Indian journal of clinical practice april 2014 by IJCP

Indexed with IndMED

ISSN 0971-0876

www.ijcpgroup.com

Volume 24, Number 11

April 2014, Pages 1001-1100

Peer Reviewed Journal

zz American Family Physician zz Cardiology zz Community Medicine zz ENT zz Hematology zz Neurology zz Obstetrics and Gynecology zz Ophthalmology

an i c i ys ians

zz Orthopedics

Phly Physic y l mi ami

zz Pediatrics

Fademy of F n ica Aca

zz Respiratory Diseases

er merican m A eA

zz Emedinews Inspiration

ingurnal of th t a or d Jo

rp-reviewe o c In eer AP

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

Volume 24, Number 11, April 2014 from the desk of THE group editor-in-chief

1005 Replacing IV Nitroglycerin in Times of Shortage

Dr Deepak Chopra Chief Editorial Advisor Padma Shri, Dr BC Roy National & DST National Science Communication Awardee

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

American Family Physician

1006 Recommendations for Preconception Counseling and Care

Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

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

Narges Farahi, Adam Zolotor

1013 Practice Guidelines 1015 Photo Quiz CARDIOLOGY

1017 Double-Chambered Right Ventricle with Transient 2:1 Atrioventricular Block: A Rare Presentation

Monika Maheshwari, SK Kaushik

Community Medicine

1019 Extended-spectrum Î˛-lactamase and AmpC Î˛-lactamase

Production among Gram-negative Bacilli Isolates Obtained from Urinary Tract Infections and Wound Infections

Pottahil Shinu, Rajesh Bareja, Manoj Goyal, Varsha A Singh, Priya Mehrishi, Monika Bansal, Vinod Kumar Narang, Prem Singh Grover, Virendra Singh, Shailesh Yadav, Ahmed Nabeel

ENT

1027 Laryngeal Myxoma: Emergency Management

BR Singh, Arti Pandey, Ankit M Thackral

1034 Profound Sensorineural Hearing Loss with Overlay of Middle Ear Pathology-Diagnostic Implications

Indranil Chatterjee, Neha Taneja, AK Sinha, Suman Kumar

Hematology

1038 Unusual Presentation of Angioimmunoblastic T-cell Lymphoma as a Solitary Lymph Node

N Ashalatha, BN Kumarguru, BS Dayananda, AH Nagarajappa

Neurology

1043 A Rare Case of Diencephalic Seizures Secondary to Hemorrhagic Stroke

Anand Gopal Bhatnagar Editorial Anchor Advisory Bodies Heart Care Foundation of India

KK Aggarwal

Muhammed Zohaib Ghatala, Swamikannu Murugan, Shriraam Mahadevan, Soundarajan Booma

Obstetrics and Gynecology

1046 Cervical Stenosis: A Rare Complication of Cesarean Section

Anita Kharat, Suman Kumari

1048 Medical Management of Ectopic Pregnancy with Methotrexate

Sumant R Shah, Sandip Sonara, Bhavesh Patel, Nidhi Patel

1053 Pregnancy Outcome in Women with Dengue Infection in Northern India

Prabhat Agrawal, Ruchika Garg, Soumya Srivastava, Urvashi Verma, Rekha Rani

Obstetrics and Gynecology 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

1057 Induction of Labor: A Review

Kavita Goel, Jaya K Gedam, Disha A Rajput, Minal V Bhalerao

Ophthalmology

1065 Adult Unilateral Chorioretinal Atrophy Secondary to Acquired Rubella

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

Meenakshi Patil, Neelam Redkar, Maruti Karale, Manish Dodmani

Orthopedics

1068 Evaluation of Results of Different Treatment Modalities in

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.

Management of Diaphyseal Fractures of Humerus

Vipin Sharma, Bhanu Awasthi, SM Mehta, RS Yadav, Sudhir Babhulkar

PEDIATRICS

1075 High-Frequency Ventilation: Excellent Rescue

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.

Sudivya Sharma, Prashast Jain

1077 Congenital Juvenile Xanthogranuloma of Foot, a Nodular Lesion: An Unusual Case in 2-month-old Infant

Ram Avtar, Onkar Kaur, Anand K Verma, Raj Kumar Chandoke

1081 Bronchoscopy in Children

Sudivya Sharma

RESPIRATORY DISEASES

1085 Chronic Dry Cough in Allergic Respiratory Diseases: Diagnostic and Management Approach

Pralhad P. Prabhudesai

AROUND THE GLOBE

1092 News and Views eMEDINEWS INSPIRATION

1094 Determination and Persistence

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.

eMEDI QUIZ

1095 Quiz Time LIGHTER READING

1096 Lighter Side of Medicine

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Replacing IV Nitroglycerin in Times of Shortage Intravenovs (IV) nitroglycerin is needed in myocardial infarction, hypertensive crisis and acute decompensated heart failure. In shortage following are the alternatives. ÂÂ NTG paste: In acute coronary syndrome, use nitro paste or sublingual tablets. ÂÂ NTG spray: One can use 400 µg of nitro spray and titrates one spray every 4 minutes, which results in a 100 µg

per min dose.

ÂÂ S/L NTG: Give multiple sublingual tablets of nitroglycerin instead of using nitro paste. With one 100 µg

tablet, absorption is roughly 70-80 µg/min. If blood pressure holds after about 5 minutes one can double the dose. Because some patients' blood pressure drops with nitroglycerin, start with one sublingual nitroglycerin tablet, and then escalate to bilevel positive air pressure (BiPAP) or continuous airway pressure (CPAP) with nitroglycerin in the most severely ill patients. Do X-rays the chest to confirm fluid overload before starting furosemide because symptoms are sometimes confused with chronic obstructive pulmonary disease (COPD) exacerbation, pneumonia or lung cancer, and giving furosemide can make them much worse or increase mortality. If the patient is wheezing, use a bronchodilator.

ÂÂ Drip angiotensin-converting enzyme (ACE) inhibitors: In acute heart failure one can start with enalaprilat for

preload reduction and nicardipine for afterload reduction. One can start with low-dose enalaprilat 1.25 mg IV. The exception would be hypotensive patients.

ÂÂ Try nitroprusside: It reduces both preload and afterload. ÂÂ Try nicardipine: For acute decompensated heart failure start 1 µg/kg/min of nicardipine; is this the optimal

dose for patients.

ÂÂ Do Not use: Nesiritide; loop diuretics as first line as furosemide makes patients worse in the first 10-20

minutes of management, which is the critical time in APE resuscitation.

Suggested Protocol 1. Sublingual nitroglycerin, 1-2 tablets every 5 mins × 3 -- reassess BP 2. If well-controlled, then transition to NTP or Isordil p.o. (Nitro paste or longer acting NTG) 3. If not well-controlled (>160/100) then consider IV enalapril -- 0.625-1.25 mg IV bolus or IV hydralazine 5-10 mg IV bolus or IV nitroprusside.

Indian Journal of Clinical Practice, Vol. 24, No. 11, April 2014

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American Family Physician

Recommendations for Preconception Counseling and Care NARGES FARAHI, ADAM ZOLOTOR

Abstract Given that nearly one-half of pregnancies are unintended, preconception care should be considered an integral part of primary care for women of reproductive age. Common issues in preconception care include family planning, achieving a healthy body weight, screening and treatment for infectious diseases, updating appropriate immunizations, and reviewing medications for teratogenic effects. Women who want to become pregnant should take folic acid supplements to reduce the risk of neural tube defects. Control of chronic diseases is essential for optimizing pregnancy outcomes. Family physicians should work with patients to control conditions such as diabetes mellitus, hypertension, and seizure disorders while simultaneously offering family planning services to avoid unintended pregnancies. Bariatric surgery is increasingly common and may improve fertility in many women with previous insulin resistance. Family physicians should counsel women undergoing bariatric surgery to prevent pregnancy during rapid weight loss and provide assistance with contraception. In addition, patients have special nutritional requirements after bariatric surgery.

Keywords: Pregnancies, preconception care, chronic diseases, pregnancy outcomes, contraception

he Centers for Disease Control and Prevention defines preconception care as a set of interventions aimed at identifying and modifying biomedical, behavioral, and social risks to a woman’s health or pregnancy outcome through prevention and management. The goal is to ensure that the woman is as healthy as possible before conception to promote her health and the health of her future children. Preconception care is integral to primary care for women in their reproductive years. It is not a single medical visit, but rather should be incorporated into every medical decision and treatment recommendation for these women.1

Nearly one-half of all pregnancies in the United States are unintended. Family planning is an essential component of preconception care and allows optimal opportunity for health promotion and preventive care. Pri mary care clinicians should consider asking all patients of reproductive age about intention to become pregnant and providing contraceptive counseling tailored to patients’ intentions.1,2 The Centers for Disease Control and Pre vention’s U.S. medical eligibility criteria for contraceptive use can assist clinicians in counseling patients about

NARGES FARAHI, MD, is an assistant professor in the Department of Family Medicine at the University of North Carolina School of Medicine in Chapel Hill. ADAM ZOLOTOR, MD, DrPH, is an associate professor in the Department of Family Medicine at the University of North Carolina School of Medicine. Source: Adapted from Am Fam Physician. 2013;88(8):499-506.

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contraceptive choices, and provides evidence-based guid ance on the safety of contraceptive methods for women with specific characteristics and medical conditions.3 All women and men should be encouraged to develop a reproductive life plan, including individual goals about childbearing and a plan for achieving them.1 Reproductive life planning tools are available for patients and clinicians at http://www.cdc.gov/ preconception/reproductiveplan.html. For primary care physicians, caring for a woman of reproductive age should include identifying health risks to her and her future children, and implementing interventions to reduce these risks. General issues in preconception care are summarized in Table 1.4-9 Screening and treatment for infectious dis eases, and providing appropriate immuni zations are also important in these patients (Table 2).1,10-20 Nutritional Considerations

Folic Acid Folic acid supplementation of 400 mcg daily started before pregnancy and continued until six to 12 weeks postconception reduces the rate of neural tube defects by nearly 75%.1,21,22 One study showed that women receiving preconception counseling from their pri mary care physicians are five times more likely to take folic acid before conception.23 Women taking folic acid antagonists or who have carried a fetus affected by a neural tube defect or other birth defects linked

American Family Physician Table 1. General Issues in Preconception Care Issue

Recommendations

Environmental exposures

Assess for workplace exposures to toxicants; industries that are known to use toxic chemicals include clinical and laboratory health care, dry cleaning, printing, manufacturing, and agriculture Assess for household exposures to potentially harmful agents such as heavy metals, solvents, and pesticides Counsel patients about avoiding mercury exposure by not consuming large fish (e.g., shark, swordfish, tilefish, king mackerel) and limiting other fish intake4

Family genetic history

Screen for personal or family history of congenital anomalies or genetic disorders Refer couples for genetic counseling when risk factors are identified, and provide carrier testing when appropriate to determine risk to future pregnancy5

Medications

Assess for the use of teratogenic medications For women with chronic diseases, switch to safer medications when possible, and use the fewest medications at the lowest dosages needed to control the disease6

Psychiatric illness

Screen for depression and anxiety disorders Counsel patients about the risks of untreated depression during pregnancy, as well as the risks of treatment7

Psychosocial factors

Screen for intimate partner violence Evaluate the patient’s safety, and provide referral to appropriate resources8

Substance use

Screen for alcohol use, and provide referral for women with alcohol dependence Screen for tobacco use, and provide smoking cessation treatment when needed; counsel patients about the effect of smoking on pregnancies and child health Provide brief behavioral interventions to reduce tobacco, alcohol, and drug use9

Information from references 4 through 9.

with folic acid deficiency (e.g., oral facial cleft, struc tural heart disease, limb defect, urinary tract anomaly, hydrocephalus) should take 4 to 5 mg of folic acid daily starting three months before conception and continuing until 12 weeks postconception.24,25 Women with certain health risks (e.g., epilepsy, insulin-dependent diabetes mellitus, obesity with a body mass index [BMI] greater than 35 kg per m2, family history of a neural tube defect) should also take this higher dosage.24

Overweight In the United States, 26% of women 20 to 39 years of age are overweight (BMI of 25 to 29.9 kg per m2), and 29% are obese (BMI of 30 kg per m2 or higher).26 Women who are overweight or obese are at risk of diabetes, gestational diabetes, and hypertension. These conditions are associated with adverse pregnancy outcomes, including macroso mia, shoulder dystocia, operative delivery, congenital anomalies, intrauterine growth restriction, spontaneous abortion, stillbirth, preeclampsia, and eclampsia.27 There are numerous effective interventions for women who are overweight or obese. A systematic review found that out of five commercial diets, Weight Watchers was

the least costly, and women maintained a 3.2% weight loss two years after intervention. The review noted that medically supervised programs are more expensive and have higher rates of attrition, but are associated with greater weight loss (15% to 25%), compared with other types of programs.28 Women who are overweight or obese are more likely to have difficulty with conception because of insulin resis tance and oligomenorrhea. Weight loss and medications can improve these symptoms, as well as fertility.29,30

Bariatric Surgery There were 220,000 bariatric surgeries in 2008; one-half were performed in women of reproductive age.31 Many women undergoing gastric surgery have a history of oligomenorrhea or amenorrhea from insulin resistance, and they should be advised that fertility may return as they lose weight. Women are generally directed to pre vent pregnancy for 12 to 18 months after surgery to sta bilize weight loss and optimize nutrition status,32 but observational studies have shown that the time from surgery to conception does not increase obstetric and neonatal complications.33 Oral contraceptives may be less effective after malabsorptive bariatric surgery.

Indian Journal of Clinical Practice, Vol. 24, No. 11, April 2014

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American Family Physician Table 2. Infectious Disease Screening and Immunizations in Preconception Care Screening/immunization

Recommendations

Infectious disease Chlamydia12

Screen all women younger than 25 years and women who are at risk of infection Treat infected patients

Gonorrhea13

Screen high-risk women Treat infected patients

Herpes simplex virus infection

Counsel about the risk of vertical transmission

Human immunodeficiency virus infection14

Universal screening

Syphilis15

Screen high-risk women

Counsel about the risk of vertical transmission (treatment reduces this risk) Treat infected patients

Tuberculosis

Screen high-risk women Treat women with active and latent disease before pregnancy

Immunization Hepatitis B16

Vaccinate all high-risk women before pregnancy Counsel chronic carriers about prevention of vertical transmission

Influenza17

Vaccinate all women who will be pregnant during influenza season and women at risk of influenzarelated complications

Measles, mumps, rubella18 Screen for immunity Vaccinate all nonimmune women who are not pregnant Counsel patients to avoid pregnancy for three months after vaccination Tetanus, diphtheria, pertussis19

Tetanus vaccination may protect against neonatal tetanus Vaccinate with Tdap during pregnancy (optimal timing is 27 to 36 weeks’ gestation) to reduce the risk of neonatal pertussis

Varicella20

Screen for immunity Vaccinate all nonimmune women who are not pregnant Counsel patients to avoid pregnancy for one month after vaccination

Tdap = Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis. Information from references 1, and 10 through 20.

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There is little evidence-based data to guide precon ception care of women who have had bariatric surgery. These patients are at risk of nutrient deficiencies, including vitamins A, D, E, K, C, B1, B6, B12; folic acid; and iron. It is generally recommended that they take at least two multivitamins per day in addition to extra iron (approximately 65 mg), folic acid (400 mcg), vitamin D (400 to 800 IU), and vitamin B12 (350 mcg). Women should be assessed for common nutrient deficiencies before pregnancy with a complete blood count.31,32

Underweight Low prepregnancy weight (BMI less than 18.5 kg per m2) is associated with preterm birth and low birth weight. Low body weight is also associated with nutrient deficiencies, osteoporosis, amenorrhea, infertility, and arrhythmias. Infants whose mothers had low prepreg nancy body weight are at higher risk of gastroschisis. Women with low BMI should be assessed for eating disorders and counseled about how being underweight can affect their health and pregnancy.1,34 Chronic Medical Conditions Table 3 includes preferred medications for chronic dis eases and those to avoid during pregnancy.1,6,30,35-42

Diabetes Diabetes is the most common serious disease to affect the maternal-fetal dyad. The disease affects nearly 10% of women of reproductive age,43 and about 1% of preg nancies are complicated by pregestational diabetes.37 Pregestational diabetes increases the risk of miscarriage, congenital fetal anomalies, and perinatal death.44 Glucose is teratogenic at high levels, and rates of con genital fetal anomalies are directly related to glycemic control in the first trimester. Good glycemic control during organogenesis reduces rates of congenital malformations.44-46 Preconception A1C levels should approach those considered normal in patients without diabetes; national organizations recommend varying targets of 7% or lower.38,47 Pregnancy is associated with higher rates of hypoglycemia, decreased hypoglycemic aware ness, increased rates of diabetic ketoacidosis, and the progression of diabetic retinopathy and nephropathy.38 Preconception counseling improves pregnancy out comes in women with diabetes and should be part of dia betes care for reproductive-aged women. Preconception care should include educating women about the impact of diabetes on pregnancy outcomes and the impact of

American Family Physician pregnancy on diabetes,38 optimizing glycemic control, screening for vascular complications of diabetes, evalu ating medication use, and encouraging effective family planning.37

Hypertension Chronic hypertension affects 3% of women of repro ductive age.43 Chronic hypertension in pregnancy is associated with higher rates of preterm birth, placental abruption, intrauterine growth restriction, preeclamp sia, and fetal death.48 Women with chronic hypertension are at risk of worsening hypertension and end-organ damage, and 25% of women with hypertension develop superimposed preeclampsia during pregnancy.49

Pregnancy outcome is related to the degree of hyper tension.50 There is no evidence that treating mild to moderate hypertension in pregnancy improves perinatal outcomes.48 Treating severe hypertension (systolic blood pressure of 180 mm Hg or higher, or diastolic blood pressure of 110 mm Hg or higher) improves pregnancy outcomes.51 Caring for women of reproductive age with hyperten sion should include educating them about the risks of hypertension during pregnancy and that their medica tion regimen may need to be changed before conception. Women with long-standing hypertension who are plan ning pregnancy should be assessed for retinopathy, renal disease, and ventricular hypertrophy.37

Table 3. Medication Guidelines for Common Medical Conditions in Women Considering Pregnancy Medical condition

Medication guidelines

Comments

Acne

Isotretinoin should be avoided

Isotretinoin is associated with miscarriage and birth defects1

Asthma

Inhaled corticosteroids and beta agonists are preferred

Use of oral corticosteroids in the first trimester is associated with reduced birth weight, increased risk of oral cleft, and higher rates of preeclampsia35 Inhaled corticosteroids are recommended for preventive treatment and may avoid the need for oral treatment36 When oral corticosteroids are indicated for treatment of severe asthma, the risk of uncontrolled severe asthma to the mother and fetus is greater than the risk of oral corticosteroids37

Diabetes mellitus

ACE inhibitors and ARBs are associated with fetal renal Most oral antidiabetic agents should be discontinued and insulin started; metformin may anomalies and fetal death37,38 be continued in the preconception period30 Adverse effects in animal studies; limited data in humans38 ACE inhibitors, ARBs, and statins should be avoided

Hypertension

ACE inhibitors, ARBs, and atenolol should be avoided

ACE inhibitors and ARBs are associated with fetal renal anomalies and fetal death37,38; adverse effects in animal studies, limited data in humans38 Atenolol is associated with lower birth weight39

Hyperthyroidism

Propylthiouracil is preferred in the first trimester; Possible teratogenicity in the first trimester with methimazole; methimazole is preferred in the second and propylthiouracil-associated hepatotoxicity in subsequent third trimesters trimesters40

Seizure disorder

Many major antiepileptic drugs (e.g., valproate, phenytoin, carbamazepine, phenobarbital) are teratogenic

Rates of congenital anomalies are related to higher doses and polytherapy

Heparin or low-molecular-weight heparin is preferred

Warfarin is teratogenic1,37,42

Thrombophilia

Monotherapy should be used when possible at the lowest effective dosage6,41

Warfarin should be avoided ACE = Angiotensin-converting enzyme; ARB = Angiotensin receptor blocker. Information from references 1, 6, 30, and 35 through 42.

Indian Journal of Clinical Practice, Vol. 24, No. 11, April 2014

1009

American Family Physician Thyroid Disease

Seizure Disorders

Thyroid disease can significantly impact pregnancy out comes. Hypothyroidism affects 2.5% of women of repro ductive age, and even more have subclinical disease.52 Many patients with hypothyroidism are inadequately treated. Hypothyroidism in the first trimester is associ ated with cognitive impairment in children. Hypothy roidism (clinical and subclinical) in pregnant women increases the risk of preterm birth, low birth weight, placental abruption, and fetal death.53,54 Women who are adequately treated before pregnancy and those diagnosed and treated early in pregnancy have no increased risk of perinatal morbidity.55 It is essential to monitor women on thyroid replacement therapy and educate them about its impact on pregnancy. During pregnancy, thyroid replacement dosages typically need to be increased by four to six weeks’ gestation, possibly by 30% or more. Routine screening for subclinical hypo thyroidism is not recommended; however, women with risk factors and symptoms of thyroid diseases should be screened, and subclinical hypothyroidism should be treated.40 Hyperthyroidism can result in significant mater nal and neonatal morbidity, and outcomes correlate with disease control. Guidelines recommend achieving euthyroidism before pregnancy.40

Seizure disorders are the most common neurologic diseases to affect pregnant women, and both the diseases and its treatments can adversely affect pregnancy. Approxi mately one-third of women with a seizure disorder will experience more frequent seizures in pregnancy. Seizure disorders are associated with miscarriage, low birth weight, developmental disabilities, microcephaly, and hemorrhagic disease of the newborn (induced by antiepileptic drugs). Seizure disorders increase the risk of con genital anomalies, whether or not the mother is taking medication.41 Given increased rates of neural tube defects with many antiepileptic drugs, supplementation with 4 mg of folic acid daily should be initiated at least one month before conception and continued in the first trimester.37

Asthma Women with poorly controlled asthma before pregnancy are more likely to experience worsening symptoms during pregnancy.56 Poorly controlled asthma poses risks to the fetus, such as neonatal hypoxia, intrauterine growth restriction, preterm birth, low birth weight, and fetal and neonatal death.57 Preconception care should focus on optimizing asthma control with medications, and identifying and reducing exposure to allergens. Patients should be counseled on smoking cessation and avoidance of secondhand smoke exposure.6

Thrombophilia Women with thrombophilia are more likely to develop venous and arterial clots during pregnancy and are at risk of preeclampsia. Effects on the fetus include pla cental infarction, intrauterine growth restriction, pla cental abruption, recurrent miscarriage, fetal stroke, and fetal death.42 Warfarin, an anticoagulant commonly used in the treatment of thrombophilia, is teratogenic. It is important to educate women with thrombophilia about the risks of pregnancy so that they can make informed decisions about conception. Pre conception care allows women to change to a treatment regimen that is safer for the fetus before pregnancy and to consider genetic testing for inherited thrombophilia.37

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Approach to the Patient A 32-year-old woman with diabetes and hypertension presented for follow-up. She was interested in gastric bypass surgery. Her blood pressure was 154/89 mm Hg, her BMI was 41 kg per m2, and her A1C level was 7.9%. She was taking metformin and lisinopril. She had never been pregnant and was not using contraception. She would like to have children, but had been unable to conceive for many years and considered herself infertile. The patient was encouraged to develop a reproductive life plan, and she and her partner determined that they wished to delay having children until she was healthier. After discussion of her contraceptive options, she elected to have an intrauterine device placed. She was counseled about dietary changes, physical activity, and weight loss, and was referred for evaluation for gastric bypass surgery. Her medications were titrated to opti mize treatment of diabetes and hypertension, with a goal of discontinuing medications when she lost weight. One year after surgery, the patient’s BMI was 29 kg per m2, and she no longer required medications for diabetes or hypertension. Her A1C level was 6.5%. She had been taking multiple vitamins, including folic acid, since her surgery to avoid nutrient deficiencies, and she wished to have her intrauterine device removed. REFERENCES 1. Johnson K, Posner SF, Biermann J, et al.; CDC/ ATSDR Preconception Care Work Group; Select Panel on Preconception Care. Recommenda tions to improve preconception health and health care—United States. MMWR Recomm Rep. 2006;55(RR-6):1-23.

American Family Physician 2. Moos MK, Dunlop AL, Jack BW, et al. Healthier women, healthier reproductive outcomes: recommendations for the routine care of all women of reproductive age. Am J Obstet Gynecol. 2008;199(6 suppl 2):S280-S289. 3. Centers for Disease Control and Prevention. U.S. medical eligibility criteria for contraceptive use, 2010. MMWR Recomm Rep. 2010;59(RR-4):1-86. 4. McDiarmid MA, Gehle K. Preconception brief: occupational/environmental exposures. Matern Child Health J. 2006;10(5 suppl):S123-S128. 5. Shapira SK, Dolan S. Genetic risks to the mother and the infant: assessment, counseling, and management. Matern Child Health J. 2006;10(5 suppl):S143-S146. 6. Cragan JD, Friedman JM, Holmes LB, Uhl K, Green NS, Riley L. Ensuring the safe and effective use of medications during pregnancy: planning and prevention through preconception care. Matern Child Health J. 2006;10 (5 suppl):S129-S135. 7. Frieder A, Dunlop AL, Culpepper L, Bernstein PS. The clinical content of preconception care: women with psychiatric conditions. Am J Obstet Gynecol. 2008;199 (6 suppl 2):S328-S332. 8. American College of Obstetricians and Gynecologists. Domestic violence. ACOG Education Bulletin 257. Washington, DC: ACOG; 1999. 9. Floyd RL, Jack BW, Cefalo R, et al. The clinical content of preconception care: alcohol, tobacco, and illicit drug exposures. Am J Obstet Gynecol. 2008;199(6 suppl 2): S333-S339. 10. Coonrod DV, Jack BW, Stubblefield PG, et al. The clinical content of preconception care: infectious diseases in preconception care. Am J Obstet Gynecol. 2008;199 (6 suppl 2):S296-S309. 11. Coonrod DV, Jack BW, Boggess KA, et al. The clinical content of preconception care: immunizations as part of preconception care. Am J Obstet Gynecol. 2008;199 (6 suppl 2):S290-S295. 12. U.S. Preventive Services Task Force. Screening for chlamydial infection: recommendations and rationale. Am J Prev Med. 2001;20(3 suppl):90-94. 13. U.S. Preventive Services Task Force. Screening for gonorrhea. May 2005. http://www.uspreventiveservicestaskforce. org/uspstf/uspsgono.htm. Accessed February 29, 2012. 14. U.S. Public Health Service Task Force recommendations for the use of antiretroviral drugs in pregnant HIV-1infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States. MMWR Recomm Rep. 2002;51(RR-18):1-38. 15. U.S. Preventive Services Task Force. Screening for syphilis infection. July 2004. http://www. uspreventiveservicestaskforce.org/uspstf/uspssyph.htm. Accessed August 27, 2013. 16. Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immu nization Practices (ACIP) part II: immunization of adults

[published correction appears in MMWR Morb Mortal Wkly Rep. 2007;56(42):1114]. MMWR Recomm Rep. 2006;55(RR-16):1-33. 17. Fiore AE, Uyeki TM, Broder K, et al. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010 [published corrections appear in MMWR Recomm Rep. 2010;59(31):993, and MMWR Recomm Rep. 2010;59(35):1147]. MMWR Recomm Rep. 2010;59(RR-8):1-62. 18. Watson JC, Hadler SC, Dykewicz CA, Reef S, Phillips L. Measles, mumps, and rubella—vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1998;47(RR-8):1-57. 19. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in pregnant women—Advisory Committee on Immunization Practices (ACIP), 2012. MMWR Morb Mortal Wkly Rep. 2013;62(7):131-135. 20. Marin M, Güris D, Chaves SS, Schmid S, Seward JF. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(RR-4):1-40. 21. National Collaborating Centre for Women’s and Children’s Health; National Institute for Health and Clinical Excellence. Antenatal care: routine care for the healthy pregnant women. London, England: RCOG Press; 2008. 22. Lumley J, Watson L, Watson M, Bower C. Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. Cochrane Database Syst Rev. 2000;(2):CD001056. 23. Elsinga J, de Jong-Potjer LC, van der Pal-de Bruin KM, le Cessie S, Assendelft WJ, Buitendijk SE. The effect of preconception counselling on lifestyle and other behaviour before and during pregnancy. Womens Health Issues. 2008;18(6 suppl):S117-S125. 24. Wilson RD, Davies G, Désilets V, et al.; Genetics Committee and Executive and Council of the Society of Obstetricians and Gynaecologists of Canada. The use of folic acid for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can. 2003;25(11):959-973. 25. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991;338(8760):131-137. 26. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA. 2004;291(23):2847-2850. 27. Siega-Riz AM, Siega-Riz AM, Laraia B. The implications of maternal over weight and obesity on the course of pregnancy and birth outcomes. Matern Child Health J. 2006;10(5 suppl):S153-S156. 28. Tsai AG, Wadden TA. Systematic review: an evaluation of major commercial weight loss programs in the United States. Ann Intern Med. 2005;142(1):56-66.

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American Family Physician 29. Neveu N, Granger L, St-Michel P, Lavoie HB. Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome. Fertil Steril. 2007;87(1):113-120. 30. Qublan HS, Yannakoula EK, Al-Qudah MA, El-Uri FI. Dietary intervention versus metformin to improve the reproductive outcome in women with polycystic ovary syndrome. A prospective comparative study. Saudi Med J. 2007;28(11):1694-1699. 31. Shankar P, Boylan M, Sriram K. Micronutrient deficiencies after bariatric surgery. Nutrition. 2010;26(11-12):1031-1037. 32. Landsberger EJ, Gurewitsch ED. Reproductive implications of bariatric surgery: pre- and postoperative considerations for extremely obese women of childbearing age. Curr Diab Rep. 2007;7(4):281-288. 33. Wax JR, Cartin A, Wolff R, Lepich S, Pinette MG, Blackstone J. Pregnancy following gastric bypass for morbid obesity: effect of surgery-to-conception interval on maternal and neonatal outcomes. Obes Surg. 2008;18(12):1517-1521. 34. Gardiner PM, Nelson L, Shellhaas CS, et al. The clinical content of preconception care: nutrition and dietary supplements. Am J Obstet Gynecol. 2008;199(6 suppl 2): S345-S356. 35. Schatz M. The efficacy and safety of asthma medications during pregnancy. Semin Perinatol. 2001;25(3):145-152. 36. National Asthma Education and Prevention Program (National Heart, Lung, and Blood Institute). Working Group on Asthma and Pregnancy. Working Group report on managing asthma during pregnancy: recommendations for pharmacologic treatment. NIH publication 04-5236. Bethesda, Md.: National Institutes of Health; 2005. 37. Dunlop AL, Jack BW, Bottalico JN, et al. The clinical content of preconception care: women with chronic medical conditions. Am J Obstet Gynecol. 2008;199 (6 suppl 2):S310-S327. 38. National Collaborating Centre for Women’s and Children’s Health; National Institute for Clinical Excellence. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the Postnatal Period. London, England: RCOG Press; 2008. 39. Lydakis C, Lip GY, Beevers M, Beevers DG. Atenolol and fetal growth in pregnancies complicated by hypertension. Am J Hypertens. 1999;12(6):541-547. 40. De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(8):2543-2565. 41. ACOG educational bulletin. Seizure disorders in pregnancy. Number 231, December 1996. Committee on Educational Bulletins of the Ameri can College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 1997;56(3):279-286.

42. Silver RM, Warren JE. Preconception counseling for women with throm bophilia. Clin Obstet Gynecol. 2006;49(4):906-919. 43. Maternal and Child Health Bureau. Women’s Health USA 2002. Rockville, Md.: U.S. Department of Health and Human Services; 2002. 44. Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner RE. Pre-conception care of diabetes, congenital malformations, and spontaneous abortions. Diabetes Care. 1996;19(5): 514-541. 45. Kitzmiller JL, Gavin LA, Gin GD, Jovanovic-Peterson L, Main EK, Zigrang WD. Preconception care of diabetes: glycemic control prevents congenital anomalies. JAMA. 1991;265(6):731-736. 46. Pregnancy outcomes in the Diabetes Control and Complications Trial. Am J Obstet Gynecol. 1996;174(4):1343-1353. 47. American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care. 2011;34(suppl 1): S11-S61. 48. Ferrer RL, Sibai BM, Mulrow CD, Chiquette E, Stevens KR, Cornell J. Management of mild chronic hypertension during pregnancy: a review. Obstet Gynecol. 2000;96 (5 pt 2):849-860. 49. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000;183(1):S1-S22. 50. McCowan LM, Buist RG, North RA, Gamble G. Perinatal morbidity in chronic hypertension. Br J Obstet Gynaecol. 1996;103(2):123-129. 51. Sibai BM, Anderson GD. Pregnancy outcome of intensive therapy in severe hypertension in first trimester. Obstet Gynecol. 1986;67(4):517-522. 52. Klein RZ, Haddow JE, Faix JD, et al. Prevalence of thyroid deficiency in pregnant women. Clin Endocrinol (Oxf). 1991;35(1):41-46. 53. Leung AS, Millar LK, Koonings PP, Montoro M, Mestman JH. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol. 1993;81(3):349-353. 54. Casey BM, Dashe JS, Wells CE, et al. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol. 2005;105(2):239-245. 55. Tan TO, Cheng YW, Caughey AB. Are women who are treated for hypo thyroidism at risk for pregnancy complications? Am J Obstet Gynecol. 2006;194(5):e1-e3. 56. Kircher S, Schatz M, Long L. Variables affecting asthma course during pregnancy. Ann Allergy Asthma Immunol. 2002;89(5):463-466. 57. Liu S, Wen SW, Demissie K, Marcoux S, Kramer MS. Maternal asthma and pregnancy outcomes: a retrospective cohort study. Am J Obstet Gynecol. 2001;184(2):90-96.

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Practice Guidelines AHA Releases Recommendations on Ankle-Brachial Index Measurement and Interpretation The ankle-brachial index (ABI) is the ratio of the systolic blood pressure at the ankle to the systolic blood pressure at the brachial artery. It is one of the most widely available markers of atherosclerosis and least expensive to perform. In the primary care setting, it is effectively used to assess cardiovascular risk and diagnose peripheral artery disease (PAD). The American Heart Association (AHA) released a scientific statement on the measurement and interpretation of ABI, including standardization of measurement technique and the threshold for diagnosing PAD.

Protocol for Determining ABI with the Doppler Method To determine the ABI with the Doppler method, the patient should be at rest for five to 10 minutes in the supine position. The head and heels should be supported, and the room should be at a comfortable temperature. The patient should not smoke at least two hours before ABI measurement. The blood pressure cuff should contour at least 40% of the limb circumference. Cuffs should not be placed on a distal bypass or on an ulcer, and open lesions should be covered with an impermeable dressing to avoid contamination. Patients must remain still during the measurement; if they are unable to remain still (e.g., tremor), another method of measurement should be used. The cuff should be positioned around the ankle with the straight wrapping method, as with brachial measurement, and the lower edge should be 2 cm above the superior aspect of the medial malleolus. Using an 8- to 10-MHz Doppler probe with gel applied over the sensor, the device should be placed in the area of the pulse at a 45- to 60-degree angle to the

Source: Adapted from Am Fam Physician. 2013;88(12):866-867.

skin surface. The probe should be moved to find the clearest signal. To detect the pressure, the cuff should be inflated progressively to 20 mm Hg above the level of flow signal disappearance and then slowly deflated to detect signal reappearance. If flow is still detected at the maximum level of inflation (300 mm Hg), the cuff should be deflated immediately to avoid pain. Doppler should also be used to detect brachial blood flow during the arm pressure measurement. The same sequence of limb pressure measurement should be used, and the sequence should be the same for all patients within the same practice. If the first arm measurement is 10 mm Hg or greater than the other arm, then it should be repeated at the end of the sequence, and the two numbers averaged. For example, when beginning with the right arm and using the counterclockwise sequence (i.e., right arm, right posterior tibial, right dorsalis pedis, left posterior tibial, left dorsalis pedis, left arm), the right arm measurement would be repeated and the two measurements should be averaged. However, if the difference between the two numbers is greater than 10 mm Hg, only the second measurement should be used to lessen the white coat effect. If the entire sequence of ABI measurements is repeated, then the order of measuring the four limb pressures should be reversed (e.g., a clockwise sequence should follow a counterclockwise sequence). The ABI should be reported separately for each leg, and should be calculated by dividing the higher of the posterior tibial or dorsalis pedis blood pressure by the higher of the right or left arm systolic blood pressure.

Recommendations for ABI Interpretation If there is clinical suspicion of PAD based on symptoms and clinical findings, ABI measurement should be the first-line noninvasive option to confirm the diagnosis. An ABI of 0.9 or less is the threshold for confirming lower-extremity PAD. If the ABI is greater than 0.9 but there is suspicion of PAD, postexercise ABI measurement or other noninvasive options, such as imaging, should be used.

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American Family Physician A postexercise ankle pressure decrease greater than 30 mm Hg or an ABI decrease greater than 20% may be considered a criterion for PAD. If the ABI is greater than 1.4 but there is clinical suspicion of PAD, a toe-brachial index measurement or other noninvasive options, such as imaging, should be used. When interpreting ABI during follow-up, a decrease greater than 0.15 can effectively detect significant PAD progression. ABI alone should not be used to monitor revascularized patients.

In asymptomatic individuals, ABI can provide incremental information beyond standard risk scores to predict future cardiovascular events. Persons who have an ABI of 0.9 or less, or 1.4 or greater, are at increased risk of cardiovascular events and mortality, regardless of the presence of PAD symptoms or other cardiovascular risk factors. An ABI between 0.91 and 1.0 is considered borderline for cardiovascular risk. Additional evaluation is appropriate in these cases.

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Photo Quiz Facial Palsy in a 38-Year-Old Man A 38-year-old man presented with a painful rash on his right ear that had lasted for seven days. Over the previous four days, he developed ipsilateral tinnitus and progressive difficulty in closing his right eye and mouth. He had no notable medical history. On examination, he had multiple vesicles on an erythematous base on the concha of his right ear (Figure 1). Neurologic examination showed rightsided hearing impairment and lower motor neuron facial palsy with lagophthalmos, an inability to smile on the affected side, and loss of definition in the right nasolabial fold (Figure 2). Question Based on the patient’s history and physical examination findings, which one of the following is the most likely diagnosis?

Figure 1.

Figure 2.

A. Bell palsy. B. Neurosarcoidosis. C. Parry-Romberg syndrome. D. Ramsay Hunt syndrome.

SEE THE FOLLOWING PAGE FOR DISCUSSION.

Source: Adapted from Am Fam Physician. 2013;88(11):771-772.

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American Family Physician Summary Table Condition

Characteristics

Bell palsy

Unilateral facial weakness and drooping; difficulty closing an eye; loss of furrows in the brow; most cases resolve spontaneously

Neurosarcoidosis

Bilateral or unilateral seventh cranial nerve palsy; other cranial nerve palsies can also be associated; most resolve spontaneously but may recur

Parry-Romberg syndrome

Unilateral facial atrophy; includes degeneration of the soft tissue on one side of the face; autoimmune reaction; more common in women

Ramsay Hunt syndrome

Unilateral peripheral facial palsy; herpes zoster infection of the external ear or tympanic membrane with involvement of facial or auditory nerves; tinnitus, vertigo, or deafness may occur

Discussion The answer is D: Ramsay Hunt syndrome, or herpes zoster oticus, is characterized by herpes zoster infection of the external ear or tympanic membrane with involvement of the facial and/or auditory nerves.1 The clinical manifestation includes unilateral peripheral facial palsy, with or without tinnitus, ver tigo, or deafness.1,2 Ramsay Hunt syndrome can usually be diagnosed based on clinical findings.1 A Tzanck smear of the vesicular fluid can be performed to evaluate for multinucleated giant cells, which are indicative of varicella or herpes zoster infection.1,2 A viral culture is generally not required, but can differentiate between varicella and herpes simplex virus.1 Initiation of antiviral therapy within 72 hours of rash onset leads to the best outcomes in most adults.1,3-5 However, less than 50% of patients achieve complete neurologic recovery.1 Topical antiviral therapy is effective against cutaneous infection of herpes simplex virus but is not effective on the herpes zoster rash.1 The use of systemic corticosteroids is controversial, but may be considered for healthy older adults with severe pain and no contraindications.1 The pain of herpes zoster can be a significant problem, especially in older persons.1,3,5 Most patients experience pain during the acute phase that requires regular analgesics. Occlusive ointments and creams or lotions containing corticosteroids should be avoided.1 Postherpetic neuralgia is a common com plication of herpes zoster infection and is defined as any pain occurring 90 to 120 days after rash onset.1,3 Postherpetic neuralgia has an overall incidence of 8% to 15%, but is most common in older persons.1 Bell palsy is a common cause of facial drooping. Patients present with unilateral facial weakness, difficulty closing an eye, and

loss of furrows in the brow. Most cases are idiopathic and will resolve spontaneously.6 Neurosarcoidosis occurs in 5% to 10% of patients with sarcoidosis. The most common clinical manifestation of neurosarcoidosis is a bilateral or unilateral seventh cranial nerve palsy, although other cranial nerve palsies are possible. The condition usually resolves spontaneously but may recur, possibly years after the initial presentation. Parry-Romberg syndrome is a rare progressive unilateral facial atrophy. It is thought to be an autoimmune disease and is more common in women. Symptoms include degeneration of the soft tissue, typically on one side of the face. REFERENCES 1. Fitzpatrick TB, Wolff K, eds. Fitzpatrick’s Dermatology in General Medicine. 7th ed. New York, NY: McGraw-Hill; 2008. 2. McKee PH, Calonje E, Granter SR, eds. Pathology of the Skin: With Clinical Correlations. 3rd ed. Philadelphia, Pa.: Elsevier Mosby; 2005. 3. Uscategui T, Dorée C, Chamberlain IJ, Burton MJ. Anti viral therapy for Ramsay Hunt syndrome (herpes zoster oticus with facial palsy) in adults. Cochrane Database Syst Rev. 2008;(4):CD006851. 4. Whitley RJ. A 70-year-old woman with shingles: review of herpes zoster [published corrections appear in JAMA. 2010;303(8):734, and JAMA. 2009;302(17):1864]. JAMA. 2009;302(1):73-80. 5. Sampathkumar P, Drage LA, Martin DP. Herpes zoster (shingles) and postherpetic neuralgia. Mayo Clin Proc. 2009;84(3):274-280. 6. Gronseth GS, Paduga R. Evidence-based guide line update: steroids and antivirals for Bell palsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2012;79(22): 2209-2213.

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CARDIOLOGY

Double-Chambered Right Ventricle with Transient 2:1 Atrioventricular Block: A Rare Presentation MONIKA MAHESHWARI*, SK KAUSHIKâ&#x20AC;

Abstract We report herein a case of 35-year-old male with a history of complex congenital heart disease, consisting of double-chambered right ventricle (DCRV) with ventricular septal defect and presenting with transient 2:1 atrioventricular (AV) block on electrocardiogram. This unique presentation has not yet been described in literature, hence it was worth describing this rare complication of DCRV.

Keywords: Double-chambered right ventricle, atrioventricular heart block, moderator band

ouble-chambered right ventricle (DCRV) is a rare congenital heart disease characterized by the division of the right ventricular (RV) cavity into two chambers by anomalous muscle bundle or a hypertrophied moderator band.1 Electrocardiogram (ECG) usually shows features of RV overload, in form of RV hypertrophy or right bundle branch block.2 We describe herein the first case of unrepaired DCRV complicated with transient 2:1 atrioventricular (AV) block in ECG. CASE REPORT A 35-year-old male who was a diagnosed case of DCRV with ventricular septal defect (VSD) presented in outdoor with complaint of episodes of syncope on mild exertion since 2 months. On examination, his vital parameters were stable. Cardiac auscultation revealed a harsh, Grade 4/6 systolic murmur at left lower sternal border. Transthoracic echocardiogram confirmed DCRV and showed a prominent muscle band transversing from the RV free wall to the interventricular septum and dividing RV into two parts (RV1, RV2) with an apical muscular VSD. Color Doppler demonstrated a turbulent jet of blood from RV2 to RV1 through perforation in the anomalous muscular bundle (Fig. 1). On doing ECG, there was transient 2:1 AV block evident in lead V2 (Fig. 2). *3rd Year Resident â&#x20AC; Senior Professor and Ex.-Head Dept. of Cardiology Jawaharlal Nehru Medical College, Ajmer, Rajasthan Address for correspondence Dr Monika Maheshwari Navin Niwas, 434/10, Bapu Nagar, Ajmer, Rajasthan - 305 001 E-mail: opm11@rediffmail.com

F i g u r e 1 . Tr a n s t h o r a c i c E C G s h o w i n g D C RV with a prominent muscle band dividing RV into two parts and an apical muscular VSD. Color Doppler demonstrating a turbulent jet of blood from RV2 to RV1 through perforation in the anomalous muscular bundle.

Figure 2. Electrocardiogram with transient 2:1 AV block evident in lead V2.

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CARDIOLOGY DISCUSSION

REFERENCES

DCRV is rare with overall incidence of 0.5-2%.3 Treatment of choice is resection of anomalous muscle bundle and repair of associated lesions during childhood.4 The long-term prognosis for patients after the intracardiac repair of DCRV is excellent, but in some reported cases, AV block occurred during the postoperative period, which required insertion of a permanent pacemaker.5 However, in our case there was no past history of surgical correction of the congenital lesion and 2:1 AV block developed spontaneously as a complication of unrepaired DCRV.

1. Bashore TM. Adult congenital heart disease: right ventricular outflow tract lesions. Circulation 2007;115(14):1933-47.

Conclusion We hypothesize that structural anomalies involved in DCRV like muscular band hypertrophy and substitution of myocardium by fibrotic tissue with myofilaments disarray, would have lead to development of AV block in our patient.

2. Byrum CJ, Dick M 2nd, Behrendt DM, Hees P, Rosenthal A. Excitation of the double chamber right ventricle: electrophysiologic and anatomic correlation. Am J Cardiol 1982;49(5):1254-8. 3. Singh NK, Karn JP, Gupta A, Senthil S. Double-chambered right ventricle with ventricular septal defect presenting in adulthood. J Assoc Physician India 2011;59:451-3. 4. Penkoske PA, Duncan N, Collins-Nakai RL. Surgical repair of double-chambered right ventricle with or without ventriculotomy. J Thorac Cardiovasc Surg 1987;93(3):385-93. 5. Hachiro Y, Takagi N, Koyanagi T, Morikawa M, Abe T. Repair of double-chambered right ventricle: surgical results and long-term follow-up. Ann Thorac Surg 2001;72(5):1520-2.

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A new cross-sectional study presented at the Anxiety and Depression Association of America (ADAA) Conference 2014 has revealed that patients with anxiety or depression who are hospitalized for acute myocardial infarction (AMI) have lesser odds of receiving cardiac catheterization and subsequent angioplasty or bypass surgery than their mentally well counterparts. Additionally, the study reported lower mortality rates after AMI in patients with anxiety and depressive disorders compared with the general population.

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A novel study conducted in UK has reported that one in four hypertensive patients only partially take their antihypertensive medication or do not take the drugs at all. The study authors noted that nearly 10% were totally nonadherent to antihypertensive therapy while 15% were only partially taking their medication. The highest prevalence of partial and total nonadherence was noted among patients with uncontrolled hypertension and those referred for renal denervatio.

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A much debated presentation at the American College of Cardiology 2014 Scientific Sessions has reported that the rate of major adverse cardiac events (MACE) is significantly lower in the heparin-treated patients at 28 days in comparison to bivalirudin. The single-center randomized trial also reported no differences in bleeding complications in the two groups. It was noted that at four weeks, the primary efficacy end point (MACE, defined as all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularization [TLR]) had occurred in 8.7% of bivalirudin-treated patients and in 5.7% of heparin-treated patients.

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Community Medicine

Extended-spectrum β-lactamase and AmpC β-lactamase Production among Gram-negative Bacilli Isolates Obtained from Urinary Tract Infections and Wound Infections Pottahil Shinu*, Rajesh Bareja*, Manoj Goyal†, Varsha A Singh*, Priya Mehrishi*, Monika Bansal‡, Vinod Kumar Narang*, Prem Singh Grover*, Virendra Singh*, Shailesh Yadav†, Ahmed Nabeel#

Abstract Extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases continue to be a major problem in healthcare settings. Due to the scarcity of information regarding the antibiotic susceptibility patterns particularly from urinary tract infections (UTIs) and wound infections, the current study was carried out to assist the clinicians to prescribe appropriate antibiotics against gram-negative clinical isolates. In the current study, urine (n = 620) and pus (n = 228) samples were collected from different sites (at various clinical departments) and subjected to direct microscopic examination, culture and antibiotic susceptibility testing (AST). In the AST testings, the isolates that exhibited reduced zone of inhibition to one or more of the antibiotics such as cefotaxime (≤27 mm), ceftriaxone (≤25 mm), ceftazidime (≤22 mm), cefpodoxime (≤17 mm) and aztreonam (≤27 mm) were considered as potential ESBL producers and the ESBL production was confirmed using phenotypic screening test (doubledisk synergy test) and phenotypic confirmatory test (combined-disk test). However, isolates showing resistance or decreased sensitivity to cefoxitin, cefotaxime, ceftriaxone, ceftazidime, cefpodoxime or aztreonam and sensitive to cefepime were considered as a screen positive AmpC producer and subjected to AmpC disk tests. The current study concluded that 72.41% and 21.76% of ESBL and AmpC producers were detected, respectively in our hospital. It was also observed that the double-disk synergy and combined-disk tests were equally effective for ESBL detection. Further, AmpC disk test is simple, easy to perform and interpret, requiring less expertise for the rapid detection of AmpC isolates.

Keywords: Extended-spectrum β-lactamases, AmpC β-lactamases, gram-negative isolates, antibiotic susceptibility testing

novel class of enzymes imparting resistance to β-lactam antibiotics has emerged over the last few decades, mostly owing to the antibiotic selection pressure and most alarming are the extended-spectrum β-lactamases (ESBLs) produced by Enterobacteriaceae that have spread worldwide since the first report in 1983.1 ESBLs are the enzymes produced by gram-negative bacilli that have the potential to

*Assistant Professor Dept. of Microbiology †Dept. of Pharmacology ‡Dept. of Physiology #Dept. of Community Medicine MMIMSR, Mullana, Ambala, Haryana Address for correspondence Dr Pottahil Shinu Assistant Professor Dept. of Microbiology MMIMSR, MM University Mullana, Ambala, Haryana E-mail: shinup1983@gmail.com

hydrolyze β-lactam antibiotics containing an oxyimino group (third-generation cephalosporins [3GCs] and aztreonam) and are inhibited by β-lactamase inhibitors such as clavulanic acid, sulbactam and tazobactam. Cephamycins (e.g., cefoxitin) or carbapenems (e.g., imipenem, meropenem and ertapenem) are not affected by these enzymes.2 ESBL production has been reported in a variety of organisms including the members of Enterobacteriaceae and other nonenteric bacilli as well.3,4 Currently, a majority of the clinical laboratories test for production of ESBLs; however, the testing of clinical isolates for the production of plasmidmediated AmpC β-lactamases is usually ignored. Like ESBLs, AmpC β-lactamases have a broad-substrate profile including penicillins, cephalosporins (apart from zwitterionic cephalosporins) and monobactams. In addition, it hydrolyzes cephamycins and is not inhibited by commercially available β-lactamase inhibitors. Generally, AmpC β-lactamases are associated with multiple antimicrobial resistance, limiting the

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Community Medicine therapeutic regimens.5,6 AmpC β-lactamase production has been reported in Escherichia coli, Klebsiella pneumoniae, Salmonella spp., Citrobacter freundii, Enterobacter aerogenes and Proteus mirabilis.7 Recently, the incidence of ESBL and AmpC β-lactamaseproducing strains among gram-negative bacilli isolates has considerably increased resulting in the limitation of therapeutic alternatives.8,9 Further, various outbreaks of infections associated with ESBL and AmpC β-lactamases have been reported across the globe in the last decades.10,11 Furthermore, geographical distribution of ESBL producers may vary from countries to countries and even between institutions to institutions.12-15 Various investigators reported the prevalence of ESBL and AmpC β-lactamase production in India with considerable variation between different hospitals and even between various sites of infections such as urinary tract infections (UTIs) and wound infections.11,16-19 Due to the scarcity of information regarding the antibiotic susceptibility patterns particularly from UTIs and wound infections, the clinicians may likely prescribe inappropriate antibiotics for empirical treatments. Considering these issues, the present study was designed to assess the current levels of resistance to antibiotics that are commonly used in our hospital and also to review the prevalence of ESBL and AmpC β-lactamase production among gram-negative bacterial isolates obtained from wound infections and UTIs. Material and methods

Study Design The study was conducted among all the patients (suspected to be having UTIs and wound infections) who were examined by all the clinical departments of MM Institute of Medical Sciences and Research, Ambala, India (a 750 bedded tertiary healthcare teaching hospital). During the study period, (between March, 2012 and February, 2013), urine (n = 620) and pus (n = 228) samples were collected from different sites (at various clinical departments) and were immediately transported to the Dept. of Microbiology. Immediately after receipt, specimens were subjected to direct microscopic examination (wet mount examination for uncentrifuged urine and Gram staining for pus specimens), culture and antibiotic susceptibility testing.

Bacterial Strains and Antibiotic Susceptibility Testing All the pus samples were cultured on blood agar (HiMedia, Mumbai, India) and MacConkey agar

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(HiMedia, Mumbai, India). However, the urine specimens were inoculated on Cysteine Lactose Electrolytes Deficient (CLED) agar (HiMedia, Mumbai, India) and incubated at 37°C for 18-24 hours. After incubation, the bacterial isolates were identified by standard laboratory protocols.20 The antibiotic susceptibility testing of gram-negative bacilli was performed on Mueller-Hinton agar (HiMedia, Mumbai, India) by modified Kirby-Bauer disk diffusion method as recommended by the Clinical Laboratory Standards Institute (CLSI) using ampicillin (10 μg), amoxicillin-clavulanic acid (20 μg + 10 μg), piperacillintazobactam (100 + 10 μg), piperacillin (100 μg), cinoxacin (100 μg), carbenicillin (100 μg), ceftriaxone (30 μg), cefepime (30 μg), ceftazidime (30 μg), cefoxitin (10 μg), cefpodoxime (30 μg), cefotaxime (30 μg), ceftizoxime (30 μg), aztreonam (30 μg), imipenem (10 μg), gentamicin (10 μg), amikacin (30 μg), tobramycin (10 μg), tetracycline (30 μg), cotrimoxazole (1.25/23.75 μg), ciprofloxacin (5 μg), lomefloxacin (10 μg ), nitrofurantoin (300 μg), gatifloxacin (5 μg), norfloxacin (10 μg). The inoculated AST plates were incubated at 37°C for 16-18 hours and the results were interpreted as per CLSI guidelines.21

Screening Test for ESBL and AmpC β-lactamases Isolates that exhibited reduced zone of inhibition to one or more of the antibiotics such as cefotaxime (≤27 mm), ceftriaxone (≤25 mm), ceftazidime (≤22 mm), cefpodoxime (≤17 mm) and aztreonam (≤27 mm) were considered as potential ESBL producers.22 However, isolates showing resistance or decreased sensitivity to cefoxitin, cefotaxime, ceftriaxone, ceftazidime, cefpodoxime or aztreonam and were sensitive to cefepime were considered as a screen positive AmpC producer and subjected to AmpC disk test.23

Phenotypic Screening Test This test for ESBL producers (double-disk synergy test [DDST]) was performed as suggested by Jarlier et al, wherein an enhancement in the zone of inhibition between a β-lactam disk and one containing the β-lactamase inhibitor was indicative of the presence of ESBL.24

Phenotypic Confirmatory Test (Combined-disk Test) This test was carried as per CLSI recommendations, briefly; ceftazidime (30 μg) versus ceftazidime/ clavulanic acid (30 μg/10 μg), (HiMedia, Mumbai, India), used as a phenotypic confirmatory test wherein a ≥ 5 mm increase in the zone diameter for

Community Medicine the antimicrobial agent tested in combination with β-lactamase inhibitor versus its zone when tested alone indicates ESBL production.21 AmpC disk test was carried out as recommended by Black et al, briefly; a sterile disk (6 mm) moistened with sterile saline (20 μL) and inoculated with several colonies of test organism was placed beside a cefoxitin disk (almost touching) on the Mueller-Hinton agar plate lawned with a culture of E. coli ATCC 25922 and incubated overnight at 35°C. A positive test appeared as a flattening or indentation of the cefoxitin inhibition zone in the vicinity of the test disk and a negative test had an undistorted zone.24

Table 1. Distribution of All Gram-negative Bacilli Isolates Obtained from Wound Infections and UTIs Gram-negative isolates obtained

Specimens Pus (%)

Urine (%)

E. coli (77)

16 (20.7)

61 (79.22)

P. aeruginosa (38)

22 (57.8)

16 (42.11)

K. pneumoniae (34)

3 ( 8.82)

31 (91.18)

P. mirabilis (19)

3 (15.78)

16 (84.21)

K. oxytoca (19)

4 (21.05)

15 (78.95)

C. freundii (11)

4 (36.36)

7 (63.64)

Quality Control

E. aerogenes (7)

3 (42.86)

4 (57.14)

Every new batch of culture media was incubated at 37°C overnight to ensure the sterility. E. coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 were used as quality control strains for antimicrobial susceptibility testing. However, a non-ESBL-producing organism E. coli ATCC 25922 and an ESBL-producing organism K. pneumoniae ATCC 700603 were used while testing ESBL screening and phenotypic confirmatory tests.

M. morganii (14)

2 (14.29)

12 (85.71)

A. lwoffii (8)

8 (100)

Total (227)

65 (28.63)

162 (27.31)

Statistical Analysis Significance between the resistance level of various drugs in ESBL and non-ESBL, AmpC and non-AmpC isolates was performed using the Fisher’s exact test (Graphpad Prism online version). Results Table 1 demonstrates the distribution of all gramnegative bacilli isolates obtained from wound infections and UTIs. Of the 848 nonrepetitive specimens processed (urine [n = 620] and pus [n = 228]), a total of 269 bacterial isolates were obtained. Out of the 269 (31.72%) nonrepetitive isolates (urine [n = 182] and pus (n = 87]), 30 isolates were Staphylococcus aureus, Staphylococcus epidermidis (n = 5) and Staphylococcus epidermidis (n = 7), respectively. After exclusion of these gram-positive organisms, a total of 227 gramnegative isolates were subjected to further analysis. Of the 227 gram-negative bacilli isolates, 96 (40.85%) showed resistance or decreased sensitivity to any one of the 3GCs such as cefotaxime (≤27 mm), ceftriaxone (≤25 mm), ceftazidime (≤22 mm), cefpodoxime (≤17 mm), aztreonam (≤27 mm) and isolates were further screened for ESBL production using DDST and confirmed using combined-disk synergy test (CDST) (Phenotypic confirmatory test). Of these 96 isolates, 80 (80/96) isolates were confirmed for ESBL production using CDST. Interestingly, it was observed

that both DDST and CDST independently detected all the ESBL producers. Of these, 24 isolates were E. coli, K. pneumoniae (n =16), P. aeruginosa (n = 10), P. mirabilis (n = 7), M. morganii (n = 6) and C. Freundii, respectively. Table 2 summarizes the detection of ESBL and AmpC β-lactamases among gram-negative isolates as indicated by various detection methods. Interestingly, we have also noticed the co-existence phenotype of both ESBLs and AmpC in 11.68% isolates of which 7 (7/227) and 6 (6/227) isolates were E. coli and Klebsiella spp., respectively. Table 3 illustrates the distribution of antibiotic resistance among ESBL and non-ESBL producers. Further, it is evident from Table 3 that a significant number of ESBL-producing strains were found to be resistant to antimicrobial agents. However, in non-ESBL-producing isolates resistance was found to be relatively low. It is also evident from Table 3 that ceftazidime is the most effective indicator of ESBL production among the 3GCs. Table 4 demonstrates the distribution of antibiotic resistance among AmpC (n = 26) and non-AmpC (n = 201) β-lactamase producers. Of the 227, gram-negative isolates, 49 isolates showed resistance or decreased sensitivity to cefoxitin, cefotaxime, ceftriaxone, ceftazidime, cefpodoxime, aztreonam and were sensitive for cefipime. Of these, 26 (26/49) isolates were confirmed for AmpC β-lactamase production using AmpC disk test method. Out of the 26 AmpC β-lactamase confirmed cases, seven and 17 isolates were E. coli and Klebsiella spp., respectively. ESBL-producing isolates were resistant to more antimicrobial agents than non-ESBL-producing isolates. Multidrug resistance was seen in 56 (73.75%)

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Community Medicine Table 2. Detection of ESBL and AmpC β-lactamases among Gram-negative Isolates as Indicated by Various Detection Methods Microorganism

Screening test (Positive) ESBL Pus (n = 65)

Confirmatory test (Positive) AmpC

Urine (n = 162)

Pus (n = 65)

ESBL

Urine (n = 162)

Pus (n = 65)

Combined ESBL and AmpC β-lactamase production ESBL and AmpC production

AmpC

Urine (n = 162)

Pus Urine Pus Urine (n = 65) (n = 162) (n = 65) (n = 162)

E. coli (n = 77)

5 (7.69%) 23 (14.19%) 2 (3.07%) 22 (13.58) 4 (6.16%) 20 (12.35) 2 (3.07%) 13 (8% 2 (3. 07%) 5 (3.08%)

P. aeruginosa (n = 38) K. pneumoniae sub. sp. (n = 34) P. mirabilis (n = 19) K. oxytoca (n = 19)

14 (21.54%) 1 (1.53%)

5 (3.09%)

3 (4.62%)

1 (0.62)

12 (18.4%) 4 (2.47%) 2 (3.07%)

14 (8.64%) 2 (3.07%)

14 (8.64)

1 (1.53%) 9 (5.55%) 1 (1.53%) 6 (3.7%)

1 (1.53%)

6 (3.7%)

3 (4.62%)

5 (3.08%)

2 (3.07%)

1 (0.62)

C. freundii (n = 11)

3 (4.62%)

3 (1.8%)

E. aerogenes (n = 7) M. morganii (n = 14) A. lwoffii (n = 8)

2 (3.08%)

4 (2.46%)

2 (3.08%) -

Total (n = 227)

1 (1.53) 4 (2.47%) -

2 (3.07%) 5 (3.08%) 1 (1.53%)

1 (1.53%)

3 (4.62%) 3 (1.85%)

1 (1.54%) 4 (2.46%)

5 (3.08%)

2 (3.07%) 5 (3.08%)

2 (3.07%)

1 (1.53%)

5 (3.08%)

31 (47.69%) 65 (40.12%) 11 (16.9%) 38 (23.4%) 25 (38.4%) 55 (33.9%) 7 (10.7%) 19 (11%) 4 (6.15%) 9 (5.5%)

Table 3. Distribution of Antibiotic Resistance among ESBL (n = 80) and non-ESBL (n = 147) Producers Antibiotics

ESBL producers (n = 80) (%)

Non-ESBL producers (n = 147) (%)

P value

80 (100)

124 (84.35)

0.0001

Amoxicillin-clavulanic acid

42 (52.5)

36 (24.45)

0.0001

Piperacillin-tazobactam

30 (37.5)

25 (17)

0.001

56 (70)

31 (21.08)

0.0001

Ampicillin

Piperacillin Cinoxacin*

78 (97.4)

89 (60.55)

0.0001

Carbenicillin*

79 (98.75)

72 (48.98)

0.0001

Ceftriaxone

78 (97.4)

39 (26.53)

0.0001

Cefepime

78 (97.5)

34 (23.13)

0.0001

Ceftazidime

80 (100)

36 (24.49)

0.0001

Cefoxitin Cefpodoxime Cefotaxime Ceftizoxime*

28 (35)

45 (30.61)

0.0001

79 (98.74)

32 (21.77)

0.0001

76 (95)

38 (25.85)

0.0001

76 (95)

34 (23.13)

0.0001

Aztreonam

77 (96.25)

34 (23.13)

0.0001

Imipenem

Gentamicin

41 (51.23)

38 (25.85)

0.0002

Amikacin

18 (22.5)

24 (16.32)

0.2846

Cont’d ...

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Community Medicine Antibiotics

ESBL producers (n = 80) (%)

Non-ESBL producers (n = 147) (%)

P value

Tobramycin

15 (18.75)

30 (20.41)

0.0001

Tetracycline

59 (73.75)

42 (28.57)

0.0001

Cotrimoxazole

62 (77.7)

40 (27.21)

0.0001

Ciprofloxacin

43 (53.75)

28 (19.04)

0.0001

Lomefloxacin*

49 (61.23)

26 (17.68)

0.0001

Nitrofurantoin*

2 (2.4)

1 (0.68)

0.2842

Gatifloxacin**

38 (47) 5.

24 (16.32)

0.0001

Norfloxacin*

34 (42.5)

27 (18.36)

0.0001

*Tested for urinary isolates only. **Tested for both wound infections and urinary tract infections.

Table 4. Distribution of Antibiotic Resistance among AmpC (n = 26) and non-AmpC (n = 201) Î˛-lactamase Producers Antibiotics

AmpC producers (n = 26) (%)

Non-AmpC producers (n = 201) (%)

P value

Ampicillin

26 (100)

183 (91.04)

0.2368

Amoxicillin-clavulanic acid

26 (100)

49 (24.38)

0.0001

Piperacillin-tazobactam

26 (100)

37 (18.41)

0.0001

Piperacillin

26 (100)

43 (21.39)

0.0001

Cinoxacin*

24 (92.31)

122 (60.7)

0.0009

Carbenicillin*

25 (96.15)

102 (50.74)

0.0001

Ceftriaxone

24 (92.31)

61 (30.34)

0.0001

Cefepime

79 (26.92)

59 (29.35)

0.0001

Ceftazidime

25 (96.15)

57 (28.36)

0.0001

Cefoxitin

25 (96.15)

58 (28.86)

0.0001

Cefpodoxime

22 (84.62)

52 (25.87)

0.0001

Cefotaxime

24 (92.31)

61 (30.35)

0.0001

Ceftizoxime*

24 (92.31)

55 (27.36)

0.0001

Aztreonam

25 (96.16)

51 (25.37)

0.0001

Imipenem

Gentamicin

21 (80.77)

54 (26.87)

0.0001

Amikacin

18 (69.23)

29 (14.43)

0.0001

Tobramycin

16 (61.54)

42 (20.9)

0.0001

Tetracycline

19 (73.08)

62 (30.85)

0.0001

Cotrimoxazole

20 (76.92)

59 (29.35)

0.0001

Ciprofloxacin

13 (50)

39 (19.4)

0.0001

Lomefloxacin*

12 (46.15)

34 (16.91)

0.0014

Nitrofurantoin*

1 (3.85)

1 (0.5)

0.2164

Gatifloxacin**

9 (34.62)

34 (16.92)

0.0579

Norfloxacin*

10 (38.46)

41 (20.4)

0.0469

*Tested for urinary isolates only. **Tested for both wound infections and urinary tract infections.

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Community Medicine ESBL-positive isolates and 35 (23.81%) non-ESBL isolates. This difference was highly significant (p < 0.01). On the other hand, AmpC β-lactamase-producing isolates were resistant to more antimicrobial agents than non-AmpC-producing isolates. Multidrug resistance was seen in 18/26 (69.23%) AmpC-positive isolates and 39/201(19.4%) non-AmpC isolates. This difference was highly significant (p < 0.01). Discussion ESBL-producing gram-negative bacteria are emerging worldwide, challenging the clinicians, public health professionals and hospital infection-control teams.12 ESBLs are the enzymes produced by gramnegative bacilli that have the potential to hydrolyze β-lactam antibiotics containing an oxyimino group (3GCs and aztreonam) and are inhibited by β-lactamase inhibitors such as clavulanic acid, sulbactam and tazobactam. However, cephamycins (e.g., cefoxitin) or carbapenems (e.g., imipenem, meropenem and ertapenem) are not affected by these enzymes.2 Like ESBLs, AmpC β-lactamases, a group of β-lactamases, are capable of hydrolyzing penicillins, cephalosporins (apart from zwitterionic cephalosporins) and monobactams. In addition, it hydrolyzes cephamycins and is not inhibited by commercially available β-lactamase inhibitors. Further, AmpC β-lactamases are associated with multiple antimicrobial resistance, limiting the therapeutic regimens.5,6 Furthermore, the incidence of ESBL and AmpC β-lactamase-producing strains among gram-negative bacilli isolates has considerably increased resulting in the limitation of therapeutic alternatives.8,9 In India, the prevalence of ESBL and AmpC β-lactamase producers vary among various hospitals and even between various sites of infections such as UTIs and wound infections. However, most of the hospitals in India are lacking accessibility to prevailing antimicrobial susceptibility patterns. This may circuitously result in the inappropriate prescription of antibiotics for empirical treatments.11,16-19 In view of these issues, the present study was designed to assess the current levels of resistance to antibiotics that are commonly used in our hospital and also to review the prevalence of ESBL and AmpC β-lactamase production among gram-negative bacterial isolates obtained from wound infections and UTIs. In the current study, the incidence of ESBL-producing organisms was found to be 72.41%. However, this incidence rate is much lower than the previous investigations carried out in other regions of the country.25-27 This reduced ESBL production among

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Indian Journal of Clinical Practice, Vol. 24, No. 11, April 2014

the gram-negative isolates could be attributed to the rational use of extended-spectrum cephalosporins and appropriate infection-control measures adopted in our hospital. However, the rate of AmpC β-lactamases (21.76%) production was relatively higher than that of Singhal et al (8%) and Hemalatha et al (9.2%) but was lower than the various documented figures in India.9,28-31 Interestingly, we have also observed the co-existence of ESBL and AmpC production among 6.15% E. coli and 5.53% of Klebsiella spp. These co-existent phenotypes could be due to the transfer of plasmids (encoding both AmpC and ESBL enzyme-producing genes) between members of the family Enterobacteriaceae.5,6 Various phenotypic and genotypic tests have been proposed to detect ESBL and AmpC production. However, phenotypic methods are less expensive, easy to perform and to interpret. The phenotypic methods include screening and confirmatory tests.21 In the current study, among the 3GCs, ceftazidime demonstrated resistance to all the phenotypically confirmed ESBL producers, indicating the potential of ceftazidime to detect ESBL production more effectively than other 3GCs. This data was in consistence with previous reports as well.32,33 However, among the phenotypic ESBL detection methods, the DDST demonstrated 100% concordance with phenotypic combined confirmatory disk test for ESBL detection and this data was comparable with Tsering et al.33 But among the AmpC β-lactamase producers, cefoxitin resistance was found to be a good indicator (detected 96.15% cases) as reported by previous investigators.34,35 Multidrug-resistant strains of bacteria possess resistance to two or more antimicrobials.36 Multidrugresistant strains are expected to be more common among organisms harboring genes for ESBL and AmpC β-lactamases.5 This study also reveals that the incidence of multidrug-resistant strains is significantly (p < 0.05) higher in ESBL and AmpC β-lactamase producers than non-ESBL and non-AmpC producers. It is evident from Tables 3 and 4 that most of the ESBLproducing strains were resistant to 3GC and 4GC. In addition, it was observed that the resistance to amikacin (22.5% and 69.23%), ciprofloxacin (53.75% and 50%), gatifloxacin (47.5% and 34.62%) and cotrimoxazole (77.7% and 76.92%) among ESBL and AmpC producers, respectively (Tables 3 and 4). This increased incidence of multidrug resistance is attributed to the plasmidmediated drug resistance, which is often acquired by transfer of genetic information from one organism to another. Such transferable plasmid also codes for resistance to other antimicrobial agents as well.

Community Medicine Therefore, multidrug resistance is expected to be more common in ESBL-producing organisms.37 However, all the ESBL and AmpC-producing isolates were sensitive to imipenem, indicating the potential of continued efficacy of carbapenems as the first-line agents for treatment of organisms producing ESBL and AmpC β-lactamases.

10.

11.

conclusion In conclusion, 72.41% and 21.76% of ESBL and AmpC producers were detected, respectively in our hospital. It was also observed that the DDSTs and CDSTs were equally effective for ESBL detection. Further, AmpC disk test is simple, easy to perform and interpret, requiring less expertise for the rapid detection of AmpC isolates. In addition, imipenem was found to be the most sensitive antibiotic for treatment of ESBL and AmpC β-lactamases- producing gram-negative isolates.

12.

13.

14.

References 1. Bradford PA. Extended-spectrum beta-lactamases in the 21st century: characterization, epidemiology, and detection of this important resistance threat. Clin Microbiol Rev 2001;14(4):933-51, table of contents. 2. Philippon A, Labia R, Jacoby G. Extended-spectrum beta-lactamases. Antimicrob Agents Chemother 1989;33(8):1131-6.

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3. Al-Jasser AM. Extended-spectrum beta-lactamases (ESBLs): A global problem. Kuwait Med J 2006;38(3): 171-85. 4. Stürenburg E, Mack D. Extended-spectrum betalactamases: implications for the clinical microbiology laboratory, therapy, and infection control. J Infect 2003;47(4):273-95. 5. Bradford PA, Urban C, Mariano N, Projan SJ, Rahal JJ, Bush K. Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmidmediated AmpC beta-lactamase, and the foss of an outer membrane protein. Antimicrob Agents Chemother 1997;41(3):563-9. 6. Rodríguez-Martínez JM, Pascual A, García I, MartínezMartínez L. Detection of the plasmid-mediated quinolone resistance determinant qnr among clinical isolates of Klebsiella pneumoniae producing AmpC-type betalactamase. J Antimicrob Chemother 2003;52(4):703-6.

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AmpC beta lactamase producers among Escherichia coli isolates in a tertiary care hospital in Jaipur. Indian J Pathol Microbiol 2008;51(3):367-9. Jain A, Mondal R. Prevalence & antimicrobial resistance pattern of extended spectrum beta-lactamase producing Klebsiella spp isolated from cases of neonatal septicaemia. Indian J Med Res 2007;125(1):89-94. Datta P, Thakur A, Mishra B, Gupta V. Prevalence of clinical strains resistant to various beta-lactams in a tertiary care hospital in India. Jpn J Infect Dis 2004;57(4):146-9. Goossens H, Grabein B. Prevalence and antimicrobial susceptibility data for extended-spectrum beta-lactamaseand AmpC-producing Enterobacteriaceae from the MYSTIC Program in Europe and the United States (19972004). Diagn Microbiol Infect Dis 2005;53(4):257-64. Babini GS, Livermore DM. Antimicrobial resistance amongst Klebsiella spp. collected from intensive care units in Southern and Western Europe in 1997-1998. J Antimicrob Chemother 2000;45(2):183-9. Hanberger H, Garcia-Rodriguez JA, Gobernado M, Goossens H, Nilsson LE, Struelens MJ. Antibiotic susceptibility among aerobic gram-negative bacilli in intensive care units in 5 European countries. French and Portuguese ICU Study Groups. JAMA 1999;281(1):67-71. Günseren F, Mamikoğlu L, Oztürk S, Yücesoy M, Biberoğlu K, Yuluğ N, et al. A surveillance study of antimicrobial resistance of gram-negative bacteria isolated from intensive care units in eight hospitals in Turkey. J Antimicrob Chemother 1999;43(3):373-8. Babypadmini S, Appalaraju B. Extended spectrum betalactamases in urinary isolates of Escherichia coli and Klebsiella pneumoniae - prevalence and susceptibility pattern in a tertiary care hospital. Indian J Med Microbiol 200;22(3):172-4. Tankhiwale SS, Jalgaonkar SV, Ahamad S, Hassani U. Evaluation of extended spectrum beta lactamase in urinary isolates. Indian J Med Res 2004;120(6):553-6. Mohanty S, Singhal R, Sood S, Dhawan B, Das BK, Kapil A. Comparative in vitro activity of beta-lactam/betalactamase inhibitor combinations against gram negative bacteria. Indian J Med Res 2005;122(5):425-8. Akram M, Shahid M, Khan AU. Etiology and antibiotic resistance patterns of community-acquired urinary tract infections in J N M C Hospital Aligarh, India. Ann Clin Microbiol Antimicrob 2007;6:4. Winn WC, Allen SD, Janda WM, Koneman EW, Procop G, Schreckenberger PC, et al. Introduction to microbiology Part II: Guidelines for the Collection, Transport, Processing, Analysis and Reporting of Cultures from Specific Specimen Sources. In: Koneman’s Color Atlas and Textbook of Diagnostic Microbiology. 6th edition, Lippincott William & Wilkins: Philadelphia 2006:p.67-105. Wayne PA. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twentieth Informational Supplement M100S20; 2010.

8. Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev 1998;11(4): 589-603.

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9. Sinha P, Sharma R, Rishi S, Sharma R, Sood S, Pathak D. Prevalence of extended spectrum beta lactamase and

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Community Medicine Testing; Thirteenth Informational Supplement. NCCLS. NCCLS documents M100-S13 Wayne, Pennsylvania, USA, National Committee for Clinical Laboratory Standards. NCCLS documents; 2003. 23. Black JA, Moland ES, Thomson KS. AmpC disk test for detection of plasmid-mediated AmpC beta-lactamases in Enterobacteriaceae lacking chromosomal AmpC betalactamases. J Clin Microbiol 2005;43(7):3110-3. 24. Jarlier V, Nicolas MH, Fournier G, Philippon A. Extended broad-spectrum beta-lactamases conferring transferable resistance to newer beta-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. Rev Infect Dis 1988;10(4):867-78. 25. Metri Basavaraj C, Jyothi P Peerapur, Basavaraj V. The prevalence of ESBL among Enterobacteriaceae in a tertiary care hospital of North Karnataka, India. J Clin Diag Res 2011; 5(3):470-5. 26. Chaudhuri BN, Rodrigues C, Balaji V, Iyer R, Sekar U, Wattal C, et al. Incidence of ESBL producers amongst Gram-negative bacilli isolated from intra-abdominal infections across India (based on SMART study, 2007 data). J Assoc Physicians India 2011;59:287-92. 27. Das A, Ray P, Garg R, et al. Extended spectrum beta lactamase production in gram-negative isolates from cases of septicaemia. In: Proceedings of Silver Jubilee Conference. All India Institutes of Medical Sciences: New Delhi 200:p.21-5. 28. Singhal S, Mathur T, Khan S, Upadhyay DJ, Chugh S, Gaind R, et al. Evaluation of methods for AmpC betalactamase in gram negative clinical isolates from tertiary care hospitals. Indian J Med Microbiol 2005;23(2):120-4. 29. Hemalatha V, Padma M, Sekar U, Vinodh TM, Arunkumar AS. Detection of Amp C beta lactamases production in Escherichia coli & Klebsiella by an inhibitor based method. Indian J Med Res 2007;126(3):220-3.

30. Manchanda V, Singh NP. Occurrence and detection of AmpC beta-lactamases among Gram-negative clinical isolates using a modified three-dimensional test at Guru Tegh Bahadur Hospital, Delhi, India. J Antimicrob Chemother 2003;51(2):415-8. 31. Patel MH, Trivedi GR, Patel SM, Vegad MM. Antibiotic susceptibility pattern in urinary isolates of gram negative bacilli with special reference to AmpC β-lactamase in a tertiary care hospital. Urol Ann 2010;2(1):7-11. 32. Cormican MG, Marshall SA, Jones RN. Detection of extended-spectrum beta-lactamase (ESBL)-producing strains by the Etest ESBL screen. J Clin Microbiol 1996;34(8):1880-4. 33. Tsering DC, Das S, Adhiakari L, Pal R, Singh TS. Extended spectrum beta-lactamase detection in gram-negative bacilli of nosocomial origin. J Glob Infect Dis 200;1(2):87-92. 34. Yilmaz NO, Agus N, Bozcal E, Oner O, Uzel A. Detection of plasmid-mediated AmpC β-lactamase in Escherichia coli and Klebsiella pneumoniae. Indian J Med Microbiol 2013;31(1):53-9. 35. Bakthavatchalu S, Shakthivel U, Mishra T. Detection of ESBL among AmpC producing Enterobacteriaceae using inhibitor-based method. Pan Afr Med J 2013;14:28. 36. Nemeth J, Ledergerber B, Preiswerk B, Nobile A, Karrer S, Ruef C, et al. Multidrug-resistant bacteria in travellers hospitalized abroad: prevalence, characteristics, and influence on clinical outcome. J Hosp Infect 2012;82(4):254-9. 37. Yu Y, Zhou W, Chen Y, Ding Y, Ma Y. Epidemiological and antibiotic resistant study on extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Zhejiang Province. Chin Med J (Engl) 2002;115(10):1479-82.

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Free and Subsidized Treatment to Hemophilic Patients in Delhi’s Three Hospitals By the intervention of the Delhi High Court, now hemophilic BPL patients will get free and subsidized treatment for life, if they are not able to afford the cost of the treatment. Justice M.M. Singh of Delhi High Court disposed of the petition on April 1st 2014, filed on behalf of one patient suffering from hemophilia. On 26th March, 2014, this Court directed Government of NCT of Delhi to place on record the Scheme under which hemophilia patients were being given free treatment. The Delhi Government was also directed to explain as to why petitioner’s case did not fall within the parameters of the aforesaid Hemophilia Scheme. As per the submissions by the Principal Secretary, Health and Family Welfare, Government of NCT of Delhi “In pursuance of directions of the Hon’ble High Court and meetings held by the Committee, the following course of action has been decided upon in so far as Govt. of NCT of Delhi is concerned:” Facility to provide antihemophilic factor (AHF) for hemophilia patients shall be provided in three hospitals of this Government namely, Lok Nayak, DDU and GTB hospitals. Dr. Naresh Gupta, Professor of Medicine and Head, Clinical Hematology, MAMC will be the Coordinator/Nodal Officer. Medical Superintendents of Lok Nayak, DDU Hospitals will also designate a nodal officer for this purpose.

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ENT

Laryngeal Myxoma: Emergency Management BR Singh*, Arti Pandey†, Ankit M Thackral‡

Abstract A 65-year-old male presented with stridor and dysphonia in emergency clinic of Govt. CIMS Medical College, Bilaspur, Chhattisgarh. Indirect laryngoscopic examination revealed a polypoidal lesion in glottic chink. CT scan evaluation confirmed the findings of clinical examination. Patient was relived of symptoms after emergency tracheotomy followed by surgical removal of polypoidal lesion from right vocal cord by microlaryngeal surgery. Histopathological examination revealed myxoma. Clinical examination after 8 months showed significant improvement in hoarseness of voice with no evidence of recurrence of lesion.

Keywords: Myxoma, larynx, vocal cord, polyp

yxoma is a benign mesenchymal tissue tumor. The term ‘myxoma’ was first introduced by Virchow in 1871 for a tumor with a histology similar to the mucinous tissue of the umbilical cord.1 In 1948, Stout was redefined myxoma as a true mesenchymal neoplasm consisting of undifferentiated stellate cells in loose myxoid stroma that did not metastasize.2 The histological criteria for myxoma as true neoplasm that does not metastasize and exclude the presence of recognizable cellular component of other mesenchymal tissue specially chondroblasts, lipoblasts and rhabdomyoblasts. Occurrence of myxoma is most common in heart. In the head-neck region, most common locations are facial bones specially mandible and maxilla (3-6%).3 Laryngeal myxomas are extremely rare. According to my review, in English literature about 17 cases of laryngeal myxoma are reported, out of that three cases are females.

mass was seen in the glottic region, which was completely obstructing the glottic chink. On computed tomography (CT) scan, neck a low-density lesion about 17 × 12 mm in size was seen completely occupying the chink (Fig. 1). Emergency tracheotomy was done followed by direct laryngoscopy and microlaryngeal

CASE REPORT A 65-year-old male presented to casualty with 4 months history of change in voice and dyspnea since 6 days. It was sudden in onset, gradually progressive. He had severe stridor. Previously, he visited two private hospitals and all the basic investigations within normal limits. He does not have any history of diabetes, hypertension asthma, alcoholism and smoking. On indirect laryngeal examination, a large polypoidal

*Assistant Professor †Associate Professor ‡Senior Resident Dept. of ENT Chhattisgarh Institute of Medical Sciences, Bilaspur, Chhattisgarh

Figure 1. CT scan of neck.

Figure 2. Postoperative specimen.

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Figure 4. Follow-up after 8 months showing significant improvement in hoarseness of voice with no evidence of recurrence of lesion.

Figure 3. Histopathological examination revealed portions of squamous mucosa with an ulcerated mesenchymal neoplasm composed of bland looking elongated stellate-shaped cells set against abundant myxoid background with scattered congested blood vessels.

surgery was performed under general anesthesia and the findings were confirmed as a double-pink polypoidal mass arising from the right vocal cord, pedunculated with a short and broad-base attachment extending up to the posterior commissure (Fig. 2). The mass was excised with healthy margins and specimen was sent for histopathological examination. Microscopic examination revealed portions of squamous

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mucosa with an ulcerated mesenchymal neoplasm composed of bland looking elongated stellate-shaped cells set against abundant myxoid background with scattered congested blood vessels. Focal scattered microabscesses were also seen (Fig. 3). No increased mitosis, necrosis or nuclear pleomorphism seen. Followup after 8 months showed significant improvement in hoarseness of voice with no evidence of recurrence of lesion (Fig. 4). Discussion A myxoma is of benign mesenchymal origin, mostly occurs in subcutaneous soft tissue, intramuscular or cardiac chamber.4 Most common benign tumors of the larynx are vocal polyp, vocal nodules, Reinkeâ&#x20AC;&#x2122;s edema, vocal cyst and papilloma. Myxoma can occur in all age groups from birth to old age, although it is most commonly present in third or fourth decade of life and etiology is not known.1,5 In the head-neck region, myxoma involves in maxilla and mandible (3-6%) as odontogenic origin known as fibromyxoma or myxofibroma. It most common site of involvement is vocal cord, aryepiglottic

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ENT fold and epiglottis within the larynx. Clinically, laryngeal myxoma presents as hoarseness followed by dyspnea, dysphonia and dysphagia depending on the size and site of the tumor. Myxoma may infiltrate the surrounding tissues, so it has a high chance and predisposition to local recurrence because of this behavior. During surgery myxoma is excised with normal tissue to prevent recurrence.6 It can always be confused with vocal polyp, so a high index of suspicion is needed to detect myxoma. The differential diagnosis of laryngeal myxoma is the myxoid degeneration of laryngeal polyp that histologically has scanty vascularity, no fibrin, no hemorrhage as opposed to a plentiful vascularity and hemorrhage with hemosiderin laden macrophages in the myxoid changes of polyp.7 Differential diagnosis of myxoma also includes liposarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, neurofibroma and angiomyxoma.6 Treatment of choice for laryngeal myxoma is complete excision with healthy margins. Conclusion In conclusion, laryngeal myxoma is a rare benign mesenchymal tumor and can be easily confused with laryngeal polyp and should be included in differential diagnosis of laryngeal masses.

References 1. Garca MF, Cankaya H, Turan M, Kosem M. Laryngeal myxoma resembling a laryngeal polyp: Case Report. Van Tip Dergigi 2013;20(2):100-2. 2. Ritchie A, Youngerman J, Fantasia JE, Kahn LB, Cocker RS. Laryngeal myxoma: A case report and review of the literature. Head Neck Pathol 2013 Aug 22. [Epub ahead of print] 3. Young-Soo S, Si-Hyong J, Kyueng-Whan M, Woong N, SeMin J, Young-Jin J, et al. Myxoma of the larynx presenting as a nodule. Korean J Pathol 2008;42(5):306-7. 4. Ali S, Macdougall G, Wallace W. Myxoma-rare laryngeal presentation. Int J Otorhinolaryngol 2008;11(1): 5. Baruah P, Jha DN, Karak AK, Kumar R. Laryngeal myxoma. J Laryngol Otol 2001;115(3):231-2. 6. Kanlıada D, Başaran B, Mete Ö, Değer K. Laryngeal myxoma mimicking intracordal cyst. Türk Otolarengoloji Arflivi 2012;50(2):26-7. 7. Kim KM, Kim SC, Jeong HJ, Kie JH. Myxoma: lifethreatening benign nonepithelial tumor of the larynx. Yonsei Med J 1997;38(3):187-9.

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BMC’s Trauma Centers Receive Reverification for 3 Years The trauma center at Boston Medical Center (BMC) has been re-verified for 3 years as a Level I Adult Trauma Center and Level II Pediatric Trauma Center by the Verification Review Committee (VRC), an ad hoc committee of the Committee on Trauma (COT) of the American College of Surgeons (ACS). BMC is the busiest provider of trauma and emergency services in New England, with more than 1,30,000 emergency visits and approximately 2,000 trauma admissions per year on the same campus. Staffed with seven full-time, dedicated trauma and critical care attending surgeons, the BMC trauma center is the longest continuously verified Level I trauma center in New England. Trauma centers must meet the required established in the Resources for Optimal Care of the Injured Patient manual. The ACS Committee on Trauma’s verification program does not designate trauma centers. The Massachusetts Department of Public Health is the agency that designates all trauma centers and has made ACS verification (along with other criteria) a requirement. The US Food and Drug Administration (FDA) has recently approved a hearing aid, made by the Danish company William Demant, that reduces tinnitus. The device is especially targeted at the U.S. Veterans Administration, a government-led program for US military veterans. There is a big market for such a hearing aid in the US since it was estimated that in 2011; 8,40,865 members of the VA had tinnitus.

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Profound Sensorineural Hearing Loss with Overlay of Middle Ear Pathology-Diagnostic Implications Indranil Chatterjee*, Neha Taneja*, AK Sinha*, Suman Kumar*

Abstract This study aimed to demonstrate the diagnosis of profound mixed hearing loss which is inappropriate to be studied vigorously to prove that at the level of profound degree of severity there is a little contribution of conductive pathology. Two groups of 15 subjects each in the age range of 18-25 years with mean age of 21 years were included. Group I consisted of pure sensorineural hearing loss of profound degree and Group II was made up of pure sensorineural hearing loss of profound degree who later reported with middle ear disorder. Pure tone measurements were conducted on all the subjects following standard procedures. Conductive hearing loss was induced with insertion of the insert ear plugs/ear moulds without sound bore for subjects in Group I and pure tone threshold measurements were repeated. Air-conduction and bone-conduction thresholds were compared for subjects in Group II prior and later to check for any middle ear pathology. Results showed that when Group I was induced with conductive hearing loss, the pure tone average did not change and for Group II, there was no change in air-conduction thresholds by later developed outer ear/middle ear pathologies. Diagnosis of profound sensorineural hearing loss with the overlay of middle ear pathology will bring insights into physiology of hearing and highlight the important issues of management of middle ear pathology, not for the purpose of improvement of absolute hearing thresholds but for the case of wearing of amplification device restricting the further growth of pathology, etc.

Keywords: Profound sensorineural hearing loss, profound mixed hearing loss, conductive hearing loss, pure tone measurement, middle ear pathology

ombination of conductive hearing loss and sensorineural hearing loss in the same ear is known as mixed hearing loss. The hearing deficiency may have started originally as conductive hearing loss and later developed a superimposed sensorineural hearing loss resulting in mixed hearing loss or vice versa. In some cases, onset of conductive and sensorineural hearing loss may be simultaneous.1 The basic audiologic assessment is used to assess or monitor the status of the peripheral auditory system (the outer, middle and inner ear). The case history, otoscopic evaluation and, if necessary, cerumen management precede assessment.2 Bone-conduction threshold measurement is an integral part of a basic audiologic evaluation.3-5 Some clinicians use immittance measures

*Ali

Yavar Jung National Institute for the Hearing Handicapped, Eastern Regional Centre, Bon Hooghly, Kolkata Address for correspondence Dr Indranil Chatterjee Ali Yavar Jung National Institute for the Hearing Handicapped, Eastern Regional Centre, BT Road, Bon Hooghly, Kolkata - 700 090 E-mail: inchant@rediffmail.com

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as part of initial audiometric evaluation and in some instances immittance measures are used to replace puretone bone-conduction testing.6 However, immittance measures should be viewed as a strong complement to, but not a replacement for, bone-conduction threshold measures.7 The main function of the middle ear system is to match the impedance mismatch of the two media sound has to travel in order to reach cochlea, that is, air and the cochlear fluid. The transformer action of the middle ear compensates approximately 25-30 dB of mismatches. The path of sound waves at lower and moderate levels through air-conduction is from the external ear meatus, which vibrates the tympanic membrane and the these vibrations are conducted to the cochlea through the vibration of the ossicles. Air-conduction sound crossover by means of the bone-conduction mechanism at high intensity.8,9 As sound travels from the air into the skull, 40 dB is attenuated.10 Pseudoresponses were reported through the bone vibrator at the lower frequencies in severe to profound sensorineural hearing loss cases. At higher intensities, the bone vibrator produces mechanical vibration, which

ENT is felt by the patient rather than heard and is called vibrotactile response, which are mistaken as the air bone gap.11,12 One test that became popular to know the pseudoresponse was to hold the bone vibrator to damp the vibration. If, on holding the bone vibrator, case did not respond to the bone conducted signal, it confirmed the vibrotactile responses. However, with the advancement in the diagnostic audiology, this method is no longer in use.13 Impedance audiometry findings and speech discrimination scores have enhanced our skills for diagnosis. With severe air-conduction loss and impedance audiometry results indicating middle ear involvement, the diagnosis of mixed hearing loss is made. In many of the clinical set ups, on the basis of cases with profound degree of deafness with impedance finding, case history or visual inspection of tympanic membrane suggesting middle ear involvement, diagnosis of profound mixed hearing loss is made. ‘MP’ has been provided as the code for referring to the profound mixed hearing loss. Profound mixed hearing loss is also mentioned in literature.1 Aim This study was undertaken to demonstrate that the diagnosis of profound mixed hearing loss in patients with profound sensorineural hearing loss with overlay of middle ear pathology, is not appropriate, both theoretically and practically and may cause confusion for the audiologists as well as otolaryngologists to choose the line of treatment and counseling for the patient especially when the major objective of the surgical intervention is restoration of hearing. Method

Subjects Group I consisted of 15 subjects with pure sensorineural hearing loss of profound degree in the age range of 18-25 years with mean age of 21 years. Group II was made up of 15 subjects who were known patients of pure sensorineural hearing loss of profound degree and later reported with middle ear disorders in the age range of 18-25 years with mean age of 21 years.

Test and Procedure Puretone threshold measurements were conducted on all the cases following standard procedures. Conductive hearing loss was induced with the insertion of the insert ear plugs/ear moulds without sound bore

for the subjects in Group I and puretone threshold measurements were repeated. Air-conduction and bone conduction thresholds were compared for subjects in Group II prior and later to having middle ear pathology. Results The puretone threshold of subjects belonging to Group I with profound degree of sensorineural hearing loss were measured. Impedance audiometry revealed normal mobility of the ear drum and middle ear pressure. Otological examination revealed no abnormality of the eardrum. The average of puretone thresholds for the airconduction and the bone-conduction for right ear of subjects belonging to Group I is shown in Table 1. For the purpose of calculating average, the “no response’ was considered as the upper limit of the audiometer. Conductive hearing loss was induced by means of inserting insert ear plug in the external auditory meatus/ear moulds without sound bore and puretone threshold were obtained in the right ear for all subjects of Group I. The averages of improvised puretone thresholds for the subjects are shown in Table 2. Table 1. Average of Hearing Threshold of 15 Subjects of Group I with Profound Sensorineural Hearing Loss Puretone threshold

250 Hz

500 Hz

1000 Hz

2000 Hz

4000 Hz

8000 Hz

85.6

99.3

109

110.6

113

99.3

33.6

53.6

68.3

69.3

AC = Air-conduction; DC = Bone-conduction.

Table 2. Average of Improvised (Induced Conductive Hearing Loss) Hearing Threshold of 15 Subjects of Group I with Profound Sensorineural Hearing Loss Improvised puretone threshold

250 Hz

500 Hz

1000 Hz

2000 Hz

4000 Hz

8000 Hz

87.3

101

107.4

112

113.6

100

68.6

Table 3. Average of Puretone Hearing Threshold of 15 Subjects of Group II with Profound Sensorineural Hearing Loss Puretone threshold

250 Hz

500 Hz

1000 2000 Hz Hz

4000 Hz

8000 Hz

92.3

100.6 109.3 107.3

115.6

100 (NR)

40.3

56.6

70 (NR)

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ENT Table 4. Average of Puretone Hearing Threshold of 15 Subjects of Group II with Profound Sensorineural Hearing Loss with Middle Ear Pathology Puretone threshold

250 Hz

500 Hz

1000 Hz

2000 Hz

4000 Hz

8000 Hz

93.3

104

111.3

107

116.3

100 (NR)

40.3

56.6

70 (NR)

As per the case records, the average puretone thresholds for the 15 subjects belonging to Group II are shown in Table 3. Impedance audiometry results indicated normal mobility of the ear drum and middle ear pressure. All the subjects had diagnosis of profound sensorineural hearing loss. At a later point of time, the patients of Group II reported with complaints of pain, itching sensation, fullness of the ear or having ear discharge. The repeat impedance finding in each case was either B type tympanogram or the variation of A type tympanogram with changed middle ear pressures. All the cases then were diagnosed as profound mixed hearing loss as practiced in most of the clinics across the world. The averages of puretone threshold are shown in Table 4. Otolaryngological examinations of these patients were in confirmation with the audiological examination.

The puretone average of Group I, when induced with conductive hearing loss, did not change (observable from 106.3 dBHL to 106.8 dBHL only). Bone-conduction thresholds also had no effect with the induction of the conductive hearing loss in subjects of Group I as can be seen in Tables l and 2. No change in the air-conduction thresholds indicated that the transmission of the sound was through the head instead of the outer or middle ear to the inner ear. Even though the external ear was blocked for the subjects of Group I, the sound transmission at higher intensity was not affected. In other words, the conductive pathology induced in the external ear failed to cause any significant amount of conductive hearing loss; therefore, profound sensorineural hearing loss remains as it is even when the ear canal was blocked. As shown in Figure 2, there was no change of air-conduction thresholds of the subjects of Group II who had profound sensorineural hearing loss and later developed outer/middle ear pathologies such as impact wax, middle ear infections and perforation of the tympanic membrane. The clinical data also supports the results of the experiment with subjects of Group I, but all the cases in Group II had revised diagnosis of profound mixed hearing loss. As shown in the experiment with the subjects of Group I, the blocking of external auditory meatus failed to induce any conductive hearing loss, leading to

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ACT-Conventional ACT-Improvised 112 113 113.6 120 101 109107.4 110.6 99.3100 99.3 100 85.687.3 80 60 40 20 0 250Hz 500Hz 1KHz 2KHz 4KHz 8KHz

Figure 1 . Comparison of air-conduction thresholds of Group I with and without induced middle ear pathology.

ACT-PSNHL

dBHL

Conductive hearing loss is classically defined as the hearing loss as a result of pathology in the outer and/ or middle ear. Clinically conductive pathology of outer or middle ear causes reduction of air-conduction thresholds in the low frequencies as the mass in the middle ear is increased and in very few cases conductive hearing can create high-frequency hearing loss known as high-tone conductive hearing loss. Conductive hearing loss is easy to identify from the puretone audiogram, impedance audiometry as well as speech audiometry. Pure conductive hearing loss may vary from mild-tosevere degree and maximum conductive hearing loss is about 70 dB.1 This is because the transmission of the sound through the outer ear and the middle ear no longer exists as the intensity of the sound is high and the transmission is through the skull. In profound degree of hearing loss, puretone average exceeds 90 dBHL. In subjects with pure sensorineural hearing loss of profound degree, when the conductive loss was simulated by means of plugging the external auditory meatus with the insert ear plugs or the ear moulds without the sound bore, there was no change in the air-conduction thresholds as shown in Figure 1.

dBHL

Discussion

ACT-MEP

111.3 107 115.6 116.3 120 104 109.3 93.3 107.3 100 100 100.6 100 92.3 80 60 40 20 0 250Hz 500Hz 1KHz 2KHz 4KHz 8KHz

Figure 2. Comparison of air-conduction thresholds of Group II with and without middle ear pathology.

ENT no demonstrable hearing loss; therefore, it is suggested to retain the diagnosis as profound sensorineural hearing loss and add to it the existence of blocked external auditory meatus. When the air-conduction thresholds exceed 90 dBHL, the sound is transmitted through the head instead of outer and middle ear route or in other words the conductive (outer and middle ear) mechanism is bypassed, making it difficult to assess impact of overlay of middle ear pathology on hearing thresholds of puretone in cases having profound degree of hearing impairment. The unaltered air- and bone-conducted thresholds for Group I and II clearly establish the relationship that at high intensities, sounds bypass outer and middle ear to reach the cochlea. Therefore, in cases with profound degree of hearing loss with overlay of middle ear pathology, the revised diagnosis of â&#x20AC;&#x2DC;profound sensorineural hearing loss with overlay of middle ear pathologyâ&#x20AC;&#x2122; is more appropriate than profound mixed hearing loss as in such cases conductive hearing loss cannot be demonstrated. Profound sensorineural hearing loss with overlay of middle ear pathology will bring insight into the physiology of hearing and highlight the important issue of management of middle ear pathology not for the purpose of improvement of the absolute hearing threshold but for ease of wearing of amplification device, restricting the further growth of the middle ear pathology and for counseling for aural hygiene. Diagnosis of profound sensorineural hearing loss with overlay of middle ear pathology will also be useful for the audiologist and the otolaryngologists for choosing and counseling the line of treatment for the cases. Unwarranted surgical intervention in profound sensorineural hearing loss with middle ear pathology may be avoided, if the main objective of the surgery is restoration of hearing. Conclusion When the thresholds of hearing exceed profound degree due to the sensorineural hearing loss with overlay of middle ear pathology, the diagnosis of hearing loss should be made in more explicit way rather than as profound mixed hearing loss as the conduction of sound into the cochlea is through the skull bypassing the outer and middle ear. Measuring the hearing loss because of conductive overlay in case with profound sensorineural hearing loss is, in fact, very difficult. Therefore, it is suggested that the diagnosis of profound sensorineural hearing loss should be retained and existence of middle ear pathology should be added, instead of regular practice of diagnosing as profound mixed hearing loss.

Diagnosis of profound sensorineural hearing loss with overlay of middle ear pathology will bring insight into the physiology of hearing and highlight the important issue of management of middle ear pathology not for the purpose of improvement of the absolute hearing threshold but for ease of wearing of amplification device, restricting the further growth of the pathology and counseling for aural hygiene. Diagnosis of profound sensorineural hearing loss with middle ear pathology will also be useful for the audiologist and the otolaryngologists for choosing and counseling the line of treatment for the cases. Unwarranted surgical intervention in profound sensorineural hearing loss with middle ear pathology may be avoided if the main objective of the surgery is restoration of hearing. References 1. Sataloff RT, Sataloff J. Occupational hearing loss. 2nd edition. Dekker M (Ed.), New York; 1993. 2. American Speech-language-Hearing Association. Preferred practice patterns for the professions of speech-language pathology and audiology. ASHA 1993;35(3 Suppl):1-101. 3. Tonndorf J. Bone conduction. Studies in experimental animals. Acta Otolaryngol 1966:Suppl 213:1+. 4. Tonndorf J. A new concept of bone conduction. Arch Otolaryngol 1968;87(6):595-600. 5. Tonndorf J. Bone conduction. In: Foundation of Modern Auditory Theory. Tobias JV (Ed.), Academic Press: New York 1972:p.84-99. 6. Hall JW, Ghoraveb BY. Diagnosis of middle ear pathology and evaluation of conductive hearing loss. In: Diagnostic Audiology. Jacobson JT, Northern JL (Eds.), Pro-Edn: Austin, TX 1991:p.l61-98. 7. Robinette MS, Cevette MJ. Case History. Intergrating Audiometric Results, and Clinical Decisions Analysis. In: Handbook of Clinical Audiology. Katz J (Eds.), Williams and Williams, 1994:p.142-56. 8. Sparrevohrt UR. Some audiometric investigations of monaurally deaf persons. Acta Otolaryngol 1946;34: 1-10. 9. Zwislocki J. Acoustic attenuation between the ears. J Acoust Soc Am 1953;25:752-9. 10. Chaiklin JB. Interaural attenuation and cross-hearing in air conduction audiometry. J Audit Res 1967;7,:413-24. 11. Martin FN, Wittich WW. A comparison of forehead and mastoid tactile bone conduction thresholds. Eye Ear Nose Throat Mon 1966;45(12):72 passim. 12. Nober EH. Cutile air and bone conduction thresholds of the deaf. Except Child 1970;36(8):571-9. 13. Nober FN. The invalid low frequency air-bone gap. Maico Audiological Library Series 1967:p7-8.

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Hematology

Unusual Presentation of Angioimmunoblastic T-cell Lymphoma as a Solitary Lymph Node N Ashalatha*, BN Kumarguru†, BS Dayananda‡, AH Nagarajappa#

Abstract Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphoma (PTCL) characterized by systemic disease. It is a rare subtype of non-Hodgkin’s lymphomas. However, it forms a major subset of PTCL. Lymph node is the primary site of disease and virtually all patients present with generalized lymphadenopathy. Case report: A 42-year-old male presented with fever of short duration and a solitary axillary lymph node swelling on the right side. Systemic examination revealed moderate ascites and hepatosplenomegaly. Hematological investigations showed pancytopenia and abnormal liver function. Axillary lymph node showed histological features suggesting AITL and was confirmed by a panel of immunohistochemistry (IHC). Conclusion: AITL presenting as solitary axillary lymph node enlargement is unusual. Such atypical presentation mandates careful clinical and laboratory evaluation. IHC is an effective ancillary tool for confirmation of diagnosis of this distinct clinicopathological entity.

Keywords: Angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, non-Hodgkin’s lymphoma, solitary axillary lymph node enlargement, pancytopenia, immunohistochemistry

ngioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma (PTCL) characterized by systemic disease, a polymorphous infiltrate involving lymph nodes with a prominent proliferation of endothelial venules and follicular dendritic cells (FDCs). Spleen, liver, skin and bone marrow are also frequently involved.1 Though, it is one of the more common specific subtypes of PTCL, accounting for approximately 20% of cases, it constitutes only 1-2% of all non-Hodgkin’s lymphoma.1,2

It occurs in the middle-aged and elderly with an equal incidence in males and females.1 Originally described in 1974, as ‘immunoblastic lymphadenopathy’ by Rappaport and Lukes, AITL is recognized in the current World Health Organization (WHO) classification

*Assistant Professor †Tutor ‡Professor #Professor and Head Dept. of Pathology Bangalore Medical College and Research Institute, Bangalore, Karnataka Address for correspondence Dr N Ashalatha Assistant Professor Dept. of Pathology Victoria Hospital, Bangalore Medical College and Research Institute Bangalore - 560 002, Karnataka E-mail: drbnkg007@hotmail.com

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as a PTCL with distinct clinicopathologic features.3 The postulated normal counterpart is CD4+ follicular helper T-cell (TFH).1 This subset of T-cell is located at the boundary between the mantle zone and germinal center light zone and is supposed to provide help to germinal center B-cells during their terminal differentiation.4 The patients present with generalized lymphadenopathy (up to 90%), hepatosplenomegaly (50-79%), cutaneous rash (50%), hypergammaglobulinemia (50%), pleural effusion (37%) and autoimmune phenomena (20%).5 The laboratory findings include circulating immune complexes, cold agglutinins with hemolytic anemia, positive rheumatoid factor and antismooth muscle antibodies. Epstein-Barr virus (EBV)-positive cells are nearly always present. Characteristically, the neoplastic cells show phenotype of normal TFH expressing CD10, CXCL13 and PD1 in 60-100% of cases.1 Cytogenetic and molecular studies have consistently shown clonal chromosomal abnormalities and monoclonal or oligoclonal T-cell populations in most cases, which strongly supports a T-cell neoplasm.6 Patients with AITL have a poor prognosis with conventional treatment, with a median overall survival <3 years. Patients achieving a good clinical response seem to benefit from a consolidation with high-dose therapy and autologous stem cell transplantation.2

Hematology Case Report A 42-year-old male presented with fever of 4 days duration and easy fatigability. General physical examination revealed a solitary lymph node in the right axilla measuring 4 × 2.5 × 2 cm. No other lymph nodes were enlarged. Abdominal examination revealed moderate ascites, hepatomegaly and massive splenomegaly. Blood investigations were done. Hemoglobin was decreased (5.4 g/dL), leukocyte count was reduced (2,300 cells/mm3), platelet count was reduced (62,000/mm3). Peripheral smear also suggested pancytopenia. Coomb’s test was negative. Bone marrow examination did not reveal any pathological findings. Human immunodeficiency virus (HIV) was

negative and hepatitis B surface antigen (HBsAg) was nonreactive. Biochemical investigations showed increased levels of postprandial glucose (150 mg/dL), total proteins (11 g/dL), alkaline phosphatase (207 U/L) and lactate dehydrogenase (LDH) (693 U/L). Serum albumin was reduced (3.3 g/dL). Ultrasonography of abdomen showed moderate ascites mild hepatomegaly and massive splenomegaly. Considering these features the present case corresponds to Ann Arbor Stage III ES, International Prognostic Index (IPI) score of four and prognostic index for PTCL/unspecified (PIT) score of 2. The axillary node was excised and sent for histopathological examination. Grossly the lymph node measured 3.5 × 2.5 × 1.5 cm. Cut section showed

Figure 1. Photomicrograph of tissue section showing effacement of lymph node architecture (H&E, x40).

Figure 2. Photomicrograph of lymph node section showing post-capillary venules lined by plump endothelial cells (arrows) (H&E, x400).

Figure 3. Photomicrograph of lymph node section showing tumor cells having convoluted nuclear borders and prominent nucleoli and good number of mitotic figures (arrows) (H&E, x400).

Figure 4. Photomicrograph of lymph node section showing background of reactive lymphocytes, eosinophils, plasma cells and histiocytes (H&E, x400).

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Hematology

Figure 5. Photomicrograph of lymph node section showing diffuse immunopositivity for CD3 neoplastic cells (IHC, x400).

Figure 6. Photomicrograph of lymph node section showing diffuse immunopositivity for CD10 neoplastic cells (IHC, x200).

Figure 7. Photomicrograph of lymph node section showing scattered immunopositivity for CD30 neoplastic cells (IHC, x 400).

Figure 8. Photomicrograph of lymph node section showing CD20+ reactive residual B-cells (IHC, x200).

homogeneous grey-white appearance. Sections from the lymph node showed effacement of architecture and follicular depletion (Fig. 1). Prominent arborising postcapillary venules lined by plump endothelial cells were seen (Fig. 2). Clusters of tumor cells having vesicular nuclei and prominent nucleoli, showed vaguely convoluted borders, clear to pale cytoplasm and mitotic figures (Fig. 3). Mature lymphocytes, plasma cells, histiocytes and significant number of eosinophils were also seen in the background of patchy hyaline material (Fig. 4). Immunohistochemistry (IHC) was performed, which showed neoplastic cells as diffusely distributed CD3+ cells (Fig. 5) and CD10+ cells (Fig. 6). CD30+ cells were scattered and comparatively scant (Fig. 7). Residual reactive B lymphocytes were CD20+ (Fig. 8). These findings confirmed the histological diagnosis of AITL.

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Indian Journal of Clinical Practice, Vol. 24, No. 11, April 2014

Discussion AITL is a rare and complex lymphoproliferative disorder, clinically characterized by widespread lymphadenopathy, extranodal disease, immune-mediated hemolysis and polyclonal hypergammaglobulinemia.3 It represents a distinct clinicopathological entity among nodal PTCLs.4 AITL is a systemic disease involving lymph nodes, spleen and bone marrow.6 AITL was first described by Ree et al who reported progression of two such cases into typical AITL.6 It is an aggressive PTCL whose natural history is poorly understood.5 Mourad et al4 recorded the median age of 62 years while Cho et al7 recorded the median age of 58.5 years in their studies. AITL occurs in middle-aged and elderly with an equal incidence in males and females.1 Rodriguez-Justo et al5 and Attygalle et al6 observed

Hematology occurrence of AITL in middle-aged and elderly with male preponderance. Lymph node is the primary site of disease and virtually all patients present with generalized lymphadenopathy.1,3,5,6 Cho et al7 recorded generalized lymphadenopathy as commonest presentation (91%) in their study. In contrast, the middle-aged patient in the present case presented with solitary right axillary lymph node. Lymph node enlargement was accompanied by an episode of fever and easy fatigability. RodriguezJusto et al5 observed organomegaly (hepatomegaly or splenomegaly) in 33% of cases. Attygalle et al6 and Cho et al7 also observed hepatosplenomegaly in their studies. Mourad et al4 observed pleural effusion or ascities or edema in 16% of cases in their study. Even in the present case, the patient had hepatosplenomegaly, deranged liver function and ascities. Most of the cases present at an advanced stage (III-IV).2,4,5 Peripheral blood picture suggested pancytopenia. However, bone marrow did not show tumor infiltration and Coombâ&#x20AC;&#x2122;s test was negative. Thirty-three percent of cases had hemolytic autoimmune anemia in study conducted by Rodriguez-Justo et al.5 Mourad et al4 recorded anemia in 65% of cases and positive Coombâ&#x20AC;&#x2122;s test in 33% of cases. Rodriguez-Justo et al5 and Cho et al7 observed bone marrow involvement in 22% cases and 70% cases in their studies. Mourad et al4 observed bone marrow involvement in 38% of anemic patients. Serum lactate dehydrogenase (LDH) level was elevated in the present case. Similar elevations of serum LDH were noted in studies conducted by Mourad et al4 and Cho et al.7 Mourad et al4 considered five criteria for histological diagnosis: Partial or diffuse effacement of the nodal architecture, vascular proliferation with prominent arborization of high endothelial venules, extrafollicular meshwork of FDCs, atypical population of CD3+ T-cells and large CD20+ B-cells. Similar criteria were considered in the present case. But CD20+ B-cells were present as reactive residual component of the lesion. The constellation of microscopic features of this case corresponded with pattern II of AITL described by Attygalle et al.6 In the present case, neoplastic cells were diffusely positive for CD3 and CD10. CD30+ cells showed scattered positivity and were comparatively scant. CD20+ cells represented reactive residual B-cells. Mourad et al4 observed that neoplastic cells were CD3 in 100% cases and CD10 in 71% cases in their study. Cho et al7 noted that CD3 and CD5 were strongly positive and aberrant expression of CD10 was observed in 65% of cases. Attygalle et al6 observed that CD10

identified the tumor cells in 90% of AITL. In contrast, Rodriguez-Justo et al5 observed that only small proportion of neoplastic cells (5-10%) expressed CD10. CD30 staining was done in only three cases and was positive in all the three cases.5 The etiology and pathogenesis of AITL are unknown. In a high percentage of cases the diagnosis is preceded by allergic reactions, infections and/or exposure to drugs, particularly antibiotics.2 EBV and Human herpes virus (HHV6 and HHV8) may play a role in pathogenesis of AITL and this might explain its response to antiviral therapy with valacyclovir.5 Although, it has not been thoroughly investigated, it was suggested that the increase in T-cell immunoblasts would indicate transformation into a PTCL/unspecified. An increase in EBV infected B-cells may also occur and in rare cases, an overt diffuse large B-cell lymphoma develops.4 The physiologic role of CD10 is thought to involve hydrolysis of polypeptides such as inflammatory mediators in the extracellular milieu. Expression of CD10 may regulate apoptosis by interfering with negative or positive signals present in the extracellular environment. It is possible that aberrant CD10 expression in neoplastic T-cells in AITL may be an indicator of disturbed apoptotic cell death.6 Interestingly, it has been suggested that production of interleukin-21 by TFH is responsible for B-cell activation and hypergammaglobulinemia seen in AITL.5 It has been recently shown that CXCL13, a chemokine critically involved in B-cell migration into germinal centers, was highly upregulated in the TFH subset.4 It was hypothesized that the clinical effects of AITL are due to marked dysregulation of the immune system rather than to direct complications of tumor growth.4 Peculiar histologic features of AITL, where tumor cells are greatly outnumbered by the surrounding reactive cells and found in intimate contact with the expanding meshwork of FDCs. Hence, AITL can be considered as an immunologically functional disease in which the clinical behavior is determined by the resultant cross-talk between the malignant cells and the immunologic microenvironment.4 T-cell receptor genes show clonal rearrangement in 75-90% of cases. Clonal immunoglobulin gene rearrangement may be found in 25-30% cases. Trisomy 3 and 5 and an additional X-chromosome are the most frequent cytogenetic abnormalities detected in AITL.1,2 Conclusion Solitary axillary lymph node enlargement is an unusual presentation of AITL. In view of such

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Hematology atypical presentation and taking into consideration the aggressive nature of this distinct clinicopathological entity, careful clinical and laboratory evaluation is necessary. Immunophenotyping serves as an effective auxiliary weapon for the confirmation of diagnosis.

Acknowledgment We sincerely thank Dr Clementina Ramarao, Professor of Pathology, Kidwai Institute of Medical Oncology, Bangalore for the kind cooperation extended to us for diagnosing this rare entity.

References 1. Dogan A, Gaulard P, Jaffe ES, et al. Angioimmunoblastic T-cell lymphoma. In: World Health Organization Classification of Tumors of Haematopoietic and Lymphoid Tissues. 4th edition, Campo E, Harris NL, Jaffe ES, et al (Eds.). Swerdlow SJ. IARC Press: Lyon 2008:p.309-11. 2. Iannitto E, Ferrari AJ, Minardi V, Tripodo C, Kreipe HH. Angioimmunoblastic T-cell lymphoma. Crit Rev Oncol Hematol 2008;68(3):264-71.

3. Alizadeh AA, Advani RH. Evaluation and management of angioimmunoblastic T-cell lymphoma: a review of current approaches and future strategies. Clin Adv Hematol Oncol 2008;6(12):899-909. 4. Mourad N, Mounier N, Brière J, Raffoux E, Delmer A, Feller A, et al; Groupe d’Etude des Lymphomes de l’Adulte. Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d’Etude des Lymphomes de l’Adulte (GELA) trials. Blood 2008;111(9):4463-70. 5. Rodriguez-Justo M, Attygalle AD, Munson P, Roncador G, Marafioti T, Piris MA. Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centres: a neoplasia with origin in the outer zone of the germinal centre? Clinicopathological and immunohistochemical study of 10 cases with follicular T-cell markers. Mod Pathol 2009;22(6):753-61. 6. Attygalle A, Al-Jehani R, Diss TC, Munson P, Liu H, Du MQ, et al. Neoplastic T cells in angioimmunoblastic T-cell lymphoma express CD10. Blood 2002;99(2):627-33. 7. Cho YU, Chi HS, Park CJ, Jang S, Seo EJ, Huh J. Distinct features of angioimmunoblastic T-cell lymphoma with bone marrow involvement. Am J Clin Pathol 2009;131(5):640-6.

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AlProlix Approved by US FDA for Hemophilia B The US Food and Drug Administration (FDA) has recently approved the first long-lasting recombinant coagulation factor IX product, Alprolix, for use in children and adults with hemophilia B. The drug will help control and prevent bleeding episodes, manage bleeding during surgical procedures and prevent or reduce the frequency of bleeding episodes. The FDA stated that this is the first hemophilia B treatment that requires less frequent injections when used to prevent or diminish the frequency of bleeding. Supporting previous reports linking arterial stiffness to the amount of β-amyloid (Aβ) present in the brain of nondemented elderly patients, a new study has reported that arterial stiffness is also strongly associated with the accumulation of AΒ over almost 2 years in these adults. The study is published online March 31 in JAMA Neurology. The study included participants from the Pittsburgh site of the Ginkgo Evaluation of Memory Study (GEMS). At baseline 48% of 91 participants were AΒ positive, 75% of these participants were Aβ positive at follow-up.

Imatinib Facilitates Allogeneic Transplant in Ph+ ALL The routine incorporation of a tyrosine kinase inhibitor (TKI), such as imatinib, into the initial treatment of patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) has improved clinical outcomes such that some have questioned the need for routine allogeneic hematopoietic cell transplantation (allo-HCT) in this population. An analysis of a large prospective intergroup trial evaluated the outcomes of patients with Ph+ ALL treated with induction chemotherapy before and after a protocol amendment to incorporate imatinib [1]. Although imatinib resulted in a higher complete remission rate and superior overall survival at four years, the survival benefit appeared to reflect the ability of patients taking imatinib to maintain complete remission long enough to proceed with allo-HCT, supporting the approach of imatinib followed by allo-HCT. Further studies are needed to determine whether allo-HCT can be omitted in a subset of patients with Ph+ ALL, such as those who achieve a rapid response with no detectable minimal residual disease. (http://www.uptodate.com)

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Indian Journal of Clinical Practice, Vol. 24, No. 11, April 2014

Neurology

A Rare Case of Diencephalic Seizures Secondary to Hemorrhagic Stroke Muhammed Zohaib Ghatala*, Swamikannu Murugan†, Shriraam Mahadevan‡, Soundarajan Booma#

Abstract Diencephalic seizure or sympathetic storm is a rare condition characterized by paroxysmal episodes of acute increase in heart rate, blood pressure, respiratory rate, temperature and diaphoresis with extensor posturing that can occur, following brain injury. Here we report a case of a 45-year-old male with hemorrhagic stroke who had symptoms of diencephalic seizure during his hospital stay.

Keywords: Diencephalic seizure, sympathetic storm, brain injury, hemorrhagic stroke

iencephalic seizure was first described by Penfield in 1929, in a patient with a cerebral disorder who had paroxysmal episodes of acute increases in blood pressure (BP), heart rate and respiratory rate with lacrimation and extensor posturing. Since then, there have been several reports of similar cases and the suggestion that these seizures were associated with cerebral autonomic dysfunction secondarily because no evidence of seizure activity was detected by electroencephalography (EEG). We report on a patient with an intracerebral hemorrhage who developed characteristics of diencephalic seizures. The patient responded well to sodium valproate and adrenergic blockers.

Case Report A 45-year-old male presented with acute onset left hemiplegia, progressive decrease in the level of consciousness and one episode of generalized tonicclonic seizure. His past medical history was significant for hypertension and residual right upper and lower limb weakness from a hemorrhagic stroke at the age

*Senior House Officer †Consultant Physician Dept. of Internal Medicine ‡Consultant Endocrinologist Sundaram Medical Foundation, Shanthi Colony, Anna Nagar, Chennai, Tamil Nadu #Senior Registrar Dept. of General Medicine St. Martha’s Hospital, Bengaluru, Karnataka Address for correspondence Dr Muhammed Zohaib Ghatala #67, AJ Block, 3rd Street Anna Nagar, Chennai - 600 040, Tamil Nadu E-mail: zghatala@gmail.com

of 31 years. He was also an alcoholic but there was no history suggesting substance abuse. He was on regular antihypertensive medication with long-acting calcium channel blockers. On examination, the patient had a BP of 150/90 mmHg, heart rate of 88/min, normal body temperature and as he was not able to maintain airway, he was intubated. The patient was in post-ictal state with a Glasgow coma scale (GCS) of 6/15, he had paucity of movements of the left upper and lower limb and his left pupil was 2 mm in diameter but reactive to light. Given the patient’s history and clinical exam, an urgent computed tomography (CT) scan of the brain was done, which showed hemorrhage in the right lentiform nucleus (2.5 × 5.6 × 3.9 cm) with intraventricular extension, moderate midline shift, contralateral obstructive hydrocephalus and ipsilateral edema. There was also evidence of left middle cerebral artery (MCA) gliosis and encephalomalacia. The patient was admitted in the intensive care unit and he was managed with labetalol for his BP, loading dose and then maintenance dose of phenytoin for seizure prophylaxis which was later changed to sodium valproate, anti-edema measures were taken with hypertonic fluids and nasogastric tube feeding was started. On Day 3, his sensorium improved, and he was opening eyes to painful stimulus with paucity of movements of limbs. On Day 4, tracheotomy was done and he was weaned off the ventilatory support. On Day 11, the patient dropped his BP because of which labetalol was discontinued. However, later on during his hospital course, his BP was high again and was managed with short-acting metoprolol and amlodipine.

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Neurology Discussion

Table 1. Vitals of Patient on Day 54 Showing Episodic Sympathetic Surge Time

12 am

190/100

138

100.2

02 am

120/80

98.6

04 am

110/80

98.6

06 am

110/70

98.6

08 am

130/80

98.6

10 am

120/80

98.6

12 pm

120/80

98.6

02 pm

120/80

98.4

04 pm

130/90

98.4

06 pm

130/70

98.6

08 pm

186/110

126

99.4

10 pm

130/80

11 pm

160/90

104

The above table shows vitals on a randomly selected day (Day 54), for a better understanding of the episodic sympathetic surge. BP = Blood pressure in mmHg; PR = Pulse rate per minute; T = Temperature in degree Fahrenheit; RR = Respiratory rate per minute.

On Day 39, the hypertonic fluid infusion was discontinued. From Day 51, the patient was noticed to have repeated episodes of sudden onset tachypnea (RR-24-42/min), tachycardia (90-146/min), increased BP (180/100-200/130), diaphoresis with extensor posturing. These episodes occurred at an average of 3-4 times/day and lasted for 10-150 minutes. These episodes did not respond to conventional antiepileptic benzodiazepines. Diagnostic investigations for paroxysmal hypertension, arrhythmias and seizure activity were negative. Twenty-four hour urine for metanephrines was within normal limits. CT scan of the abdomen showed no evidence of an adrenal gland mass. EEG showed diffuse bilateral slow wave dysfunction with mild accentuation to right side. Dexamethasone suppression test ruled out hypercortisolism. Holter recording was unyielding. His thyroid profile was within normal limits. With this background, the patient was diagnosed with diencephalic seizure secondary to cerebral hemorrhage. These episodes of diencephalic dysautonomia responded moderately to α1-blocker, but had a significant response when we replaced the shortacting β1-blocker that the patient was already getting with a long-acting β1-blocker.

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Diencephalic seizure is a rare condition. It presents with autonomic dysregulation. Symptoms include intermittent hyperthermia, hypertension, tachypnea, tachycardia, diaphoresis and extensor posturing. In the literature, various terms have been used in reference to this condition like paroxysmal sympathetic storms, midbrain dysregulatory syndrome and paroxysmal autonomic instability with dystonia.1 This condition results from traumatic brain injury, intracranial hemorrhage, brain tumors, hydrocephalus and hypoxic brain injury. However, in our extensive literature search we found that traumatic brain injury was by far the most common cause of diencephalic seizure. It is still unclear as to what causes the sympathetic storm in these patients. Some of the possible causes include dysfunction of autonomic centers in the diencephalon (thalamus or hypothalamus) or their connection to cortical, subcortical and brainstem loci that control autonomic function and loss of parasympathetic inhibitory response to sympathetic surge produced under stress.2,3 It is primarily a diagnosis of exclusion. With our patient, we checked his thyroid profile, did an EEG, dexamethasone suppression test, 24 hours urine metanephrines and Holter monitoring before concluding that the sympathetic surge was because of diencephalic seizures. In one study of 814 patients with diencephalic seizures, the EEG findings were consistent with paroxysmal slow waves and 6 or 14 c/sec positive spikes.4 This condition can be managed with bromocriptine, clonidine, dantrolene, lorazepam, morphine sulfate and nonselective β-blockers such as propranolol.5 Usually, a combination of these drugs is used. Authors of various published studies in the past have stated that selective β1-blockers are not as effective as nonselective β-blockers or combined α1- and β-blockers but, interestingly, our patient responded well to a long-acting selective β1-blocker (metoprolol) in combination with sodium valproate. Conclusion Diencephalic seizure is a relatively rare condition characterized by sympathetic surge. As many physicians rarely see this condition during their medical practice, this is an often misdiagnosed condition. It is very important to recognize the symptoms and start the appropriate treatment. We suggest that these patients be treated with long-acting β-blockers in combination

Neurology with an anti-epileptic medication. In our case, the patient responded well to long-acting metoprolol and sodium valproate. References 1. Blackman JA, Patrick PD, Buck ML, Rust RS Jr. Paroxysmal autonomic instability with dystonia after brain injury. Arch Neurol 2004;61(3):321-8. Erratum in: Arch Neurol 2004;61(6):980. 2. Ramdhani NA, Sikma MA, Witkamp TD, Slooter AJ, de Lange DW. Paroxysmal autonomic instability with

dystonia in a patient with tuberculous meningitis: a case report. J Med Case Rep 2010;4:304. 3. Lemke DM. Riding out the storm: sympathetic storming after traumatic brain injury. J Neurosci Nurs 2004;36(1):4-9. 4. Shimoda Y. The clinical and electroencephalographic study of the primary diencephalic epilepsy or epilepsy of brain stem. Acta Neuroveg (Wien) 1961;23:181-91. 5. Levy ER, McVeigh U, Ramsay AM. Paroxysmal sympathetic hyperactivity (sympathetic storm) in a patient with permanent vegetative state. J Palliat Med 2011;14(12):1355-7.

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A research paper published online March 25 in Translational Psychiatry has put forward phenomenal findings by researchers at the University of Michigan. The researchers have used skin fibroblasts from patients with bipolar disorder (BD) to create the very first stem cell lines specific to the disorder. Melvin McInnis, the principal investigator of the Prechter Bipolar Research Fund and its programs, said that this research could help in achieving personalized medicine both for the understanding of pathophysiology of the disorder and to ascertain what interventions will be effective.

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A recent study published in JAMA Internal Medicine reports that antihypertensive medications not only lower the blood pressure but may also result in falls in elderly patients. In comparison with individuals who were not taking antihypertensive medications, those taking antihypertensives had a 30-40% increased risk of falls resulting in a serious fall-related injury. Furthermore, the risk for a serious fall-related injury doubled in those who had a history of falls.

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Novel research suggests that among individuals with severe depression treated with electrode convulsive therapy (ECT), electrode placement and patient age significantly affect treatment outcomes. The study including 230 adults with severe depression revealed that right unilateral ECT was more effective in those aged >60 years than in younger patients, with remission rates of 70% and 46%, respectively. The study was presented at the American Association for Geriatric Psychiatry (AAGP) 2014 Annual Meeting.

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A novel meta-analysis published in the Journal of Neurology, Neurosurgery and Psychiatry has stated that patients with Parkinson’s disease might be at an increased risk for osteoporosis. Additionally, these subjects may be more likely to have extra fractures. Pooled analysis of two studies revealed that patients with Parkinson’s had an odds ratio of 2.61 for developing osteoporosis compared with healthy controls.

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Women with the highest levels of alpha-amylase, a biomarker of stress, when they were trying to conceive were nearly one-third less likely to conceive than their less-stressed peers, and twice as likely to meet the clinical definition of infertility, according to a prospective cohort study. Courtney Denning-Johnson Lynch, PhD, director of reproductive epidemiology at the Ohio State University Wexner Medical Center, Columbus, and colleagues published their findings online March 23 in Human Reproduction.

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Obstetrics and Gynecology

Cervical Stenosis: A Rare Complication of Cesarean Section ANITA KHARAT*, SUMAN KUMARI†

Abstract Deliveries through cesarean section are steadily increasing since the last two decades. Although rare, complications do occur after cesarean section. A very rare complication of cesarean section is cervical stenosis, leading to hematometra and hematosalpinx. We report a case of a 38-year-old woman who presented with pain in abdomen and secondary amenorrhea since 15 years, after her last delivery which was conducted by cesarean section. On examination, a provisional diagnosis of hematometra due to cervical stenosis was made, which was confirmed at laparotomy. Due to adhesions and pinpoint stenosed cervix, she was managed by total abdominal hysterectomy with right salpingo-oophorectomy and left salpingectomy was done.

Keywords: Cesarean section, hematometra, hematosalpinx, cervical stenosis, complication

eliveries through cesarean section are steadily increasing since the last two decades. Deliveries by cesarean section have increased by about 25% in teaching hospitals and by at least 50% in private hospitals. With the increasing incidence of cesarean, we are taking this surgery very casually. Although rare, complications remind us of the necessity of vigilance in surgery. A very rare complication of cesarean section is cervical stenosis, leading to hematometra and hematosalpinx. We are here presenting a rare case of cervical stenosis as a complication of cesarean section.

CASE REPORT A 38-year-old woman P3L1Dl intrauterine fetal death (IUFD)-1, presented to OPD of Terna Medical College and Hospital with pain in abdomen and secondary amenorrhea since 15 years, after her last delivery which was cesarean delivery. Initially, this pain abdomen was cyclical in nature; later on, it became continuous and generalized in nature. Around 15 years back, she had cesarean section for transverse lie with IUFD at private hospital in Patna. She had some complication during that cesarean section for which she was kept

*Associate

Professor Professor Dept. of Obstetrics and Gynecology Terna Medical College and Hospital, Nerul, Navi Mumbai, Maharashtra Address for correspondence Dr Anita Kharat 102/ Jaysoham, Apartment, Sant Ramdas Road, Mulund (East), Mumbai - 400 081 E-mail: dranitakharat@gmail.com

†Assistant

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Indian Journal of Clinical Practice, Vol. 24, No. 11, April 2014

for prolonged period at hospital and required blood transfusion. Later, she developed amenorrhea until date, and had vaginal spotting. Few years back, she underwent hysteroscopy at the same private clinic for amenorrhea, after failure of withdrawal bleed, but hysteroscopy could not succeed. Detailed report is not available. Her first baby died at the age of ½ year, was full-term normal home delivery; second baby is alive and it was home delivery; third was transverse lie with IUFD, for which cesarean was done.

On Examination Patient was thin built, afebrile with mild pallor and normal vitals. Her systemic examination was normal. On abdominal examination, vertical scar of previous surgery was noted. A mass of 16-18 weeks size uterus was felt in lower abdomen, with tenderness all over. Vaginal examination revealed a very small cervix with stenosed os. Vagina was normal. Uterus was bulky, 18-week size, soft and irregular, with restricted mobility. Fornices were tender. So, a provisional diagnosis of hematometra due to cervical stenosis was made. Ultrasonography and CT scan of abdomen and pelvis was done; however, report suggested the diagnosis of Asherman syndrome. Bulky uterus with endometrial septation and hematosalpinx were noted. Free fluid in the peritoneal cavity was noted. Routine blood investigations were normal. Patient was kept for hysteroscopy and adhesionolysis but this procedure could not be done because of cervical stenosis. So, laparotomy was planned with blood ready for transfusion if required.

Obstetrics and Gynecology

Figure 1. Patient was managed by total abdominal hysterectomy with right salpingo-oophorectomy and left salpingectomy was done.

Contâ&#x20AC;&#x2122;d on page 1056...

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1047

Obstetrics and Gynecology

Medical Management of Ectopic Pregnancy with Methotrexate Sumant R Shah*, Sandip Sonara†, Bhavesh Patel‡, Nidhi Patel†

Abstract Objective: The aim of this study is to determine the efficacy of methotrexate treatment for ectopic pregnancies in our settings, which will in-turn help us reduce maternal mortality and morbidity. Material and methods: This was a retrospective study of 40 cases of unruptured ectopic pregnancy treated with methotrexate in civil hospital, Ahmedabad. Clinical presentation, treatment, progress, outcome, side effects and future fertility follow-up were analyzed using database from May 2008 to June 2012. Results: The success rate of methotrexate therapy in our study was 85% (n = 35) and 15% (n = 06) required surgical intervention compared to reported success rate of 67-100% published in various studies. The mean average time of resolution of ectopic pregnancy was 32 days for a single dose and 58 days for repeat second doses. Successful fertility outcome with intrauterine pregnancy was observed in three patients. Conclusion: Methotrexate treatment of ectopic pregnancies is safe and effective with no major side effects. Intramuscular methotrexate has the advantage of tubal conservation and saves patients from surgical intervention. Our study showed single dose methotrexate to be an effective treatment option for selected patients with unruptured tubal ectopic pregnancy.

Keywords: Methotrexate, maternal mortality, ectopic pregnancy

ctopic pregnancy is an acute emergency if not timely diagnosed and treated. Timely diagnosis and appropriate treatment can reduce the risk of maternal mortality and morbidity related to ectopic pregnancy. It is an important diagnosis to exclude when a woman presents with bleeding in early pregnancy. A report of the incidence from elsewhere is showing a rise from 0.5% to 1.2%. There has been a rise of 3-5% in pregnancies from assisted reproductive techniques. The clinical presentation of ectopic pregnancy has changed from a life-threatening disease to a more benign condition for which nonsurgical treatment options are available with systemic methotrexate, methotrexate or expectant management. Medical management with methotrexate fulfilling the criteria in selected cases were tried and found to be equally successful. Medical management was found to be equally effective as surgical management particularly taking consideration of future fertility.

*Professor and Unit Head †Resident Doctor (IIIrd Year) ‡Consultant Gynecologist Dept. of Obstetrics and Gynecology BJ Medical College and Civil Hospital, Ahmedabad, Gujarat Address for correspondence Dr Sandip Sonara 4, Marigya Society, 100 Ft. Road, Satellite Ahmedabad - 380 015, Gujarat E-mail: drsandipsonara@gmail.com

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Indian Journal of Clinical Practice, Vol. 24, No. 11, April 2014

Methotrexate can be administered systemically as a single dose regimen; this was introduced to minimize side effects, to improve patient compliance and to reduce the overall costs. Methotrexate has been shown to be safe with virtually no adverse effects reported on reproductive outcome. Careful follow-up and assessment are required for all women presenting with pain in the few days following methotrexate therapy before assuming that the treatment has failed and if there is need for surgical intervention. Material and Methods Between May 2008 and June 2012, (n = 40) patients of diagnosed ectopic pregnancy treated as in-patients with methotrexate regimen were retrospectively identified from hospital records of the Dept. of Obstetrics and Gynecology, Civil Hospital, Ahmedabad. The diagnosis of ectopic pregnancy was made using both transvaginal ultrasound and measurement of b-human chorionic gonadotropin (b-hCG). All cases selected for medical management gave their informed written consent before starting the treatment. The selection criteria for patients suspected to have ectopic pregnancy but with low serum b-hCG or cases of pregnant women patients who were hemodynamically stable with b-hCG level of ≤10,000 mIU/mL and if clinically feasible >10,000 mIU/mL, adnexal mass ≤4 cm

Obstetrics and Gynecology and if clinically feasible >4 cm, absent cardiac activity and the presence of hemoperitoneum >100 mL. Baseline investigations such as full blood count, b-hCG, renal and liver functions tests and blood group. RH factor were done on Day 1 and single dose of 50 mg/m2. Methotrexate was administered. Serial b-hCG was repeated on Days 4 and 7. If b-hCG on Day 7 was at least 15% lower than that on Day 4, the patient was discharged and followed up as an outpatient. If the b-hCG level on Day 7 was the same or higher than that on Day 4, the patient received a second dose of 50 mg/m2 methotrexate. Follow-up serum b-hCG was performed weekly. Single dose methotrexate treatment was considered successful when b-hCG levels became negative without further administration of methotrexate dose or surgery. The ultrasound examination was performed. Cases with persistent plateauing serum b-hCG concentration were defined as 15% fall or <15% rise in serum b-hCG concentrations. Second dose of methotrexate was installed in both cases of either increasing b-hCG or plateauing b-hCG. Follow-up b-hCG was performed weekly until negative with value of b-hCG <5 mIU/mL. For patients with hemodynamic instability, signs of tubal rupture, increasing abdominal pain, falling hemoglobin level surgical intervention were considered. The toxicity of methotrexate treatment was evaluated by noting side effects such as lower abdominal pain, vaginal bleeding, mouth ulcers, sore throat, gastrointestinal side effects or complaints of any rashes. Nonsensitized Rhesus negative women received anti-D immunoglobulins 250 μg as per the department protocol. Women treated with methotrexate were advised to refrain from sexual intercourse until serum b-hCG was negative, and not to conceive within 3 months of treatment. Results In this study, the majority of patient (45%) were between 20-25 years (n = 18) (Table 1). The success rate of methotrexate decreased as maternal age increased. Gravidity was between one and six with 40% (n = 12) primipara. The majority of patient with gestation age at diagnosis was <6 weeks 62.5% (n = 25) (Table 2). The success rate of methotrexate decreased with increasing gestational age. Adnexal mass ranged from 2 to 4 cm. In patients with adnexal mass >4 cm, the success rate was less. In women with 2-3 cm adnexal mass success rate is 82.1% (n = 28) (Table 3). There was no marked difference in the site of ectopic gestation. The average value of b-hCG on Day 1 in patients treated with

single dose of methotrexate was 3,000 mIU/mL (range 100-8,847) and those treated with two doses or more was 10,000 mIU/mL (Table 4). An increase in the Day 4 value was observed in some cases, mainly due to the trophoblastic tissue breakdown releasing the hormone (Table 5). Methotrexate has a cytotoxic effect on trophoblastic tissue. Although, it arrests mitosis in cytotrophoblast, the syncytiotrophoblast mass may still increase and produce β-hCG. The average time of resolution for serum b-hCG level was 32 days for single dose of methotrexate and 58 days for those receiving two doses. Time of resolution for serum b-hCG was defined as the total number of days from the beginning of treatment until β-hcg level became negative (<5 mIU/mL). The total number of women treated with single dose was 87.5% (n = 35) and (n = 5) 12.5% received two doses. Success rate in group of patient given single dose methotrexate was 82.85% and in patients with two dose methotrexate it was 100%. The overall success rate of treatment in our study was 85% (n = 34). Surgical intervention was required for 15% (n = 6) of patients with tubal rupture and abdominal pain (Table 6). One patient complained of lower abdominal pain between Days 2-7 and early surgical intervention by laparotomy followed by salpingectomy. Two cases were managed by laparoscopic salpingotomy. Mild vaginal bleeding, not more than the initial bleeding was noted with no reported case of gastrointestinal side effects. Fifteen percent (n = 6) women had history of previous ectopic pregnancy, three women had history of pelvic tuberculosis and 40% (n = 16) had history of miscarriages. Three women reported successful intrauterine pregnancy outcome after 1 year. Discussion Ectopic pregnancy occurs in around 1% of pregnant women and may seriously compromise women’s health and future fertility. With increase in the use of artificial reproduction technique and increase in pelvic inflammatory disease due to increased sexual promiscuity incidence of ectopic pregnancy has increased. It will help this community as a whole in preserving future childbearing function. Ectopic pregnancy can be diagnosed before the patient’s condition has deteriorated and the cornerstone of diagnosis is the use of transvaginal ultrasound and serum hCG measurement. Single dose methotrexate appears effective and has better patient compliance. Treatment success is inversely correlated to β-hcg concentration. The most important selection criteria for medical management is the absence of pain

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Obstetrics and Gynecology and the prediction that the pregnancy will not rupture before its resolution. Surgery and medical management are the two ways to treat ectopic pregnancy. Both are effective and the choice depends on clinical situation, site of ectopic mass and access to technology. Systemic single dose methotrexate seems to offer the greatest benefits in terms of efficacy and tolerability. It has proved to be a good alternative to laparoscopy in selected cases. The success rate of systemic methotrexate in our study was 85% (n = 34), 12.5% (n = 5) were treated with two doses of methotrexate 15% and (n = 6) required surgical intervention. Patients with small unruptured ectopic pregnancies achieved a success rate of 82.1% with five women requiring a second dose. Srivichai et al reported a success rate of 90.6% in 96 out of 106 patients who were successfully treated with methotrexate though four required a second dose. In all comparative studies, the success rate was found to be same as in our study. The reason being that at the beginning of starting the methotrexate regimen in our institution women with increasing β-hcg values and complaints of abdominal pain were taken early for surgical intervention for fear of rupture of the ectopic

Table 4. b-hcg Level on Day 1 On admission b-hcg level

No. of Percentage No. of Success patients (%) successful rate (%) patients

< 10,000

87.5

> 10,000

12.5

Table 5. Fall in b-hcg Level on Days 4 and 7 and Outcome Total No. of patients

Percentage No. of Success (%) successful rate (%) patients

> 15%

80%

90.6

< 15%

20%

62.5

Table 6. Success Rate No. of patients

Percentage (%)

Successful

Unsuccessful

No. of patients

Percentage (%)

Present

2.5

Absent

97.5

Table 1. Age of Patients Age (years)

No. of patients

Percentage (%)

20-25

25-30

37.5

31-35

35-40

7.5

100

Table 2. Month of Amenorrhea Month of amenorrhea

No. of patients

Percentage (%)

< 1 ½ MA

62.5

> 1 ½ MA

22.5

No MA

Table 3. Size of Ectopic Mass and Outcome Size of mass

No. of patients

< 4 cm

82.1

> 4 cm

91.1

1050

Percentage No of Success (%) successful rate (%) patients

Indian Journal of Clinical Practice, Vol. 24, No. 11, April 2014

Table 7. Cardiac Activity

pregnancy. With more experience of using the drug the success rate improved. Treatment failure based strictly on a high increase in β-hcg level from Day 4 to 7 may be a hasty judgment. Pain after methotrexate treatment could be due to tubal abortion or stretching of the tube by hematoma contributing to increased failure rate in most of the medical management. Differentiating ‘separation pain’ due to tubal abortion from pain due to tubal rupture can be difficult and may lead to early surgical intervention. Mahboob reported a success rate of 80% by treating 12 out of 15 women with single dose methotrexate with initial β-hcg levels equal to 5,000 mIU/mL. In the same series, an increase in the treatment failure group with advanced maternal age ≥35 years and history of spontaneous abortions was noted corresponding to our study where success rate of methotrexate treatment decreased as maternal age increased. In our study,

Obstetrics and Gynecology nine women aged over 30 years had a failure rate of (n = 4). Lee reported a success rate of 96% with β-hcg <6,000 mIU/mL and 58% when β-hcg was >6,000 mIU/mL. He noted that initial β-hcg is the only predictor of success for repeated injection of methotrexate in single dose regimen. The incidence of infertility as a risk factor reported in literature was 30% for ectopic pregnancy. However, it accounted for 15% (n = 9) in our study (primary-7 and secondary-2). Many studies have identified the risk factors for ectopic pregnancy. A third of cases are associated with tubal damage caused by infection or surgery and another third with appendicectomy, which is a rare factor. No cause can be established for the remaining third. Techniques of assisted reproduction increase the risk of ectopic pregnancy by 2-4%. Multiple dose regimen for hemodynamically stable women with an unruptured tubal ectopic pregnancy with serum hcg concentrations < 3,000 mIU/mL and a single-dose methotrexate for serum hcg < 1,500 mIU/mL is recommended. Women with a pretreatment β-hcg level of 3,000-4,000 mIU/mL have a greater probability of surgery or multiple dose treatment. The time of resolution of serum b-hCG in our study was 32 days with a single dose and 58 days with two doses of methotrexate as compared to 27.3 days and 35 days, respectively in other series. Thia noted the time of resolution was 33 days with one dose and 55 days with two doses, similar to our study. Erdem reported the mean time of resolution as 26.5 (10-37) days in patients who were successfully treated with methotrexate. These results are consistent with other studies. Methotrexate regimen reduces the incidence of persistent trophoblast. Persistent trophoblast is detected by the failure of serum hcg levels to fall as expected after initial treatment, often a problem occurring after salpingostomy rather than salpingectomy. In 12 cases treated with laparoscopy, one case of persistent trophoblast was observed and this could have been prevented with medical management of ectopic pregnancy and β-hcg follow-up to avoid complications such as delayed hemorrhage owing to persistent trophoblast. In our study, cardiac activity was absent in 97.5% (n = 39) patients and 2.5% (n = 1) patient cardiac activity was present, which required surgical intervention (Table 7). In our study, 37.5% (n = 15) of women complained of lower abdominal pain and 15% (n = 6) were treated surgically due to increasing hemoperitoneum. Most studies showed increased lower abdominal pain

between 2-7 days after treatment. This complication of methotrexate is disturbing in an outpatient with an ectopic pregnancy. No other side effect of methotrexate was observed in our study. In Thia’s series, 40% (n = 4) of patients were hospitalized for pelvic pain 2 days after treatment and their pain regressed without surgery. One patient developed mild rash in light exposed skin areas. No such complaint was observed in the studied patients managed as in-patients. In the same study, 28.2% (n = 9) of patients complained of abdominal pain between Days 4 and 8 and one patient was found to have a ruptured cornual ectopic pregnancy at laparoscopy. Minor side effects reported in the same series were mucositis in 19.1% (n = 21) and 10.9% (n = 12) of the patients suffered gastric pain and diarrhea. No side effects were reported with single dose treatment in a series of 30 patients with a success rate of 97%. Increased abdominal pain on Days 5-10 after medical management of ectopic pregnancy has to be closely monitored for possible rupture. Methotrexate therapy was associated with high rates (80%) of subsequent fertility compared to our study, successful intrauterine pregnancy following methotrexate was observed in three women. Conclusion Methotrexate has proven to be an effective medical management for ectopic pregnancies in a society where tubal conservation is of utmost importance. The medical management by methotrexate seems to offer several benefits over surgical treatment. It is less invasive, less expensive and does not need expertise like laparoscopy. Future reproductive expectations are better with methotrexate with higher intrauterine pregnancy rates and lower ectopic rates subsequently. However, the risk of tubal rupture after medical treatment combined with a prolonged follow-up for an ectopic pregnancy to resolve requires monitoring for rupture and methotrexate side effects making compliance important in patient selection. The predictors of success in our study are low β-hcg and adnexal mass <4 cm. Single dose methotrexate offers a safe and effective nonsurgical method of treating selected patients and one important advantage of medical therapy is the potential for considerable savings in treatment costs. Suggested Reading 1. Thia EW, Loi K, Wang JJ, Siow A. Methotrexate treatment for ectopic pregnancy at the KK Women’s and

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Obstetrics and Gynecology Children’s Hospital, Singapore. Singapore Med J 2009;50 (11):1058-61. 2. Merisio C, Anfuso S, Berretta R, Gualdi M, Pultrone DC, Melpignano M. Single-dose methotrexate for ectopic pregnancy treatment: preliminary data. Acta Bio Med 2005;76(1):33-6. 3. Zargar M, Razi T, Barati M. Comparison of single and multidose of methotrexate in medical treatment of ectopic pregnancy. Pak J Med Sci 2008;24:586-9. 4. Kirk E, Condous G, Bourne T. The non-surgical management of ectopic pregnancy. Ultrasound Obstet Gynecol 2006;27(1):91-100. 5. Hajenius PJ, Mol BW, Bossuyt PM, Ankum WM, van der Veen F. Interventions for tubal ectopic pregnancy. Cochrane Database Syst Rev 2007;(1):CD000324. 6. Barnhart KT, Gosman G, Ashby R, Sammel M. The medical management of ectopic pregnancy: a meta-analysis comparing “single dose” and “multidose” regimens. Obstet Gynecol 2003;101(4):778-84. 7. Lipscomb GH, Puckett KJ, Bran D, Ling FW. Management of separation pain after single-dose methotrexate therapy for ectopic pregnancy. Obstet Gynecol 1999;93(4):590-3. 8. Cho GJ, Lee SH, Shin JW, Lee NW, Kim T, Kim HJ, et al. Predictors of success of repeated injections of single-dose methotrexate regimen for tubal ectopic pregnancy. J Korean Med Sci 2006;21(1):86-9.

9. Bouyer J, Coste J, Shojaei T, Pouly JL, Fernandez H, Gerbaud L, et al. Risk factors for ectopic pregnancy: a comprehensive analysis based on a large case-control, population-based study in France. Am J Epidemiol 2003;157(3):185-94. 10. Fernandez H, Gervaise A. Ectopic pregnancies after infertility treatment: modern diagnosis and therapeutic strategy. Hum Reprod Update 2004;10(6):503-13. 11. Erdem M, Erdem A, Arslan M, Oc A, Biberoğlu K, Gursoy R. Single-dose methotrexate for the treatment of unruptured ectopic pregnancy. Arch Gynecol Obstet 2004;270 (4):201-4. 12. Tawfiq A, Agameya AF, Claman P. Predictors of treatment failure for ectopic pregnancy treated with single-dose methotrexate. Fertil Steril 2000;74(5):877-80. 13. The management of tubal pregnancy. Royal College of Obstetricians and Gynaecologists Guidelines 2004;21:1-10. 14. Slaughter JL, Grimes DA. Methotrexate therapy. Nonsurgical management of ectopic pregnancy. West J Med 1995;162(3):225-8. 15. Stovall TG, Ling FW, Gray LA. Single-dose methotrexate for treatment of ectopic pregnancy. Obstet Gynecol 1991; 77(5):754-57. 16. Stovall TG, Ling FW, Gray LA, Carson SA, Buster JE. Methotrexate treatment of unruptured ectopic pregnancy: a report of 100 cases. Obstet Gynecol 1991;77(5):749-53.

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Hyperimmune Globulin for the Management of Primary CMV Infection During Pregnancy not Effective Effect of treatment with hyperimmune globulin for the management of primary cytomegalovirus (CMV) infection during pregnancy is equivalent to that of placebo, reports a new study published in the April 3 issue of the New England Journal of Medicine. The phase II CHIP study was a randomized, placebo–controlled, double– blind trial conducted at 11 centers in Italy from June 2009 to November 2011. About 124 pregnant women who acquired primary CMV infection between 5 and 26 weeks’ gestation were randomized within 6 weeks of acquiring the infection to receive either hyperimmune globulin or placebo (0.9% saline solution) intravenously. Overall transmission rate was 30% in the treatment group versus 44% in the placebo group. Additionally, the treatment group had a higher percentage of obstetrical adverse events than placebo group.

Organic Food does not Reduce Women’s risk of Cancer Women who mostly or always eat organic foods have the same overall chance of developing cancer as women who never eat it, according to a new study from the UK’s University of Oxford and published in the British Journal of Cancer that followed over 600,000 middle-aged women for nearly a decade. The word “organic” and the standards that apply to it are slightly different in various countries, but generally it forbids the use of synthetic pesticides and chemical fertilizers in the production of food. Outside the organic movement, pesticides are widely used in agriculture, and there are concerns that residues from these get into the food chain and could increase the risk of cancer. But so far, the evidence for this is not strong enough to give any clear answers.

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Indian Journal of Clinical Practice, Vol. 24, No. 11, April 2014

Obstetrics and Gynecology

Pregnancy Outcome in Women with Dengue Infection in Northern India Prabhat Agrawal*, Ruchika Garg†, Soumya Srivastava†, Urvashi Verma†, Rekha Rani†

Abstract Background: Dengue is the most prevalent mosquito-borne infection worldwide. Vertical transmission after maternal dengue infection to the fetus and pregnancy losses in relation to dengue infection have been reported. Objective: The aim of the study was to assess the maternal and fetal consequences of dengue fever (DF) infection during pregnancy. Methodology: A retrospective analysis of all pregnant women with DF was done over a period of 1 year. Clinical, laboratory, maternal and fetal outcomes and early neonatal outcomes were collected from patients with confirmed dengue infection. Result: An upward trend was observed with a striking feature of severe thrombocytopenia in 36% cases. Oligohydramnios and low birth weight were the most common and peculiar outcomes. Preterm delivery with increased risk of cesarean section was noted. Vertical transmission occurs in pregnancy but no evidence of congenital anomaly could be traced.

Keywords: Dengue fever, pregnancy, dengue hemorrhagic fever

engue fever (DF) is a febrile disease found in the tropics. It is a major public health problem in tropical countries. It is caused by virus serotypes of the genus Flavivirus, family flaviviridae, Group IV ssRNA. Dengue is transmitted to humans by mosquito Aedes aegypti. Despite previous outbreaks, a large number of people remain susceptible because there are four different strains of the dengue virus. Dengue infection in pregnancy carries the risk of hemorrhage in both the mother and the newborn. There is serious risk of premature birth and fetal death. In case of infection close to term, there is risk of vertical transmission.

METHODOLOGY A retrospective analysis of all pregnant women with confirmed dengue infection during pregnancy admitted in July 2011 to December 2012 in PG Dept. of Medicine and Dept. of Obstetrics and Gynecology at SN Medical College, Agra was conducted in 25 patients. Dengue

*Lecturer PG Dept. of Medicine †Lecturer Dept. of Obstetrics and Gynecology SN Medical College, Agra, Uttar Pradesh Address for correspondence Dr Prabhat Kumar Agrawal D-1, Sulahkul Nagar, Bodla Road, Agra, Uttar Pradesh E-mail: ruchikagargsnmc@gmail.com

infection was confirmed either by presence of specific immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (ELISA) or dengue nonstructural proteins (NS) antigen and the outcome is illustrated in Table 1. RESULT In our study on 25 patients suffering with DF, data was collected regarding obstetric and fetal outcome during a period of 1 year. An upward trend was observed with 72% as multigravida and 28% as primigravida. DF was seen in 24%, dengue hemorrhagic fever (DHF) in 56%, dengue shock syndrome (DSS) in 20%. Twelve percent patients were in first trimester, 12% in second trimester and 76% in third trimester. Dengue serology IgM was positive in 20 cases (80%), NSAg positive in 17 cases (68%) and both IgM and NSAg positive in 14 cases (56%). There were six cases of early pregnancy with DF, out of which four (16%) had abortion and two cases (8%) could progress to term. There was no mortality seen in early pregnancy. Second and third trimester had varied presentation. Preterm delivery was seen in 17 cases (68%), in three cases (12%) pregnancy progressed to term. Eight patients (32%) underwent emergency lowersegment cesarean section (LSCS) (4 for fetal distress and 4 for cephalopelvic disproportion), while 11 patients (44%) delivered normally. Antepartum hemorrhage (APH) due to abruptio placentae was seen in eight patients (32%), postpartum hemorrhage (PPH) was found in six patients (32%), oligohydramnios in 52%

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Obstetrics and Gynecology Table 1. Diagnosis and Outcome of Pregnancy in Women with Dengue Infection Included in the Study Gestational age 36 WKS (P), Primi (P) 31 WKS (M), Multi (M)

Platelet count NSAg1 IgM Ab. unit (µ/mL)

Clinical diagnosis

56,000

+ve

–ve

82,000

+ve

DF with PIH

30 WKS (M)

20,000

+ve

8 WKS (P)

28,000

+ve

IgM malaria +ve –ve

30 WKS (M)

50,000

+ve

18 WKS (P)

25,000

13 WKS (M)

Obstetric Neonatal outcome outcome Preterm labor (PTL) with fetal Emergency (Em.) LBW, neonatal distress (FD) LSCS jaundice Mild oligohydramnios Managed Term AGA baby (Oligo.) conservatively Maternal morbidity

Chronic fever with DHF

APH with PTL with Oligo.

Em. PTL LSCS with PPH

DHF

Pain with bleeding P/V

Missed abortion

+ve

DHF

Mild pain with rash

Managed till term

–ve

+ve

18,500

–ve

+ve

DHF

39 WKS (M)

28,000

+ve

38 WKS (M)

38,000

–ve

+ve

35 WKS (M)

27,000

+ve

DHF

APH with PET with Oligo. with FD

36 WKS Twins (M)

26,000

+ve

DF with PET

APH with PROM with Oligo.

Preterm delivery (PTD)

LBW twins with ARDS

29 WKS (P)

1,29,000

–ve

+ve

DSS

Managed conservatively

NVD at term

AGA baby

36 WKS (M)

14,000

+ve

DHF with ICH

PTL with Oligo.

PTD with PPH Cardiac arrest

LBW

36 WKS (M)

18,000

+ve

DHF with cerebral edema

APH with Oligo with IUD

PTD

Fresh stillbirth

+ve

DSS with FD

APH with Oligo. with FD with PTL

Em. LSCS with PPH

LBW

–ve

DHF with DIC

APH with FD with PTL

35 WKS (M)

20,000 82,000

AGA baby

Anomaly scan and fetal ECHO Missed abortion (N) Mild Oligo. with pain abdomen

Managed conservatively

Cardiopulmonary arrest DHF with prev. Rexplored-6L Post-LSCS hemoperitoneum 1 LSCS Blood removed DSS

LBW, ARDS

ARDS with Oligo. and shock

Term AGA baby Expired LBW, ARDS

Intracranial Em. with LSCS hemorrhage ICH PPH (Expired)

7 WKS (M)

84,000

–ve

+ve

Bleeding P/V

Em. LSCS with PPH Missed abortion

35 WKS (M)

21,000

+ve

DSS

Oligo. with APH with FD

IUD

28 WKS (P)

22,000

+ve

DHF

PTL with Oligo. with DIC

PTD with IUGR

29 WKS (P)

16,000

+ve

DSS

34 WKS (M)

20,000

+ve

DHF with ARDS

Oligo. with anemia with BPV

PTD

35 WKS (M)

68,000

–ve

+ve

DHF with PET

Oligo. with APH with anemia with PTL

PTD with PPH

LBW

32 WKS (M)

74,000

+ve

–ve

DF with ARDS

Oligo. with H/O prolonged fever

Em LSCS with PPH

LBW

38 WKS (M)

20,000

+ve

DHF

Hematuria with LP's

Em LSCS with PPH (Expired)

6 WKS (M)

15,000

+ve

–ve

DHF

Bleeding tendency

36 WKS (P)

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Indian Journal of Clinical Practice, Vol. 24, No. 11, April 2014

LBW (Expired)

LBW with ICH with rash (Expired)

IUD

LBW (Exp.) with ARDS (Expired) LBW with ICH Missed abortion with rash (Expired)

Obstetrics and Gynecology Table 2. Comparison of Results of our Study with that of Basurko et al. Basurko C

Our study

Premature labor

41%

52%

Oligohydramnios

46%

52%

APH

9.3%

32%

PPH

10%

36%

IUD

3.8%

Abortions

3.8%

16%

7.5%

16%

Neonatal death

1.9%

18%

APH = Antepartum hemorrhage; PPH = Postpartum hemorrhage; IUD = Intrauterine device; FD = Fetal distress.

and low birth weight (LBW) in 52%. Two patients had intrauterine device (IUD) (8%). Out of all live births (68%), five neonates expired during early neonatal period and four (16%) babies required neonatal intensive care unit (NICU). Maternal mortality was seen in three cases (12%) common causes of which were PPH and shock. No congenital anomaly could be traced in the babies born. The comparisons of the results of our study with that of Basurko et al is given in Table 2. DISCUSSION Classical DF is defined as an acute febrile illness with high continuous fever for 3 days or more, with two or more other clinical manifestations involving headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestation or leukopenia, and is supported by serology or occurrence at same location and time as other confirmed cases (World Health Organization [WHO] guidelines). According to WHO definition of DHF all four of the following criteria must be fulfilled: Fever, hemorrhagic tendency, thrombocytopenia and evidence of plasma leak as evidenced by hematocrit 20% higher than expected or a drop in hematocrit of 20% or more from the baseline following intravenous (IV) fluid, pleural effusion or ascites. DHF is characterized by fever, hemorrhagic tendencies (petechial hemorrhages, gum bleeding, generalized rash), thrombocytopenia and evidence of plasma leakage, as well as possible association with hepatomegaly and circulatory disturbances. DSS is manifested when DHF symptoms include rapid and weak pulse, narrow pulse pressure <20 mmHg and hypotension. Platelet deficiency is a constant feature in dengue infection. With DHF, increased vascular permeability

resulting in hemoconcentration and plasma leakage is evidenced by pleural effusion, ascites and hypoproteinemia. Some of these syndromes may be confused with HELLP (hemolysis, elevated liver enzyme and low platelet count) syndrome but a high index of suspicion of dengue infection is required. The physiological changes of pregnancy have to be kept in mind before interpreting the laboratory findings. The normal hematocrit range in pregnant woman may be as low as 34% (normal for a nonpregnant woman is 37-47%). There are various other entities in pregnancy resembling dengue viz. idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APA syndrome) or inherited diseases or pregnancyrelated complications such as pre-eclampsia, sepsis or disseminated intravascular coagulation in obstetric cases may cause thrombocytopenia. In 75% of the cases, thrombocytopenia cannot be attributed to any of these etiologies. CONCLUSIONS Thus DF led to poor maternal and perinatal outcomes in our setting. Preventive measures should be employed in the region. Dengue in pregnancy requires early diagnosis and treatment. A high index of clinical suspicion is essential in any pregnant female with fever during epidemics. Further studies are mandatory as evidence-based data in the management of dengue specific for pregnancy, are sparse. Travel during pregnancy to dengue endemic areas poses a risk to both mother and fetus. Pregnancies complicated by dengue infection require close monitoring for potential maternal and fetal complications. The striking feature observed was the presence of severe thrombocytopenia in 78% patients, oligohydramnios and LBW being common in 52% cases. In addition, coexistence of other vector-borne diseases was also noted. Transplacental infection occurs, but protective antibodies pass transplacentally and fetal effect may be minimal given sufficient immune response. In near term disease, severe fetal or neonatal illness or death may occur. Such illness may also predispose the newborn to subsequent DHF. Conservative medical and obstetrical management is the treatment of choice. Only women who went into labor required platelet transfusion. Outcome seemed to correlate with the gestational age at which dengue infection was acquired.

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Obstetrics and Gynecology Coelho, Rita Maria Ribeiro Nogueira. Dengue during pregnancy: a study of thirteen Cases. Am J Infect Dis 2009;5(4):288-93.

Suggested Reading 1. Restrepo BN, Isaza DM, Salazar CL, Ramírez JL, Upegui GE, Ospina M, et al. Prenatal and postnatal effects of dengue infection during pregnancy. Biomedica 2003;23(4):416-23. 2. Tan PC, Rajasingam G, Devi S, Omar SZ. Dengue infection in pregnancy: prevalence, vertical transmission, and pregnancy outcome. Obstet Gynecol 2008;111(5):1111-7. 3. Christiane Fernandes Alvarenga, Vânia Glória Silami, Patrícia Brasil, Maria Elizabeth Herdy Boechat, Janice

4. Basurko C, Carles G, Youssef M, Guindi WE. Maternal and fetal consequences of dengue fever during pregnancy. Eur J Obstet Gynecol Reprod Biol 2009;147(1):29-32. 5. Ismail NA, Kampan N, Mahdy ZA, Jamil MA, Razi ZR. Dengue in pregnancy. Southeast Asian J Trop Med Public Health 2006;37(4):681-3. 6. Phupong V. Dengue fever in pregnancy: a case report. BMC Pregnancy Childbirth 2001;1(1):7.

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...Cont’d from page 1047 On laparotomy, dense adhesions between anterior abdominal wall and uterus were noted. Peritoneal spillage of blood with flimsy adhesions all around was seen. Uterus was bulky, 16-week size, soft bag like, with bilateral hematosalpinx. Adhesions were removed with sharp and blunt dissection. Due to adhesions and pinpoint stenosed cervix, total abdominal hysterectomy with right salpingooophorectomy and left salpingectomy was done (Fig. 1). Cut section of uterus showed complete cervical stenosis with a band like structure in the lower part of uterus. Cavity contained old dark blood. Postoperative period was uneventful, and preoperative abdominal pain, tenderness completely subsided.

extension of lower uterine incision, while taking out transverse lie baby and inadvertent taking of posterior lip of cervix with incision line while closing. Thomas et al reported a similar case of cervical stenosis following cesarean section and vesicovaginal fistula (VVF) repair.3 Cervical stenosis, most of the time, presents with features of hematometra and in premenopausal women it presents with endometriosis like features. Inflammation is the cause of pain in abdomen. We were not able to do cervical dilatation and hematometra drainage because of fear of perforation and it could not have relieved symptoms.

Discussion

1. Suh-Burgmann EJ, Whall-Strojwas D, Chang Y, Hundley D, Goodman A. Risk factors for cervical stenosis after loop electrocautery excision procedure. Obstet Gynecol 2000;96(5 Pt 1):657-60.

Acquired cervical stenosis is most commonly associated with uterine malignancy, extensive surgical manipulation at cervix and menopause. The incidence observed for cervical stenosis widely varies from 0% to 26%.1 In our case, we do not know the exact cause of cervical stenosis. There is possibility of placenta previa associated with transverse lie. Poothavelil et al reported a case of hematometra following cesarean section for placenta previa.2 In our case; it could be the

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References

2. Poothavelil MB, Hamdi I, Zunjurwad G. Occlusion of upper genital tract following lower segment caesarean section for placenta praevia. Sultan Qaboos Univ Med J 2008;8(2):215-8. 3. Thomas S, Roy P, Biswas B, Jose R. Complete cervical stenosis following cesarean section & VVF repair. J Obstet Gynaecol India 2012;62(Suppl 1):49-51.

Obstetrics and Gynecology

Induction of Labor: A Review kavita goel*, jaya k gedam†, DISHA A RAJPUT †, MINAL V BHALERAO*

Abstract Induction of labor is a common obstetric procedure, and is indicated when the benefits to either mother or fetus outweigh those of continuing the pregnancy. Cervical assessment (Bishop score) at the time of initiation is the best independent predictor of induction success. Although multiple agents are available for labor induction, the most commonly used methods are mechanical methods, prostaglandins and oxytocin. Indication for induction of labor, clinical presentation, safety, cost and patient preference may be used in selecting the method of induction. The goal of labor induction must always be to ensure the best possible outcome for mother and newborn.

Keywords: Labor, induction of labor, oxytocin, prostaglandins

ver the past several decades, obstetricians are fascinated with the process of parturition. Thus, the concerns for maternal well-being and timing of birth have been extensively studied to generate multiple approaches to initiate labor. Some of the methods are still used in current practices. Other methods such as vaginal or uterine douches, stimulant injections thrown into the rectum, and the use of ergot alkaloid have been abandoned because of their “ineffectiveness or poisonous effects on the infant”.1

The incidence of labor induction has continued to rise over the past several decades.2 In developed countries, the number of infants delivered at term following induction of labor can be as high as one in four deliveries.3-5 The World Health Organization (WHO) Global Survey on Maternal and Perinatal Health, conducted in 24 countries which included nearly 3,00,000 observations, showed that 9.6% of them were delivered by labor induction. The survey found that African countries have lower rates of induction of labor (lowest: Niger 1.4%) compared with Asian and Latin American countries (highest: Sri Lanka 35.5%).6 Induction of Labor Induction of labor refers to artificial stimulation of uterine contractions before the true onset of spontaneous labor in order to achieve vaginal delivery *Senior

Resident Professor Dept. of Obstetrics and Gynecology ESI-PGIMSR, MGM Hospital, Parel, Mumbai, Maharashtra Address for correspondence Dr Jaya K Gedam Dr SS Rao Road, ESI-PGIMSR, MGM Hospital, Parel, Mumbai - 12, Maharashtra E-mail: jayagedam@gmail.com

†Associate

by medical or surgical means. Augmentation of labor refers to increasing the frequency and the intensity of already existing uterine contractions in a patient in true labor but progressing inadequately, in order to achieve vaginal delivery. Indications and Contraindications For induction of labor, the benefits of early delivery to either mother or fetus should outweigh the risks of pregnancy continuation.7 The indications and contraindications for induction of labor are given in Tables 1 and 2, respectively. Before labor induction, thorough examination of the maternal and fetal condition is necessary (Table 3). Indications and contraindications for induction should be reviewed. Risks and benefits of labor induction should be discussed with the patient and relatives including the risk of cesarean delivery. Confirmation of gestational age is very important and fetal lung maturity status should be performed if indicated (Table 4).7,8 A cervical examination should be performed and documented (Bishop score). Fetal presentation and position should be confirmed. Clinical pelvimetry should be performed and cephalopelvic disproportion (CPD) should be ruled out. According to WHO guidelines, labor induction should be performed at a center, where qualified staff and OT facilities are available for cesarean section. Uterine activity and electronic fetal monitoring (EFM) should be done for all patients undergoing labor induction. Prediction of Labor Induction Success

Bishop’s Score In 1964, Bishop developed a scoring system to evaluate multiparous women for elective induction at term (Table 5).9,10

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Obstetrics and Gynecology Table 1. Indications for Labor Induction

Absolute indications Hypertensive disorders: Pre-eclampsia/Eclampsia Postdated pregnancy Premature rupture of membranes Chorioamnionitis Intrauterine growth restriction Fetal complications: Isoimmunization, oligohydramnios, nonreassuring fetal status Maternal medical complications: Diabetes mellitus, renal disease, chronic pulmonary disease Intrauterine fetal death Relative indications Hypertensive disorders: Chronic hypertension Polyhydramnios Fetal anomalies requiring specialized neonatal care Psychosocial conditions: Previous precipitate labor, distance from hospital Previous stillbirth

Table 4. Criteria for Confirmation of Gestational Age and/or Fetal Pulmonary Maturity Parameters Confirmation of gestational age

≥36 weeks have elapsed since a positive serum or urine human chorionic gonadotropin pregnancy test. Ultrasound measurement at <20 weeks of gestation supports gestational age of 39 weeks or greater. Fetal pulmonary maturity

Table 2. Contraindications for Labor Induction

Absolute contraindications Vasa previa or complete placenta previa Transverse or oblique fetal lie Umbilical cord prolapse Prior classical uterine incision or transfundal uterine surgery Active genital herpes infection Absolute cephalopelvic disproportion, contracted pelvis Relative contraindications Malpresentation (breech) Cervical carcinoma

Fetal criteria

Confirm indication

Confirm gestational age

Rule out contraindications

Assess fetal lung maturity status if required

Perform clinical pelvimetry to rule out cephalopelvic disproportion

Estimate fetal weight (clinically or USG)

Assess cervical condition (Bishop score)

Confirm fetal presentation and lie

Discuss risks and benefits with patient and relatives

Confirm fetal well-being

The higher the Bishop score, the more ‘ripe’ or ‘ favorable’ the cervix is for labor induction. Most studies define an unfavorable cervix as a Bishop score of 6 or less. The higher risk of cesarean delivery

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If term gestation cannot be confirmed by two or more of the above obstetrical, clinical or laboratory criteria, amniotic fluid analyses can be used to provide evidence of fetal lung maturity. A variety of tests are available. The parameters for evidence of fetal pulmonary maturity are as follows: yy Lecithin/sphingomyelin (L/S) ratio >2.1 yy Presence of phosphatidylglycerol (PG) yy TD x FLM assay ≥70 mg surfactant/1 g albumin present yy Presence of saturated phosphatidylcholine (SPC) ≥500 ng/mL in nondiabetic patients (≥1,000 ng/mL for pregestational diabetic patients) yy Lamellar body count exceeding 30,000/µL

Table 3. Criteria for Induction of Labor Maternal criteria

Fetal heart tones have been documented as present for ≥30 weeks by Doppler ultrasound.

Modified data from Induction of Labor. ACOG Practice Bulletin No 107. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009;114:386. Fetal Lung Maturity. ACOG Practice Bulletin No. 97. American College of Obstetricians and Gynecologists. Obstet Gynecol 2008;112:717.

associated with failure of induction in nulliparous women at term with low Bishop score is wellestablished in the literature.

Cervical Length Cervical length may predict the success of spontaneous onset of labor post-term. This has been evaluated in numerous studies by sonography. However, results showed sonographic cervical length assessment to perform poorly compared to Bishop score for predicting a successful induction.11

Obstetrics and Gynecology Table 5. Modified Bishop Score Score Parameter Dilation (cm) Effacement (%) Length* (cm) Station Consistency Cervical position

0 Closed 0-30 >4 -3 Firm

1 1-2 40-50 2-4 -2 Medium

2 3-4 60-70 1-2 -1 or 0 Soft

Posterior

Mid-position Anterior

3 5 or more 80 or more 1-2 +1 or +2

Bishop EH. Pelvic scoring for elective induction. Obstet. Gynecol.1964;24:266.

*Modification by Calder AA, Brennand JE. Labor and normal

Table 7. Standardized Oxytocin Regimen yy Dilution: 10 U oxytocin in 1,000 mL normal saline for resultant concentration of 10 mU oxytocin/mL yy Infusion rate: 2 mU/min or 12 mL/hr yy Incremental dose: 2 mU/min or 12 mL/hr every 45 minutes until contraction frequency adequate yy Maximum dose: 16 mU/min or 96 mL/hr Hayes EJ, Weinstein L. Improving patient safety and uniformity of care by a standardized regimen for the use of oxytocin. Am J Obstet Gynecol 198:622.

delivery: induction of labor. Curr Opin Obstet Gynecol. 1991;3:764. This modification replaces percent effacement as one of the parameters of the Bishop Score.10

Table 8. Labor Stimulation with Oxytocin: Examples of Low- and High-dose Oxytocin Dosing Regimens Regimen

Starting dose (mU/min)

Incremental dose (mU/min)

Dosage interval (min)

Low-dose

0.5-2.0

1-2

15-40

3-6*

15-40

Table 6. Methods of Cervical Ripening Mechanical methods Surgical methods Medical methods Membrane stripping Mechanical dilators Hygroscopic dilators yy Laminaria tents yy Lamicel Foley balloon catheter yy Without extra amniotic saline infusion yy With extraamniotic saline infusion

Amniotomy

Oxytocin Prostaglandins yy E2 (Dinoprostone) yy E1 (Misoprostol) Progesterone receptor antagonists (Mifepristone) Nitric oxide donors Estrogen Relaxin Hyaluronic acid

Fetal Fibronectin

High-dose

Induction of Labor. ACOG Practice Bulletin No 107. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2009;114:386. *The incremental increase is reduced to 3 mU/min in the presence of hyperstimulation and reduced to 1 mU/min with recurrent hyperstimulation.

finally leading to thinning and dilatation of the cervix.14 There is enzymatic dissolution of collagen fibrils of cervix, along with an increase in water content or swelling. These changes are induced by hormones (estrogen, progesterone, relaxin), as well as cytokines, prostaglandins and nitric oxide synthesis enzymes.15 Methods used for cervical ripening include mechanical and pharmacologic methods (Table 6). Mechanical Methods

An elevated fetal fibronectin (FFN) concentration in cervicovaginal secretions has been used to predict success of labor induction. An elevated FFN may be caused by disruption or inflammation of the chorionicdecidual interface. A prospective trial concluded that FFN does not predict vaginal delivery in nulliparous women.12 Only obstetric history and digital examination predicted accurately vaginal delivery within 24 hours.13

Mechanical methods of cervical ripening were among the first methods used for labor induction and have been used for centuries. They are often less costly, result in less hyperstimulation, are easy to store and may result in fewer side effects for mother and fetus are the advantages.16 Risk of infection, disruption of a low-lying placenta and some maternal discomfort on manipulation of the cervix are some disadvantages.

Cervical Ripening

Membrane Stripping

Cervical ripening is an important predictor of labor outcome. It is a complex chemical change resulting in physical softening and distensibility of the cervix,

Stripping or sweeping of the fetal membranes is digital separation of the chorioamniotic membrane from the wall of the cervix and lower uterine segment.

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Obstetrics and Gynecology This causes the release of endogenous prostaglandins from the adjacent membranes and decidua, as well as from the cervix.16 Numerous studies have conducted routine membrane stripping at 38 or 39 weeks to either prevent prolonged or post-term pregnancies.17 Complications include rupture of membranes, hemorrhage from disruption of an occult placenta previa and the development of chorioamnionitis. Mechanical Dilators Mechanical dilators include hygroscopic dilators (laminaria or lamicel), balloon (Foley catheter) and balloon with extra-amniotic saline infusion (EASI). Hygroscopic Dilators Cervical dilators are made from organic seaweed (laminaria) or synthetic hydrophilic materials (lamicelpolyvinyl alcohol polymer). They are introduced into the cervical canal and left in situ for 6-12 hours where they increase in diameter because of their hydrophilic properties, achieving a gradual stretching, dilatation and effacement of the cervix. In the last two decades, there has been a reduction in the use of hygroscopic and osmotic dilators for the induction of labor in favor of the mechanical and pharmacologic agents. Risk of maternal and fetal infections with hygroscopic and osmotic dilators is more as compared with the use of other pharmacologic agents.18 They are contraindicated in cases of ruptured membranes. Placement of dilators also requires additional training and may be associated with rupture of membranes, vaginal bleeding and patient discomfort or pain. Extra-amniotic Balloon and Extra-amniotic Saline Infusion The Foley catheter affects cervical ripening in two ways: Gradual dilatation and separation of the deciduas from the amnion stimulating prostaglandin release. Foley catheters of size 14-26 F with inflation volume of 30-80 mL, and the EASI with infusion rates of 30-40 mL/hour have been shown to be safe and efficacious. The advantages of Foley catheter when compared with prostaglandins include lower cost, stability at room temperature, reduced risk of uterine tachysystole with or without fetal heart rate (FHR) changes, and applicability in an outpatient setting. It seems that higher insufflations volumes (80 mL) may be more efficacious than lower volumes (30 mL).19,20 The concomitant use of oxytocin with Foley catheter does not seem to shorten the duration of labor.21

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The mean induction to delivery time was shorter with the concomitant use of Foley catheter with vaginal misoprostol. There was no increase in labor complications or adverse perinatal outcomes.22 A meta-analysis of randomized controlled trial (RCT) concluded that there was no significant difference between Foley catheter balloon and locally applied prostaglandins in cesarean delivery rates. However, prostaglandins had a significantly increased risk of excessive uterine activity.23 A RCT concluded that induction of labor using mechanical methods compared to prostaglandins resulted in similar cesarean section rates along with a lower risk of excessive uterine activity. Mechanical methods compared with oxytocin had lower risk of cesarean section.24 The Foley catheter can be associated with risks of rupture of membranes, vaginal bleeding in women with a low-lying placenta, febrile morbidity and displacement of the presenting part.25

Surgical Method of Induction Amniotomy Amniotomy, artificial rupture of membranes, is a procedure carried out by iatrogenic rupture of the chorioamniotic membranes by either toothed clamp (Allis or Kocherâ&#x20AC;&#x2122;s clamp) or multiple punctures with some pointed structure like 26-guage needle. It is commonly performed in multiparous women with favorable Bishop score with success. However, to minimize the risk of cord prolapse, fetal vertex should not be floating and be well-applied to the cervix. The FHR should be assessed before and after the procedure, and the character and color of the amniotic fluid should be recorded. The concomitant use of amniotomy and intravenous (IV) oxytocin is more effective compared with amniotomy alone, with most women delivering vaginally within 24 hours.26

Pharmacologic Techniques Prostaglandins As stated earlier in mechanism of cervical ripening, prostaglandins act on cervix by dissolution of collagen fibrils and an increase in water content of the cervix. Also, prostaglandins increase intracellular calcium levels, causing myometrial contractions. Prostaglandins are already found in the myometrium, deciduas and fetal membranes during pregnancy. Initially given by intramuscular and oral routes, nowadays locally applied prostaglandins, vaginally or intracervically, are the routes of choice because of patient acceptability

Obstetrics and Gynecology with fewer side effects. Side effects include fever, chills, vomiting and diarrhea, etc. Overall, induction with prostaglandins was associated with an increase in successful vaginal delivery within 24 hours, a reduction in the rate of cesarean delivery and an increase in the risk of uterine tachysystole with FHR changes.27 Prostaglandins should not be used in women with a prior cesarean delivery or myomectomy because of an increased risk of uterine rupture.28 Uterine activity and FHR monitoring should be maintained after administration of prostaglandins for cervical ripening.7 PGE2 Dinoprostone Local application of prostaglandin E2 (PGE2) is commonly used for cervical ripening. Its gel form (Prepidil) is available in a 2.5 mL syringe containing 0.5 mg of dinoprostone. With the woman supine, the tip of pre-filled syringe is placed intracervically to deposit the gel just below the internal cervical os. After administration, she remains supine for at least 30 minutes. Doses may be repeated every 6 hours with a maximum of two doses in 24 hours recommended. A 10 mg dinoprostone vaginal insert (Cervidil) is also approved for cervical ripening. This is a thin, flat, rectangular polymeric wafer held within a small, white mesh polyester sac with long attached tail. It provides slower release of drug (0.3 mg/hr). It is used as a single dose placed transversely in posterior vaginal fornix. Following insertion, a woman should remain supine for at least 2 hours. The insert is removed after 12 hours or with labor onset. These two preparations are costly, and need refrigerated storage to remain stable. Prostaglandin E1

Misoprostol (Cytotec) is a synthetic prostaglandin E1 (PGE1) analog initially used with nonsteroidal antiinflammatory drugs (NSAIDs) to prevent gastric ulcers and is available as 100 and 200 µg tablets. Misoprostol for preinduction cervical ripening is an ‘off-label’ use.29 Misoprostol is less costly, safe and is also stable at room temperature. Misoprostol can be administered orally or placed vaginally with few systemic side effects. A Cochrane meta-analysis of trials revealed that vaginal misoprostol improved cervical ripening with an increased rate of vaginal delivery within 24 hours compared with placebo.30 Compared with PGE2 also, it gave similar results. However, uterine tachysystole with fetal heart changes was more common. Most studies suggested that restricting the dose of misoprostol to 25 µg every 4 hours significantly reduced the above risk.31

In a meta-analysis, oral misoprostol use was found clearly superior to placebo, as women administered 25 and 50 µg oral misoprostol dosages were more likely to deliver vaginally within 24 hours, needed less oxytocin and had a lower cesarean rate.32 Some investigators have described titrating oral misoprostol to its desired effect with less uterine overactivity compared to vaginal misoprostol.33 Low- dose oral misoprostol (20 µg) is achieved by making a solution (e.g., dissolving a 200 µg tablet in 200 mL tap water) and administered every 2 hours. Other modes of administration include buccal and sublingual route of misoprostol administration.34 A systematic review concluded that the sublingual route of misoprostol administration is equally efficacious as the vaginal one for labor induction. However, the concerns regarding safety, dosing, side effects and adverse maternal and neonatal outcome need to be studied in future trials for routine recommendation in obstetrics.35 Progesterone Receptor Antagonists RU-486 (Mifepristone) is a more selective progesterone receptor antagonist and has been used for early pregnancy termination. Because of its action, trials had been undergoing for its applicability in cervical ripening and labor induction. The studies suggested that mifepristone reduced the rate of cesarean section as compared to placebo. Therefore, future trials are needed to compare mifepristone with other established cervical ripening agents.36 Nitric Oxide Donors Nitric oxide donors act by increasing the expression of cyclooxygenase-2 (COX-2) in the cervix, thus improving cervical distensibility without causing uterine contractions. Benefits include its use in the outpatient setting, low-cost and ease of administration. Side effects may include maternal hemodynamic changes associated with a vasodilator, including hypotension and tachycardia. Women reported headaches and palpitations as the most common side effects of intravaginal administration of isosorbide mononitrate, 40 mg.37 A trial comparing isosorbide mononitrate with placebo resulted in no difference in admission to delivery interval despite a clinical effect on cervical ripening.38 Therefore, further trials are needed for isosorbide mononitrate use as a cervical ripening agent before its acceptance. Several other approaches to cervical ripening have been documented in literature, including estrogen, relaxin

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Obstetrics and Gynecology and hyaluronic acid, etc. None of them were found to be clinically useful and they have now been superseded by the use of mechanical methods and prostaglandins.

Medical Methods of Induction Oxytocin Oxytocin is a polypeptide neurohormone originating from the hypothalamus and secreted from the posterior lobe of the pituitary gland, representing the agent most frequently used for labor induction. Gestational age is a major factor affecting the dose response to oxytocin with the uterus responding to oxytocin at approximately 20 weeks gestation, with increasing responsiveness with advancing gestational age primarily due to an increase in myometrial oxytocin binding sites. Thereafter, myometrial sensitivity to oxytocin remains more or less same from 34 weeks to term till active labor commences, and the sensitivity increases many fold. Due to this mechanism, oxytocin is better in augmenting labor than in inducing labor, and even less efficacious as a cervical ripening agent. Oxytocin is mainly given by IV infusion. It is not active orally because it is degraded by gastrointestinal enzymes. The plasma half-life is short, around 3-6 minutes and steady state concentrations are reached within 30-40 minutes of continuous IV infusion. It is prepared by diluting 10 units in 1,000 mL of an isotonic solution. The standardized dosing regimen consists of infusion rate of 2 mU/min or 12 mL/hour with an incremental dose of 2 mU/min or 12 mL/hour every 45 minutes until contraction frequency is adequate (Table 7). Maximum dose is 16 mU/min or 96 mL/hour. IV oxytocin is considered superior to placebo with a significant number of women delivering vaginally within 24 hours.39 Two regimes of oxytocin administration are commonly practiced. The low-dose regimen consists of a starting dose of 0.5-2 mU/min with an incremental dose of 1-2 mU/min every 15-40 minutes and the highdose regimen has a starting dose of 6 mU/min and an incremental dose of 3-6 mU/min every 15-40 minutes (Table 8). Which regimen of oxytocin is superior is debatable; however, both regimens are acceptable for the induction of labor.40 The high-dose protocol was not only associated with significant shorter induction to delivery time but was also associated with a higher incidence of uterine hyperstimulation and need for oxytocin discontinuation. Whatever regimen is decided upon, each hospital should develop protocols for their administration as per their own experience and safety, and should revise it from time to time. This has reduced mean maximum oxytocin infusion rate and improved

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neonatal outcomes without increasing cesarean delivery rate.41 WHO recommended if prostaglandins are not available, IV oxytocin alone can be used for induction of labor.2 The comparison of oxytocin with PGE2 revealed that prostaglandins decrease the induction to delivery time. Oxytocin induction may increase the rate of interventions in labor. Complications Associated with Induction of Labor

Uterine Overactivity This is the most frequently encountered complication of oxytocin or prostaglandin administration. The most commonly used terms to describe are hyperstimulation, tachysystole and hypertonus. The American College of Obstetricians and Gynecologists (ACOG) offers the following definitions: ÂÂ

Tachysystole can be defined as a persistent pattern of ≥ 5 contractions in 10 minutes.

ÂÂ

Hypertonus is described as a single contraction lasting longer than 2 minutes.

ÂÂ

Hyperstimulation is described as tachysystole or hypertonus associated with FHR abnormalities.42

One of the advantages of oxytocin administration is that if uterine hyperstimulation is noticed, the infusion can quickly be stopped. This usually results in the resolution of such uterine overactivity. In addition, placing the woman in the left lateral position, administering oxygen and IV fluids may be of benefit. If FHR tracing abnormalities persist and uterine hyperstimulation is ongoing, the use of a tocolytic such as terbutaline may be considered.

Failed Induction There are currently no criteria for a failed induction. The obstetrician should understand that cervical ripening itself can take some time, and that the establishment of an active labor is important to label labor as failed induction. A study concluded that 40% of the women who remained in the latent phase after 12 hours of oxytocin and membrane rupture were delivered vaginally. Therefore, it is important not to label labor induction a failure in the latent phase until oxytocin has been administered for at least 12 hours after membrane rupture.43 Failed induction is not necessarily an indication for cesarean section. Other options include a further attempt to induce labor (the timing should depend on the clinical situation and the patient’s wishes) or waiting for spontaneous labor.

Obstetrics and Gynecology Cesarean Section Increasing incidence of labor induction has contributed to the increasing cesarean section rate. Compared to spontaneous onset of delivery, induction of labor is associated with an increased risk for emergency cesarean section both among nulliparous and multiparous women.44-46

Greater Need for Pain Relief Induced labor significantly differs from the physiological spontaneous onset labor, with a longer and often painful latent phase. Prostaglandins may be associated with significant discomfort. Simple analgesia may suffice, but some women will require stronger opiate/epidural analgesia.

Uterine Rupture Uterine rupture is rare and in most instances occurs in women with prior uterine surgery such as cesarean delivery or myomectomy. Other risk factors are grand multiparity, marked uterine overdistension either with a macrosomic fetus, multiple gestation, polyhydramnios, or fetal malpresentation. Most studies suggest that the use of oxytocin for labor induction or augmentation is not associated with a significant increase in the risk of uterine rupture in women with a prior cesarean delivery. The ACOG states that the use of misoprostol in women with prior cesarean delivery or major uterine surgery has been associated with an increase in uterine rupture and, therefore, should be avoided in the third trimester. References 1. Thomas R. observations on the caesarean section and on other obstetrics complications. Manchester: Bradley’s Library Oxford; 1865. 2. WHO recommendations for induction of labour. World Health Organization: Geneva; 2011. 3. Caughey AB, Sundaram V, Kaimal AJ, Cheng YW, Gienger A, Little SE, et al. Maternal and neonatal outcomes of elective induction of labor. Evidence report/technology assessment no.176. AHRQ Publication no.09-E005. Rockville (MD): Agency for Health Research and Quality; 2009. 4. Declercq ER, Sakala C, Corry MP, Applebaum S. Listening to Mothers II. Report of the Second National U.S. Survey of Women’s Childbearing Experiences. Childbirth Connection: New York, NY; 2006. 5. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F, Kirmeyer S, et al; Centers for Disease Control and Prevention National Center for Health Statistics National Vital Statistics System. Births: final data for 2005. Natl Vital Stat Rep 2007;56(6):1-103.

6. WHO Global Survey on Maternal and Perinatal Health. Induction of labour data. World Health Organization: Geneva; 2010. 7. ACOG Committee on Practice Bulletins - Obstetrics. ACOG Practice Bulletin No. 107: Induction of labor. Obstet Gynecol 2009;114(2 Pt 1):386-97. 8. ACOG Practice Bulletin No. 97: Fetal lung maturity. American College of Obstetricians and Gynecologists. Obstet Gynecol 2008;112(3):717-26. 9. Bishop EH.Pelvic scoring for elective induction. Obstet Gynecol 1964;24:266-8. 10. Brennand JE, Calder AA. Labor and normal delivery: induction of labor. Curr Opin Obstet Gynecol 1991;3(6): 764-8. 11. Hatfield AS, Sanchez-Ramos L, Kaunitz AM. Sonographic cervical assessment to predict the success of labor induction: a systematic review with metaanalysis. Am J Obstet Gynecol 2007;197(2):186-92. 12. Sciscione A, Hoffman MK, DeLuca S, O’Shea A, Benson J, Pollock M, et al. Fetal fibronectin as a predictor of vaginal birth in nulliparas undergoing preinduction cervical ripening. Obstet Gynecol 2005;106(5 Pt 1):980-5. 13. Reis FM, Gervasi MT, Florio P, Bracalente G, Fadalti M, Severi FM, et al. Prediction of successful induction of labor at term: role of clinical history, digital examination, ultrasound assessment of the cervix, and fetal fibronectin assay. Am J Obstet Gynecol 2003;189(5):1361-7. 14. Maul H, Mackay L, Garfield RE. Cervical ripening: biochemical, molecular, and clinical considerations. Clin Obstet Gynecol 2006;49(3):551-63. 15. Jozwiak M, Bloemenkamp KW, Kelly AJ, Mol BW, Irion O, Boulvain M. Mechanical methods for induction of labour. Cochrane Database Syst Rev 2012;3:CD001233. 16. Mitchell MD, Flint AP, Bibby J, Brunt J, Arnold JM, Anderson AB, et al. Rapid increases in plasma prostaglandin concentrations after vaginal examination and amniotomy. Br Med J 1977;2(6096):1183-5. 17. Andersen BB, Knudsen B, Lyndrup J, Fælling AE, Illum D, Johansen M, et al. Acupuncture and/or sweeping of the fetal membranes before induction of labor: a prospective, randomized, controlled trial. J Perinat Med 2013;41(5): 555-60. 18. Gelber S, Sciscione A. Mechanical methods of cervical ripening and labor induction. Clin Obstet Gynecol 2006;49(3):642-57. 19. Kashanian M, Nazemi M, Malakzadegan A. Comparison of 30-mL and 80-mL Foley catheter balloons and oxytocin for preinduction cervical ripening. Int J Gynaecol Obstet 2009;105(2):174-5. 20. Delaney S, Shaffer BL, Cheng YW, Vargas J, Sparks TN, Paul K, et al. Labor induction with a Foley balloon inflated to 30 mL compared with 60 mL: a randomized controlled trial. Obstet Gynecol 2010;115(6):1239-45. 21. Pettker CM, Pocock SB, Smok DP, Lee SM, Devine PC. Transcervical Foley catheter with and without oxytocin for cervical ripening: a randomized controlled trial. Obstet Gynecol 2008;111(6):1320-6.

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Obstetrics and Gynecology 22. Carbone JF, Tuuli MG, Fogertey PJ, Roehl KA, Macones GA. Combination of Foley bulb and vaginal misoprostol compared with vaginal misoprostol alone for cervical ripening and labor induction: a randomized controlled trial. Obstet Gynecol 2013;121(2 Pt 1):247-52. 23. Wei G, Bull H, Zhou X, Tabel H. Intradermal infections of mice by low numbers of African trypanosomes are controlled by innate resistance but enhance susceptibility to reinfection. J Infect Dis 2011;203(3):418-29. 24. Jozwiak M, Bloemenkamp KW, Kelly AJ, Mol BW, Irion O, Boulvain M. Mechanical methods for induction of labour. Cochrane Database Syst Rev 2012;(3):CD001233. 25. Maslovitz S, Lessing JB, Many A. Complications of transcervical Foley catheter for labor induction among 1,083 women. Arch Gynecol Obstet 2010;281(3):473-7. 26. Howarth GR, Botha DJ. Amniotomy plus intravenous oxytocin for induction of labour. Cochrane Database Syst Rev 2001;(3):CD003250. 27. Kelly AJ, Kavanagh J, Thomas J. Vaginal prostaglandin (PGE2 and PGF2a) for induction of labour at term. Cochrane Database Syst Rev 2003;(4):CD003101. 28. Lydon-Rochelle M, Holt VL, Easterling TR, Martin DP. Risk of uterine rupture during labor among women with a prior cesarean delivery. N Engl J Med 2001;345(1):3-8. 29. ACOG Committee Opinion. American College of Obstetrician and Gynecologist. ACOG Committee Opinion. Number 283, May 2003. New U.S. Food and Drug Administration labeling on Cytotec (misoprostol) use and pregnancy. Obstet Gynecol 2003;101(5 Pt 1):104950. 30. Hofmeyr GJ1, Gülmezoglu AM. Vaginal misoprostol for cervical ripening and induction of labour. Cochrane Database Syst Rev 2003;(1):CD000941. 31. Crane JM, Butler B, Young DC, Hannah ME. Misoprostol compared with prostaglandin E2 for labour induction in women at term with intact membranes and unfavourable cervix: a systematic review. BJOG 2006;113(12):1366-76. 32. Alfirevic Z, Weeks A. Oral misoprostol for induction of labour. Cochrane Database Syst Rev 2006;(2):CD001338. 33. Kundodyiwa TW, Alfirevic Z, Weeks AD. Low-dose oral misoprostol for induction of labor: a systematic review. Obstet Gynecol 2009;113(2 Pt 1):374-83. 34. Souza AS, Amorim MM, Feitosa FE. Comparison of sublingual versus vaginal misoprostol for the induction of labour: a systematic review. BJOG 2008;115(11):1340-9.

35. Muzonzini G, Hofmeyr GJ. Buccal or sublingual misoprostol for cervical ripening and induction of labour. Cochrane Database Syst Rev 2004;(4):CD004221. 36. Hapangama D, Neilson JP. Mifepristone for induction of labour. Cochrane Database Syst Rev 2009;(3):CD002865. 37. Ekerhovd E, Bullarbo M, Andersch B, Norström A. Vaginal administration of the nitric oxide donor isosorbide mononitrate for cervical ripening at term: a randomized controlled study. Am J Obstet Gynecol 2003;189(6):1692-7. 38. Bollapragada SS, MacKenzie F, Norrie JD, Eddama O, Petrou S, Reid M, et al. Randomised placebo-controlled trial of outpatient (at home) cervical ripening with isosorbide mononitrate (IMN) prior to induction of labour-clinical trial with analyses of efficacy and acceptability. The IMOP study. BJOG 2009;116(9):1185-95. 39. Alfirevic Z, Kelly AJ, Dowswell T. Intravenous oxytocin alone for cervical ripening and induction of labour. Cochrane Database Syst Rev 2009;(4):CD003246. 40. Patka JH, Lodolce AE, Johnston AK. High- versus lowdose oxytocin for augmentation or induction of labor. Ann Pharmacother 2005;39(1):95-101. 41. Clark S, Belfort M, Saade G, Hankins G, Miller D, Frye D, et al. Implementation of a conservative checklistbased protocol for oxytocin administration: maternal and newborn outcomes. Am J Obstet Gynecol 2007;197(5):480. e1-5. 42. American College of Obstetricians and Gynecologists: Induction of labour. Practice Bulletin No.10, November 1999a. 43. Rouse DJ, Weiner SJ, Bloom SL, Varner MW, Spong CY, Ramin SM, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU). Failed labor induction: toward an objective diagnosis. Obstet Gynecol 2011;117(2 Pt 1):267-72. 44. Jonsson M, Cnattingius S, Wikström AK. Elective induction of labor and the risk of cesarean section in lowrisk parous women: a cohort study. Acta Obstet Gynecol Scand 2013;92(2):198-203 45. Ehrenthal DB, Jiang X, Strobino DM. Labor induction and the risk of a cesarean delivery among nulliparous women at term Obstet Gynecol 2010;116(1):35-42. 46. Vardo JH, Thornburg LL, Glantz JC. Maternal and neonatal morbidity among nulliparous women undergoing elective induction of labor. J Reprod Med 2011;56(1-2):25-30.

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Ophthalmology

Adult Unilateral Chorioretinal Atrophy Secondary to Acquired Rubella Meenakshi Patil*, Neelam Redkar†, Maruti Karale‡, Manish Dodmani#

Abstract Rubella retinopathy in adults is uncommon. Here we report a case of 25-year-old healthy female who presented with blurring of vision of right eye, and was detected to have chorioretinal atrophy on fundus examination. Detailed investigations of the patient to evaluate the cause of chorioretinal atrophy were done in which her serology against rubella was found strongly positive. This is an uncommon case of acquired adult unilateral rubella retinopathy, which is a rare presentation of rubella infection in adults.

Keywords: Acquired rubella, viral retinopathy

ubella virus is a member of the family Togaviridiae and is only found in humans; there is no known animal reservoir. Rubella is usually a mild acute viral infection of short duration, which characteristically includes fever, rash and lymphadenopathy. Congenital chronic fetal rubella infection may cause various systemic and ocular malformations. Adults are more likely to experience a prodromal phase with malaise, low-grade fever, headache and conjunctivitis. Rubella has a broadspectrum of other possible manifestations and atypical presentations can be seen in adults.1,2

Case Report A 25-year-old female, married since 5 years and having two children, presented to our hospital with history of right hemicranial headache and blurred vision of right eye since 3 months. There was history of fever and upper respiratory tract infection 15 days prior to appearance of her symptoms. There was no history of rash, joint pains and no other significant history. Her general and systemic clinical examination was unremarkable.

*Assistant Professor †Professor ‡Senior Resident #Junior Resident Dept. of Medicine Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra Address for correspondence Dr Meenakshi Patil Flat no. 702, Awesome Heights Society, Off Military Road Marol, Andheri (East) - 400 072, Mumbai, Maharashtra E-mail: meenakshi.patil90@gmail.com

On ophthalmic examination for blurred right eye vision, her right eye visual acuity was 6/9 and her right eye fundus showed large chorioretinal atrophic patch in the inferotemporal region (Fig. 1). Her left eye visual acuity was normal at 6/6 and left eye fundus was normal. Patient’s investigations were initiated to evaluate the cause for chorioretinal atrophy. Her enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) was negative, venereal disease research laboratory (VDRL) for syphilis was negative, antibodies against tuberculosis and tuberculin test were negative. Antibodies to hepatitis C and hepatitis B antigen test were negative. Her erythrocyte sedimentation rate (ESR), antinuclear antibody test (ANA), double-stranded deoxyribonucleic acid (dsDNA), rheumatoid factor, complete blood counts, urine and stool examination,

Figure 1. Right eye fundus showing large chorioretinal atrophic patch in the inferotemporal region.

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Ophthalmology chest X-ray and ultrasonography were normal. Her TORCH test (ELISA for Toxoplasmosis, Rubella, Cytomegalovirus (CMV) and Herpes simplex virus [HSV]-1&2) revealed both immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies positive for rubella; IgM antibody titers - 20 IU/mL (positive >10 IU/mL) and IgG antibody titers were 160 IU/mL (positive >10 IU/mL). IgG antibodies were positive for toxoplasma, CMV and HSV-1 but IgM was negative suggestive of past infection. Her magnetic resonance imaging (MRI) brain was normal. Patient was treated symptomatically with analgesics for headache and dark goggles were advised. Repeat TORCH test after one and half months showed negative rubella IgM and decrease in IgG titers to 110 IU/mL. Patient’s symptoms of headache improved over 1 month with some improvement in visual acuity, though mild blurring of vision persisted. Thus, after detailed work-up of patient to rule out other causes of chorioretinitis and chorioretinal atrophy and with the evidence of positive serology for rubella, diagnosis of chorioretinal atrophy secondary to acquired rubella chorioretinitis was made.

believed to be an ongoing disease capable of developing subretinal neovascularization, greater pigment epithelial mottling, and progressive retinal changes, including choroidal atrophy.3,4 Salt and pepper pigmentary disturbance is the most common ocular complication in congenital rubella but it is not common in adult acquired rubella.5 A clinical diagnosis of rubella may be difficult to make because many exanthematic diseases may mimic rubella infection. Typical rubilliform rashes may also be induced by other viruses like Enteroviruses, Chikungunya virus, Ross virus and Parvovirus B19. In addition, as many as 50% rubella infections may be subclinical; therefore, laboratory studies are important to confirm the diagnosis of acute rubella infection.

Discussion

The laboratory diagnosis of rubella can be made either through serologic testing or by viral culture. But the process of culture is difficult and the facilities for culture are lacking in most of the laboratories. Hence, serodiagnosis is considered the most useful and reliable method for detection of infection. Acute rubella infection is usually established by demonstration of seroconversion in paired sera or by demonstration of rubella-specific IgM antibodies in a single specimen. IgM antibodies usually attain their maximum concentration within 10-14 days after the onset of illness but the duration of response is variable. In general, following primary infection, they persist for 6-12 weeks, although some patients may exhibit a more prolonged response, which may extend for as long as a year. ELISA is a rapid, reliable and sensitive method of measuring rubella-specific IgM antibodies in the serum sample of patients with acute rubella infection.7 Natural rubella infection normally confers lifelong immunity. In India, about 50% of children acquire rubella antibodies by the age of 5 years and 80-90% become immune by the age of 15. A study among unvaccinated girls, 10-16 years of age, found that 86.5% had antibodies against rubella. Another study funded by the Serum Institute of India Pvt. Ltd. manufacturers of the MMR (mumps, measles, rubella) vaccine in India, conducted among unvaccinated girls with a mean age of 10.7 years reported that 90% were protected despite not being vaccinated.8,9

Rubella (which means ‘little red’ and is also known as German measles) was originally thought to be a variant of measles. It is a mild disease in children and adults, but can cause devastating problems if it infects the fetus, especially if infection is in the first few weeks of pregnancy. The sequelae of congenital rubella syndrome are congenital heart defects, neurologic problems, ophthalmic problems (cataract, glaucoma, retinopathy), hepatosplenomegaly and intrauterine growth retardation. Man is the only host. Rubella virus is spread via an aerosol route and occurs throughout the world. The initial site of infection is the upper respiratory tract. The virus replicates locally (in the epithelium, lymph nodes) leading to viremia and spreads to other tissues. As a result the disease symptoms develop. There is usually no prodrome in young children but in older children and adults, disease results in low-grade fever, rash, sore throat and some individuals get arthralgia and arthritis (especially adult women). The patient is infectious from about 1 week before onset of rash to about 1 week after that. Complications of rubella in adults are extremely rare (1 in 6,000 cases). Rubella encephalopathy, panencephalitis, orchitis and neuritis are some of the rare complications.1,2 Rubella retinitis can be associated with significant secondary chorioretinal atrophy. Rubella retinopathy is

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The ocular complications of rubella must be differentiated from other causes of vasculitis and retinitis. In our patient, diagnostic tests to rule out other causes of vasculitis and retinitis were solicited: VDRL, serology for CMV, toxoplasmosis antibodies, HIV, herpes, ESR, chest radiographs, rheumatologic tests and white blood cell count, which were within normal limits.6

Ophthalmology In India, the measles vaccine is already given in the Government Universal Immunization Program (UIP) at the age of 9-12 months and the combined MMR vaccine is given at the age of 15 months as an optional vaccine in the private sector.10 Our patient was not vaccinated for rubella. Because the antibody levels to rubella in our patient were high during the subacute stage and decreased within 2 months, we believe this patient had unilateral rubella retinitis with chorioretinal atrophy, a condition rarely described in adult rubella infection. There are very few case reports of adult rubella chorioretinitis described in literature.11 References 1. Best JM. Rubella. Semin Fetal Neonatal Med 2007;12(3): 182-92. 2. Heggie AD, Robbins FC. Natural rubella acquired after birth. Clinical features and complications. Am J Dis Child 1969;118(1):12-7. 3. Deutman AF, Grizzard WS. Rubella retinopathy and subretinal neovascularization. Am J Ophthalmol 1978;85(1):82-7.

4. Menne K. Congenital rubella retinopathy - a progressive disease. Klin Monbl Augenheilkd 1986;189(4):326-9. 5. Khurana RN, Sadda SR. Images in clinical medicine. Salt-and-pepper retinopathy of rubella. N Engl J Med 2006;355(5):499. 6. Schuil J, van de Putte EM, Zwaan CM, Koole FD, Meire FM. Retinopathy following measles, mumps, and rubella vaccination in an immuno-incompetent girl. Int Ophthalmol 1998;22(6):345-7. 7. Morgan-Capner P. 1989;299(6695):338-9.

Diagnosing

rubella.

BMJ

8. Ramamurty N, Murugan S, Raja D, Elango V, Mohana, Dhanagaran D. Serosurvey of rubella in five blocks of Tamil Nadu. Indian J Med Res 2006;123(1):51-4. 9. Yadav S, Wadhwa V, Chakarvarti A. Prevalence of rubella antibody in school going girls. Indian Pediatr 2001;38(3):280-3. 10. Sunderlal, Adersh, Pankaj. Textbook of community medicine. 1st edition, CBS Publishers and Distributers: New Delhi and Bangalore 2007. ISBN:81-239-1441-5. 11. Damasceno N, Damasceno E, Souza E. Acquired unilateral rubella retinopathy in adult. Clin Ophthalmol 2010;5:3-4.

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Cataract Surgery Improves Vision in Eyes with AMD Cataract surgery improves vision irrespective of the severity of age-related macular degeneration (AMD), reported a large clinical study published online in Ophthalmology. Researchers noted that outcomes for 793 patients with 1232 cataracts revealed marked gains in best-corrected visual acuity, ranging from 6.8 letters in eyes with advanced AMD to 11.2 letters in those with mild disease.

Contact Lenses Recommended for Babies after Cataract Surgery It is standard for adults and children who undergo cataract surgery to be implanted with an artificial lens in their eye. But a clinical trial funded by the National Eye Institute suggests that the ideal treatment for infants should be surgery followed by the use of contact lenses for several years, and then an eventual lens implant. A cataract is a cloud on the lens of the eye. Removal of cataracts involves a quick, safe surgical procedure, which is usually followed by the artificial lens - called an intraocular lens (IOL) - being implanted. Most people would associate cataracts with elderly people, but infants can also be born with cataracts. About 1,200 to 1,600 babies are diagnosed each year with cataracts.

Contact Lenses ‘as Effective’ as IOLs This is confirmed by the results of the new trial - published in JAMA Ophthalmology - which suggests that contact lenses are not only as effective as an IOL, but they are safer. Cataracts can occur in both eyes, but the new study only looked at cataracts in infants that affect one eye, which are called “congenital unilateral cataracts.” The trial took place across 12 clinical centers and enrolled 114 infants with a congenital unilateral cataract who were between 1 and 6 months old. The parents visiting these clinics were informed about the potential risks and benefits of surgery before participating in the study. Half of the infants were randomized into receiving an IOL and the other half received contact lenses. When the babies reached toddler-age, the researchers used a visual acuity test using flash cards imprinted with finer and finer patterns. The idea is that patterns that are visible to the toddlers will grab their attention, while cards that appear blank will not. At ages 1 and 4.5 years old, there were no differences in visual acuity between the IOL and contact lens groups. But the IOL group did have more post-surgical complications.

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Orthopedics

Evaluation of Results of Different Treatment Modalities in Management of Diaphyseal Fractures of Humerus Vipin Sharma*, Bhanu Awasthi†, SM Mehta‡, RS Yadav#, Sudhir Babhulkar$

Abstract Introduction: This paper presents evaluation of 103 patients of diaphyseal fractures of humerus treated by different modalities with a mean follow-up of two years. Material and methods: This is a prospective and retrospective study conducted at Dr Rajendra Prasad Govt. Medical College and Hospital, Kangra (Tanda), HP, India during the year 2005-2006. It aimed at finding out comparison of the results obtained by different modes of treatment in fractures of humeral diaphysis. We studied a total of 103 patients out of which a prospective study involved 72 patients and a retrospective study (2003-2004) involved 31 patients (whose records were available). All the cases were examined clinically and radiologically and were managed with an appropriate method of treatment. The closed fractures were classified by Muller’s classification while Gustillo Anderson was used for open fractures. The nonoperative methods included cooptation or U-shaped brachial splint or U-slab, hanging arm cast, Velpeau dressing, Shoulder spica cast and functional brace. The patients with failure of closed reduction, with complex fracture geometry or open fractures were treated by operative methods. The patients were followed up weekly for the first three weeks and than at six weekly intervals to a maximum of two years (range 16-26 months) or till the union was achieved. From the prospective study, three patients were lost to follow-up and hence excluded from the study. Functional outcome was assessed by Modified Stewart and Hundley (1955) criteria. Results: Out of 100 patients there were (44 A fractures [A1-13, A2-9, A3-22], 36 B fracture [B1-26, B2-9, B3-1] and 20 C fractures [C1-15, C2-4, C3-1]). Out of these 14 fractures were associated with open injury (2 Grade I , 4 Grade II, 4 Grade IIIa, 3 Grade IIIb, 1 Grade IIIc). Forty-six cases treated conservatively united at 24 weeks (15.65 weeks) and 54 patients, which were treated by different modalities united at 36 weeks (Ex-fixator), 22 weeks (Nail), 20.3 weeks (Plate and screws). Good results were obtained in 100% by Velpeau dressing in children, 85% by U-slab, 50% by plate and screws and 33.3% with nailing. There were postoperative complications like infection (6%), radial nerve palsy (2%) and nondelayed union (5-6%). Conclusion: Conservative management is method of choice in management of closed diaphyseal fractures of humerus as it gives early union, better limb function and is devoid of any of the routine postoperative complications. Patients with failed conservative treatment, open fractures and fractures with complex geometry are better managed operatively. ORIF with plate and screws has proven to be better than nailing procedures in present series in terms of giving better functional outcome. Patients treated with external fixator had mostly fair and poor outcome as injuries dealt by them were open type III injuries.

Keywords: Fracture humerus, external fixator, open fractures

iaphyseal fractures of humerus are commonly seen in orthopedic practice. Incidence of this fracture is about 3%. Due to advanced industrialization and high speed driving the incidence of this injury is on the increase. Earlier, this fracture was supposed to be caused by less violent force, and

was thought to be easier to manage by conservative or nonoperative methods after closed reduction and adopting simpler modes of immobilization like hanging arm cast, cooptation or U-shaped brachial splint, Velpeau dressing, abduction humeral splint/shoulder spica cast, skeletal traction and functional brace.

*Assistant Professor †Professor and Head ‡Associate Professor #Ex-Professor and Head Dept. of Orthopedics, Dr Rajendra Prasad Govt. Medical College and Hospital, Kangra (Tanda), HP $Professor Emeritus, Dept. of Orthopedics, Indira Gandhi Medical College and Hospital, Nagpur Director, Sushrut Hospital, Research Centre and Postgraduate Institute of Orthopedics, Nagpur

High energy trauma in present times has led to fractures with higher degree of comminution and soft tissue damage leading to more invasive approach for their treatment. Surgical intervention is also necessary when closed management of these fractures fails. Intramedullary interlocking nailing and locking compression plate are viable options for operative management of these fractures. They provide stable fixation even in fractures with a complex geometry and

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Orthopedics underlying osteoporosis and help achieve early limb function.

Table 1. Modified Stewart and Hundley Criteria (1955) Score

Criteria

Material and Methods

Good

No pain, limitation of adjacent joint mobility < 20° and angulation <10°.

Fair

Pain after efforts of fatigue, limitation of mobility ranging between 20° and 40° and angulation >10°.

Poor

Permanent pain, limitation of mobility >40° and nonunion.

This is a prospective and retrospective study aimed at finding out comparison of the results obtained by different modes of treatment in fractures of humeral diaphysis. We studied a total of 103 patients out of which the prospective study involved 72 patients and the retrospective study (2003-2004) involved 31 patients (whose records were available). All the cases were examined clinically and radiologically and were managed with an appropriate method of treatment. The closed fractures were classified by the method of Müller et al1 while for open fractures classification by the method of Gustillo et al2 was used. The patients were also examined for involvement of neurovascular structures. The mode of treatment adopted was recorded. The patients were followed up weekly for the first three weeks and than at six weekly intervals for eight months or till the union was achieved. On every follow-up, the patients were regularly examined clinico-radiologically for evidence of union. From prospective study, three patients were lost to follow-up and hence excluded from the study. Any complications developed during the course of treatment were also noted. The mode of treatment consisted of operative and nonoperative techniques. The nonoperative methods available included cooptation or U-shaped brachial splint or U-slab, hanging arm cast, Velpeau dressing, shoulder spica cast and functional brace. In our study, the indication for operative treatment was either failure of the nonoperative treatment or open fractures so the cases selected for surgery were the problem fractures. The operative methods available included external fixator, intramedullary nail (only K nail/V nail/rush nail/interlocking nail), plate and screws. Union was defined as absence of pain and motion at the fracture site with manual manipulation and consolidation of visible callus along with obliteration of the fracture line as seen on radiographs. Degrees of union were classified is three categories. Retarded healing was defined as the lack of any clinical or radiographic signs of healing at six week after injury. The ASIF/AO classification of delayed union (failure to unite in 4-8 months) and nonunion (failure to unite in >8 months) was used in this study. On final follow-up of the case, functional assessment was done according to Modified

Stewart and Hundley criteria noting union, range of motion at adjacent joints and subjective complaints (Table 1).3 Results Out of 100 patients, there were 44 A fractures (A113, A2-9, A3-22), 36 B fracture (B1-26, B2-9, B3-1), and 20 C fractures (C1-15, C2-4, C3-1). Out of these 14 fractures were associated with open injury (2 Grade I, 4 Grade II, 4 Grade IIIa, 3 Grade IIIb, 1 Grade IIIc). Male-to-female ratio was 3:1. The mean age in the present study was 31.54 years SD ± 18.70 years (range 1-95 years). There was a preponderance of humeral fractures in the age group 21-40 years. Seventy-two percent of the patients had rural background as compared to 28% of the patients from urban areas. There was no specific predilection for a particular side of the limb in any age group. Majority of the fractures were caused by fall in both the sexes. Dependents (students and children) were the most vulnerable in the age group 0-20 years. As per fracture location in diaphysis there were 19 proximal diaphyseal fractures, 46 middle shaft fractures and 35 distal shaft fractures. Maximum number of cases (46%) were located in the middle third of humeral shaft. Maximum numbers (38%) of the fractures were transverse. On first examination, there were 12 nerve palsies (radial nerve palsies 10%, median nerve 1% and ulnar nerve 1%) out of which seven were in the distal and 5 in middle shaft fractures. Twenty-one percent cases had associated skeletal injuries. Forty-six cases had managed conservatively (40 with U-slab, 5 with Velpeau dressing and 1 with hanging cast). Forty-six cases treated conservatively were all closed fractures that united at 24 weeks (mean time 15.65 weeks; with U-slab 16.2 weeks, hanging cast 18 weeks and Velpeau dressing 10.8 weeks). There was no delayed or nonunion. In 54 cases, which were managed operatively (44 by plate and screws, 6 by intramedullary nailing

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Orthopedics and 4 by external fixator), 40 were closed fractures, 10 were Grade I, II and IIIa fractures while 4 were IIIb and IIIc fractures. Meantime for union was 20.9 weeks, 40 patients showed union by 24 weeks and 49 cases united by one year and five reported nonunion. In 44 cases, treated by plate and screws meantime for union was 20.3 weeks. Out of total 44 patients, four united at 12 weeks, 32 united by 36 weeks, four went into delayed union and united by one year and remaining 4 were nonunions. Six patients managed by intramedullary nailing showed mean union at 22 weeks. Four of these united at 18 weeks, one united at 24 weeks and one united at 36 weeks. Four patients operated by external fixator showed mean union by 36 weeks. While one united at 36 weeks, two united by one year and I showed nonunion. In proximal diaphyseal case (n = 19) 18 had united at 36 weeks and I reported delayed union. In cases of middle shaft (n = 46) only 39 united, seven showed non/delayed union. In distal shaft (n = 35), 32 united and three went into delayed/nonunion. In present study, closed fractures were first to unite and open Grade III fractures united last of all p = 0.013 (significant). On follow-up examination by Modified Stewart and Hundley3 criteria, restriction of < 20° was noted in

Table 2. Distribution of Cases Depending on Operative/Nonoperative Technique and Final Result Result

Operative cases

Nonoperative cases

Total

No.

Good

44.4

Fair

35.2

Poor

20.4

Total

100

patients treated by Velpeau dressing in children, U-slab and plate and screws. Good results were obtained in 100% patients treated by Velpeau dressing, 85% patients treated by U-slab and 50% patients treated by plate and screws. Restriction of 20-40° was noted in patients treated by nailing methods. None of the cases managed by external fixator qualified for good results. Thus, in the operative series 44.4% good results were obtained as compared to 85% good results in the nonoperative series (Tables 2 and 3). Seventy-five percent poor results were obtained in cases managed by external fixator application, the reason being that they were Grade IIIb and IIIc injuries, with significant preoperative wound contamination. Abduction at the shoulder was the movement most commonly restricted in cases managed operatively (maximum restriction being observed in intramedullary nailing due to subacromial impingement of the nail). Some loss of extension at elbow was the next movement to be affected. Other complications noted in operated series were postoperative infection (6%), postoperative radial nerve palsies (2%), nonunion and delayed union (5% and 6%). Nerve palsies automatically recovered after 12 weeks. There was no vascular injury. Discussion The present study involved 100 cases with an average age 31.59 years with standard deviation (SD) ± 18.7 years (range 1-95 years). Most of the patients belonged to the age group of 21-40 years. This age group is exposed to more active lifestyle and is more prone to high velocity trauma. This was comparable to age incidence in other studies.4,5 In this series, there were 75 males and 25 females (M/F 3:1). In other study,5 there were 25 males and five females with diaphyseal fractures of humerus (M/F 5:1). Others reported 29 men and 19 women with diaphyseal humeral fractures.6 The greater incidence among males

Table 3. Distribution of Cases Depending upon Final Result and Methods of Stabilization Result

U-slab

H. cast

V. dressing

Ext. Fix.

Nail

Pl. and screws

Total

No.

Good

100

33.3

Fair

100

66.7

31.8

Poor

18.2

Total

100

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Orthopedics could be attributed to their being earning hands of their families and hence leading a more mobile and active life. The predominance of right side in humeral fractures has been observed in some studies.5 In the present study, right side was involved in 48% cases and the left in 52% cases, thus showing almost equal distribution in both the sides. This was inconsonance with other studies.7 The two most common mechanisms of diaphyseal fractures of humerus are fall and motor vehicle accidents.8 Road traffic accidents and assault by blunt objects were the mode of injury in 86.5% cases.7 In our study, the predominant mode of injury was fall (49%) followed by motor vehicle accidents (34%), pedestrian injuries (13%) and others like gunshot injuries (4%). This was probably due to hilly terrain of the area involved in our study.

Figure 1. 12-A3 Fracture humerus.

Figure 2. 12-A3 Fracture showing early callus at 2 weeks by U-slab.

Radial nerve palsies were associated with 18% of the diaphyseal fractures of the humerus.9 Although Holstein Lewis fracture (oblique distal third) is best known for its association with neurologic injury, radial never palsy is most commonly associated with middle third humeral shaft fractures.10 In the present study, nerve palsies were observed in 12% cases out of which 10% were radial 1% median and 1% ulnar and all were neuropraxias. Of these nerve injuries seven were in the distal third fractures and five in the middle third fractures. In the present study, recovery occurred in 90% patients within 3-12 weeks. In one case, there was postoperative radial nerve palsy, which also recovered in six weeks. Most nerve injuries represent a neuropraxia or axonotmesis, 90% will resolve in 3-4 months.10

and remodeling potential. The average time for union for nonoperative cases was 15.69 weeks. The average time for union was 19 weeks in another study.12 Hunter (1982)13 reported 60 humeral shaft fractures treated with U-slab. Ninety-three percent fractures united. Some other studies reported union with conservative means like functional bracing from 3 to 22.5 weeks with a mean of 8.5 weeks and a mode of seven weeks except one having metastatic bone disease.14 Sarmiento in 200015 reported a series of 620 patients having humeral diaphyseal fractures treated with prefabricated brace. Six percent of open and 2% of closed fractures had nonunion. Eighty-seven percent patients had angulation < 16% in anteroposterior view and 81% patients healed with < 16% angulation in lateral view. At the time brace removal, 98% of the patients had limitation of shoulder motion of 25째 or less. The results of treatment of closed humeral shaft fractures are excellent using a variety of techniques including bracing, hanging casts. Fifty-four percent cases were treated operatively (4% were stabilized by external fixation, 6% by intramedullary nails and the rest 44% with plate and screws. The average time for union for patients treated by operative means was 20.9 weeks.

Associated skeletal injuries were present in 21% diaphyseal fractures of humerus and were comparable to available literature.11 In our series, 46% cases were managed nonoperatively (40% cases were treated by U-slab, 1% cases by hanging cast, 5% by Velpeau dressing) (Figs. 1 and 2). Meantime for union in different methods noted individually was as follows: U-slab - 16.2 weeks, hanging cast - 18 weeks, Velpeau dressing - 10.8 weeks. At 24 weeks, all the 46 cases managed conservatively had united. In our series best results were obtained with Velpeau dressing in children as they had good growth

In the patients treated by open reduction internal fixation (ORIF) with plate and screws mean time for union was 20.3 weeks in our study (Figs. 3 and 4). Out of 44 cases, four united at 12 weeks (Fig. 5) and by 36 weeks, 36 cases had united. Four cases were delayed, which united at one year and the remaining four were nonunions. The nonunions were either due to faulty surgical technique or due to poor bone stock and comminution at fracture site. In this series, they were more evident than in nailing procedures because of large number of patients treated by plate and screws. Such patients were reoperated by interlocking nailing

In some studies 40% fractures were transverse, 25% fractures were comminuted and 18% were oblique, 15% were spiral and 2% were segmental.4 In the present study, 38% of cases were transverse, 28% comminuted, 19% were oblique, 14% were spiral and 1% were segmental.

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Figure 3. 12-A2 Fracture humerus.

Figure 4. Fixation with LCP immediate post-op.

Figure 5. Showing union at 12 weeks.

Figure 6. 12-B1 Fracture Figure 7. Four weeks post-op humerus. follow-up.

Figure 8. 12-B1 Fracture humerus.

and bone grafting. In literature, excellent results have been reported in patients treated by plate and screw fixation.12,16-18 In cases of intramedullary nail fixation mean time for union was 22 weeks (Figs. 6-9). Of the six cases, 4 united at 18 weeks, (Fig. 10) 5th at 24 weeks and 6th case united at 36 weeks. In some literature excellent results were reported with intramedullary nailing.4,19 Some other studies reported the good results in nondelayed unions when combined with bone grafting or autologous marrow.20,21 Some other studies reported higher fracture comminution and more complications especially with antegrade approach to nailing.22-24 Out of four cases who were applied external fixator, I united at 36 weeks and 2 united by one year (Figs. 11 and 12). The last case landed up with nonunion. The mean time of union with external fixator was 36 weeks. Available literature has shown good to excellent result in six out of nine high energy humerus fractures treated with external fixation.25 Other study showed union in 17 out of 20 complex humeral fractures with Hoffman external fixation at 21 weeks.26

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Figure 9. Fixation with K nail: immediate post-op.

Figure 10. Same fracture showing union at 18 weeks.

In our study, we got fair to poor results in management of humeral diaphyseal fractures with external fixator as these were badly contaminated open Grade III B and Grade III C injuries. The average time for union in the proximal third was 15.3 weeks, middle third 20.3 weeks and distal third 17.25 weeks. Proximal third fractures healed sooner as in other study.7 Meantime for union in

Orthopedics References 1. Muller ME, Nazarian S, Koch P, Schatzker J. The comprehensive classification of fractures of long bones. Springer-Verlag: Berlin, etc; 1990. 2. Gustilo RB, Anderson JT. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones: retrospective and prospective analyses. J Bone Joint Surg Am 1976;58(4):453-8. 3. Stewart MJ, Hundley JM. Fractures of the humerus; a comparative study in methods of treatment. J Bone Joint Surg Am 1955;37-A(4):681-92. Figure 11. 12-A2, Grade IIIb fracture humerus (external fixation).

Figure 12. Removal of fixator and union at 36 weeks.

89 cases, which united by 36 weeks was 18.2 weeks. Rest 11 went into nondelayed unions (1 in prox shaft, 7 in middle shaft, 3 in distal shaft).

4. Stern PJ, Mattingly DA, Pomeroy DL, Zenni EJ Jr, Kreig JK. Intramedullary fixation of humeral shaft fractures. J Bone Joint Surg Am 1984;66(5):639-46. 5. Pachnanda DD. Kuntscher nailing in fractures shaft humerus. Indian J Orthopaedics 1994;3:48-50. 6. Lin J. Treatment of humeral shaft fractures with humeral locked nail and comparison with plate fixation. J Trauma 1998;44(5):859-64.

Closed fractures were first to unite (mean = 17.6 weeks) and open fractures were late to unite (Grade I 20.4 weeks, Grade II 24 weeks, Grade III 36 weeks). This was comparable to available literature showing the average time to radiographic healing for open fractures being 21 weeks (range 8-30 weeks).

7. Shabeer M, Shukla J, Mehrotra A, et al. Evaluation of results of dynamic compression plating and early mobilization in the management of fracture shaft humerus. Indian J Orthopedics 1988;32(2):100-2.

Good results were obtained in 100% patients treated by Velpeau dressing and 85% patient treated by U-slab. This was comparable to available literature.13-15 In patients treated surgically 50% good results were obtained in patients operated by plate and screws, which was better than that obtained by treatment with other surgical modalities and in consonance with available studies. There were 6% nonunions and 5% delayed unions. The rate of nonunion following a humeral shaft fractures ranges from 0 to 16%. The results of our series were concordant with the above observation.

9. Mast JW, Spiegel PG, Harvey JP Jr, Harrison C. Fractures of the humeral shaft: a retrospective study of 240 adult fractures. Clin Orthop Relat Res 1975;(112):254-62.

Conclusion Conservative management is method of choice in management of closed diaphyseal fractures of humerus as it gives early union, better limb function and is devoid of any of the routine postoperative complications. Patients with failed conservative treatment, open fractures and fractures with complex geometry are better managed operatively. ORIF with plate and screws has proven to be better than nailing procedures in present series in terms of giving better functional outcome. Patients treated with external fixator had mostly fair and poor outcome as injuries dealt by them were mainly open Grade IIIb and IIIc injuries.

8. Zagorski JB, Latta LL, Zych GA, Finnieston AR. Diaphyseal fractures of the humerus. Treatment with prefabricated braces. J Bone Joint Surg Am 1988;70(4):607-10.

10. Pollock FH, Drake D, Bovill EG, Day L, Trafton PG. Treatment of radial neuropathy associated with fractures of the humerus. J Bone Joint Surg Am 1981;63(2):239-43. 11. Ward EF, Savoie FH, Hughes JF. Fractures of the diaphyseal humerus. In: Skeletal Trauma. Vol. 1, Browner BD, Jupiter JB, Levine AM, Trafton PG (Eds.), WB Saunders: Philadelphia 1992:p.1177-200. 12. Bell MJ, Beauchamp CG, Kellam JK, McMurtry RY. The results of plating humeral shaft fractures in patients with multiple injuries. The Sunnybrook experience. J Bone Joint Surg Br 1985;67(2):293-6. 13. Hunter SG. The closed treatment of fractures of the humeral shaft. Clin Orthop Relat Res 1982;(164):192-8. 14. Sarmiento A, Kinman PB, Galvin EG, Schmitt RH, Phillips JG. Functional bracing of fractures of the shaft of the humerus. J Bone Joint Surg Am 1977;59(5):596-601. 15. Sarmiento A, Zagorski JB, Zych GA, Latta LL, Capps CA. Functional bracing for the treatment of fractures of the humeral diaphysis. J Bone Joint Surg Am 2000;82(4):478-86. 16. Dameron TB Jr, Grubb SA. Humeral shaft fractures in adults. South Med J 1981;74(12):1461-7. 17. RĂźedi T, Moshfegh A, Pfeiffer KM, AllgĂśwer M. Fresh fractures of the shaft of the humerus -conservative or operative treatment? Reconstr Surg Traumatol 1974;14(0): 65-74.

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Orthopedics 18. Vander Griend R, Tomasin J, Ward EF. Open reduction and internal fixation of humeral shaft fractures. Results using AO plating techniques. J Bone Joint Surg Am 1986;68(3): 430-3. 19. Hall RF Jr, Pankovich AM. Ender nailing of acute fractures of the humerus. A study of closed fixation by intramedullary nails without reaming. J Bone Joint Surg Am 1987;69(4): 558-67. 20. Li XK, Wang HQ, Wei YY, Wu ZX. Treatment of nonunions of humeral fractures with interlocking intramedullary nailing. Chin J Traumatol 2008;11(6):335-40. 21. Garnavos C, Mouzopoulos G, Morakis E. Fixed intramedullary nailing and percutaneous autologous concentrated bone-marrow grafting can promote bone healing in humeral-shaft fractures with delayed union. Injury 2010;41(6):563-7.

22. Chao TC, Chou WY, Chung JC, Hsu CJ. Humeral shaft fractures treated by dynamic compression plates, Ender nails and interlocking nails. Int Orthop 2005;29(2):88-91. 23. McCormack RG, Brien D, Buckley RE, McKee MD, Powell J, Schemitsch EH. Fixation of fractures of the shaft of the humerus by dynamic compression plate or intramedullary nail. A prospective, randomised trial. J Bone Joint Surg Br 2000;82(3):336-9. 24. Chapman JR, Henley MB, Agel J, Benca PJ. Randomized prospective study of humeral shaft fracture fixation: intramedullary nails versus plates. J Orthop Trauma 2000;14(3):162-6. 25. Smith DK, Cooney WP. External fixation of high-energy upper extremity injuries. J Orthop Trauma 1990;4(1):7-18. 26. Browner BD, Edwards CC, Hritz M. Hoffman external fixation treatment of complex fractures. Orthop Trans 1982;6:357-8.

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Gout Risk High in Those with Psoriasis, Psoriatic Arthritis Individuals with psoriasis have nearly twice the risk, and those with psoriatic arthritis (PsA) have nearly 5 times as high a risk, for gout as those without psoriasis, according to the first prospective cohort study to address this relationship. The age- and multivariate-adjusted relative risks (HRs) for gout were 1.71 (95% confidence interval [CI], 1.36 2.15) for psoriasis and 4.95 (95% CI, 2.72-9.01) for psoriasis with concomitant PsA, report Joseph F. Merola, MD, from the Department of Dermatology and the Division of Rheumatology, Allergy and Immunology, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, and colleagues. They present their findings in an article HYPERLINK “http://ard.bmj.com/content/early/2014/03/20/ annrheumdis-2014-205212.abstract” published online in the Annals of the Rheumatic Diseases.

The Impact of Long-term Vitamin D Insufficiency on Fracture Risk A study presented at the World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases shows that long-term low levels of vitamin D intake are associated with higher 10-year fracture risk in elderly women. Vitamin D insufficiency in seniors has been shown to contribute to increased risk of osteoporotic fractures. Previous studies have used single vitamin D measurements to investigate effects on bone. However, in elderly women, relatively little is known about the effects of long-term vitamin D insufficiency on bone health. The study by Swedish researchers used sequential assessment of serum vitamin D to determine if sustained hypovitaminosis D in elderly women leads to increased 10-year fracture incidence. Fracture prevention is a key focus of IOF’s global campaign ‘Capture the Fracture’. The campaign specifically targets secondary fracture prevention by promoting the implementation of coordinator-based fracture liaison services in hospitals and clinics worldwide.

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PEDIATRICS

High-Frequency Ventilation: Excellent Rescue Sudivya Sharma, Prashast Jain

Abstract High-frequency ventilation (HFV) is a type of mechanical ventilation which utilizes a respiratory rate greater than four times the normal value and very small tidal volumes.1,2 This combination of small tidal volumes delivered for very short periods of time creates the lowest possible distal airway and alveolar pressures produced by a mechanical ventilator and exhalation is passive. It is an upcoming but promising modality.

Keywords: High-frequency ventilation, lung injury, peak end-expiratory pressure, hypoxemia, recruitment

igh-frequency ventilation (HFV) is a type of mechanical ventilation which utilizes a respiratory rate greater than four times the normal value and very small tidal volumes.1,2 This combination of small tidal volumes delivered for very short periods of time creates the lowest possible distal airway and alveolar pressures produced by a mechanical ventilator and exhalation is passive. It is an upcoming but promising modality. Physiological principles since long have maintained that ventilation at tidal volumes less than the anatomical dead space should be ineffective (i.e., inspired air not reaching the alveolae). Data from a 1980 study dispelled that myth, showing unequivocally that ventilation with tidal volumes as small as 20-30 mL in dogs, a mere fraction of the anatomical dead space, could maintain adequate ventilation.3 These unexplained observations sparked transport and mixing theories predicting that carbon dioxide (CO2) removal should vary in direct proportion to breathing frequency (although, the relationship with tidal volume is more complex)4,5 and these predictions were later confirmed experimentally.6

Although mechanical ventilation can clearly be lifesustaining for those who are critically ill, excessive tidal volumes can stretch the lung, leading to overdistention and further lung injury.7 Inadequate positive endexpiratory pressure (PEEP) can promote repetitive alveolar collapse followed by reopening, which may be injurious to the lung (an injury known as atelectrauma). Lung homogeneity is also thought to be important, since

PGIMS Rohtak, Haryana Address for correspondence Dr Sudivya Sharma Flat. No.77, B-Wing, Mahavir Krupa Building TJ Road, Sewri (W), Mumbai - 400 015, Maharashtra

injurious forces can develop at junctions of normal and abnormal lung even when the applied pressures are modest.8 Thus, HFV, in a well-recruited, homogeneous lung, could avoid these problems. Jet ventilators utilize various inspiratory to expiratory time ratios—between 1:1.1 and 1:12—to help achieve optimal exhalation. Conventional mechanical breaths are sometimes used to aid in reinflating the lung. Optimal PEEP is used to maintain alveolar inflation and promote ventilation-to-perfusion matching.9 The mechanisms of gas exchange in HFV are: ÂÂ

Convective ventilation

ÂÂ

Asymmetric velocity profile

ÂÂ

Taylor dispersion

ÂÂ

Pendelluft

ÂÂ

Molecular diffusion

ÂÂ

Cardiogenic mixing.

The indications for the same are laryngeal, tracheal and bronchial procedures; for emergency management of airway in bronchopleural and transesophageal fistulas; acute respiratory distress syndrome; pulmonary interstitial emphysema and refractory hypoxemia. Types ÂÂ

High-frequency positive pressure ventilation (HFPPV): Rate is 60-120/ min, delivered through the endotracheal tube using a conventional ventilator whose frequency is set near its upper limits.

ÂÂ

High-frequency jet ventilation (HFJV): Rate is 120600/min, provided by the Bunnell Life Pulse HighFrequency Ventilator, a high pressure ‘jet’ of gas flows out of the adaptor and into the airway.

ÂÂ

High-frequency oscillatory ventilation (HFOV): Rate is 180-3,000 breaths/min. Both inhalation and

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PEDIATRICS exhalation are maintained by active pressures. The pressure oscillates around constant distending pressure (equivalent to mean airway pressure), which in effect is the same as PEEP. ÂÂ

High-frequency percussive ventilation (HFPV) is a hybrid of conventional mechanical ventilation and HFOV and has been used to salvage patients with persistent hypoxemia on conventional mechanical ventilation.10

ÂÂ

High-frequency flow interruption (HFFI): A small, brief pulse of gas is allowed to enter the airway. Frequencies for HFFI are typically limited to maximum of about 15 hertz.

Patient selection Some patients have recruitable lung (i.e., lung tissue in which alveolar air volume is increased with small increases in airway pressure), whereas others have nonrecruitable lung. Among patients with homogeneous, recruitable lung, increasing mean airway pressure may well be beneficial; however, among patients with heterogeneous and nonrecruitable lung, increasing mean airway pressure may lead to overdistention of some lung regions without increased aeration of collapsed or flooded alveoli. The interactions are complicated and are dependent on relative lung and chest-wall compliance, left and right ventricular function, volume status and other factors.11 Advantages HFV-based ventilatory strategies offer two potential advantages over controlled ventilation. First, HFV uses very small tidal volumes, allowing higher endexpiratory lung volumes with less overdistention than is possible with controlled ventilation. Second, despite the small tidal volumes, high respiratory rates during HFV allow the maintenance of normal or nearnormal PaCO2 levels. Subglottic HFJV is an alternative ventilatory approach in airway surgery. HFJV offers optimal endolaryngeal working conditions, immobility of vocal cords, adequate oxygenation and ventilation.12 Adverse effects These adverse effects include pneumothorax, pneumopericardium, pneumoperitoneum, pneumo mediastinum, pulmonary interstitial emphysema, intraventricular hemorrhage, necrotizing tracheobronchitis and bronchopulmonary dysplasia. The elevated mean airway pressures with HFV have been associated with increased requirements for pressor medications and probably end-organ failures.

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Conclusion The three most important concepts for lung protection are early intervention (before acute respiratory distress syndrome is established); optimal lung recruitment; and careful avoidance of lung overdistention over the entire period of mechanical ventilation. HFV seems to be the ideal lung-protective ventilatory mode, especially in patients who have refractory hypoxemia. References 1. Briscoe WA, Forster RE, Comroe JH Jr. Alveolar ventilation at very low tidal volumes. J Appl Physiol 1954;7(1):27-30. 2. Krishnan JA, Brower RG. High-frequency ventilation for acute lung injury and ARDS. Chest 2000;118(3):795-807. 3. Bohn DJ, Miyasaka K, Marchak BE, Thompson WK, Froese AB, Bryan AC. Ventilation by high-frequency oscillation. J Appl Physiol Respir Environ Exerc Physiol 1980;48(4):710-6. 4. Fredberg JJ. Augmented diffusion in the airways can support pulmonary gas exchange. J Appl Physiol Respir Environ Exerc Physiol 1980;49(2):232-8. 5. Weinmann GG, Mitzner W, Permutt S. Physiological dead space during high-frequency ventilation in dogs. J Appl Physiol Respir Environ Exerc Physiol 1984;57(3):881-7. 6. Slutsky AS, Drazen FM, Ingram RH Jr, Kamm RD, Shapiro AH, Fredberg JJ, et al. Effective pulmonary ventilation with small-volume oscillations at high frequency. Science 1980;209(4456):609-71. 7. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342(18):1301-8. 8. Mead J, Takishima T, Leith D. Stress distribution in lungs: a model of pulmonary elasticity. J Appl Physiol 1970;28(5):596-608. 9. Schuster DP, Klain M, Snyder JV. Comparison of high frequency jet ventilation to conventional ventilation during severe acute respiratory failure in humans. Crit Care Med 1982;10(10):625-30. 10. Eastman A, Holland D, Higgins J, Smith B, Delagarza J, Olson C, et al. High-frequency percussive ventilation improves oxygenation in trauma patients with acute respiratory distress syndrome: a retrospective review. Am J Surg 2006;192(2):191-5. 11. Malhotra A, Drazen JM. High-frequency oscillatory ventilation on shaky ground. N Engl J Med 2013;368(9):863-5. 12. Janjević D, Dolinaj V, Piazza C, Jović R, Marinković J, Kalezić N. Subglottic high frequency jet ventilation in surgical management of bilateral vocal fold paralysis after thyroidectomy. Acta Clin Croat 2012;51(3):451-6.

PEDIATRICS

Congenital Juvenile Xanthogranuloma of Foot, a Nodular Lesion: An Unusual Case in 2-month-old Infant Ram Avtar*, Onkar Kaur†, ANAND K VERMA‡, RAJ KUMAR CHANDOKE#

Abstract A 2-month-old infant presented with a circumscribed nodule on left foot since birth. Excision biopsy showed juvenile xanthogranuloma, an uncommon diagnosis in an unusual site; common sites being head and neck. Uncommon sites are groin, genital organs, limbs and even internal organs. It carries a favorable prognosis.

Keywords: Juvenile xanthogranuloma, nodule, fibrohistiocytic tumor

uvenile xanthogranuloma (JXG) is a disorder of non-Langerhan’s cell group of histiocytic proliferative diseases.1 It is an uncommon benign soft tissue lesion first reported by Adamson.1 It presents as nodular or plaque like lesion in soft tissue sites. Although head and neck are common sites; it can involve all parts including groin, scrotum, genitals, trunk, and proximal part of limbs, even internal organs like lungs, liver and bone (Erdheim-Chester disease). It is present at birth in approximately 5-35% of total cases and rest usually present within 6-9 months of life.2 This case is being reported as it presented on dorsum left foot, which is a rare site and was present since birth. Case Report

Figure 1. Shiny globular swelling over dorsum of left foot showing flexion of great toe.

A 2-month-old child presented with a well-defined globular swelling of size 3 × 3 cm over dorsum of left foot just distal to the ankle joint (Fig. 1). It was noted since birth and had remained stationary in size since then. There were no other similar lesions and

*Head Dept. of Orthopedics †Senior Medical Officer ‡Senior Specialist #Consultant and Head Dept. of Pathology ESI-PGIMSR and Model Hospital, Basaidarapur, New Delhi Address for correspondence Dr Raj Kumar Chandoke Consultant and Head Dept. of Pathology ESI-PGIMSR and Model Hospital, Basaidarapur Ring Road, New Delhi - 110 015 E-mail: drchandoke@gmail.com

Figure 2. Operative photograph showing tumor.

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PEDIATRICS no associated symptoms were present. Surface of the swelling was shiny although there were no signs of inflammation.3 Palpation of mass did not cause the infant any distress. It was firm in consistency with well-defined edges, nonfluctuant, nonpulsatile, not adherent to the skin and underlying structure. No associated lymphadenopathy was present. All routine blood investigations were within normal limits. On X-ray, no bony lesion was present. Magnetic resonance imaging report mentioned a well-defined rounded mass in the subcutaneous plain in dorsum of foot with low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, indicating no evidence of high flow vessels with signal voids on these sequences. Figure 3. Operative photograph after removal of tumor from subcutaneous plane.

Aspiration cytology done from lesion showed scattered spindle cells with bland nuclei, foamy cells suggestive of benign mesenchymal lesion. Excision biopsy was advised for definitive nomenclature. Sharply defined noncapsulated globular mass of size 2.5 Ă&#x2014; 2.5 cm was excised from the subcutaneous plane. It was not involving any of the neighboring structures (Figs. 2 and 3). Microscopy revealed small fascicles composed of spindle-shaped cells with presence of inflammatory cells, plump foamy histiocytes and Touton giant cells. The findings were consistent with JXG (Figs. 4 and 5). Discussion

Figure 4. Soft tissue tumor: Fascicular arrangement of spindle cells and histiocytes (H&E 100x).

Figure 5. Foamy histiocytes and inflammatory cells (H&E 400x).

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JXG is a benign fibrohistiocytic lesion accompanied by lipid deposits, first described by Adamson in 1905.1 It is originally thought to be derived from dermal dendrocytes. Solitary or multiple red-brown papulonodules, 1-10 mm in diameter or larger are found on the head and neck, upper part of the trunk and proximal parts of the limbs.2 In the present case, the lesion was in dorsum of foot. Cutaneous presentation, being most common, may involve soft tissues as well as other organs.3 In our case, there was no organ involvement. JXG has been documented in visceral organs such as lungs, bone, genitalia, gastrointestinal tract (GIT), heart, eyes and oral cavity.3,4 JXG is a disease of young age with median age of onset within 6-9 months, but lesion may be present at birth in 5-35% of children. Children below 6 months present with multiple nodules in head and neck region with male preponderance, which is higher in young infants.1 Severe congenital systemic JXG has been reported in monozygotic twins.2 JXG is associated with diseases like neurofibromatosis (NF-1), juvenile chronic myelogenous leukemia (CML),

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PEDIATRICS other hematological malignancies, Niemann-Pick disease and urticaria pigmentosa. This entity should be separated clinically by various differentials like hemangioma and NF (firm lesion, and with café-au lait spot).3,5 Histopathological diagnosis is established on the basis of the nodule showing poorly demarcated dense histiocytic infiltrate involving the dermis and up to 85% cases infiltrating deep tissue in subcutis and sometimes skeletal muscles with variable number of Touton giant cells. In the present case, the lesion was excised from the subcutaneous plane. These plump foamy histiocytes are large, polygonal or spindle-shaped, with eosinophilic cytoplasm and positive for CD68, HAM 56, vimentin, lysozymes, a1-antichymotrypsin, but negative for smooth muscle actin, CD34 and S 100 protein.6,7 Staining for these markers may be more intense at the periphery of the lesion. Electron microscopy (EM) shows lipid vacuole, lysosome, cholesterol clefts and myeloid bodies but no Birbeck granules. Other histological variants like spindle-cell xanthogranuloma with spindle-shaped histiocytes arranged in a storiform pattern, scallopedcell xanthogranuloma with scalloped histiocytes with homogenous cytoplasm are known.2 JXG, although presents early in age, has good prognosis as it shows spontaneous regression in fair number of cases.1,8,9 Pathogenesis being unknown, various theories like infection and physical stimulation have been implicated.10-12 Although the etiology of JXG is unknown, cholesterol has been found to be the main lipid associated with it. Despite spontaneous regression, excision is required for an esthetic and diagnostic reason as was in the present case. Recurrences are uncommon.6,12 Conclusion JXG, an uncommon entity of young children, can occur as early as at birth with nodule or plaque like presentation of any site. Biopsy confirmation and surgical excision should be done if no functional compromise has been assessed before. It is mostly

cutaneous and prognostically favorable histiocytic tumor of infancy. References 1. Cypel TK, Zuker RM. Juvenile xanthogranuloma: case report and review of the literature. Can J Plast Surg 2008;16(3):175-7. 2. Weedon D (Ed.). Weedon’s Skin Pathology. 3rd edition, Churchill Livingstone Elsevier: USA 2010:p.953-4. 3. Dehner LP. Juvenile xanthogranulomas in the first two decades of life: a clinicopathologic study of 174 cases with cutaneous and extracutaneous manifestations. Am J Surg Pathol 2003;27(5):579-93. 4. Freyer DR, Kennedy R, Bostrom BC, Kohut G, Dehner LP. Juvenile xanthogranuloma: forms of systemic disease and their clinical implications. J Pediatr 1996;129(2):227-37. 5. Kesavan TM, Sreedevi PK. Juvenile xanthogranuloma. Indian Pediatr 2005;42(9):950. 6. Sonoda T, Hashimoto H, Enjoji M. Juvenile xanthogranuloma. Clinicopathologic analysis and immunohistochemical study of 57 patients. Cancer 1985;56(9):2280-6. 7. Zelger B, Cerio R, Orchard G, Wilson-Jones E. Juvenile and adult xanthogranuloma. A histological and immunohistochemical comparison. Am J Surg Pathol 1994;18(2):126-35. 8. Jung T, Emmert S, Günzl HJ, Neumann C, Rünger TM. Congenital manifestations of juvenile xanthogranuloma (large nodular form). Hautarzt 2000;51(6):423-6. 9. Margulis A, Melin-Aldana H, Bauer BS. Juvenile xanthogranuloma invading the muscles in the head and neck: clinicopathological case report. Ann Plast Surg 2003;50(4):425-8. 10. Chang MW. Update on juvenile xanthogranuloma: unusual cutaneous and systemic variants. Semin Cutan Med Surg 1999;18(3):195-205. 11. Zvulunov A, Barak Y, Metzker A. Juvenile xanthogranuloma, neurofibromatosis, and juvenile chronic myelogenous leukemia. World statistical analysis. Arch Dermatol 1995;131(8):904-8. 12. Cohen BA, Hood A. Xanthogranuloma: report on clinical and histologic findings in 64 patients. Pediatr Dermatol 1989;6(4):262-6.

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There are many children who do not see dentists regularly, and a lack of oral care is commonly seen in children younger than 3 years. A study published online March 31 in Pediatrics addressed this issue and stated that primary care physicians can easily reduce tooth decay in indigent children by extending fluoride treatment, oral health education, exams and referrals. An oral healthcare program provided services to children enrolled in Medicaid from the time of the first tooth eruption until age 42 months. Researchers evaluated the program’s success and noted that the decayed, missing and filled teeth (DMFT) rate increased from 1.53 per child in 1998 to 1.84 in 2004 and then dropped back to 1.59 in 2009.

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PEDIATRICS

Bronchoscopy in Children Sudivya Sharma

Abstract Bronchoscopy signifies the instrumentation of the airway with a bronchoscope to visualize the airway beyond the scope of a laryngoscope, for diagnostic and therapeutic purposes. Pediatric bronchoscopy includes two endoscopic techniques, flexible and rigid bronchoscopy. This article presents an overview of bronchoscopy in the pediatric population with respect to its indications, utility and contraindications.

Keywords: Bronchoscopy, pediatric bronchoscopy, airway, indications, flexible, rigid, hypoxia

ronchoscopy refers to instrumentation of the airway with a bronchoscope in order to visualize the airway beyond the scope of a laryngoscope, for diagnostic and therapeutic purposes. Pediatric bronchoscopy entails two endoscopic techniques: Flexible and rigid bronchoscopy. It can be emergent or elective. It gives anatomical and dynamic information of the airway. For children, special equipment; sound knowledge of anatomy, physiology and pathology of pediatric airway; tertiary care settings, monitoring of electrocardiogram and oxygen saturation; experienced anesthesiologist and foresight of complications are a must.1

Why? Introduction of scope is a strong stimulus, and requires deep sedation and muscle relaxation. In addition, it is traumatic, can be complicated with bronchospasm, bradycardia, hypoxia, coughing, hemorrhage, pneumothorax, pneumomediastinum and surgical emphysema. Hence, the indications should be established and the timing is crucial. For example, bronchoscopy for removal of aspirated foreign body is an accepted gold standard and the earlier, the better. Retained foreign bodies lead to formation of granulation tissue, making their extraction more difficult. The time required for bronchoscopy should be minimum because of the shared airway with the anesthesiologist. The mode of maintaining patient’s oxygenation could be by apneic technique (intermittent mask ventilation),

PGIMS, Rohtak, Haryana Address for correspondence Dr Sudivya Sharma Flat No. 77, B-Wing, Mahavir Krupa Building TJ Road, Sewari (W), Mumbai - 400 015 E-mail: drsudivyasharma@gmail.com

circuit attachment to the scope or jet ventilation. More than the indication for bronchoscopy, the tolerance of the patient for such a procedure should be assessed.2,3 When? Indications include persistent stridor in children, once laryngomalacia has been ruled out. It helps in diagnosing congenital, anatomical and acquired anomalies. ÂÂ Persistent wheezing due to foreign body aspiration or structural anomalies of tracheobronchial wall. ÂÂ Hemoptysis due to artificial airways, tracheostomies, pulmonary alveolar hemorrhage, congenital vascular anomalies, infections, inflammations, tumors. ÂÂ Persistent or recurring atelectasis due to mucus plugging, extrinsic compression, inflammatory granulation tissue. ÂÂ Persistent or recurring pneumonias. ÂÂ Localized hyperlucency due to intrinsic (foreign body, bronchomalacia, granulation tissue) or extrinsic obstruction (adenopathies, aberrant vessels, congenital or acquired mediastinal mass). ÂÂ Bronchoalveolar lavage (BAL) and biopsy samples. ÂÂ Aspiration of secretions. ÂÂ Foreign body.4-6 How? Bronchoscopes are two types: Flexible and rigid. Our focus of discussion is mainly rigid bronchoscopes, which could be of ventilating or venturi type. Storz ventilating bronchoscope has a port for attaching anesthetic breathing circuit, whereas in venturi scopes gas exchange is brought by jet insufflation with oxygen. The latter have problems of carbon dioxide retention and barotrauma. Pediatric bronchoscopes are shorter

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PEDIATRICS Table 1. Suggested ETT and Rigid Bronchoscope Sizes for Children Age

Cricoid airway diameter (mm)

Premature

4.0

Tracheal tube

Bronchoscope size

Size ID

ED (mm)

Size

2.5-3.0

3.5-4.0

2.5

3.2

4.0

Term newborn

4.5

3.0-3.5

4.0-4.9

3.0

4.2

5.0

6 months

5.0

3.5-4.0

4.9-5.4

3.0

4.2

5.0

1 year

5.5

4.0-4.5

5.4-6.2

3.5

4.9

5.7

2 years

6.0

4.5-5.0

6.2-6.9

3.5

4.9

5.7

3 years

7.0

5.0-5.5

6.9-7.4

4.0

5.9

6.7

5 years

8.0

5.5-6.0

7.4-7.9

5.0

7.0

7.8

10 years

9.0

6.5 cuffed

5.0*

14 years

11.0

6.5 cuffed

5.0*

larger bronchoscope may be helpful, if there is a large air leak and IPPV is being used.

ETT = Endotracheal tube; ED = External diameter; ID = Internal diameter; IPPV = Intermittent positive pressure ventilation.

than those used in adults. They measure between 16 and 30 cm long with an internal diameter between 3.2 and 7 mm. To these measurements, one must also add the thickness of the wall of the tube, which ranges between 2 and 3 mm depending on the manufacturer, to obtain the external diameter. Anticholinergic and anxiolytic can be used for premedication. General anesthesia is mandatory, muscle relaxation could be done using intermittent succinylcholine or non-depolarizing agent. Spontaneous respiration with deep anesthesia is also an option in selective cases. Adequacy of mask ventilation should be ensured before administering relaxants. In addition, local anesthesia can be sprayed onto the glottis to prevent laryngospasm, coughing and to decrease the general anesthetic requirements. The ideal position for the visualization of the larynx and intubation is the combination of anterior flexion of the neck with hyperextension of the atlanto-occipital joint. Select appropriate size scope, introduce after direct laryngoscopy, shoulder bolster is placed after it crosses the glottis. The correct size is the one that allows an audible leak at 20 cm H2O pressure. Contraindications Severe refractory hypoxemia, hemodynamic instability and uncorrected hemorrhagic diathesis are absolute contraindications of bronchoscopy. The relative ones are very premature neonates, severe pulmonary hypertension, congenital cyanotic cardiomyopathy with increased bronchial collateral circulation, etc. Hypoxia Hypoxia can occur for many reasons. If the scope is placed in a bronchus, hypoxia may occur despite the

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presence of the side ports and the scope may need to be repeatedly withdrawn. Excessive suctioning will remove gases including oxygen and cause increased atelectasis. Introduction of the telescope into the bronchoscope seals its distal end. However, it also diminishes the crosssectional area of lumen through which the patient can breathe, significantly increasing the work of breathing and potentially causing hypercarbia in spontaneously breathing patient. This is a particular problem in infants. Even with assisted ventilation, hypercarbia leading to respiratory acidosis can be a problem because the expiratory pressure generated by passive elastic recoil of chest and lung may be insufficient to expel air through the smallest scopes.Â BAL and prolonged aspiration maneuvers, mainly in newborns and infants, favor alveolar collapse and increase the risk of hypoxia and hypercarbia. Due to vagal irritation, or in children with bronchial hyper-reactivity, there may also be some degree of bronchospasm. These changes can be attenuated by maintaining a stable hemodynamic situation, choosing instruments of the proper size, previously administering bronchodilators and supplemental oxygen, optimizing the sedation-anesthesia and performing the procedure quickly.7 Recovery A brief period of observation is required after the procedure. Most complications occur early and are readily apparent at the time of the procedure. Full consciousness needs to be recuperated and oral tolerance should be checked before making the decision to discharge the patient. No food or drink should be offered until 2 hours after the procedure.

PEDIATRICS Conclusion Despite the advent of fiberoptic bronchoscopy, rigid bronchoscopy is still widely used. The basic reason is the high incidence of foreign bodies in children. It is still useful as a diagnostic or therapeutic tool when there is compromised ventilation, when extensive biopsies are necessary or when atelectasis should be resolved with the elimination of mucus plugging. The majority of the indications are therapeutic. Whenever possible, it should be performed in a tertiary referral center. There must be excellent communication between the anesthetist and the endoscopist to ensure that adequate oxygenation is maintained via the shared airway.

2. Roberts S, Thornington RE. Paediatric bronchoscopy. Contin Educ Anaesth Crit Care Pain 2005;5(2):41-4. 3. Pérez Ruiz E, Barrio Gómez De Agüero MI; Grupo Técnicas, Sociedad Española de Neumología Pediátrica. Flexible bronchoscopy in children: Indications and general considerations. An Pediatr (Barc) 2004;60(4): 354-66. 4. Lerra S, Raj R, Aggarwal S, Saini VK, Nagarkar NM. A long standing foreign body in bronchus in an adult. A diagnostic dilemma. JK Science 2011;13(1):27-8. 5. Díaz-Agero P, Gonzalez FC, Alonso GJL. Indicaciones y técnica de la broncoscopia rígida. Pg.53-70.

References

6. Pérez-Frías J, Caro-Aguilera P, Pérez-Ruiz E, MorenoRequena L. Foreign body management. Combined bronchoscopy in a Paediatric Pulmonology Unit. An Pediatr (Barc) 2010;72(1):67-71.

1. Gormley SMC, Crean PM. Basic principles of anaesthesia for neonates and infants. Contin Educ Anaesth Crit Care Pain 2001;1(5):130-3.

7. de Blic J, Marchac V, Scheinmann P. Complications of flexible bronchoscopy in children: prospective study of 1,328 procedures. Eur Respir J 2002;20(5):1271-6.

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ÂÂ

A study published online March 24 in the Journal of Clinical Oncology has reported that children with stage 4N metastatic neuroblastoma exhibited better outcomes than those with other stages of metastatic disease. Stage 4N patients had significantly better estimated 5-year event-free survival (77%) and overall survival (85%) than the non-4N stage patients (35% and 42%, respectively).

ÂÂ

A study presented at the 16th International Congress on Infectious Diseases has revealed that pregnant women given the flu vaccine have a 50% reduced risk of developing influenza. The risk to their newborns in the first 24 weeks of life is also decreased. The study results reported fewer cases of influenza in infants of mothers in the vaccination group than in infants of mothers in the placebo group (19 vs 37). The vaccine efficacy rate was about 49%.

ÂÂ

A multifaceted quality improvement initiative has proven successful in keeping newborn premature infants in the desired temperature range and reducing complications including intubation, reports a new study published online March 31 in Pediatrics. A multidisciplinary team encompassing medical and nursing staff from neonatology, obstetrics, and anesthesiology and members of the bioengineering department made use of polyethylene occlusive wrap, transwarmer mattresses, prewarmed double caps and a consistent operating room temperature between 21°C and 23°C. The number of infants with temperature <36°C decreased from 55% to 6.2% at baseline compared with full implementation; the incidence of moderate hypothermia decreased from 35% to 10.5% among infants with a gestational age of <28 weeks, from 44% to 1% among infants at 29-32 weeks of gestational age, and from 79% to 9.7% among infants at 33-34 weeks of gestational age; the infants who remained intubated at 24 hours fell from 39% to 17.6%.

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RESPIRATORY DISEASES

Chronic Dry Cough in Allergic Respiratory Diseases: Diagnostic and Management Approach Pralhad P. Prabhudesai

Abstract Cough is considered as a single most common complaint for which patients globally seek medical attention. A multitude of allergic etiologies contribute to the development of chronic cough in adults, which makes the diagnosis and treatment quite challenging. Allergic cough is a distinct entity where there is no respiratory obstruction and there is presence of a family history, past history and/or concomitant allergic conditions. Sensitivity to allergens is readily demonstrable by skin testing. It is also characterized by a therapeutic response to epinephrine and a periodic nature. The intention of this article is to highlight the common causes of chronic dry cough associated with allergic diseases, to differentiate allergic cough from various other causes of chronic cough associated with asthma syndromes (which include related airway disorders like ‘classic’ asthma [cough-variant asthma], nonasthmatic eosinophilic bronchitis and atopic cough) and to discuss its management strategies.

Keywords: Chronic cough, allergic cough, occupational and environmental causes, mechanisms, management options Chronic Cough: A Worldwide Problem Cough is a forceful expiration against closed glottis. This maneuver prevents the entry of harmful substances into the lungs and movement of secretions and other airway constituents upward from mouth.1,2 Coughing, apart from being a physiological barrier against irritant substances that reach the respiratory tract, is also a symptom of diseases of both respiratory and nonrespiratory origin.1 Cough is considered as the single most common complaint globally for which patients seek medical attention.3 An individual’s lifestyle, quality-of-life and sense of well-being can be significantly affected by the presence of cough.1,2 A cough can be arbitrarily classified as acute (that lasts for <3 weeks), subacute (that lasts between 3 and 8 weeks) and chronic (that lasts for >8 weeks). Cough lasting longer than this duration can be precluded as being post-infectious cough. The estimated prevalence of chronic cough is between 11 and 20%.3,4 This type of cough is observed commonly in females and in obese individuals.5 Chronic cough is the fifth most common symptom reported by patients who visit the outpatient clinics.2 Morbidities associated with chronic cough include lack of sleep, exhaustion, urinary incontinence and syncope. There can also be socioeconomic encumbrances due to work absenteeism. Consulting Chest Physician Lilavati Hospital, Mumbai, Maharashtra E-mail: aumclinic@hotmail.com

Rib fractures, pneumothorax, pneumomediastinum and subcutaneous emphysema are some serious side effects associated with chronic cough.2 Link between Cough and Allergy: What Evidences Say?

Chronic Cough and Allergy Chronic cough has been linked to the presence of asthma and allergic rhinitis.6 Cough can occur as a symptom of allergic diseases such as seasonal allergic rhinitis, which is an inflammatory condition of the nasal mucous membranes. This type of cough is usually associated with rhinorrhea, nasal stuffiness/ congestion, nasal itching and sneezing.7 Occupational and environmental factors such as cigarette smoking and pollutants are known aggravating factors or triggers for cough and these may also exacerbate cough that was initially caused by other mechanisms.8,9 Presence of high levels of particulates has been linked to productive or chronic nocturnal dry cough in adults and school children. People, especially children living in localities which are close to areas of heavy traffic have been known to suffer from increased respiratory symptoms including cough and increased symptoms from respiratory viral infections.9

Causes of Allergic Cough The most common causes of chronic cough in nonsmoking adults (who have not received treatment with angiotensin-converting enzyme inhibitors and have

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RESPIRATORY DISEASES normal chest radiogram) include upper airway cough syndrome, gastroesophageal reflux disease and asthma syndromes. In this review, we will be discussing in detail about the association of cough with asthma syndromes and allergic diseases. Asthma syndromes represent a collection of related airway disorders including: ÂÂ

‘Classic’ asthma, the so-called cough-variant asthma

ÂÂ

Nonasthmatic eosinophilic bronchitis

ÂÂ

Atopic cough.10

Upper airway cough syndrome is a common condition that occurs in 20-40% (up to 87%) of patients who present with cough. This syndrome incorporates many diagnoses in the upper respiratory tract, including allergic rhinitis, nonallergic rhinitis, post-infectious (post-viral) cough, sinusitis and anatomic abnormalities of the nose and sinuses. All these conditions are linked to retention of mucosal secretions that drain into the posterior pharynx.12 Cough-variant Asthma

Both upper and lower respiratory causes of cough such as allergic rhinitis, asthma, allergic bronchopulmonary mycoses can be triggered by exposure to allergens such as dust mite, animal or cockroach allergens, fungi and pollen at indoor or outdoor environments (see Table 1).9

Cough and Allergic Diseases Allergic cough has certain characteristics that are common to all allergic diseases such as:11 ÂÂ

Presence of a family history of allergy

ÂÂ

History of past and/or concomitant allergic conditions (such as urticaria, eczema)

ÂÂ

Sensitivity to allergens that can be elicited by skin testing

ÂÂ

Therapeutic response to epinephrine

ÂÂ

Periodic nature of the allergic condition.

Cough is essentially produced on exposure to allergens and relieved on removing them. The sensitivity can be decreased by immunizing with the ‘concerned’ allergen, if the allergen is an inhalant. Important characteristic features of common allergic diseases have been described as follows.11 Table 1. Occupational and Environmental Causes of Allergic Cough Occupational factors

Environmental factors

Occupational rhinitis

Exposure to dust mite, animal or cockroach allergens, fungi and pollen

Occupational asthma

Exposure to cigarette smoking or other respiratory irritants

Occupational eosinophilic bronchitis

Exposure to indoor particulate pollution from biomass combustion

Hard metal disease

Exposure to air pollutants such as nitrogen oxides from gas cooking stoves or outdoor traffic

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Upper Airway Cough Syndrome

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In referral populations of adult nonsmokers, coughvariant asthma accounts for about 24-29% of diagnoses for chronic cough. Chronic and/or recurrent respiratory symptoms associated with reversible airflow obstruction and airway inflammation are the characteristic features of asthma. Stimulation of airway sensory nerves by inflammation is thought to be responsible for the occurrence of cough in these patients. Heightened cough sensitivity has been observed in patients with both asthma and chronic obstructive pulmonary disease.12 In contrast, allergic cough is not associated with any airflow obstruction.11 Eosinophilic Bronchitis Chronic cough is also an important entity in patients with eosinophilic bronchitis and the condition has two important similarities with asthma: ÂÂ

Presence of an eosinophilic airway infiltrate

ÂÂ

Response to corticosteroids.

There is no evidence of variable airflow obstruction or bronchial hyper-reactivity in patients with eosinophilic bronchitis but there is evidence of basement membrane thickening and elevated levels of exhaled nitric oxide that is reflective of airway eosinophilia. Patients with eosinophilic bronchitis, by definition, have sputum eosinophilia >3%.12 Atopic Cough This type of cough has clinical features of chronic nonproductive cough, sputum eosinophilia and lacks bronchial hyper-responsiveness. In contrast to eosinophilic bronchitis, atopic cough has eosinophilia only in the upper airway and the condition usually does not respond to inhaled corticosteroids.12 The Japanese Cough Research Society criteria for recognizing atopic cough include.10 ÂÂ

Nonproductive cough lasting for >8 weeks without wheezing or dyspnea.

RESPIRATORY DISEASES ÂÂ

ÂÂ

Presence of one or more findings indicative of an atopic constitution, including a past history and/or complications of allergic diseases excluding asthma. No bronchial reversibility (defined as less than a 10% increase in forced expiratory volume in 1 sec (FEV1) after inhalation of 300 μg salbutamol sulfate

ÂÂ

Normal bronchial responsiveness.

ÂÂ

Increased cough reflex.

ÂÂ

Cough-resistant to bronchodilator therapy.

ÂÂ

No abnormal findings indicative of cough etiology on chest X-ray.

ÂÂ

Normal FEV1 (≥80% of predicted value) and normal forced vital capacity (FVC) and FEV1/FVC ratio.

ÂÂ

An assessment of health status and cough severity should be done.

ÂÂ

Chest radiograph and spirometry which are considered as mandatory should be advised.

ÂÂ

Bronchial provocation testing should be performed in patients with chronic cough without a clinically obvious etiology and normal spirometry.

ÂÂ

Bronchoscopy should be performed in all patients with chronic cough and suspected foreign body inhalation.

ÂÂ

High resolution computed tomography may be helpful in patients with chronic cough in whom other more targeted investigations are normal.

ÂÂ

Optimal management strategies should be chosen based on the most likely aggravator(s) by using a combination of diagnostic testing and treatment trials.

ÂÂ

Effects of treatment should be quantified.

Characteristics of Allergic Cough Allergic cough is characterized by a loud barking sound with intensity and force that is similar to sneezing in hay fever. This type of cough is paroxysmal and nonproductive in nature, and may last from a few minutes to hours or days.11 In contrast, cough associated with cough-variant asthma is dry and nocturnal in nature while atopic cough is isolated in nature with cough hypersensitivity and normal airway responsiveness. Eosinophilic bronchitis, on the other hand, is characterized by a troublesome cough that is devoid of asthma symptoms and hyper-responsiveness.8 Pathophysiological events, following allergen exposure are generally biphasic.6 ÂÂ The early phase is mediated by mast cell-derived mediators. ÂÂ The late phase response that occurs from 4 to 12 hours after exposure and persists up to 24 hours, involves increased recruitment and activation of inflammatory cells such as T cells, neutrophils, macrophages and eosinophils. Evaluation and Diagnosis

Evaluation and History Taking The trigger for chronic cough can be gleaned from a detailed history of the patient. The evaluation should include a number of key components. The British Thoracic Society Cough Guidelines recommendations for evaluating a patient with chronic cough include:5 ÂÂ

A detailed history (including a thorough occupational history) should be taken in all patients.

ÂÂ

Physical examination should be performed with focus on the afferent sites of the vagus nerve most commonly associated with irritation leading is chronic cough.

Diagnosis With respect to allergic cough, the radiographic as well as physical examination of the chest and sputum analysis may be within normal limits. Patients with allergic cough may not look or feel sick, but may complain of an itchy, scratchy or rubbing sensation deep in the throat, leading to an irritation which can reflexly cause coughing spells.11

Differential Diagnosis of Common Allergic Respiratory Conditions Causing Cough Although allergic cough may resemble asthmatic cough, it can be differentiated by a normal chest examination and the lack of sibilant and sonorous rales and prolonged expiration that is observed in asthmatic cough. Additionally, patients with asthmatic cough have dyspnea and complaints of pressure over the sternum, whereas in patients with allergic cough there is no obstruction to respiration and other complaints.11 A negative result of methacholine challenge may rule out asthma as a cause of chronic cough.3 Differentiating features of the asthma syndromes have been presented in Table 2.8,11 Managing Chronic Dry Cough in Patients with Allergic Respiratory Diseases For cough associated with allergic conditions such as allergic rhinitis, in addition to avoidance of the offending allergen, oral antihistamines such as loratadine,

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RESPIRATORY DISEASES Table 2. Features of Cough Caused by Airway Diseases Symptoms

Atopy

Asthma

Cough-variant asthma

Atopic cough

Eosinophilic bronchitis

Cough, breathlessness, wheeze

Cough only

Cough and sputum

Common

As in general population

Variable airflow obstruction

−

Airway hyper-responsiveness

−

Capsaicin cough hyper-responsiveness

−

Bronchodilator response

−

Corticosteroid response

Response to H1 antagonist

n/a

30%

Rare

10%

Progression to asthma Sputum eosinophilia (>3%)

Frequent

Always

Submucosal eosinophils

↑

BAL eosinophilia

↑

↓

↑

Mast cells in ASM

↑

↓

Basement membrane thickness

↑

ASM = Airway smooth muscle; BAL= Bronchoalveolar lavage; n/a = Not applicable; NK = Not known. + = Often present; ± = Sometimes present; − = Not present; ↑ = Increased; ↓ = Not increased.

10 mg once a day is recommended. Nasal cromolyn, corticosteroids and azelastine may also be helpful. Upper airway cough syndrome can be managed with a trial of H1 antihistamines and decongestants for a period of 1-2 weeks. Patients who respond or partially respond to this treatment are advised to continue on the same for one more week and nonresponders are cough-variant asthma can be managed with the use of inhaled steroids by metered-dose inhaler with spacer or salbutamol by metered-dose inhaler with spacer as needed. Improvement of cough is usually noted within 1 week and resolution may take 6-8 weeks. Patients with this type of cough may require long-term maintenance therapy with an anti-inflammatory agent. For managing eosinophilic bronchitis, inhaled budesonide, 400 μg twice-daily for a period of 1-2 weeks is recommended; equivalent doses of other inhaled corticosteroids are also effective. Patients with this condition may require long-term therapy. Avoidance of aggravants is advised if the condition is found to be associated with an environmental irritant such as acrylic resin.3

Value of Antitussive Agents A trial of antitussive therapy is generally indicated for patients with chronic dry cough when the cause of an increased cough reflex is not known or when

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the treatment against potential aggravating factors remains unsatisfactory.13 Most antitussives available are combinations of dextromethorphan or codeine with antihistamines, expectorants, decongestants and/or antipyretics. Codeine is a commonly used, centrally-acting cough suppressant and its effectiveness in suppressing artificially-induced, disease-related and chronic cough has been established from animal models and in humans. Codeine has analgesic and sedative effects in addition to its antitussive property, which may be useful in relieving painful cough. The American College of Chest Physicians (ACCP) evidencebased clinical practice guidelines recommend cough suppressants such as codeine and dextromethorphan for short-term symptomatic relief of cough in patients with chronic bronchitis.14 Conclusions Allergic cough is characterized by the presence of marked familial history, past history and/or concomitant allergic conditions, sensitivity to allergens readily demonstrable by skin testing, therapeutic response to epinephrine and its periodic nature. Chronic cough is a common symptom in a multitude of allergic diseases in adults, which makes the diagnosis and treatment quite challenging. Differential diagnosis and

RESPIRATORY DISEASES a systematic therapeutic approach might simplify the management of cough related to allergies. Avoidance of offending allergen is the first-line of defense to reduce the possibility of an allergic attack. Various therapeutic options available for the management of cough associated with allergic conditions. Use of antitussive agent such as codeine or dextromethorphan is suggested for the short-term symptomatic relief of dry cough.

Key Messages ÂÂ

ÂÂ

Chronic cough is a common symptom in a multitude of allergic diseases in adults, which makes the diagnosis and treatment quite challenging. Differential diagnosis and a systematic therapeutic approach might simplify the management of cough related to allergies.

the management of cough in adults. Thorax 2006;61 Suppl 1:i1-24. 6. Brozmanová M, Calkovský V, Plevková J, Bartos V, Plank L, Tatár M. Early and late allergic phase related cough response in sensitized guinea pigs with experimental allergic rhinitis. Physiol Res 2006;55(5):577-84. 7. Gawchik S, Goldstein S, Prenner B, John A. Relief of cough and nasal symptoms associated with allergic rhinitis by mometasone furoate nasal spray. Ann Allergy Asthma Immunol 2003;90(4):416-21. 8. Chung KF, Pavord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet 2008;371(9621):1364-74. 9. Tarlo SM. Cough: occupational and environmental considerations: ACCP evidence-based clinical practice guidelines. Chest 2006;129(1 Suppl):186S-196S. 10. Magni C, Chellini E, Zanasi A. Cough variant asthma and atopic cough. Multidiscip Respir Med 2010;5(2):99-103.

References

11. Prigal SJ. Allergic cough. Chest 1942;8(4):115-20.

1. Singh N, Singh V. Combating cough - etiopathogenesis. J Assoc Physicians India 2013;61(5 Suppl):6-7.

12. White KM, Tankersley MS, Kelkar PS. Mechanisms of cough in asthma and allergic airway disease. Allergy Frontiers 2009;3:187-201.

2. Iyer RK, Joshi JM. Future drugs for the treatment of dry cough. J Assoc Physicians India 2013;61(5 Suppl):14-6. 3. Irwin RS, Madison JM. The diagnosis and treatment of cough. N Engl J Med 2000;343(23):1715-21. 4. Rai SP. Chronic cough. J Assoc Physicians India 2013;61(5 Suppl):28-30. 5. Morice AH, McGarvey L, Pavord I; British Thoracic Society Cough Guideline Group. Recommendations for

13. Pavord ID, Chung KF. Management of chronic cough. Lancet 2008;371(9621):1375-84. 14. Irwin RS, Baumann MH, Bolser DC, Boulet LP, Braman SS, Brightling CE, et al; American College of Chest Physicians (ACCP). Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest 2006;129(1 Suppl):1S-23S.

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Around the Globe

News and Views ÂÂ The 13-valent pneumococcal conjugate vaccine

(PCV-13) may offer moderate protection against the most common forms of pneumococcal community-acquired pneumonia in healthy elderly people, reports the large prospective “Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA)” study, presented at the 16th International Congress on Infectious Diseases. The vaccine was 45.5% effective at preventing a first episode of vaccine-type pneumococcal pneumonia, compared with placebo. Additionally, it was 45.0% effective at preventing a first episode of nonbacteremic/noninvasive vaccine-type pneumococcal pneumonia and 75.0% effective at preventing vaccine-type invasive pneumococcal pneumonia. ÂÂ Horizontal rectus muscle plication is effective for strengthening muscles as a treatment for strabismus, according to a new study published online March 27 in JAMA Ophthalmology. Plication has a number of advantages over resection, including less surgical trauma; preservation of the vascular supply to the anterior segment of the eye; potential for early surgical reversibility; and no risk of loss of the muscle in the event of suture breakage or other surgical mishap, whereas in resection tendon loss is prevented only by suture integrity. ÂÂ An experimental glucagonlike peptide-1 (GLP-1)

agonist administered intranasally before meals has been noted to improve postmeal markers of glycemic control without severe adverse events in patients with type 2 diabetes in a recent study. The study has been published online in Diabetes Care. Study results revealed that mean HbA1c was 7.7% for those who were randomized to the GLP-1 compound and 7.5% for 8 patients randomized to intranasal placebo. ÂÂ Foot pain in psoriatic arthritis (PsA) was predicted by synovitis, erosion, subluxation of the metatarsophalangeal (MTP) joints, obesity and female sex but unlike foot pain in rheumatoid arthritis, it was not predicted by elevated plantar pressure, according to a comparison study published in the April issue of Rheumatology. ÂÂ A much debated presentation at the American

College of Cardiology 2014 Scientific Sessions has reported that the rate of major adverse cardiac

events (MACE) is significantly lower in the heparin-treated patients at 28 days in comparison to bivalirudin. The single–center randomized trial also reported no differences in bleeding complications in the two groups. It was noted that at 4 weeks, the primary efficacy end point (MACE, defined as all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularization [TLR]) had occurred in 8.7% of bivalirudin-treated patients and in 5.7% of heparintreated patients. ÂÂ One-year data from the transcatheter valve therapy

(TVT) registry has reported that 56% of patients undergoing transcatheter aortic-valve replacement (TAVR) therapy are still alive and have not been readmitted to the hospital for any cause. The overall mortality at one year was just above 26%. Additionally, the rate of stroke at one year was 3.6%; a rate that is significantly lower than that in previous trials. The study results were presented at the American College of Cardiology 2014 Scientific Sessions.

ÂÂ A study published in the April issue of Rheumatology

has reported that foot pain in psoriatic arthritis (PsA) is predicted by synovitis, erosion, subluxation of the metatarsophalangeal (MTP) joints, obesity and female sex; however, unlike foot pain in rheumatoid arthritis, it may not be predicted by elevated plantar pressure. The study authors compared 34 patients with confirmed PsA with 22 control patients to identify the independent predictors of forefoot pain at the MTP joints.

ÂÂ Limiting dietary sodium intake increases renin-

angiotensin-aldosterone system (RAAS) blockade efficacy in diabetics with chronic kidney disease, reports a novel research published in the Lancet Diabetes and Endocrinology. Researchers at University Medical Center Groningen in the Netherlands conducted a double-blind, placebo-controlled, crossover randomized trial in 45 patients with type 2 diabetic nephropathy. Sodium restriction and hydrochlorothiazide were noted to considerably reduce albuminuria; residual geometric mean albuminuria with baseline treatment was 711 mg/day, with sodium restriction it was 393 mg/day, with hydrochlorothiazide it was 434 mg/day, and with the combination, it dropped to 306 mg/day.

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Around the Globe ÂÂ Comprehensive analyses of observational and

randomized clinical trials have suggested that vitamin D given alone has no effect on increase in bone-mineral density or reduction of risk for fractures or falls in older people. Vitamin D was however, found to be beneficial in pregnant women, for tooth decay in children, and in patients with chronic renal disease.

and placebo-treated subjects (53.1% vs 54.8%). NT-proBNP concentration did not differ between the 2 arms; it was 167 ng/L in both groups. The incidence of major adverse cardiac events (MACE) was 3.1% in the metformin group and 1.1% in the placebo group. ÂÂ Another study presented at ACC 2014 reports that

most athletes with heart problems requiring an implantable cardioverter defibrillator (ICD) can eventually be allowed to participate in sports. Dr David Cannom from the University of California, Los Angeles and Dr Rachel Lampert from the Yale University School of Medicine established a prospective registry to establish the safety of sports for athletes with ICDs. About 372 athletes participating in organized or high-risk sports (mean age 33 years) were identified. They noted that over 31 months of follow-up, none of the patients died or had a cardiac arrest requiring resuscitation during sports activities. There were no arrhythmia-or shock-related injuries during the activity either.

ÂÂ Results from the early-phase stand up to cancer

study have reported that buparlisib, a reversible pan-PI3K inhibitor, combined with letrozole, an aromatase inhibitor, may be effective in treating estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer. Researchers evaluated the safety and tolerability of oral letrozole in combination with buparlisib in a phase Ib trial of 51 patients with ER-positive metastatic breast cancer that did not respond to endocrine therapies. The combination was well-tolerated and 2 of 20 patients in the continuous arm achieved a complete and a partial remission, while 11 patients (55%) had stable disease (lasting at least 6 months in six patients, or 30%). No patient in the intermittent arm showed a response, yet 14 (45%) had stable disease (lasting at least 6 months in 10 patients, or 32%).

ÂÂ A novel study published online April 2 in JAMA

ÂÂ A study presented at the American College of

Cardiology 2014 Scientific Sessions states that metformin is of no help when given to patients without diabetes who had just suffered an ST-segment acute MI (STEMI). The drug does not preserve left ventricular ejection fraction (LVEF) after STEMI compared with placebo in those without diabetes. The study results revealed no significant difference in the primary end point, LVEF on MRI, between metformin–treated

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Dermatology has reported that children with symptoms of atopic dermatitis (AD) might have persistence of symptoms into their teens, and beyond. The long-term longitudinal study included 7,157 children, aged 2-17 years. At every age, from 2-26 years, more than 80% of participants exhibited continued symptoms of AD and reported using topical medications to control the symptoms. By 20 years of age, about 50% of the patients had experienced at least a single 6-month symptomfree period.

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emedinews inspiration

Determination and Persistence

his is a real life story of engineer John Roebling building the Brooklyn Bridge in New York, USA back in 1870. The bridge was completed in 1883, after 13 years. In 1870, a creative engineer named John Roebling was inspired by an idea to build a spectacular bridge connecting New York with the Long Island. However bridge building experts throughout the world thought that this was an impossible feat and told Roebling to forget the idea. It just could not be done. It was not practical. It had never been done before. Roebling could not ignore the vision he had in his mind of this bridge. He thought about it all the time and he knew deep in his heart that it could be done. He just had to share the dream with someone else. After much discussion and persuasion he managed to convince his son Washington, an up and coming engineer, that the bridge in fact could be built. Working together for the first time, the father and son developed concepts of how it could be accomplished and how the obstacles could be overcome. With great excitement and inspiration and the headiness of a wild challenge before them, they hired their crew and began to build their dream bridge. The project started well, but when it was only a few months underway a tragic accident on the site took the life of John Roebling. Washington was also injured and left with a certain amount of brain damage, which resulted in him not being able to talk or walk. “We told them so.” “Crazy men and their crazy dreams.” “It’s foolish to chase wild visions.” Everyone had a negative comment to make and felt that the project should be scrapped since the Roebling’s were the only ones who knew how the bridge could be built. In spite of his handicap Washington was never discouraged and still had a burning desire to complete the bridge and his mind was still as sharp as ever. He

tried to inspire and pass on his enthusiasm to some of his friends, but they were too daunted by the task. As he lay on his bed in his hospital room, with the sunlight streaming through the windows, a gentle breeze blew the flimsy white curtains apart and he was able to see the sky and the tops of the trees outside for just a moment. It seemed that there was a message for him not to give up. Suddenly an idea hit him. All he could do was move one finger and he decided to make the best use of it. By moving this, he slowly developed a code of communication with his wife. He touched his wife’s arm with that finger, indicating to her that he wanted her to call the engineers again. Then he used the same method of tapping her arm to tell the engineers what to do. It seemed foolish but the project was under way again. For 13 years Washington tapped out his instructions with his finger on his wife’s arm, until the bridge was finally completed. Today the spectacular Brooklyn Bridge stands in all its glory as a tribute to the triumph of one man’s indomitable spirit and his determination not to be defeated by circumstances. It is also a tribute to the engineers and their team work, and to their faith in a man who was considered mad by half the world. It stands too as a tangible monument to the love and devotion of his wife who for 13 long years patiently decoded the messages of her husband and told the engineers what to do. Perhaps this is one of the best examples of a never-saydie attitude that overcomes a terrible physical handicap and achieves an impossible goal. Often when we face obstacles in our day-to-day life, our hurdles seem very small in comparison to what many others have to face. The Brooklyn Bridge shows us that dreams that seem impossible can be realized with determination and persistence, no matter what the odds are.

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eMedi Quiz

Quiz Time 1.

Injury to radial nerve in lower part of spiral groove

A. Spares nerve supply to extensor carpi radialis longus.

B-oxidation of odd-chain fatty acids produces

A. Succinyl CoA B.

Propionyl CoA Acetyl CoA

Results in paralysis of anconeus muscle.

Leaves extension at elbow joint intact.

D. Malonyl CoA

D. Weakens pronation movement. 2.

The cells belonging to the following type of epithelium are provided with extra reserve of cell membrane

Injury to radial nerve in lower part of spiral groove

Spares nerve supply to extensor carpi radialis

A. Transitional

longus.

Results in paralysis of anconeus muscle.

Leaves extension at elbow joint intact.

Weakens pronation movement.

The cells belonging to the following type of

Stratified squamous

C. Stratified cuboidal D.

Stratified columnar

In a patient with a tumor in superior medistinum compressing the superior vena cava, all the following veins would serve as alternate pathways for the blood to return to the right atrium, except

A. Lateral thoracic vein

epithelium are provided with extra reserve of cell membrane A. Transitional C.

Stratified squamous

Hemiazygos vein

Stratified cuboidal

D. Vertebral venous plexus

Stratified columnar

Internal thoracic vein

Answers to eMedi Quiz Published in March 2014 Issue Q1. D. Phenobarbitone with a pKa of 7.2 is largely ionized at acid pH and will be about 40% nonionized in plasma. Q2. B. Interstitial lung disease Q3. C. Bone erosions Q4. D. Superior vena caval obstruction Q5. A. The sample should be kept at 4째C. Q6. B. Sympathetic ophthalmia Send your answers to the Editor-Indian Journal of Clinical Practice. E-mail: editorial@ijcp.com The correct answers will be published in the next issue of IJCP.

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lighter reading

Humor

High Blood Pressure When a physician remarked on a new patient’s extraordinarily ruddy complexion, he said, “High blood pressure, Doc. It comes from my family.” “Your mother’s side or your father’s?” I asked. “Neither,” he replied. “It’s from my wife’s family.” “Oh, come now,” I said. “How could your wife’s family give you high blood pressure?”

Quote

Lighter Side of Medicine “The hardest battle you are ever going to fight is the battle to be just you.” −Dr. Felice Leonardo Buscaglia

Make Sure

During Medical Practice A rape victim became pregnant. Oh my God! Why was emergency contraceptive not given to her?

He sighed. “You oughta meet ’em sometime, Doc!

Laugh A While Scientists Competition Once there was a competition conducted with Scientists from America, France and China.

On this, Scientists from France came with the report: “We crossed flies and bees. Now, the hybrid flies over the trash fields and produces honey.” Chinese gave others run for their money. They said: “We crossed a melon with cockroaches. And now when you cut this melon, seeds run away by themselves...”

Organized Crime No matter how much the government fights it, organized crime just seems to get more organized every day. The police pulled in a Mob kingpin recently and reminded him he had the right to make a phone call. “Just fax the arrest report to my lawyer,” the mobster said calmly.

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©IJCP Academy

The Americans reported: “We crossed chickens with cows. And now the new breed simultaneously produces milk, meat and eggs.” Make sure that all victims of rape are given an emergency contraceptive. KK Aggarwal

ILLUSION

Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767). Indian Journal of Clinical Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so. The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript. Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper. Covering letter –

– –

The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper. Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors. Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

Manuscript – Three complete sets of the manuscript should be submitted and preferably with a CD; typed double spaced throughout (including references, tables and legends to figures). –

The manuscript should be arranged as follow: Covering letter, Checklist, Title page, Abstract, Keywords (for indexing, if required), Introduction, Methods, Results, Discussion, References, Tables, Legends to Figures and Figures.

–

All pages should be numbered consecutively beginning with the title page.

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors. Title page Should contain the title, short title, names of all the authors (without degrees or diplomas), names and full location of the departments and institutions where the work was performed,

name of the corresponding authors, acknowledgment of financial support and abbreviations used. – The title should be of no more than 80 characters and should represent the major theme of the manuscript. A subtitle can be added if necessary. – A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included. – The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page. – A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text. Summary – The summary of not more than 200 words. It must convey the essential features of the paper. – It should not contain abbreviations, footnotes or references. Introduction – The introduction should state why the study was carried out and what were its specific aims/objectives. Methods – These should be described in sufficient detail to permit evaluation and duplication of the work by others. – Ethical guidelines followed by the investigations should be described. Statistics The following information should be given: – The statistical universe i.e., the population from which the sample for the study is selected. – Method of selecting the sample (cases, subjects, etc. from the statistical universe). – Method of allocating the subjects into different groups. – Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques. –

Confidence intervals for the measurements should be provided wherever appropriate.

Results – These should be concise and include only the tables and figures necessary to enhance the understanding of the text.

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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 Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes. Q. J. Expt. Physiol. 1955;40:89-111.

Figures – Two complete sets of glossy prints of high quality should be submitted. The labelling must be clear and neat. – All photomicrographs should indicate the magnification of the print. – Special features should be indicated by arrows or letters which contrast with the background. – The back of each illustration should bear the first author’s last name, figure number and an arrow indicating the top. This should be written lightly in pencil only. Please do not use a hard pencil, ball point or felt pen. – Color illustrations will be accepted if they make a contribution to the understanding of the article. –

Do not use clips/staples on photographs and artwork.

–

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

Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected summary, etc.)_______________________________ 2. Total number of pages ________________________ 3. Number of tables ____________________________ 4. Number of figures ___________________________

Books

5. Special requests _____________________________

Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

6. Suggestions for reviewers (name and postal address)

Articles in Books

2.____________ 2.________________

Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.

3.____________ 3.________________

4.____________ 4.________________

Tables –

These should be typed double spaced on separate sheets with the table number (in Roman Arabic numerals) and title above the table and explanatory notes below the table.

Legends – These should be typed double spaces on a separate sheet and figure numbers (in Arabic numerals) corresponding with the order in which the figures are presented in the text. –

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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. 24, No. 11, April 2014

Indian 1.____________Foreign 1.________________

7. All authors’ signatures________________________ 8. Corresponding author’s name, current postal and e-mail address and telephone and fax numbers __________________________________________

Online Submission Also e- Issue @ www.ijcpgroup.com For Editorial Correspondence

Dr KK Aggarwal

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

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

POSTAL REGISTRATION NO. DL (S)-01/3200/2012-2014 Posted in N.D. PSO New Delhi