IJCP MArch 2012

Volume 22, Number 10



Review Article



Clinical Study



Case Report



Legal Question



Photo Quiz



Around the Globe



Practice Guidelines

March 2012, Pages 485-544

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

Volume 22, Number 10, March 2012

from the desk of group editor-in-chief

489 FDA OKs First Drug-eluting Stents for Use in MI

KK Aggarwal

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

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma, Dr Kamala Selvaraj

review article

491 Premenstrual Syndrome - A Monthly Menace

497 Geriforte, A Polyherbal Tonic in Combating Geriatric Stress: A Clinical Review

Cardiology Dr Praveen Chandra Dr M Paul Anand, Dr SK Parashar

Paediatrics Dr Swati Y Bhave Dr Balraj Singh Yadav Dr Vishesh Kumar

Diabetology Dr Vijay Viswanathan Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar

Monika Bansal, Manoj Goyal, Shailesh Yadav, Virender Singh

Shantanu Ghosh, Santashree Mazumdar, Tapas Das

507 Syncope: Evaluation and Management SR Mittal

clinical study

512 Clinical and Investigative Profile of Ring- enhancing Lesions on Neuroimaging

PS Mahato, AS Dabhi, PB Thorat

519 Prevalence and Antibiotic Sensitivity Pattern of Bacteria Isolated from Nosocomial Infections in a Surgical Ward

Dermatology Dr Hasmukh J Shroff Nephrology Dr Georgi Abraham

Rama Sikka, JK Mann, Deep, MG Vashist, Uma Chaudhary, Antriksh Deep

case report

Neurology Dr V Nagarajan

526 Antenatal Diagnosis of Bilateral Renal Agenesis with Potter’s Sequence: A Rare Case

Anand Gopal Bhatnagar Editorial Anchor

Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

Hetal Parikh, Sameer Raniga, Nitin Parikh, Palak Vaghela

529 Multiple Developmental Urogenital Anomalies: A Therapeutic Challenge

N Rajamaheswari, Sugandha Agarwal, Archana Bharti Chhikara, K Seethalakshmi

legal question

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

532 Our State IMA has Submitted a Memorandum to the Government Requesting Action Against the Menace of Stray Dogs. What Else can We Do?

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

MC Gupta

photo quiz

Š Copyright 2012 IJCP Publications 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 Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

533 Yellowish Papules on a Middle-aged Man

around the globe

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.

535 News and Views

practice guidelines

536 Updated Guidelines on Management of Atrial Fibrillation from the ACCF/AHA/HRS

lighter reading

538 Lighter Side of Medicine

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.

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from the desk of group editor-in-chief 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)

FDA OKs First Drug-eluting Stents for Use in MI

D

rug-eluting stents (DES) have been used in diabetics and/or acute myocardial infarction (AMI) as off-label use up till now. With the FDA approving specific stents in these conditions, its legal implications are many.

DES are preferred to bare-metal stents because they reduce the incidence of restenosis and target vessel revascularization. Similar outcomes have also been shown in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Since, patients with an AMI (within 48-72 hours) were excluded from the pivotal SIRIUS and TAXUS IV trials, primary PCI is considered an ‘off-label’ use in the United States for all DES. In the HORIZONS-AMI trial, 3,006 patients with STEMI patients were randomly assigned to either paclitaxel-eluting Taxus stents (PES) or BMS in a 3:1 ratio. The 12-month rates of ischemia-driven target vessel revascularization were significantly lower after treatment with PES a difference that was entirely due to a lower rate of target lesion revascularization.

Based on the results HORIZONS-AMI trial, two DES from Boston Scientific have become the FIRST to be

approved by the US FDA for treating patients with AMI. 

Ion: Paclitaxel-eluting platinum chromium



Taxus Liberté - Paclitaxel-eluting

The Ion stent, which employs polymer and drug elution similar to that of the Taxus, differs with respect to its platinum chromium metal alloy structure and design, which allow for thinner struts and more flexibility within the coronary arteries.

Diabetic stent FDA approved US FDA has also approved Medtronic Resolute Integrity DES, which is the first stent the agency has approved to treat coronary artery diseases in diabetics.

Diabetics suffering from coronary artery disease represent 30% of the nearly one million PCI procedures performed yearly in the US and 1.2 lakhs in India. Such procedures are inherently more difficult in patients with diabetes because their coronary arteries are narrower than those not afflicted by the condition.

The Resolute Integrity DES offers several notable benefits, starting with outstanding deliverability, which means it is exceptionally easy to navigate the stent on the delivery system through the coronary vasculature to the narrowed arterial segment that requires treatment.

Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

489

Obituary

Dr VP Sood On March 3, 2012, we lost a leading luminary in the field of medicine.

Dr VPSood, a renowned ENT surgeon of the country passed away at a hospital in USA. An accomplished and compassionate clinician, Dr Sood was a giant among his peers with several notable achievements in his glorious career.

Dr Sood served for 15 years since 1965 in three leading medical institutions of the country, Maulana Azad Medical College, New Delhi, Himachal Pradesh Medical College, Shimla and All India Institute of Medical Sciences, New Delhi.

He can rightly be called as the Father of Rhinoplasty in India. He was the Founder and Past President - All India Rhinology Society. He introduced Annual All India Rhinoplasty Courses in 1977 and Annual National Endoscopic Sinus Surgery Courses in 1989 first time in the India. He was also Past President Association of Otolaryngologists of India.

He established the Dr Sood Nasal Research Foundation and was actively involved in teaching programmes and lectures under the purview of his Foundation to impart practical training in Rhinoplastic and Endoscopic Sinus Surgery to ENT surgeons, of our country as well as from the neighboring countries.

He was a much sought after guest speaker and faculty member at various International Conferences and Courses as well as national ENT conferences.

His hard work and dedication towards his conferred upon him several awards.

For us at IJCP, the loss is tremendous. He was the Founder Editor of the Asian Journal of Ear, Nose and Throat. As Founder Editor, he nurtured this journal right from its infant state to what it is today, a highly respected and widely read journal.

We at IJCP and eMedinewS deeply mourn the passing away of Dr VP Sood and extend our condolences to the bereaved family.

May his soul rest in peace‌

review article

Premenstrual Syndrome - A Monthly Menace Monika Bansal*, Manoj Goyal**, Shailesh Yadav†, Virender Singh‡

Abstract Most women feel some discomfort before or during their periods, but if the discomfort is of such a severity that starts interfering with some aspects of life: The diagnosis of premenstrual syndrome or tension (PMS or PMT) should be considered. About 8095% of females of childbearing age have some premenstrual symptoms. PMS affects upto 30% of women with regular menstrual cycles. Some women (about 3-8% of menstruating women) have a more severe and disabling form of PMS having a psychiatric designation called premenstrual dysphoric disorder (PMDD). The etiology of PMS remains unknown and may be complex and multifactorial, but hormones, neurotransmitters and genetic factors have a role to play. Behavioral symptoms along with physical symptoms should be present to establish a diagnosis. Certain lifestyle changes and dietary modifications along with a number of drug options can improve the quality-of-life of a patient of PMS upto a considerable extent.

Keywords: Premenstrual symptoms, premenstrual dysphoric disorder

M

ost women feel some discomfort before or during their periods, but if the discomfort is of such a severity that starts interfering with some aspects of life: The diagnosis of premenstrual syndrome or tension should be considered.

Premenstrual syndrome (PMS), also called PMT or premenstrual tension is a collection of physical, psychological and emotional symptoms related to a woman’s menstrual cycle that develop during 7-14 days before the onset of menses and subsides when menstruation occurs.1 About 80-95% of females of childbearing age have some PMS. PMS affects upto 30% of women with regular menstrual cycles. Some women (about 3-8% of menstruating women) have a more severe and disabling form of PMS. This form of PMS has its own psychiatric designation termed as premenstrual dysphoric disorder (PMDD).2 Etiology The etiology of PMS remains unknown and may be complex and multifactorial. The role of ovarian hormones is unclear, but symptoms often improve when ovulation is suppressed.3 Changes in hormone *Assistant Professor, Dept. of Physiology **Associate Professor †Professor Dept. of Pharmacology ‡Professor, Dept. of Microbiology MMIMSR, Mullana, Ambala, Haryana Address for correspondence Dr Monika Bansal Assistant Professor Dept. of Physiology, MMIMSR, Mullana, Ambala, Haryana E-mail: dr_manojgoyal@yahoo.co.in

levels may influence centrally-acting neurotransmitters such as serotonin, but circulating sex hormone levels are typically normal in women with PMS. Some evidence suggests that the disorder is related to enhanced sensitivity to progesterone in women with underlying serotonin deficiency. Deficiencies in prostaglandins, related to an inability to convert linoleic acid to prostaglandin precursors, may be involved in PMS. Genetic factors also seem to play a role, as the concordance rate is two times higher in monozygotic twins than in dizygotic twins.4 Clinical Picture Upto 85% of menstruating women report having one or more PMS, and 2-10% report disabling and incapacitating symptoms. More than 150 symptoms have been ascribed to PMS.5 The most common physical manifestations of PMS are abdominal bloating and an extreme sense of fatigue, both of which occur in 90% of women with this disorder; breast tenderness and headaches are among the other major physical complaints, occurring in >50% of cases. The most common behavioral symptom of PMS is labile mood, occurring in >80% women. Other frequent behavioral complaints include irritability, tension, depressed mood, increased appetite (70%), and forgetfulness and difficulty concentrating (>50%).

Diagnosis PMS must be distinguished from simple premenstrual symptoms (e.g. bloating, breast tenderness) that do not interfere with daily functioning and are characteristic of normal ovulatory cycles.

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review article The three key elements of diagnosis are:  



Symptoms consistent with PMS Consistent occurrence of symptoms only during the luteal phase of the menstrual cycle Negative impact of symptoms on function and lifestyle.6,7

Many criteria for identifying women with PMS have been proposed.

The American College of Obstetricians and Gynecologists (ACOG) diagnostic criteria (2000) for PMS are given below.6 All of the following must be met: 











At least one of the following physical symptoms present during the five days before menses for three consecutive menstrual cycles: Breast tenderness, swelling of the extremities, headache and abdominal bloating.

At least one of the following psychological symptoms present during the five days before menses for three consecutive menstrual cycles: Depression, angry outbursts, irritability, anxiety, confusion and social withdrawal.

Symptoms relieved within four days of menses, not recurring until at least the 13th day of the next cycle.

Symptoms adversely affect work performance and/or family or social life.

Symptoms cannot be explained by the use of hormones or other medication, or drugs or alcohol use.

Symptoms occur reproducibly during two cycles of prospective recording.8

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) also defines and gives diagnostic symptoms of PMDD.9 When PMS or PMDD is suspected, patients should be instructed to keep a premenstrual daily symptom record for several consecutive months so that cycle-tocycle variability can be examined.5 Management Treatment goals for PMS are to:  



Ameliorate or eliminate symptoms Reduce their impact on activities and interpersonal relationships Minimize adverse effects of treatment.

Initially, all patients with PMS should be offered nonpharmacological therapy. Medication should be offered

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to patients with persistent symptoms of PMS and those who meet criteria for PMDD.7

Nonpharmacologic Therapy:9-11 





Education: About the biologic basis and prevalence of PMS. Structured sleep schedule with consistent sleep and wake times especially during the luteal phase Dietary changes like restriction of sodium and caffeine intake



Aerobic exercises



Stress management



 

Psychological intervention includes behavioral relaxation therapy

cognitive

Maintaining a daily symptom record Complementary approaches like acupuncture, that probably helps due to its effect on serotonergic and opioidergic neurotransmission that modulates various psychosomatic functions.12

Dietary Supplementation6,8,10,13 Certain dietary supplements that are being evaluated in women with PMS are vitamins A, E, folic acid and B6, L-tryptophan, calcium, magnesium and evening primrose oil. Various controlled trials have shown the beneficial effect of these supplements. Vitamin E helps by reducing the production of prostaglandins that cause cramps and breast tenderness. Vitamin B6, calcium and magnesium are cofactors in the synthesis of neurotransmitters such as serotonin and dopamine from tryptophan. Serotonin is deficient in patients with PMS. They help in reduce bloating, breast tenderness and fluid retention.

Evening primrose oil (Oenothera biennis) contains polyunsaturated fatty acids, linoleic and gammalinoleic acids. These are dietary precursors of prostaglandins (PGE1 and PGE2) deficiency of which allows an enhanced response to physiological levels of b-endorphins, angiotensin II and ovarian hormones.9,14 High glycemic index (GI) carbohydrates may increase brain serotonin due to increase in plasma ratio of tryptophan to other large neutral amino acids.13,15 Some herbs like black cohosh, ginger, raspberry leaf, dandelion and chasteberry and natural progesterone creams derived from wild yams and soybeans are also being used but with an unproven efficacy.

Pharmacologic Therapy If symptoms are not adequately relieved by nonpharmacologic measures the addition of pharmacologic

review article treatment should be individualized to target the most troublesome symptoms in each patient. Various drug options can be helpful.

Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and sertraline have been shown to be very efficacious in the treatment of both physical and behavioral symptoms of PMS. Common adverse effects are insomnia, drowsiness, fatigue, nausea, nervousness, headache, tremor and sexual dysfunction. These can be minimized by the use of lowest effective dose, whereas morning dosing can minimize insomnia.6,9,10,16 Anxiolytic agents such as alprazolam are not recommended because of their addictive potential, tolerance and significant side effects. Although, some beneficial effects have been demonstrated for other psychotropic agents, including bupropion, tricyclic antidepressants, buspirone and lithium, as well as the b-blockers; (atenolol and propranolol), treatment with these drugs is not recommended because the potential harms outweigh any benefit.17 Combined serotonin and noradrenaline reuptake inhibitor such as venlafaxine is also being useful in PMS.9 Bromocriptine has been shown to relieve breast tenderness and menstrual migraine in women with PMS, but side effects limit its usefulness.10,18 Spironolactone, an aldosterone antagonist structurally similar to steroid hormones, is the only diuretic that has been shown to effectively relieve PMS symptoms such as breast tenderness and fluid retention. Thiazide diuretics have not been found to be beneficial in the treatment of patients with PMS.6,10

is limited by significant adverse effects and treatment costs. Danazol has been found to be effective in treatment of PMS symptoms. However, long-term therapy is limited by side effects such as masculiniztion (e.g., decreased breast size, deepening of the voice, weight gain) as well as adverse effects on liver function tests and serum lipid profiles.9,10,20 GnRH agonists are synthetic analogs of naturallyoccurring GnRH and suppress ovulation by inhibiting the release of pituitary gonadotropins. They are leuprolide, goserelin, nafarelin, histrelin. GnRH agonists have been shown to be more effective in treating behavioral and physical symptoms of PMS. Side effects and cost may limit GnRH agonist therapy in patients with severe PMS.21,22 The hypoestrogenic effects of GnRH agonists can lead to atrophic vaginitis, urinary tract symptoms, and a decrease in skin collagen content. Use of these agents for longer than six months can significantly increase the risk of osteoporosis and cardiovascular disease. Tibolone is an investigational synthetic steroid with weak estrogenic, progestogenic and androgenic activity. Although, this agent has primarily been studied in the treatment of menopause and osteoporosis, it has been shown to provide significant improvement in premenstrual symptoms compared with placebo and a multivitamin.16

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), especially mefenamic acid and naproxen sodium is based on the theory that PMS symptoms are related to prostaglandin excess.11 Most NSAIDs should be effective, but mefenamic acid and naproxen sodium have been the most studied. Mefenamic acid therapy given during the luteal phase is effective in relieving symptoms, but gastrointestinal toxicity prohibits its use. Naproxen sodium improves physical symptoms and headache in women with PMS. Overall, NSAIDs may alleviate a wide range of symptoms, but they do not appear to improve mastalgia. All NSAIDs must be used with caution in patients with underlying gastrointestinal or renal disorders.19

The administration of estrogen late in the luteal phase (to minimize premenstrual decline in the hormone) relieves premenstrual migraine. For overall symptom management, estrogen must be given continuously to suppress ovarian activity. Because unopposed estrogen can promote endometrial hyperplasia and carcinoma, cyclic progesterone must be added. But progesterone may induce PMS symptoms, thereby limiting the efficacy of estrogen.23 To avoid this a combination of estrogen and local progesterone (levonorgestrel intrauterine system) is being studied, with systemic levels of progesterone remaining low.9 Testosterone implants have also been used when decreased libido is a major symptom. Although oral contraceptive pills (OCPs) are widely prescribed for the management of PMS, they have not been shown to be consistently effective. Any benefits are probably due to the estrogenic component; therefore, monophonic pills may be most appropriate.

OCPs may improve physical symptoms such as bloating, headaches, abdominal pain and breast tenderness, but they can also exacerbate these symptoms.

Agents used to alter the menstrual cycle, danazol, gonadotropin-releasing hormone (GnRH) agonists, estrogen and progesterone have been studied in the treatment of PMS and PMDD. Although, efficacy has been demonstrated for some of these agents, their use

A new combined oral contraceptive containing 30 Îźg of ethinylestradiol and 3 mg of drospirenone (a new progesterone having antimineralocorticoid and antiandrogenic activity) has shown significant reduction in symptoms of PMS apart from being useful as an oral

Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

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review article contraceptive. It is used from Day 1 of the cycle for 21 days, followed by seven-day break.9 Surgical Treatment Surgical treatment, principally hysterectomy plus bilateral oophorectomy followed by hormone replacement therapy with unopposed estrogen may be considered in severely affected patients who fail to respond to other therapies. To confirm whether the procedure is going to be effective or not, a test with GnRH analog should be done before surgery.24 Conclusion

9.

Govind A, O’Brien PM. Dysmenorrhea and premenstrual syndrome. Gynecology for postgraduates and practitioners. 2nd edition, Sengupta BS, Chattopadhyay SK, Varma TR, Sengupta PS (Eds.), Elsevier: New Delhi 2007:96-108.

10. Wyatt K, Dimmock PW, O’Brien PM. Premenstrual syndrome. In: Clinical Evidence. 4th issue. Barton S (Ed.), BMJ Publishing Group: London 2000:1121-33.

11. Moline ML, Zendell SM. Evaluating and managing premenstrual syndrome. Medscape Womens Health 2000;5:1-16.

12. Habek D, Habek JC, Barbir A. Using acupuncture to treat premenstrual syndrome. Arch Gynecol Obstet 2002;267(1):23-6.

The symptoms of PMS are distressing and disabling.

Moreover, the exact cause of PMS is not known but appears to be due to increased sensitivity to normal ovarian hormones particularly progesterone secondary to serotonin deficiency. A number of nondrug and drug options although with limited efficacy, are available, which if individualized to target the most troublesome symptoms in each patient, the results can be encouraging and the quality-of-life of patients suffering from PMS can be improved upto a significant extent.

13. Rapkin A. A review of treatment of premenstrual syndrome and premenstrual dysphoric disorder.

Psychoneuroendocrinology 2003;28 Suppl 3:39-53.

References

17. Freeman EW, Rickels K, Sondheimer SJ, Polansky M. A double-blind trial of oral progesterone, alprazolam, and placebo in treatment of severe premenstrual syndrome.

JAMA 1995;274(1):51-7.

1.

Johnson SR. Premenstrual syndrome, premenstrual dysphoric disorder, and beyond: a clinical primer for practitioners. Obstet Gynecol 2004;104(4):845-59.

2.

Deuster PA, Adera T, South-Paul J. Biological, social, and behavioral factors associated with premenstrual syndrome. Arch Fam Med 1999;8(2):122-8.

3.

Daugherty JE. Treatment strategies for premenstrual syndrome. Am Fam Physician 1998;58(1):183-92, 197-8.

4.

Kendler KS, Karkowski LM, Corey LA, Neale MC. Longitudinal population-based twin study of retrospectively reported premenstrual symptoms and lifetime major depression. Am J Psychiatry 1998;155(9):1234-40.

14. Bayles B, Usatine R. Evening primrose oil. Am Fam Physician 2009;80(12):1405-8.

15. Murakami K, Sasaki S, Takahashi Y, Uenishi K, Watanabe T, Kohri T, et al. Dietary glycemic index is associated with decreased premenstrual symptoms in young Japanese women. Nutrition 2008;24(6):554-61.

16. Drug Facts and Comparisons. St.Louis: MO Facts and Comparisons, 2002.

18. Herzog AG. Continuous bromocriptine therapy in menstrual migraine. Neurology 1997;48(1):101-2.

19. Burke A, Smyth E, FitzGerald GA. Analgesic-antipyretic agents; pharmacotherapy of gout. In: Goodman and Gilman’s: The Pharmacological Basis of Therapeutics.

11th edition, Brunton LL, Lazo JS, Parker KL (Eds.), The McGraw Hill Companies: USA 2006:671-715.

20. Freeman EW, Sondheimer SJ, Rickels K. Gonadotropinreleasing hormone agonist in the treatment of premenstrual symptoms with and without ongoing dysphoria: a controlled study. Psychopharmacol Bull 1997;33(2):303-9.

5.

American College of Obstetricians and Gynecologists.

Current information and opinions on subjects related to women’s health (Pamphlet) Washington, DC. American Congress of Obstetricians and Gynecologists.

March 2010.

6.

ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 15, April 2000.

Premenstrual syndrome. Obstet Gynecol 2000;95:1-9.

22. Leather AT, Studd JW, Watson NR, Holland EF. The treatment of severe premenstrual syndrome with goserelin with and without ‘add-back’ estrogen therapy: a placebocontrolled study. Gynecol Endocrinol 1999;13(1):48-55.

7.

Steiner M, Born L. Diagnosis and treatment of premenstrual dysphoric disorder: an update. Int Clin Psychopharmacol 2000;15 Suppl 3:S5-17.

23. Kessel B. Premenstrual syndrome. Advances in diagnosis and treatment. Obstet Gynecol Clin North Am 2000;27(3):625-39.

8.

Wyatt KM, Dimmock PW, Jones PW, Shaughn O’Brien PM. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. BMJ 1999;318(7195):1375-81.

24. Kumar P, Malhotra N. Premenstrual syndrome and other menstrual phenomena. In: Jeffcoate’s Principles of Gynaecology. 7th edition, Jaypee Brothers Medical Publishers (P) Ltd.: New Delhi 2008:627-36.

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21. Sundström I, Nyberg S, Bixo M, Hammarbäck S, Bäckström T. Treatment of premenstrual syndrome with gonadotropin-releasing hormone agonist in a low dose regimen. Acta Obstet Gynecol Scand 1999;78(10):891-9.

review article

Geriforte, A Polyherbal Tonic in Combating Geriatric Stress: A Clinical Review Shantanu Ghosh*, Santashree Mazumdar**, Tapas Dasâ€

Abstract The elderly population with declining health pose significant challenges for attending physicians. Often, the cause/s of the deterioration is not identifiable or is irreversible. Some elderly patients, including those who do not have acute illness or severe chronic disease, eventually undergo a process of functional decline, progressive apathy and a loss of desire to eat and drink. Declining health in the elderly may be multifactorial and may be caused by chronic concurrent diseases and functional impairments. Manifestations include weight loss, decreased appetite, poor nutrition and inactivity. Four syndromes are prevalent and predictive of adverse outcomes viz. impaired physical function, malnutrition, depression and cognitive impairment. A comprehensive initial assessment should include information on physical and psychologic health, functional ability, socioenvironmental factors and nutrition. Several medicines and food supplements are available for the elderly as per their individual requirements. Geriforte tablets with their beneficial effects in elderly patients contain herbs, which have potent antioxidant, neuroprotective, adaptogenic, nootropic, immunostimulatory and cardioprotective activities. In this review article, we summarize seven clinical studies of Geriforte tablets with an emphasis on geriatric stress and as tonic in the elderly.

Keywords: Geriforte, elderly, stress

A

ging is a life-long process, which begins before we are born and continues throughout life. The functional capacity of our biological systems increases during the first years of life, reaches its peak in early adulthood and naturally declines thereafter.

The slope of decline is largely determined by external factors throughout the life course. Health in older age is therefore to the largest extent a reflection of the living circumstances and actions of an individual during the entire life span.1 Worldwide, the proportion of people aged 60 and over is growing faster than any other age group. Between 1970 and 2025, a growth in older persons of some 694 million or 223% is expected. In 2025, there will be a total of about 1.2 billion people over the age of 60. By 2050, there will be two billion with 80% of them living in developing countries.2

*Special Medical Officer Jawaharlal Nehru Medical College, Bhagalpur, Bihar **Head, Dept. of Biochemistry University of Calcutta, Kolkata †Professor and Head Medical College and Hospital, Kolkata Address for correspondence Dr Santashree Mazumdar Head, Dept. of Biochemistry, University of Calcutta 35, Ballygunge Circular Road, Kolkata - 700 019 E-mail: smbioc@gmail.com

Aging is an inevitable biological process that affects the factors attributable for development of life.3 The definitive mechanisms of aging across species and systems still remain unclear.4 Stress is an important factor that accelerates aging process. It is manifested by increase in reactive oxygen species (ROS) levels.5 The decline in the homoestatic reserves in the aging process starts around the fifth decade of life, and is influenced by factors such as genetics, diet, environment and lifestyle. Today, much more important than chronologically-determined aging is successful aging, defined as the maintenance of physical and mental functioning and involvement with social and relationship activities. Recommendations to this end include orientations about diet and exercise to improve quality-of-life. A healthy lifestyle includes regular exercise, considered one of the most important components.6 With aging, multiple changes occur that affect the nutritional status of an individual. Sarcopenia, or the loss of lean muscle mass, can lead to a gain in body fat that may not be apparent by measuring body weight.

It may be more noticeable by loss of strength, functional decline and poor endurance. It also leads to reduced total body water content.7 Other changes that occur with aging include changes in bone density leading to osteoporosis, decreased gastric

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review article acid secretion, which impairs iron and B12 absorption, xerostomia and slower peristalsis with resultant constipation. Appetite and thirst dysregulation also occur. Changes in dentition alter the ability to chew and may lead to changes in food choices. Many other factors such as sedentary lifestyle, social isolation, loneliness or depression can lead to malnourishment.

Medications also alter absorption of nutrients or how food tastes. Poverty and cognitive impairment are other issues that may affect eating habits and food choices.

The overall nutritional requirements of the older adult do not change. What does change is the caloric intake due to the loss of lean muscle mass. The nutrient requirements for older adults include increased intake of vitamins D, B12, and B6 and calcium. Vitamin B12 deficiency causes depression, neurological disorders and macrocytic anemia. Protein is a nutrient that is often thought of as one to increase in aging. Unless the older adult requires additional protein for healing and strength, this is not necessarily the case.8 Tufts University developed a Modified MyPyramid for Older Adults, which emphasizes eating nutrient-dense foods, the importance of fluid intake and activities that may be typical of the older age group. The modified pyramid also suggests that supplements (for nutrients such as calcium and vitamins D and B12) may help people meeting their nutritional needs when food alone does not yield adequate amounts.9 Stress is a physiological response to environmental challenges and threats. The presence of too much or too little stress over an extended period of time can be physically or psychologically damaging.10 Oxidative stress occurs due to increase in prooxidants and/or decrease in antioxidants. Enhancing antioxidative defense status may be an important factor that counteracts aging and age-associated disorders.11 Recently, there has been greater emphasis on herbal preparations that are beneficial in psychosomatic disorders. Apart from psychotropic drugs, many formulations have been mentioned which exhibit a rejuvenative property. ‘Geriforte’, a polyherbal formulation is one of the known indigenous formulations to arrest the degenerative process. Several recent clinical and experimental studies have evaluated the therapeutic properties of Geriforte and majority of them have shown encouraging results. Geriforte tablets contains herbs with potent antioxidant, neuroprotective, adaptogenic, nootropic, immunostimulatory and cardioprotective activities.

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Pharmacological actions of individual herbs in Geriforte tablet Chyavanaprasha: It has potent restorative and tonic activity and used in weakness, and emaciation.12 Various trials have shown its rejuvenating, adaptogenic, cardioprotective and neuroprotective activities. It also delays the sickness and maintains well-being after various radiation exposures.13,14 Capparis spinosa: It is a potent antioxidant.15 It provides better protection to liver, spleen and kidney; thus helps to maintain the well-being.16 Cichorium intybus: The active principles are escutetin and its glycosides, which have cholagogue, hepatoprotective, stomachic and diuretic activities.17 C. intybus extract has high Fe2+-chelating, and radical scavenging activity towards 1,1-diphenyl-2picrylhydrazyl (DPPH) showing effective antioxidant activity.18 Solanum nigrum: It contain solasonine, sapogenins, which improve the microcirculation due to their smooth muscle relaxant activity; increase the cardiac activity.

It also has potent hepatoprotective activity. These actions keep the person healthy.19 Phenolic compounds present in S. nigrum extract also have antioxidant activity.20 Cassia occidentalis: Anthroquinone derived from C. occidentalis has tremendous action on the colon of the human being and transfer with purgative activity, thereby maintaining regular bowel movements.21 It is used as a general tonic in weakness, and illness. It has hepatostimulant activity as well as hepatoprotective activity.22 Terminalia arjuna: Experimental studies have shown the bark of T. arjuna to have significant inotropic and hypotensive effect, increasing coronary artery flow and protecting myocardium against ischemic damage. It also has mild diuretic, antithrombotic, prostaglandin E2-enhancing and hypolipidemic activities.23 T. arjuna mainly contain plant sterols (β-sitosterol) and arjunic acid, respectively, whereas ethanotic fraction is enriched with derivatives of arjunic acid like arjunoglycoside (I, II, II and IV), arjungenin, arjunolone, arjunetin, tanins and ellagic acid. Some pure compounds: Arjunolic acid, terminoside, ellagic acid and tanins have cardioprotective, antiplatelet aggregative, nitric oxide suppressant, antioxidant, membrane stabilizing and hepatoprotective activity. All these help to maintain good health.24 Achillea millefolium: It has anti-inflammatory, antispasmodic, antidysenteric, antihemorrhagic and

review article urinary antiseptic properties. It is beneficial in dyspepsia. British herbal compendium cites its use in cough, cold, slow-healing wounds and other inflammatory skin conditions.25 Selenium present in A. millefolium has tremendous antioxidant activity and is useful as a general tonic and cardiotonic agent.26 Tamarix gallica: Galls of T. gallica contain the polyphenols, gallic acids, ellagic acids, which have health-promoting actions.27 The extract also has potent hepatoprotective activity, which may be due to its antioxidant activity.28 Crocus sativus: It has nootropic, antispasmodic, expectorant, stomachic and diaphoretic activities.29 The rich phenolic content contributes to its usefulness as antioxidant.30 Safranal, isolated from C. sativus has some protective effects on different markers of oxidative damage in hippocampal tissue.31 The mucoprotective and antiulcerogenic activity of polyphenols protects against gastric ulcerations.32 Makardhwaj: Beneficial in heart disease, as rejuvenative and also as an aphrodisiac.33 Mandur bhasma: It has renoprotective properties.34

hepatoprotective

and

Asparagus adscendens: It is used for the treatment of spermatorrhea, chronic leukorrhea, diarrhea, dysentery, general debility, senile pruritus, asthma and fatigue.

The rhizome powder is given as a nutritive tonic.35 Caesalpinia digyna: The root extract increased levels of catalase and superoxide dismutase with significant decrease in lipid peroxidation (LPO) levels in serum, liver and kidney; showing potent antioxidant activities.36 Asparagus racemosus: It has potent adaptogenic activity. Adaptogens have antistress action and protect against infection and infirmity.37 Administration of A. racemosus root ameliorates hyperlipidemic/ hypercholesteremic and oxidative stress in hypercholesteremia.38 Withania somnifera: The alkaloids withanine, withasomine in the roots delay premature aging.

It also increases red blood cell (RBC), hemoglobin (Hb), hair melanin and has nootropic, hypotensive activities.

These make it useful as regular supplement to remain healthy.39 The roots of the plant are categorized as rasayanas, which are reputed to promote health and longevity by augmenting defense against disease, arresting the aging process, revitalizing the body in debilitated conditions, increasing the capability of the individual to resist adverse environmental factors and by creating a sense of mental well-being.40

Glycyrrhiza glabra: It significantly lowers total cholesterol, low-density lipoprotein and triglycerides levels and increase high-density lipoprotein; hence, its extract can effectively prevent progress of atherosclerosis. This is likely due to its effect on plasma lipoproteins along with the antioxidant and anti-inflammatory activities.41 The major constituents are triterpene saponins and glycyrrhizin. It provides thick protective mucous for the stomach lining and has gastroprotective action. Gastric ailments adversely affect daily performance; so, the same may provide better healthy life.42 Centella asiatica: It has been used in Ayurveda to improve mild cognitive functioning. It also acts has an antioxidant, accelerates nerve regeneration and contains multiple active fractions increasing neurite elongation in vitro. It also has favorable effects on diastolic blood pressure, peripheral neuritis, insomnia, loss of appetite and age-related cognitive decline.43 Shilajeet (Purified): Used in diabetes mellitus as it helps to regulate carbohydrate metabolism. It increases appetite and is useful in dyspepsia.44 It prevents increase in serum phospholipid level and controls hyperlipidemic stage.45 It has beneficial effect on endocrine, autonomic and brain functional changes.46 Terminalia chebula: It is a potent antioxidant.47 The extract is used for its laxative, diuretic, hepatoprotective and cardiotonic activities.48 Mucuna pruriens: It has neuroprotective and neurorestorative effects, which may be related to its antioxidant activity independent of the symptomatic effect.49 Mucuna beans contain high amounts of protein and carbohydrate and are a rich source of macro- and microelements. They are used in many free radicalmediated diseases, such as rheumatoid arthritis, diabetes, atherosclerosis, male infertility and nervous disorders. The seed extract can be used as readily natural antioxidant, and helps to maintain well-being.50 Myristica fragrans: Used as a stomachic, stimulant, carminative and to control flatulence. Recent research indicates its other uses as an aphrodisiac, antioxidant, hypolipidemic and antiulcer.51 Piper longum: It is a rejuvenating medication. It enhances bioavailability that potentiates action of other ingredients.52 Alcoholic extract of the fruits and its component, piperine have immunomodulatory activity.53 Syzygium aromaticum: It relieves pain, controls nausea, vomiting, improves digestion and has antiflatulence

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review article activity including antimicrobial activity. All these activities justify its use for well-being.54 It enhances sexual health due to its aphrodisiac activity.55 Elettaria cardamomum: The seed extract, which mainly contains essential oils, has antimicrobial and antioxidant activities. It is also used as an aromatic stimulant, and carminative agent. It has been patented as a general health supplement in expectant mothers.56 Carum copticum: It has therapeutic effects on dyspepsia, indigestion, flatulence and colic. It also has antinociceptive activity.57 The seed extract also has antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities.58 Curcuma longa: The extract is significantly effective in disease related to liver, heart, cancer and immunological disorders due to rich phytoconstituents.59 Curcumins inhibit lipid peroxidation of linoleic acid. Compounds that can scavenge ROS and inhibit LPO are useful as preventive agents against atherosclerosis, a common cause of coronary artery disease worldwide.60 Adhatoda vasica: Restoration of acid phosphatase level points out the role of the extracts in promoting the stability of cellular, nuclear and organelle membranes.

This is also used against asthma due to its gentle bronchodilatory and antiallergic activity.61 Eclipta alba: It has hepatoprotective, nootropic and antimicrobial activity. E. alba exhibited dose-dependent inhibition of oxidation of dimethyl sulfoxide indicating hydroxyl radical scavenging activity; reduction of free radical DPPH, showing its potent antioxidant activity.62 Celastrus paniculatus: Aqueous extract of the seed has cognitive-enhancing and antioxidative properties63 as well as anxiolytic activity.64 Argyreia speciosa: It is used as a stomachic and in common sexual disorders in men.65 Oral administration of the ethanolic extract of A. speciosa root (ASEE) has immunomodulatory activity.66 Berberis aristata: It is a bitter, tonic, cholagogue, stomachic, laxative, antipyretic and antiseptic.67 Abhrak bhasma: Hepatoprotective and renoprotective due to the free radical scavenging properties.68 Loh bhasma: Hematinic; significantly increases Hb, total RBC and hematocrit value.69 Yashad bhasma: Useful in diseases of the urinary tract, eyes, anemia, cough, dyspnea, nocturnal sweating and has wound healing action.70

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CLINICAL STUDIES ON GERIFORTE TABLET

Study 1: Evaluation of Geriforte as a General Metabolic Tonic in the Aged71 Aims: Evaluation of Geriforte as a general metabolic tonic in the aged. Materials and Methods: One hundred persons, 58-80 years age were recruited for the study. A control group of 25 persons of the same age, having similar clinical features were maintained with placebo. Geriforte tablets were prescribed at two tablets t.i.d. for the first and second months and then two tablets b.i.d. for the third to sixth months.

All other drugs were discontinued. The patients were evaluated for before and after treatment, at the end of third month and sixth month. Results: At the end of six months there was overall improvement in all clinical parameters mentioned. Improvement in symptoms related to nervous systems and psychiatric symptoms were noticed after third month. But improvement in appetite, general well-being, sleep, tiredness, bowel movements occurred by the second month. No toxicity was noticed in this study. Conclusion: There was satisfactory improvement in general well-being and alimentary symptoms but in psychiatric symptoms like depression, anxiety, restlessness or irritability and in symptoms like lack of concentration, attention and sleep the improvement was not proportionate.

No improvement was noticed in the control group on placebo. No toxic effects were encountered during this study.

Study 2: Evaluation of Geriforte as a General Tonic72 Aims: Evaluation of Geriforte as a general tonic.

Materials and Methods: A total of 50 patients were included in the trial. Out of these, 10 patients were lost for study. All the selected cases had no obvious pathology, clinically or by laboratory investigations.

Most of them complained of vague aches and pains, weight loss, loss of appetite and general weakness.

All the patients were put on initial dose of Geriforte two tablets t.i.d. for 15 days and thereafter on a maintenance dose of one tablet t.i.d. for 15 days and thereafter on a maintenance dose of one tablet t.i.d.

Patients were evaluated at intervals of one month.

Results: Geriforte has properties that considerably improve the ability and willingness for both mental and physical work. Seventy-five percent of patients reported that they regained very good ability to work, both physically and mentally. These patients felt significant improvement in general feeling. Nearly all

review article patients reported increase in appetite and reasonable improvement in their digestion, bowel activity and flatulence. Sleep and fatigue improved in 63% patients; 40% of the patients gained weight ≥2 kg within four months probably due to improved appetite, digestion and bodily functions. Conclusion: There was striking subjective and objective improvement in physical and mental activity and acuity, a feeling of well-being, ability to perform physical and mental work and improvement in appetite, digestive function, sleep and gain in weight in 80-85% of the cases. There were no untoward actions or toxicity on prolonged use. Geriforte served well as a general tonic for the patients of all age groups.

Study 3: Antistress Properties of an Indigenous Compound and its Significance in the Management of Psychosomatic Disorders73 Aim: To evaluate the antistress and anabolic properties of ‘Geriforte’ in normal subjects as well as in a group of psychosomatic cases. Materials and Methods: One hundred fifteen selected cases of psychosomatic disorders such as anxiety neurosis, early thyrotoxicosis, hypertension and ulcerative colitis were studied.

In addition, 40 normal individuals were included as controls. The following criteria were used to diagnose the psychosomatic cases. Of the 115 psychosomatic patients, 31 cases were given a placebo. Similarly, for comparison, 10 of the 40 apparently normal individuals were given a placebo.

Results: Specific clinical features such as palpitation, nervousness, precordial discomfort and insomnia underwent considerable improvement after therapy.

In the Geriforte group, 89.5% of cases showed a significant improvement in their physical and mental health. In the placebo group, no change was observed.

No tranquilizers or psychotropic drugs were given apart from specific conventional therapy for each clinical condition. The initial values of acetylcholine revealed a significant improvement after three months of ‘Geriforte’ therapy, except in early thyrotoxicosis cases. In the placebo group, no change was observed in the acetylcholine level. Platelet monoamine oxidase showed considerably lower values in thyrotoxicosis, hypertension and ulcerative colitis cases. In anxiety neurosis cases, the average value was similar to that in the normal series. After three months of therapy, there was a significant increase in platelet monoamine oxidase in early thyrotoxicosis and essential hypertension cases. In contrast, the placebo group did not reveal any change. Conclusion: After comprehensive follow-up, a significant improvement in clinical symptomatology

was observed in all the stress disorders. Geriforte has been shown to provide an effective control of successive muscle spasm. This herbomineral compound prevents or ameliorates neurohumoral and enzymatic changes induced by anxiety and stress. No side effects have been noted even following over-dose or prolonged use of the drug.

Study 4: A Clinical Evaluation of Geriforte in Common Stressful Illness74 Aim: Clinical evaluation of Geriforte in common stressful illness. Materials and Methods: Ninety-seven patients, 30-60 years age were included. Out of these, 61 were in the Geriforte group and the remaining 36 belonged to the control group. The duration of our study was one year. The patients received conventional forms of therapy and at the same time Geriforte was given in a dose of two tablets b.i.d. Those in the control group received only the conventional therapy without Geriforte. Results: Peptic ulcer group: Among 15 patients in the Geriforte group, 10 (66.6%) showed marked improvement, three (20%) had moderate improvement and two (13.3%) showed a borderline or fair response. Fourteen patients on Geriforte therapy reported a general sense of well-being while only two in the control group reported a sense of well-being and lack of lethargy than before. No adverse side effect was observed. Bronchial asthma group: At the end of six months, seven patients (58.3%) in the Geriforte group showed marked improvement versus control group.

Of the remaining five patients, three (25%) showed moderate improvement. Though, these patients had less severe attacks and longer symptom-free intervals, and an elevated sense of well-being, the dose of corticosteroid could not be reduced much. No adverse side effects were noticed during the therapy. One patient had borderline improvement and another remained unchanged.

Gross pulmonary emphysema was noticed in that case (aged 59 years) which did not improve. In 40% of all cases asthma was associated with chronic bronchitis.

Chronic hypotension group: In the Geriforte group, 19 patients (70.3%) improved markedly in their physical and mental strength, developed an unmistakable sense of well-being and gained extra energy to do household work. Their appetite increased as also the body weight. Hb levels too increased. The remaining eight patients (29.6%) improved moderately. Their appetite and Hb values did not increase much. However, the improvement was particularly noticeable among female subjects. No adverse effect was observed following the therapy. Conclusion: Among the four different disease conditions the maximum effectiveness of Geriforte

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review article was noted in chronic hypotension. Hence, Geriforte may be useful to a vast section of womenfolk in our country. It has been proved to be useful in the other three conditions viz., peptic ulcer, bronchial asthma and migraine. The use of Geriforte helps minimize the dose of corticosteroid in bronchial asthma and sedatives and tranquilizers in migrainous headache. Geriforte can be safely used in all the four conditions as no adverse side effect was noted during the therapy.

Study 5: Geriforte in Stress Management: A Placebo-controlled Study75 Aim: To evaluate Geriforte in stress management.

Materials and Methods: Forty male patients, diagnosed individually as suffering from adjustment disorders according to the DSM-III criteria were randomly selected for the study. All these patients showed evidence of stress and anxiety clinically. Patients with any other psychiatric disorder or a physical disorder were excluded from this study. The 40 patients were divided into two groups: Group I (experimental group; n = 20) and Group II (control group; n = 20).

They were administered the following tests initially and after six weeks of therapy: The Revised Willoughby Questionnaire and the Bernreuter S-S Self-Sufficiency Inventory. Results: It is indeed not possible to arrive at clear conclusions from this small study of only 20 patients in the experimental group. It is essential to replicate this study with large numbers of patients.

At the same time it would be necessary to study the biochemical aspects of stress, preferably the levels of corticosteroids and catecholamines and note the changes in these levels as a result of the administration of Geriforte. If such a study is carried out and the results obtained are found to be significant, the true value of Geriforte in Stress would be doubly clear. We hope to proceed in this direction. Till then we can only say we have found Geriforte useful in the management of stress.

Study 6: A Clinical Trial of Geriforte as an Antistress Agent in Cancer Patient76 Aim: To study Geriforte, being a comprehensive metabolic tonic and antistress therapy, as an antistress agent in cancer patient. Materials and Methods: The trial was conducted in two phases I and II. Phase I: A total of 100 patients attending the Regional Centre for Cancer Research and Treatment, Gwalior with proven head and neck cancer and undergoing radiotherapy were included. They were divided into two groups.

Trial A group of 50 patients was put on Geriforte tablets, two tablets b.i.d. along with specific cancer therapy

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(mostly radiotherapy). The other group of 50 cases (Control A) was put on placebo therapy along with specific cancer therapy. Phase II: Here 50 cases were included in which either there was no lesion clinically (CR), or good control (PR) was achieved after specific cancer therapy (mostly radiotherapy). So Phase II was a postradiotherapy phase. These 50 cases were again divided into two groups. Trial B group of 25 cases were put on Geriforte, two tablets b.i.d. without any other therapy. The other group (Control B) also consisting of 25 cases was put on placebo therapy. Evaluation was done in both the phases after 4-5 weeks of therapy (the usual radiation period), and after radiotherapy also patients come for follow-up initially, after 4-5 weeks. Results: The results during radiotherapy were encouraging and 60-66% showed improvement in their general complaints. Due to the encouraging results during radiotherapy we thought of trying it in the postradiotherapy period also. We observed that these patients responded as high as 88% to Geriforte therapy.

Conclusion: Cancer patients receiving Geriforte for a long time felt much better. The feeling of fatigability is reduced and capacity to work restored. Depression gives way to cheerful optimism. Though these are subjective feelings, a certain score was applied for evaluation and the data could be analyzed numerically.

They prove that Geriforte is a significantly good tonic without any side effects. Overall the cost is within the reach of average patients coming from a poor socioeconomic group.

Study 7: Efficacy and Safety of a Polyherbal Formulation in Geriatric Age Group: A Phase IV Clinical Report77 Aim: To determine the efficacy as antioxidant and safety profile of the polyherbal formulation in geriatric patients of eastern India. Materials and Methods: The study was double-blind, randomized including placebo-controlled and was approved by the Ethical Committee of SSKM Hospital. Geriatric patients attending the OPD of SSKM Hospital formed the study group. The patients were randomized to receive either the polyherbal formulation or the identical-looking placebo at a dose of two tablets b.i.d. for a period of six months. Follow-up of patient status was done monthly. Results: Significant rejuvenation of the antioxidant property, which is determined by the enzymatic and nonenzymatic antioxidants, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, reduced glutathione and malondialdehyde, in the geriatric patients were seen in patients treated with Geriforte tablets as compared to patients in the

review article placebo and control group. There were no significant adverse effects experienced by cases in any group.

Conclusion: The polyherbal formulation is effective in rejuvenating geriatric age group compared to the placebo. It is safe and compliance to the treatment was good.

Conclusion With advancing age, the elderly experience a gradual deterioration in their physical, physiological and mental health. In Ayurveda, a number of herbal formulations and dietary schedules have been especially advocated for the elderly in the hope of rejuvenating them and preventing the many problems that come with advancing age. The last few years have witnessed a general revival of interest in such herbal drugs.

Geriforte, a polyherbal formulation is an ideal geriatric tonic to solve the problems associated with aging.

Being a nonhormonal preparation, Geriforte can be used safely. Its efficacy can be attributed to the synergistic actions of the individual herbs.

The herbs in Geriforte also possess hepatoprotective, renoprotective, rejuvenative properties. The antistress, adaptogenic properties of Geriforte tablets retard degenerative changes, and accelerate cellular regeneration and repair. It helps delay the physiological changes associated with aging, revives physical capacity, raises the threshold of fatigue and promotes wellbeing. It facilitates respiratory functions, and assists cardiovascular functioning by improving circulation and reducing raised lipid levels. It regulates fat and carbohydrate metabolism, and improves appetite, digestion and assimilation.

Geriforte contains various herbs with potent antioxidant actions like , T. arjuna, W. somnifera, A. racemosus, G. glabra, T. chebula, M. pruriens, S. aromaticum, C. longa, C. intybus, S. nigrum, B. diffusa, T. cordifolia, Tribulus terrestris which synergistically correct and prevent the free radical-induced oxidative damage to various organs and systems. Antioxidants are intimately involved in the prevention of cellular damage (the common pathway for cancer, aging and a variety of diseases). They are molecules which safely interact with free radicals and terminate the chain reaction before vital molecules are damaged. The antioxidant action of Geriforte tablets scavenges free radicals and its immunomodulatory activity enhances body immunity.

Based on the seven clinical studies reviewed, Geriforte is found to be safe and effective in various geriatric

conditions like stress and in improving the general health. There were no adverse effects either clinically or with hematological or biochemical evaluation in the clinical studies. The compliance to the study was good. Therefore, it may be concluded that Geriforte is effective in stress and economical and is safe without any adverse effects for short-term and long-term use in the adequate sample size of the cases reviewed.

In addition, it provides a feeling of well-being, which is always welcomed in aging population. As a whole, Geriforte rejuvenate the entire body system and retards various systemic changes associated with aging.

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76. Saksena AK, et al. J Res Edu Ind Med 1988:101.

50. Yerra R, et al. Eur Bull Drug Res 2005;13(1):31-9.

77. Banerjee P, et al. J Ethnopharmacol 2011;134(2):429-33.

504

Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

review article

Syncope: Evaluation and Management SR Mittal

Abstract Syncope is a common symptom in clinical practice. Causes can be relatively benign or potentially lethal. Knowledge of what actually occurs during a spontaneous syncopal episode is ideally the gold standard to determine etiology.

Keywords: Syncope, hypoperfusion, cardiogenic syncope

S

yncope is a common symptom in clinical practice.

Causes can be relatively benign or potentially lethal. Careful history and routine investigations are useful. High-tech investigations usually do not give significant additional information.

reaction, hypoglycemia and hyperventilation with hypocapnia. 

DEFINiTION Syncope is a symptom complex due to sudden, transient and global cerebral hypoperfusion.1



Duration of Hypoperfusion 



3-4 seconds: Presyncope (light-headedness, blurring, dizziness [not vertigo])



6-8 seconds: Syncope, loss of consciousness and postural tone.



AIMS OF EVALUATION 

Is it syncope?



Is it life-threatening?



Need for high tech investigations?



Management



Prevention



Detailed history is the key.

IS IT SYNCOPE? Differential diagnosis includes: 

Disorders with partial or complete loss of consciousness: These include: Tonic-clonic seizure, akinetic seizure, temporal lobe epilepsy, conversion

DM, Dept. of Cardiology St. Francis Hospital, Ajmer Address for correspondence Dr SR Mittal XI /101, Brahampuri, Ajmer, Rajasthan - 305 001 E-mail: sarweshwarm@gmail.com



Tonic-clonic seizure: Frothing at mouth, tongue bite, prolonged confusion, disorientation and retrograde amnesia are diagnostic (clonic movements, incontinence and rolling of eyes can also occur in syncope).

Lack of responsiveness in absence of loss of postural tone: This can occur in akinetic seizure, conversion reaction.

Confusion, change in level of consciousness, flushing: These suggest temporal lobe epilepsy.

Hypoglycemia: It is characterized by: History of diabetes, diet/drug imbalance, hunger and tachycardia (may be absent in defective hypoglycemia warning system), pallor and perspiration. However, these findings can also be present in syncope.

Hyperventilation with hypocapnia: Classical features include hyperventilation (not breathlessness), paresthesia of lips and fingers, history of anxiety and/or depression.

Disorders without impairment of consciousness: These include; cataplexy, drop attacks, psychogenic pseudosyncope. 



Cataplexy: It is precipitated by sudden arousal, anticipation of emotions, laughter, startle, excitement or anger. Body is flacid, eyes may roll and facial muscle flicker may be present.

Drop attacks: These are characterized by (features like patient drops to their knees while walking, patient is aware of fall and is usually able to get up quickly). These are common in elderly females.

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review article Is it Potentially Life Threatening?

Potentially life-threatening causes includes: 







 



 

508

Massive internal bleed: It should be suspected if there is unexplained supine systolic blood pressure (BP) <90 mmHg, orthostatic hypotension with increase in heart rate by >20/min; Hb <9 g/dl; hematocrit is <30% and occult blood on rectal examination.

Massive pulmonary embolism: It should be suspected if there is marked breathlessness (not hyperventilation) with and after syncope, oxygen saturation is <94% while breathing room air; right ventricular failure and deep-vein thrombosis.

Cardiogenic syncope: It should be suspected if there is history of prior heart disease or intervention; history of proarrhythmic drugs; ischemic chest pain with and after syncope; no prodroma (VT) or sudden palpitation for few seconds (SVT, TachyBrady syndrome); syncope during effort (tight AS, tight MS, tight PS, severe PAH, HOCM, ↑QT type 1 and 2, catecholaminergic polymorphic VT, ARVD); syncope at rest without any precipitating factor (VT); syncope with change of posture e.g. turning in bed or change from sitting to supine (LA mass), syncope precipitated by emotion, sudden noise, alarm, telephone (↑QT type 2); startle response (VT), convulsive syncope (asystole); family history of sudden cardiac death and evidence of structural heart disease.  ECG pointers for possibility of cardiogenic syncope are describe in the accompanying Box. Bifasicular block with ↑ PR (risk of high-degree AV block).

Pre-excitation (risk of AF with fast ventricular rate).

Brugada sign:2 RBBB with J point elevation of >2 mm, coved ST elevation and T inversion in lead V1 in absence of other factors that could cause similar ECG abnormality (risk of VT). This ECG sign is important only when associated with history of unexplained arrhythmias or family history of unexplained sudden death.

T ↓ beyond V2 in absence of RBBB or juvenile pattern, Epsilon wave (localized notch on terminal part of QRS in V1), QRS duration of >110 msec in V1-V3 with normal duration in V6, S1 upstroke in V1-V3 >55 msec. Arrythmogenic RV dysplasia.

(ARVD) (Risk of VT).

Sinus bradycardia (<50/min) (risk of prolonged pause).

Sinus pause >2 seconds (risk of prolonged pause).

Tachy-Brady syndrome (syncope usually occurs during long pause following tachycardia).

Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

Long QTc >500 msec:3  LQT 1: Characterized by smooth broad-based T waves.  LQT 2: Characterized by notched, biphasic and low voltage T waves.  L QT 3: Characterized by prolonged ST segment and small peaked T waves.  LQT 1 and LQT 2: With QTc of ≥500 msec have risk of arrhythmias during exercise.  LQT 2: Precipitation of arrhythmias by auditory stimuli (e.g., noise, alarm, telephone).  LQT 3: Majority of cardiac events occur at rest.  Short QT-QTc ≤350 msec.4 at heart rate of less than 100 beats/min. It may be associated with tall peaked symmetrical T waves resembling hyperkalemia.  T-wave alternans: (Risk of polymorphic VT) Normal resting ECG does not exclude possibility of  Catecholaminergic polymorphic VT  Idiopathic VT  Arrhythmogenic RV dysplasia, transient prolongation of QT  Concealed ECG pattern of Brugada syndrome  Bundle branch re-entry VT  Fascicular VT. However, inspite of above-mentioned limitations, a normal ECG is an important negative finding and abnormal ECG is an independent predictor of cardiac syncope and increased mortality. 



Echocardiography: Helps in better evaluation of structural heart disease, ejection fraction and pulmonary artery hypertension. 

Hypertrophic cardiomyopathy is diagnosed by concentric or localized LVH, dynamic LVOT obstruction. Normal LV thickness, however, does not exclude presence of HCM mutant gene.

Correlation of syncope to arrhythmia is mandatory to establish etiological relationship: Modality of preferred investigation depends on frequency of syncope:1 Symptoms daily





Arrhythmogenic right ventricular dysplasia: Classical echocardiographic findings include: Localized or diffuse dilatation of RV; end diastolic aneurysm; increased reflectivity of moderator band and prominent apical trabeculations of RV. Echo may, however, be normal in early stages.

review article (ambulatory ECG monitoring); symptoms once in a few days (event recorder) and very infrequent symptoms (loop recorder). 

prolonged standing in hot weather; post exercise; prolonged bout of cough, laughter or sneezing and hot shower

Non life-threatening syncope: These include 

Orthostatic syncope: Occurs immediately or upto 10 minutes after assuming upright posture from supine or sitting position. Causes of orthostatic syncope include volume depletion (acute bleeding, dehydration, dialysis), primary adrenal insufficiency, drugs (antihypertensives, antipsychotic, antidepressants, sublingual nitrates). 

Psychogenic syncope: This is characterized by (Hyperventilation, paresthesia in fingers and lips, palpitation and atypical chest pain may precede syncope, usually episodes occur in presence of others, gradual rather than sudden fall, absence of injury inspite of repeated episodes, history of anxiety and/or depression.

Transient vertebrobasilar insufficiency: Vertigo, diplopia, dysarthria, ataxia precede syncope.

Circumstances that precipitate such syncope include: Hyperextension and lateral rotation of neck; spasm (migraine throbbing unilateral headache), scintilating scotoma.

Other Causes of Syncope

Subclavian Steal Syndrome It is a rare cause of syncope occurring on effort from a particular upper limb. There is reversal of flow from ipsilateral vertebral artery to subclavian artery distal to total occlusion causes cerebral ischemia. Vertigo is common.

Postural syndrome3

Sleep Syncope

orthostatic

tachycardia

Neurally-mediated syncope (reflex/vasovagal/ situational): It is preceded by abdominal symptoms, nausea, yawning, diaphoresis, prolonged fatigue (not disorientation) may follow such syncope. 



Carotid sinus hypersensitivity: Following circumstances act as precipitating factors: Shaving; tight collar; turning head to one side and internal carotid artery angioplasty.

Secondary: Peripheral neuropathy, diabetes, chronic renal failure, B12 deficiency; autoimmune diseases (SLE, rheumatoid arthritis, mixed connective tissue disease); Guillain-Baire syndrome and spinal cord lesions.

Syncope on standing: Decrease without hypotension in first five minutes of standing with increase in heart rate of >30/min. The cause of syncope is not clear.

Increased cerebrovascular resistance is considered responsible. 



Autonomic dysfunctions:2 No diaphoresis and suggest autonomic dysfunction, relatively fixed heart rate.

Primary: Pure autonomic failure - clinical features include (erectile dysfunction, gastroparesis, constipation, anhidrosis, heat intolerance, neurogenic bladder).

Additional striatonigral degeneration produces additional features of Parkinsonism. Additional olivo-pontocerebellar degeneration produces additional cerebellar ataxia and pyramidal signs.

Acute autonomic failure.5





Situations producing neurally-mediated syncope: Defecation, urination, swallowing; aspiration of pleural, pericardial or peritoneal fluid; unpleasant sight, sound or smell; painful stimulus, neuralgia, visceral pain; overcrowding; instrumentation;

Waking-up with feeling of fainting and abdominal discomfort followed by fainting. It is common in type 3 prolonged QT.

Convulsive Syncope Suggestive features include: Old age; more frequent occurrence with cardiac arrhythmias and asystole; clonic movements (nonrhythmic and rarely sustained for more than half a minute) and complex movements like lip-licking, chewing, head turning may be present.

INVESTIGATIONs6

Carotid Compression1 Contraindications: Carotid bruit, stroke, history of VT or VF Procedure: Longitudinal digital pressure over carotid at the level of angle of mandible for five seconds.

Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

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review article One side to be followed by other side after an interval of two seconds.

64 Slice CT Coronary Angiography 

Response: Sinus pause of >3 seconds suggests carotid sinus hypersensitivity. Results do not necessarily correlate with cause of syncope. Test may be positive in asymptomatic elderly.

Head up Tilt Table Test1 Procedure: Foot rest supported, head up tilting at 70- 80° for 30-45 minutes.



It is helpful in diagnosing anomalous origin of coronaries- a cause of syncope in children. (Other causes of syncope in children are HOCM, severe AS, ↑ QT, ↓ QT, neurally-mediated syncope, Brugada syndrome, WPW syndrome, ARVD, catecholaminergic VT).

Brain imaging, carotid Doppler, EEG and chest radiography are not indicated.

Indications for Hospitalization

Response: As described below.

BP

Heart rate

Possible cause

↓ ≤ 25/10

↑

Volume depletion/drugs

↓ ≤ 25/10

↓

Neurally-mediated syncope

↓ <25/10

-

Autonomic dysfunction

-

↑

Postural orthostatic tachycardia syndrome

Following findings suggest high-risk patients who should be hospitalized. Two mnemonics help in remembering the various parameters.

BRACES B: BNP >300 pg/ml, bradycardia R: Rectal examination (occult blood)

Results do not necessarily correlate with cause of syncope. Negative predictive value is high.

A: Anemia (Hb <9 g)

High-tech Evaluation

E: ECG- presence of Q except in lead III

When simple examinations are unhelpful, more sophisticated high-tech investigations have a very low yield at a very high cost.

S: Saturation <94% while breathing room air

Indications for high-tech investigations cardiogenic syncope

Investigation of choice

Suspicion of exercise-induced ischemia or arrhythmia (in absence of LVOT obstruction)

TMT

Frequent unexplained syncope with strong suspicious of cardiac arrhythmia

EPS (low positive predictive value)

Pre-excitation

EPS

Suspicion of ARVD

MRI

C: Chest pain (ischemic in character)

CHESS C: Chronic heart failure H: Hematocrit <30% E: ECG (abnormal) S: Shortness of breath S: Systolic BP <90 mmHg PREVENTION

Cardiogenic  

Signal averaged ECG  

QRS duration ≥114 msec.

Low amplitude signals in terminal portion of QRS ≥38 msec. These findings suggest susceptibility for VT. Test has low positive predictive value, but high negative predictive value.



Avoid precipitating factor.



Maintain adequate salt and water intake.



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Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

In unexplained and recurrent syncope in persons with high risk jobs and high suspicion of ventricular arrhythmias, empirical automatic implantable cardiovertor defibrillator (AICD) is justified.

Neurally-mediated Syncope

Microvolt T-wave Alternans Spectral analysis of small changes in T-wave amplitude in alternating beats. The test has high negative predictive value but low positive predictive value.

Guided by underlying cause





Periodic flexion and extension of ankle and knee if prolonged standing is unavoidable.

With onset of prodrom, leg crossing, handgrip and arm tensing or lying down. b-blockers (there is no consistent benefit).

review article 

Carotid sinus hypersensitivity (permanent pacemaker implantation).





Orthostatic Syncope Nonpharmacologic: Elevation of head-end of bed by six inches; Move feet and leg for few minutes before rising; Rise slowly and step-wise. Supine-move legs sit- move legs- stand; Elastic compression stocking waist height, at least 30 mm compression at ankle; Tilt training - standing against the wall for 30 minutes twice-daily; Gradually increase duration.

Pharmacotherapy: Various drugs are used such as mineralocorticoid (e.g. fludrocortisone), a-agonist (e.g. midodrine), a-2 agonist (e.g. clonidine), norepinephrine and dopamine reuptake inhibitors (e.g. bupropion), acetylcholinesterase (e.g. pyridostigmine inhibitors), splanchnic vasoconstrictors (e.g. octerotride), SSRI (e.g. escetalopam, fluoxetine). No consistent benefit with any drug is shown in long-term trials.



Syncope is a transient symptom.



No diagnostic signs are present after episode.



 





Neurally-mediated syncope, which is benign, is the most common cause.

Potentially lethal conditions must be excluded.

Autonomic failure is disabling multidisciplinary approach.

and

needs

Syncope may be multifactorial especially in the elderly.

Knowledge of what actually occurs during a spontaneous syncopal episode is ideally the gold standard to determine etiology.

Cases of infrequent syncope loop recorder is likely to become increasingly important and in future, may be appropriate before many current conventional investigations.

ICD may help high-risk patients with unidentified etiology but strong suspicion of tachyarrhythmias.

References 1.

Calkins H, Zipes DP. Hypotension and syncope.

In: Braunwald’s Heart Disease. 9th edition, Bonow RO, Mann DL, Zipes DP, Libby P (Eds.), Elsevier. St. Louis 2012:885-95.

2.

Somers VK. Cardiovascular manifestation of autonomic disorders. In: Braunwald’s Heart Disease. 9th edition, Bonow RO, Mann DL, Zipes DP, Libby P (Eds.), Elsevier: St. Louis 2012:1949-61.

3.

Tester DJ, Ackerman MJ. Genetion of cardiac arrhythmias. In: Braunwald’s Heart Disease. 9th edition, Bonow RO, Mann DL, Zipes DP, Libby P (Eds.), Elsevier: St. Louis 2012:81-90.

4.

Olgin J, Zipes DP. Specific arrhythmias: Diagnosis and treatment. In: Braunwald’s Heart Disease. 9th edition, Bonow RO, Mann DL, Zipes DP, Libby P (Eds.), Elsevier: St. Louis 2012:771-824.

5.

Carlson MD, Grubb BP. Diagnosis and management of syncope. In: The Heart 13th edition, Fuster V, walsh RA, Harrington RA (Eds.), Hurst’s. Mc Graw Hill: New York 2011:1125-38.

6.

Miller JM, Zipes DP. Diagnosis of cardia arrhythmias.

In: Braunwald’s Heart Disease. 9th edition, Bonow RO, Mann DL, Zipes DP, Libby P (Eds.), Elsevier: St. Louis 2012:687-709.

CONCLUSIONS 

With conventional approach, etiology may remain undefined in nearly 50% cases.2

Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

511

clinical study

Clinical and Investigative Profile of Ring-enhancing Lesions on Neuroimaging PS Mahato*, AS Dabhi**, PB Thorat**

Abstract Aims: To analyze and evaluate ‘ring-enhancing’ appearance as a sign in the differential diagnosis of neurological lesions in the brain and clinically correlate such an appearance with patients’ mode of presentation, etiological factors, outcome and mode of management. Study Design: A cross-sectional study was done in 40 patients in whom ring-enhancing lesions were found on neuroimaging. They were retrospectively analyzed in view of their clinical presentation and investigative profile.

Material and Methods: The study was conducted at the Dept. of Medicine, Shri Sayajirao General (SSG) Hospital, Vadodara, Gujarat. The study was conducted over a period of 24 months in 40 patients. Results: We observed that infective pathology was the most common etiology in patients with multiple ring-enhancing lesions of the brain. Tuberculosis (TB) and neurocysticercosis (NCC) were the most common infections. Neoplastic etiology was the commonest noninfective etiology. Conclusion: Our study establishes the role of TB as the leading cause of ring-enhancing lesions in the Indian setup as compared to tumors in the Western world. It might serve a basis for early recognition and intervention in these patients. We suggest that in patients with multiple ring-enhancing lesions of the brain, a CSF examination and imaging of chest should always be performed.

Keywords: Tuberculoma, neurocysticercosis, seizures, headache

A

variety of infective and noninfective processes display a pattern of ring enhancement on neuroimaging, which often prohibits a reliable diagnosis and clinical correlation is essential. In developing countries often it is not possible to perform brain biopsies because of limited neurosurgical and neuropathological facilities.1 In this study, an attempt has been made to establish the etiological diagnoses of ring-enhancing lesions of the brain using clinical findings and neuroimaging abnormalities, and by blood and cerebrospinal fluid (CSF) examinations. This is important since they present with diagnostic and therapeutic challenges simultaneously.2 This study is undertaken with a view to study patients with such lesions on neuroimaging, keeping in mind the diversity in relation to their clinical presentation, etiological factors and methods of investigation and impact of various modes of management.

AIMS OF STUDY 



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Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

Clinical correlation of such an appearance with patients’ mode of presentation, etiological factors, outcome and mode of management.

MATERIAL AND METHODS Forty patients (more than 12 years of age) with ringenhancing lesions on neuroimaging admitted to different medical wards of Shri Sayajirao General (SSG) Hospital, Vadodara, Gujarat were included in this retrospective cross-sectional study.

Inclusion Criteria 



*Third Year Resident **Associate Professor Dept. of Medicine Medical College and SSG Hospital, Vadodara Address for correspondence Dr Ajay S Dabhi 38, Alkanagar, Near Priyalaxmi Mill, Old Alembic Road, Vadodara - 390 003 E-mail: dr_ajay_44@yahoo.co.in

To analyze and evaluate ‘ring-enhancing’ appearance as a sign in the differential diagnosis of neurological lesions in the brain.

Only adult patients (more than 12 years of age) were included.

All patients with ring-enhancing lesions on neuroimaging were included in the study and retrospectively analyzed in view of their clinical presentation and investigative profile.

Exclusion Criteria None.

clinical study Methods A detailed clinical history was noted as described in the study proforma in all patients with neuroimaging suggestive of ring-enhancing lesions. A detailed past, family and personal history was taken in all patients.

A thorough general and systemic examination, especially evaluation of neurological status was done in view of different etiologies for such a presentation.

Laboratory tests done included a complete blood count with erythrocyte sedimentation rate (ESR), electrolytes and routine biochemical tests. Specific laboratory tests for establishing etiology were performed like screening for HIV-1 and 2, blood cultures, sputum examination and culture. CSF analysis for protein, sugar, cell count and morphology. CSF ADA, IgM toxoplasmosis antibodies, cryptococcal antigen were done when indicated. Imaging studies done included computed tomography (CT) brain with contrast or magnetic resonance imaging (MRI) brain with contrast as was indicated. Ancillary investigations like X-ray chest and USG of abdomen, CT scan of chest, abdomen was done whenever the clinical situation demanded.

DIAGNOSIS AND TREATMENT Probable etiological diagnoses were based on the presence of supportive findings detected after clinical evaluation and above mentioned battery of investigations. The diagnosis remained probable because in none of the patients histopathological verification was obtained. Patients were provided appropriate symptomatic treatment (corticosteroids, mannitol, antiepileptic drugs and/or analgesics if required). Appropriate specific treatment according to the suggested diagnosis was provided. Some of

the above mentioned laboratory investigations were periodically repeated during hospitalization and on outdoor follow-up to monitor the disease activity on modifying the ongoing treatment.

RESULTS Forty indoor patients admitted to medical ward satisfying the inclusion criteria were selected for the study. Table 1 shows the age and sex distribution. The age of patients ranged from 16 to 70 years. Majority of patients were in the age group of 31-40 years (27.5%).

Out of 40 patients in the study group, 25 were males (62.5%) and 15 were females (37.5%). The overall sex ratio was 1.6:1.

Clinical features of different etiologies are summarized in Table 2. Headache emerged as the most common complaint that the patients presented with. Out of a total of 40, 23 (57.5%) patients complained of headache.

The second most common presenting complaint was that of seizures in 21 (52.5%); fever seen in 17 patients (42.5%), vomiting in 16 (40%) patients and loss of consciousness in 21 patients (52.5%).

Table 1. Age and Sex Distribution (n = 40) Age 12-20

Male

Female

Total

1 (2.5%)

1 (2.5%)

2 (5%)

21-30

2 (5%)

2 (5%)

4 (10%)

31-40

6 (15%)

5 (12.5%)

11 (27.5%)

41-50

7 (17.5%)

3 (7.5%)

10 (25%)

51-60

6 (15%)

2 (5%)

8 (20%)

61-70

2 (5%)

3 (7.5%)

5 (12.5%)

Total

24 (60%)

16 (40%)

40 (100%)

Table 2. Clinical Features of Different Etiologies* Fever

Headache

Vomiting

Tuberculoma

52.3

66.6

42.8

38

47.6

52.3

47.6

47.6

Metastasis

14.2

42.8

14.2

14.2

57.1

42.8

57.1

85.7

NCC

Visual Seizures Unconsciousness Constitutional Neurological complaints disturbances deficits

-

50

25

25

100

25

-

100

Abscess

100

100

66.6

33.3

-

33.3

66.6

100

Glioma

-

-

100

100

-

100

-

100

Toxoplasmosis

100

-

100

-

-

-

100

100

Medulloblastoma

-

100

100

-

100

-

-

100

Infarct

-

-

-

-

100

100

-

100

Hematoma

-

-

-

-

-

100

-

100

*All figures in percentage.

NCC: Neurocysticercosis.

Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

513

clinical study Constitutional disturbances were present in significant number of patients (45%). Twenty-nine patients (72.5%) had focal neurological deficit(s) at the time of presentation.

Past History Eight patients (20%) had a past history of some form of tuberculosis (TB). Five had pulmonary TB and three patients had a past history of TBME. Out of these patients, five (12.5%) were already taking Anti-Kochâ&#x20AC;&#x2122;s treatment (AKT) and probably had drug-resistant form of disease. Eight patients (20%) had HIV/AIDS. Six were taking antiretroviral treatment (ART). Two patients had past history of malignancy of lung and bladder and were on radiotherapy and chemotherapy.

Examination Fifteen (37.5%) patients had pallor and six (15%) patients had cervical lymphadenopathy. Lymphadenopathy was more commonly seen in patients with HIV.

61% patients with ADA >10%. Neuroimaging was done and findings are summated in Table 3. Sixty percent patients had multiple lesions. Calcification was noted in inflammatory pathologies. Calcified scolex was seen in neurocysticercosis (NCC). 27.5% of patients had evident mass effect and 22.5% had meningeal enhancement (Table 4).

Distribution by final diagnosis is summarized in Table 5. Out of total 40 patients, 21 patients (52.5%) were diagnosed as having tuberculoma, seven patients (17.5%) were found to have cerebral metastases with evidence of primary focus elsewhere. Four patients (10%) had NCC. Three patients (7.5%) had evidence of cerebral abscess. Other lesions comprising of glioma, toxoplasmosis, medulloblastoma, infarct and hematoma were seen in one patient each. This compared favorably with previous studies.

On central nervous system (CNS) examination, 48% of patients were conscious; 5% patients had papilledema.

Cranial neuropathies and focal neurological deficits were found in 26% of patients.

We observed that infective pathology was the most common etiology in patients with multiple ringenhancing lesions of the brain. TB and NCC were the most common infections. Neoplastic etiology was the commonest noninfective etiology. In majority, brain lesions were metastatic manifestation of a systemic neoplastic disorder.

Investigations

DISCUSSION

Mean hemoglobin was 10.2 g/dl and ESR 72 mm at end of first hour. Twenty percent patients were HIV positive. Seventeen percent had evident TB on chest X-ray and 10% had evidence of chest metastases.

A general discussion of all the study subjects is followed by a discussion of the individual maladies.

The peak age incidence in a study in CMC, Vellore was between 31-40 years.3 The peak age incidence in our study was 40 years. Headache was mentioned by 14 patients with tuberculoma (66.6%), three patients with intracranial malignancy (42.8%), two patients of NCC (50%) and three patients with cerebral abscess (100%).

CSF analysis was done in 45% cases. Average cell count was 86 cells/mm3. Average CSF protein was 153.6 mg/dl. CSF sugar was less than half the matching RBS in 27% cases. Average CSF ADA was 11.5% with Table 3. Radiological Features of Different Etiologies Pathology Tuberculoma site (multiple/ (14/21) total)

Mets (6/7)

NCC (3/5)

Abscess Glioma (3/3) (0/1)

Toxoplasmosis (1/1)

Medulloblastoma (1/1)

Infarct (1/1)

Hematoma (1/1)

Frontal

6

3

-

3

1

-

1

-

1

Temporal

4

2

1

1

-

-

-

1

-

Parietal

8

4

4

1

-

-

-

1

1

Occipital

4

2

3

-

-

-

-

1

-

Central Grey matter

2

-

-

1

-

1

-

-

-

Infratentorial

4

1

-

1

-

1

1

-

-

Extra-axial

1

-

-

-

-

-

-

-

-

In the above table nos. refer to no. of cases and not to no. of lesions. The sum of cases in the table would appear to be more than no. of cases as some cases involved multiple sites, and have been counted more than once.

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Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

clinical study Table 4. Perilesional Parenchymal Changes Diagnosis

Edema Midline shift

Hydrocephalus

Meningeal enhancement

Tuberculoma

13

5

4

4

Metastasis

6

4

3

2

NCC

-

-

-

-

Abscess

3

2

-

2

Glioma

1

-

-

-

Toxoplasmosis

1

1

-

-

Medulloblastoma

-

-

-

-

Infarct

1

-

-

-

Hematoma

1

1

-

-

Kumar et al2

Present study

Tuberculoma

50%

52.5%

Primary tumors

9.1%

5%

Metastasis

17.5%

Parasitic

36.36%

12.5%

Abscess

4.55%

7.5%

-

5%

Sex incidence

Enberg et al (n = 53)4

39 years (median)

Males - 47.9%, Females - 52.1%

Cagatay et al (n = 42)5

33.9 years (median)

Males - 33.3%, Females - 66.6%

31 years (mean)

Males - 49%, Females - 51%

Fan et al (n = 100)6

Table 7. Craniopathies in Tuberculoma Patients Investigator

3rd nerve 5th nerve 6th nerve 7th nerve (%) (%) (%) (%) -

5.3

11.4

9.3

Thomas et al8

6

-

18.5

17.7

Present study

4.7

-

23.8

9.5

57.1% of metastases and all patients with NCC had seizures. Loss of consciousness was observed in 52.3% of patients with tuberculoma and 42.8% of patients with intracranial malignancy.

Neurological deficits were commonest in patients with NCC (100%) and metastases (85.7%) and variably seen in tuberculoma (47.6%), ranging from monoparesis to quadriparesis (Fig. 1). Cranial NCC were seen in seven cases of tuberculoma (33.3%) and facial nerve was most commonly involved.

3r

d

ne r

ve

pa

ls y

y e

pa ls

y

ne rv

7t h

ne rv

e

pa ls

si s pa re 6t h

ra pa

re si

si s

s

Tuberculoma

M on o

H

Age incidence

Individual Pathologies

Pa

18 16 14 12 10 8 6 4 2 0

em ip ar e

No. of patients

Others

Investigator

Ahmadinejad et al7

Table 5. Pathology-wise distributions of Ringenhancing Lesions Pathology (all figs. rounded off)

Table 6. Peak Age and Sex Incidences in Tuberculoma Patients

Figure 1. Focal neurological deficits in patients at presentation.

Headache was more predictive of raised intracranial tension than vomiting. Fever was more predictive of an infective/inflammatory pathology especially with acute pathology such as abscess.

Visual symptoms were highly suggestive of the site of initial lesion, like occipital lobe and cranial nerve palsies especially the abducent nerve with features of raised ICT. About 47.6% patients with tuberculoma,

The mean age of patients was 34.4 years with 72% of patients between 21-40 years of age. The mean age obtained in various studies is as shown in Table 6 which is in accordance with our findings.

Twenty-one patients, (12 males and 9 females) with an average age of 34.42 years had intracranial tuberculomas. Males predominated in all age groups.

The sex incidence in various other studies is as shown in Table 6.4-6 In our study, low-grade fever (52%), headache (66%), vomiting (42%), visual complaints (38%), convulsions (47%), constitutional symptoms (47%) and altered consciousness (52%) were the most common presenting complaints. Table 7 shows cranial nerve involvement in patients of CNS TB as obtained in various studies7,8 which compare favorably with our study.

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clinical study Seventeen percent patients had evidence of old or active pulmonary TB on chest X-ray. We noted a frequent association of multiple ring-enhancing lesions of the brain with miliary and cavitary pulmonary TB. In 10 patients (50%) with multiple ring-enhancing lesions of the brain, we observed CSF abnormalities consistent with tuberculous meningitis. On neuroimaging, 57% patients had multiple lesions. The distribution of these lesions compared with other studies is shown in Table 8.

Cerebral Metastases In our series, metastatic deposits in the cerebral parenchyma were the most common non-infective cause of ring-enhancing lesions of the brain. Average age of the patients suffering from metastasis was 56.1 years. Two patients presented with history of a known primary tumor, one of them was under radiotherapy.

One patient presented with paraparesis and had metastases involving the spine. In two patients, the primary tumor was discovered after the brain lesion presented. Presenting complaints of the patients are compared with other study in Table 9.9 Seventy-one percent had multiple lesions on neuroimaging. All patients with parenchymal metastases involved the supratentorial brain. All demonstrated perilesional edema to variable degree and were largely confined to the white matter.

Neurocysticercosis In the present study, 50% patients had multiple lesions on neuroimaging. All patients had history of seizures.

Signs of raised intracranial tension like headache, vomiting and loss of consciousness were seen in 25% of patients. Comparison with previous study is shown in Table 10.10 In our series, patients with NCC responded well to treatment with albendazole and corticosteroids.

Cerebral Abscess Average age was 48.6 years. Fever and headache occurred in all patients. One patient presented with visual complaints followed by loss of consciousness.

Two patients were diabetic. No case underwent surgical treatment. One patient expired due to the disease.

Frontal and parietal cortices were involved in all cases while 33% cases involved the cerebellum.

Toxoplasmosis The solitary case of cerebral toxoplasmosis was a rare case. Patient was HIV-positive and on ART. Presenting features were compared to other study in Table 11.11

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Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

The patientâ&#x20AC;&#x2122;s HIV-positive status suggested the diagnosis of either primary CNS lymphoma, or toxoplasmosis.

The latter was diagnosed on basis of positive IgM antibodies to Toxoplasma gondii in the serum of the patient.

Majority of the patients with toxoplasmosis have multiple enhancing lesions. Most lesions occur in the basal ganglia and the frontal and parietal lobes.

Most patients of toxoplasmosis respond promptly to appropriate therapy and alternative diagnoses should be considered if no response to therapy is seen in two weeks.

Table 8. Distribution of Intracranial Tuberculomas Kumar et al2 36% patients had multiple lesions

Present study 57% patients have multiple lesions

Supratentorial

55%

76%

Infratentorial

56%

19%

Location

Table 9. Presenting Features in Patients with Cerebral Metastases Symptoms

Present series

Mahaley MS9

Headaches

42.8%

88%

Seizures

57.1%

29%

Vomiting

14.2%

22%

Hemiparesis

46.4%

35%

Visual problems

14.2%

27%

Table 10. Presenting Features in Patients with NCC Clinical features

Present study (n = 4)

Rajshekhar and Chacko (n = 93)10

Seizures

100%

78%

Raised ICT

25%

55%

0

18%

Meningoencephalitis

Table 11. Presenting Features in Patients with Toxoplasmosis Symptoms

Current study case

Ragnaud et al11

Focal neurological deficit

R. hemiparesis

62%

Fever

+

58%

Multifocal

+

59%

Perifocal edema

+

58%

Ring enhancement

+

60%

clinical study Table 12. Presenting Features in Patients with Medulloblastoma Present study case

Becker et al12

Kochi et al13

Bourgouin et al14

Cerebellar hemispheric

+

67%

67%

50%

Hydrocephalus

-

<50%

Did not comment

Did not comment

Cystic degeneration

-

Did not comment

More than childhood

82%

from areas of the world where TB is endemic, even if they have no other evidence of TB, and neuroimaging suggest a nontuberculous etiology of the lesion.

LIMITATIONS  



Glioma A solitary case of a frontal glioma was seen in a 34-year-old female. The patient had history of headache and vomiting with visual complaints, followed by loss of consciousness. Neuroimaging revealed a solitary glioma in the left frontal lobe with mass effect. Patients with primary tumors are more likely to have single lesion.





Medulloblastoma Patient presented with headache, vomiting and seizures followed by left-sided hemiparesis. Cerebellar medulloblastoma was diagnosed on neuroimaging.

Presenting features are compared to other studies in Table 12.12-14 Adult tumors have a much higher incidence of cystic and necrotic degeneration and therefore are less homogenous than their childhood counterparts. This necrosis accounts for the peripheral ring enhancement seen in adults as compared to children.13,14 Infarct and Hematoma Two patients in the study had suffered from an ischemic cerebrovascular stroke with hemorrhagic transformation in the right temporoparietal and occipital regions, and a hemorrhagic stroke with formation of a right frontoparietal hematoma, respectively that revealed peripheral ring enhancement on neuroimaging.

In six patients, we were unable to ascribe a probable cause of multiple ring-enhancing lesions of the brain after clinical evaluation and neuroimaging. Improvement following empirical antituberculous treatment suggests that even in undiagnosed patients CNS TB remains a possibility. Authors from other parts of the world have also advocated that in patients with enhancing brain lesions a trial with antituberculous drugs is of a diagnostic significance, particularly in those coming

The sample size was small.

Only patients of lower and middle class availing services of general hospital are studied. People from higher socioeconomic status could not be included in the study for unknown reasons.

Due to lack of resources certain laboratory parameters like CSF TB PCR, CSF BACTEC, CSF cryptococcal antigen, ELISA for Taenia solium, etc. could not be studied; similarly both CT brain and MRI brain could not be done in all patients. Hence, direct comparison between CT and MRI in patients could not be studied.

Histopathological verification of etiological diagnosis on the basis of brain biopsy was not possible due to lack of resources.

Many patients were lost to follow-up. Out of 40 patients who were included, only 21 patients could be followed-up to completion of their treatment.

CONCLUSION A large number of infectious and noninfectious diseases can cause multiple ring-enhancing lesions of the brain. We reviewed the most common diseases in our setup. The most common etiologies were that of TB, metastases, parasitic (especially neurocysticercosis) and cerebral abscess. Other rare causes include primary brain tumors and cerebrovascular stroke.

Our study establishes the role of TB as the leading cause of ring-enhancing lesions in the Indian setup as compared to tumors in the Western world. It might serve a basis for early recognition and intervention in these patients. On the basis of our experience we suggest that in patients with multiple ring-enhancing lesions of the brain a CSF examination and imaging of chest should always be performed. The work-up of these patients should include clinical evaluation, imaging and a battery of laboratory tests. The specific diagnosis may remain a challenge in many cases.

REFERENCES 1.

Garg RK, Desai P, Kar M, Kar AM. Multiple ring enhancing brain lesions on computed tomography: an Indian perspective. J Neurol Sci 2008;266(1-2):92-6.

2.

Kumar N, Narayanaswamy AS, Singh KK. Ring enhancing CT lesions - a diagnostic dilemma. J Assoc Physicians India 1995;43(6):391-3.

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clinical study 3.

Rajshekhar V, Chandy MJ. Tuberculomas presenting as isolated intrinsic brain stem masses. Br J Neurosurg 1997;11(2):127-33.

4.

Enberg GM, Quezada B Mde L, de Toro VC, Fuenzalida LL. Tuberculous meningitis in adults: review of 53 cases.

Rev Chilena Infectol 2006;23(2):134-9.

5.

Cagatay AA, Ozsut H, Gulec L, Kucukoglu S, Berk H, Ince N, et al. Tuberculous meningitis in adults - experience from Turkey. Int J Clin Pract 2004;58(5):469-73.

6.

Fan HW, Wang HY, Wang HL, Ma XJ, Liu ZY, Sheng RY. Tuberculous meningitis in Chinese adults: a report of 100 cases. Zhonghua Nei Ke Za Zhi 2007;46(1):48-51.

7.

Ahmadinejad Z, Ziaee V, Aghsaeifar M, Reiskarami SR. The prognostic factors of tuberculous meningitis. Int J Infect Dis 2003;3(1).

8.

Thomas MD, Chopra JS, Walia BN. Tuberculous meningitis (T.B.M.) (a clinical study of 232 cases). J Assoc Physicians India 1977;25(9):633-9.

9.

518

Mahaley MS. Commentary on diagnosis and surgical management of metastatic brain tumor. J Neurol Oncol 1986;4(3):191-3.

Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

10. Rajshekhar V, Chacko G, Haran RP, Chandy MJ, Chandi SM. Clinicoradiological and pathological correlations in patients with solitary cysticercus granuloma and epilepsy: focus on presence of the parasite and oedema formation. J Neurol Neurosurg Psychiatry 1995;59(3):284-6.

11. Ragnaud JM, Morlat P, Dupon M, Lacoste D, Pellegrin JL, Chene G. Cerebral toxoplasmosis in AIDS. 73 cases.

Clinical Epidemiology Group on AIDS in Aquitania.

Presse Med 1993;22(19):903-8.

12. Becker RL, Becker AD, Sobel DF. Adult medulloblastoma: review of 13 cases with emphasis on MRI. Neuroradiology 1995;37(2):104-8.

13. Koci TM, Chiang F, Mehringer CM, Yuh WT, Mayr NA, Itabashi H, et al. Adult cerebellar medulloblastoma: imaging features with emphasis on MR findings. AJNR Am J Neuroradiol 1993;14(4):929-39.

14. Bourgouin PM, Tampieri D, Grahovac SZ, LÊger C, Del Carpio R, Melançon D. CT and MR imaging findings in adults with cerebellar medulloblastoma: comparison with findings in children. AJR Am J Roentgenol 1992;159(3):609-12.

clinical study

Prevalence and Antibiotic Sensitivity Pattern of Bacteria Isolated from Nosocomial Infections in a Surgical Ward Rama Sikka*, JK Mann**, Deep†, MG Vashist‡, Uma Chaudhary¶, Antriksh Deep§

Abstract Background and Aims: Nosocomial infections among surgical patients are common and many are preventable. It is critical to understand microbiology of these infections in order to create appropriate strategies to reduce this risk. This study was planned to delineate the occurrence, microbiology and sensitivity pattern of such infections among surgical patients.

Subject and Methods: Various from 130 patients admitted to the surgery ward were cultured, identified and antibiotic sensitivity was performed by standard methods. Results: From 130 patients, 146 isolates were recovered. Of these 140 (95.9%) were bacterial and six (4.1%) were of Candida spp. Most frequently observed nosocomial infections were SSIs (55.4%) followed by infections of urinary tract (28.4%), respiratory tract infections (10.8%) and bacteremia was observed in only 5.4% patients. The predominant pathogen isolated from polymicrobial episodes were E. coli, S. aureus, K. pneumoniae, A. baumanii and P. aeruginosa.

Resistance to b-lactams was high and carbapenems were found to be most effective drugs against GNBs. Conclusions: Gramnegative organisms are the predominant pathogens causing infections in surgical patients. The increasing trend of resistance to b-lactams is posing a great problem. So for proper management of critically ill patients and patients undergoing various operative procedures and other medical interventions, hospital antibiotic policies need frequent revisions.

Keywords: Nosocomial infections, surgical site infections, antimicrobial resistance

N

osocomial infections or healthcare-associated infections encompass all clinically evident infections that do not originate from patient’s original admitting diagnosis.1 The incidence of nosocomial infections is about 5-10% in most developed nations while in India, one in four patients admitted into hospital acquire nosocomial infection.2 Common nosocomial infections in surgical patients include surgical site infections (SSIs), urinary tract infections (UTIs), pneumonias and blood stream infections (BSIs). In 1986, NNIS report, the overall incidence of nosocomial infections was 33.5 per 1,000 discharges, the range extended from 13.3 per 1,000 discharges to 46.7 per 1,000 discharges in surgical patients. *Professor **Resident †Senior Resident, Dept. of Microbiology ‡Senior Professor, Dept. of Surgery ¶Senior Professor and Head §Associate Professor Dept. of Microbiology Pt. BD Sharma PGIMS, Rohtak, Haryana Address for correspondence Dr Rama Sikka Professor, Dept. of Microbiology Pt. BD Sharma PGIMS, Rohtak, Haryana E-mail: ramasehgal30@yahoo.com

The higher incidence of infections among surgical patients was largely attributable to SSIs.3 SSIs account for approximately a quarter of all nosocomial infections.

These infections can range from superficial wound infections, which have minimal mortality rates but add a considerable cost to patient care, to necrotizing soft tissue infections, which are associated with prolonged hospitalization, significant healthcare expense and a high mortality rate.4 The incidence of infection varies from surgeon-to-surgeon, from hospital-to-hospital, from one surgical procedure to another, and most importantly from one patient to another. In clean surgical procedures, in which the gastrointestinal, gynecologic and respiratory tracts have not been entered, Staphylococcus aureus from the exogenous environment or the patient’s skin flora is the usual cause of infection. In other categories of surgical procedures, including clean contaminated, contaminated and dirty, the polymicrobial aerobic and anaerobic flora closely resembling the normal endogenous microflora of the surgically resected organ are the most frequently isolated pathogens.5 Emmerson et al in 1996 reported that surgical wound infections accounted for 12.3% of all hospital acquired infections.6 Basa et al in their study observed that department of surgery had the

Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

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clinical study highest infection rate among all clinical departments and 50% of the cases were due to gram-negative bacteria.7 UTIs also accounts for a large number of nosocomial infections in surgical patients. The single most important factor for nosocomial bacteriuria and UTI is the presence of indwelling urinary catheter.8 This issue of nosocomial infections in surgical patients is further complicated by emergence of polyantimicrobial resistant strains of hospital pathogens.9 Multiple antibiotic resistance to all useful classes of antibiotics has gradually increased among a number of gramnegative hospital pathogens especially the Klebsiella spp., Enterobacter spp., Pseudomonas aeruginosa and Acinetobacter spp.10 Having a knowledge of spectrum of organisms causing SSIs and their resistance pattern is important when considering strategies for controlling the development and spread of resistance. Keeping in mind the above facts, this study was planned to delineate the occurrence, microbiology and sensitivity pattern of such infections for a better management thereby, reducing both mortality and costs.

vancomycin (30 µg), ofloxacin (5 µg), gatifloxacin (5 µg), amoxycillin/clavulanic acid (20 µg/10 µg), pristinamycin (15 µg), nitrofurantoin (50 µg) and norfloxacin (10 µg).

Subject and Methods

All the antibiotic discs used were obtained from Hi-Media Laboratories Pvt. Ltd.

Study Center This was a prospective study carried out at a teaching tertiary care hospital in India over a period of one and a half year.

Patient Selection One hundred thirty patients admitted to surgical ward, who developed signs and symptoms of SSIs, pyrexia, bacteremia, pyuria or respiratory infection after 48 hours of admission were included in the study. Patients with any signs of infection at the time of admission were excluded from study.

Processing of Specimen Pus sample or two wound swabs, urine, sputum and blood were collected aseptically from the operated patients and were transported immediately to the Microbiology lab. The pathogens were identified by standard laboratory procedures including Gram’s staining, motility, colony characters and biochemical reactions.11 Antibiotic susceptibility testing was done

by Kirby-Bauer disc diffusion method.12 Following antimicrobials were used: For Gram-positive Aerobic Isolates Penicillin (2 units), oxacillin (1 µg), cephalexin (30 µg) doxycycline (30 µg), erythromycin (15 µg), clindamycin (2 µg), linezolid (30 µg), cotrimoxazole (25 µg),

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Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

For Gram-negative Aerobic Isolates Amoxycillin (10 µg), cephalexin (30 µg), gentamicin (10 µg), amikacin (30 µg), amoxycillin/clavulanic acid (20 µg/10 µg), piperacillin/tazobactam (100 µg/ 10 µg), cefepime (30 µg), ceftazidime/clavulanic acid (30 µg/10 µg), cefoperazone/sulbactam (75 µg/30 µg), cefotaxime (30 µg), ciprofloxacin (5 µg), meropenem (10 µg), aztreonam (30 µg), ceftazidime (30 µg), netilmicin (30 µg), gatifloxacin (5 µg), nitrofurantoin (50 µg) and norfloxacin (10 µg).

For Pseudomonas Species Ceftazidime (30 µg), gentamicin (10 µg), amikacin (30 µg), piperacillin/tazobactam (100 µg/10 µg), cefepime (30 µg), aztreonam (30 µg), ofloxacin (5 µg), imipenem (10 µg), ceftriaxone (30 µg), netilmicin (30 µg), ceftizoxime (30 µg) and norfloxacin (10 µg).

Results A total of 130 patients were investigated in the present study, out of which 103 (79.2%) were males and 27 (20.8%) were females and the age ranged between 7-80 years (20.8% of patients in age group of 31-40 years).

Maximum number of operated patients suffered wound infections (55.4%) followed by infections of urinary tract (28.4%). Infection of respiratory tract and bacteremia was observed in only 10.8% and 5.4% patients, respectively.

Pathogens A total of 146 isolates were recovered, of which 140 (95.9%) were bacterial and six (4.1%) were of Candida spp. and among the bacterial isolates, Escherichia coli (54.9%) was the commonest one. It was observed that majority of episodes were monomicrobial (85.7%) rather than polymicrobial (14.3%). Most frequently observed nosocomial infections were SSIs (55.4%) followed by infections of urinary tract (28.4%), respiratory tract infections (10.8%) and bacteremia was observed in only 5.4% patients. Most frequently isolated organisms from surgical site were E. coli (58%), Klebsiella pneumoniae (9.9%), S. aureus (8.6%), Enterobacter spp. and P. aeruginosa (6.2% each), Acinetobacter baumanii (4.9%), Citrobacter spp. (3.7%) and Proteus vulgaris (2.5%). Among the urine isolates

clinical study the most common isolate was E. coli (50%) and Candida was the second most common isolate. K. pneumoniae (9.9%) was the most commonly isolated organism from sputum sample (Table 1). The predominant pathogen isolated from polymicrobial episodes were E. coli, S. aureus, K. pneumoniae, A. baumanii and P. aeruginosa, Enterobacter spp., Citrobacter spp. and P. vulgaris were observed only in single episode each.

and aztreonam. Although, no isolate from urine sample was resistant to amikacin but they were resistant to gentamicin. Imipenem was the most effective drug as no isolate was resistant to it (Table 3).

Table 1. Site-wise Distribution of Various Isolates in Nosocomial Infections among Surgical Patients Type of isolate

Site Surgical

Urine

Respiratory tract

Blood

E. coli

47

22

2

1

K. pneumoniae

8

4

4

1

Enterobacter spp.

5

4

3

-

P. aeruginosa

5

2

-

1

Citrobacter spp.

3

5

2

1

A. baumanii

4

1

3

1

P. vulgaris

2

-

-

-

S. aureus

7

-

-

2

Candida spp.

-

6

-

-

81

44

14

7

Antimicrobial Susceptibility Pattern On performing antimicrobial susceptibility testing of GNBs other than P. aeruginosa showed high frequency of resistance to b-lactams, quinolones as well as b-lactam- b-lactamase inhibitor was observed.

Resistance to aztreonam was also found to be very high (90-100%). However, least resistance was observed to carbapenems with maximum resistance being observed in 25% isolates of Enterobacter spp. (Table 2).

About 85-100% urinary isolates were also resistant to norfloxacin but resistance against nitrofurantoin was relatively low (35-75%). Isolates of P. aeruginosa showed high level of resistance to cephalosporins

Total

Table 2. Resistance Pattern of Gram-negative Bacteria other than P. aeruginosa from Surgical Patients (%age) Bacterial isolates

Am

G

Ak

Cf

Gf

Ac

Cp

Ca

Cps

Ce

Cpm

Pt

Ao

Nt

Mr

E. coli (72)

98.6

95.8

58.3

93.1

88.8

84.7

98.6

91.6

80.5

94.4

91.6

66.6

98.6

93.1

4.2

K. pneumoniae (17)

100

94.1

76.4

88.2

94.1

88.2

100

100

94.1

94.1

82.3

76.4

100

94.1

0

Enterobacter spp. (12)

100

100

91.6

100

91.6

83.3

100

100

83.3

100

83.3

75

100

91.6

25

Citrobacter spp. (11)

100

81.8

72.7

81.8

72.7

81.8

100

72.7

72.7

100

90.9

90.9

90.9

81.8

18.2

Acinetobacter spp. (9)

100

100

100

100

100

100

100

88.8

77.7

100

100

77.7

100

88.8

22.2

P. vulgaris (2)

100

100

50

50

100

0

100

100

100

100

100

100

100

100

0

Am: Amoxycillin; G: Gentamicin; Ak: Amikacin; Cf:Ciprofloxacin; Gf: Gatifloxacin; Ac: Amoxycillin/clavulanic acid; Cp: Cephalexin; Ca: Ceftazidime; Cps: Cefoperazone/Sulbactam; Ce: Cefotaxime; Cpm: Cefipime Pt: Piperacillin/Tazobactam; Ao: Aztreonam; Nt: Netilmicin; Mr: Meropenem.

Table 3. Resistance Pattern of P. aeruginosa Isolates obtained from Various Clinical Specimens Antibiotics

Pus (n = 5)

Urine (n = 2)

Blood (n = 1)

Total (n = 8)

(n)

(%)

(n)

(%)

(n)

(%)

(n)

(%)

Ceftazidime

5

100

2

100

0

0

7

87.5

Cefepime

5

100

1

50

1

100

7

87.5

Ceftriaxone

5

100

1

50

1

100

7

87.5

Ceftizoxime

5

100

0

0

1

100

6

75

Gentamicin

5

100

2

100

1

100

8

100

Amikacin

5

100

0

0

1

100

6

75

Netilmicin

5

100

1

50

1

100

7

87.5

Aztreonam

5

100

2

100

1

100

8

100

Imipenem

0

0

0

0

0

0

0

0

Piperacillin/Tazobactam

3

60

1

50

0

0

4

50

Ofloxacin

5

100

1

50

1

100

7

87.5

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clinical study Among the 18 isolates of S. aureus, 44.4% were resistant to oxacillin and ofloxacin, whereas no isolate was resistant to vancomycin and linezolid.

Discussion Nosocomial infections become prominent in surgical wards because of surgical intervention and operative procedures and furthermore hospitals particularly acute care units, surgical and medical units are important breeding ground for the development and spread of antibiotic resistant bacteria. A total of 146 isolates were recovered from 130 patients enrolled in the present study over a period of one and a half year; out of which 95.9% were bacterial and 4.1% were fungal. The incidence of fungal infection was similar to Kamat et al9 but lower than other studies, which may be due to shorter period of stay of our study group in hospital.

Most frequently observed nosocomial infections in the current study were SSIs (55.4%) followed by infections of urinary tract (28.4%), respiratory tract infections (10.8%) and bacteremia, which was observed in only 5.4% patients. The prevalence of SSIs was comparable to Kamat et al,9 who reported prevalence of 46.7% in surgical patients. However, Littaua et al13 reported much lower incidence (2.9%) but they included both surgical and medical admissions in their study group.

The protocols for preoperative, operative and postoperative prophylaxis, the pre- and postoperative stay of patients vary in different institution and all these factors have great impact on development of SSIs. Prevalence of UTIs was also comparable to other authors.9,14 However, difference in different types of NIs in different countries may be due to different system employed for epidemiological control of hospital infections. The cultures of wound swab and urine sample yielded polymicrobial growth in 14.3% cases in our study. Singh et al15 and Moraes et al16 have reported polymicrobial growth in 11.3% and 23.3% cases, respectively.

Gram-negative pathogens dominated the whole spectrum, being isolated in 91.35% of cases. We believe that this distribution is most likely a consequence of gram-negative bacteria gaining foothold in nosocomial infections in our hospital.

E. coli remained the most common pathogen followed

by K. pneumoniae and S. aureus in SSIs. Littaua et al13 and NNIS report (1984)3 have also reported the similar results. However, Daschner et al17 and Stratchounski et al18 reported S. aureus and P. aeruginosa as the most common pathogen in SSIs, respectively. The difference in findings

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Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

can be explained by the fact that the study group of these authors comprised of intensive care unit (ICU) patients while patients enrolled in our study were admitted in surgical ward. Breaking the skin barriers during surgery or biopsy allows the normal flora of skin like S. aureus to proliferate and moreover surgery involving gastrointestinal tract often gives chance to microflora of gut to cause SSIs. The most frequent isolate among patients of UTI was E. coli (50%) and Candida was the second most common isolate. Catheterization of patients following major surgeries is a common practice and is responsible for causing UTI in most cases. Laupland et al19 and Hsueh et al20 have also reported similar results. In our study, among the cases of pneumonia, K. pneumoniae (9.9%) was the most commonly isolated organism but some workers have found P. aeruginosa as most common isolate among pneumonia patients.

In our setup, P. aeruginosa is more commonly isolated from ICU patients than from wards. Antimicrobial resistance pattern of GNBs showed high level of resistance to quinolones, gentamicin and cephalosporins.

High level of resistance to cephalosporins suggests that resistance observed was mainly due to production of b-lactamases. However, resistance to amikacin was relatively less viz. 57.97% and carbapenems remained the most effective drug against gramnegative organisms. All the strains of P. aeruginosa were sensitive to imipenem but 60% strains showed resistance to piperacillin-tazobactam. Shenoy et al also reported that all strains of P. aeruginosa in their study were sensitive to imipenem and meropenem.21 Domingo et al also found imipenem as most effective drug against P. aeruginosa.22 Looking at the oxacillin resistance among S. aureus, it must be assumed in our setup that almost 40-50% strains are likely to be methicillin-resistant S. aureus (MRSA).

These data reveal high level resistance to b-lactams among gram-negative and emerging MRSA. These observations are alarming since virtually all the patients are prescribed first- or second-generation cephalosporins as prophylaxis before surgery. Linezolid and vancomycin were the most effective drugs against S. aureus and resistance to these drugs is also soon expected. On observing the multidrug resistance (MDR), it was found that all the bacterial isolates were MDR. This finding is of great concern because if the situation remains the same we will be left with no therapeutic options in the future.

Conclusion Despite aggressive efforts to limit the rapid rise of antimicrobial resistance, the problem of developing

clinical study resistance to multiple antibiotics continues to worsen as demonstrated by various studies including the present study. However, the current situation is the result of ineffective infection control measures and antibiotic policies. So for proper management of critically ill patients and patients undergoing various operative procedures and other medical interventions, hospital antibiotic policies need frequent revisions.

Hospital wide antibiograms may mask unit-specific susceptibility pattern. These unit-specific antibiograms may help surgeon in selection of empirical therapy in surgical patients.

References 1.

Emori TG, Gaynes RP. An overview of nosocomial infections, including the role of the microbiology laboratory. Clin Microbiol Rev 1993;6(4):428-42.

Microbiology. 14th edition, Collee JG, Fraser AG, Marmion BP, Simmons A (Eds.), Churchill Livingstone: New York 1996:p.131-49, 166-7.

12. Bauer AW, Kirby WM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol 1966;45(4):493-6.

13. Littaua R, Tupasi T. Nosocomial infections at the Makati Medical Center: a prospective study and analysis of risk factors. Phil J Microbiol Infect Dis 1986;15(l):l-6.

14. National Nosocomial Infections Surveillance (NNIS) report, data summary from October 1986-April 1997, issued May 1997. A report from the NNIS System. Am J Infect Control 1997;25(6):477-87.

15. Singh AK, Sen MR, Anupurba S, Bhattacharya P. Antibiotic sensitivity pattern of the bacteria isolated from nosocomial infections in ICU. J Commun Dis 2002;34(4):257-63.

16. Moraes BA, Cravo CA, Loureiro MM, Solari CA, Asensi MD. Epidemiological analysis of bacterial strains involved in hospital infection in a university hospital from Brazil.

Rev Inst Med Trop Sao Paulo 2000;42(4):201-7.

2.

Saranya NK. Nosocomial infections. Available at: medscape.com/viewarticle/535488. Accessed on 2009.

3.

Dellinger EP. Nosocomial infection: Discussion. Available at: http://www.medscape.com/viewarticle/535488.

Accessed on 2009.

4.

Malangoni MA. Surgical site infections: the cutting edge.

Infect Dis Clin Pract 2001;10(6):319-23.

5.

Nichols RL. Preventing surgical site infections: a surgeonâ&#x20AC;&#x2122;s perspective. Emerg Infect Dis 2001;7(2):220-4.

6.

Emmerson AM, Enstone JE, Griffin M, Kelsey MC, Smyth ET. The Second National Prevalence Survey of infection in hospitals - overview of the results. J Hosp Infect 1996;32(3):175-90.

7.

Basa GM. An epidemiologic and clinical investigation of nosocomial infection at the Cebu (Velez) General Hospital.

Phil J lnt Med 1984;22:254-61.

19. Laupland KB, Bagshaw SM, Gregson DB, Kirkpatrick AW, Ross T, Church DL. Intensive care unit-acquired urinary tract infections in a regional critical care system. Crit Care 2005;9(2):R60-5.

8.

Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in medical intensive care units in the United States. National Nosocomial Infections Surveillance System. Crit Care Med 1999;27(5):887-92.

20. Hsueh PR, Chen ML, Sun CC, Chen WH, Pan HJ, Yang LS, et al. Antimicrobial drug resistance in pathogens causing nosocomial infections at a university hospital in Taiwan, 1981-1999. Emerg Infect Dis 2002;8(1):63-8.

9.

Kamat U, Ferreira A, Savio R, Motghare D. Antimicrobial resistance among nosocomial isolates in a teaching hospital in Goa. Indian J Community Med 2008;33(2):89-92.

21. Shenoy S, Baliga S, Saldanha DR, Prashanth HV. Antibiotic sensitivity patterns of Pseudomonas aeruginosa strains isolated from various clinical specimens. Indian J Med Sci 2002;56(9):427-30.

10. Struelens MJ. The epidemiology of antimicrobial resistance in hospital acquired infections: problems and possible solutions. BMJ 1998;317(7159):652-4.

11. Collee JG, Miles RS, Watt B. Tests for identification of bacteria. In: Mackie and McCartney Practical Medical

17. Daschner FD, Frey P, Wolff G, Baumann PC, Suter P. Nosocomial infections in intensive care wards: a multicenter prospective study. Intensive Care Med 1982;8(1):5-9.

18. Stratchounski LS, Kozlov RS, Rechedko GK, Stetsiouk OU, Chavrikova EP; Russian NPRS Study Group.

Antimicrobial resistance patterns among aerobic gramnegative bacilli isolated from patients in intensive care units: results of a multicenter study in Russia. Clin Microbiol Infect 1998;4(9):497-507.

22. Domingo KB, Mendoza MT, Torres TT. Catheterrelated urinary tract infections: incidence, risk factors and microbiological profile. Phil J Microbial Infect Dis 1999;8(4):133-8.

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case report

Antenatal Diagnosis of Bilateral Renal Agenesis with Potterâ&#x20AC;&#x2122;s Sequence: A Rare Case Hetal Parikh*, Sameer Raniga**, Nitin Parikh, Palak Vaghela

Abstract Bilateral renal agenesis is an uncommon prenatal diagnosis. It is a lethal anomaly with 50% of the fetuses being stillborn; the rest would die shortly after birth. It is also associated with many other congenital anomalies many of which have autosomal dominant or recessive inheritance. Absence of kidneys in renal fossae with pulmonary hypoplasia and oligohydramnios or anhydramnios strongly suggests the diagnosis of bilateral renal agenesis.

Keywords: Potterâ&#x20AC;&#x2122;s facies, pulmonary hypoplasia, oligohydramnios, congenital anomalies, fetus, sonography

B

ilateral renal agenesis is an uncommon prenatal diagnosis with an incidence of 1:10,000. It is a lethal anomaly with 50% of the fetuses being stillborn; the rest would die shortly after birth, due to severe pulmonary hypoplasia. It is also associated with many other congenital anomalies including skeletal, genitourinary, tracheoesophageal and brain anomalies, many of which have autosomal dominant or recessive inheritance. Therefore, the risk of such anomalies in the subsequent pregnancy is also increased.

CASE REPORT A 26-year-old primigravida presented at 18 weeks of gestation (by last menstrual period) for routine antenatal care. Her medical and obstetric histories were unremarkable. She was subjected for routine antenatal ultrasound examination. Ultrasonographic examination showed a single live intrauterine fetus with mean gestational age of 18 weeks and five days, with amniotic fluid index of zero.

repeat study 24 hours later (Figs. 1 and 2). The fetal lungs were hypoplastic, as suggested by reduced ratio between the maximum transverse thoracic diameter and the maximum transverse abdominal diameter. No other demonstrable congenital anomaly could be found.

The pregnancy was terminated 24 hours after the ultrasound examination, and a stillborn baby was delivered.

Physical examination of the stillborn baby revealed low-set ears, a flat nose, redundant and dehydrated skin, wide set eyes and receding chin consistent with Potterâ&#x20AC;&#x2122;s facies (Fig. 3).

Postmortem ultrasound of the baby also revealed absence of both the kidneys in renal fossae as well as the pelvic cavity. The urinary bladder could not be delineated. Postmortem chest X-ray of the baby

Evaluation of fetal abdomen revealed absence of both kidneys in renal fossae as well as in the pelvic cavity with presence of lying down adrenal sign. The fetal urinary bladder could not be delineated during the entire study period of one hour as well as on a

*Specialist, Dept. of Obstetrics and Gynecology Armed Forces Hospital, Muscat, Oman **Consultant Radiologist Khoula Hospital, Muscat, Oman Address for correspondence Dr Sameer Raniga Po Box: 794, PC: 117, Muscat, Oman E-mail: samhet10200@yahoo.com

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Figure 1. Axial scan of the fetal abdomen shows that both the renal fossae are not occupied by kidneys, and are occupied by the adrenal glands producing lying adrenal sign.

case report spine. In the longitudinal plane, the kidneys are ovoid.

They are typically less echogenic than the bowel. The capsule of the kidney is a thin echogenic line, and the renal sinus is a cluster of echoes located centrally.3

Figure 2. Coronal scan of the fetal abdomen shows absence of both the kidneys in paravertebral region.

Bilateral renal agenesis is an uncommon prenatal diagnosis with an incidence of 1:10,000.1 It is usually sporadic in nature, but may present with a familial history. It results from a lack of induction of the metanephric blastema by the ureteral bud. Newborns with bilateral renal agenesis have low-set floppy ears, broad, flat nose, redundant and dehydrated skin, wide set eyes, prominent fold arising at the inner canthus of each eye, parrot beak nose and receding chin. These features are known as Potter’s facies.1,2,4 These babies often die of respiratory failure within a few hours of birth due to pulmonary hypoplasia. Lungs of newborns with at least one functional kidney usually develop normally. Thus, unilateral renal agenesis is often not associated with oligohydramnios and pulmonary hypoplasia.5

Figure 3. Photograph of the face of the baby shows low-set ears, a flat nose, redundant and dehydrated skin, wide set eyes and receding chin consistent with Potter’s facies.

In most centers, targeted ultrasound for detailed anatomical survey of the fetus is carried out at around 18-20th week of gestation. At this time, based on the reduced amniotic fluid volume, suspicion of bilateral renal agenesis is high. Scheduled detailed anatomical survey by ultrasound will reveal the absence of the kidneys in renal fossae. Prior studies have shown that the prenatal finding of empty renal fossae may be due to renal agenesis, renal ectopia or a fusion anomaly.3,6,7 The ultrasound findings of bilateral renal agenesis are: 

 

Figure 4. Postnatal radiograph shows bell-shaped thorax, suggestive of pulmonary hypoplasia.

revealed bilateral pulmonary hypoplasia, with bellshaped thorax (Fig. 4). Autopsy of the stillborn baby confirmed bilateral renal agenesis.

DISCUSSION Kidneys can be seen as early as 12 weeks’ gestation1,2 located on either side of the spine in the posterior abdomen. In the transverse plane, the kidneys appear as two round structures adjacent to either side of the

Nonvisualization of both the kidneys in bilateral renal fossae, as well as in the entire abdominal cavity Lying down adrenal sign Renal fossae occupied by the bowel gas in late third trimester



Severe oligohydramnios



Nonvisualization of urinary bladder



Pulmonary hypoplasia



Associated other congenital anomalies.

If kidneys are not found in the renal fossa, most are either ectopic (42%) or congenitally absent (47%).3 Most ectopic kidneys are located in the pelvis, but occasionally ectopic kidneys may be found in the thorax. When an empty renal fossae is identified on prenatal sonography, careful assessment of the fetal pelvis is warranted to search for a pelvic kidney.

Adrenal tissues may be confused with renal tissue.

When normal renal tissue is not present, the adrenal preserves its characteristic echogenic medulla

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case report and anechoic cortex, shows enlargement, loses its characteristic ‘V’ or ‘Y’ shape, appears more elliptical and may assume a long slender pancake or disc shape that has been described as lying down adrenal sign.8-10 Presence of intestinal gas in the renal fossae at imaging should lead to a consideration of renal agenesis or ectopia.9,11 Serial evaluation over a period of 4-6 hours to confirm absence of urine production as demonstrated by failure to visualize the fetal bladder may be very useful in establishing the diagnosis with certainty.4 However, absence of kidneys in renal fossae with pulmonary hypoplasia and oligohydramnios or anhydramnios strongly suggests the diagnosis of bilateral renal agenesis.

Bilateral renal agenesis is a lethal malformation.

Keeping in mind the poor prognosis of the condition, any intellectual would ask the relevance of diagnosing the anomalies associated with bilateral renal agenesis.

Bilateral renal agenesis is associated with many autosomal dominant and recessive syndromes.

Recurrence of the syndrome with autosomal dominance inheritance is 50% and with autosomal recessive inheritance is 25%.

Nine percent of first-degree relatives of fetuses with bilateral renal abnormalities have renal malformations themselves, many of which are asymptomatic. If parents have two affected infants, the risk of silent renal anomaly among the first-degree relatives increases to 30%. With a history of single affected fetus, the risk of recurrence of renal agenesis in subsequent pregnancy is 3%. If one parent has unilateral renal agenesis, the risk increases.

In one study,3 42% cases of postnatally proven bilateral renal agenesis had other congenital anomalies, often involving multiple systems. Bilateral renal agenesis is associated with caudal regression syndrome (absence or dysplasia of sacrum, renal and lower extremity anomalies; MURCS association-Mullerian duct aplasia, renal aplasia, cervicothoracic somite dysplasia; VATER association-vertebral defects, anal atresia, tracheoesophageal fistula, esophageal atresia and radial and renal dysplasia) Smith-Lemli-Opitz syndrome (autosomal recessive syndrome featuring.

Microcephaly, mental retardation, genital and renal anomalies) Fraser syndrome (autosomal recessive syndrome featuring cryptophthalmos, syndactyly and genital, renal and tracheal anomalies).12 Occasionally, bilateral renal agenesis is associated with vertebral defects, complex heart defects (14%), skeletal anomalies (40%), CNS anomalies (11%) (ventriculomegaly and neural tube defects), imperforate anus, duodenal

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atresia, tracheoesophageal fistula and single umbilical artery.12 Bilateral renal agenesis is incompatible with life and is a lethal malformation. Approximately 50% of fetuses with renal agenesis are stillborn. The remainders die shortly after birth, from respiratory insufficiency resulting from pulmonary hypoplasia associated with prolonged oligohydramnios.4,12 CONCLUSION Antenatal diagnosis of bilateral renal agenesis is uncommon although important. It is a lethal anomaly with 50% of the fetuses being stillborn and the rest would die shortly after birth, due to severe pulmonary hypoplasia. The associated anomalies with autosomal dominant or recessive inheritance, involving multiple organ systems, increase the risk of similar anomalies to affect the subsequent pregnancy also.

REFERENCES 1.

Bronshtein M, Amit A, Achiron R, Noy I, Blumenfeld Z. The early prenatal sonographic diagnosis of renal agenesis: techniques and possible pitfalls. Prenat Diagn 1994;14(4): 291-7.

2.

Clarke J. University of Michigan. Department of Pediatrics, Division of Nephrology, November 5, 2003.

3.

Chow JS, Benson CB, Lebowitz RL. The clinical significance of an empty renal fossa on prenatal sonography. J Ultrasound Med 2005;24(8):1049-54; quiz 1055-7.

4.

Karimu AL. Renal agenesis and hypoplastic lung syndrome. Vol 2. No. 10.

5.

Renal Agenesis Surveillance -- United States. MMWR 1988/37(44);679-80, 685-6.

6.

Jeanty P, Romero R, Kepple D, Stoney D, Coggins T, Fleischer AC. Prenatal diagnoses in unilateral empty renal fossa. J Ultrasound Med 1990;9(11):651-4.

7.

Sherer DM, Thompson HO, Armstrong B, Woods JR Jr. Prenatal sonographic diagnosis of unilateral fetal renal agenesis. J Clin Ultrasound 1990;18(8):648-52.

8.

McGahan JP, Myracle MR. Adrenal hypertrophy: possible pitfall in the sonographic diagnosis of renal agenesis.

J Ultrasound Med 1986;5(5):265-8.

9.

Dyer RB, Chen MY, Zagoria RJ. Classic signs in uroradiology. Radiographics 2004;24 Suppl 1:S247-80.

10. Hoffman CK, Filly RA, Callen PW. The “lying down” adrenal sign: a sonographic indicator of renal agenesis or ectopia in fetuses and neonates. J Ultrasound Med 1992;11(10):533-6.

11. Mascatello V, Lebowitz RL. Malposition of the colon in left renal agenesis and ectopia. Radiology 1976;120(2):371-6.

12. Benacerraf BR. Syndromes. Ultrasound of fetal syndromes.

1st edition, Churchill Livingstone 1998:272-3.

case report

Multiple Developmental Urogenital Anomalies: A Therapeutic Challenge N Rajamaheswari*, Sugandha Agarwal**, Archana Bharti Chhikara**, K Seethalakshmi†

Abstract Case report: In cases of atretic lower vagina, drainage of hematocolpos per se is inadequate as recurrent hematocolpos from re-stenosis is common. Surgical reconstruction in these cases should be directed to relieve obstruction and ensure continued vaginal patency. A 14-year-old girl reported with primary amenorrhea and recurrence of cyclical lower abdominal pain due to re-stenosis following a primary intervention for hematocolpos. Evaluation identified an atretic lower vagina and multiple associated urinary tract anomalies like unascended right kidney, malrotated left duplex collection system, ureteric diverticula and bladder diverticulum with left ureter opening into it. Though associated Grade IV vesicoureteral reflux (VUR) posed a management dilemma, drainage of hematocolpos and restoration of vaginal continuity by pull through of the proximal vagina and approximating its edges to fourchette relieved the patient of pain, restored menstruation, resolved the VUR and obviated the need for extensive urinary reconstructive procedures. Conclusion: In case of atretic lower vagina, drainage of hematocolpos per se is inadequate as recurrent hematocolpos from re-stenosis is common and surgical reconstruction should be directed to relieve obstruction and ensure continued vaginal patency. Coexisting developmental urinary tract anomalies may not require immediate surgical intervention.

Keywords: Multiple developmental urogenital anomalies, hematocolpos, vaginal atresia, vesicoureteral reflux

O

cclusive vaginal anomaly is identified after puberty, with onset of menstruation when accumulation of menstrual blood causes pain. Surgical management of combined multiple developmental anomalies may appear to be complex with prospect of multiple surgical corrections.

Case Report This manuscript was prepared after obtaining written informed consent from father of the patient.

A 14-year-old girl presented with primary amenorrhea and lower abdominal pain with cyclical increase in severity for three months. Patient did not have any voiding difficulty.

Occurrence of acute abdominal pain at her 14th year (1.12.2010) prompted her to consult the local gynecologist, who recognized hematocolpos and let out 100 ml of altered blood by vaginal incision. It *Professor and Head **Dept. of Urogynecology †Assistant Professor, Dept. of Urogynecology Govt. Kasturba Gandhi Hospital and Institute of Social Obstetrics Madras Medical College,Triplicane, Chennai Address for correspondence Dr Archana Bharti Chhikara H.No.: 1398, Sector-15, Sonepat, Haryana - 131 001 E-mail: archanachhikara@gmail.com

temporarily relieved her of pain, however, menstruation did not resume. Hence, she approached our institute on 15.2.11 for further treatment. Clinical examination revealed a firm, nontender, mobile, midline, abdominal mass of 10 x 6 cm, which appeared to be of uterine origin. Tanner stage for secondary sexual characters corresponded to her age. Local examination under anesthesia revealed normal external genitalia, a hypospadiac urethral meatus, absent vaginal lumen without obvious vaginal bulge due to hematocolpos (cryptomenorrhea).

Ultrasound imaging revealed a 12 x 4 cm mass suggestive of hematocolpos and an unascended right kidney. Intravenous urography confirmed the unascended right kidney in midline at L3-L4 level and revealed a duplex collecting system with malrotation on the left side. Both ureters appeared grossly normal and bladder contour revealed extrinsic compression due to pelvic mass. Micturating cystourethrogram revealed a Grade IV vesicoureteral reflux (VUR) on the left side. Magnetic resonance (MR) urogram revealed the following: 



Posteroinferior bladder diverticulum measuring 37.9 x 13.8 mm with left ureter opening into it (Fig. 1).

Distal left ureteric diverticulum 14.9 x 13.6 mm (Fig. 1).

measuring

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case report ď&#x192;&#x153;

A bicornuate uterus with hyperintense fluid collection in cervix and vagina confirming the hematocolpos (Fig. 2).

Cystoscopy showed a hypospadiac meatus with short urethra. The trigone was severely distorted and both ureteric orifices were displaced laterally due to the pelvic mass. A wide open left ureteric orifice was entering into the diverticulum of bladder. Further examination revealed an atretic distal vagina and a huge globular mass palpable (rectally) above the atretic vaginal segment.

Left ureter 3

1

On 28.3.11 (four months after first attempt) surgical exploration was done. A staged surgical protocol was considered in view of multiple developmental urogenital anomalies.

2 Ureteral diverticulum 4 Bladder Figure 1. MR urogram showing left ureter opening into the bladder diverticulum (arrow 1) and left distal ureteric diverticulum (arrow 2). Also shown are left ureter (arrow 3) and bladder (arrow 4).

A U-shaped incision was made between the perineum and hypospadiac meatus and sharp dissection was required through the hard fibrotic tissue for a distance of 5 cm from the fourchette to gain access to the hematocolpos (huge globular mass with thick fibrotic wall). Reaching the hematocolpos through atretic vagina (fibrotic) without injuring the rectum was challenging especially following an unsuccessful past attempt. Per rectal finger guidance facilitated the dissection.

The close proximity of the bladder diverticulum with insertion of left ureter into it forewarned about the possibility of inadvertent injury to bladder or lower ureter during the intervention. To safeguard the left ureter, a preoperative retrograde ureteric stenting was attempted which could not be accomplished due to extensive anatomical distortion caused by the mass.

MR urogram 3

Guidance with Foleyâ&#x20AC;&#x2122;s catheter enabled dissection without injuring urinary tract. The hematocolpos was drained by incising its thick fibrotic wall and about 300 ml of altered blood was drained.

1

Postoperatively, the patient was relieved of abdominal pain and resumed her first menstruation 45 days after the surgery. Re-examination during menstruation established the patency of vagina. Postoperative micturating cystogram revealed no VUR on left side.

Discussion

2 Urethra 4 Figure 1. MR urogram showing large hematocolpos (arrow 1), bladder diverticulum (arrow 2). Also shown are right unascended kidney (arrow 3) and urethra (arrow 4).

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Obstructive lesions leading to hematocolpos require prompt action to relieve pain, retrograde menstruation and pressure effect on adjacent viscera. Re-stenosis with recurrent mass and pain is a frequent sequel following any vaginal reconstructive surgery which may make future attempts more difficult. During the primary surgical intervention emphasis should be laid

case report on achieving persistent vaginal patency, else recurrent hematocolpos and its associated symptoms would demand repeated surgical interventions. Considering the past surgical failure, an extensive mobilization of proximal vagina was carried out, which facilitated tension-free pull-through of proximal vagina through the space created by the lengthy dissection and approximation of its edges to fourchette to form the introitus. Progressive hematocolpos in unobstructed upper vagina resulted in the chronic stretching, distension and elongation of upper vagina and provided adequate length that further enabled the approximation of its edges.

junction due to bladder diverticula. The vaginal obstruction and hematocolpos is likely to aggravate the distortion and displacement of the lower urinary tract which may be reversible.

Hematocolpos is a rare cause of external mass compression on the lower urinary tract causing acute urinary retention most likely due to distal vaginal occlusions. However, a long atretic lower vagina even with massive collection only in upper vagina may not feature with urinary retention as it may not compress the outflow tract.

Usually, surgical management of combined multiple developmental anomalies may appear to be complex with prospect of multiple surgical corrections. At times, drainage and restoration of continuity and ensuring continued vaginal patency may be adequate to cure the patient. However, patient must be well-counseled for sequel like re-stenosis leading to amenorrhea, pelvic mass and need for further reconstructive surgical interventions.

Coexisting bicornuate uterus (mullerian duct anomaly) categorizes her as Class III of the American Fertility Society classification.

The management dilemma in the patient was to combine vesical divertculectomy and ureteric re-implantation of the left ureter (due to significant VUR) in a single sitting during the drainage of the hematocolpos versus a staged approach. VUR in this case may be congenital or secondary to distortion of the vesicoureteral

VUR could be managed conservatively initially due to the absence of urinary tract infections. Diverticulectomy was not considered as the voiding function was not compromised due to diverticulae. Considering the benefits over risks, staged management strategy was adopted. Persistence of reflux or infection will warrant the re-implantation of ureter in future and at the time of re-implantation ureteral and bladder diverticulum will be surgically excised even if it remains asymptomatic.

References 1.

Yu TJ, Lin MC. Acute urinary retention in two patients with imperforate hymen. Scand J Urol Nephrol 1993;27(4):543-4.

2.

Rock JA, Breech LL. Surgery for anomalies of the mullerian ducts. In: Lindeâ&#x20AC;&#x2122;s Operative Gynecology. 10th edition, Lippincott: Philadelphia 2008:p.539-84.

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legal question

Our State IMA has Submitted a Memorandum to the Government Requesting Action Against the Menace of Stray Dogs. What Else can We Do? MC Gupta

1. Your concern is genuine.

1. According to a recent news report dated 11-2-2012, “Ferocious dogs feeding on carcasses at the village dump yard attacked 9-year-old Mandeep Kaur who was bitten to death. More than six children have been attacked and injured by stray dogs in the past one year alone. http://www.tribuneindia. com/2012/20120211/main7.htm 2. According to WHO >35,000 people die of rabies in India every year accounting for about 81% of global deaths. In addition, there are probably as many unreported deaths.

3. Even otherwise, about 3.5 million dog bites are registered every year in India. Probably double this number remains unreported.

The annual antirabies vaccine sale proceeds to multinational companies consequential to dog bite in India amount to more than Rs. 100 crore.

2. Law must be respected. However, overzealous interpretation and application of law against the interests of those for whom the law is meant (the society) must be resisted and opposed.

3. Those so called ‘dog lovers’ who object to killing of dogs in the name of prevention of cruelty need to be reminded of section 11 of sections 11 (3) (b) and 11 (3) (c) of The Prevention of Cruelty to Animals Act, 1960, given below:

“11. Treating animals cruelly:

(1) ……

(2)……

(3) Nothing in this section shall apply to (a) …… (b) the destruction of stray dogs in lethal chambers 20 (by such other methods as may be prescribed) or Advocate and Medicolegal Consultant, New Delhi

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(c) the extermination or destruction of any animal under the authority of any law for the time being in force;”

4. It is clear that the destruction of stray dogs in lethal chambers or by such other methods as may be prescribed or the extermination or destruction of any animal under the authority of any law for the time being in force is perfectly legal.

5. The above does not necessarily mean that stray dogs must be destroyed in India. They can be destroyed in another country as well. Dog meat is a delicacy in China and Korea. An arrangement, even commercially viable, can be made between India and other countries for export of dogs or dog meat. There is no reason why beef, frog-legs, pork, chicken, etc. can be exported but not dog meat. If butcheries in India can butcher cows and pigs and goat and sheep and buffaloes and chicken, etc., there is no reason why they cannot butcher dogs as well. Or, a Chinese or Korean company can be allowed to establish its own dog butchery in India for 100% export. The money earned from such export can be used for treatment of dog bite cases and paying compensation to them.

6. The IMA should get an exhaustive report on dog bite and dog menace by a committee of experts. This report should then be submitted to the government and should also be published in JIMA. 7. The IMA should then engage legal expertise to prepare a draft representation on the basis of data from relevant sources, including the above mentioned report, and such representation should be officially submitted to the government with a request that necessary action (as requested) may be taken within three months. If no action is taken by the government, the next step would be filing of a PIL by the IMA. 8. It is positive actions like this that will earn name and reputation for the IMA rather than its internal fights or public felicitations.

photo quiz

Yellowish Papules on a Middle-aged Man

A

33-year-old man presented with a skin eruption that had appeared three months earlier.

Examination revealed yellowish papules over the elbows, buttocks, knees, flank, and palmar creases (see accompanying figure). The lesions were 3 to 7 mm and firm to palpation. The patient had no significant medical history.

Question Based on the patientâ&#x20AC;&#x2122;s history and physical examination, which one of the following is the most likely diagnosis?

A. Cellulitis.

B. Eruptive xanthoma.

C. Psoriasis.

D. Smallpox.

E. Varicella.

SEE THE NEXT PAGE FOR DISCUSSION...

Source: Adapted from Am Fam Physician. 2011;83(1):73-74.

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photo quiz Discussion

Summary Table

The answer is B: Eruptive xanthoma.

Condition

Characteristics

Xanthomas are localized lipid deposits in the skin, tendons, and subcutaneous tissue associated with a lipid abnormality. They are clinically classified as eruptive, planar, tuberous, or tendinous. Eruptive xanthomas are the most common type and appear as crops of discrete yellowish papules that may have erythematous bases. They often appear in areas subject to pressure or trauma, such as the buttocks, extensor surfaces, and flexural creases.1,2

Cellulitis

Bacterial infection; rash includes pustules and is red, warm to the touch, and can be tender

Psoriasis

Erythematous, scaly plaques, usually on the elbows and knees

Eruptive xanthomas are associated with hypertriglyceridemia and chylomicronemia due to a genetic disorder (primary hyperlipoproteinemia), or an underlying disease process (secondary hyperlipoproteinemia), such as diabetes mellitus, hypothyroidism, nephrotic syndrome, pancreatitis, or retinoid or estrogen therapy.3,4 Although eruptive xanthomas are usually associated with hyperlipoproteinemia, they can occur in normolipemic patients with local trauma.5-8 The condition may be associated with ophthalmologic and gastrointestinal findings, such as lipemia retinalis (salmon-colored retina with creamy white retinal vessels), abdominal pain, and hepatosplenomegaly.

Smallpox

Vesicles or pustules similar to eruptive xanthomas, but all in the same stage of development; small red spots on the mucous membranes (enanthem) are also present

Varicella

Vesicles on an erythematous base (“dew drop on a rose petal”); viral prodrome; rash develops over one week

Eruptive xanthoma Crops of discrete yellowish papules that may have erythematous bases; often appear in areas subject to pressure or trauma, such as the buttocks, extensor surfaces, and flexural creases

Varicella usually causes vesicles on an erythematous base, which is the classic “dew drop on a rose petal” appearance. Patients have a viral prodrome and develop the rash over one week.

Diagnosis of eruptive xanthoma includes measuring fasting blood glucose and lipid levels, including triglycerides, cholesterol, low-density lipoprotein, verylow-density lipoprotein, and high-density lipoprotein.

The patient’s biopsy result demonstrated a dermal infiltrate of foamy macrophages, with lymphocytes, and neutrophils, which is suggestive of eruptive xanthoma.

Fasting cholesterol was greater than 1,000 mg per dL (25.90 mmol per L), and triglycerides were greater than 3,500 mg per dL (39.55 mmol per L). Treatment involves dietary restrictions and medications to control the hyperlipidemia.

REFERENCES

Cellulitis is a bacterial infection. Fever is uncommon, but may be present. The rash appears as pustules and is red, warm to the touch, and can be tender to palpation.

Although psoriasis can occur over the extensor surfaces, it usually appears as erythematous, scaly plaques.

Psoriasis is most common on the elbows and knees, but can also occur on the palms, soles, scalp, and back.

Smallpox may be similar to xanthomas in size and shape, but are vesicular and in the same stage of development. Smallpox lead to small red spots on the mucous membranes (enanthem).

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1.

Russo GG. Hyperlipidemias [published correction appears in Clin Dermatol. 1996;14(6):685]. Clin Dermatol.

1996;14(4):367-374.

2.

Parker F, Bagdade JD, Odland JF, Bierman EL. Evidence for the chylomicron origin of lipids accumulating in diabetic eruptive xanthoma: a correlative lipid biochemical, histochemical, and electron microscopic study. J Clin Invest. 1970;49(12):2172-2187.

3.

Cruz PD Jr, East C, Bergstresser PR. Dermal, subcutaneous, and tendon xanthomas: diagnostic markers for specific lipoprotein disorders. J Am Acad Dermatol. 1988;19 (1 pt 1):95-111.

4.

Dicken CH, Connolly SM. Eruptive xanthomas associated with isotretinoin (13-cis-retinoic acid). Arch Dermatol.

1980;116(8):951-952.

5.

Miwa N, Kanzaki T. The Koebner phenomenon in eruptive xanthoma. J Dermatol. 1992;19(1):48-50.

6.

Roederer G, Xhignesse M, Davignon J. Eruptive and tuberoeruptive xanthomas of the skin arising on sites of prior injury. Two case reports [published correction appears in JAMA. 1989;261(9):1280]. JAMA. 1988;260(9):1282-1283.

7.

Goldstein GD. The Koebner response with eruptive xanthomas. J Am Acad Dermatol. 1984;10(6):1064-1065.

8.

Parker F. Normocholesterolemic xanthomasis. Arch Dermatol. 1986;122(11):1253-1257.

around the globe

News and Views Government to provide free generic drugs at public hospitals: Ghulam Nabi Azad New Delhi: Admitting that the healthcare system was ‘overwhelmed’ by inequities, Health Minister Ghulam Nabi Azad said Government would provide universal healthcare in the 12th Plan and take steps to ensure free generic drugs at all public health facilities so as to reduce out of pocket expenditure of patients. “In the 12th Plan, in our attempt to provide universal health care, steps would be taken to provide free generic drugs at all public health facilities for reducing financial burden on the patients,” said Azad while addressing a National Consultation on “Social determinants of Health”.

About 70% of out of pocket expenditure on healthcare in India is on drugs. (Source: The Economic Times, 27 Feb., 2012) You need not have chest pain for heart attack Mumbai: For long, a sudden chest pain was considered the main symptom of a heart attack, but a comprehensive study conducted by a Florida-based chest pain centre has found that many patients taken to hospitals for heart attacks never had chest pain. Consequently, they were less likely to be treated aggressively, according to a report on the NYT website.

The study done at the chest pain center of Lakeland Regional Medical Center, Florida, showed that of 1.1 million people, 42% of women admitted to hospitals for heart attack never experienced chest pain, while the figure was 30.7% in the case of men.

The study, of which the Center’s director John G Canto is an author, was recently published in the Journal of the American Medical Association. According to leading cardiologist Ashwin Mehta, well over 20-30% of people admitted to hospitals in India have had painless heart attack. “My observation is that people suffering from hypertension and diabetes may have a painless heart attack.

In such cases, the signals of discomfort are vague and weak. As a result, they get less opportunity for treatment,” Mehta said. (Source: TOI, Mar. 6, 2012)

Bariatric risks rise with CKD, but still low Complications after bariatric surgery occurred significantly more often in patients with chronic kidney disease (CKD), but rates remained low, authors of a cohort study concluded. The complication rate increased with CKD severity, from 4.6% in patients with normal kidney function or stage 1 CKD to 9.9% for patients with stage 5 CKD. (Source: Medpage Today) Cabinet OKs tougher penalties under Motor Vehicle Act New Delhi: The Union Cabinet approved the proposed changes in the Motor Vehicle Act. This paves way for passing the legislation in Parliament to increase penalty on traffic rule violators across the country. The new bill which will be introduced in the Rajya Sabha during the Budget session has provision to slap ` 500 fine for not wearing seat belt and helmet or for jumping a red light for the first time. The bill introduces fines for using mobile phone while driving. The fines will multiply in case the same offender violates the traffic rules subsequently. As per the new provision drunk driving would be dealt with high penality and even jail term.

Drunk driving will be graded according to alcohol levels in the blood with a punishment that can go up to a 2-year jail term and ` 5,000 fine or both. Repeat traffic offences will fetch stiff fines with jumping red lights or not using seat belts and helmets attracting fine between ` 500-1,500.

The first offence of using cellphone will mean ` 500 fine and subsequent infringements can set the offender back by ` 5,000 in penalties. To discourage the use of cellphones, which have emerged as a key reason for road accidents all over the world, the new bill has proposed stiff fines. (Source: TOI, March 1, 2012) Screening Pap smears tied to higher cure rate Women with screen-detected cervical cancer had a 26% absolute increase in cure rate as compared with women who were symptomatic at diagnosis, results of a Swedish study showed. (Source: Medpage Today)

Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

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practice guidelines

Updated Guidelines on Management of Atrial Fibrillation from the ACCF/AHA/HRS

T

he American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), and the Heart Rhythm Society (HRS) have released updated guidelines for the management of atrial fibrillation. Since the previous guidelines were issued in 2006, new data have become available on strict versus lenient heart rate control, the combined use of antiplatelet and anticoagulation therapy, and the use of dronedarone. Table 1 summarizes the new and modified recommendations. Recommendations on the thrombotic agent dabigatran and the Watchman device for atrial appendage closure were not included in this update because neither was approved for clinical use by the U.S. Food and Drug Administration at the time of organizational approval of these guidelines.

Rate Control Parameters for optimal rate control in patients with atrial fibrillation are controversial, and there is no standard method for assessing heart rate control to guide treatment. Generally accepted criteria for rate control include a ventricular rate between 60 and 80 beats per minute at rest and between 90 and 115 beats per minute during moderate exercise. The definition of adequate rate control has been based primarily on short-term hemodynamic benefits. This definition has not been well studied with respect to quality of life, symptoms, development of cardiomyopathy, and ventricular response to atrial fibrillation. Data have not demonstrated clinically relevant differences in outcomes between strict rate control (less than 80 beats per minute at rest and less than 110 beats per minute during moderate exercise) and lenient rate control (less than 110 beats per minute at rest). Lenient rate control requires fewer outpatient visits and examinations, and is generally more convenient for patients. Because it has not been proven inferior to strict rate control, lenient rate control is a reasonable strategy in patients with permanent atrial fibrillation. Data also have shown no benefit of rhythm control compared with rate control in patients with atrial fibrillation and systolic heart failure.

Source: Adapted from Am Fam Physician. 2011;84(11):1298-1306.

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Combination Anticoagulant and Antiplatelet Therapy Studies have shown that oral anticoagulation therapy with warfarin is superior to the combination of aspirin and the antiplatelet agent clopidogrel for preventing vascular events in patients with atrial fibrillation.

Treatment with clopidogrel and aspirin was associated with a risk of bleeding similar to that of treatment with warfarin. In patients with atrial fibrillation who are not suitable candidates for warfarin therapy, treatment with clopidogrel and aspirin was shown to reduce the risk of major vascular events, especially stroke, compared with patients taking aspirin plus placebo. However, the combination of aspirin and clopidogrel also increased the risk of major hemorrhage. Use of clopidogrel and aspirin plus warfarin (i.e., triple therapy) has been proposed for treating and preventing complications of two or more coexisting conditions (e.g., atrial fibrillation, mechanical valve prosthesis, presence of drug-eluting stent). This combination is associated with an increased risk of bleeding complications, and no randomized trials of this strategy have been reported.

Dronedarone Therapy Dronedarone, which is similar to amiodarone, has been shown to reduce hospitalization for cardiovascular problems in patients with paroxysmal or persistent atrial fibrillation or atrial flutter and risk factors for thromboembolism. The recommended oral dosage of dronedarone is 400 mg twice per day with meals.

Major adverse effects include bradycardia and QT prolongation. Dronedarone also has been shown to increase mortality in patients with a recent episode of decompensated heart failure and depressed left ventricular function.

Sinus Rhythm Maintenance Catheter ablation has been shown to provide one year or more of freedom from recurrent atrial fibrillation; however, additional studies are needed to determine long-term effectiveness of sinus rhythm maintenance.

Ablation has been studied in patients with symptomatic paroxysmal atrial fibrillation that has not responded to treatment with one or more antiarrhythmic drugs, with normal or mildly dilated atria, normal or mildly reduced ventricular function, and absence of severe pulmonary disease.

practice guidelines Table 1. 2011 Focused Update Recommendations on Managing Atrial Fibrillation Recommendation

Comments

Rate control Treatment to achieve strict control of heart rate (less than 80 beats per minute at rest or less New recommendation than 110 beats per minute during a six-minute walk) is not beneficial compared with achieving Class III (no benefit) a resting heart rate of less than 110 beats per minute in patients with persistent atrial Level of evidence: B fibrillation who have stable ventricular function (left ventricular ejection fraction greater than 40 percent) and no or acceptable symptoms related to the arrhythmia, although uncontrolled tachycardia may be associated over time with a reversible decline in ventricular performance.

Combination anticoagulant and antiplatelet therapy The addition of clopidogrel to aspirin therapy to reduce the risk of major vascular events, including stroke, may be considered in patients with atrial fibrillation in whom oral anticoagulation with warfarin is unsuitable because of patient preference or the physicianâ&#x20AC;&#x2122;s assessment of the patientâ&#x20AC;&#x2122;s ability to safely sustain anticoagulation therapy.

New recommendation Class IIb Level of evidence: B

Dronedarone therapy Use of dronedarone is reasonable to decrease the need for hospitalization for cardiovascular events in patients with paroxysmal atrial fibrillation or after conversion of persistent atrial fibrillation. Dronedarone can be initiated during outpatient therapy.

New recommendation

Dronedarone should not be administered to patients with class IV heart failure or patients who have had an episode of decompensated heart failure in the past four weeks, especially if they have depressed left ventricular function (left ventricular ejection fraction of 35 percent or less).

New recommendation

Class IIa Level of evidence: B Class III (harm) Level of evidence: B

Sinus rhythm maintenance Catheter ablation performed in experienced centers is useful in maintaining sinus rhythm in select patients with significantly symptomatic, paroxysmal atrial fibrillation who have been unsuccessfully treated with an antiarrhythmic drug and have normal or mildly dilated left atria, normal or mildly reduced left ventricular function, and no severe pulmonary disease.

Modified recommendation (class of recommendation changed from IIa to I, wording revised, and level of evidence changed from C to A) Class I Level of evidence: A

In patients with atrial fibrillation without structural or coronary heart disease, initiation of propafenone or flecainide can be beneficial on an outpatient basis in those with paroxysmal atrial fibrillation who are in sinus rhythm at the time of drug initiation.

Modified recommendation (wording clarified) Class IIa Level of evidence: B

Catheter ablation is reasonable to treat symptomatic persistent atrial fibrillation.

New recommendation Class IIa Level of evidence: A

Catheter ablation may be reasonable to treat symptomatic paroxysmal atrial fibrillation in patients with significant left atrial dilatation or significant left ventricular dysfunction.

New recommendation Class IIb Level of evidence: A

Classes: I = procedure/treatment should be performed/administered; IIa = it is reasonable to perform/administer treatment; IIb = procedure/treatment may be considered; III (no benefit) = treatment should not be performed/administered or is not useful; III (harm) = treatment is harmful or potentially harmful and should not be performed/administered.

Levels of evidence: A = multiple populations evaluated (data from multiple randomized clinical trials or meta-analyses); B = limited populations evaluated (data from a single randomized clinical trial or nonrandomized studies); C = very limited populations evaluated (consensus opinion of experts, case studies, or standard of care).

Adapted from Wann LS, Curtis AB, January CT, et al.; ACCF/AHA Task Force. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline) [published correction appears in Circulation. 2011;124(5):e173]. Circulation. 2011;123(1):108-110, 112-113.

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lighter reading

Fill me with the fruits of your Spirit, Lord.

Fill me with love, so that I seek to understand and appreciate the rich variety and diversity of life that surrounds me.

quote

Fill me, Lord

Fill me with joy, so that I celebrate your presence in each and every moment I am on this earth.

Fill me with patience, so that I stop rushing long enough to witness your miraculous work taking place all around me (and within me!)

Fill me with kindness, so that I take the extra time to help the one in need, even when it isn’t convenient for me.

Fill me with faithfulness, so that I place my mind, heart and all that I do in the service of your Gospel.

Fill me with gentleness, so that others know that I believe in a God who loves and cares for all people.

Fill me with self-control, so that I act not on my impulses and urges, but rather on my beliefs and values, which are rooted in you. Fill me with these fruits of your spirit, Lord!

laugh a while

Fill me with peace, so that I know how to ease those angry and sometimes violent urges that well up inside of me.

“It must be borne in mind that the tragedy of life does not lie in not reaching your goal. The tragedy of life lies in having no goal to reach.”

—Benjamin E. Mays

Vote for the Devil A candidate for city council was doing some door-to-door campaigning, and things were going pretty well, he thought, till he came to the house of a grouchy-looking fellow. After the candidate’s little speech, the fellow said, “Vote for you? Why I’d rather vote for the Devil!” “I understand,” said the candidate, “but in case your friend is not running, may I count on your support?”

—Dr GM Singh

Calcitonin

Lab Update

An Inspirational Story

Lighter Side of Medicine

To help diagnose and monitor C-cell hyperplasia and medullary thyroid cancer; to screen those at risk for multiple endocrine neoplasia type 2 (MEN 2).

—Dr Arpan Gandhi and Dr Navin Dang

— Dr GM Singh

Dr. Good and Dr. Bad

Make Sure

During Medical Practice

Situation: A patient with sepsis developed thrombocytopenia.

A 14-day-old neonate presented with pneumonia. On history, it was found that mother had complains of dysuria, mucopurulent cervical discharge, episodes of sometimes cervical bleeding and lower abdominal.

Oh my God! You should have treated the mother with azithromycin.

Dr KK Aggarwal

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It is due to sepsis

Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

©IJCP Academy

©IJCP Academy

Make sure to remember that pneumonia in neonates can be prevented by treating mother, having Chlamydia trachomatis infection, with azithromycin.

It is due to drugs

Lesson: More than 50% of patients with sepsis show thrombocytopenia in their peripheral smear.

Dr KK Aggarwal

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.

–

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

–

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.

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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

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.

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Do not use clips/staples on photographs and artwork.

–

Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as “Fig.”.

Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected

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.

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

Indian Journal of Clinical Practice, Vol. 22, No. 10, March 2012

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 KK Aggarwal

Group Editor-in-Chief Indian Journal of Clinical Practice E-219, Greater Kailash, Part-1 New Delhi - 110 048. Tel: 40587513 E-mail: editorial@ijcp.com Website: www.ijcpgroup.com

R.N.I. No. 50798/90 Date of Publication 13th of Same Month Date of Posting 13-14 Same Month

DL (S)-01/3200/2012-2014 Posted in N.D. PSO New Delhi