 mg oral dose. In humans and rats, <5% of the oral dose was observed as free resveratrol in blood plasma.3-5 The most abundant resveratrol metabolites in humans, rats and mice are trans-resveratrol-3-O-glucuronide and transresveratrol-3-sulfate.6 Walle suggests sulfate conjugates are the primary source of activity,3 Wang et al suggests the glucuronides7 and Boocock et al also emphasized the need for further study of the effects of the metabolites, including the possibility of deconjugation to free resveratrol inside cells. Goldberd, who studied the pharmacokinetics of resveratrol, catechin and quercetin in humans, concluded “it seems that the potential health benefits of these compounds based upon the in vitro activities of the unconjugated compounds are unrealistic and have been greatly exaggerated”.

MECHANISM OF ACTION Resveratrol is chemically 3,5,4’-trihydroxy-trans-stilbene.

It protects the cells DNA as it a powerful antioxidant.

Antioxidants prevent cell damage caused by free radicals.

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OBSTETRICS AND GYNECOLOGY Some studies indicate resveratrol activates SIRT18,9 and peroxisome proliferator-activated receptorgamma, coactivator-1-alfa (PGC-1α) and improves the functioning of the mitochondria.9 In cells treated with resveratrol, a 14-fold increase in the action of manganese superoxide dismutase (MnSOD2) is observed.10 MnSOD reduces superoxide to hydrogen peroxide (H2O2), but H2O2 is not increased due to other cellular activity. It has been implicated in lifespan extension, inhibits cancer (e.g. pancreatic cancer)11,12 and provides resistance to reperfusion injury and irradiation damage.13-15 These effects have also been observed with resveratrol. Resveratrol interferes with all three stages of carcinogenesis: (1) initiation, (2) promotion and (3) progression. Experiments in cell cultures of varied types and isolated subcellular systems in vitro imply many mechanisms in the pharmacological activity of resveratrol.

These mechanisms include modulation 16 of the transcription factor NF-κB, inhibition of the cytochrome P450 isoenzyme CYP1A117 (although this may not be relevant to the CYP1A1-mediated bioactivation of the procarcinogen benzo(a)pyrene),18 alterations in androgenic19 actions and expression and activity of cyclooxygenase (COX) enzymes. In vitro, resveratrol “inhibited the proliferation of human pancreatic cancer cell lines”. Resveratrol was reported to be effective against neuronal cell dysfunction and cell death, and in theory, could be effective against diseases such as Huntington’s disease and Alzheimer’s disease.20,21 Again, this has not yet been tested in humans for any disease.

Resveratrol has direct inhibitory action on cardiac fibroblasts and may inhibit the progression of cardiac fibrosis.22 It also significantly increases natural testosterone production from being both a selective estrogen receptor modulator23 and an aromatase inhibitor.24 Resveratrol increases intracellular glutathione levels, which protects them against cigarette smoke extract-induced oxidative stress.25 In 2012, it was shown that resveratrol is capable of competitively inhibiting various phosphodiesterases, which results in an increase in cytosolic concentration of cyclic adenosine monophosphate (cAMP), which acts as a second messenger for the activation of various enzymatic pathways. This rise of cAMP concentration allows an increase in oxidation of fatty acids, mitochondrial biogenesis, mitochondrial respiration and gluconeogenesis.26,27

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CHEMICAL PROPERTIES Resveratrol (3,5,4’-trihydroxystilbene) is a stilbenoid, a derivate of stilbene. It exists as two geometric isomers: cis- (Z) and trans- (E), with the trans-isomer shown in Figure 1 in the left side. The trans- and cis-resveratrol can be either free or bound to glucose.28 The transform can undergo isomerization to the cis-form when exposed to ultraviolet irradiation,29 a process called “photoisomerization”:30 Ultraviolet irradiation to cis-resveratrol induces further photochemical reaction, produces a fluorescent molecule named “resveratrone”.31 Trans-resveratrol in the powder form was found to be stable under “accelerated stability” conditions of 75% humidity and 40°C in the presence of air.32 The transisomer is also stabilized by the presence of transport proteins.33 Resveratrol content also was stable in the skins of grapes and pomace taken after fermentation and stored for a long period.34 EFFECTS OF RESVERATROL ÂÂ

Cardioprotective role: It appears to stimulate endothelial nitric oxide synthase (eNOS) activity;35 and inhibition of platelet aggregation.36 The cardioprotective effects of resveratrol also are theorized to be a form of preconditioning—the best method of cardioprotection, rather than direct therapy.37

ÂÂ

Antidiabetic effect: In animal models, resveratrol has been shown to act as agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ), nuclear receptor, a current pharmacological target for the treatment of type 2 diabetes.38

ÂÂ

Impact on aging and thyroid function: Resveratrol characterized by antioxidative, anti-inflammatory and apoptotic properties is believed to regulate several biological processes, mainly metabolism and aging, by modulating the mammalian silent information regulator 1 (SIRT1) of the H OH

H

HO

H

hv, 350 nm

HO

MeOH

H OH

OH OH

Figure 1. Isomerization of the trans-isomer to cis-isomer on exposure to ultraviolet irradiation.

OBSTETRICS AND GYNECOLOGY sirtuin family. Resveratrol may arrest, among various tumors, cell growth in both papillary and follicular thyroid cancer by activation of the mitogen-activated protein kinase (MAPK) signal transduction pathway as well as increase of p53 and its phosphorylation. Finally, resveratrol also influences thyroid function by enhancing iodide trapping and, by increasing thyroid-stimulating hormone (TSH) secretion via activation of sirtuins and the phosphatidylinositol-4-phosphate 5 kinase γ (PIP5Kγ) pathway, positively affects metabolism.

growth-inhibitory effect against various human cancer cells as well as in in vivo preclinical cancer models. While resveratrol is effective in suppressing the in vitro cellular invasion of ovarian cancer cells, these effects do not appear to impact on in vivo ovarian cancers in rats.44 ÂÂ

Role of resveratrol in ovarian development and oocyte apoptosis: In studies performed on rats, it was found that resveratrol may delay oocyte nest breakdown and inhibit both the primordialto-developing-follicle transition and apoptosis by decreasing the activation of Foxo3a, Bim and p27KIP1, thus augmenting the resting follicle reserves, maintaining regular estrous cycles of early aged rats and delaying climacterium.45

A lot of beneficial effect of resveratrol have been postulated, but ideal, dosages, side effects and potential long-term benefits still need further evaluation.

The oxidative stress-induced by ultraviolet radiation is one of the main causes for premature skin aging. Resveratrol has shown photoprotective effects.39,40 ÂÂ

Neuroprotective effects: In several animal model studies, resveratrol has shown to reduce brain plaque levels in Alzheimer’s.41

RESVERATROL AND ITS USE IN GYNECOLOGY Resveratrol is being extensively studied for its antiangiogenic, antioxidant, anti-inflammatory properties.

A lot of studies have been conducted in experimental models on its probable benefits to humans. ÂÂ

Use of resveratrol in endometriosis: In experimental rats resveratrol has been seen to suppresses inflammatory responses in endometrial stromal cells, due to its possible role in SIRT1 pathway. Resveratrol may have the potential to ameliorate local inflammation in endometriomas.42

Resveratrol alone is a potential agent for the treatment of endometriosis and may be an alternative to luprolide acetate. In contrast, the combination of luprolide acetate and resveratrol decreased the anti-inflammatory and antiangiogenic effects of each agent. Since resveratrol is widely used as an alternative therapy for a variety of conditions, it can undermine the effectiveness of leuprolide acetate.

Therefore, caution should be exercised when used in combination with other agents.43 ÂÂ

Role of resveratrol in ovarian cancer: Epithelial ovarian cancer represents the most lethal gynecological cancer and the high mortality rate makes this malignancy a major health concern.

Poor prognosis results from an inability to detect ovarian cancers at an early, curable stage, as well as from the lack of an effective therapy. Thus, effective and novel strategies for prevention and treatment with nontoxic agents merit serious consideration.

Resveratrol, obtained from grapes, berries, peanuts and red wine, has been shown to have a potent

REFERENCES 1. Takaoka M. Resveratrol, a new phenolic compound, from Veratrum grandiflorum. J Chem Soc Japan. 1939;60: 1090-100.

2. Schröder, Joachim. Discovery of resveratrol. Resveratrol.

2010.

3. Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004;32(12):1377-82.

4. Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, et al. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev. 2007;16(6): 1246-52.

5. Wenzel E, Soldo T, Erbersdobler H, Somoza V. Bioactivity and metabolism of trans-resveratrol orally administered to Wistar rats. Mol Nutr Food Res. 2005;49(5):482-94.

6. Yu C, Shin YG, Chow A, Li Y, Kosmeder JW, Lee YS, et al.

Human, rat, and mouse metabolism of resveratrol. Pharm Res. 2002;19(12):1907-14.

7. Wang LX, Heredia A, Song H, Zhang Z, Yu B, Davis C, et al.

Resveratrol glucuronides as the metabolites of resveratrol in humans: characterization, synthesis, and anti-HIV activity. J Pharm Sci. 2004;93(10):2448-57.

8. Alcaín FJ, Villalba JM. Sirtuin activators. Expert Opin Ther Pat. 2009;19(4):403-14.

9. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell.

2006;127(6):1109-22.

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OBSTETRICS AND GYNECOLOGY 10. Robb EL, Page MM, Wiens BE, Stuart JA. Molecular mechanisms of oxidative stress resistance induced by resveratrol: specific and progressive induction of MnSOD. Biochem Biophys Res Commun. 2008;367(2):406-12.

24. Wang Y, Lee KW, Chan FL, Chen S, Leung LK. The red wine polyphenol resveratrol displays bilevel inhibition on aromatase in breast cancer cells. Toxicol Sci. 2006;92(1): 71-7.

11. Cullen JJ, Weydert C, Hinkhouse MM, Ritchie J, Domann FE, Spitz D, et al. The role of manganese superoxide dismutase in the growth of pancreatic adenocarcinoma.

Cancer Res. 2003;63(6):1297-303.

25. Kode A, Rajendrasozhan S, Caito S, Yang SR, Megson IL, Rahman I. Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smokemediated oxidative stress in human lung epithelial cells.

Am J Physiol Lung Cell Mol Physiol. 2008;294(3):L478-88.

12. Mounting evidence shows red wine antioxidant kills cancer (press release). New York: University of Rochester Medical Center; 2008.

26. Tennen RI, Michishita-Kioi E, Chua KF. Finding a target for resveratrol. Cell. 2012;148(3):387-9.

13. Sun J, Folk D, Bradley TJ, Tower J. Induced overexpression of mitochondrial manganese-superoxide dismutase extends the life span of adult Drosophila melanogaster.

Genetics. 2002;161(2):661-72.

27. Park SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell.

2007;148(3):421-33.

14. Hu D, Cao P, Thiels E, Chu CT, Wu GY, Hippocampal long-term potentiation, longevity in mice that overexpress superoxide dismutase. Neurobiol 2007;87(3):372-84.

Oury TD, et al. memory, and mitochondrial Learn Mem.

28. Mattivi F, Reniero F, Korhammer S. Isolation, characterization, and evolution in red wine vinification of resveratrol monomers. J Agric Food Chem.

1995;43(7):1820-3.

15. Wong GH. Protective roles of cytokines against radiation: induction of mitochondrial MnSOD. Biochem Biophys Acta. 1995;1271(1):205-9.

29. Lamuela-Raventos RM, Romero-Perez AI, Waterhouse AL, de la Torre-Boronat MC. Direct HPLC analysis of cisand trans-resveratrol and piceid isomers in spanish red vitis vinifera wines. J Agric Food Chem. 1995;43(2):281-3.

16. Leiro J, Arranz JA, Fraiz N, Sanmartín ML, Quezada E, Orallo F, et al. Effect of cis-resveratrol on genes involved in nuclear factor kappa B signaling. Int Immunopharmacol.

2005;5(2):393-406.

30. Bernard E, Britz-McKibbin P, Gernigon N. Resveratrol photoisomerization: an integrative guided-inquiry experiment. J Chem Educ. 2007;84(7):1159.

17. Chun YJ, Kim MY, Guengerich FP. Resveratrol is a selective human cytochrome P450 1A1 inhibitor. Biochem Biophys Res Commun. 1999;262(1):20-4.

31. Yang I, Kim E, Kang J, Han H, Sul S, Park SB, et al.

Photochemical generation of a new, highly fluorescent compound from non-fluorescent resveratrol. Chem Commun (Camb). 2012;48(32):3839-41.

18. Schwarz D, Roots I. In vitro assessment of inhibition by natural polyphenols of metabolic activation of procarcinogens by human CYP1A1. Biochem Biophys Res Commun. 2003;303(3):902-7.

32. Prokop J, Abrman P, Seligson AL, Sovak M. Resveratrol and its glycon piceid are stable polyphenols. J Med Food.

2006;9(1):11-4.

19. Benitez DA, Pozo-Guisado E, Alvarez-Barrientos A, Fernandez-Salguero PM, Castellón EA. Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines. J Androl.

2007;28(2):282-93.

20. Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides.

J Biol Chem. 2005;280(45):37377-82.

21. Parker JA, Arango M, Abderrahmane S, Lambert E, Tourette C, Catoire H, et al. Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet. 2005;37(4):349-50.

22. Olson ER, Naugle JE, Zhang X, Bomser JA, Meszaros JG. Inhibition of cardiac fibroblast proliferation and myofibroblast differentiation by resveratrol. Am J Physiol Heart Circ Physiol. 2005;288(3):H1131-8.

23. Bhat KP, Lantvit D, Christov K, Mehta RG, Moon RC, Pezzuto JM. Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models. Cancer Res. 2001;61(20):7456-63.

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33. Pantusa M, Bartucci R, Rizzuti B. Stability of transresveratrol associated with transport proteins. J Agric Food Chem. 2014;62(19):4384-91.

34. Bertelli AA, Gozzini A, Stradi R, Stella S, Bertelli A. Stability of resveratrol over time and in the various stages of grape transformation. Drugs Exp Clin Res. 1998;24(4):207-11.

35. Duffy SJ, Vita JA. Effects of phenolics on vascular endothelial function. Curr Opin Lipidol. 2003;14(1):21-7.

36. Olas B, Wachowicz B. Resveratrol, a phenolic antioxidant with effects on blood platelet functions. Platelets.

2005;16(5):251-60.

37. Das DK, Maulik N. Resveratrol in cardioprotection: a therapeutic promise of alternative medicine. Mol Interv.

2006;6(1):36-47.

38. Wang L, Waltenberger B, Pferschy-Wenzig EM, Blunder M, Liu X, Malainer C, et al. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ: a review. Biochem Pharmacol. 2014;92(1): 73-89.

OBSTETRICS AND GYNECOLOGY 39. Afaq F, Mukhtar H. Botanical antioxidants in the prevention of photocarcinogenesis and photoaging. Exp Dermatol. 2006;15(9):678-84.

40. Baliga MS, Katiyar SK. Chemoprevention of photocarcinogenesis by selected dietary botanicals. Photochem Photobiol Sci. 2006;5(2):243-53.

41. Anekonda TS. Resveratrol: a boon for treating Alzheimer’s disease? Brain Res Rev. 2006;52(2): 316-26.

endometriosis: a possible role of the sirtuin 1 pathway.

J Obstet Gynaecol Res. 2014;40(3):770-8.

43. Bayoglu Tekin Y, Guven S, Kirbas A, Kalkan Y, Tumkaya L, Guvendag Guven ES. Is resveratrol a potential substitute for leuprolide acetate in experimental endometriosis? Eur J Obstet Gynecol Reprod Biol. 2015;184:1-6.

44. Stakleff KS, Sloan T, Blanco D, Marcanthony S, Booth TD, Bishayee A. Resveratrol exerts differential effects in vitro and in vivo against ovarian cancer cells. Asian Pac J Cancer Prev. 2012;13(4):1333-40.

42. TaguchiA, Wada-Hiraike O, Kawana K, Koga K, YamashitaA, 45. Kong XX, Fu YC, Xu JJ, Zhuang XL, Chen ZG, Luo LL. Shirane A, et al. Resveratrol suppresses inflammatory Resveratrol an effective regulator of ovarian development and oocyte. J Endocrinol Invest. 2011;34(11):e374-81. responses in endometrial stromal cells derived from ■■■■

Duration of Lactation Associated with Bone Density Maternal bone density decreases after childbirth, but only among women who lactate for at least 4 months. The lactation period is unrelated to vitamin D status. A PhD thesis at Sahlgrenska Academy has explored the issue.

The most important role of vitamin D is to help maintain calcium homeostasis in the body. According to some hypotheses, there is a correlation between maternal vitamin D status and bone density during pregnancy and lactation. A recently completed PhD thesis at Sahlgrenska Academy, University of Gothenburg, identified an association between lactation period and bone density, though unrelated to vitamin D status.

Belly Fat Linked to Gestational Diabetes Risk Women with high levels of abdominal fat in their first trimester are at increased risk for diabetes later in pregnancy, a new study suggests.

The study included nearly 500 women, aged 18-42, who had ultrasounds to assess their abdominal fat at 11-14 weeks of pregnancy. Those with higher levels of fat were more likely to develop diabetes at 24-28 weeks of pregnancy. But the study only showed an association, and not a cause-and-effect relationship, between belly fat and diabetes risk in pregnancy.

Menopause Therapy: “Don’t Suffer Silently,” Says UK NICE The UK National Institute for Health and Care Excellence (NICE) has issued its first-ever guidance on menopause, which emphasizes that help and information are available to women suffering from symptoms and that a range of treatment options, such as hormone-replacement therapy (HRT) as well as nondrug treatments, can be discussed with their doctors.

The new guidelines were widely reported in the UK media, along with a variety of reactions. NICE notes that menopause is a gradual process that occurs on average, at age 51 in UK women, and it estimates that 80% of women going through perimenopause/menopause suffer from common symptoms such as hot flashes and night sweats. Other debilitating symptoms include mood changes, sleep disturbances, joint and muscle pain, and headaches.

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A 28 Weeks Pregnancy with Huge Ovarian Cyst: A Rare Case Report MONICA VERMA*, LAXMI MARU†, DEVYANI TIWARI‡

ABSTRACT Majority of ovarian cysts are functional and resolve spontaneously by the second trimester. Finding huge ovarian cyst like in our patient is a rarity. It affected the growth of the ongoing pregnancy causing intrauterine growth retardation.

Keywords: Ovarian cyst, pregnancy, intrauterine growth retardation, tocolytics

T

he presence of ovarian cyst in pregnancy is unusual with prevalence of around 1-2% and the incidence of malignancy being 1-3%. Such masses rarely grow beyond 5 cm and by the second trimester are also not commonly found. Such ovarian tumors are left for conservative management unless they show signs of malignancy or grow to sizes as big as to prevent the growth of the baby. We present a case of a healthy 28-week pregnancy with a huge 15 kg ovarian cyst, which was managed by a laparotomy followed by tocolytics.

CASE REPORT A 30-year-old woman third gravida with previous one section with one vaginal birth after cesarean (VBAC) presented to us in the emergency. Being third gravida, she knew that her abdomen was growing very fast.

She presumed to have been carrying two babies. She went for her first antenatal visit in her 5th month of pregnancy in the periphery, where an ultrasound was done and an ovarian cyst was diagnosed. She was referred to us with this finding. She was very apprehensive toward the diagnosis and fear associated of it being a malignancy. The patient reported to us

*Assistant Professor †Professor and Head ‡Resident Doctor Dept. of Obstetrics and Gynecology MGMMC and MYH, Indore, Madhya Pradesh Address for correspondence Dr Monica Verma Assistant Professor, Dept. of Obstetrics and Gynecology MGMMC and MYH, Indore - 452 001, Madhya Pradesh E-mail: mv27sep@gmail.com

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only at 7th month. She presented with overdistended abdomen of 36 weeks size and a cystic mass was felt.

Uterus was not felt and no fetal parts or fetal heart sounds were heard. A sonography was repeated and it showed a huge mass of the ovary with solid and cystic components and strong possibility of neoplasia.

However, the baby was healthy of 28 weeks with no abnormality. After correcting the anemia patient was taken up for laparotomy under gestational age. Huge ovarian cyst of 40 × 40 × 15 cm was present on the right side with a normal uterus. The left ovary also appeared polycystic. The right ovary appeared to be benign on gross inspection. It was removed completely without rupturing it. On weighing, it was found to be of around 15 kg. The left ovary was aspirated and clear fluid of around 100 mL was removed. It was left in situ. The specimen ruptured spontaneously because of the thin and papery wall and the material inside it was sticky and slimy like a mucinous one. The patient was managed with duvadilan and progesterone to prevent preterm labor. The postoperative period of the patient went uneventful with both mother and baby in good health. The uterine fundal height was now corresponding to that of 28 weeks. The histopathology showed serous cystadenoma of the ovary. The patient delivered at 40 weeks vaginally.

She had spontaneous labor and delivered a healthy but intrauterine growth retarded (IUGR) child weighing 2 kg.

DISCUSSION Finding ovarian cysts in pregnancy is not an extreme rarity. After 16 weeks frequency of ovarian cysts is

OBSTETRICS AND GYNECOLOGY reported between 0.5% and 3.0%.1 Such cysts do increase with pregnancy but cysts taking such large sizes is very unusual. Functional cysts are the most common ovarian tumors diagnosed in pregnancy. These ovarian cysts carry the risk of torsion, hemorrhage, malignancy, early pregnancy losses, IUGR and also preterm labor.

with an ovarian cyst of 15 kg. There have been case reports from Haldwani, Uttarakhand4 and Pakistan5 Both patients were multigravidas and had healthy pregnancies.

An ultrasound is quite accurate for the detection and assessment of risk of malignancy. Morphological criteria are more accurate for identification of benign cyst than malignant mass. It should be the first imaging modality of investigation for ovarian mass in pregnant or nonpregnant women.2 Expectant management is recommended for most pregnant patients with asymptomatic, nonsuspicious cystic masses. Surgical intervention during pregnancy is indicated for large or symptomatic tumors and those that appear highly suspicious for malignancy on imaging.3

Ovarian cysts in pregnancy must be managed conservatively unless an ultrasound suggests malignancy. Majority of ovarian cysts are functional and resolve spontaneously by the second trimester.

Finding huge ovarian cyst like in our patient is a rarity.

It affected the growth of the ongoing pregnancy causing IUGR. But, the surgical intervention prevented many more foreseen complications to both the mother and the baby.

Large cyst like our patient can prevent growth of the baby and give discomfort to the mother in the form of respiratory and heart function compromise.

If ruptured inside the abdomen, it could cause pseudomyxoma peritonei. A timely laparotomy multiplied the chances of a good fetal outcome and also prevented from the risk of prematurity. The extent of surgery depends on the intraoperative diagnosis of a benign versus malignant tumor. We opted for a conservative approach in the form of oophorectomy as it clearly appeared a benign ovarian tumor. The other ovary also showed polycystic appearance, which explained the condition and tendency. There have not been many case reports of such advanced pregnancy

1. Goffinet F. Ovarian cysts and pregnancy. J Gynecol Obstet Biol Reprod (Paris). 2001;30(1 Suppl):S100-8.

CONCLUSION

REFERENCES

2. Valentin L. Use of morphology to characterize and manage common adnexal masses. Best Pract Res Clin Obstet Gynaecol. 2004;18(1):71-89.

3. American College of Obstetricians and Gynecologists.

ACOG Practice Bulletin. Management of adnexal masses.

Obstet Gynecol. 2007;110(1):201-14.

4. Pandey N, Chauhan P, Rawat U, Jain G. Huge mucinous cystadenoma complicating third trimester with previous two caesarean. Acta Medica International. 2014;1(1):43-5.

5. Noreen H, Syed S, Chaudhri R, Kahloon LE. A large unilocular mucinous cystadenoma in third trimester. J Coll Physicians Surg Pak. 2011;21(7):426-8.

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New, Investigational PARP1/2 Inhibitor BGB-290 Shows Promise Against Ovarian Cancer Treatment with BGB-290, a new, investigational, highly selective inhibitor of PARP1/2, was safe, tolerable and yielded clinical responses in patients with advanced ovarian cancer, according to data from a phase I clinical trial presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Nov. 5-9.

As of June 30, 2015, 29 patients with relapsed or refractory solid tumors had been enrolled in the clinical trial.

Among the 14 ovarian cancer patients for whom there were evaluable data, seven had an objective response, as assessed by RECIST 1.1 criteria. One was a complete response and six were partial responses. One of the six patients with a partial response had disease progression and withdrew from the trial after being treated with BGB-290 for 420 days. All other responders remained on treatment with response sustained.

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PEDIATRICS

Role of Zinc in Growth and Immunity in Children SHWETA PATHAK

ABSTRACT With the progressive elimination of dietary protein-energy deficits, deficiencies of micronutrients are emerging as the limiting factors in ensuring childrenâ&#x20AC;&#x2122;s optimal health. Zinc is one such nutrient whose importance has been emphasized now as a major contributor in promoting physical growth, mental development and a healthy immune system. Deficiency of this micronutrient can cause an overall impairment of a childâ&#x20AC;&#x2122;s physical and mental development. Oral zinc therapy results in complete remission of symptoms.

Keywords: Micronutrients, zinc, deficiency, immune system, mental development

W

ith the progressive elimination of dietary protein-energy deficits, deficiencies of micronutrients are emerging as the limiting factors in ensuring childrenâ&#x20AC;&#x2122;s optimal health. Animal studies in the 1930s first documented the essentiality of zinc for growth and survival of animals.1 Unfortunately, it was not until the 1960s and the seminal work of Prasad2 that the importance of zinc deficiency in human populations was appreciated.

Adequate dietary zinc is necessary for taste perception, reproduction, immunocompetence, skin integrity, wound healing, skeletal development, brain development, behavior, vision and gastrointestinal function in humans. It is apparent, therefore, that zinc regulates many physiological and psychological functions and is required to promote health and well-being.

FUNCTION On the cellular level, the function of zinc can be divided into three categories: (1) catalytic, (2) structural and (3) regulatory.

Catalytic Role Over 300 different enzymes depend on zinc for their function. At least one zinc containing enzyme is found in each of the six major categories of enzymes designated by the International Union of Biochemistry Commission on Enzyme Nomenclature.3

Dept. of Pediatrics and Neonatology Fortis Escorts and Research Centre, Faridabad, Haryana E-mail: dr.shwetapgupta@gmail.com

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Structural Role Zinc plays an important role in the structure of proteins and cell membranes. A finger-like structure, known as a zinc finger motif, stabilizes the structure of many proteins. Loss of zinc from biological membranes increases their susceptibility to oxidative damage.

Regulatory Role Zinc finger motifs also regulate gene expression by acting as transcription factors. Zinc also plays a role in cell signaling, hormone release, nerve impulse transmission and regulation of apoptosis. The current recommended dietary allowance for zinc taken by mouth is: 3 mg for 6 months old to 3 years old; 5 mg for 4-8 years old; 8 mg for 9-13 years old; 11 mg for males 14-18 years old; 9 mg for 14-18 years old females; 12 mg for 14-18 years old pregnant females and 13 mg for 14-18 years old breastfeeding females (Food and Nutrition Board, Institute of Medicine, National Academies 2001).4 DEFICIENCY

Severe Deficiency Much information about severe zinc deficiency was derived from the study of individuals born with Acrodermatitis enteropathica, a genetic disorder resulting from impaired uptake and transport of zinc. The symptoms include slowing or cessation of growth, delayed sexual maturation, characteristic skin rashes, chronic and severe diarrhea, immune system deficiencies, diminished appetite, impaired taste sensation, swelling of the corneas and behavioral

PEDIATRICS disturbances. Oral zinc therapy results in complete remission of symptoms.4

Marginal Deficiency Even milder zinc deficiency contributes to many health problems, especially in children living in developing countries. Such deficiency contributes to impaired physical and neuropsychological development and increased susceptibility to life-threatening infections in young children. In fact, zinc deficiency has been estimated to cause more than 4,50,000 deaths in children under less than 5 years annually, comprising 4.4% of global childhood deaths.5 Zinc and Growth Retardation Meta-analyzes from zinc intervention trials and several randomized, controlled trials have provided evidence that zinc deficiency contributes to intrauterine growth retardation and stunting in children, depressed cellular immunity and also reduces insulin-like growth factor I production and growth hormone levels.6,7 Early stunting is likely to persist through adolescence if children remain in the same environment but can be reversed by zinc supplementation, which increases linear growth and weight gain in such children.8

thymulin, a zinc-dependent thymic hormone important for T-cell function.9,10 Numerous studies indicate that zinc-deficient animals have suppressed immune responses and increased susceptibility to a diverse range of infectious agents including herpes simplex virus; bacteria such as Mycobacterium tuberculosis and various protozoan and helminthic parasites. In humans, double-blind, placebocontrolled trials of daily zinc supplementation showed that zinc reduces the incidences and durations of acute and chronic diarrhea by 25-30%, of acute lower respiratory tract infection (LRTI) by 45% and of clinical disease caused by Plasmodium falciparum.10 Increased Susceptibility to Infectious Disease in Children ÂÂ

Diarrhea: It’s estimated that deaths of more than 1.8 million children less than 5 years is caused by diarrhea in developing countries annually.

Impaired immunity due to zinc deficiency is probably responsible for causing infectious diarrhea, and persistent diarrhea further worsens the malnutrition. Zinc supplementation along with oral rehydration therapy can significantly reduce the duration and severity of acute and persistent childhood diarrhea. The World Health Organization (WHO) and the United Nations Children’s Fund currently recommend zinc supplementation as part of the treatment for diarrheal diseases in young children.11,12

ÂÂ

Pneumonia: Zinc supplementation may also reduce the incidence of lower respiratory infections, such as pneumonia. Two meta-analyzes have found that zinc supplementation reduces the incidence of pneumonia or respiratory tract illnesses in children less than 5 years of age.

ÂÂ

Malaria: Some studies have indicated that zinc supplementation may reduce the incidence of clinical attacks of malaria in children. A placebocontrolled trial in preschool-aged children in Papua New Guinea found that zinc supplementation reduced the frequency of P. falciparum malaria by 38%. But, a randomized controlled trial in over 42,000 children aged 1-48 months found that zinc supplementation did not significantly reduce mortality associated with malaria and other infections. Due to conflicting reports, it is not yet clear whether zinc supplementation has utility in preventing or treating childhood malaria.13

Delayed Neurological and Behavioral Development Low maternal zinc status has been associated with diminished attention in newborn infants and poorer motor function at 6 months of age.

Zinc is essential for brain development and central nervous system function and is present in synaptic vesicles in a group of glutaminergic neurons. In this form, zinc may modulate responses for a number of neurotransmitters, both excitatory and inhibitory. Some, randomized clinical trials have shown improvements of neurocognitive function in children aged 6-9 years, improved psychomotor development in the first year of life in very low-birth weight (VLBW) infants, and improvements in behavioral aspects in both infants and children following zinc supplementation.9 Impaired Immune System Function Zinc is known to play a central role in the immune system. Adequate intake is essential for normal development and function of cells mediating both innate (neutrophils, macrophages and NK cells) and adaptive (B-cells and T-cells) immune responses. Zinc deficiency adversely affects a number of immune functions, causing decreased production of certain cytokines; reduced activation of zinc-dependent enzymes and transcription factors; decreased activity of

A deficiency of zinc progresses in a pattern that is different from that for most nutrients. Unlike other

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PEDIATRICS nutritional deficiencies, dietary zinc deficiency is manifested initially as a reduction in skeletal growth of children because the concentration of zinc in bone is quite large. Bone zinc is impacted adversely by dietary zinc restriction, particularly in growing children.1 ESTIMATION OF ZINC LEVELS Two general approaches have been zinc status. One strategy has been to indices”, including concentrations of or body fluids or measurements of enzymes and proteins.

used to assess measure “static zinc in tissues zinc-containing

REFERENCES 1. Todd WR, Elvejheim CA, Hart EB. Zinc in the nutrition of the rat. Am J Physiol. 1934;107:146-56.

2. Prasad AS. Discovery of human zinc deficiency and studies in an experimental human model. Am J Clin Nutr.

1991;53(2):403-12.

3. Vallee BL, Auld DS. Active zinc binding sites of zinc metalloenzymes. Matrix Suppl. 1992;1:5-19.

4. King JC, Cousins RJ. Zinc. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ (Eds.). Modern Nutrition in Health and Disease. 10th Edition, Baltimore: Lippincott Williams & Wilkins; 2006. pp. 271-85.

Another approach involves the measurement of “dynamic indices” that reflect the performance of zinc-dependent physiological or psychological functions. Current indicators for zinc deficiency, such as plasma, serum or hair zinc concentrations, have poor sensitivity and specificity, and do not change with marginal zinc deficiency. Other static indices of human zinc status have failed to be useful. Red blood cell (RBC) and leukocyte zinc concentration are relatively unresponsive to mild or moderate zinc deficiency.14

5. Fischer Walker CL, Ezzati M, Black RE. Global and regional child mortality and burden of disease attributable to zinc deficiency. Eur J Clin Nutr. 2009;63(5):591-7.

Timed urinary zinc excretion rates are decreased in severe zinc deficiency but are not responsive to more moderate changes in dietary zinc.14

8. Imdad A, Bhutta ZA. Effect of preventive zinc supplementation on linear growth in children under 5 years of age in developing countries: a meta-analysis of studies for input to the lives saved tool. BMC Public Health. 2011;11 Suppl 3:S22.

Deuster et al (1986) did not find a strong correlation between dietary zinc intake and serum zinc, although they did find a relationship between zinc intake and RBC zinc. In a study of induced zinc deficiency, Prasad (1991) found that 5 mg zinc/day did not result in a decrease in plasma zinc until 4-5 months. However, zinc concentration in lymphocytes, granulocytes and platelets decreased within 8-12 weeks and may be a more sensitive indicator of mild zinc deficiency.10 Therefore, current biochemical methods of assessment of human zinc status remain a limitation for routine clinical evaluation of zinc nutritional status.

SUMMARY Nutrition is important in promotion and maintenance of good health. An inadequacy encountered in early stages of growth and development can be hazardous.

Zinc is one such nutrient whose importance has been emphasized now as a major contributor in promoting physical growth, mental development and a healthy immune system. Deficiency of this micronutrient can cause an overall impairment of a child’s physical and mental development.

6. Caulfield LE, Zavaleta N, Shankar AH, Merialdi M. Potential contribution of maternal zinc supplementation during pregnancy to maternal and child survival. Am J Clin Nutr. 1998;68(2 Suppl):499S-508S. 7. Ferguson AC. Prolonged impairment of cellular immunity in children with intrauterine growth retardation. J Pediatr.

1978;93(1):52-6.

9. Prasad AS. Zinc: role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care.

2009;12(6):646-52.

10. Shankar AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998;68(2 Suppl):447S-463S. 11. The United Nations Children’s Fund/World Health Organization. WHO/UNICEF Joint Statement: Clinical Management of Acute Diarrhoea. New York: Geneva; 2004. pp. 1-8.

12. Sazawal S, Black RE, Bhan MK, Jalla S, Bhandari N, Sinha A, et al. Zinc supplementation reduces the incidence of persistent diarrhea and dysentery among low socioeconomic children in India. J Nutr. 1996;126(2): 443-50.

13. Sazawal S, Black RE, Ramsan M, Chwaya HM, Dutta A, Dhingra U, et al. Effect of zinc supplementation on mortality in children aged 1-48 months: a communitybased randomised placebo-controlled trial. Lancet.

2007;369(9565):927-34.

14. Zalewski PD. Zinc and immunity: implications for growth, survival and function of lymphoid cells. J Nutr Immunol. 1996;4(3):39-80.

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PSYCHIATRY

An Atypical Presentation of Obsessive Compulsive Disorder with Repeated Somersaults NITISHA VERMA*, SHILPA ADARKAR†, DEORAJ SINHA‡, RAVINDRA M KAMATH#

ABSTRACT Obsessive compulsive disorder is a common psychiatric disorder where compulsive behaviors are usually in the form of repeated checking or washing. Here we present a case with an atypical presentation of compulsive behavior as repeated somersaults.

Keywords: Obsessive compulsive disorder, atypical presentation, somersault

O

bsessive compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2-3% in the general population.1 The common presentation of compulsive behaviors are in the form of repeated checking, washing, counting, need to ask or confess, symmetry and precision and hoarding.2

Sometimes, OCDs can have atypical presentations with impairment in hearing3 or visual impairment.4 Here we present a case where compulsions were in the form of doing repeated somersaults to an extent that it was confused with psychosis.

CASE REPORT A 29-year-old male, a customer service agent with an airlines, presented with odd and strange behavior in form of doing repeated somersaults since last 4 months.

He would do these acts even in front of other people.

At his home, he would try to jump over his bed, washbasin and even toilet seat, and at his workplace he

*Resident †Associate Professor ‡Assistant Professor #Professor and Head Dept. of Psychiatry Topiwala National Medical College and BYL Nair Charitable Hospital Mumbai, Maharashtra Address for correspondence Dr Nitisha Verma Dept. of Psychiatry OPD 13,1st Floor, OPD Building, Topiwala National Medical College and BYL Nair Charitable Hospital Mumbai Central, Mumbai, Maharashtra E-mail: nitishaverma30@yahoo.com

would try to do a somersault over his computer table.

His actions scared his parents and employers and he was asked not to come to work. His behavior worsened over time and he sustained a fracture to his right ankle in his attempt to do a somersault over a staircase. He would do those acts at the railway stations and also in a moving train. He would do a somersault once in every 5-10 minutes and would spend around 5-6 hours in a day on those actions.

His parents recorded some of those episodes and took him to a neurologist from where he was referred to the Psychiatry OPD. The patient was very restless during his first visit, was repeatedly doing somersaults in the OPD and was not fully cooperative for a detailed interview and mental status examination. As the clinical presentation resembled some disorganization in behavior, he was started on tablet haloperidol 3 mg, tablet trihexyphenidyl 4 mg and tablet clonazepam 0.5 mg for behavioral control, which was increased to 4.5 mg of haloperidol after 7 days. No abnormality was detected in his computed tomography (CT) scan and electroencephalogram (EEG) and his routine blood investigations were within normal limits. As no improvement was perceived after a month of treatment, he was admitted and a change in diagnosis was considered.

A possibility of compulsive behaviors was thought of and the patient was asked leading questions about the same. He reported that he did those somersaults in response to urges which he reported to be his own, recurrent, irrational, intrusive and unwanted. Though the patient could not elaborate about his ‘obsessions’, he said that the ‘urge’ arises out of his frustration and guilt over his past life experiences and inabilities

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PSYCHIATRY and that it decreased to some extent after doing the somersault. He also said that he had to go on repeating the somersault until it was done properly or else he felt that something bad would happen to him. There was no evidence of any delusion, hallucinations or other negative symptoms including apathy, alogia, anhedonia or avolition either during his hospital stay or on history. Hence his diagnosis was revised to OCD, predominantly compulsive acts on the International Classification of Diseases (ICD)-10. His score on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was 20 and he was started on capsule fluoxetine 20 mg, which was increased to 80 mg over a period of 3 weeks. Later tablet fluvoxamine was added in a dose of 50 mg and was increased up to 150 mg. He was also taught the Thought Stop technique and was asked to chart his urges and compulsions on a regular basis. His parents were counseled about the nature of the illness and asked not to get overinvolved or too much critical with the patient. With all these measures, the patient and his family members perceived around 60-70% improvement in the symptoms after around a month of hospital stay and his Y-BOCS score dropped to 10.

DISCUSSION The clinical presentation in this case resembled disorganized behavior and the patient was thought to be psychotic and started on antipsychotics. Later after a detailed evaluation, a change in diagnosis to OCD was

considered. Such unusual presentations of OCD can be wrongly diagnosed and mistreated as indicated in two other case reports.

One case report mentions atypical presentation with hearing impairment which was secondary to inattention due to unwanted, intrusive and repeated thoughts3 and the other one mentions bilateral visual impairment secondary to compulsive behavior in the form of repeated cleaning of both eyes with fingers, which had led to corneal opacities.4 CLINICAL IMPLICATION Misdiagnosis or a delay in diagnosis might lead to loss of time, money and working hours. Detailed evaluation of unusual presentations is a key to avoid these problems and give appropriate and better patient care.

REFERENCES 1. Sadock BJ, Sadock VA, Ruiz P. Synopsis of Psychiatry, 11th Edition. New Delhi: Wolters Kluwer; 2015. pp.10-418.

2. Sadock BJ, Sadock VA, Ruiz P. Synopsis of Psychiatry, 11th Edition. New Delhi: Wolters Kluwer; 2015. pp.10-423.

3. Singh I, Rana AK, Singh MK, Tripathi RK. An atypical presentation of obsessive compulsive disorder with difficulty in hearing. Indian J Psychol Med. 2009;31(2):96-7.

4. Kareem SA, Nambi S. Unusual presentation of blindness.

Indian J Clin Pract. 2012;22(9):468-9.

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Confirmed: Neurologic, Psychiatric Disorders Distinct A meta-analysis examining neuroimaging studies of neurologic and psychiatric disorders concludes that they are distinct illnesses.

“The basal ganglia, insula, lateral and medial temporal cortex, and sensorimotor areas showed greater impairment in neurological disorders; whereas the medial frontal cortex, anterior and posterior cingulate, superior frontal gyrus and occipital cortex (bilateral lingual gyrus and left cuneus) showed greater impairment in psychiatric disorders,” the investigators, led by Nicolas A. Crossley, PhD, from Kings College London, United Kingdom, write. The study was published in the November issue of the British Journal of Psychiatry.

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MEDILAW

Laws Applicable on a Quack KK AGGARWAL

IPC Section 420. Cheating and dishonestly inducing delivery of property.—Whoever cheats and thereby dishonestly induces the person de­ceived to deliver any property to any person, or to make, alter or destroy the whole or any part of a valuable security, or anything which is signed or sealed, and which is capable of being converted into a valuable security, shall be punished with imprisonment of either description for a term which may extend to 7 years, and shall also be liable to fine.

IPC Section 468. Forgery for purpose of cheating.— Whoever commits forgery, intending that the 1 [document or electronic record forged] shall be used for the purpose of cheating, shall be punished with imprisonment of either de­scription for a term which may extend to 1 years, and shall also be liable to fine.

IPC Section 471. Using as genuine a forged 1 [document or electronic record].—Whoever fraudulently or dishonestly uses as genuine any 1 [document or electronic record] which he knows or has reason to believe to be a forged 1 [document or electronic record], shall be punished in the same manner as if he had forged such 1 [document or electronic record].

192. Fabricating false evidence.—Whoever causes any circumstance to exist or 1 [makes any false entry in any book or record, or electronic record or makes any document or electronic record containing a false statement], intending that such circumstance, false entry or false statement may appear in evi­dence in a judicial proceeding, or in a proceeding taken by law before a public servant as such, or before an arbitrator, and that such circumstance, false entry or false statement, so ap­ pearing in evidence, may cause any person who in such proceeding is to form an opinion upon the evidence, to entertain an errone­ous opinion touching any point material to the result of such proceeding, is said “to fabricate false evidence”.

Senior Physician and Cardiologist, Moolchand Medcity, New Delhi Group Editor-in-Chief, IJCP Group and eMedinewS

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Illustrations a.

A, puts jewels into a box belonging to Z, with the intention that they may be found in that box, and that this circumstance may cause Z to be convicted of theft. A has fabricated false evidence.

b. A makes a false entry in his shop-book for the purpose of using it as corroborative evidence in a Court of Justice. A has fabricated false evidence. c.

A, with the intention of causing Z to be convicted of a criminal conspiracy, writes a letter in imitation of Z’s handwriting, purporting to be addressed to an accomplice in such criminal conspiracy, and puts the letter in a place which he knows that the officers of the Police are likely to search. A has fabricated false evidence.

193. Punishment for false evidence.—Whoever intentionally gives false evidence in any stage of a judicial proceeding, or fabri­ cates false evidence for the purpose of being used in any stage of a judicial proceeding, shall be punished with imprisonment of either description for a term which may extend to 7 years, and shall also be liable to fine, and whoever intentionally gives or fabricates false evidence in any other case, shall be punished with imprisonment of either de­ scription for a term which may extend to 3 years, and shall also be liable to fine. Explanation 1.—A trial before a Court-martial; 1[***] is a judicial proceeding. Explanation 2.—An investigation directed by law preliminary to a proceeding before a Court of Justice, is a stage of a judicial proceeding, though that investigation may not take place before a Court of Justice. Illustration A, in an enquiry before a Magistrate for the purpose of ascer­taining whether Z ought to be committed for trial, makes on oath a statement which he knows to be false. As this enquiry is a stage of a judicial proceeding, A has given false evidence. Explanation 3.—An investigation directed by a Court of Justice according to law, and conducted under the authority of a Court of Justice, is a stage of a judicial proceeding, though that inves­tigation may not take place before a Court of Justice. Illustration A, in any enquiry before an officer deputed by a Court of Justice to ascertain on the spot the boundaries of land, makes on oath a statement

MEDILAW which he knows to be false. As this enquiry is a stage of a judicial proceeding. A has given false evidence.

IPC Section 419. Punishment for cheating by personation.—Whoever cheats by personation shall be punished with imprisonment of either de­scription for a term which may extend to 3 years, or with fine, or with both.

416. Cheating by personation.—A person is said to “cheat by personation” if he cheats by pretending to be some other person, or by knowingly substituting one person for another, or representing that he or any other person is a person other than he or such other person really is. Explanation.—The offence is committed whether the individual personated is a real or imaginary person.

Illustrations a.

A cheats by pretending to be a certain rich banker of the same name. A cheats by personation.

b. A cheats by pretending to be B, a person who is deceased. A cheats by personation.

MCI Act 15: 3. Any person who acts in contravention of any provision of sub-section (2) shall be punished with imprisonment for a term which may extend to 1 year or with fine which may extend to one thousand rupees, or with both.

15. Right of Persons Possessing Qualifications in the Schedules to Be Enrolled.

1.

2.

Subject to the other provisions contained in this Act, the medical qualifications included in the Schedules shall be sufficient qualification for enrolment on any State Medical Register.

Save as provided in section 25, no person other than a medical practitioner enrolled on a State Medical Register: a. shall hold office as physician or surgeon or any other office (by whatever designation called) in Government or in any institution maintained by a local or other authority; b. shall practice medicine in any state; c. shall be entitled to sign or authenticate a medical or fitness certificate or any other certificate required by any law to be signed or authenticated by a duly qualified medical practitioner: d. shall be entitled to give evidence at any inquest or in any court of law as an expert under

section 45 of the Indian Evidence Act, 1872 on any matter relating to medicine.

27. Privileges of Persons Who Are Enrolled on the Indian Medical Register Subject to the conditions and restrictions laid down in this Act, regarding medical practice by persons possessing certain recognised medical qualifications, every person whose name is for the time being borne on the Indian Medical Register shall be entitled according to his qualifications to practice as a medical practitioner in any part of India and to recover in due course of law in respect of such practice any expenses, charges in respect of medicaments or other appliances, or any fees to which he may be entitled.

Delhi Medical Council Act: 26 Penalty for falsely claiming to be registered.—If any person whose name is not for the time being entered in the register, falsely represents that il is so entered, or uses in connection with his name or title any words or letters reasonably calculated to suggest that his name is so entered, he shall, on conviction, be punished with fine which may extend to five thousand rupees.

27. False assumption of Medical Practitioner or Practitioner under this Act to be an offence.—Any person who falsely assumes that he is a medical practitioner or practitioner as defined in Clause (7) of Section 2 and practises the modern scientific system of medicine, shall be punishable with rigorous imprisonment which may extend up to 3 years or with fine which may extend up to Rs, 20,000 or with both.

Explanation: Under this section, punishment (can be awarded only to medical practitioners as defined in Section 2(7) of this Act and no punishment may be awarded to any one practicing Veterinary medicine or Veterinary surgery or Homeopathic or the Ayurvedic or the Siddha or the Unani System of Medicine or those holding BAMS or BIMS degree.

The Pharmacy Act, 1948 42. Dispensing by unregistered persons.

(1) On or after such date as the State Government may by notification in the Official Gazette appoint in this behalf, no person other than a registered pharmacist shall compound, prepare, mix, or dispense any medicine on the prescription of a medical practitioner67 [***]; Provided that this sub-section shall not apply to the dispensing by a medical practitioner of medicine for his own patients, or with the general or special sanction

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MEDILAW of the State Government, for the patients of another medical practitioner.68 [Provided further that where no such date is appointed by the Government of a State, this sub-section shall take effect in that State on the expiry of a period of69 [8 years] from the commencement of the pharmacy (Amendment) Act, 1976.]

(2) Whoever contravenes the provisions of sub-section (1) shall be punishable with imprisonment for a term which may extend to 6 months, or with fine not exceeding one thousand rupees or with both.

(3) Cognizance of an offence punishable under this section shall not be taken except upon complaint made by70 [order of the State Government or any officer authorized in this behalf by the State Government or by order of the Executive Committee of the State Council]: Clause (iii) of Rule 2 (ee) of the Drugs and Cosmetics Rules, 1945 (ee) “Registered person— i.

medical

practitioner”

means

a

holding a qualification granted by an authority specified or notified under section 3 of the Indian Medical Degrees Act, 1916 (7 of 1916), or specified in the Schedules to the Indian Medical Council Act, 1956 (102 of 1956); or

ii. registered or eligible for registration in a medical register of a State meant for the registration of persons practicing the modern scientific system of medicine5 [excluding the Homeopathic system of medicine]; or register5

[other than a iii. registered in a medical register for the registration of Homeopathic practitioners] of a State, who although not falling within sub-clause (i) or sub-clause (ii) is declared by a general or special order made by the State Government in this behalf as a person practicing the modern scientific system of medicine for the purposes of this Act; or iv. registered or eligible for registration in the register of dentists for a State under the Dentists Act, 1948 (16 of 1948); or v. who is engaged in the practice of veterinary medicine and who possesses qualifications approved by the State Government.

IPC 417: Punishment for cheating: Whoever cheats shall be punished with imprisonment of either description

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for a term which may extend to 1 year, or with fine. or with both.

IPC 418: Cheating with knowledge that wrongful loss may ensue to person whose interest offender is bound to protect: Whoever cheats with the knowledge that he is likely thereby to cause wrongful loss to a person whose interest in the transaction to which the cheating relates, he was found, either by law, or by a legal contract, to protect, shall be punished with imprisonment of either description for a term which may extend to 3 years, or with fine, or with both.

Section 23 in The Indian Penal Code 23. “Wrongful gain”.—“Wrongful gain” is gain by unlawful means of property to which the person gaining is not legally entitled. “Wrongful loss”.—“Wrongful loss” is the loss by unlawful means of property to which the person losing it is legally entitled. Gaining wrongfully, losing wrongfully.—A person is said to gain wrongfully when such person retains wrongfully, as well as when such person acquires wrongfully. A person is said to lose wrong­fully when such person is wrongfully kept out of any property, as well as when such person is wrongfully deprived of property.

24. “Dishonestly”.—Whoever does anything with the intention of causing wrongful gain to one person or wrongful loss to another person, is said to do that thing “dishonestly”.

25. “Fraudulently”.—A person is said to do a thing fraudulently if he does that thing with intent to defraud but not otherwise.

44. “Injury”.—The word “injury” denotes any harm whatever ille­gally caused to any person, in body, mind, reputation or proper­ty.

269. Negligent act likely to spread infection of disease danger­ous to life.—Whoever unlawfully or negligently does any act which is, and which he knows or has reason to believe to be, likely to spread the infection of any disease dangerous to life, shall be punished with imprisonment of either description for a term which may extend to 6 months, or with fine, or with both.

270. Malignant act likely to spread infection of disease danger­ous to life.—Whoever malignantly does any act which is, and which he knows or has reason

MEDILAW to believe to be, likely to spread the infection of any disease dangerous to life, shall be punished with imprisonment of either description for a term which may extend to 2 years, or with fine, or with both.

336. Act endangering life or personal safety of others.— Whoever does any act so rashly or negligently as to endanger human life or the personal safety of others, shall be punished with impris­onment of either description for a term which may extend to 3 months, or with fine which may extend to two hundred and fifty rupees, or with both.

337. Causing hurt by act endangering life or personal safety of others.—Whoever causes hurt to any person by doing any act so rashly or negligently as to endanger human life, or the personal safety of others, shall be punished with imprisonment of either description for a term which may extend to 6 months, or with fine which may extend to five hundred rupees, or with both.

338. Causing grievous hurt by act endangering life or personal safety of others.—Whoever causes grievous hurt to any person by doing any act so rashly or negligently as to endanger human life, or the personal safety of others, shall be punished with impris­onment of either description for a term which may extend to 2 years, or with fine which may extend to one thousand rupees, or with both.

The Drugs and Cosmetics Act, 1940 24. Persons bound to disclose place where drugs or cosmetics are manufactured or kept.—Every person for the time being in charge of any premises whereon any drug 1 [or cosmetic] is being manufactured or is kept for sale or distribution shall, on being required by any Inspector so to do, be legally bound to disclose to the Inspector the place where the drug 1 [or cosmetic] is being manufactured or is kept, as the case may be.

The Drugs and Cosmetics Act, 1940 [27A Penalty for manufacture, sale, etc., of cosmetics in contravention of this Chapter. —Whoever himself or by any other person on his behalf manufactures for sale or for distribution, or sells, or stocks or exhibits or offers for sale— 136 (i) any cosmetic deemed to be spurious under section 17D or adulterated under section 17E shall be punishable with imprisonment for a term

which may extend to 3 years and with fine which shall not be less than fifty thousand rupees or three times to value of the cosmetics confiscated, whichever is more; (ii) any cosmetic other than a cosmetic referred to in clause (i) in contravention of any provisions of this Chapter or any rule made thereunder shall be punishable with imprisonment for a term which may extend to 1 year or with fine which may extend to twenty thousand rupees, or with both.]

The Indian Medical Degrees Act, 1916 6. Penalty for falsely assuming or using medical titles.—Whoever voluntarily and falsely assumes, or uses any title or description or any addition to his name implying that he holds a degree, diploma, licence or certificate conferred, granted or issued by any authority referred to in section 3, or recognized by the General Council of Medical Education of the United Kingdom, or that he is qualified to practise western medical science, shall be punishable with fine which may extend to two hundred and fifty rupees, or, if he subsequently commits, and is convicted of, an offence punishable under this section, with fine which may extend to five hundred rupees: Provided that nothing in this section shall apply to the use by any person of any title, description, or addition which, prior to the commencement of this Act, he used in virtue of any degree, diploma, licence or certificate conferred upon, or granted, or issued to him.

Cognizance of Offence 7.

No Court shall take congnizance of an offence punishable under this Act, except upon complaint made by order of the 3 (State Government) or upon complaint made, with the previous sanction of the 3 (State Government) by a Council of Medical Registration established by an enactment for the time being inforce in 5 (the State).

No. MCI-6(2)/2014-Med./Medical Council of India General Body 3rd Session (continuing 139th session) Minutes of the General Body Meeting held on 26th & 27th March, 2015.

Amendment 831. Delhi Medical Council’s recommendation for amendment in Section 15(3) of IMC Act, 1956.

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MEDILAW Read: the matter with regard to Delhi Medical Council’s recommendation for amendment in Section 15(3) of IMC Act, 1956.

414 The Council approved the following recommendations of Ethics Committee as approved by the Executive Committee at its meeting held on 13.06.2014 :“……….This issue was discussed in length and it was observed that as per the Indian Medical Council Act, 1956, Section 15, Sub-section (3)..”any person who acts in contravention of any provision of sub-section (2) shall be punished with imprisonment for a term which may extend to 1 year, or with fine which may extend to one thousand rupees, or with both.”

The Ethics Committee feels that this Clause needs to be amended as under: Existing

Proposed Amendments

1 Year

5 Years

Rs. 1,000/-

Rs. 1,00,000/-

The recommendations of the Ethics Committee be placed before the Executive Committee for their consideration.

The Ethics Committee made this recommendations keeping in view the fact that a large number of patients are reported to die due to practice by quacks and there is need for stringent measures to be taken to curve the menace of the society.” The minutes of the above item were read and confirmed in the meeting itself.

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Legal Quote Nizam’s Institute of Medical Sciences vs Prasanth S. Dhananka & Ors on 14 May, 2009 “We must emphasize that the Court has to strike a balance between the inflated and unreasonable demands of a victim and the equally untenable claim of the opposite party saying that nothing is payable. Sympathy for the victim does not, and should not, come in the way of making a correct assessment, but if a case is made out, the Court must not be chary of awarding adequate compensation.”

State Consumer Disputes Redressal Commission, Kodali Venkateswara Rao vs Saumya Medicare International ... on 19 January, 2010: AP state “Based on the principles laid down earlier in medical negligence cases the Hon’ble Supreme Court in its recent decision in Martin F.D. Souza Vs. Mohd. Ishfak reported in 2009 Indian Law SC 174 once again made clear that in proof of the allegation of medical negligence it has to be supported by expert evidence, else, the complaint is liable to be dismissed.”

Raghunath Raheja v Maharashtra Medical Council, AIR 1996 Bom 198 “We are of the view that when a patient or his near relative demands from the Hospital or the doctor the copies of the case papers, it is necessary for the Hospital authorities and the doctors concerned to furnish copies of such case papers to the patient or his near relative.”

Jacob Mathew vs State of Punjab and Anr: 5th day of August 2005: 334/2005/SCI/ 144-145 of 2004 “The standard of care has to be judged in the light of knowledge or equipment available at the time of the incident and not at the date of the trial.”

Nizam Institute of Medical Sciences Vs. Prasanth S. Dhananka and Ors, SC/4119 of 1999 and 3126 of 2000 “There may be cases which do not raise such complicated questions and the deficiency in service may be due to obvious faults which can be easily established such as removal of the wrong limb or the performance of an operation on the wrong patient or giving injection of a drug to which the patient is allergic without looking into the outpatient card containing the warning.”

Indian Journal of Clinical Practice, Vol. 26, No. 6, November 2015

MEDICOFINANCE

Benefits of Estate Planning ESTATE PLANNING Estate planning refers to the process of transfer of one’s properties from one generation to the next generation, with a primary goal to protect, preserve and manage for the assets during your life and after death. It is generally perceived to be for the rich/wealthy people who have enough assets or valuables to leave behind for their heirs. However, estate planning is essential for all, regardless of one’s financial standing. Just analyze your assets and you would be surprised at its volume. Most of us make the mistake of not recognizing our assets, and in turn, our final estate. Estate generally includes Bank balances, cash, property, income from property, shares and debentures, jewelry, insurance policies, provident fund, recurring and fixed deposits, among other assets. Estate planning tools can be classified in two segments: During lifetime and after death.

Controlled estate planning will help you plan against: ÂÂ

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Inadequate income if disability occurs: Electing the maximum benefits from your employer sponsored plans and filling in the gaps with personal disability coverage and insurance waivers of premium.

Inadequate income for his family at his death: To maintain the same standard of living, the family will typically need 80% of the present gross income.

This must be adjusted periodically for inflation, additional debts incurred, education funding needs and special family circumstances.

Wills A Will is a legal document that lays out the fate of one’s property after his death. It states who receives the property and in what proportion. To make it sure that most of estate is transferred to the beneficiaries in the manner one desires, will plays a very significant role.

Insurance From the point of view of Return on Investment, insurance is not an ideal investment tool. Returns from insurance plans rarely beat inflation. One should keep in mind that whole life insurance plan is primarily an estate for the heirs. The longer the term of the policy, the lower will be the amount of premium, i.e., maximum benefit at the lower cost. Insurance policies, such as whole life covers, can be valuable assets that

one leaves behind for legal heirs. Whole life insurance plans provide insurance throughout one’s life or up to specified predetermine age. The maximum age of coverage differs from insurer to insurer. The maximum age of expiry for a whole-life policy could be up to 100 years of age. The sum assured is paid out to the nominee on death of insured or to insured at a predetermined age. Whole life policy payouts include the death benefits and bonus accrued. As a measure of estate planning, the whole life insurance policy is the best in the insurance stable.

Succession Succession is another tool of estate planning wherein the legal heirs inherit the property from their ancestors.

In this tool although there is an exemption of property tax but generally this tool results in dispute between family members. But, if same is adopted amicably, it can work out as a very useful tool of estate planning.

Partition Partition is another tool of estate planning. Under this tool one can make partition of assets/properties or even income in a manner one wants his heirs to own or share. It is a good tool to avoid dispute among the family members and can be done during one’s lifetime as well as after death. It can either be mutual (amicable) or through a court. But taking it as a tool of estate planning, one should do it during lifetime after considering all factors and wishes.

Gifts Gift is another good tool for estate planning during lifetime. A person can make a gift of any property (movable or immovable) during his lifetime. It can be made by discretion of a person in favor of anyone.

Although in a case of gift of an immovable property, there is no exemption of stamp duty, but one can ensure the safe transfer of immovable property in favor of his heirs. It is also important to mention that there is no gift tax on gifts made to relatives as defined in Income Tax Act.

Power of Attorney Power of Attorney gives a person or an organization the legal power to deal with your affairs when your

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MEDICOFINANCE self are not able to do so. The person or organization you appoint is referred to as ‘attorney’ or ‘agent’. The person so appointed can act on your behalf in a manner you require. This route entitles one to do certain acts without his presence and according to the directions given. The power of attorney may be general, to do all acts and deal with all issues relating to all assets or it may be specific, to deal with a particular asset or matter.

Power of Attorney is a good delegation of authority but is not the best tool of estate planning.

Trusts For incorporating a Trust, there need to be: ÂÂ

Intention to create a Trust

ÂÂ

Purpose of the Trust

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Beneficiaries of the Trust i.e., the persons for whose benefit the Trust is created

ÂÂ

Trust Property and transfer of the Trust Property to the Trustee of the Trust.

Components of a Trust ÂÂ

Author of the Trust (Settlor): A person who settles the Trust or the author of the Trust.

ÂÂ

Trustee: The person who is appointed by the settler to administer the trust and who accepts the responsibility of acting as a trustee.

ÂÂ

Beneficiary: The person for whose benefits the trust is created is called the beneficiary.

ÂÂ

Trust Property: The subject matter of the trust is called the Trust Property viz. Immovable property,

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Bank balances, jewelry, investment, etc.

ASSET PROTECTION: PERSONAL RESIDENCE The final available alternative to protect a personal residence is by transferring the ownership of the residence to a trust commonly referred to as a personal residence trust (PRT). This is a trust established initially for the benefit of the doctor and the doctor’s spouse and later for the benefit of the doctor’s children

or other beneficiaries. Because, the trust is irrevocable it is treated as the owner of the residence, although the doctor retains full control over his residence by appointing a friendly trustee. The trust allows the doctor to sell the existing home, buy a new home and refinance. In practice, PRTs have proven to be a simple and an extremely effective way of protecting a personal residence.

Other Non-liquid Investments Assets owned by a doctor through an LLC or a limited partnership are not deemed owned by the doctor because these legal entities have their own separate legal existence. If a doctor transfers the ownership of his apartment building into an LLC, the doctor will no longer be treated as the owner of the apartment building. He will now be treated as the owner of a membership interest in the LLC. This means that a plaintiff suing the doctor will no longer be able to reach the apartment building directly, he would now have to pursue the doctor’s interest in the LLC. Forcing the plaintiff to pursue an ownership interest in an LLC or in a limited partnership is a lot more advantageous for the doctor because interests in LLCs and limited partnerships are not subject to attachment by a plaintiff. This is known as the charging order protection. The charging order protection limits a plaintiff’s remedy to a lien against the distributions from the legal entity, without conferring on the plaintiff any voting or management rights. Because, the doctor will remain in control of the entity and can defer distributions, the plaintiff will have no way of enforcing the judgment against the doctor’s LLC or limited partnership interests or the assets owned by these entities. As a practical matter, LLCs and limited partnerships create a formidable obstacle to the creditor’s collection efforts and usually force the creditor to drop his collection efforts or to settle. These entities should be considered by doctors for all valuable assets with the exception of their personal residence.

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AROUND THE GLOBE

SECONDARY PREVENTION OF CVD: OVERVIEW Cardiovascular disease (CVD), including ischemic heart disease and stroke, is the leading cause of death in both developed and developing countries.1 Atherosclerosis and its progression is a critical risk factor influencing the morbidity and mortality of CVD worldwide.2 Several risk factors for CVD are modifiable by lifestyle change and inexpensive pharmacotherapy, thus making it preventable.3 Patients with history of acute myocardial infarction (MI) and multiple risk factors are at risk of new coronary events.1 ÂÂ

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“Very high risk” subjects require aggressive control of risk factors. This group includes patients with coronary artery disease (CAD) and multiple risk factors (especially diabetes), severe or poorly controlled risk factors (especially active smoking status), multiple risk factors of the metabolic syndrome (particularly high-density lipoproteincholesterol [HDL-C] <40 mg/dL and non-HDL cholesterol ≥130 mg/dL) and those with acute coronary syndromes (ACS).4 “CAD equivalent” should be managed as aggressively as patients with established CAD. These patients, although without known CAD, have similar risk of subsequent CV events as that seen in patients with CAD. Those with noncoronary atherosclerotic disease, diabetes, chronic kidney disease and multiple risk factors that confer a 10-year risk >20%, are among the groups included in the “CAD equivalent” category.4

“Secondary prevention,”- Identifying and controlling the major CV risk factors such as hypertension, dyslipidemia, smoking, obesity, inactivity and diabetes in patients with known CAD potentially reduce subsequent morbidity and mortality in such patients.

This approach is termed “secondary prevention,”4 which has been recommended as a key strategy for

reducing levels of coronary heart disease (CHD).5 Guidelines recommend that all patients with clinical atherosclerotic CVD should receive secondary preventive interventions.6-8 In patients who have had a MI or revascularization procedure, comprehensive risk factor modification reduces mortality, decreases subsequent cardiac events and improves quality-of- life.9 Secondary prevention focuses on individuals who have manifestations of CVD, but where aggressive control of risk factors can impact preventing recurrences of disease.10 In some high-risk patients, considerable residual risk remains despite lifestyle changes. In these patients to prevent mortality, drug therapy, including medications to lower blood pressure and blood cholesterol, is advocated.1,5 Some patients may need early mechanical revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG).6 But, the long-term results postsurgery are compromised by progressive atherosclerosis in native coronary arteries and saphenous vein bypass grafts. Only 60% of vein grafts remain patent 10 years after surgical intervention, and 50% of those that are patent have clinically important stenosis.

Hence, post-CABG patients are at high-risk for subsequent ischemic events, including death, MI and stroke.11 ROLE OF STATINS IN SECONDARY PREVENTION Increased cholesterol levels being the main constituent of atheroma in atherosclerotic CVD have been associated with CVD.12 Statins stabilize vulnerable atherosclerotic plaques by a wide range of biologic effects, including a decrease in the level of low-density

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AROUND THE GLOBE lipoprotein-cholesterol (LDL-C) and high-sensitive C-reactive protein (hs-CRP), as well as a modest increase in the level of HDL-C and are regarded as one of the most effective treatment strategies.13 The clinical effect of statins is directly related to the magnitude of the reduction and achieved levels of LDL-C.14

ROLE OF ROSUVASTATIN IN SECONDARY PREVENTION OF CVD ÂÂ

Rosuvastatin shows better beneficial effects on myocardial salvage than atorvastatin in STsegment elevation myocardial infarction (STEMI) patients, including long-term cardiac function was concluded by a pilot study comparing the effect of a hydrophilic and a hydrophobic statin on cardiac salvage after STEMI. In the study, 75 STEMI patients who had received emergency reperfusion therapy were enrolled and randomized into the hydrophilic statin group (rosuvastatin; 5 mg/day, n = 38) and hydrophobic statin group (atorvastatin; 10 mg/day, n = 37) for 6 months. After 6 months, rosuvastatin (-37.6% ± 17.2%) and atorvastatin (-32.4% ± 22.4%) equally reduced LDL-C levels (p = 0.28). However, rosuvastatin (+3.1% ± 5.9%, p < 0.05), but not atorvastatin (+1.6% ± 5.7%, p = 0.15), improved left ventricular ejection fraction (LVEF). Rosuvastatin reduced B-type natriuretic peptide (BNP) levels compared with atorvastatin (-53.3% ± 48.8% vs -13.8% ± 82.9%, p < 0.05). The myocardial salvage index was significantly higher in the rosuvastatin group than the atorvastatin group (78.6% ± 29.1% vs 52.5% ± 38.0%, p < 0.05) (Fig. 1).23

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A single high-dose of rosuvastatin (40 mg) loading prior to PCI reduced periprocedural myocardial injury in patients with ACS who underwent PCI. In a randomized trial in 445 patients with non-STEMI, rosuvastatin loading 16 hours before PCI resulted in a 53% reduction in the risk of periprocedural MI and a 63% reduction in the risk of 30-day major adverse cardiac events (MACEs), including

Statins also show pleiotropic effects independent of their action on blood lipids:15 modulation of endothelial function, anti-inflammatory action, antioxidant properties, plaque stabilization, effects on thrombosis and vasculogenesis.16 Randomized controlled trials (RCTs) have proven that statins are most effective in those already suffering from CVD as well as have beneficial effect in those without previous CVD but with other high-risk factors such as elevated cholesterol levels diabetes and high blood pressure.12 Statins in RCTs have shown to reduce CV morbidity and mortality from CAD as secondary prevention. Early statin initiation after acute ACS is related to a reduction in mortality and recurrent CV events.17 A single high-dose of statin pretreatment before PCI in patients with ACS is associated with a reduced incidence of short-term adverse events and periprocedural MI.18 The SATURN (Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin versus atorvastatin) study evaluating the long-term antiatherosclerotic efficacy of high-intensity statins observed that long-term high-intensity statin therapy caused greater plaque regression and comparable major adverse CV events rates in ACS when compared with non-ACS patients.19

Atorvastatin 80

8

60

2

3.1 1.6

0 -2

20 0 -20

-13.8

-40 -60

-53.3

-100 Change in LVEF

-120

80

78.6

60

52.5

40 20

-80

-4 -6

100

40

6 4

120

Change in level (%)

10

Change in level (%)

Change in level (%)

Rosuvastatin

0 Reduction in BNP

Change in myocardial salvage index

Figure 1. Changes in LVEF, BNP and myocardial salvage index with rosuvastatin and atorvastatin treatment.

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AROUND THE GLOBE elective (not emergency) CAG or scheduled PCI with ≥1 significant stenosis ≥75% and ≥1 untouched nonculprit target lesion of ≤50% stenosis that could be imaged by intravascular ultrasonography (IVUS), and either LDL-C ≥140 mg/dL or total cholesterol (TC) ≥220 mg/dL in untreated patients or LDL-C ≥100 mg/dL or TC ≥180 mg/dL in those previously treated for hyperlipidemia. Based on the results, it was suggested that rosuvastatin might be useful in the setting of secondary prevention in patients with stable CAD, including those switched from other lipid-lowering drugs.7 The beneficial effect of rosuvastatin even in patients with prior use of lipid-lowering drugs, which suggests that further reduction of LDL-C with rosuvastatin could induce significant atheroma regression, supporting “the lower the better” hypothesis in secondary prevention, at least from the aspect of IVUS plaque imaging.30

cardiac death, nonfatal MI, nonfatal stroke and any ischemia-driven revascularization, compared to no statin pretreatment.18,24 ÂÂ

High-dose rosuvastatin loading before PCI significantly improved 12-month clinical outcomes in patients with ACS who underwent an early invasive strategy. The incidence of MACEs occurred in 20.5% of patients in the control group and 9.8% of patients in the rosuvastatin group (p = 0.002).18,25

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High loading-dose rosuvastatin therapy (20 mg 12 hours before PCI, and a further 20 mg 2 hours before PCI) before PCI was associated with the reduction of periprocedural MI, MACEs and inflammatory response in another randomized study in 67 Chinese patients with non-ST-segment elevation ACS.18,26

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Single high-dose (20 mg) of rosuvastatin prior to PCI reduced postprocedural myocardial injury in patients with ACS, with a concomitant attenuation of postprocedural increase in hs-CRP and interleukin 6 levels shown in another placebo-controlled study.18,27

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Rosuvastatin pretreatment (20 mg/d) starting 1 week before elective coronary artery bypass surgery reduces myocardial damage after coronary surgery. The results of the study confirmed the protective effect of pretreatment with rosuvastatin and continuing through the postoperative period.

Rosuvastatin reduces the inflammatory response to cardiopulmonary bypass without treatmentrelated complications.28

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In SPACEROCKET (Secondary Prevention of Acute Coronary Events—Reduction of Cholesterol to Key European Targets Trial) - a multicenter RCT in patients with acute MI - rosuvastatin 10 mg lowered mean cholesterol more effectively than simvastatin and achieved better results for the latest, more stringent, ESC target. The superior lipid lowering effect of rosuvastatin makes it a good candidate for intensive lipid-lowering.21,29

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The COSMOS (Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects) study: demonstrating significant coronary plaque regression in 76-week administration of rosuvastatin in Japanese patients with stable CAD, including patients with prior use of lipid-lowering drugs, together with potent LDL-C lowering as well as a significant increase of HDL-C and improvement of the LDL-C/HDL-C ratio. The study included patients who were undergoing

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Rosuvastatin significantly improved lipid profiles, with an acceptable safety profile, contributing to regression and stabilization of atherosclerotic plaques in Japanese patients with CAD as concluded by subanalysis of the COSMOS study to determine the effects of rosuvastatin at doses of up to 20 mg/day. The main findings of this subanalysis of COSMOS were that high doses of rosuvastatin (mean dose, 16.9 mg/day) were well-tolerated and improved lipid profiles as an antiatherogenic drug

Rosuvastatin: A Snapshot ÂÂ 3-HMG-CoA reductase inhibitor that reduces LDL-C levels to the greatest extent of all currently marketed statins.20 ÂÂ Enhanced HMG-CoA reductase binding due to addition of a stable polar methane-sulfonamide group, which provides low lipophilicity and enhanced ionic interaction with HMG-CoA reductase enzyme, which improves its binding affinity to the enzyme.21 ÂÂ Pleiotropic effects independent of HMG-CoA reductase inhibition: Improvements in endothelial function, anti-inflammatory, antithrombotic and antioxidant effects.21 ÂÂ Unique features: Selective uptake by hepatic cells, hydrophilic nature and lack of metabolism by cytochrome p450 (CYP) 3A4 isoenzyme → low potential for CYP3A4-mediated drug interactions and adverse events in those requiring concomitant therapy with a statin and agents metabolized by CYP3A4.22

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AROUND THE GLOBE in Japanese patients with CAD, without causing any serious adverse events. Long-term treatment with rosuvastatin also had a good safety profile.31

invasive procedure can prevent contrast-induced acute kidney injury (CI-AKI) and improve short-term clinical outcome.

Objective: Determination of protective effect of highdose rosuvastatin, in addition to standard preventive measures on-admission, against CI-AKI.33

IBIS-4 TRIAL32

Conclusion High-intensity rosuvastatin therapy led to regression of coronary atherosclerosis in non-infarct-related arteries without changes in radiofrequency of IVUS (RF-IVUS).

Objective: Determination of impact of high-intensity statin therapy on plaque burden, composition and phenotype in non-infarct-related arteries of STEMI patients undergoing PCI. One hundred three STEMI patients were subjected to IVUS and RF-IVUS of the two non-infarct-related epicardial coronary arteries (non-IRA) after successful primary PCI. High-intensity rosuvastatin (40 mg/ day) treatment was given to patients over 13 months and serial intracoronary imaging with the analysis of matched segments was available for 82 patients with 146 non-IRA. The primary IVUS endpoint was the change in percent atheroma volume (PAV).32

Results ÂÂ Thirteen months later, LDL-C decreased from a median of 3.29 to 1.89 mmol/L and HDL-C increased from 1.10 to 1.20 mmol/L. ÂÂ PAV of the non-IRA decreased by -0.9%. ÂÂ Patients with regression in at least one non-IRA were more common (74%) than those without (26%). ÂÂ Percent necrotic core was unchanged (-0.05%) as did the number of RF-IVUS defined thin cap fibroatheromas (124 vs. 116).

Results ÂÂ

The incidence of CI-AKI was significantly lower in the statin group than in controls (6.7% vs. 15.1%; Fig. 2).

ÂÂ

The benefits against CI-AKI were consistent, even applying different CI-AKI definition criteria and in all the pre-specified risk categories.

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The statin group exhibited lower 30-day incidence of adverse CV and renal events (death, dialysis, MI, stroke or persistent renal damage) than control group (3.6% vs. 7.9%, respectively).

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Statin treatment on admission correlated with a lower rate of death or nonfatal MI at 6 months follow-up (3.6% vs. 7.2%, respectively).

ROMA II TRIAL34

Conclusion High-dose statin reloading improves procedural and long-term clinical outcomes in stable patients on chronic statin therapy.

Objective: Reloading dose of rosuvastatin vs. atorvastatin administered within 24 hours before PCI in reducing periprocedural myonecrosis and major adverse cardiac and cerebrovascular event (MACCE) in patients on chronic statin treatment undergoing elective PCI.34

PRATO-ACS TRIAL33 20.00

Rosuvastatin

Conclusion

Consecutive statin-naïve non-ST elevation ACS patients slated for early invasive strategy

15.10 Incidence of CI-AKI (%)

High-dose rosuvastatin given on admission to statinnaïve patients with ACS scheduled to undergo early

Control

15.00

10.00 6.70 5.00

0.00 Statin group (n = 252) Rosuvastatin 40 mg on admission, followed by 20 mg/day

590

Control group (n = 252) No statin treatment

Indian Journal of Clinical Practice, Vol. 26, No. 6, November 2015

Treatment

Figure 2. Incidence of CI-AKI in statin vs. control group.

AROUND THE GLOBE Patients with stable angina on chronic statin treatment suitable for elective PCI (n = 350)

7. Eckel RH, Jakicic JM, Ard JD, et al. Circulation. 2014;129(25 Suppl 2):S76-99.

8. Perk J, De Backer G, Gohlke H, et al. Eur Heart J. 2012;33(13):1635-701.

RG

AG

CG

Rosuvastatin 40 mg group (preprocedural reloading dose) (n = 175)

Atorvastatin 80 mg group (preprocedural reloading dose) (n = 175)

Control group (chronic statin therapy without reloading) (n = 100) Standard therapy: Aspirin + clopidogrel 24 hours before surgery

Elective PCI

12- and 24-hour post-PCI CK-MB levels (primary endpoint)

MACCE: Followup at 1, 6 and 12 months (primary endpoint)

9. Hall SL, Lorenc T. Am Fam Physician. 2010;81(3):289-96.

10. Wong ND. Nat Rev Cardiol. 2014;11(5):276-89.

11. Kulik A, Levin R, Ruel M, et al. J Thorac Cardiovasc Surg.

2007;134(4):932-8.

12. Pichandi S, Pasupathi P, Raoc YY, et al. Int J Cur Sci Res. 2011;1(2):47-56.

13. Tian J, Gu X, Sun Y, et al. BMC Cardiovasc Disord.

2012;12:70.

14. Dohi T. Circ J. 2015;79(1):44-50.

15. XL Yu, Qi Dong, HY Li, et al. Exp Clin Cardiol.

2014;20(1):738.

Results ÂÂ The co-primary endpoint of myonecrosis i.e., 12- and 24-hour post-PCI creatine kinase muscle and brain (CK-MB) elevation >3 × occurred more frequently in the CG than in the RG and in the AG (at 24-h: 25.0 vs 7.1; p = 0.003 and 25.0 vs 6.1; p = 0.001). ÂÂ At 1, 6 and 12 month follow-up, the other coprimary endpoint of cumulative MACCE was higher in CG than in the RG or AG (at 12-month: 41.0% vs 11.4% vs 12.0%; p = 0.001). ÂÂ No difference between the RG and AG in terms of myocardial postprocedural necrosis and MACCE occurrence at follow-up.

16. Susic D, Varagic J, Ahn J, et al. J Am Coll Cardiol.

2003;42(6):1091-7.

CONCLUSIONS

24. Yun KH, Jeong MH, Oh SK, et al. Int J Cardiol.

2009;137(3):246-51.

ÂÂ

High-dose statin reloading improves procedural and long-term clinical outcomes in stable patients on chronic statin therapy.

ÂÂ

Both rosuvastatin and atorvastatin showed similar beneficial effects on procedural and long-term outcomes.34

REFERENCES 1. Sanz G, Fuster V. Nat Clin Pract Cardiovasc Med. 2009;6(2):101-10.

2. Kumar R, Garg R, Aggarwal S, et al. Am J Med Sci and Med. 2014;2(3): 58-63.

3. Hsu S, Ton VK, Dominique Ashen M, et al. Clin Cardiol.

2013;36(7):383-93.

17. Nakamura M, Yamashita T, Yajima J, et al. J Cardiol.

2011;57(2):172-80.

18. Hu M, Tomlinson B. Integr Blood Press Control. 2013;6: 15-25.

19. Puri R, Nissen SE, Shao M, et al. Arterioscler Thromb Vasc Biol. 2014;34(11):2465-72.

20. Toth PP. Postgrad Med. 2014;126(2):7-17 21. Luvai A, Mbagaya W, Hall AS, et al. Clin Med Insights Cardiol. 2012;6:17-33.

22. Trivedi H, Mehta HS, Parmar M, et al. Indian Medical Gazette. 2014: p. 313-320.

23. Chitose T, Sugiyama S, Sakamoto K, et al. Atherosclerosis.

2014;237(1):251-8.

25. Yun KH, Oh SK, Rhee SJ, et al. Int J Cardiol. 2011;146(1): 68-72.

26. Luo J, Li J, Shen X, et al. Int J Cardiol. 2013;167(5):2350-3.

27. Wang Z, Dai H, Xing M, et al. J Cardiovasc Pharmacol Ther. 2013;18(4):327-33.

28. Mannacio VA, Iorio D, De Amicis V, et al. J Thorac Cardiovasc Surg. 2008;136(6):1541-8.

29. Hall AS, Jackson BM, Farrin AJ, et al. Eur J Cardiovasc Prev Rehabil. 2009;16(6):712-21.

30. Takayama T, Hiro T, Yamagishi M, et al. Circ J. 2009;73(11):2110-7.

31. Kawashiri MA, Yamagishi M, Sakamoto T, et al.

Cardiovasc Ther. 2013;31(6):335-43

4. Padial LR. Medicographia. 2009;31:384-91.

32. Räber L, Taniwaki M, Zaugg S, et al. Eur Heart J. 2014 pii: ehu373.

5. Byrne M, Walsh J, Murphy AW. J Psychosom Res. 2005;58(5):403-15.

33. Leoncini M, Toso A, Maioli M, et al. J Am Coll Cardiol.

2014;63(1):71-9

6. Smith SC Jr, Benjamin EJ, Bonow RO, et al. Circulation.

2011;124(22):2458-73.

34. Sardella G, Lucisano L, Mancone M, et al. Int J Cardiol.

2013;168(4):3715-20.

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AROUND THE GLOBE

News and Views ÂÂ

Severe, untreated isolated vitamin D deficiency can lead to muscle pain and decreased muscle strength, and a few cases of rhabdomyolysis have even been described. Treating a vitamin D-deficient patient with a statin can decrease his or her muscle pain.

When patients received vitamin D supplementation and the deficiency was corrected, 80% of them were then able to take a statin.

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Eating a diet rich in fruits and vegetables as a young adult may help lower coronary artery calcium (CAC), a known predictor of CV events, up to two decades later, suggests new research published online October 26 in Circulation.

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The US Food and Drug Administration (FDA) has approved a buprenorphine buccal film product for the treatment of chronic pain severe enough to require daily, around-the-clock, long-term opioid treatment, for whom alternative treatment options are not sufficient.

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Nearly 40% of patients who presented with idiopathic acute anterior uveitis (AAU) had undiagnosed spondyloarthritis (SpA), reported two cohort studies, which evaluated a newly developed algorithm called the Dublin Uveitis Evaluation Tool (DUET). The findings were published in Annals of the Rheumatic Diseases.

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592

Chronic constipation in adults could be a sign of more serious gastrointestinal (GI) disorders, including ischemic colitis, colorectal cancer, gastric cancer, and diverticulitis, suggested a new study presented at the American College of Gastroenterology 2015 Annual Meeting.

A new systematic review and meta-analysis has found that the currently available tests with urinebased biomarkers may not be accurate enough to replace standard methods for diagnosis of bladder cancer. The findings were published online October 27 in the Annals of Internal Medicine.

A world-first study by Queensland University of Technology’s Sleep in Early Childhood Research Group has revealed that pre-schoolers exposed to more light earlier in day tend to weigh more.

Researchers noted that moderate intensity light exposure earlier in the day was associated with increased body mass index (BMI) while children who received their biggest dose of light in the

Indian Journal of Clinical Practice, Vol. 26, No. 6, November 2015

afternoon were slimmer. The data were presented at the ASA Sleep Downunder Conference. ÂÂ

An eight-item questionnaire, called the STOPBang questionnaire, might be used in the primary care setting to help identify patients who have obstructive sleep apnea (OSA), suggests new research presented at the annual CHEST meeting.

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Early magnetic resonance imaging (MRI) bone marrow lesions in knees at high-risk of knee osteoarthritis (OA) seemed to represent early radiographic OA, reported an observational study published online in Annals of the Rheumatic Diseases.

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The risk of developing gout was up to 60% higher among patients with sleep apnea vs individuals without sleep apnea, Yuqing Zhang, MD, DSc, from the Boston University Clinical Epidemiology Research and Training Unit and the Department of Medicine at Boston Medical Center in Massachusetts, and colleagues write. They report their findings online October 19 in Arthritis & Rheumatology.

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“Cannabis users were significantly younger, more frequently men, and consumed tobacco and alcohol more frequently than non-cannabis users,” researcher Valerie Wolff, MD, PhD, of the University Hospital Strasbourg, and colleagues wrote in the Journal of the American College of Cardiology, published online Oct. 26.

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New research, scheduled to be presented at the American Academy of Pediatrics National Conference & Exhibition, suggests that maternal stress levels benefit from skin-to-skin contact after birth.

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Asthma patients can reduce their medication safely and save money; however, patients should do this only under professional guidance, suggests new research published in The Journal of Allergy and Clinical Immunology.

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Low-carb diets are more effective than low-fat diets in weight loss and reducing cardiovascular risk, suggests a new meta-analysis published in PLoS One.

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Women with early breast cancer had similar disease control and survival with accelerated partial breast irradiation (APBI) or whole-breast irradiation (WBI),

AROUND THE GLOBE reported a The Lancet. ÂÂ

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randomized

trial

published

Patients with acromioclavicular joint dislocation who opt for non-surgical treatment typically experience fewer complications and return to work sooner in comparison with those who undergo surgery, suggested new research published in the Journal of Orthopaedic Trauma.

The oriental liver fluke, Opisthorchis viverrini, known to cause cancer, secretes a growth factor and drives wound healing and blood vessel growth, suggests new research by James Cook University scientists.

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A phage, called “CR5,” showed strong antimicrobial activity against the bacterium, Cronobacter sakazakii, a type of food-borne bacterium that often kills infants after infecting them via infant formula, reported new research published October 23 online in Applied and Environmental Microbiology.

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An updated practice bulletin from the American College of Obstetrics and Gynecology (ACOG), published in the November issue of Obstetrics & Gynecology, affirms the use of operative vaginal delivery as a way to avoid cesarean delivery and improve outcomes for mothers and babies.

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allergy risk. The findings are published in the Canadian Medical Association Journal.

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A history of bilateral salpingo-oophorectomy does not reduce the odds of death from cardiovascular disease among postmenopausal women with type 2 diabetes; however, there may be an association between oophorectomy and CVD in women aged 45 and younger, suggests a new study published online in Diabetes Care.

People who fell below the lean-muscle-mass cutoff proposed by Dr Richard N Baumgartner et al (Am J Epidemiol.1998;147:755-763) and by the European Working Group on Sarcopenia in Older People (EWGSOP 1) (Age Ageing. 2010;39:412-423) had a significant 2.3-fold greater risk of having a lowtrauma fracture within 3 years, Andrea Trombetti, MD, from the Geneva University Hospitals and Faculty of Medicine, Switzerland, reported in an oral session at the recent American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting.

Treatment with the late-sodium-current blocker ranolazine does not improve outcomes in patients with chronic angina and incomplete revascularization after undergoing PCI, suggests new research presented at TCT 2015 and simultaneously published in the Lancet.

New research suggests that introducing peanuts to babies between 4-11 months of age can reduce

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The US Food and Drug Administration (FDA) has approved the first replacement therapy for hereditary Factor X deficiency, derived from human plasma.

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Smoking was not associated with prevalent nonalcoholic fatty liver disease, but low levels of certain micronutrients did appear to have an association, reported a large cross-sectional analysis presented at the annual meeting of the American College of Gastroenterology.

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Patients diagnosed with Hashimoto’s disease who underwent a complete thyroidectomy saw improvement in symptoms, most notably a reduction in severe fatigue, suggested novel research presented at the International Thyroid Congress.

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A new study suggests that men with depressive symptoms and a low quality of life due to sleep problems are at increased risk of erectile dysfunction. The study is published in The Journal of Sexual Medicine.

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Hearing loss is linked with accelerated cognitive decline in older adults; however, the use of hearing aids may help safeguard seniors’ memory and thinking skills, suggested a new study published in the Journal of the American Geriatrics Society.

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Early results from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) suggest that taking vitamin D supplements during pregnancy may stop the decline in bone mass in women from December through February and may increase the bone mass of babies born then. However, a related study found that taking vitamin D supplements did not improve bone health in pregnant women or their infants, and that high-dose vitamin D supplements weakened the femoral bones in the mothers. The findings were presented at the American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting.

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Those who exhibited more ‘dispositional mindfulness’, or awareness of and attention to their current feelings and thoughts, were less likely to be obese and had less abdominal fat than people who did not exhibit as much of that awareness, suggested new research published in the International Journal of Behavioral Medicine.

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Taking a probiotic strain of Bifidobacterium longum reduced physiologic and psychological stress and led to a modest improvement in memory in a small pilot study of healthy men presented during a

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AROUND THE GLOBE press briefing at the Society for Neuroscience (SfN) 2015 Annual Meeting. ÂÂ

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Annual influenza vaccination is the best defense against influenza. For the 2015-2016 influenza season, the Centers for Disease Control and Prevention (CDC) and the Advisory Committee on Immunization Practices (ACIP) continue to recommend routine annual influenza vaccination for all persons aged 6 months or older who do not have contraindications. (Medscape) Fluid therapy with a buffered crystalloid solution does not reduce the risk for acute kidney injury (AKI) or kidney failure relative to saline among intensive care unit (ICU) patients who need intravenous fluids, according to a new study in JAMA. These findings contradict previously reported observational data that suggested buffered crystalloids may decrease the risk for AKI and death compared with saline in critically ill patients. (Medscape)

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Researchers have created a test that could boost in vitro fertilization success rates to as much as 80%.

The test, called MitoGrade, measures the levels of abnormal mitochondrial DNA present in embryos, allowing doctors to determine which embryos are most viable for a successful pregnancy.

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Survival rates of the rare anaplastic thyroid carcinoma, which has a very poor prognosis, show significant improvement when patients are treated with an aggressive combined-modality therapy, although the toxicities associated with such therapies can take their toll, suggests new research presented at the 2015 International Thyroid Congress and Annual Meeting of the American Thyroid Association (ITC/ATA).

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A new Journal spouse almost

changes in diet, physical activity or other behaviors that impact obesity. ÂÂ

Treatment of nonalcoholic steatohepatitis (NASH) with vitamin E and pentoxifylline leads to improvements in liver enzymes, suggests a new study presented at the American College of Gastroenterology meeting.

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New research from the Department of Pulmonary Medicine and Sleep Disorders and All India Institute of Medical Sciences, India suggests that yoga exercises provide improvements that are as effective as traditional pulmonary rehabilitation methods in improving pulmonary function, exercise capacity, and indices of systemic inflammation in patients with COPD.

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Sleep apnea may increase the risk of developing gout, reported a new study published in Arthritis & Rheumatology.

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Rafael D. Romo, PhD, RN, from the Division of Geriatrics, University of California, San Francisco, and colleagues report in a research letter published online October 19 in JAMA Internal Medicine that older people do not have a good sense of their own life expectancies, nor are they adept at predicting their own prognoses. They suggest that these findings have implications for decision making around future health interventions, and for communication strategies to help facilitate informed decisions.

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In a study that included 106 patients given NASH-specific therapy, those in the treatment group (vitamin E and pentoxifylline) had median decreases in alanine aminotransferase (ALT) of 58.4% compared with a decline of 42.7% in the no-treatment group (p = 0.029), reported Naim Alkhouri, MD, of the Cleveland Clinic in a poster session at the American College of Gastroenterology meeting.

study, published online in the American of Epidemiology, suggests that when one becomes obese, the other’s risk of obesity doubles. This could be due to similar ■■■■

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LIGHTER READING

Two traveling angels stopped to spend the night in the home of a wealthy family. The family was rude and refused to let the angels stay in the mansion’s guest room. Instead the angels were given a small space in the cold basement.

As they made their bed on the hard floor, the older angel saw a hole in the wall and repaired it. When the younger angel asked why, the older angel replied, “Things aren’t always what they seem.” The next night the pair came to rest at the house of a very poor, but very hospitable farmer and his wife.

After sharing what little food they had the couple let the angels sleep in their bed where they could have a good night’s rest. When the sun came up the next morning the angels found the farmer and his wife in tears. Their only cow, whose milk had been their sole income, lay dead in the field.

The younger angel was infuriated and asked the older angel, “How could you have let this happen? The first man had everything, yet you helped him.” she accused. “The second family had little but was willing to share everything, and you let the cow die.” “Things aren’t always what they seem.” the older angel replied. “When we stayed in the basement of the mansion, I noticed there was gold stored in that hole in the wall. Since the owner was so obsessed with greed and unwilling to share his good fortune, I sealed the wall so he wouldn’t find it. Then last night as we slept in the farmer’s bed, the angel of death came for his wife. I gave him the cow instead. Things aren’t always what they seem.”

Sometimes that is exactly what happens when things don’t turn out the way they should. If you have faith, you just need to trust that every outcome is always to your advantage. You might not know it until sometime later. Should you find it hard to get to sleep tonight, remember the homeless family who has no bed to lie in.

Should you find yourself stuck in traffic, don’t despair; there are people in this world for whom driving is an unheard–of privilege. Should you have a bad day at work, think of the man who

has been out of work for many months struggling to feed his family. Should you notice a new gray hair in the mirror, think of the cancer patient in chemo who wishes she had hair to examine. Should you find yourself at a loss and pondering what is life all about, asking, “What is my purpose?”, be thankful, there are those who didn’t live long enough to get the opportunity.

An American tourist asked a boat guy in Zanzibar, “Do you know Biology, Psychology, Geography, Geology or Criminology?” The boat guy said, “No. I don’t know any of these.” The tourist then said, “What the hell do you know on the face of this Earth? You will die of illiteracy!”

The boat guy said nothing. After a while the boat developed a fault and started sinking.

The boatman then asked the tourist, “Do you know Swimology and Escapology from Crocodiology?”

The tourist said, “No!” The boat guy replied, “Well, today you will Drownology and Crocodiology will eat you. I will not Helpology and you will Dieology because of your Badmouthology.”

Doctor, Doctor! I keep getting pains in the eye when I drink coffee! Doc: Have you ever tried taking the spoon out FIRST?

Dr. Good and Dr. Bad SITUATION: A patient with stable angina was on β-blockers.

It will also increase survival

It will relieve angina but not survival

© IJCP Academy

TWO TRAVELING ANGELS

HUMOR

INSPIRATIONAL STORY

Lighter Side of Medicine

LESSON: In patients with stable coronary heart disease who have not had a recent acute MI, β-blockers are indicated to treat angina but not to improve survival (J Am Coll Cardiol. 2014;64(3):247-52).

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Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767).

Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so.

The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript.

Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper.

Covering letter –

– –

The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper.

Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors.

Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

Manuscript – Three complete sets of the manuscript should be submitted and preferably with a CD; typed double spaced throughout (including references, tables and legends to figures).

–

The manuscript should be arranged as follow: Covering letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, Results, Discussion, References, Tables, Legends to Figures and Figures.

–

All pages should be numbered consecutively beginning with the title page.

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors.

Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the departments and institutions where the work was performed,

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name of the corresponding authors, acknowledgment of financial support and abbreviations used.

– The title should be of no more than 80 characters and should represent the major theme of the manuscript.

A subtitle can be added if necessary.

– A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included.

– The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page.

– A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text.

Summary – The summary of not more than 200 words. It must convey the essential features of the paper.

– It should not contain abbreviations, footnotes or references.

Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives.

Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others.

– Ethical guidelines followed by the investigations should be described.

Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected.

– Method of selecting the sample (cases, subjects, etc. from the statistical universe).

– Method of allocating the subjects into different groups.

– Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques.

–

Confidence intervals for the measurements should be provided wherever appropriate.

Results – These should be concise and include only the tables and figures necessary to enhance the understanding of the text.

Discussion –

This should consist of a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g., practicality and cost.

References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses).

At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution.

Examples of common forms of references are: Articles Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes.

Q. J. Expt. Physiol. 1955;40:89-111.

Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat.

– All photomicrographs should indicate the magnification of the print.

– Special features should be indicated by arrows or letters which contrast with the background.

– The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen.

– Color illustrations will be accepted if they make a contribution to the understanding of the article.

–

Do not use clips/staples on photographs and artwork.

–

Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as “Fig.”.

Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected summary, etc.)_______________________________ 2. Total number of pages ________________________ 3. Number of tables ____________________________ 4. Number of figures ___________________________

Books

5. Special requests _____________________________

Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

6. Suggestions for reviewers (name and postal address)

Articles in Books

2.____________ 2.________________

Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.

3.____________ 3.________________

4.____________ 4.________________

Tables –

These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.

Legends – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text.

–

The legend must include enough information to permit interpretation of the figure without reference to the text.

Indian 1.____________Foreign 1.________________

7. All authors’ signatures________________________ 8.

Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

Online Submission Also e-Issue @ www.ijcpgroup.com For Editorial Correspondence

Dr KK Aggarwal

Group Editor-in-Chief Indian Journal of Clinical Practice E-219, Greater Kailash, Part-1 New Delhi - 110 048. Tel: 40587513 E-mail: editorial@ijcp.com Website: www.ijcpgroup.com

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R.N.I. No. 50798/90 Date of Publication 13th of Same Month Date of Posting 13-14 Same Month

POSTAL REGISTRATION NO. DL (S)-01/3200/2015-2017 Posted in N.D. PSO New Delhi