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Indian Journal of

CLINICAL PRACTICE 157-208 Pages

September 2011

Volume 22, Number 4

Traumatic Nail and Skin Changes in a Case of Spinal Cord Injury Patient

Dr KK Aggarwal Group Editor-in-Chief

Head Office: E - 219, Greater Kailash, Part - 1, New Delhi - 48, India. e-Mail: emedinews@gmail.com, Website: www.ijcpgroup.com

emedinews is now available online on www.emedinews.in or www.emedinews.org From the Desk of Editor-in-Chief Padma Shri and Dr BC Roy National Awardee

Dr KK Aggarwal President, Heart Care Foundation of India; Sr Consultant and Dean Medical Education, Moolchand Medcity; Member, Delhi Medical Council; Past President, Delhi Medical Association; Past President, IMA New Delhi Branch; Past Hony Director. IMA AKN Sinha Institute, Chairman IMA Academy of Medical Specialities & Hony Finance Secretary National IMA; Editor in Chief IJCP Group of Publications & Hony Visiting Professor (Clinical Research) DIPSAR

8th September 2011, Thursday Another Bomb Blast in Delhi IA powerful bomb exploded outside Delhi High Court gate number 5 on Wednesday morning. The blast took place at around 10.15 am. It left 11 people dead and more than 100 injured. This is the second such incident at the High Court this year. Half of all early casualties seek medical care over first hour. To know the total number of casualties, double this number after one hour. This formula is often used by the media to predict the tolls. It is also useful to predict demand for care and resource needs. The most severely injured arrive after the less injured who self– transport to the closest hospitals, so always expect upside down triage. It is important that we as doctors know how bomb blast cause injuries in order to tackle the repercussions of bomb blasts. Bomb blast injuries can be categorized into four types: • Primary blast injuries are a direct result of the impact of the over pressurized blast wave on the body. It involves injuries to the hollow gas–filled organs like the lungs, ear drum or intestines leading to their rupture. • Secondary blast injuries occur due to flying debris and bomb fragments causing penetration or penetrating injuries to organs such as eyes.

10 years, in comparison with the Caucasian population. Thereby, the vascular age of a 30–year–old in India would be comparable only to that of a 40–year–old in, say, the United Kingdom. (Source: http://www.thehindu.com/news/states/tamil–nadu/ article2427481.ece, September 6, 2011). U.S. smoking rates dropping slowly Smoking prevalence in the U.S. has fallen over the last five years, but not at a consistent rate, CDC researchers said. The percentage of adults who smoke fell from 20.9% in 2005 to 19.3% in 2010 (P<0.05 for trend), a 1.6% drop that amounts to about three million fewer smokers than there would have been with no decline, Brian King, PhD, of the CDC, and colleagues reported in the Sept. 6 Morbidity & Mortality Weekly Report. (Source: Medpage Today) Spiritual Update Am I a spiritual seeker? Every one cannot be a spiritual seeker. In fact majority are not interested in seeking spiritual knowledge and they keep themselves busy in the worldly desires. To become a good seeker one needs to acquire many qualities.

• Tertiary blast injuries occur when individuals are thrown by the blast wind leading to fractures due to the fall.

Gastro Update How is biliary atresia diagnosed? There are many liver diseases which cause symptoms similar to those of biliary atresia. Consequently, many tests may have to be performed before biliary atresia can be diagnosed conclusively.

• Quaternary blast injuries are due to direct effect of burn or crush injuries. The most important aspect is not to waste energies and resources on patients with non-serious injuries. Look for eardrum rupture and signs of respiratory imbalance. Their absence indicates a non-serious injury.

• Serum bilirubin: Conjugated hyperbilirubinemia, defined as any level exceeding either 2 mg/dL or 20% of total bilirubin, is always abnormal. Interestingly, infants with biliary atresia typically show only moderate elevations in total bilirubin, which is commonly 6–12 mg/dL, with the direct (conjugated) fraction comprising 50–60% of total serum bilirubin.

• If the ear drums are intact, the patient can be discharged with first–aid treatment.

• GGTP levels may be within the reference range in some forms of cholestasis of hepatocellular origin.

• If ear drum is ruptured, immediately do an X–ray chest. Keep the patient under observation for eight hours as primary blast injuries may have a delayed presentation. Hence, otoscopic ear exam can be used as a screening procedure for triage. Decreased oxygen saturation on pulse oximetry signals early blast lung injury, even before symptoms become apparent..

• Aminotransferase levels are not particularly helpful in establishing a diagnosis, although a markedly elevated alanine aminotransferase level (>800 IU/L) indicates significant hepatocellular injury and is more consistent with the neonatal hepatitis syndrome.

Dr KK Aggarwal Editor in Chief ———————————————————————————— Vascular ageing value higher in Indias CHENNAI: Even as the Indian Council of Medical Research is getting set to launch a country–wide study to arrive at Indian diagnostic reference values, here are the results of a study involving over 8,000 participants that underline the urgency of such a task. The results of the first phase of Sri Ramachandra University’s PURSE–HIS project, conducted between April 2008 and June 2011, clearly demonstrates the fact that a different set of reference or ‘normal’ values will have to be narrowed down for the Indian ethnic group. There is undoubtedly a need for a different set of reference values for the Indian population, S. Thanikachalam, who led the project at SRU, said. “For instance, one– third of the population has conditions conducive to the development of a vascular illness – stroke, heart attack, peripheral vascular disease, among others.” In fact, the study showed that the normal reference value for vascular aging among Indians was much higher than in the Caucasian population. Carmel Mary McEniery, senior researcher, University of Cambridge, said the aging was advanced by at least

• Ultrasonography may demonstrate absence of the gallbladder and no dilatation of the biliary tree. Unfortunately, the sensitivity and specificity of these findings, even in the most experienced centers, probably do not exceed 80%. • Hepatobiliary imaging, using technetium–labeled di–isopropyl iminodiacetic acid (DISIDA) nuclear scintiscan, is useful in evaluating infants with suspected biliary atresia. Unequivocal evidence of intestinal excretion of radiolabel confirms patency of the extrahepatic biliary system. It is important to keep the following two in mind: First, reliability of the scintiscan is diminished at very high conjugated bilirubin levels (>20 mg/dL). Second, the test has been associated with a 10% rate of false–positive or false–negative diagnostic errors. • Percutaneous liver biopsy is widely regarded as the most valuable study for evaluating neonatal cholestasis. Morbidity is low in patients without coagulopathy. When examined by an experienced pathologist, an adequate biopsy specimen can differentiate between obstructive and hepatocellular causes of cholestasis, with 90% sensitivity and specificity for biliary atresia. • Intraoperative cholangiography definitively demonstrates anatomy and patency of the extrahepatic biliary tract. —Dr. Neelam Mohan, Director Pediatric Gastroenterology, Hepatology and Liver Transplantation, Medanta – The Medicity

Indian Journal of

Online Submission

Clinical Practice

Volume 22, Number 4, September 2011

Contents

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

From the Desk of Group Editor-in-Chief

Transfusion-related Acute Lung Injury

161

KK Aggarwal

Dr KK Aggarwal CMD, Publisher and Group Editor-in-Chief Dr Veena Aggarwal Joint MD & Group Executive Editor

Original Article

Anand Gopal Bhatnagar Editorial Anchor

Efficacy and Safety of a Polyherbal Formulation, Bleminor, in Facial Blemishes 163

IJCP Editorial Board

Sudhakar Grandhi, SV Dange, Suprabha Hegde

Dr Alka Kriplani Asian Journal of Obs & Gynae Practice Dr VP Sood Asian Journal of Ear, Nose and Throat

Clinical Study

Dr Praveen Chandra Asian Journal of Clinical Cardiology Dr Swati Y Bhave Asian Journal of Paediatric Practice Dr Vijay Viswanathan The Asian Journal of Diabetology Dr KMK Masthan Indian Journal of Multidisciplinary Dentistry Dr M Paul Anand, Dr SK Parashar Cardiology Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty Diabetology

Efficacy of Valethamate Bromide in Cervical Dilatation During Labor

169

S Jayasree, N Umadevi, M Rajani

Cytohistomorphological Study of Cysticercosis in Different Sites with Review of Literature

175

R Thamil Selvi, Pammy Sinha, PM Subramaniam, PG Konapur, PR Rekha

Dr Ajay Kumar Gastroenterology Dr Hasmukh J Shroff Dermatology Dr Georgi Abraham Nephrology Dr Sidharth Kumar Das Rheumatology Dr V Nagarajan Neurology Dr Thankam Verma, Dr Kamala Selvaraj Obs and Gyne Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

Review article

Carbapenemases: The New Face of Antimicrobial Resistance

180

Kriti Malhotra, Rani Walia, Shafiqua Aslam, Manoj Goyal

Human Papillomavirus Infections: A Review of Clinical Manifestations and Management Strategies Sarita Goyal, MC Gupta, Kamal Aggarwal

183

Indian Journal of

Clinical Practice

Volume 22, Number 4, September 2011

Contents

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

Case report

Traumatic Nail and Skin Changes in a Case of Spinal Cord Injury Patient

Printed at IG Printers Pvt. Ltd., New Delhi E-mail: igprinter@rediffmail.com printer_ig@yahoo.com

188

Amit Agrawal, Adarsh Lata Singh, Anand Kakani, Anup Paliwal

ÂŠ Copyright 2011 IJCP Publications Pvt. Ltd. All rights reserved. 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 Pvt. Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

Photo quiz

Blistering Eruption on the Leg of an Adult

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. 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.

190

Practice Guidelines

Updated Dietary Guidelines from the USDA and HHS

194

emedinews section

From eMedinewS

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From the Desk of Group Editor-in-Chief Clinical Practice

Transfusion-related Acute Lung Injury

Dr KK Aggarwal

Padma Shri and Dr BC Roy National Awardee Sr. Physician and Cardiologist, Moolchand Medcity, New Delhi President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS Chairman Ethical Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)

Transfusion of even 1 unit of a plasma-containing blood product sometimes causes acute lung injury (ALI) or acute respiratory distress syndrome (ARDS).1,2 What can cause TRALI (transfusion-related acute lung injury): Fresh-frozen plasma, platelet and packed red blood cell transfusions? Definition: New ALI occurring during or within six hours after a transfusion. Pathogenesis: A ‘two-event’ hypothesis holds that recipient granulocytes are primed, either by transfused active substances or by virtue of the patient’s underlying clinical condition. Preformed antileukocyte antibodies contained in the transfusion product then ‘activate’ these functionally hyperactive granulocytes. Which donors: Antileukocyte antibodies are more likely to be found in blood donated by multiparous women due to sensitization to fetal antigens during pregnancy. When to suspect: Whenever dyspnea, hypoxemia and pulmonary infiltrates occur during or within six hours after transfusion of any plasma-containing blood product. Differential Diagnosis  Transfusion-associated circulatory overload  Hemolytic transfusion reaction  Anaphylaxis of immunoglobulin A (IgA)-containing products to a IgA deficiency recipient Management is supportive (mechanical ventilation, supplemental oxygen, diuretics when volume overload is present). Clinical improvement will occur spontaneously as lung injury resolves. Action: Individuals who have developed TRALI should receive no further plasma-containing blood products from the implicated donor. Prevention  Take plasma products only from male donors.  Screen previously-pregnant and previously-transfused apheresis donors for HLA antibodies.  Start testing for the detection of white blood cell antibodies. References 1. Bux J, Sachs UJ. The pathogenesis of transfusion-related acute lung injury (TRALI). Br J Haematol 2007;136(6):788-99. 2. Khan H, Belsher J, Yilmaz M, Afessa B, Winters JL, Moore SB, et al. Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients. Chest 2007;131(5):1308-14. Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

161

Original Article

Efficacy and Safety of a Polyherbal Formulation, Bleminor, in Facial Blemishes Sudhakar Grandhi*, SV Dange**, Suprabha Hegdeâ&#x20AC;

Abstract Facial blemishes, sometimes known as hyperpigmentation, are often characterized by skin discoloration or dark spots and are a result of acne whiteheads, blackheads or pimples. This clinical study was conducted to evaluate the clinical efficacy and safety of Bleminor in the management of facial blemishes. Sixty subjects of either sex, aged more than 18 years with facial blemishes were included in the study. All the subjects were instructed to apply Bleminor twice-daily over the affected area for a period of six weeks. No other topical or systematic antibiotics were permitted during the trial. Subjects were clinically evaluated on entry, and after 2, 4 and 6 weeks of treatment. Statistical analysis was carried out using GraphPad Prism Software Version 4.03 by using repeated measures of ANOVA. All the subjects completed the study and significant reduction in facial blemishes was observed after six weeks of treatment and also displayed significant moisturizing and soothing effects. There were no significant adverse reactions, either reported or observed, during the entire study period and overall compliance to the treatment was good. The beneficial clinical efficacy of Bleminor in the management of facial blemishes could be due to the synergistic actions of its ingredients. Therefore, it may be concluded that Bleminor is clinically effective and safe in the management of facial blemishes. Key words: Facial blemishes, Bleminor

lemishes, also known as hyperpigmentation, are often characterized by skin discoloration or dark spots and are a result of acne whiteheads, blackheads or pimples. This is the result of an increase in cutaneous melanin deposition either by increased melanin synthesis or, less commonly, by a greater number of melanocytes. The amount of color change depends on the location of the melanin deposition.1 Facial skin blemishes are caused by skin acne and progressive acne scars as a result of inflammation within the dermis brought on by acne. The scar is created by the wound trying to heal itself resulting in too much collagen in one spot. This infection ultimately leads to the formation of whiteheads or blackheads. To make matters worse, the improper treatment of these acne lesions, such as picking or squeezing leads to the formation of scars or minor blemishes. Other *Consulting Dermatologist **Consulting Physician Dhaanashree Hospital, Pune â&#x20AC; Research Associate, R&D Center The Himalaya Drug Company, Makali, Bangalore Address for correspondence Dr Suprabha Hegde Research Associate R&D Center The Himalaya Drug Company Makali, Bangalore - 562 123 E-mail: dr.suprabha@himalayahealthcare.com

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

blemishes, particularly acne, are caused by clogged pores. Blemishes are often caused by toiletries and cosmetics, particularly night creams, foundations and moisturizers. Those cosmetics that are most likely to cause blemishes are referred to as comedogenics. Individuals with a predisposition to blemishes should use cosmetics labeled as noncomedogenic. Environmental factors, such as pollution, can irritate the skin and cause blemishes. Causes of facial blemishes include inflammatory skin conditions involving the dermoepidermal junction (eczema, psoriasis, lichen planus, acne, systemic lupus erythematosus, chronic dermatitis and cutaneous T-cell lymphoma), trauma, phototoxicity, allergic reactions, drugs such as chlorpromazine, chloroquine, tetracycline, bleomycin, doxorubicin, 5-fluorouracil, busulfan, antimalarial drugs and hormones (e.g., estrogen), exposure to chemicals such as silver, gold and arsenic. Pigmentary changes tend to affect darker-skinned individuals with greater frequency and severity. Post-inflammatory hyperpigmentation can arise in all skin types, but more frequently affects African Americans, Hispanics/Latinos, Asians, Native Americans, Pacific Islanders and those of Middle Eastern descent.2 163

original article The underlying cause should be treated if possible. The etiology of hyperpigmentation is not completely understood, thus, therapies that can act at different stages of pigmentation can produce better clinical results than single therapy acting at a single stage.3 Blemishes can also become worse when they come into contact with irritants such as hair and clothing. Stress and hormonal changes can also cause blemishes. In particular, a hormone called androgen can result in blemishes when it becomes particularly active. This is because the hormone increases production of sebum, the skin’s natural oil. As this oil accumulates, it increases the chance for bacteria to grow and clog the pores. Women are particularly prone to hormonal changes when they enter adulthood and menopause. They are also more likely to develop blemishes during pregnancy or menstruation because of the related hormonal changes. For those suffering from blemishes due to hormonal changes, certain medications can be beneficial. Oral contraceptives and antiandrogens can be helpful for women, while oral corticosteroids are beneficial to both genders. Topical application of hydroquinone (2-4% concentrations) is applied to reduce the facial blemishes. It is a phenolic compound that blocks the conversion of dihydroxyphenylalanine (DOPA) to melanin by inhibiting tyrosinase.4,5 Its mechanism of action may also involve inhibition of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis, selective cytotoxicity toward melanocytes and melanosome degradation.6,7 Adverse events reported with hydroquinone use include contact dermatitis, nail discoloration, permanent leukoderma and hypopigmentation of the surrounding normal skin that has been treated with this drug.5 Topical retinoid such as tretinoin (all-trans-retinoic acid) is administered in facial blemishes caused by phototoxicity. Tretinoin at a concentration of 0.05-0.1% reduces pigmentation by inhibiting tyrosinase transcription as well as by interrupting melanin synthesis.8 While tretinoin may be effective in reducing hyperpigmentation, it typically takes at least 24 weeks for clinical improvement to be evident.9 It may also increase pigmentation secondary to irritation10 and may cause erythema and peeling.11 Other retinoids including adapalene, tazarotene and topical isotretinoin have also been used.12,13 164

Azelaic acid (15-20%), a C9 dicarboxylic acid, is a reversible inhibitor of tyrosinase.14 It also has both cytotoxic and antiproliferative effects on melanocytes. Adverse effects include pruritus, mild erythema, scaling and burning.15 Kojic acid (KA; 2%) is produced by the fungus Aspergilline oryzae and is a tyrosinase inhibitor.16 KA may be effective if a patient has difficulty tolerating other first-line therapies but KA may be more irritating when compared to other therapies.17 Glycolic acid (5-10%) is an alpha-hydroxy acid and decreases pigmentation by many mechanisms including thinning the stratum corneum, enhancing epidermolysis, dispersing melanin in the basal layer of the epidermis and increasing collagen synthesis in the dermis;18 however, it has its own adverse effects. Hence, Bleminor, a polyherbal formulation containing potent herbs like Glycyrrhiza glabra, Prunus amygdalus, Bombax malabaricum, Shorea robusta, Rheum emodi, and Vateria indica, was evaluated for its efficacy and safety in facial blemishes. Aim of the Study The present study was planned to evaluate the clinical efficacy and safety of Bleminor in facial blemishes. Material and Methods An open clinical study conducted on 60 patients presenting with facial blemishes attending the OPD of Dhaanashree Hospital, Pune, between August 2009 and June 2010, were included in the study. After obtaining informed consent, baseline history was obtained that included personal data, description of symptoms and details of past medical history, family history, history of possible exacerbating factors, etc. The demographic details of the subjects are listed in Table 1. Thereafter, all subjects underwent clinical Table 1. Demographic Data of Subjects on Entry (n = 60) Parameter

Bleminor

Age in years (mean ± SD)

32.12 ± 09.02

Weight in kg (mean ± SD)

69.04 ± 10.40

Sex ratio (M:F)

24:36

History of smoking (No. of cases)

History of alcohol consumption (No. of cases)

Diet (veg/mixed)

12/48

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

original article examination and thorough skin examination. All the subjects were instructed to apply Bleminor twice-daily over the affected area for a period of six weeks. No other topical or systematic antibiotics were permitted during the trial. Subjects were clinically evaluated for facial blemishes, dark spots or pigmentation, moisturizing and soothing effects on entry, and after 2, 4 and 6 weeks of treatment. No other topical or systematic antibiotics were permitted during the trial. During each follow-up visit, local skin examination was done and observations were recorded. Inclusion Criteria

Sixty subjects of either sex, aged more than 18 years, with facial blemishes and who were willing to give the informed consent were included in the study. Exclusion Criteria

Subjects below 18 years of age with active skin infection or with known history or present condition of allergic response to cosmetic/pharmaceutical products, toiletries or their components or ingredients in the test products were excluded from the study. Pre-existing systemic disease necessitating long-term medications, genetic and endocrinal disorders, and pregnant and lactating women were also excluded from the study. Follow-up and Assessment

All the subjects were evaluated at the end of 2nd week, 4th week and 6th week for the various clinical parameters like blemishes, dark spots or pigmentation, moisturizing and soothing effects of the investigational product. Improvement in the facial blemishes and reduction in dark spots/pigmentation was graded as follows: Grade

% Reduction in facial blemishes

0 1 2 3

<25% reduction in facial blemishes 25-49% reduction in facial blemishes 50-74% reduction in facial blemishes >75% reduction in facial blemishes

Moisturizing and soothing effects and overall response were assessed on a visual analog score ranging from 0 to 3 where 0-nil, 1-mild, 2-moderate and 3-good. Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

Primary and Secondary Endpoints

The predefined primary efficacy endpoints were rapid clinical improvement in blemishes. The predefined secondary endpoints for short- and long-term safety were assessed by incidence of adverse events and patient compliance to the therapy. Adverse Events

All adverse events reported or observed by subjects were recorded with information about severity, date of onset, duration and action taken regarding the study drug. Relation of adverse events to study medication was predefined as ‘Unrelated’ (a reaction that does not follow a reasonable temporal sequence from the administration of the drug), ‘Possible’ (follows a known response pattern to the suspected drug, but could have been produced by the patient’s clinical state or other modes of therapy administered to the patient), ‘Probable’ (follows a known response pattern to the suspected drug that could not be reasonably explained by the known characteristics of the patient’s clinical state), and ‘Certain’ (the adverse events must have definitive relationship to the study drug, which cannot be explained by concurrent disease or any other agent). Subjects were allowed to voluntarily withdraw from the study if they experienced serious discomfort during the study or sustained serious clinical events requiring specific treatment. For subjects withdrawing from the study, efforts were made to ascertain the reason for dropout. Noncompliance (defined as failure to take <80% of the medication) was not regarded as treatment failure, and reasons for noncompliance were noted. Statistical Analysis

Statistical analysis was performed by repeated measures of ANOVA using Friedman test followed by Dunnett’s multiple comparison post-hoc test. The scores for symptomatic relief of various parameters were expressed as mean ± SD. The minimum level of significance was fixed at p < 0.01. Statistical analysis was carried out using GraphPad Prism Software Version 4.03. Results All the 60 subjects completed the study. The effect of Bleminor on facial blemishes is shown in Table 2. In subjects treated with Bleminor, most subjects 165

original article Table 2. Evaluation of the Effects of Bleminor in Facial Blemishes Clinical symptoms

Initial

2 weeks

4 weeks

6 weeks

Facial blemishes

2.91 ± 0.32

2.13 ± 0.65

1.33 ± 0.48

0.63 ± 0.23*

Reduction in dark spots/pigmentation

2.96 ± 0.24

2.12 ± 0.60

1.63 ± 0.54

1.08 ± 0.42*

Moisturizing effect

–

0.36 ± 0.16

1.28 ± 0.34

2.3 ± 0.41*

Soothing effect

–

0.40 ± 0.97

1.50 ± 0.97

2. ± 0.67*

Values are expressed in mean ± SD. *P < 0.01 as compared to ‘At entry’ values.

started responding to the therapy at the end of two weeks of treatment. Significant reduction in facial blemishes was observed from 2.91 ± 0.32 at entry to 2.13 ± 0.65, 1.33 ± 0.48 and 0.63 ± 0.23 at the end of 2, 4 and 6 weeks of treatment, respectively with significance of p < 0.01. The mean baseline score of dark spots/pigmentation reduced from 2.96 ± 0.24 at entry to 2.12 ± 0.60, 1.63 ± 0.54 and 1.08 ± 0.42 at the end of 2, 4 and 6 weeks of treatment, respectively though values were clinically not significant. In addition, significant moisturizing and soothing effects were reported by the subjects treated with Bleminor with significance of p < 0.01. No hypersensitivity or flaring of lesions were seen during the study. No significant adverse reactions were either reported or observed during the entire study period and overall compliance to the treatment was excellent. Discussion Facial blemishes are a common condition with hyperpigmentation or a mark or flaw that spoils the appearance of the facial skin. It is often characterized by skin discoloration or dark spots, as a result of acne whiteheads, blackheads or pimples. Management of blemishes remains as a therapeutic challenge.

All these properties of these ingredients help to keep facial skin clean and nourished. They also decrease the inflammation of acne due to their anti-inflammatory and antimicrobial effects.

An open clinical study was carried out to evaluate the safety and efficacy of Bleminor. A total of 60 subjects were evaluated in the study. There was a significant reduction (p < 0.01) in the facial blemishes. No significant adverse reactions were reported or observed. All the subjects completed the study.

The present study clearly demonstrates that Bleminor significantly reduces facial blemishes and has associated parameters like moisturizing and soothing effects. Most subjects started responding to the therapy at the end of two weeks of treatment and further showed significance with continued treatment. There was no hypersensitivity or flaring of lesions evident during the study period. No significant adverse reactions were either reported or observed during the entire study period and overall compliance to the treatment was good. The beneficial clinical efficacy of Bleminor in the

Bleminor has antiblemish activity and it enhances complexion. It helps to maintain clear skin. Bleminor contains G. glabra, P. amygdalus, B. malabaricum, S. robusta, R. emodi and V. indica. These herbs have antiinflammatory, antioxidant and nourishing activities. 166

G. glabra L. has been used in herbal medicine for skin eruptions, including dermatitis, eczema and pruritus.19 Another trial shows that the efficiency of glycyrrhizin as an enhancer agent is greater in gel formulations than it is in the emulsions.20 It has demulcent, antiallergic, anti-inflammatory, antiulcer and antioxidant activities that are helpful in use of the medication in various disorders.21 The kernels of P. amygdalus are nutritious, demulcent and preferred nervine tonic. The chief protein present in oil of P. amygdalus is globulin—amandin—rich in arginine content.22 Regular application nourishes the body. B. malabaricum contains glycosides, lupeol, hentriacontane and has astringent, stimulant, demulcent and refrigerant activities. It is effective in various skin diseases due to its antimicrobial and anti-inflammatory activities.23 S. robusta contains oleanolic acid and tannins as the prime alkaloids. It has astringent, detergent, antiseptic and antidiarrheal activities.24 Rhizome of R. emodi possesses antioxidant and cytotoxic activities.25

Conclusion

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

original article management of facial blemishes could be due to the synergistic actions of its potent herbs. Therefore, it may be concluded that Bleminor is clinically effective and safe in the management of facial blemishes.

12. Shroot B. Pharmacodynamics and pharmacokinetics of topical adapalene. J Am Acad Dermatol 1998;39 (2 Pt 3):S17-24.

References

13. Leenutaphong V, Nettakul A, Rattanasuwon P. Topical isotretinoin for melasma in Thai patients: a vehicle-controlled clinical trial. J Med Assoc Thai 1999;82(9):868-75.

1. Weismann K, Lorentzen HF. Dermoscopic color perspective. Arch Dermatol 2006;142(9):1250.

14. Nazzaro-Porro M. Azelaic acid. J Am Acad Dermatol 1987;17(6):1033-41.

2. Davis EC, Callender VD. Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color. J Clin Aesthet Dermatol 2010;3(7):20-31.

15. Fitton A, Goa KL. Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders. Drugs 1991;41(5):780-98.

3. Rendon M, Berneburg M, Arellano I, Picardo M. Treatment of melasma. J Am Acad Dermatol 2006;54 (5 Suppl 2):S272-81.

16. Romaguera C, Grimalt F. Dermatitis from PABA and hydroquinone. Contact Dermatitis 1983;9(3):226.

4. Grimes PE. Management of hyperpigmentation in darker racial ethnic groups. Semin Cutan Med Surg 2009;28(2):77-85.

17. Cayce KA, McMichael AJ, Feldman SR. Hyperpigmentation: an overview of the common afflictions. Dermatol Nurs 2004;16(5):401-6, 413-6; quiz 417.

5. Badreshia-Bansal S, Draelos ZD. Insight into skin lightening cosmeceuticals for women of color. J Drugs Dermatol 2007;6(1):32-9.

18. Victor FC, Gelber J, Rao B. Melasma: a review. J Cutan Med Surg 2004;8(2):97-102.

6. Halder RM, Richards GM. Management of dyschromias in ethnic skin. Dermatol Ther 2004;17(2):151-7. 7. Palumbo A, d’Ischia M, Misuraca G, Prota G. Mechanism of inhibition of melanogenesis by hydroquinone. Biochim Biophys Acta 1991;1073(1):85-90. 8. Roméro C, Aberdam E, Larnier C, Ortonne JP. Retinoic acid as modulator of UVB-induced melanocyte differentiation. Involvement of the melanogenic enzymes expression. J Cell Sci 1994;107(Pt 4):1095-103. 9. Griffiths CE, Finkel LJ, Ditre CM, Hamilton TA, Ellis CN, Voorhees JJ. Topical tretinoin (retinoic acid) improves melasma. A vehicle-controlled, clinical trial. Br J Dermatol 1993;129(4):415-21. 10. James WD, Berger TG, Elston DM. Contact dermatitis and drug eruptions. In: Andrews’ Diseases of the Skin Clinical Dermatology. 10th edition, Odom RB, James WD, Berger TG (Eds.), Saunders Elsevier: Toronto (ON) 2006:91-138. 11. Grimes PE. Melasma. Etiologic and therapeutic considerations. Arch Dermatol 1995;131(12):1453-7.

19. Saeedi M, Morteza-Semnani K, Ghoreishi MR. The treatment of atopic dermatitis with licorice gel. J Dermatolog Treat 2003;14(3):153-7. 20. Nokhodchi A, Nazemiyeh H, Ghafourian T, HassanZadeh D, Valizadeh H, Bahary LA. The effect of glycyrrhizin on the release rate and skin penetration of diclofenac sodium from topical formulations. Farmaco 2002;57(11):883-8. 21. Khare CP. Indian Medicinal Plants: An illustrated Dictionary. 1st edition, Reprint, Springer 2007:p289-90. 22. Khare CP. Indian Medicinal Plants. Illustrated Dictionary. Springer 2007:p518-9. 23. Khare CP. Indian Medicinal Plants: Illustrative Dictionary, Springer 2004:p573. 24. Khare CP. Indian Medicinal Plants: Illustrative Dictionary, Springer 2004:p602-3. 25. Rajkumar V, Guha G, Ashok Kumar R. Antioxidant and anti-cancer potentials of Rheum emodi rhizome extracts. Evid Based Complement Alternat Med 2011;2011:697986.

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

167

Clinical Study

Efficacy of Valethamate Bromide in Cervical Dilatation During Labor S Jayasree*, N Umadevi**, M Rajani†

Abstract Objective: To study the effect of valethamate bromide on cervical dilatation in human labor. Material and methods: 500 women in labor with unscarred uterus were selected. They were divided into two groups of 250 each, which were identical in maternal age, gestational age, presentation of fetus, mode of induction, etc. One group was given 1 ml valethamate bromide half-hourly (maximum three doses) intravenously starting from a cervical dilatation of 3 cm. The control group was given 1 ml normal saline as placebo at the same cervical dilatation half-hourly (maximum three doses). The duration of first stage, second stage and third stage of labor, any maternal side effects, fetal side effects, cesarean rate, third stage bleeding, etc. were compared between two groups. Observation: The duration of first stage of labor was 146.43 minutes for primi and 76.19 minutes for multigravida in study group, whereas it was 219.66 minutes and 106.25 minutes, respectively in control group (p < 0.001). The average duration of second stage of labor was 28.58 minutes for primi and 14.59 minutes for multigravida in study group, whereas it was 36.47 minutes and 20.47 minutes, respectively in the control group (p < 0.001). The blood loss in third stage of labor was more with study group (314.53 ml against 277 ml). After excluding those who were induced with prostaglandins, third stage bleeding was 215.5 ml in study group against 193.8 ml in control group. The LSCS rate was reduced in study group compared to the control group (10.4% vs 14.8%). The side effects were mild and transient and the main side effect was maternal tachycardia (5.6%). Conclusions: Valethamate bromide is an effective drug in reducing the total duration of labor in both primi and multigravidae. The blood loss in third stage of labor was more in study group, but it was within normal limits. Greater amount of bleeding was seen in those who were induced with prostaglandins. The side effects were mild. Key words: Valethamate bromide, cervical dilatation, labor, prostaglandins

abor is a normal physiological process. In modern obstetrics, O’Driscoll1 introduced the concept of active management of labor. The aim of this concept is to reduce the total duration of labor. The progress of labor depends a lot on the strength and frequency of uterine contractions. The ball and valve action of presenting part and a hormone called relaxin which brings about relaxation of cervical smooth muscles also play a role in the smooth progress of labor. But many a time instead of good uterine contractions, the cervix fails to dilate which results in prolonged labor. The causes of inadequate cervical dilatation can be due to: 

Incoordinate uterine contractions



Previous cervical tear

*Assistant Professor **Professor and Head, Dept. of Obstetrics and Gynecology †Associate Professor, Govt. Medical College, Kozhikode, Kerala

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

 

Cervical spasm of unknown etiology Relative cervical spasm secondary to uterine inertia.

Several drugs are being used to reduce the cervical tone and to facilitate good cervical dilatation. Valethamate bromide is a quarternary ammonium antimuscarinic agent, which acts by blocking the cholinergic receptors, the ganglia and by direct musculotropic action. This study conducted in the Dept. of Obstetrics and Gynecology, IMCH, Medical College, Calicut evaluated the effect of valethamate bromide on cervical dilatation and any serious side effects associated with it. Material and Methods We conducted a prospective study from November 2009 to February 2010 in the Dept. of Obstetrics and Gynecology, IMCH, Medical College, Calicut. Five hundred women were included in the study and were randomized to study and control groups. These 169

Clinical study two groups were identical in all variables including maternal age, gestational age, presentation of fetus and mode of induction. Per vaginal examination was done at the onset of labor to rule out obvious cephalopelvic disproportion (CPD). Those with history of previous cesarean section were excluded from the study. Two hundred fifty women were included in the study group and 250 in the control group. Each patient in the study group was given 1 ml of valethamate bromide intravenously at a cervical dilatation of 3-4 cm. The drug was repeated after every 30 minutes to a maximum dose of 3 ml. The patients in the control group received 1 ml normal saline at half-hourly intervals to a maximum of three doses at the same cervical dilatation. The interval between the first dose of the drug and full dilatation of cervix was calculated in both groups. The maternal pulse rate, after giving each dose of the drug was noted. Any difference in fetal heart rate were also observed. Other maternal side effects like flushing of skin and vomiting were looked for. Duration of the second stage and third stage of labor in both groups was assessed. Blood loss in the third stage of labor was quantified. Those who developed postpartum hemorrhage (PPH) were analyzed in detail. Apgar of the baby at 1 minute was also assessed. Those who underwent lower segment cesarean section (LSCS) during labor for various indications were considered as ‘dropped’ from the study.

The average duration of second stage of labor was 14.59 minutes in multigravidae in the study group and 20.47 minutes in the control group. This difference was also statistically significant (p < 0.001) (Table 2). The average duration of third stage of labor in the study group was eight minutes 45 seconds and nine minutes in control group, which shows that there is no significant difference between the two groups (Table 3). The blood loss in third stage of labor was 314.53 ml in the study group, whereas it was 277 ml in the control group (Table 4). Subjects who were induced with prostaglandins were excluded and blood loss in the third stage of labor was compared between the two groups. It was found that the average blood loss was 215.5 ml in the study group and 193.8 ml in the control group (Table 5). Table 1. The Average duration of First Stage of Labor Study

Control

Primigravida

146.43’

219.66’

Multigravida

76.19’

106.25

Table 2. The Average duration of Second Stage of Labor Study

Control

Primigravida

28.58’

36.47’

Multigravida

14.59’

20.47’

Table 3. The Average duration of Third Stage of Labor Group

Observation The duration of first stage of labor in the study group was 146.43 minutes for primigravida and 76.19 minutes for multigravida. In the control group, this was 219.66 minutes for primigravida and 106.25 minutes for multigravida. This shows a significant reduction in the duration of first stage of labor in the study group (p < 0.001) (Table 1). The average duration of second stage of labor was 28.58 minutes in primigravidae in the study group, whereas it was 36.47 minutes in the control group. 170

Duration

Study

Control

8 min 45 sec

9 min

Table 4. Blood Loss in the Third Stage of Labor Group 2 Blood loss

Study

Control

314.53 ml

277 ml

Table 5. Blood Loss in Third Stage of Labor in those who were not Induced with Prostaglandins Group Blood loss

Study

Control

215.5 ml

193.8 ml

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

Clinical study Table 6. Side Effects Observed Side effects

No. of cases observed Study

Control

Maternal tachycardia

Vomiting

Maternal tachycardia of more than 100 beats/minute was seen in 14 patients in the study group following injection of the drug. But no maternal tachycardia was observed in the control group. Six women developed vomiting in the study group whereas only one patient in the control group had vomiting. But these side effects were mild and transient (Table 6). Seven women developed PPH (>500 ml blood loss in the third stage). Four were from the study group and three from the control groups. Out of the four PPH cases in the study group, two were due to atonicity of uterus and the remaining two were due to vaginal and cervical lacerations. Among the three PPH cases in the control group, two were due to atonicity and one was due to vaginal lacerations. Out of these seven, five were primigravidae and two were multigravidae. Six of these were induced with prostaglandins. One patient in study group required blood transfusion. Twenty-six patients underwent LSCS in the study group (14.4%); this number in the control group was 37 (14.8%). Oxytocin requirement was equal in both groups. Discussion Despite good uterine contractions, duration of labor is often prolonged due to cervical dystocia. Even though the smooth muscle content of cervix is scanty, the spasm of these muscle fibers affect the progress of labor and may exhaust the uterine muscles. Valethamate bromide is a powerful spasmolytic agent with neurotropic as well as musculotropic actions. It can be safely used in labor to prevent cervical dystocia and to reduce the duration of labor.2,3 The unique feature of valethamate bromide is that it harmoniously blends the anticholinergic properties of atropine and the musculotropic action of papaverine and at the same time excluding the side effects of both. It Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

acts on the muscarinic receptors of smooth muscles and competes for the receptor site with acetylcholine. This is an example of competitive antagonism. But, the action of valethamate bromide is selective and therefore, it does not exhibit the usual side effects of anticholinergic drugs. Different studies have established the efficacy of valethamate bromide in reducing the duration of first stage of labor. Sarin et al,4 Purwar et al,5 Mukhopadhyay et al,6 Puri et al7 and Batukan et al8 have reported a significant reduction in the duration of labor. In our study also, there was a considerable reduction in the first stage of labor. The duration of second stage was also found to be reduced in the study group. But, there was no significant difference in the duration of third stage of labor. Four patients in the study group and three in the control group developed PPH. But six of them were induced with prostaglandins. The average blood loss in third stage was more in those who were induced with prostaglandins. No difference was observed in the Apgar of babies between the study group and control group in our study. No significant change in fetal heart rate pattern was observed following the administration of the drug. Side effects documented with this drug are mainly tachycardia, flushing of the skin, vomiting and dryness of mouth. In our study, maternal tachycardia was the major side effect (5.6%). The change was transient. Six patients (2.4%) in the study group had vomiting also. Conclusion  Valethamate bromide is an effective drug in reducing the total duration of labor in both primi and multigravidae.  Even though the blood loss in third stage of labor was slightly more with study group, this difference was significantly reduced when those who were induced with prostaglandins were excluded. The blood loss was also within normal limits.  The side effects associated with the drug are mild. It can be safely used in those who are mechanically induced and those with spontaneous onset of labor. 171

Clinical study References 1. O‘Driscoll K, Stronge JM, Minogue M. Active management of labour. Br Med J 1973;3:135-7. 2. Sharma JB, Pandri P, Kumar A, Murthy NS. Drotaverine hydrochloride vs valethamate bromide in acceleration of labor. Int J Gynecol Obstet 2001;74(3):255-60. 3. Kuruvila S, Jasper P, Peedicayil A, Mathai M. A randomized controlled trial of valethamate bromide in acceleration of labor. Int J Gynaecol Obstet 1992;38(2):93-6. 4. Sarin AR, Snigla P, Rani R. Role of valethamate bromide (Epidosin) in acceleration of labour. Indian Med Gaz 1982;370-2.

5. Purwar M, Balsara R. Acceleration of labor by intravenous epidosin in primigravidas: a randomized controlled trial. Indian J Clin Pract 1996;6:71-2. 6. Mukhopadhyay AK, Ghosh S, Roy B, et al. Effect of epidosin forte in cervical dilatation in labour. J Obstet Gynaecol India 2000;50(2):45-8. 7. Puri M, Rathees, Garg R. Effect of epidosin on cervical dilatation during labor. J Obstet Gynecol India 1988;38: 427-30. 8. Batukan AC, Özgün MT, Türkyilmaz C, Dolanbay M, Müderris II. The effect of valethamate bromide in acceleration of labor: a double-blind placebo-controlled trial. J Turkish German Gynaecol Assoc 2006;7(3): 202-5.

172

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

Clinical Study

Cytohistomorphological Study of Cysticercosis in Different Sites with Review of Literature R Thamil Selvi*, Pammy Sinha**, PM Subramaniam**, PG Konapur**, PR Rekha†

Abstract Introduction: Cysticercosis is a parasitic infestation caused by pork tape worm, Taenia solium, which normally develops in the muscles of pig. Fine needle aspiration cytology (FNAC) is used as rapid technique in the diagnosis of cysticercosis. Aim: The objective is to highlight the role of FNAC in the diagnosing of subcutaneous cysticercosis. Material and Methods: A retrospective study of seven years from 2003 to 2010 was done in the Dept. of Pathology. A total of about 17 patients presented with palpable nodules at different sites as subcutaneous and intramuscular nodules. FNAC was performed on five patients only. Clear fluid was aspirated from two of the swellings and pus from three. FNAC was not done in other 12 cases. Subsequent excision biopsies were received and evaluated. The sections were reviewed and findings were correlated with the cytological findings. Results and Discussion: All 17 patients who presented with subcutaneous and intramuscular nodules and were clinically diagnosed as tuberculous lymphadenitis, reactive lymphadenitis, sebaceous cyst, dermoid cyst, lipoma, neurofibroma and cysticercosis, were included in the present study. However, microscopically three cases revealed parasitic inflammation as suggested on the basis of cytomorphological findings and two showed cystic lesions, but none showed presence of calcospherules or fragments of wall and hooklet. Follow-up biopsy confirmed the diagnosis of cysticercosis. Conclusion: To conclude, FNAC is a reliable and cost-effective procedure in diagnosing subcutaneous nodules. In all inflammatory or cystic or inflammatory cystic lesions, the presence of eosinophils or palisaded histiocytes, should point towards the possibility of cysticercosis. Key words: Subcutaneous nodules, cysticercosis, fine needle aspiration cytology, histopathology

uman cysticercosis commonly manifests as subcutaneous and intramuscular nodules. It is endemic in America, Africa and Asia. In India, it is more common in northern parts. The common sites of involvement include brain, muscle, eye and heart. The human is the definitive host in which the tape worm develops to maturity producing eggs which are passed out in the feces. Eggs can therefore be found in fecally-contaminated water or food as well as on the hands of the infected person. Autoinfection occurs as a result of the entry of eggs into stomach due to retroperistalsis but probably more frequently by hand to mouth infection with the person’s own feces.1 The preoperative diagnosis of

cysticercosis can be made by radio imaging (computed tomography [CT] scan and magnetic resonance imaging [MRI]) and serological tests like complement fixation test, radioimmunoassay and enzyme, linked immunosorbent assay (ELISA). Fine needle aspiration cytology (FNAC) is now available as a preoperative cost-effective tool for the rapid diagnosis of subcutaneous cysticercosis. The diagnosis is confirmed by the histopathological examination of the excised nodule. Apart from studying the role of FNAC in the diagnosis of subcutaneous cysticercosis, the present study was also done to analyze the cytomorphology of actual parasite and the cytological features suggestive of cysticercosis in those cases where the actual parasite could not be demonstrated.

*Associate Professor **Professor †Assistant Professor Dept. of Pathology Vinayaka Mission’s Kirupananda Variyar Medical College Salem, Tamil Nadu Address for correspondence Dr R Thamil Selvi Associate Professor Dept. of Pathology Vinayaka Mission’s Kirupananda Variyar Medical College Salem, Tamil Nadu - 636 308

Material and Methods

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

This is a retrospective study of seven years from 2003 to 2010, done in the Dept. of Pathology, Vinayaka Mission Kirupananada Variyar Medical College, Salem. All 17 patients who presented with palpable subcutaneous and intramuscular nodules at different sites were included in this study. FNAC was performed on five patients with 22-gauge needle. Aspirated 175

Clinical study

Figure 1. Clinical presentation - neck swelling (left side).

Figure 2. FNAC - acute inflammatory cells like neutrophils and eosinophils (H&E, 45x).

materials were smeared on the glass slides and stained with hematoxylin and eosin (H&E) stain after fixation in 95% alcohol and with Leishman stain after air drying. Subsequent excision biopsies were also received and evaluated. The sections were reviewed and findings were correlated with the cytological findings.

five were males. The mean age was 25.76 years. The nodules were seen at various sites like scalp (1), eye (3), chest wall (3), back (2), hypochondrium (1), lumbar region (1), infrascapular region (1), submandibular region (1) (Fig. 1), axillary region (1) and tongue (1) nasolabial region (1) subcostal region (1).

Results

Mean duration of swellings was three months (varied from two weeks to one year). Two patients had swelling all over the body. None of the patients had seizures or cysticercosis in the brain as per CT scan report.

This study includes 17 patients in the age Group 6-80 years. In the present study, 12 patients were females and Table 1. Clinical Presentation and Clinical Diagnosis

176

S. No

Age

Sex

Sites

Clinical presentation

Clinical diagnosis

Case 1

Scalp

3 x 2 cm, soft and nontender

Dermoid cyst

Case 2

Chest wall

2 x 1 cm, firm

Neurofibroma

Case 3

Left hypochondrium

2 x 2 cm, firm and nontender mass

Neurofibroma

Case 4

Right lumbar region

3 x 2 cm, firm and nontender

Lipoma

Case 5

Right orbital region

3 x 2 cm, soft and nontender

Sebaceous cyst

Case 6

Chest wall

2 x 1 cm, firm

Neurofibroma

Case 7

Right conjunctiva

2 x 1 cm, soft and tender

Conjunctival cyst

Case 8

Chest wall

2.5 x 2.0 cm, mobile and firm

Neurofibroma

Case 9

Left infrascapular region

2 x 1 cm, mobile and firm

Lipoma

Case 10

Left submandibular swelling

6 x 4 cm, not mobile and tender

Lymphadenopathy

Case 11

Back

2 x 1 cm, soft and mobile

Sebaceous cyst

Case 12

Left axillary region

3 x 3 cm, mobile and tender

Lymphadenopathy/ Cysticercosis

Case 13

Back

3 x 2 cm, mobile firm mass

Lymphadenopathy

Case 14

Conjunctival swelling

2 x 1 cm, mobile firm mass

? Cysticercosis

Case 15

Tongue

2 x 1.5 cm, firm

Cysticercosis

Case 16

Nasolabial region

2 x 1 cm, firm

Nasolabial cyst

Case 17

Subcostal region

1 x 0.5 cm, mobile firm

Neurofibroma

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

Clinical study and in two cases clear fluid. In rest of the cases FNAC was not done.

Figure 3. Histopathological section shows picture of cysticercosis (H&E, 45x).

In five cases, the cytological findings were very much suggestive of a parasitic cyst; however, no parasite could be seen. The smears showed a mixed inflammatory infiltrate comprising of neutrophils, lymphocytes, eosinophils, histiocytes and giant cells (Figs. 2, 3 and 4). None of these cases showed the presence of hooklets. A cytological diagnosis of parasitic cyst was suggested and excision was advised. Follow-up biopsy confirmed the diagnosis of cysticercosis. Histopathology of the nodules in 11 cases showed cysticercosis. The other three biopsies showed a parasite with granuloma. Two cases showed dead parasite only. One case was associated with squamous cell carcinoma (Fig. 5). Among the 15 cases, only one case was associated with malignancy i.e., squamous cell carcinoma (Table 2). Of the 17 biopsied cases, only 15 underwent CT scans, which showed no cerebral involvement. In a developing country like India, a rapid, safe, cost-effective and reliable cytologic diagnosis of subcutaneous cysticercosis is offered by FNAC on an outpatient basis. Discussion

Figure 4. Histopathological section shows picture of cysticercosis (H&E, 45x).

Figure 5. Histopathological section shows picture of squamous cell carcinoma. (Malignant squamous cells and Keratin pearls) (H&E, 45x).

All the patients presented with painless slow growing nodule, soft to firm in consistency and the provisional diagnoses, sebaceous cyst, dermoid cyst , neurofibroma, lipoma, lymphadenopathy and cysticercosis were made (Table 1). In three cases, the aspiration yielded pus Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

Cysticercosis is a global public-health problem, especially so, in developing countries including India. Human cysticercosis is the larval infestation of the cestode Taenia solium. The cysticercus can be found in any organ, but is especially common in skeletal muscle, subcutaneous tissue, eyes and the central nervous system. T. solium worms may reach a length of several meters.2 The cyst contains fluid and a single invaginated scolex. The scolex has a rostellum, four suckers and 22-32 small hooklets. The cyst wall is multilayered, 100-200 mm thick and covered by microvilli. The outer, cuticular layer appears smooth and hyalinized and is frequently raised in projections.3 The inner layer or parenchyma is loose and reticular, containing mesenchymal cells and calcerous corpuscles.4 The calcareous corpuscles are a unique feature of cestode tissue. The corpuscles take on a bluish purple color in H&E.5 The cysticercus larva completes development in about two months. It is semi-transparent, opalescent white, and elongate oval in shape and may reach a length of 0.6-1.8 cm.2 T. solium eggs are spherical and 30-40 Âľm in diameter.6 177

Clinical study Table 2. Cytomorphological and Histopathological Correlation S. No

Age

Sex

Sites

Clinical diagnosis

FNAC diagnosis

Histopathological diagnosis

Case 8

Chest wall

Neurofibroma

Inflmmatory cyst

Cysticercosis

Case 10

Left submandibular swelling

Lymphadenopathy

Cystic lesion (cyst macrophages)

Cysticercosis with squamous cell carcinoma

Case 11

Back

Sebaceous cyst

Inflmmatory cyst Epitheloid cells+

Cysticercosis with granuloma

Case 12

Left axillary region

Lymphadenopathy/ Cysticercosis

Inflmmatory cyst (eosinophils)

Dead parasite with granuloma

Case 13

Back

Lymphadenopathy

Cyst macrophages

Cysticercosis

The cytomorphological identification of larvae in FNAC smears by different workers has widened the diagnostic utility of FNAC in skin nodules.3,7,8 Suspicion about a parasitic lesion starts with the presence of eosinophils, neutrophils, palisading histiocytes and giant cells in an aspirate from a subcutaneous nodule. The diagnosis of cysticercus is made when fragments of larval cuticle and parenchyma are identified. The presence of scolex in cytology smears is an uncommon finding.8-10 No scolex was seen in any of our aspirates. The tissue response to cysticercus has been divided into five stages.11 The initial response comprises of macrophages and lymphocytes. Afterwards a wellformed layer of palisading histiocytes is seen. Eosinophils appear as the chronic inflammatory response. Later on, polymorphs invade the necrotizing parasite. However, most of these parasites often do not invoke any host tissue response as the parasites produce taeniaestatin Table 3. Comparison with Other Studies

178

Kamal et al

Khurana et al16

Arora et al

Present study

Number of cases studied

132

298

5/15

Clinical suspicion

Aspiration of clear fluid

Aspiration of pus

Inflammation

Calcosperules

132

Fragments of wall

132

Hooklets

and other poorly defined molecules that interfere with the cellular immune response.12 Viable cysticerci may not cause any inflammatory response. However, when they degenerate, there is an infiltration of inflammatory cells, associated with the development of foreign body granulomas. The viable cyst and the necrotic and calcified lesions all have distinctive cytomorphological patterns. The viable cyst yields clear fluid and shows fragments of bladder wall in a clear acellular background. Arora et al, studied 298 cases where cytomorphological characteristic fragments of bladder wall corresponding to viable or partially necrotic lesions were seen in 203 cases. Identification of fragments of an invaginated larva (i.e., hooklets, scolex or spiral wall) established the diagnosis in 33 of the suspected lesions. Cytomorphologically all these cases were from either necrotic or calcified lesions.13 Kamal et al described presence of polymorphous inflammation and fragments of wall in subcutaneous cysticercosis (Table 3).4 Verma et al studied aspirates from 182 cases of subcutaneous cysticercosis and semi-quantitated the type and degree of inflammatory response, and the amount and preservation of the parasite. They concluded that the tissue response is variable with 88-92% being eosinophils, 50-70% palisading histiocytes, 68-80% epithelioid cell granulomas and 46-74% giant cells.14 Conclusion To conclude, FNAC is a reliable and cost-effective procedure in diagnosing subcutaneous nodules. It Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

Clinical study is one of the tools for rapid preoperative diagnosis and may even obviate the need for open biopsy.15 Cysticercosis is more common than usually thought. In all inflammatory/cystic/inflammatory cystic lesions, the possibility of cysticercosis should be kept in mind and a careful search for hooklets is indicated, wherever clear fluid is aspirated with eosinophilic prominence. References 1. Southwick, Frederick (2007-12-10). Chapter 12. ‘Parasitic Infections’ Infectious Diseases: A Clinical Short Course. 2nd edition, McGraw-Hill Medical Publishing Division. p. 313-4. 2. Markell EK, John DT, Krotoski WA. Medical Parasitology. 8th edition, Saunders: Pennsylvania, 1999. 3. Vuong PN. Fine needle aspiration cytology of subcutaneous cysticercosis of the breast. Case report and pathogenic discussion. Acta Cytol 1989;33(5):659-62. 4. Kamal MM, Grover SV. Cytomorphology of subcutaneous cysticercosis. A report of 10 cases. Acta Cytol 1995;39(4):809-12. 5. Ash LR, Orihel TC. Larval cestode parasite in humans. In: Atlas of Human Parasitology. 3rd edition, American Society of Clinical Pathologists: Chicago, IL 1990: 236-7.

8. Verma K, Kapila K. Fine needle aspiration diagnosis of cysticercosis in soft tissue swellings. Acta Cytol 1989;33(5):663-6. 9. Kumar ND, Misra K. Fine-needle aspiration cytology of subcutaneous cysticercosis. Diagn Cytopathol 1991;7(2):223-4. 10. Rajwanshi A, Radhika S, Das A, Jayaram N, Banerjee CK. Fine-needle aspiration cytology in the diagnosis of cysticercosis presenting as palpable nodules. Diagn Cytopathol 1991;7(5):517-9. 11. Mahmood SA, Thomas JA. Host-parasite relationship in human cysticercosis. Indian J Med Res 1984;80(2): 532-40. 12. White AC Jr, Robinson P, Kuhn R. Taenia solium cysticercosis: host-parasite interactions and the immune response. Chem Immunol 1997;66(2):209-30. 13. Arora VK, Gupta K, Singh N, Bhatia A. Cytomorphologic panorama of cysticercosis on fine needle aspiration. A review of 298 cases. Acta Cytol 1994;38(3):377-80. 14. Kapila K, Sahai K, Vermak K. Semi-quantitative analysis of soft-tissue reactions in fine needle aspirates from tissue cysticercosis. Cytopathology 2003;14(4): 208-11.

6. Davis, LE. ‘Neurocysticercosis’ Emerging Neurological Infections. Power C, Johnson RT (Ed.), Taylor & Francis Group, 2005:261-87.

15. Adhikari RC, Aryal G, Jha A, Pant AD, Sayami G. Diagnosis of subcutaneous cysticercosis in fine needle aspirates: a study of 10 cases. Nepal Med Coll J 2007;9(4):234-8.

7. Kung IT, Lee D, Yu HC. Soft tissue cysticercosis diagnosis by fine-needle aspiration. Am J Clin Pathol 1989;92(6):834-5.

16. Khurana N, Jain S. Cytomorphological spectrum of cysticercosis - a review of 132 cases. Indian J Pathol Microbiol 1999;42(3):303-5.

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

179

Review article

Carbapenemases: The New Face of Antimicrobial Resistance Kriti Malhotra*, Rani Walia**, Shafiqua Aslam†, Manoj Goyal‡

Abstract With the advent of antibiotics, a new era ushered in bringing within its folds, a strong defense against the invading deadly microorganisms. This phenomenon is referred to as antimicrobial resistance. Carbapenemases are b-lactamases which hydrolyse carbapenems. The enzyme, New Delhi metallo-beta-lactamase (NDM-1) breaks this ring, rendering the drug ineffective. NDM-1 producing bacteria are resistant to many existing antibiotics including carbapenems - a class of drug often reserved for emergency use and last resort treatment. Key words: Antimicrobial resistance, carbapenems, carbapenemases, b-lactamases, NDM-1

ccording to the laws of Darwinian evolution, antimicrobials use creates a selection pressure on microorganisms: Weak ones are killed but stronger ones might adapt and survive. When pathogenic microorganisms can multiply beyond some critical mass in the face of invading antimicrobials, treatment outcome is compromised. This phenomenon is referred to as antimicrobial resistance (AMR). With the advent of antibiotics, a new era ushered in bringing within its folds, a strong defense against the invading deadly microorganisms. The war against them began in 1928, when bacteriologist ‘Alexander Fleming’ realized that the growth of Staphylococcus aureus was inhibited in the Petri-dish contaminated with mould.1 With the time, new drugs were being developed, microbes also kept adapting to the hostile environment, created by these ‘killer molecules’- antibiotics.2 To start with, penicillin was effective against S. aureus but resistance started developing and came in the form of MRSA (methicillin-resistant S. aureus) treatable with vancomycin. Resistance has developed to vancomycin *Junior Resident **Professor and Head †Professor ‡Assistant Professor Dept. of Pharmacology Maharishi Markandeshwar Institute of Medical Sciences and Research Ambala, Haryana Address for correspondence Dr Manoj Goyal Assistant Professor Dept. of Pharmacology Maharishi Markandeshwar Institute of Medical Sciences and Research Ambala, Haryana - 133 203 E-mail: dr_manojgoyal@yahoo.co.in

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also over the past decade as VRSA (vancomycin-resistant S. aureus). The next in the category is linezolid which has been effective against VRSA but scattered reports have suggested resistance to this drug as well.3 During the past many decades, while making an attempt to control infection there has been an inadvertent and irrational use of these powerful molecules to save mankind from these microbes. They started developing resistance to our weapons to survive, which proceeded to more dangerous and multiple-resistant organisms. The antibiotic resistance of bacteria only leads to a loss of functional system. ‘Evolution’ requires a gain of functional system for bacteria to evolve into man. Therefore, antibiotic resistance of bacteria is not an example of evolution in action, but rather variation within the bacterial kind. It’s the testimony to the wonderful design God gave the bacteria, master adaptors and survivors in the sin-cursed world.4 Globally it’s and always has been very difficult to discover novel and effective antibacterial agents with therapeutic potential for treating infections caused by gram-negative pathogens. Further, this may come as a bad news for the treatment against lethal bacteria, ‘superbugs’ like the ones recently discovered NDM-1 (New Delhi metallo-beta-lactamases).5 NDM-1, which is named after the Indian city, where it was first found, has the ability to jump from one type of bacterium to another meaning that many more common bacteria could become resistant to all known antibiotics causing pandemics of nontreatable diseases. If this ends up in a bacterium which is already resistant to many other Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

Review ARticle antibiotics, then such a development would constitute a nightmare scenario.6 b-lactam antibiotics which include penicillins, have a ring structure which acts to halt the replication of bacteria. The enzyme, NDM-1 breaks this ring, rendering the drug ineffective.7 NDM-1 producing bacteria are resistant to many existing antibiotics including carbapenems - a class of drug often reserved for emergency use and last resort treatment. So far only two types of microbes have been found to host NDM-1; one is the gut bug Escherichia coli which has trebled since the turn of the century. Other one can invade the lungs called Klebsiella pneumoniae. Both offenders can lead to urinary tract infection and blood poisoning.8 Infectious Disease Society of America (IDSA) has labeled the resistant organisms as the ‘ESKAPE’ pathogens, because they effectively escape the effects of antibacterial drugs which include E- Enterococcus faecium, S- S. aureus (MRSA), K- K. pneumoniae - E. coli, A- Acinetobacter baumannii, P- Pseudomonas aeruginosa, E- Enterobacter species.1 It all started when these organisms viz. K. pneumoniae and E. coli producing carbapenemases were originally isolated from a nonresident Indian staying in Sweden. Carbapenemases are b-lactamases which hydrolyse carbapenems. They belong to the molecular Classes A, B and D. Class A comprises of carbapenemases sensitive to inhibition by clavulanic acid mostly chromosomally encoded. Class B carbapenemases are metallo-b-lactamases. The resistance continues to increase because of the ability of the plasmids to acquire additional resistance determinants, turning many pathogens producing b-lactamases into multidrug-resistant ones. The Class D carbapenemases most frequently confer resistance only in the presence of porin alternations. The frequent use of b-lactamase inhibitors in hospitals and general practice poses a selection pressure which favors spread of such strains in hospital and community. With the changing outlook, even the pharmaceutical companies are shifting from the development of newer antibiotics because of them becoming auto-obsolete. The drug development pipeline in this category is not very encouraging. One of the reasons for this may be most multinational companies are channelizing money into research and development to develop drugs for chronic diseases like Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

diabetes and cardiovascular ailments which are more lucrative because of the sheer size of patients inflicted with those ailments. Also the drug discovery process is itself risky and fraught with many failures, with some molecules faltering on safety and efficacy account even at the final stages. The industry has a thin and a drying pipeline of high-end antibiotics to fight against these infections, which may sometimes be fatal. In India too, ‘there are hardly any drugs to fight against these superbugs’, doctors and industry experts say. Physicians and surgeons are treating NDM-1 with an antibiotic cocktail in a hope of controlling the spread of contagion with the medicines like broad-spectrum antibiotics, and carbapenems (the recent additions) including imipenem/cilastatin, and others like tigecycline.5 According to the Lancet report, bacteria with the NDM-1 gene have proven resistant to all antibiotics except tigecycline and colistin.9 The superbug is making international headlines requiring very close monitoring of the researchers. One must empirically treat serious infections with a regimen. Resistance has reached unacceptable levels in the pathogens most common in developing countries and trends show further increase. It appears to spread rapidly with more important consequences for the individual patient and public health. Till promising drugs come-in to combat this ‘threat’ the guidelines given by Center for Disease Control and prevention (CDC) must be followed viz., proper infection control measures which may include contact isolation for persons infected with NDM-1, good hand washing lasting for 15-20 seconds with antibacterial soap before and after touching the patient, administering food or medications, whenever changes of dressing are done, both before and after and whenever gloves are visibly soiled one should be cautious. Using gloves for all procedures with proper disposal of contaminated dressings are the other measures which may bring about tremendous change. Instructions to the patient and the family concerning infection control measures are other few precautions for controlling its spread10 For global containment of antimicrobial resistance before irreparable damage is done to mankind, meticulous infection control practice and judicious antibiotic use should be adopted apart from creating awareness among the general public because all of us are at risk. 181

Review ARticle References 1. Adhikari N. A brewing public health crisis: antibiotic resistance. J Inst Med 2009;31(3):1-2. 2. http://www.darwinismrefuted.com embryology_01.html. Retrieved on 24.10.2010. 3. Tsiodras S, Gold HS, Sakoulas G, Eliopoulos GM, Wennersten C, Venkataraman L, et al. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet 2001;358:207-8. 4. Purdom G. Antibiotic resistance of bacteria: an example of evolution in action? 2007 July 10. Available from http://www.answersingenesis.org/articles/am/v2/n3/ antibiotic-resistance-of-bacteria. 5. Mukherjee R. Drugs to fight superbugs scare. Times of India, 2010 Oct. 16: New Delhi/Chandigarh pg. 12 (col. 1).

6. Edwards T. What is NDM-1 bacteria, the new superbug threat? The First Post 2010 Aug. 11. Available from http://www.thefirstpost.co.uk/67066. 7. Hamzelou J. Does NDM-1 herald the end of antibiotic era? Short Sharp Sci. 2010;10(30):12. 8. Hope J. Alarm over â&#x20AC;&#x2DC;unbeatableâ&#x20AC;&#x2122; enzyme that could make all bacterial diseases resistant to antibiotics. 2010 August 12. Available from http://www.dailymail.co.uk/ health/ article-1302035. 9. Clare S. Superbug ndm-1: symptoms and treatment. 2010 August 15. Available from http://healthmad.com/ conditions-and-diseases/superbug-ndm-1-symptomsand-treatment/2. 10. Fidler DP. Globalization, international law, and emerging infectious diseases. Emerg Infect Dis 1996; 2(2):77-84.

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review article

Human Papillomavirus Infections: A Review of Clinical Manifestations and Management Strategies Sarita Goyal*, MC Gupta**, Kamal Aggarwal†

Abstract Human papillomavirus (HPV) is the most common cause of sexually transmitted infections (STI) in the world, an most important cause of cervical cancer and the second most common malignancy in the world. HPV causes benign lesions of the anogenital area, skin, oropharynx, respiratory tract and conjunctiva. The management of HPV involves use of vaccines which have not only been used for prophylactic purposes but also as therapeutic agents, thus, eventually decreasing the incidence of cervical cancer in women. Key words: Human papillomavirus, sexually transmitted infections, cervical cancer, malignancy

uman papillomaviruses (HPV) are a family of viruses that cause infection in many species, most notably humans. It is the most common cause of sexually transmitted infections (STI) in the world,1 and the most important cause of cervical cancer, the second most common malignancy in the world.2 However, in India, it is the most frequent malignancy in women of all ages3 and India carries one-fourth of world’s cervical cancer burden.4 HPV are small DNA viruses that infect a range of species, from fish to humans. There are over 100 genotypes currently identified,5 out of which approximately 30 are known to cause disease in the genital area. HPV subtypes are classified into high-risk (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82) and low-risk (HPV 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81 and CP 6108) for malignancy, with an additional three types identified as probable high-risk (HPV 26, 53 and 66).6 The prevalence of HPV in sexually active adults is thought to be >50%. Despite the high rate of infection, 70-90% of HPVinfected individuals clear the virus naturally within 1-2 years. In the West, the greatest incidence of HPV infection is between the ages of 18-25, while in India,

*Demonstrator **Senior Professor and Head, Dept. of Pharmacology †Professor, Dept. of Dermatology, Venereology and Leprosy Pt. BD Sharma Postgraduate Institute of Medical Sciences, Rohtak Address for correspondence Dr Sarita Goyal 9J/14, Medical Campus, Rohtak, Haryana - 124 001 E-mail: drsaritagoyal@rediffmail.com

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

it is most common between the ages of 26-35, due to the later average onset of sexual activities.5 Diseases Caused by HPV HPV causes benign lesions of the anogenital area, skin, oropharynx, respiratory tract and conjunctiva. Ninety percent of benign anogenital warts are caused by HPV 6 and 11.7 Infections with high-risk HPV genotypes contribute to the malignancies of the skin, oropharynx, uterine cervix and the anogenital area of both males and females. Approximately 5-15% of women are infected with high-risk HPV types yearly8 and approximately 70% of cancer cases globally are caused by HPV 16-18.7 Benign Manifestations Genital Warts

Five to twenty-five percent of sexually transmitted disease (STD) clinic patients in India, have been reported to have anogenital warts. Condyloma acuminata are the most conspicuous manifestations of HPV infections. HPV 6 and 11 have been detected in upto 95% of condyloma acuminata, with the most common sites of infection in females being the vulva, vestibule, vagina, perineum and perianal region; and the most common sites of infections in males being the penis, urethra and perianal region. Other Sites of Benign Infection

HPV 2, 4, 7, 26, 27, 28 and 29 commonly causes warts on the skin (most often on the hands, feet, knuckles and periungual areas). Lesions of the respiratory tract or 183

Review ARticle respiratory papillomatosis are most commonly caused by HPV 6 and 11. HPV can also cause papillomas in the oral cavity and in the conjunctiva.8 Malignant Manifestations Cervical Cancer

Nearly, half a million women globally are newly affected by cancer of the cervix each year. The majority of these women live in developing countries. In India, the annual incidence of cervical cancer is approximately 1,30,000 new cases with 70-75,000 deaths annually. The majority of the cases are squamous cell carcinomas (SCCs) while adenocarcinomas are less common.9 Globally, HPV 16 is most prevalent in SCCs while HPV 18 is most prevalent in adenocarcinoma; together, HPV 16 and 18 account for 70% of cervical cancers. In India, however, HPV 16 is the most prevalent type in both SCCs and adenocarcinomas, accounting for approximately 90% of all cervical cancers.5,10 Other Sites of Malignant Infections

HPV DNA (both HPV 16 and 18) has been found in 40-50% of all penile cancers. HPV has been isolated from approximately 20-50% of vulvar cancers studied.9 In several studies, 83-95% of anal cancers have proven positive for oncogenic HPV types.11,12 HPV has been found in upto 50% of oropharyngeal and tonsillar cancers.13 HPV types 5 and 7 have been linked to nonmelanoma skin cancers (NMSCs) in organ transplant patient and individuals with epidermodysplasia verruciformis.14 Managing HPV The management of HPV involves use of vaccines which have not only been used for prophylactic purposes but also as therapeutic agents. Vaccines appear to be a very important tool in countering HPV infection at an early stage and thus, eventually decreasing the incidence of cervical cancer in women. Vaccination aims at preventing infection by generating neutralizing antibodies to block HPV viral infection (prophylactic vaccines) or to eliminate infection by inducing a virus-specific T-cellmediated response (therapeutic vaccines).15 Prophylactic Vaccines With the advent of prophylactic vaccines a method of prevention of anogenital lesions as well as cervical cancer 184

now exists. Prophylactic vaccines prevent incident infections by inducing antibodies against HPV capsid proteins L1 and L2.16 However, prophylactic vaccines do not provide therapeutic efficacy against pre-existing HPV infections and HPV-associated lesions.15 It has been observed that when L1 and L2 proteins are expressed in vitro, they self-assemble into a structure identical to the viral capsid known as â&#x20AC;&#x2DC;virus-like particlesâ&#x20AC;&#x2122; (VLP).17-19 The VLP induces a humoral immune response similar to a live virion but does not produce infection in the recipient because it lacks viral nucleic acid.2 HPV L1 VLPs show great promise as prophylactic HPV vaccines in ongoing clinical trials, but L2-based preventive vaccines are yet to be tested in patients.16 Villa et al20 showed 12- to 26-fold stronger antibody response two months after vaccination with quadrivalent HPV types 6, 11, 16, 18, L1 VLP vaccine in women with vaccine type specific antibodies at baseline. Pinto et al21 demonstrated that, apart from eliciting antibody response, L1 VLPs vaccine induces L1-specific T-cell response (both CD4+ and CD8 + T cells and in vitro production of both Th1- and Th2-type cytokines). Thus, prophylactic vaccines may have some role in clearing established HPV infections by mounting a CMI response. Several studies have demonstrated clearance of persistent HPV infections after L1 VLPs vaccination.22 VLPs have shown to be highly immunogenic and also shown to elicit higher titers of neutralizing antibodies in many animal studies as well as early human studies.4 Polyvalent prophylactic vaccines are desirable as there is little cross-reactivity among the HPV types.17 Several studies with bivalent HPV (types 16, 18) L1 VLP vaccine and quadrivalent HPV (types 6, 11, 16 and 18) L1 VLP vaccines have shown good efficacy in terms of inducing adequate antibody response, immunogenicity, safety, prevention of incident infection and protection against HPV-related squamous intraepithelial neoplasia (SIL).23 Several studies have been done on phase I of HPV LP1 VLP vaccine in healthy adults which show that these vaccines are safe, immunogenicand highly-tolerated. They produce a higher titer than natural infection, with or without adjuvants and without any major side effects.24 Polyvalent vaccines, both bivalent and quadrivalent vaccine are recombinant vaccines against HPV.25 Bivalent vaccine targets HPV 16 and HPV 18, which are responsible for 70% of cervical Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

Review ARticle cancers.26 Quadrivalent vaccine also targets, HPV 16 and HPV 18, plus the HPV types 6 and 11 responsible for >80% of genital warts. Both vaccines has been FDAapproved for cervical malignancy.27 Bivalent vaccine contains HPV 16 and 18 VLPs, with an aluminum salt plus monophosphoryl lipid A (AS04) adjuvant.2 It is administered as three 0.5 ml, intramuscular injections at 0, 1 and 6 months.2 Vaccine is highly immunogenic with >98% seropositivity after 4.5 years and good long-term safety profile. Cross-protection against incident infection with HPV types 45 and 31 has also been seen with the bivalent HPV types 16, 18 vaccines. The bivalent vaccine is used only in females.22 Quadrivalent vaccine was the first quadrivalent HPV types 6, 11, 16, 18 recombinant vaccine to be approved by the Food and Drug Administration (FDA) on June 8, 2006.18 Advisory Committee on Immunization Practices (ACIP) has recommended this vaccine for females aged 11-12 years but it may be administered in females aged 9-26 years.26 It is most effective when administered before initiation of sexual activity. Immunization schedule is completed by three intramuscular injections (preferably deltoid muscle) with 0.5 ml of vaccine at 0, 2 and 6 months.27 The exact duration of efficacy of the vaccine is not yet known but studies show good efficacy for at least five years.2 This vaccine was FDA-approved for the prevention of cervical cancers, cervical precancers (cervical intraepithelial neoplasia [CIN]) 2/3 and noninvasive cervical cancers), vulvar precancers (VIN 2/3) and vaginal precancers (VaIN 2/3) caused by HPV types.16,18 It is also approved for the prevention of genital warts and low-grade cervical lesions (CIN 1) caused by HPV types 6, 11, 16 and 18. This vaccine can be used both in males and females.18 Safety Profile of the Vaccines Side effects are uncommon occurrence (1%).18 The most common adverse event was pain at the injection site, followed by swelling, erythema, fever and pruritus.1 Systemic side effects such as nausea, nasopharyngitis, dizziness, diarrhea, vomiting, myalgia, cough, toothache, upper respiratory tract infections, malaise, arthralgia and insomnia may be seen.18 Serious adverse events may occur in <0.1% individuals, reportedly bronchospasm, gastroenteritis, hypertension and vaginal hemorrhage. Contraindications to the vaccine include Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

pregnancy, severe acute illness or hypersensitivity to the vaccine components or to yeast. It is recommended that patients should be observed for at least 15 minutes after the administration of vaccine, in order to make sure fainting does not occur in a dangerous situation, for instance, driving home.28 Recommendations for Vaccination Quadrivalent and bivalent are preventative vaccines and do not treat HPV infection or cervical cancer. They are recommended for women who are 9-25 years old who have not been exposed to HPV. Vaccination before adolescence therefore makes it more likely that the recipient has not been exposed to HPV. However, since it is unlikely that a woman will have already contracted all four viruses, and because HPV is primarily sexually transmitted, the US Center for Disease Control and Prevention has recommended vaccination for women upto 26 years of age. New evidence suggests that all HPV vaccines are effective in preventing cervical cancer for women upto 45 years of age.29 The vaccine can be given to patients who have abnormal pap smear results, who are breasfeading or who are immunocompromised.29 The Indian Academy of Pediatrics (IAP) currently recommends vaccination of females who can afford the vaccine prior to sexual debut. At this time, the vaccine is not covered under the Expanded Program on Immunization.26 Vaccination of Males

In UK HPV vaccines are licensed for boys aged 9-15. An advisory panel in September 2009, recommended that the US FDA licensed quadrivalent vaccine in the United States for males aged 9-26 for the prevention of genital warts and anal cancer.30 Since, penile and anal cancers are much less common than cervical cancer, from health point of view, vaccinating men as well as women decreases the virus pool within the population. Quadrivalent vaccine are in particular demand among gay men, who are at higher risk for genital warts, penile cancer and anal cancer. Therapeutic Vaccines The main purpose of therapeutic vaccine is to stimulate a strong, long-lasting and specific cellmediated immune response for the reduction and eradication of HPV-induced infections. It must range from eradication of cervical warts to eradication of 185

Review ARticle HPV-induced malignancy by targeting nonstructural early viral antigens of HPV, such as E6 and E731 because these proteins are expressed throughout the life cycle of virus as well as in HPV transformed cells.4,15 These vaccines are used to treat established HPV infections, HPV-related cervical precancers and cancers by targeting E6 or E7 oncoproteins.4,16 They are especially useful to prevent recurrences after primary excision or destruction of the precancer/ cancer. Therapeutic vaccines targeting E6 and E7 may provide the best opportunity to control HPV-associated malignancies.16 Various candidate therapeutic HPV vaccines are currently being tested whereby E6 and E7 are administered in live vectors, as peptides or proteins, in nucleic acid form, as components of chimeric VLPs or in cell-based vaccines.16 Among different forms of therapeutic HPV vaccines, DNA vaccines appear to be the most promising ones, as naked DNA is relatively safe, stable, easy to produce, able to sustain high levels of antigen expression in cells and can be repeatedly administered without the risk of antibody production.15 However, DNA vaccines have limited potency due to the lack of amplifying and spreading abilities due to the suboptimal intracellular, processing/presentation of tumor antigens.32 Most of the candidate therapeutic vaccines are in experimental stage or in early clinical trials. Barriers to Vaccination Several barriers exist to introduction of HPV vaccines for widespread use in India and other developing nations. Vaccination of adolescents in three doses is more difficult logistically than vaccination of new borns. Social attitudes toward sexual behavior in India, are more conservative than those of Western nations, and thus the acceptance of a vaccine for an STI is likely to be lower. The vaccine is relatively expensive, and long-term efficacy has yet to be proven, both of which are barriers to appropriation of resources for its inclusion in mass vaccination programs. Although, both the bivalent and quadrivalent vaccines protect against HPV 16, the most prevalent type in India, there is no vaccine that protect against all oncogenic HPV types. Thus, there has to be continued need for screening of vaccinated women, as there is no guarantee that they will not develop cervical cancer from other HPV types.33 186

Possible Role of HPV Vaccines for Other HPV Diseases The effect of prophylactic HPV vaccines to prevent anal HPV infection and anal cancer is yet to be determined. HPV type 16 is associated with upto 70% of lower tongue and pharyngeal cancers, and although adequate data is yet to be generated, vaccination may be preventive against these malignancies. Gardasil has been shown to prevent potential precursors to anal vulvar vaginal and penile cancers. HPV vaccines are expected to protect against HPV-induced cancers of these areas as well as HPV-induced oral cancers.8 Conclusions HPV vaccines hold great promise in the prevention and treatment/control of HPV-related diseases. With the success of the prophylactic HPV vaccines, cervical cancer may soon become one of the vaccine preventable malignancies. However, to be more effective, rare types of HPV causing cervical cancers should also be included in the vaccines. As more scientific evidences are gathered, it may be possible to prevent and treat a number of other HPV-related conditions by these vaccines. In order to decrease the burden of HPV infection in India, there must be nationwide education regarding HPV, acceptance of vaccines and allocation of resources to secreening programs and adolescent immunization against HPV. Early vaccination against HPV can significantly reduce the morbidity of anogenital warts as well as the morbidity and mortality of cervical cancer in India. References 1. Urman CO, Gottlieb AB. New viral vaccines for dermatologic disease. J Am Acad Dermatol 2008; 58(3):361-70. 2. Wang KL. Human papillomavirus and vaccination in cervical cancer. Taiwan J Obstet Gynecol 2007;46(4): 352-62. 3. WHO/ICO Information Centre on HPV and Cervical Cancer. Summary report on HPV and Cervical Cancer Statistics in India, 2007. Available from www.who.int/ hpvcentre. (last accessed on Aug 4, 2008). 4. Gnanamony M, Peedicayil A, Abraham P. An overview of human piapillomaviruses and current vaccine strategies. Indian J Med Microbiol 2007;25(1):10-7. 5. Das BC, Hussain S, Nasare V, Bharadwaj M. Prospects and prejudices of human papillomavirus vaccines in India. Vaccine 2008;26(22):2669-79. Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

Review ARticle 6. Stewart BW (Ed). World Cancer Report. IARC Press, Lyon, France, 2003. 7. Bryan JT. Developing an HPV vaccine to prevent cervical cancer and genital warts. Vaccine 2007;25(16):3001-6. 8. IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, in human Papillomaviruses. IARC Press: Lyon, France 2005. 9. Parkin DM, Bray F. Chapter 2: The Burden of HPVrelated cancers. Vaccine 2006;24(Suppl 3):53111-25. 10. Clifford G, Franceschi S, Diaz M, Munoz N, Villa LL. Chapter 3: HPV type-distribution in women with and without cervical neoplastic diseases. Vaccine 2006;24(Suppl):53/26-34.

21.

22.

23.

11. Daling JR, Madeleine MM, Johnson LG, Schwartz SM, Shera KA, Wurscher MA, et al. Human papillomavirus, smoking and sexual practices in the etiology of anal cancer. Cancer 2004;101(2):270-80. 12. Frisch M, Fenger C, van den Brule AJ, SĂ¸rensen P, Meijer CJ, Walboomers JM, et al. Variants of squamous cell carcinoma of the anal canal and perianal skin and their relation to human papillomaviruses. Cancer Res 1999;59(3):753-7. 13. Barnes LE, Reichart JW, Sidransky P (Eds.). World Health Organization classification of tumors, pathology and genetics of head and neck tumors. IARC Press, Lyon, France, 2005. 14. Gewirtzman A, Bartlett B, Tyring S. Epidermodysplasia verruciformis and human papilomavirus. Curr Opin Infect Dis 2008;21(2):141-6.

24. 25. 26. 27.

15. Hung CF, Monie A, Alvarez RD, Wu TC. DNA vaccines for cervical cancer: from bench to bedside. Exp Mol Med 2007;39(6):679-89.

28.

16. Roden R, Wu TC. Preventative and therapeutic vaccines for cervical cancer. Expert Rev Vaccines 2003;2(4): 495-516.

29.

17. Rowen D. Human papillomavirus infection and anogenital warts. In: Sexually Transmitted Infections. 1st edition, Kumar B, Gupta S (Eds.), Elsevier: New Delhi 2005:215-24. 18. Sharma R, Sharma CL. Quadrivalent human papillomavirus recombinant vaccine: the first vaccine for cervical cancers. J Cancer Res Ther 2007;3(2):92-5.

30. 31. 32.

19. Dillner J, Arbyn M, Dilner L. Translational mini-review series on vaccines: monitoring of human papillomavirus vaccination. Clin Exp Immunol 2007;148(2):199-207. 20. Villa LL, Ault KA, Giuliano AR, Costa RL, Petta CA, Andrade RP, et al. Immunologic responses following administration of a vaccine targeting human

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papillomavirus Types 6, 11, 16 and 18. Vaccine 2006; 24(27-28):5571-83. Pinto LA, Edwards J, Castle PE, Harro CD, Lowy DR, Schiller JT, et al. Cellular immune responses to human papillomavirus (HPV)-16 L1 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles. J Infect Dis 2003;188(2):327-38. Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomized controlled trial. Lancet 2004;364: 1757-65. Brown DR, Bryan JT, Schroeder JM, Robinson TS, Fife KH, Wheeler CM, et al. Neutralisation of human papillomavirus type 11 (HPV-11) by serum from women vaccinated with yeast-derived HPV-11 L1 virus like particles: correlation with competitive radioimmunoassay titer. J Infect Dis 2001;184(9):1183-6. Rouzier R, Uzan C, Collinet P. HPV vaccination: principles, results and future perspectives. J Gynecol Obstet Biol Reprod (Paris) 2007;36(1):13-8. Schmiedeskamp MR, Kockler DR. Human paipllomavirus vaccines. Ann Pharmacother 2006;40(7-8): 1344-52. Ackerman LK. Update on immunizations in children and adolescents. Am Fam Physician 2008;77(11): 1561-8, 1571-2. Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER, et al. Quadrivalent human papillomavirus vaccine. MMWR Recomm Rep 2007; 56:1-24. Reports of Health Concerns Following HPV Vaccination. Centers for Vaccine Safety Disease Control and Prevention (CDC). November 5, 2009. HPV Vaccine Update. Your Cancer Today. 2007-12-11. http://www.yourcancertoday.com/news/HPV-update. html Castle PE, Scarinci I. Should HPV vaccine be given to men? BMJ 2009;339(7726):872-3. Lin YY, Alphs H, Hung CF, Roden RB, Wu TC. Vaccines against human papillomavirus. Front Biosci 2007;12:246-64. Massa S, Simeone P, Muller A, Benvenuto E, Venuti A, Franconi R. Antitumor activity of DNA vaccines based on the human papillomavirus - 16 E7 protein genetically fused to a plant virus coat protein. Hum Gene Ther 2008;19(4):354-64. Kane MA, Sherris J, Coursaget P, Aguado T, Cutts F. Chapter 15: HPV vaccine use in developing world. Vaccine 2006;308:618-21.

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Case report

Traumatic Nail and Skin Changes in a Case of Spinal Cord Injury Patient Amit Agrawal*, Adarsh Lata Singh**, Anand Kakani†, Anup Paliwal‡

Abstract Apart from the pressure ulcers, other dermatological findings including skin and nail complications are increasingly recognized after spinal cord injury. We report a case of a 45-year-old gentleman, a known case of cervical injury with sensory impairment in both the lower limbs (left more than right), who presented with progressive nail changes in the left lower limb. The patient had habit of rubbing the feet against ground and because of sensory impairment, his left foot was continuously traumatized resulting in skin and nail changes. Although, the clinical impact of these findings is usually low, however, these lesions can be troublesome in some patients. Key words: Nail changes, nail disorders, spinal cord injury, sensory loss

part from the pressure ulcers, other dermatological findings including skin and nail complications are increasingly recognized after spinal cord injury.1,2 Although, the clinical impact of these findings is apparently low, however, these lesions can be troublesome to the patient.3 A 45-year-old gentleman, a known case of cervical injury with sensory impairment in both the lower limbs (left more than right), presented with progressive nail changes in the left lower limb. On examination, there were nail changes in the left lower limb on both dorsal and ventral aspect mainly involving the tips and the skin on the ventral aspect of the toes was unhealthy (Fig. 1). Right foot was healthy. During detailed history taking, his wife revealed that he had the habit of moving his legs continuously. Because of this habit his left foot was continuously exposed to trauma that was correlated with nail and skin changes in left foot. Because of the intact sensory function in the right foot it was not exposed to such injury. A wide-spectrum of *Associate Professor (Neurosurgery), Dept. of Surgery **Associate Professor, Dept. of Dermatology †Assistant Professor ‡Resident Dept. of Surgery Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra Address for correspondence Dr Amit Agrawal Associate Professor (Neurosurgery) Clinical and Administrative Head Division of Neurosurgery Datta Meghe Institute of Medical Sciences Sawangi (Meghe), Wardha - 442 005, Maharashtra E-mail: dramitagrawal@gmail.com, dramit_in@yahoo.com

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Figure 1. Clinical photograph showing nail and skin changes in left foot.

dermatological findings (a total of 22) including local fungal infections (the commonest), psoriatic lesions, hyperkeratotic lesions, bacterial infections, seborrheic dermatitis, acne, alopecia, scabies and allergic reaction have been described in patients with spinal cord injury.3 Clinical apparent changes in skin and nails commonly occur in patients with cervical spinal injuries and the nail changes are commoner in the lower extremities.1 Denervation and autonomic dysfunction both have been implicated for these skin changes.1 Ongoing trauma, faulty biomechanics, infections, concurrent dermatological or systemic diseases and their treatments are known contributory factors.4,5 In present case, the patient had the habit of rubbing the Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

Case Report feet against ground and because of sensory impairment, his left foot was getting continuously traumatized resulting in skin and nail changes. Apart from the local measures (re-hydration of the nail plate, cuticle and the nail folds), patient education regarding proper skin care3,4 and elimination of the exacerbating factors is of utmost importance in preventing the skin and nail complications.4

2. Stover SL, Omura EF, Buell AB. Clinical skin thickening following spinal cord injury studied by histopathology. J Am Paraplegia Soc 1994;17(2):44-9. 3. Rubin-Asher D, Zeilig G, Klieger M, Adunsky A, Weingarden H. Dermatological findings following acute traumatic spinal cord injury. Spinal Cord 2005;43(3):175-8.

References

4. Cohen PR, Scher RK. Geriatric nail disorders: diagnosis and treatment. J Am Acad Dermatol 1992;26(4): 521-31.

1. Stover SL, Hale AM, Buell AB. Skin complications other than pressure ulcers following spinal cord injury. Arch Phys Med Rehabil 1994;75(9):987-93.

5. American Academy of Dermatology. Guidelines of care for nail disorders. J Am Acad Dermatol 1996;34(3): 529-33.

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Photo quiz

Blistering Eruption on the Leg of an Adult

62-year-old white man presented with blistering of the skin on his lower extremity. The rash began two weeks prior on the anterior surface of his right ankle and did not improve with a one-week course of ciprofloxacin. A similar rash subsequently developed on the lateral surface of his right thigh. He denied any foreign travel, trauma, or insect bites. He had a history of hypothyroidism, for which he took levothyroxine. He had no known medication allergies. He worked as a truck driver and had no pets. The patient did not have fever, gastrointestinal symptoms, or joint pain. Apart from the skin changes and swelling of the leg, the review of systems was unremarkable. Physical examination revealed large, confluent, erythematous patches with clusters of clear and hemorrhagic vesicles, bullae, and sporadic ulcerations over the right lateral leg and anterior ankle (see accompanying figure). There was no mucosal involvement or inguinal lymphadenopathy. The rash was pruritic, but there was no pain or numbness. The examination was negative for Nikolsky sign (i.e., epidermal detachment from minimal pressure applied to normal skin adjacent to the lesion). Question Based on the patientâ&#x20AC;&#x2122;s history and physical examination, which one of the following is the most likely diagnosis? A. Bullous pemphigoid. B. Dermatitis herpetiformis. C. Erythema multiforme. D. Pemphigus vulgaris. E. Porphyria cutanea tarda. Discussion The correct answer is A: bullous pemphigoid. The autoimmune condition is characterized by tense bullae on normal or erythematous skin.1 Typical age Source: Adapted from Am Fam Physician. 2011;84(2):231-232.

of onset is between 60 and 80 years; however, cases of juvenile bullous pemphigoid occur. Incidence of the disease increases with age.1,2 Patients may present with pruritus or urticaria with bullous formation occurring over weeks to months.3 Fluid contained in the bullae may be clear, or hemorrhagic if the base is bleeding. Rupture of the bullae results in erosions and crusting.1 Skin involvement can be localized, with lesions confined to the lower extremities, abdomen, and forearms; or generalized, with a widespread distribution of bullae.1,2 Mucosal involvement occurs in 10 to 25 percent of affected patients.3 The diagnosis is based on histologic examination, which reveals separation of the epidermis and dermis. Direct immunofluorescence testing shows deposition of immunoglobulin G autoantibodies targeting two hemidesmosomal proteins on the basement membrane of the epidermis.1,3 Serum antibody titers for the two antigens may also be performed. Prednisone, alone or in combination with a steroid-sparing agent, is the cornerstone of treatment.2,3 Topical corticosteroids may be sufficient for mild cases. The prognosis is good for most patients.2 Dermatitis herpetiformis is an autoimmune condition typified by clusters of erythematous papules, excoriations, and vesicles that arise as a consequence of gluten sensitivity. The lesions are extremely pruritic and tend to be distributed symmetrically Contâ&#x20AC;&#x2122;d on page 193...

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Photo Quiz ...Cont’d from page 190

Summary Table Condition

Characteristic

Bullous pemphigoid

Tense bullae with clear or hemorrhagic fluid; may begin as urticaria or pruritus with bullous formation over weeks to months; mucosal involvement rare; Nikolsky sign absent; onset typically between 60 and 80 years of age

Dermatitis herpetiformis

Clusters of pruritic and erythematous papules, excoriations, or vesicles symmetrically distributed on extensor surfaces; associated with celiac sprue; onset typically between 20 and 40 years of age

Erythema multiforme

Acute type IV hypersensitivity reaction characterized by macules, papules, and “target” lesions; begins on distal extremities and spreads proximally; minimal involvement of mucous membranes

Pemphigus vulgaris

Flaccid blisters located on head, trunk, and intertriginous areas; mucosal involvement; Nikolsky sign present; onset typically between 40 and 60 years of age

Porphyria cutanea tarda

Blistering of the skin occurring on sun-exposed areas; may exhibit hypertrichosis of the forehead and cheeks, hyperpigmentation, and urine discoloration; associated with hepatitis C, hemochromatosis, and alcoholism

along extensor surfaces.2,4 Dermatitis herpetiformis is associated with celiac sprue, but it can occur with other autoimmune disorders and malignancies. Most patients are between 20 and 40 years of age, but the condition may occur at any age.2,4 Erythema multiforme is an acute type IV hypersensitivity reaction to certain medications, herpes simplex virus or mycoplasma infection, and other triggers.5,6 It is a self-limited condition characterized by macules, papules, and “target” lesions that may contain a small bulla or vesicle.5 The rash begins on the distal extremities and spreads proximally.6 The skin lesions are usually symmetric, and there is minimal

involvement of mucous membranes. Diagnosis is based largely on history and clinical presentation.5 Pemphigus vulgaris is an autoimmune disease that affects the skin and mucous membranes. The predominant skin lesions are flaccid blisters. The blisters are located on the head, trunk, and intertriginous areas, and onset is typically between 40 and 60 years of age. Pemphigus vulgaris is associated with Nikolsky sign and has a mortality rate of 5 to 15 percent.2,7 It is associated with other autoimmune diseases, including myasthenia gravis and thymoma.2 Porphyria cutanea tarda results from a deficiency in a heme-synthesizing enzyme. Blistering of the skin occurs on sun-exposed areas, especially the hands and forearms, and occasionally the face. Patients may also exhibit hypertrichosis of the forehead and cheeks, skin hyperpigmentation, and urine discoloration. Risk factors for the disease include hepatitis C, hemochromatosis, and alcoholism.8 References 1. Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller A, Leffell DJ. Fitzpatrick’s Dermatology in General Medicine. 7th ed. New York, NY: McGraw-Hill; 2008. 2. Southwell B, Riaz F, Khachemoune A. Bullous pemphigoid: a short review. Dermatol Nurs. 2009;21(6):322-326. 3. Patrício P, Ferreira C, Gomes MM, Filipe P. Autoimmune bullous dermatoses: a review. Ann N Y Acad Sci. 2009; 1173:203-210. 4. Alonso-Llamazares J, Gibson LE, Rogers RS III. Clinical, pathologic, and immunopathologic features of dermatitis herpetiformis: review of the Mayo Clinic experience. Int J Dermatol. 2007;46(9):910-919. 5. Lamoreux MR, Sternbach MR, Hsu WT. Erythema multiforme. Am Fam Physician. 2006;74(11): 1883-1888. 6. Volcheck GW. Clinical evaluation and management of drug hypersensitivity Immunol Allergy Clin North Am. 2004;24(3):357-371, v. 7. Ahmed AR, Moy R. Death in pemphigus. J Am Acad Dermatol. 1982;7(2):221-228. 8. Thadani H, Deacon A, Peters T. Diagnosis and management of porphyria. BMJ. 2000;320(7250): 1647-1651.

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Practice Guidelines

Updated Dietary Guidelines from the USDA and HHS

he U.S. Department of Agriculture (USDA) and the U.S. Department of Health and Human Services (HHS) jointly created the updated version of the Dietary Guidelines for Americans, 2010. The Dietary Guidelines for Americans are reviewed every five years, by law. Previous versions of the guidelines stated that the recommendations were meant for healthy Americans older than two years, whereas the 2010 update changed this wording to specify that the recommendations apply not only to those who are healthy, but also to those who are at increased risk of chronic disease.

and maintain a healthy body weight; and consuming more nutrient-dense foods and beverages in place of those high in sodium, saturated fats, added sugars, and refined grains. The key recommendations from the guidelines specifically address how to balance caloric intake for weight management; reduce consumption of less healthy foods; increase overall intake of healthier foods and nutrients; and develop healthy eating patterns (Table 1). The guidelines emphasize that most personsâ&#x20AC;&#x2122; nutritional needs are best met solely by consuming foods, but that fortified foods and dietary supplements may be helpful in some cases.

The updated guidelines are based on two main concepts: focusing on balancing caloric intake over time to reach

The guidelines cover additional dietary recommendations specific to certain population groups, including

Table 1. Overview of Key Recommendations from the Dietary Guidelines for Americans, 2010 Balance caloric intake for weight management Control total caloric intake to manage body weight Increase physical activity and reduce time spent doing sedentary activities Maintain appropriate caloric balance during childhood, adolescence, adulthood, pregnancy and breastfeeding, and older age Prevent or reduce overweight and obesity by improving eating and physical activity behaviors Reduce intake of less healthy foods Get less than 10 percent of calories from saturated fatty acids; avoid consuming trans fatty acids Limit alcohol consumption to no more than one drink per day in women and two drinks per day in men Limit consumption of foods with refined grains Reduce daily sodium intake to < 2,300 mg; or < 1,500 mg in persons who are black, older than 50 years, or who have hypertension, diabetes mellitus, or chronic kidney disease Reduce intake of calories from solid fats and added sugars Increase intake of healthier foods and nutrients Choose a variety of protein foods; replace those higher in solid fats with proteins lower in solid fats Choose foods that provide more potassium, fiber, calcium, and vitamin D Consume at least one-half of grains as whole grains Increase intake of vegetables, fruits, and fat-free or low-fat dairy products; eat a variety of vegetables Increase the amount and variety of seafood in diet Use oils in place of solid fats, when possible Build healthy eating patterns Account for all foods and beverages consumed to assess overall healthy eating pattern goals Follow food safety recommendations Make sure eating pattern meets appropriate nutrient and caloric needs Source: Adapted from Am Fam Physician. 2011;84(3):332-334.

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Practice Guidelines persons 50 years and older, and women who are pregnant or breastfeeding, or who are capable of becoming pregnant. For older persons, recommendations involve consuming foods fortified with vitamin B12 (e.g., fortified cereals) or taking dietary supplements to ensure adequate vitamin levels. Women who are pregnant or breastfeeding are advised to consume 8 to 12 oz of seafood per week, but to limit consumption of white (albacore) tuna to 6 oz per week and to avoid consuming tilefish, shark, swordfish, and king mackerel. Pregnant women are advised to take an iron supplement. For women capable of becoming pregnant, the guidelines address iron intake by recommending

that this population choose foods that include heme iron, provide additional iron sources, and are high in nutrients that enhance iron absorption (e.g., vitamin C). These women also are advised to consume 400 mcg of synthetic folic acid per day. Also included in the guidelines are basic food safety principles to help reduce the risk of foodborne illness, and a section about helping Americans make healthy choices to improve overall nutrition and physical activity in the United States. The updated guidelines also noted and took into consideration that almost 15 percent of households recently have been unable to obtain sufficient food to meet dietary needs. n

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emedinews section

From eMedinewS

The Natural Remedy for Superbugs? Coriander Oil could be Used to Cure Food Poisoning and MRSA, Say Scientists

economies unless governments, international agencies and other major institutions take action to monitor, prevent and control the problem.

Coriander oil could be used to cure a host of infections including food poisoning and the superbug MRSA, say researchers. The herb extract is resistant to a range of toxic bacteria which cause infections that are resistant to drugs, a study has found. Portuguese scientists tested samples of the oil - taken from the seeds of a coriander plant - against 12 lethal bacteria. All showed reduced growth and most were killed by a solution containing <1.6% of the oil. The team from the University of Beira Interior found the oil attacks and kills the outer membrane of bacteria cells, including salmonella, Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Dr Fernanda Domingues, who co-authored the study, said coriander oil could help the millions who suffer from food-borne illnesses every year. ‘It could become a natural alternative to common antibiotics,’ she said. ‘We envisage the use of coriander in lotions, mouth rinses and even pills, to fight multidrug-resistant bacterial infections that otherwise could not be treated. (Source: http://www.dailymail.co.uk/health/article2029248/Coriander-oil-used-cure-food-poisoningMRSA-say-scientists.html#ixzz1VvpOf8Qm)

Changes over the past century in the way food is made and marketed have contributed to the creation of an ‘obesogenic’ environment in which personal willpower and efforts to maintain a healthful weight are largely impossible, the report noted. (Source: http://www.washingtonpost.com/national/healthscience/half-of-us-adults-will-be-obese-by-2030report-says/2011/08/25/gIQAYthweJ_story.html, Aug 25, 2011)

Half of US Adults will be Obese by 2030, Report Says

Women, who were between 10 and 17 years at the start of the famine and who had been severely exposed to it, had a statistically significant 38% increased risk of CHD in later life. After incorporating factors like age at the start of the famine, smoking and education, there was a 27% higher risk of heart disease for the severely exposed women as compared to those unexposed.

Based on trends, half of the adults in the United States will be obese by 2030, unless the government makes changing the food environment a policy priority, according to a report released on 25th August 2011, on the international obesity crisis in the British Medical Journal, The Lancet. Those changes include making healthful foods cheaper and less-healthful foods more expensive largely through tax strategies, the report said. Changes in the way foods are marketed would also be called for, among many other measures. A team of International Public Health Experts argued that the global obesity crisis will continue to grow worse and add substantial burdens to healthcare systems and 196

Starving to Stay Thin? Be Prepared for Heart Disease This must come up as a wake-up call for young girls starving to be size zero. Scientists have found that under-nutrition during adolescent years is associated with an increased risk of coronary heart disease (CHD) in later life. A study of almost 8,000 women who were children, teenagers or young adults during the Dutch famine in 1944-45 conducted by researchers from the University Medical Centre in Utrecht, the Netherlands, has shown that under-nutrition particularly in adolescent years - is associated with an increased risk of CHD in later life.

The study published on on 25th August 2011, in the European Heart Journal has provided the maiden direct evidence that acute under-nutrition during the time that children are growing up can have an important impact on their future health. Doctors recommend that women eat 2,000 calories a day to stay healthy. (Source: TOI, Aug. 26, 2011) Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

emedinews Section Slow-release NSAIDs are Linked to Higher Risk of GI Bleeding A systematic review of observational studies on nonsteroidal anti-inflammatory drugs (NSAIDs) and upper-GI (gastrointestinal) bleeding and perforation has revealed that the risk of GI complications caused by NSAID use varies according to which NSAID was given and by dosage. The overall relative risk of upper-GI bleeding and perforation for traditional NSAIDs that were not COX-2 inhibitors was 4.50 (95% confidence interval (CI), 3.82-5.31). Lower relative risks were observed for ibuprofen (2.69, 95% CI 2.17-3.33), rofecoxib (2.12, 95% CI 1.59-2.84), aceclofenac (1.44, 95% CI 0.65-3.2) and celecoxib (1.42, 95% CI 0.85-2.37), while the relative risk for diclofenac was estimated at 3.98 (95% CI 3.36-4.72) and naproxen 5.63 (95% CI 3.83-8.28). The study also found that NSAIDs with a long half-life or slowrelease formulation were associated with a greater risk of GI bleeding or perforation, reinforcing advice that the risks and benefits of taking NSAIDs need to be weighed very carefully and that prolonged use should be avoided if at all possible. —Dr Monica and Brahm Vasudev

Add Homocysteine to Improve CVD Risk Stratification Risk stratification for cardiovascular disease (CVD) improved significantly with the addition of homocysteine level to the Framingham Risk Score as per a study in the Journal of the American College of Cardiology. Homocysteine level >15 µmol/l predict a 172% increased risk of CVD. National Institutes of Health Revises Conflict of Interest Rules The National Institutes of Health (NIH) revised on 23rd August 2011, its 16-year-old conflict of interest rules for medical researchers, lowering the amount of money that constitutes a financial conflict and expanding the required disclosures. The 1995 regulations effectively put responsibility for tracking scientists’ financial conflicts of interest on their universities. The rule required researchers to disclose conflicts to their institutions, which then had to assure the NIH the conflict had been managed, reduced or eliminated. The new rule extends that requirement Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

so researchers report not only the fact of a conflict of interest, but also its details such as value, specific nature, why it is a conflict and the impact it might have on research. It lowers the amount a researcher must disclose, if received from an industry or held in company stock, to $5,000 from about $10,000. (Source: Medscape) New Target Against Type 2 Diabetes and Prediabetes Identified Researchers at the Joslin Diabetes Center have identified a new drug target for treatment of type 2 diabetes and prediabetes. In their study, they have shown that an enzyme, Sirtuin 3 (SIRT2), found in the mitochondria - the power producers of cells that convert energy into usable forms - of cells is decreased in the skeletal muscle of those with diabetes, a finding that could lead to the development of drugs to boost the activity of this enzyme in an effort to fight the disease. “Ours is perhaps the first study to understand what is going wrong in the mitochondria of those with diabetes,” said senior author C Ronald Kahn, MD, Head of the Joslin Section on Integrative Physiology and Metabolism and the Mary K Iacocca, Professor of Medicine at Harvard Medical School. The goal for the future will be to find ways to restore levels of SIRT3 or increase the activity of the existing SIRT3, perhaps with a drug, in a bid to improve insulin resistance in the muscle and improve muscle metabolism, he said. “It is a new target,” he said. “Agents which increase Sirt3 activity could, therefore, potentially reverse at least some of the adverse effects of type 2 diabetes,” the paper concludes. The study was recently published in the Proceedings of the National Academy of Sciences. (Source: New target against type 2 diabetes and prediabetes identified, Aug 23, 2011) Biscuits, Cakes up ‘Womb Cancer’ Risk Women beware. Eating biscuits, buns or cakes three times a week could give you womb cancer, says a new study. The 10-year study from the Karolinska Institute in Sweden looked at the eating habits of more than 60,000 women and found that those who gave themselves such a treat regularly were 33% more likely to suffer the disease. And for those who indulge more than three times a week, the risk jumps to 42%, reports the Daily Mail. (Source: TOI, Aug 23, 2011) 199

emedinews Section HPV Test Best for Detecting for Cervical Cancer A DNA test for cancer-causing human papillomavirus (HPV) catches risky cervical lesions better than liquid-based cytology, researchers found. Detection of the most dangerous HPV-16 and HPV-18 types predicted high-grade cervical intraepithelial neoplasia with 92% sensitivity compared with cytology’s 53.3% (p < 0.0001), Philip E Castle, PhD, of the American Society of Clinical Pathology Institute in Washington, DC, and colleagues reported. (Source: Medpage Today) MR Renography for Kidney Graft Dysfunction Low-dose MR renography may offer a noninvasive means to differentiate between acute kidney rejection and acute tubular necrosis after kidney transplantation, according to a study published in the September issue of Radiology. Blood Sugar Tests Alongside Eye Tests may Help Detect Diabetes Opticians should offer blood sugar checks alongside eye tests to help spot patients with undiagnosed diabetes. A study published in the British Journal of General Practice suggested that “a simple finger prick blood test in this setting could identify hundreds of thousands of people with type 2 diabetes. Infant UTI Guidelines Include Ultrasound Updated guidelines from the American Academy of Pediatrics (AAP) recommend urinalysis and culture when a urinary tract infection (UTI) is suspected or when antibiotic treatment will be started empirically in children 2-24 months. In first UTI the new guidelines recommend renal and bladder ultrasound with no voiding cystourethrogram (VCUG) unless the ultrasound is suggestive of anatomic abnormalities, and follow-up but no antimicrobial prophylaxis. The guidelines were published in Pediatrics. Wait for an Hour after Dinner before you Go to Sleep A new study suggests that waiting at least an hour after dinner before going to sleep reduces your risk of stroke by about two-thirds (European Society of Cardiology meeting). For every 20 minutes more that you wait, stroke risk drops another 10%. 200

Fitness Update Please don’t Stop the Music

Do you listen to music while you exercise? New research published in the Journal of Clinical Sport Psychology suggests that you should, in order to reap maximum benefits from your workouts. Many researchers have found that music enhances exercise, and this study summarized all the relevant research on the benefits of listening to music during exercise. The authors of the article reviewed a total of 20 previous studies that examined the effects of adding music to exercise in different populations, and the results were clear: Music benefits exercisers. Among the most prominent benefits of listening to Music were increased motivation to exercise as well as improvement in exercise capacity and intensity. Some studies found that music was exceptionally helpful for patients undergoing cardiovascular or pulmonary rehabilitation or treatment for diseases such as Alzheimer’s and Parkinson’s. Other studies found that adding music to exercise increased elderly exercisers’ confidence and life satisfaction. The study concluded that music is most effective when it coincided with people’s own personal preferences. Now, you have a great excuse to buy some new music for your mp3 player! —Rajat Bhatnagar, International Sports & Fitness Distribution, LLC, http://www.isfdistribution.com

What is fever associated with hypersensitivity?

Hypersensitivity is the most common cause of drug fever. Fever appears several days to three weeks after the drug has been started, but the lag time can be as long as several years. Fever can arise within hours of a re-challenge. —Dr KK Aggarwal, Group Editor-in-Chief, IJCP Group of Publications and eMedinews

Interventions fail to improve cardiac arrest outcomes Neither the timing of cardiopulmonary resuscitation (CPR) before rhythm analysis nor a device meant to boost blood circulation during CPR affected survival among patients suffering out-of-hospital cardiac arrest, a pair of interrelated randomized trials found. (Source: Medpage Today) Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

emedinews Section Lab Update Prolactin 



This test is done when a person has symptoms of a prolactinoma, such as unexplained headaches, visual impairment and/or galactorrhea. Testing may be ordered, along with other tests, when a woman is experiencing infertility or irregular menses or when a man has symptoms such as decreased libido, galactorrhea, or infertility. Prolactin levels are also often ordered in men as a follow-up to a low testosterone level. —Dr Arpan Gandhi and Dr Navin Dang

Medicolegal Update



sufficient to preserve the body for a period upto a week. To keep the corpse in good condition for a longer period, meaning upto a month, you should use a solution made up almost entirely of formaldehyde. There are several steps involved in modern embalming. First, the embalming fluid is injected directly into the deceased’s blood vessels, and pushed through the body with a mechanical pump. Next, the internal organs are hollowed of their contents and filled with embalming fluid. The chemicals are then injected beneath the skin wherever necessary, followed by a final surface embalming on injured areas of the body.

Embalming Certificate of Deceased is Required by Law in Air/Rail Transportation

Embalming is the process of chemically treating a dead body developed by the ancient Egyptians of preserving a person’s body after death or to delay the decomposition of the body, restore it to an acceptable physical appearance and reduce the presence and growth of bacteria to prevent foul smell as well as perfume or add fragrance to corpse. One of the most famous embalmed corpses today  is that of the Russian communist leader Vladimir Lenin, whose embalmed corpse is on display at the Red Square mausoleum in Moscow. The corpse is very well-preserved, and should last for at least another 100 years. The process of embalming has a very long  history, dating back to the Egyptian process of mummification. Though their techniques were quite different from those used today, the effect was the same - to preserve an individual’s body after death. In case of the ancient Egyptians, they believed that the spirit would return to the body after death, so it must remain in good condition. To preserve the corpses, they covered bodies in a drying chemical called natron, and then wrapped them in linen sheets. Today, embalming is done by injecting chemicals  directly into the bloodstream to preserve the corpse’s appearance. The most commonly used chemicals for embalming are formaldehyde and ethanol. A combination of these two chemicals is

—Dr Sudhir Gupta, Additional Professor, Forensic Medicine & Toxicology, AIIMS

Gyne Update Women Lose Knee Cartilage Faster than Men Do MRIs Show Women Lose 3-4 Times more Knee Cartilage Annually.

Women have higher risk for osteoarthritis than men do; moreover, women who have knee osteoarthritis sustain greater cartilage loss than do men with knee osteoarthritis. To determine whether differences in cartilage health distinguish men and women with no clinical evidence of knee osteoarthritis, researchers in Australia compared magnetic resonance imaging (MRI) results in 169 women and 102 men (all white). All participants underwent MRI at baseline and at a mean of 2.3 years later to measure knee cartilage volume and to detect defects at tibiofemoral and patellar sites. Men were substantially older than women (mean age, 60 vs 57). However, in analysis adjusted for age, height, weight, and baseline total bone area, women lost four times more tibial (1.6% vs 0.4%; p = 0.05) and three times more patellar cartilage (2.3% vs 0.8%; p = 0.02) annually than did men. Women also had substantially higher risk for progression of cartilage defects in the tibial area (odds ratio, 3.0) but not in the patellar area. (Source: Published in Journal Watch Women’s Health September 3, 2009) —Dr Maninder Ahuja, Secretary General IMS

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Lighter reading

Lighter Reading An Inspirational Story

Memory Test

Be Positive

Son: “I will choose my own bride!”

Three elderly men visited the doctor for a memory test. The doctor asked the first one, “What’s three times three?”

Father: “But the girl is Bill Gate’s daughter.”

“285!” the man replied.

Father: “I want you to marry a girl of my choice.”

Son: “Well, in that case… ok”

Worried, the doctor turned to the second man. “How about you? What’s three times three?”

Next Father approaches Bill Gates. Father: “I have a husband for your daughter.” Bill Gates: “But my daughter is too young to marry!” Father: “But this young man is vice–president of the World Bank.” Bill Gates: “Ah, in that case… ok” Finally Father goes to see the president of the World Bank. Father: “I have a young man to be recommended as your vice–president.” President: “But I already have more vice–presidents than I need!” Father: “But this young man is Bill Gate’s son–in– law.” President: “Ah, in that case… ok”

“Uh, Monday!” the second man shouted. Even more concerned, the doctor motioned to the third man. “Well, what do you say? What’s three times three?” “Nine!” the third man replied. “Excellent!” the doctor exclaimed. “How did you get that?” “Oh, it’s pretty simple,” the man explained. “You just subtract the 285 from Monday!” (Dr GM Singh) Idioms Excuse my French: Please forgive me for cussing. Everything but the Kitchen Sink: Almost everything and anything has been included.

This is how business is done!! Moral: Even if you have nothing, you can get anything. But your attitude should be positive. (Ms Ritu Sinha)

Ethnic Cleansing: Killing of a certain ethnic or religious group on a massive scale. (Ms Ritu Sinha) Quotes

Laugh a While As the doctor approached the school boy to give him an injection, the boy yelled out loud with pain. “What’s the matter?” said the doctor crossly. “I haven’t touched you yet.” “You’re standing on my foot!” answered the boy.

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The secret of success is to know something nobody else knows. (Aristotle Onassis) He who has never learned to obey cannot be a good commander. (Aristotle) The way to gain a good reputation, is to endeavor to be what you desire to appear. (Socrates)

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

Indian Journal of

Clinical Practice

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.

departments and institutions where the work was performed, 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.

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.

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Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the

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Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

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.

205

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

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Do not use clips/staples on photographs and artwork.

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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

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.

2. Total number of pages ________________________

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. –

206

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.

The legend must include enough information to permit interpretation of the figure without reference to the text.

summary, etc.)_______________________________ 3. Number of tables ____________________________ 4. Number of figures ___________________________

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 K.K. 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

Indian Journal of Clinical Practice, Vol. 22, No. 4, September 2011

Dr KMK Masthan Dr Hasmukh J Shroff

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Padma Shri and Dr BC Roy Awardee Sr Physician and Cardiologist, Moolchand Medcity President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group Chief Editor, eMedinewS Member, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) drkk@ijcp.com

igh doses or long-term use of PPIs or proton-pump inhibitors can lead to an increased risk of bone fractures. This holds especially true for those over the age of 50, and for people on the high dose. The latest warning is based on a FDA review of several studies of the treatment. These epidemiologic studies revealed an elevated fracture risk at the hip, wrist and spine. But the studies do not, definitively prove that PPIs are the cause of the fractures.

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FDA has instructed the manufacturers of the drugs to change the labels for both the prescription and the over-the-counter versions of the PPIs. The FDA said they should only be taken for 14 days to help ease frequent heartburn and under no circumstances should over-the-counter PPIs be taken for more than three 14-day periods in a year.

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Most researchers believe that more fractures are due to decreased calcium absorption from the diet because of the reduced stomach acid. But, it’s also possible that these drugs interfere with bone maintenance. Notably, PPIs have previously been linked to an increased risk of contracting pneumonia and the troublesome bacterium Clostridium difficile, as well as to an increased risk of dementia.

iddle-aged women who move around more in their daily life have lower levels of intra-abdominal fat, a risk factor for heart disease. Minor modifications in daily routine such as reducing the time watching TV or increasing the walk time to work, can make a difference in the long-term health. Visceral fat is a hot topic because of metabolic syndrome, which predisposes people to disease. Intra-abdominal fat, or the fat that wraps around the organs in the abdomen and chest, tends to accumulate at midlife and can contribute to developing diabetes, hypertension and heart disease. The fat around the organs is known to be more related to heart disease and diabetes. A woman does not need to appear outwardly heavy to have a potentially troublesome extra ‘tire’ around her organs. Exercise for long has been known to reduce the amount of intra-abdominal fat.

“ Always aim at complete harmony of thought and word and deed. Always aim at purifying your thoughts and everything will be well.

”

– Mahatama Gandhi

MAKE SURE

DURING MEDICAL PRACTICE A terminally ill patient who develops bed sores, is given only systemic antibiotics.

Evidence-based Medicine

Please change the position of the patient frequently and keep the skin clean and dry.

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Minor Changes in Lifestyle are All That is Required for Good Health

Make sure that good nursing care and maintenance of skin hygiene is advised first to patients with bed sores, along with topical antibiotics. KK Aggarwal

CD I

CD II

CD III

CD IV

5.5 cm W x 6.5 cm H

8.0 cm W x 6.5 H

17.0 cm W x 6.5 cm H

17.0 cm W x10.0 H

Dr KK Aggarwal Group Editor-in-Chief

Dr Praveen Chandra

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PPIs may Cause Bone Fractures When Used for More Than One-year or at Higher Doses: FDA

H Dr KK Aggarwal

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3,575.00

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3,000.00

5,200.00

2-5

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4,000.00

11,050.00

2-5

10,500.00

9,500.00

17,000.00

2-5

16,150.00

15,300.00

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Dr KK Aggarwal

Editor

Group Editor-in-Chief

Dr KK Aggarwal

Group Editor-in-Chief

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