esculapio by Asif Hanif

Journal of Services Institute of Medical Sciences Volume. 07

January - March 2011

Patron Prof. Faisal Masud (Principal SIMS & Professor of Medicine)

Editor -in-chief Prof. Aziz-ur-Rehman (Pr ofessor of Medicine)

Associate Editors Dr. N. Rehan (Director PMRC (R))

Prof. Dilawaiz Nadeem (Orthopaedic Sur ger y)

Prof. Tahira Tasneem (Haematolog y)

Dr. Anjum Razzaq (IPH)

Assistant Editors Dr. Muhammad Nasar Sayeed Khan (Psychiatr y) Dr. Tayyaba Khawar Butt (Paediatric Medicine) Dr. Muhammad Saeed Anwar (Patholog y) Dr. Sajid Nisar (Medicine) Dr. Salma Haq (Patholog y) Statistician Muhammad Ghias Composed by Ameer Ali

No. 01

Review Board

Editorial Advisory Board

Prof. Dr. Iftikhar Ahmad (Lahore) Prof. Dr. Mumtaz Hasan (Lahore) Prof. Dr. Humanyun Maqsood (Lahore) Prof. Dr. Anwar A. Khan (Lahore) Prof. Tahir Shafi (Lahore) Prof. Dr. Bashir Ahmed (Lahore) Prof. Dr. S.A.R. Gerdezi (Lahore) Prof. Dr. Shamim Ahmad Khan (Lahore) Prof. Dr. Wasif Mohayudin (Lahore) Prof. Dr. Iqbal Butt (Lahore) Prof. Dr. Rashid Latif Khan (Lahore) Prof. Dr. Tahir Saeed Haroon (Lahore) Prof. Dr. Farrukh Khan (Lahore) Prof. Dr. A. H. Nagi (Lahore) Prof. Dr. Tahir Shafi (Lahore) Prof. Dr. Kartar Dhawani (Karachi) Prof. Dr. Abdul Malik Achakzai (Quetta) Prof. Dr. Fareed A. Minhas (Rawalpindi) Prof. Dr. Zafar Iqbal (Lahore) Prof. Dr. Alaf Khan (Peshawar) Prof. Dr. Shabbir Nasir (Multan) Prof. Khalid Bashir (Lahore) Prof. Dr. J. P. Long (UK) Prof. Dr. Harry Minhas (Australia) Prof. Dr. Sasleri (UK) Dr. Zia Farooqi (Lahore) Maj. Ge. Dr. Naseem-ul-Majeed (Rawalpindi) Brig. Dr. Mowadat H. Rana (Rawalpindi) Brig. Dr. Muhammad Ayub (Rawalpindi) Dr. Zia Farooqi (Lahore)

Prof. Matee Ullah Matee (Medicine) Prof. Rakhshan Shaheen Najmi (Gynae & Obst.) Prof. Riaz Ahmad Tasnim (Urology) Prof. Rizwan Masood Butt (Neurosurgery) Prof. Sohail Khurshid Lodhi (Obst. & Gynae) Prof. Saqib Siddique (Obs. & Gynae) Prof. Sadaqat Ali Khan (Surgery) Prof. Ferdose Sultana (Anatomy) Prof. Ghazala Jaffary (Pathology) Prof. Ghulam Qadir Fayyaz (Plastic Surgery) Prof. Hamid Javed Qureshi (Physiology) Prof. Shahid Mahmood (Community Medicine) Prof. Javed Raza Gardezi (Surgery) Prof. Kamran Khalid Chima (Pulmonology) Prof. Mehmood Ayaz ( Surgery) Prof. Muhammad Ali (Paediatric Medicine) Prof. Mohammad Tahir (Paediatric Surgery) Prof. Muhammad Amjad (ENT) Prof. Muhammad Azam Bokhari (Dermatology) Prof. Muhammad Mujeeb (ENT) Prof. Muhammad Sarfraz Ahmad (Surgery) Prof. Muhammad Tayyab (Ophthalmology) Prof. Naveed Aqbal Ansari (Pharmacology) Dr. Saeed Akhtar Khan (Histopathology) Dr. Syed Zia-ud-Din (Forensic Medicine) Dr. Qamar Sardar (Radiology) Dr. Kaukab Sultana (Biochemistry) Dr. Khadija Irfan Khawaja (Endocrinology) Dr. Sobia Qazi (Infectious Diseases) Dr. Shoaib Nabi (Thoracic Surgery)

E D I TO R I A L

Chronic Lung and Liver Disease: The Complex Interrelationships: Hepatitis C Virus-associated Lung Disease Aziz-ur-Rehman

This matter is addressed in detailed in an article by Masood et al, in this issue of the Esculapio. Worldwide, HCV is a common cause of chronic liver disease, and a risk factor for liver cirrhosis and hepatocellular carcinoma. This viral infection can also be complicated by a number of extrahepatic manifestations and has been associated with both obstructive and restrictive lung disease. Fibrotic lung disease likely results from an inciting injurious event within the lung. The precise temporal sequence of events and mechanisms of disease, however, is not understood. An emerging hypothesis is that occult infections may play a pathogenetic role as cofactors for the development of pulmonary fibrosis, based on the assumption that an inflammatory agent disrupts the physiologic healing response, thus making the lung highly susceptible to injurious triggers. HCV is a well-known cause of liver fibrosis and could potentially provoke similar abnormalities in the lung, mainly because of its lymphotropism, which can induce chronic immune activation and inflammation.Conversely, hepatitis B virus appears to play only a marginal role in lung fibrosis. The extent of these abnormalities does not correlate with liver disease severity, because the virus is not known to replicate in the lung, it remains unclear whether HCV is causative or whether patients with IPF simply.There is confounding effect of smoking on the HCV/IPF association.

Esculapio - Volume 07, Issue 01, January-March 2011

Original Article

Detection of Esophageal Varices in Liver Cirrhosis Using Platelet Count as a Non-invasive Parameter Muhammad Imran, Javeid Iqbal and Raffad

Background: Bleeding of the esophageal varices is a major complication of portal hypertension. At least two-thirds of patients with cirrhosis develop esophageal varices, and about 30% of patients with cirrhosis experience variceal bleeding. Objective: To determine the diagnostic accuracy of platelet count to predict the presence of esophageal varices in patients with liver cirrhosis taking endoscopic findings as gold standard. Material & Methods: This cross-sectional observational study was carried out over a period of six months from December, 2008 to June, 2009 in five medical wards (I, II, III, IV, and Special) of Services Hospital, Lahore. Total 180 cases were chosen in this study. Initially, non-invasive parameters were used to diagnose varices; later, endoscopy was performed to confirm the diagnosis. Results: Mean age of the patients observed was 50.5Âą10.9 years. Sensitivity, specificity, PPV, NPV and diagnostic accuracy of platelet count was 99.2%, 92.2%, 97.1%, 97.3% and 97.2% respectively. Conclusion: Results of current study indicate that patients of chronic liver disease can be screened for esophageal varices using platelet count as a non-invasive parameter. Keywords: Esophageal varices, liver cirrhosis, platelet count Noninvasive assessment of esophageal varices may improve the management of patients with cirrhosis and decrease both the medical and financial burden 6 related to screening. In a study done by Sarwar et al, it was concluded that serum albumin less than 2.95g/dL, platelet count less than 88,000/ÂľL and portal vein diameter more than 11mm were associated with presence of varices.3 It has been observed in another study that a platelet count of 82,000/ÂľL (90.9% sensitivity, 41.7% specificity), portal vein diameter of 1.15 cm (75% sensitivity; 54.5% specificity) and an antero posterior splenic measurement of 10.3 cm (83.3% sensitivity; 63.6% specificity) were predictive factors for esophageal varices in liver cirrhosis.7 Platelet count, portal vein diameter and antero posterior splenic measurement can be used as noninvasive parameters to detect esophageal varices in cirrhotic patients. They may be proposed as safe and reproducible means to improve the management of cirrhotic patients who undergo screening endoscopy for esophageal varices as endoscopic exploration of varices in cirrhotic patients increases cost and involves a certain degree of invasiveness and discomfort for patients. Early endoscopic intervention for varices could be applied to those who have varices to reduce the acute mortality by variceal

Introduction Esophageal varices are the most significant complication of portal hypertension, which may be 1 associated with 20% of cirrhotic patients. The prevalence of esophageal varices in cirrhosis is from 50% to 61%.2,3 In Pakistan, prevalence of esophageal varices is 65% and that of large varices is 15% in cirrhotic patients.4 The risk of bleeding from varices is 25%-35% with majority of the initial bleeding occurring within one year of detection. The mortality from each episode of variceal bleeding is 17%-57%.5 Bleeding episodes can be predicted by the presence of red sign (cherry red spots) on the varices and by its size. The incidence of bleeding can be reduced with non selective beta-blockers. It is also suggested that prophylactic endoscopic variceal ligation can decrease the incidence of first variceal bleeding and mortality in patients with liver cirrhosis who have large varices. Therefore, annual endoscopic screening is highly recommended for patients with small esophageal varices while the procedure should be conducted once every two years for patients suffering from liver cirrhosis without diagnosed varices. Nevertheless, repeated endoscopic examinations are unpleasant for patients, and have cost impact on health care, while only half of cirrhotic patients have esophageal varices, and only 30% have large varices.5 2

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bleeding. Very few studies have been done to determine the association of platelet count with esophageal varices in our setup. The aim of this study therefore, is to explore the use of platelet count in diagnosing esophageal varices.

margin of error, 95% confidence level with sensitivity and specificity of portal vein diameter and prevalence of esophageal varices being 75%, 54.5% and 50% respectively. The mean age of the sample was 50.2Âą10.5 years. The maximum age was 60 and minimum age was 20 years. Most of the patients belonged to group 41 year to 60 years (83.3%) as illustrated in Figure-1. Out of 180 patients, 97 patients (53.9%) were male and 83 patients (46.1%) were female. The study showed that 138 patients with platelet count below 80,000/ÂľL had varices on gold standard as depicted by Table-1. It was observed that platelet count can be used as non-invasive screening tool for predicting esophageal varices with diagnostic accuracy of 97.2% and it has 99.2% sensitivity and 90.2% specificity. Moreover, platelet count has 97.1% positive predictive value and 97.3% negative predictive value for diagnosing esophageal varices.

Material & Methods This cross-sectional observational study was carried out over a period of six months from December 2008 to June 2009 in five medical wards (I, II, III, IV, and Special units) of Services Hospital, Lahore. A total of 180 patients were recruited through non-probability purposive sampling from amongst the patients (>15 and <60 years) admitted at Services Hospital, a tertiary care health facility in Lahore, Pakistan. Only those patients demonstrating evidence of cirrhosis of liver on abdominal ultrasound (coarse echo texture) were included. Following were excluded: patients with a history of previous bleed or melena, active variceal bleeding, already on prophylaxis for esophageal varices, treated with band ligation or sclerosing agents for esophageal varices, co-morbid ischemic heart disease, bone marrow disorders, autoimmune diseases or those receiving interferon or drugs causing thrombocytopenia. An informed consent was taken from all the patients and confidentiality ensured. Risks and benefits were explained to the subjects. All the patients who fulfilled the inclusion criteria were interviewed and subjected to clinical examination, laboratory investigations including platelet count, ultrasonography and upper gastrointestinal endoscopy. Initially, non-invasive parameters were used to diagnose varices; later, endoscopy was carried out to confirm the diagnosis. The cut off value for platelet count was taken as <82000/ÂľL. Ethical approval for the study was received from the Review Committee of the Center for Health Research, Lahore. The study was conducted in compliance with 'ethical principles for medical research involving human subjects' of 8 Helsinki Declaration. All the data were entered and analyzed using SPSS version 10.0. Ages of the patients were presented by calculating mean and standard deviation and gender (male, female) were presented by calculating frequency and percentages. Sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of platelet count were calculated for the diagnosis of esophageal varices taking endoscopy as gold standard.

Table-1: Comparison of platelet count vs. upper GI endoscopy (n = 180) Platelet Count

Endoscopy (Gold Standard) Negative Positive

Positive

138 (True Positive)

04 (False Positive) 142

Negative

01 (False Negative)

37 (True Negative) 38

Total

139

Total

180

Fig-1: Distribution of cases by age.

Discussion Most cirrhotic patients develop esophageal varices, with a lifetime incidence as high as 90%.9,10 Approximately one third of cirrhotic patients with esophageal varices (EV) develop an episode of esophageal hemorrhage, and subsequently have high morbidity and mortality. Therefore, early detection and prevention of EV in cirrhotic patients are crucial

Results The calculated sample size of 180 cases had 9%

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to minimizing complications. An endoscopic examination is currently considered to be the gold standard. However, screening all patients with endoscopy to guide therapy may significantly increase the cost. Non-invasive indicators of varices are desired to reduce the need for screening endoscopy in all patients with cirrhosis. Studies show that platelet count, splenomegaly, platelet count/spleen diameter ratio, advanced Child-Pugh class, serum albumin, and high portal vein diameter measured by ultrasonography may be useful non-invasive predictors of 11 EV for patients with cirrhosis. In this study an attempt was made to find out sensitivity, specificity, negative predictive value, positive predictive value and diagnostic accuracy of platelet count in the diagnosis of esophageal varices taking endoscopy as gold standard. The findings of our study have considerable consistency with the results of different local and international studies conducted in the past in which different variables have been taken into consideration as non-invasive markers to detect the esophageal varices. Various parameters which have been studied include serum albumin, prothrombin time, platelet count, portal vein diameter, splenic index, antero4 posterior diameter of spleen. In one recent study cirrhotic patients without esophageal varices on initial endoscopy were followed up with annual or biannual surveillance. During the follow up it was proven that the platelet count/spleen diameter ratio is an effective means for ruling out the presence of esophageal varices even in the long term follow-up of the patients. 12 In this study all patients were followed up and endoscopies were done, and patients with higher baseline platelet count/ spleen diameter ratio were found less likely to develop esophageal varices. In our study we have not gone through the follow-up of endoscopies, making it less invasive and more convenient for the patients. 7 In another recent study by Prihatini et al using bivariate analysis it was found that a platelet count of 82,000/uL (90.9% sensitivity; 41.7% specificity), portal vein diameter of 1.15 cm (75% sensitivity; 54.5% specificity) and an anteroposterior splenic measurement of 10.3 cm (83.3% sensitivity; 63.6% specificity) were predictive factors for esophageal varices in liver cirrhosis. Our data also showed that platelet count can be used as non-invasive parameter to detect esophageal varices in cirrhotic patients. Our results are comparable with study. In a local study, it was concluded that using the

standard criteria of portal vein diameter 13 mm, I.N.R 1.5 and platelet counts 100,000/uL for the diagnosis of portal hypertension, about 70% patients 13 had endoscopic evidence of esophageal varices. Another study showed that three non-invasive markers, ie, prothrombin index below 60%, alkaline phosphatase activity over 110 IU/L, and hyaluronate over 100 g/L were the best markers for the prediction of esophageal varices. The diagnostic accuracy for medium to large esophageal varices using these three factors was 86%. 14 Comparing the results of the previous and objectively similar studies, the results of our study are relatively encouraging. Like other studies, our study also has certain limitations. Prediction models may vary with the nature of the patient population from which these are derived. Our patients represent only those with chronic liver disease attending a teaching hospital and it will not apply to the patients attending basic health units and district hospitals. Further studies, covering these aspects, will be necessary. Secondly, we did not test the predictive ability of this study in an independent prospective validation cohort, as was done in an Italian study. 15 Thirdly, the presence of varices on endoscopy is subject to inter-observer variation. Our current method was easy to conduct and has comparable accuracy with other models used in the past which comprised of single and multiple variables in predicting the esophageal varices. The study utilized non-invasive blood tests, which every patient had to undergo to diagnose chronic liver disease with its complications, so non-invasive markers are not only simple but also practical to be used in clinical practice.

Conclusion Results of current study indicate that patients of chronic liver disease of any etiology can be screened for esophageal varices using platelet count as noninvasive parameter. Screening the patients of chronic liver disease by these parameters for varices will decrease burden of endoscopies and it will be possible to prevent first episode of variceal bleeding in these patients by various pharmacological and nonpharmacological strategies. Department of Medicine SIMS/Services Hospital, Lahore

theesculapio@hotmail.com www.sims.edu.pk/esculapio.html

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References 1. Suzuki AA, Mendes FB, Lindor KB. Diagnostic model of esophageal varices in alcoholic liver disease. Euro J Gastro enterol Hepatol 2005; 17:307-9. 2. Thomopoulos KC, Labropoulou KC, Mimidis KP, Katsakoulis EC, Iconomou G, Nikolopoulou VN. Non-invasive predictors of the presence of large esophageal varices in patients with cirrhosis. Dig Liver Dis 2003; 35: 473-8. 3. Giannini E, Botta F, Borro P, Risso D, Romagnoli P, Fasoli A et al. Platelet count/spleen diameter ratio: proposal and validation of a non-invasive parameter to predict the presence of esophageal varices in patients with liver cirrhosis. Gut 2003; 52:1200-5. 4. Sarwar S, Khan AA, Alam A, Butt AK, Shafqat F, Malik K et al. Non-endoscopic prediction of presence of esophageal varices in cirrhosis. J Coll Physicians Surg Pak 2005; 15: 528-31. 5. Alempijevic T, Bulat V, Djuranovic S, Kovacevic N, Jesic R, Tomic D et al. Right liver lobe/albumin ratio: Contribution to non-invasive assessment of portal hypertension.

10.

11.

Gastroenterol 2007; 13: 5331-5. G a r t i a - Ta s a o G. C u r r e n t management of complications of cirrhosis and portal hypertension. Gastroentrol 2001;120:726-48. Prihatini J, Lesmana LA, Manan C, Gani RA. Detection of esophageal varices in liver cirrhosis using non-invasive parameters. Acta Med Indones 2005;37:126-31. WMA (2004). World Medical Association Declaration of Helsinki: ethical principles of medical research involving human subjects. [Available at: http:// www. wma.net/e/policy/b3.htm]. Lay CS, Tsai YT, Teg CY. Endoscopic variceal ligation in prophylaxis of first variceal bleeding in cirrhotic patients with high-risk esophageal varices. Hepatol 1997; 25: 1346-1350 [CrossRef][Medline] D'Amico G, Pagliaro L, Bosch J. Pharmacological treatment of portal hypertension: an evidencebased approach. Semin Liver Dis 1999;19:475 -505 [Medline] Hong WD, Zhu QH, Huang ZM, Chen XR, Jiang ZC, Xu SH, et al. Predictors of esophageal varices in patients with HBV-related

12.

13.

14.

15.

cirrhosis: a retrospective study. BMC Gastroenterol 2009; 9:11. Giannini EG, Botta F, Borro P, Dulbecco P, Testa E, Mansi C et al. Application of the platelet count/spleen diameter ratio to rule out the presence of oesophageal varices in patients with cirrhosis: a validation study based on follow-up. Dig Liver Dis 2005; 37:779-85. Gill ML, Atiq M, Sattar S, Khokhar N. Non-endoscopic parameters for the identification of esophageal varices in patients with chronic hepatitis. J Pak Med Assoc 2004; 54:575-7. Vanbiervliet G, Barjoan-Marine E, Anty R, Piche T, Hastier P, Rakotoarisoa C et al. Serum fibrosis markers can detect large esophageal varices with a high accuracy. Eur J Gastroenterol Hepatol 2005; 17: 333-8. Bressler B, Pinto R, El-Ashry D, Heathcote EJ. Which patients with primary biliary cirrhosis or primary sclerosing cholangitis should undergo endoscopic screening for esophageal varices detection. Gut 2005; 407-10.

Esculapio - Volume 07, Issue 01, January-March 2011

Original Article

Vaginal Birth After One Previous Caesarean Section (VBAC) Madeeha Rashid and Sumera Kanwal

Objective: To determine feto-maternal outcome and mode of delivery following one previous caesarean section.

Material & Methods: This descriptive study was conducted in department of Obstetrics & Gynaecology Unit-I Services Hospital, Lahore from June 2008 to June 2009. All patients with one previous caesarean section due to non-recurrent causes with spontaneous onset of labour at term were included in this study. Detailed clinical examination including abdominal and pelvic examination and ultrasound for fetal well being and placental localization were done. Progress of labour was monitored through Partogram. Fetal monitoring was done by auscultation and CTG. Results: Among 200 patients included in this study 66.5% had vaginal delivery while 33.5% had repeat caesarean section. Four scar dehiscence and one uterine rupture that was successfully repaired were noted. Common indications for repeat CS were failed progress and fetal distress. Conclusion: A trial of scar may be given in all pregnant women with previous caesarean section except those with absolute contraindications. A woman with one previous caesarean section delivery with low transverse incision should be counseled and encouraged to attempt labour in her current pregnancy in hospital with 24 hours facilities of operation theater and blood transfusion services. Keywords: VBAC, Previous Caesarean Section, Fetal outcome. Introduction

delivery following a previous lower uterine segment caesarean delivery.4 The decrease in women with previous caesarean section undergoing trial of labour reflects patient choice as much as obstetrician’s decision. The way in which a woman is counseled will influence this choice. If doctor has no objection to a repeat caesarean section and informed the woman that her chances of 5 a repeat operation is around 30% , the woman herself would be influenced by this. Evidence suggests that there is significantly greater morbidity associated with a trial of labour, compared with an elective caesarean section which will further affect the decision.6 Thus proper counseling (for trial of labour) and evaluation of the cases of women with prior caesarean section has been considered a key method of reducing the caesarean section rate. In developing countries like Pakistan it is better to give trial of labour in patients who do not have absolute contraindications for vaginal delivery. The policy of ‘once a caesarean always a caesarean section’ must be abandoned and replaced by ‘once a caesarean 1 section always a hospital delivery’. We conducted this study to assess the usefulness of trial of scar in case of one previous caesarean and know the frequency of vaginal delivery after caesarean section and the frequency of repeat caesarean section.

Vaginal birth after one previous caesarean section represents one of the most significant and challenging issues in obstetric practice. The increasing incidence of caesarean section over the last two to three decades has put negative impact on maternal health and obstetrical care.1 American College of Obstetricians & Gynaecologists recently updated their opinion on VBAC and stated that VBAC is safer than repeat caesarean section. A woman can attempt to deliver vaginally provided that there are no absolute medical and obstetrical reasons which make it difficult. They discourage the use of prostagladins when inducing labour among women attempting VBAC.2 Uterine rupture is a fear among women with previous caesarean section but most of this fear dates back to when classical uterine incision was used. Now-a-days transverse incision in lower uterine segment is used which is a stretchy and fibrous part of the uterus so that there are fewer chances of rupture and 3 haemorrhage. Patient with prior caesarean delivery needs special management both antenatal and in labour and delivery. We know that many women can safely and successfully have a vaginal birth after caesarean delivery. Current medical evidence indicates that 60-80%of women can achieve a vaginal

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Material and Methods

Table-1: Mode of Delivery.

The study was carried out in the department of Obstetrics & Gynaecology Unit-I of Services Hospital Lahore from June 2008 to June 2009. It was a descriptive study in which 200 patients were studied. Convenient sampling technique was adapted as all patients who had been admitted either through OPD or emergency were included in the study. Patients who had any contraindication to vaginal delivery or had medical disease complicating the pregnancy were excluded from the study. The data was collected with the help of proforma which was filled for every patient admitted to labour ward with previous one caesarean section due to non recurrent causes and spontaneous onset of labour at term. This proforma included all points relevant to study and included complete history of the patients regarding age, parity, obstetrics, gynaecological, previous surgical and medical history. General physical examination and systemic examination was done. Abdominal examination included fundal height, lie of fetus, presentation and auscultation of fetal heart sounds. Vaginal examination was done to assess Bishop score. Investigations included CTG and ultrasonography for biophysical profile and fetal kick count chart. A partographic record of the progress of labour was maintained. In case of failed trial of labour the cause was carefully looked into. SPSS version 14 was used for statistical analysis.

Mode of Delivery

Patients

Percentage

Vaginal Delivery

133

66.5%

Abdominal Delivery

33.5%

Total

200

100%

Table-2: Causes of failed trial of labour. Mode of Delivery

Patients

Percentage

Fetal Distress

31.34%

Failed progress

49.2%

Scar tenderness

19.40%

Total

100%

Maternal Morbidity

Patients

Percentage

Gapped Episiotomy

1.5%

Wound Infection

PPH

Scar Dehiscence

Uterine Rupture

0.5%

Bladder injury

0.5%

Maternal Mortality

Patients

Percentage

Nursery Admission

6.5%

Still Birth

0.5%

Early Neonatal death

Table-3: Maternal outcome.

Results

Table-4: Fetal outcome.

During the study period, 200 patients with one previous caesarean section and spontaneous onset of labour were given trial of labour. 133 (66.5%) delivered vaginally and in 67 (33.5%) repeat caesarean section had to be done (Table-I). Out of 133 who delivered vaginally, 101 (75.9%) had spontaneous vaginal delivery. Ventouse delivery was done in 19 (14.28%) patients and outlet forceps were applied in 13 (9.77%). Out of 67 in whom trial of labour failed, 33 (49.2%) had repeat caesarean section due to failed progress, in 21 (31.34%) cause was fetal distress and in 13 (19.40%) scar tenderness & maternal tachycardia (Table-II). In 4 patients scar dehiscence occurred but emergency caesarean efforts were fruitful for mother as well as newborn. There was one case of uterine rupture which was paid with loss of a baby but in time rescue caesarean saved the mother.

Table-5: Inter pregnancy interval Duration

Numbers

Percentage

Less than 1 year 1 to 2 years

13.5%

109

54.5%

More than 2 year

32%

Discussion The dictum â&#x20AC;&#x2DC;once a caesarean delivery always caesareanâ&#x20AC;&#x2122; no longer holds true. Several studies suggest that in women with previous caesarean section

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for a non recurrent cause, trial of labour is safer than elective repeat caesarean section.6 This study also demonstrates that trial of scar is possible in carefully selected patients with non recurrent indications for previous LSCS. There are some absolute contraindications to allowing on attempt at vaginal delivery such as classical scar, previous rupture uterus, cephalopelvic disproportion (CPD) and malpresentations in current pregnancy. A non recurrent indication for previous caesarean section, such as breech or fetal distress is associated with much higher successful VBAC rate than recurrent indications such as CPD. Prior vaginal deliveries are excellent prognostic indicator of successful VBAC. Diabetes and obesity adversely 7 affect VBAC. The rate of normal delivery after previous caesarean section was 66.5% in our study. This is comparable to most of the studies, which indicate 60-80% of woman can achieve a normal vaginal delivery following a previous LSCS.4,8,9 A study by Birgisdottin BT et al also showed 61% success in VBAC with uterine rupture 1%; so VBAC is a safe option for women with history of one previous caesarean section.4 Caesarean section rate generally is quite high because of recent trends of discouraging or not offering women a choice to labour after a caesarean. There are many reasons but the foremost is fear of litigations and very low morbidity and mortality from caesarean section.5 Once a caesarean section is carried out, there is always a possibility of another one in the subsequent pregnancies. Vaginal birth carries some direct risks such as vaginal and perineal laceration, trauma to anal sphincter and mucosa and significant maternal morbidity in the context of attempted VBAC are emergency caesarean delivery and uterine rupture.10 But overall women attempting VBAC have decreased rates of febrile morbidity, blood transfusion and venous thromboemblism compared with elective repeat caesarean section.11 On the other hand repeat caesarean delivery has major long term effects on the outcome of future pregnancies like previous caesarean delivery is associated with increased risk of placental abruption in future pregnancies. Multiple caesarean deliveries are also associated with an increased risk of previa and morbid adherence of placenta.12, 13 A population based seven year study (1992-1998) revealed cesarean section to be associated with four fold increased risk of maternal death. Cesarean deliveries do increase maternal morbidity.14

Women are influenced by external and internal factors in their decision to choose vaginal birth after caesarean section and should be encouraged by health care providers. Also in randomized controlled trial to determine the effect of decision and for mode of delivery among women with previous caesarean section, the rate of vaginal birth was higher for women in decision analysis group compared with 15 usual care group. Study carried out by Durnwald C concludes that favorable initial pelvic examination, spontaneous labour and lack of oxytocin use are associated with successful VBAC in women with single prior low transverse caesarean section.16 A review of patients in our study also shows that success rate of VBAC was significantly high in those who had previous caesarean section for non recurrent cause, spontaneous onset of labour and favourable Bishop score, similar to Durnvald C study. The high morbidity and mortality associated with uterine rupture makes it quite an undesirable complication.17 Women with prior successful VBAC attempts are at low risk for maternal and neonatal complications during subsequent VBAC attempts. Increasing number of prior VBAC is associated with a greater probability of VBAC success as well as a low risk of uterine rupture and prenatal complications in current pregnancy. The rate of uterine rupture decreased after the first successful VBAC and did not increase thereafter. The risk of uterine dehiscence and other peripartum complications also declined statistically after the first successful VBAC.18 In our study incidence of uterine rupture is 0.5% (in one patient). This matches with worldwide studies 4,19,20 generally in the range of 0.5-1.0%. For a woman with prior uterine scar, neither repeat elective cesarean section nor VBAC is risk free. When VBAC is successful, morbidity is less than repeat caesarean section but when it fails serious consequences occur in case of rupture.6 A study in Ohio by Yapow also showed VBAC rate of 65.3%. During study they identified 21 cases of uterine rupture or scar dehiscence. Their data confirms the relatively small risk of uterine rupture during vaginal birth after caesarean that has been demonstrated in previous studies. In an institution that has in house obstetrics, anesthesia and surgical staff in which close monitoring of fetal and maternal well being is available, uterine rupture does not result in major morbidity and mortality or in neonatal 21 mortality. The study revealed 12.5% of maternal morbidity especially wound infection observed in patients

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delivered by emergency repeat cesarean section similar to study of Hibbard Ju. His study showed that patients who experience failed vaginal birth after caesarean have higher risks of uterine rupture and infectious morbidity compared with patients who have successful vaginal birth after caesarean or elective repeat caesarean delivery.22 As actual numbers of morbid events are small, caution should be exercised in interpreting results and counseling of patients. More accurate predictions for safe successful vaginal birth after caesarean delivery are needed.

increased dramatically in cesarean compared with vaginal delivery. Proper counseling for trial of labour, intensive antenatal surveillance and careful observation throughout labour in well equipped unit is required. In this way growing rate of cesarean section may be reduced.

Department of Obstetrics & Gynaecology SIMS/Services Hospital, Lahore

Conclusion

theesculapio@hotmail.com www.sims.edu.pk/esculapio.html

There is no doubt that maternal morbidity is References 1. Sadaf R, Nasreen A, Zahid M. Trial of scar in patients with previous one caesarean section. J Postgrad Med Inst 2007;21:2124. 2. ACOG Committee opinion. Induction of labour for vaginal birth after caesarean delivery. Obstetr Gynecol 2002; 99: 67980. 3. Withch AC. Uterine scar separation in patients undergoing trial of labour. Mil Med 2000;155:730-2. 4. Birgisdottin BT, Hardardottin H. Vaginal birth after one previous caesarean section. Lacknabladid 2008;94(9):591-7. 5. Ridley RT, Davis PA, Bright JH, Sinclair D. What influences a woman to choose vaginal birth after cesarean? Obstet Gynecol Neonat Nurs 2002;31:665-72. 6. Quddusi H, Anwar S. Trial of labour after caesarean delivery. A study of 100 cases. Pakistan Med Res 2005;44:54-56. 7. Brill Y, Windrim R. Vaginal birth after caesarean section; review of antenatal predictors of success. J Obstet Gynecol 2003;25(4):27586. 8. Taj G, Sohail N. Review of study of vaginal birth after caesarean section. Ann King Edward Med Univ 2008;14:13-16. 9. Avery MD, Carr CA, Burkhardt P.

10.

11.

12.

13.

14.

15.

Vaginal birth after caesarean section; a pilot study of outcome in women receiving midwifery care. J Midwifery Womens Health 2004; 49 (2): 113-7 Handa VL, Harrey L, Fox HE, Kjerulff KH. Parity and route of delivery. Does cesarean delivery reduce bladder symptoms later in life? Am J Obstet Gynecol 2004: 9: 917-927 Mozurkewick EL, Hutton EK. Elective repeat caesarean delivery versus trial of labour: A metaanalysis of the literature. Am J Obstet Gynecol 2000;183:118797. Faiz AS, Ananth CV. Etiology and risk factors for placenta previa: an overview and meta analysis of observational studies. J Matern Fetal Neonatal Med 2003; 13: 175190. Lydon Rochelle M, Holt VL, Easterling TR. First bir th caesarean and placental abruption or previa at second birth. Obstet Gynecol 2001;97:765-9. Burrows LJ, Meyn LA, Weber AM. Maternal morbidity associated with vaginal versus caesarean deliver y. Obstet Gynecol 2004;103:901-4. Montgomery AA, Emett CL. Two decision aids for mode of delivery among women with previous caesarean section; a randomized

16.

17.

18.

19.

20.

21.

22.

controlled trial: Br Med J 2007; 334:1305. Durnwald C, Mereer B. Vaginal birth after caesarean delivery. Predicting success and risk of failure. J Martern Fetal Neonatal Med 2004;1(6):388-93. Nisa M, Hassan L. Trends of vaginal delivery after one previous caesarean section in a tertiary care hospital. Pak J Med Res 2004; 43: 31-4. Mercer BM, Gilbert S. Labour outcomes with increasing number of prior vaginal birth after caesarean delivery. Obstet Gynecol 2008; 111: 285-91. Landon MB, Hauth JC. Maternal & perinatal outcomes associated with trail of labour after prior caesarean delivery. N Engl J Med 2004; 351: 2581-89. Lydon Rochelle M, Holt VL. Risk of uterine rupture during labour among women with a prior caesarean delivery: N Engl J Med 2001; 345: 3-8. Yapow, Kim ES, Lavos Rk Jr. Maternal and neonatal outcomes uterine rupture in labour. Am J Obstet Gynecol 2001; 184(7): 1576-81. Hgibbard JU, Ismail MA, Wang Y. Failed vaginal birth after a caesarean section, how risky is it? Maternal Morbidity. Am J Obstet Gynecol 2001;184(7):1365-71.

Esculapio - Volume 07, Issue 01, January-March 2011

Original Article

Association Between Intake of Milk Or Other Dairy Products Along With Fish Meat And Development of Vitiligo Sohaib Mazhar Siddiqui, Maaz Ahmad and Asif Hanif

Objective: To establish whether there is an association between intake of milk or dairy products along with fish meat and development of vitiligo. Material & Methods: This case control study was conducted in outdoor Dermatology Department Mayo Hospital, Lahore and in some urban areas of Lahore from 7th of August 2003 to 5th of September 2003. Subjects were selected among the adult population. 40 cases and 63 controls were taken. Results: 57.5 % cases and 61.90% controls were factor positive. The chi-square test was applied and p-value was found to be 0.656 which is not statistically significant. Conclusion: No association was found between drinking of milk or other dairy products with fish meat and development of vitiligo. Keywords: Fish Meat, Milk, Dairy Products, Vitiligo 72.2% of the Pakistani population believes that one should not take milk or other dairy products along with fish meat as it causes vitiligo. To confirm whether this belief in the people of Pakistan is true or 5 not, this study was conducted.

Introduction Vitiligo is a common disorder of depigmentation. It presents in childhood or in early adult life with well demarcated macules of complete pigment loss. Lesions are often symmetrical and frequently involve the face, hands and genitalia. The hair can also depigment. 1 Nearly 40% of the patients give positive family history. Central nervous system plays important role as many cases appear after stress and some show segmental distribution.2 There is no history of preceding inflammation. Trauma may induce new lesions. 1 Onset in half the cases is before 20 years of age. Convex milky white patches increase in size by confluence. New areas can be affected while the old patchy areas disappear. Skin surrounding vitiligeneous patches is often hyper-pigmented. 2 The exact etiology of vitiligo is unknown, but four main theories exist to explain it: the autoimmune hypothesis, the neural hypothesis, the self-destruct hypothesis, and the growth factor defect hypothesis. It is also believed that vitiligo is a polygenic trait. Combining elements of different theories across a spectrum of expression is the most accurate etiology. 3 It is treated both medically and surgically. Medical treatment includes the immunosuppressive therapy, phototherapy and photochemotherapy (UV radiations of 290-320 nm), and bleaching therapy. It is also treated surgically by grafting healthy skin patches over lesioned areas. 4

Material and Methods People having a familial predisposition towards vitiligo were excluded from the study because this is a major risk factor contributing towards the disease. The children were also excluded as they could give false answers in the questionnaire. The study included only the Pakistani citizens as this study was conducted to confirm the belief of this particular group. After excluding, the people suffering from vitiligo were considered as cases while the people not suffering from vitiligo were taken as controls in this study. The dependant variable in this study was vitiligo while the independent variable was history of intake of milk or dairy products along with fish meat. Hence both the cases and the controls were subdivided into cases with factor and cases without the factor. A null hypothesis that â&#x20AC;&#x153;there is no association between taking milk or other dairy products along with fish meat and development of vitiligoâ&#x20AC;? was deduced and was tested. The study was conducted in outdoor of Dermatology department, Mayo Hospital Lahore and in some selected urban areas of Lahore. The subjects included from the Mayo Hospital Lahore were mostly

Esculapio - Volume 07, Issue 01, January-March 2011

from different cities like Lahore, Sheikhupura, Gujranwala, Wazirabad, Kasur, Raiwind and different villages of other districts. People from some urban areas of Lahore were also included who did not come to Mayo Hospital. They were taken from Gulshan-eRavi, Wahdat Colony, Township and Samanabad areas of Lahore. A questionnaire comprising biodata and queries about familial predisposition, history of intake of fish meat with milk or dairy products was distributed among the study participants.

Discussion There is a belief in our society that taking milk or dairy products along with fish meat can depigment the skin.5 In this study only 26% patients presented with positive family history which as less than reported by Haroon TS.2 As vitiligo causes social and psychological sufferings among the people, they tend to avoid taking these two items together in their meals. But as the questionnaire was filled by different people of the society pertaining to both the sexes and different areas of Punjab and p-value came to be 0.656 with odd's ratio 0.83 meaning that there is no strong relationship of taking milk or dairy products with fish meat with vitiligo and it proves to be a sheer myth.

Results In this study a sample of 103 with both genders was selected of which 40 persons were cases and 63 persons were controls. The mean age of patients was 37± 1.4 years. There were 67 males and 36 females. 26% patients presented with family history among cases. Among controls non of the patients presented with positive family history. Finally all subjects were divided in, “the persons who have history of taking fish meat with milk or dairy products or not taken that”. The results are shown in table 1.

Conclusion The results show that there is no harm in taking milk or dairy products along with fish meat and people can take them without any fear of developing vitiligo.

Table-1: Intake fish with milk or dairy product. Vitiligo Yes No Total Intake fish with milk or dairy products Yes 23 39 62 No Total

103

Department of Community Medicine King Edward Medical University, Lahore

theesculapio@hotmail.com www.sims.edu.pk/esculapio.html

References 1) Kumar P, Clark M. Kumar & Clark Clinical Medicine. 5th ed. , M / S W. B. S a u n d e r s, Edinburgh, London, New York, Philadelphia, St Louis, Sydney, Toronto, 2002; p. 1312. 2) Haroon TS. ABC of dermatology, 8th ed. M/S Derma Techno

Pakistan, Lahore, 2001; p. 64. Njoo MD, Westerhof W. Vitiligo: pathogenesis and treatment. Am J Clin Derm 2001; 2(3): p. 167-181. 4) Taneja A. Treatment of Vitiligo. J Derm Treatment 2002. 13: 19258. 5) Qadwani W, Alim N, Azam SI. 3)

Myths & fallacies about health & disease among patients presenting to family physicians at the Agha Khan University Hospital Karachi, Pakistan. Pak J Med Sci 2002; 18(4): p. 287-290.

Esculapio - Volume 07, Issue 01, January-March 2011

Original Article

Association of Progression of Pulmonary Fibrosis with Severity of Liver Cirrhosis Muhammad Masood, Shahid Hamid, Sajid Nisar, Fawad Ahmed Randhawa, Ambreen Butt and Faisal Masud

Background: It has been found that frequency of pulmonary fibrosis increases in patients with cirrhosis of liver. We hypothesized that as the stage of cirrhosis advances, the frequency of pulmonary fibrosis should increase. We used child's pugh classification to stage the cirrhosis of liver. Material & Methods: Fifty five patients of age range 16 to 80 years, both males and females having established cirrhosis of liver on ultrasonography, regardless of etiology, visiting the outpatient and inpatient department for treatment were selected. Patients were divided into three groups according to child's criteria i.e group A, group B, and group C. HRCT of chest was performed on patients in all three groups to look for pulmonary fibrosis. Results: 27 (49%) patients were found to have pulmonary fibrosis on HRCT. The frequency of pulmonary fibrosis in different groups of child's classification was also assessed and it was found that class C and class B, are affected more than A. Conclusion: Pulmonary fibrosis progresses with severity of liver cirrhosis Keywords: Cirrhosis, Child's classification, pulmonary fibrosis Introduction

of pulmonary fibrosis is likely to increase. So it was hypothesized that as the stage of cirrhosis of liver advances, the frequency of pulmonary fibrosis should increase. We used the child pugh turcotte (CPT) classification to stage the cirrhosis of liver.

Liver cirrhosis is a worldwide health problem. Alcoholism and viral hepatitis are the most common causes worldwide, whereas viral hepatitis and especially hepatitis C is the most common cause of 1 cirrhosis in Pakistan. Liver cirrhosis is characterized by liver injury followed by regeneration and fibrosis. Liver fibrosis is the wound healing response of liver to repeated injuries. After injury, parenchymal cells regenerate and fibrosis occurs due to interaction between different cell types and cytokines. Profibrotic agents include type-2 CD4 positive lymphocytes, CD40 receptor and ligand interaction and cytokines like IL 4, TGF beta, platelet 2,3,4 derived growth factor. Pulmonary complications are frequently observed in liver cirrhosis.5 As the blood from the liver passes to the lungs, lungs are exposed to similar profibrotic agents as the liver, in patients with cirrhotic liver disease. So pulmonary fibrosis is the likely outcome. We in another study conducted earlier, documented the increased frequency of pulmonary fibrosis in patients with liver cirrhosis.6 Similarly other studies have shown relationship between liver cirrhosis and 7,8 interstitial lung disease. As the liver cirrhosis progresses and increases in severity, lungs are more and more exposed to profibrotic agents and severity

Objective The study was conducted to find out the association of progression of pulmonary fibrosis with severity of cirrhosis according to child's classification.

Material and Methods This study was conducted at Medical Unit-IV of Services Hospital, Lahore. Total study period was 06 months, starting from November 2003 till April 2004 & total 55 patients were recruited.

Inclusion Criteria Patients between 16 to 80 years of age presenting to medical outpatient department or admitted to Medical Unit-IV having established cirrhosis of liver on the basis of ultrasonography regardless of etiology were included in study.

Exclusion Criteria 1. Patients with pulmonary tuberculosis 2. Patients with history suggestive of chronic obstructive air way disease 14

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Table-3: Child group distribution of pulmonary

3. Patients with primary lung tumor or lung metastasis 4. Patients with sarcoidosis. 5. Patients with history suggestive of autoimmune disorders 6. Patients with history of exposure to asbestos 7. Patients on interferon or chemotherapy

fibrosis in cirrhosis Sex group Childâ&#x20AC;&#x2122;s

Numbers Percentage Total No. Pulm. Fibrosis Percentage

Group A

30.0%

Group B

62.0%

Group C

58.0%

Material and Methods Discussion

Patients were recruited according to inclusion criteria and informed consent was taken. Patients were assessed clinically for jaundice, ascites, grade of hepatic encephalopathy and laboratory tests were performed for serum bilirubin, serum albumin and prothrombin time to define the child's class. Patients were then subdivided into three groups i.e. A, B and C according to child's criteria. Child's class was assigned to each patient based on two clinical and three laboratory criteria as defined in (CTP) classification. HRCT was done on each patient to look for the pulmonary fibrosis. Each HRCT was reported by the same radiologist.

Viral hepatitis is major cause of cirrhosis in Pakistan. Prevalence of hepatitis C is more than hepatitis B.9 In western world, alcoholic liver disease accounts for 6070% cases of cirrhosis. Other causes of cirrhosis include cryptogenic cirrhosis (10-15%), biliary disease (5-10%), genetic haemochromatosis (5%), 1 Wilson's disease and alpha-1 anti trypsin deficiency. In cirrhosis there is increased hepatic deposition of collagen (type I & type II). It is now recognized that hepatic stellate cells, portal fibroblasts and myofibroblasts of bone marrow origin are primarily responsible for this collagen deposition and hepatic fibrosis and subsequent progression to cirrhosis.1,2,3 These cells are activated by fibrogenic cytokines such as transforming growth factor beta (TGF-B), angiotensin II and leptin, as well as proliferative cytokines like platelet derived growth factor and cytokines produced by chronic inflammation like tumor necrosis factor (TNF) alpha, TNF beta and interleukin-1 (IL-1).4,5,6 The frequency of interstitial lung disease in chronic liver disease of different etiologies varies between 1360%. The present study shows pulmonary fibrosis in 49% of the patients with cirrhosis as compared to 3% frequency of pulmonary fibrosis in general (western population). Idiopathic pulmonary fibrosis has been associated with cirrhosis due to hepatitis C virus and various studies have shown high prevalence of anti HCV antibodies (28.8% and 13%).9,10 However these studies have not established any cause and effect relationship between pulmonary fibrosis and cirrhosis of liver. Interstitial lung disease appears medially 4.5 Âą 3.2 years after clinical onset of chronic hepatitis and abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology.11 In the present study we looked for progression of pulmonary fibrosis with severity of cirrhosis according to child's class. It is found that frequency of pulmonary fibrosis is more in child class B & C than in Class A. Reversibility of advanced liver fibrosis has been recently documented. This has stimulated the

Results This study included 55 patients. Age range of patients was between 16 to 80 years. Patients of both sexes were included in the study. Out of 55 patients 30 (55%) were males and 25 (45%) were females. HRCT scan of the lungs was performed on all 55 patients. 27 patients (49%) showed evidence of pulmonary fibrosis on HRCT (Table 1).

Table-1: Pulmonary fibrosis in cirrhosis on HRCT Sex Tests

Numbers Number

Percentage Percentage

Present

49.0%

Absent

51.0%

Fifteen of these 27 patients with pulmonary fibrosis were male while 12 were females (Table 2).

Table-2: Sex distribution of pulmonary fibrosis in cirrhosis Sex

Numbers Number

Percentage Percentage

Male

55.0%

Female

45.0%

Out of 27 patients with pulmonary fibrosis 6 patients were from child group A, 10 from child group B and 11 from child group C (Table 3).

Esculapio - Volume 07, Issue 01, January-March 2011

researchers to develop new anti-fibrotic drugs. So treatment of cirrhosis with anti-fibrotic agents will probably reduce the severity of fibrosis in the lungs and treatment of Hepatitis C with interferon at an early stage of chronic liver disease will possibly prevent the pulmonary fibrosis. Further studies are required to establish the cause and effect relationship between cirrhosis and pulmonary fibrosis and to establish the relation of severity of pulmonary fibrosis with severity of cirrhosis, duration of cirrhosis or both.

Conclusion The study has shown strong association between cirrhosis of liver and pulmonary fibrosis but it does not show clear cause and effect relationship and also does not show definite relation between severity of cirrhosis of liver and frequency of pulmonary fibrosis. For this further research work is needed. Department of Medicine SIMS/Services Hospital, Lahore

theesculapio@hotmail.com www.sims.edu.pk/esculapio.html

References 1. Nadeem MA, Waseem T, Malik A, Grumman N, Irfan K, Hasnain SS. Hepatitis C virus: an alarmingly increasing cause of liver cirrhosis in Pakistan. J Gastroenterol Mar 2002; 16; 1: 38. 2. David R, Brenner A. Liver fibrosis. J Clin Invest 2005: 115: 209-18. 3. Molina V, Blank M, Shoenfeld Y. Fibrotic disease. Harefuah 2002; 141: 973-8. 4. Tangkijvanich P, Yee HF. Cirrhosis- Can we reverse hepatic fibrosis? Eur J Surg Suppl 2002; (587): 100 -12.

6. 7.

Thierry Vlad R. Bailliere's best practice and research In: Clinical Gastroenterology April 2000; 14 (2): 211-228. 5A Hamid S, Masood M, Masud F, Esculapio; April June 2008; 04 (1): 21 -3. Weissman E, Becker NH. Interstitial lung disease in primary biliary cirrhosis. Am J Med 1983; 285:21-7. Idilman R, Cetinkaya H, Aslan N, Sak SD, Bastimir M. Bronchoalveolar fluid analysis in individuals with chronic hepatitis C. J Med Virol 2002; 66: 34-9. Ueda T, Ohta K, Yamaghuchi M,

Hirai K, Horiuchi T, Ito K. Idiopathic pulmonary fibrosis and high prevalence of serum antibodies to hepatitis C virus. Am Rev Respir Dis 1992 July; 146 (1):266-8. 10. Irwing WL, Day S, Johnston ID. Idiopathic pulmonary fibrosis and hepatitis C virus infection. Am Rev Respir Dis 1993; 148: 1683-4. 11. Crawford JM. The liver and biliary tract. In: Kumar V, Cortan RS, Robbins SL, 6th ed. Philadelphia: WB Saunders 2001:523.

Esculapio - Volume 07, Issue 01, January-March 2011

Original Article

Role Of Ultrasound In Vitreous Hemorrhage - A Prospective Study In A Teaching Hospital Amtul Mussawar Sami, Khalid Waheed and Muhammad Tayyib

Objective: To detect and assess posterior segment pathology in cases of vitreous hemorrhage by ultrasound examination in patients presenting to ophthalmology department of Services Institute of Medical Sciences, Lahore. Material & Methods: This study included 179 patients (200 eyes) with vitreous hemorrhage who underwent A and B scan ultrasound by one examiner at Eye unit I in Services Hospital, affiliated to Services Institute of Medical Sciences, Lahore, for the duration of four years from January 2003 to January 2007. 114 were male and 65 were females. All patients had dense vitreous hemorrhage which prevented visualization of the retina. Age range was between 10 to 67 years. Before ultrasound, all the patients were completely examined in OPD including a comprehensive history, record of visual acuity and intraocular pressure. Detailed fundus examination was carried out after dilatation of pupils with mydriacyl (tropicamide) eye drops with 78 D lens and indirect ophthalmoscope. Results: Unilateral cases were 60 and bilateral cases 70. Proliferative diabetic retinopathy with vitreous hemorrhage was observed in 90 eyes, (tractional retinal detachment was present in 38 eyes, both tent like and table top configuration were observed on B scan while vitreous hemorrhage with proliferative diabetic retinopathy was observed in 52 eyes). Rhegmatogenous retinal detachment was observed in 10 eyes. Vitreous hemorrhage due to penetrating injuries occurred in 55 eyes and out of these 55, metallic intra-ocular foreign body was present in 05 eyes. Eales disease with vitreous hemorrhage was present in 25 eyes. Posterior vitreous detachment was noted in 20 eyes with vitreous haemorrhage. Conclusion: Vitreo-retinal surgeons consider A-and B-Ultrasound the most important examination tool. It should be typically performed early and frequently after presentation of patient with vitreous hemorrhage. Keywords: Ultra-sound, Retinal detachment, Vitreous hemorrhage. Posterior vitreous detachment A-scan, B-scan. Introduction

enabled ophthalmologists to study posterior segment 5 of the eye in the presence of opaque media. The development of duplex scanners and colored Doppler instruments in the 1980's has facilitated their use in ophthalmology. Sergott, Leib, Williamson, Baxter and Guthoff were responsible for their wider application of Doppler to ophthal-mology.5-7 Its uses have expended to encompass biometric calculations, tissue characterization, diagnosis of complex vitreoretinal conditions and differentiation of intraocular masses.8-11 In the orbit, ultrasound including Doppler is used for the investigation of extraocular muscles diseases12,13 and retro-bulbar optic nerve diseases,14-15 vascular anomalies 16 and orbital mass lesions.17-18 In 1990, Pavlin and colleagues described the first high frequency ultrasound (50-100MHz) in ophthal19 mology. Ultrasound biomicroscopy has allowed us

Ultrasound is an acoustic wave that consists of an oscillation of particles within a medium. Ultrasound was first used in ophthalmology in 1956 by American 1 ophthalmologists Mundt and Hughes. They used A scan mode to evaluate an intraocular tumor. B Scan was introduced in ophthalmic practice by Baum and Greenwood in 1958.2 Both A-scan and B-scan techniques are important for the diagnosis of intraocular disease. B (Brightness) mode is useful for a better demonstration of the shape and topographic relationship of lesions in the posterior segment.3 B scan provides cross sectional display of diseased tissues and is valuable in detecting unsuspected posterior segment diseases.4 The frequency used in the diagnostic ophthalmic ultrasound for posterior segment is 8-10 MHz. Over the last 30 years ultrasonography has greatly advanced and has

Esculapio - Volume 07, Issue 01, January-March 2011

to investigate subtypes of glaucoma, lesions in the 20 iris, ciliary's body, sclera and pars plana. Previously A-mode (amplitude mode) which used to gauge the depth of any structure was used with liner transducer but now-a-days, it is replaced by B-mode sector scanner using high frequency. This has an advantage of panoramic view of the orbit in addition to anticipated pathology, normal anatomy and coexisting variants. Now ultrasound is considered an essential tool in the investigation and management of many ocular and orbital disorders. 21-22 The evaluation of eyes with opaque ocular media is one of the primary indications for the use of ocular ultra23-24 sonography. Therefore preoperative ultrasonography of the globe has been recommended prior to ocular surgery when the fundus cannot be 25 visualized. Vitreous hemorrhage is one of the most important 26 causes of sudden loss of vision in an individual. The incidence is approximately seven cases /100,000 of the population. The important causes of vitreous haemorrhage are proliferative diabetic retinopathy, Eales disease, posterior vitreous detachment with or without vitreous hemorrhage and ocular trauma. The relative prevalence of these and other underlying conditions has varied in previous reports.26 Despite recent advancements in ophthalmic examination techniques, evaluation of vitreo-retinal diseases with vitreous haemorrhage often presents a diagnostic challenge even when using the standard methods of A-and B- Ultrasound. These techniques are important for the diagnosis of vireo-retinal disorders and before any surgical interventions. The purpose of this study was to detect and assess posterior segment pathology in cases of vitreous hemorrhage by ultrasound examination in patients presenting to ophthalmology department of Services Institute of Medical Sciences, Lahore.

Before ultrasound all the patients were examined in OPD including a comprehensive history, record of visual acuity and intraocular pressure. Detailed fundus examination was carried out after dilatation of pupils with mydriacyl [tropicamide] eye drops with 78 D Lens and indirect ophthalmoscope. The A-and B- Ultrasound procedures for evaluating patients with vitreous hemorrhage began with the instillation of topical anesthetic drops into the eye. This was followed by the application of methylcellulose to the face of the B-scan probe to facilitate penetration of sound into the eye. Examinations were performed with patients in supine position on the surface of the globe, to maximize sound penetration and to promote adequate patient fixation. The vitreous cavity was evaluated for hemorrhage density, mobility and other pathologies. Vitreo-retinal adhesion and retinal status were noted by careful screening of the globe in all four quadrants. The Ascan was used at the tissue sensitivity gain setting to assess reflectivity of the suspected pathology.

Results Unilateral cases were 60 and bilateral cases 70. Proliferative diabetic retinopathy with vitreous hemorrhage was observed in 90 eyes, (tractional retinal detachment was present in 38 eyes, both tent like and table top configuration were observed on B scan while vitreous hemorrhage with proliferative diabetic retinopathy was observed in 52 eyes). Rhegmatogenous retinal detachment was observed in 10 eyes. Vitreous hemorrhage due to penetrating injuries occurred in 55 eyes and out of these 55, metallic intra-ocular foreign body was present in 05 eyes. Eales disease with vitreous hemorrhage was observed in 25 eyes. Posterior vitreous detachment was present in 20 eyes with vitreous haemorrhage. Fig I , II and III.

Material And Methods This study consisted of 179 patients (200 eyes) with vitreous hemorrhage who underwent A and B-scan ultrasound by one examiner at Eye unit I in Services Hospital, affiliated to Services Institute of Medical Sciences, Lahore, over a duration of four years from January, 2003 to January, 2007. All patients had dense vitreous hemorrhage which prevented visualization of the posterior segment. 114 were male and 65 were females. Age range was between 10 years to 67 years.

Table-1: Distribution of cases

Patients

Number

Total Numbers of Patients

179

Total Numbers of Eyes

200

Unilateral Cases

Bilateral Cases

Esculapio - Volume 07, Issue 01, January-March 2011

Table-2: Causes of vitreous hemorrhage Causes Proliferative Diabetic Retinopathy

No. of Eyes

Percentage

50.27%

1. Vitreous Hemorrhage

2.Tractional Retinal Detachment with Vitreous Hemorrhage

Penetrating Injury

27.93%

Eales Disease

13.96%

Posterior Vitreous Detachment

11.17%

Rhegmatogenous Retinal Detachment with Vitreous Hemorrhage

5.58%

Penetrating Injury with Metallic intra ocular foreign body

2.97%

retinal detachment. Proliferative diabetic retinopathy with vitreous hemorrhage was observed in majority of cases in our study. This is in agreement with the report of Rabinowitz et al26 and Jameel et al;27 another national study of Faheem et al26 shows proliferative diabetic retinopathy as the second common cause of vitreous hemorrhage. Our findings contrast with 26-27 those of Leangren et al and Lean and Gregor, who reported that vitreous detachment and traction of a retinal vessel was the commonest cause of hemorrhage. In our study these causes accounted for only 11.17% of the cases. In diabetic vitreous hemorrhage, single or multiple focal adhesions are frequently seen between incompletely posterior vitreous face and fibrovascular complexes which originate from the optic disc and major retinal vessels. Hemorrhage into the vitreous tends to form clots. These appear as highly reflective, coalescent echoes, which are usually denser inferiorly. Bleeding associated with posterior vitreous detachment may be confined to the gel or sub-hyaloid space alone or may be mixed. Sub-hyaloid hemorrhage associated with posterior vitreous detachment should raise the suspicion of a retinal tear, especially in an otherwise healthy eye or in high myopes. Sub-hyaloid hemorrhage does not clot, and therefore appears as dispersed mobile small echoes requiring a high gain setting to be demonstrated. Chronic sub-hyaloid hemorrhage may gravitate inferiorly, forming an interface between a thick, highly reflective layer of blood and less dense floating blood cells. Vitreous hemorrhage due to Eales disease was noted in 13.96% of cases. Our findings also match with Jack et al, Jalkh et al Kumar and Rab et al26 who found that preoperative

Fig-1: Vitreous Hemorrhage on B-scan 70 VR specialist

60 50 40

Non VR specialist

30 20

Associate specialist

10 0 1

Fig-2: Preference of VR, non VR and associate specialist for B-scan in cases of vitreous hemorrhage Discussion The role of ultrasound in the detection of retinal pathology in eye with opaque media has been established clearly in the past. At present, there is no other method to reliably ascertain the anatomic position of the retina where direct examination is impossible. The demonstration of retinal detachment profoundly changed the management of the cases, thus distinguishing dense vitreous membranes from

Esculapio - Volume 07, Issue 01, January-March 2011

of the retinas of 84%-89% of the eyes with vitreous hemorrhage. It was noted in present study that ocular trauma is the second most common cause of vitreous hemorrhage. Total 55 eyes had vitreous hemorrhage and out of these, 05 eyes had metallic intra-ocular foreign body, which is consistent with Rabinowitz et al.26 Diagnostic techniques such as computed tomography (CT) and plain-film radiography are standard methods for identifying intra-ocular foreign bodies. In the present study, diagnostic ultrasound correctly identified the presence of foreign bodies. Typical metallic foreign body produces a very bright signal on B-scan that persists at low sensitivity; also there is marked shadowing of ocular and orbital structures just posterior to it. The use of ultrasound as an adjunct to the standard imaging techniques (CT scan) when an intra ocular foreign body is suspected in posttraumatic eyes is highly recommended. Posterior vitreous detachment with vitreous hemorrhage was observed in 11.17% of cases. Posterior vitreous detachment is more extensive in

vitreous hemorrhage; inflammatory cells are evenly distributed while vitreous hemorrhage settles inferiorly due to gravity. Posterior vitreous detachment produces smooth membranes that shows low reflectivity as compared to retinal detachment. Our study also correlates with VJ Vote et al28 who recommends A-scan and B-scan ultrasound as an important tool for vitreo-retinal specialists and non vitreo-retinal specialists (Fig -IV)

Conclusion A and B-scan ultrasound is a mandatory technique for the assessment and surgical management of patients with vitreous hemorrhage particularly in vitreo retinal pathologies. It is also useful for monitoring progression of retinal disease. Department of Eye SIMS/Services Hospital, Lahore

theesculapio@hotmail.com www.sims.edu.pk/esculapio.html

References 1. Mundt GH,Hughes WF. Ultrasonic in ocular diagnosis. Am J Ophthalmol1950;41:488-98. 2. Baum G, Greenwood I. The application of ultrasonic locating technique to ophthalmology. Arch Ophthalmol1958;60:26379. 3. Till P, Osoining KC. Ten year study on clinical echography in intraocular diseases. Bibl Ophthalmol 1975;83:49-62. 4. Hodes BL. Eye disorders; using ultrasound in ophthalmic diagnosis. Post grad Med 1976; 59:197-203. 5. Zafer D, Sajad AM ,Qader A. Role of B- Scan ultrasonography for posterior segment lesions. JLUMS 2008;07:7-12. 6. Blaivas M, Theodore D, Sierzenski PR. A study of bedside ocular ultrasonography in the emergency department. Acad Emerg Med 2001; 9;791-9. 7. Coleman DJ, Silverman, Rondeau MJ. Correlations of acoustic tissue typing of malignant melanoma and histopathologic features as a predictor of death.

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13. 14.

Am J Ophthalmol 1990;110:3808. Green RL, Byrne SF. Diagnostic ophthalmic ultrasound. In Retina; vol 1:Rvan SJ ed .Toronto. The CV Mosby Company 1998;1:191273. Gentile RC, Berninstein DM. High resolution ultrasound biomicroscopy of the pars plana and peripheral retina. Ophthalmol 1998;478-84. Snell RS, Lemp MA. Clinical anatomy of eye. Boston: Black well Scientific publication.1989;1. Grayson M. Diseases of the cornea. St.Louis; Mosby ,1983. Lofstrom JB, Bengtsson MA. Practice of anaesthesia, physiology of nerve conduction and local anaesthesia drugs. 6th edition. London. Wylie and Churchill Davidsons. 1995; 17288. Hogan M, Alvarado J, Weddell. H i s to l o g y o f h u m a n eye. Philadelphia; WB Saunders 1971. Yoneya S, Tso MOM. Angioarchitecture of the human choroid. Arch Ophthalmol 1987;

105:681. 15. Perry HD, Hatfield RV, Tso MOM. Flourescein pattern of the chorio capillaries in the neonatal rhesus monkeys. Am J Ophthalmol 1977;81:197-204. 16. Khalil AK, Kubota T, Tawara A, Inomata H.. Ultrastructural changes on the posterior iris surface. Arch Ophthalmo 1996;114(6):721-5. 17. Davson H. The Bowman lecture, the little brain. Trans Ophthalmol Soc UK 1979;99(1):21-37. 18. Hamilton RC. Techniques of orbital region anaesthesia. Br J Anaesthesia 1995:75:88-93. 19. Eisner G. Biomicroscopy of the peripheral retina. New York: Springer Publicating co. 1973. 20. Apple DJ. Anatomy and histopathology of macular region. Intl Ophthalmol Clin 1981:2(3):1-9. 21. Gissen AJ, Cavino BG, Gregus J. Differential sensitivity of mammalian nerve fibers to local anaesthetic agents. Anaesthiol 1980:467-74. 22. Wise GN .Dollery CT,Hankindl

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P. The retinal circulation .New York, Harper and Row Publisher, 1971. 23. Bellhorn RW. Control of blood vessel development. Trans Ophthalmol Soci UK 1980; 100(3):328-31. 24. Rafferty NS .The ocular lens structure ,function and pathology. New York :MARCEL

decker:1985;1-60. 25. Kanski JJ. Clinical Ophthalmology: A systemic approach,5 edition. Oxford; Butterworth Heinmann 2003; 143. 26. Rabinowitz R. Comparison between clinical and ultrasound findings in patients with vitreous hemorrhage. Eye 2004;18:253-6. 27. Ahmed J, Sheikh FF, Rizwan

A,Memoon MF. Evaluation of vitreo -retinal pathologies using B-scan ultrasound. Pak J Ophthalmol 2009; 207-11. 28. Vote BJ, Membrey WL, Casswel AG. Vitreous haemorrhage without obvious cause: national survey of management practices. Eye 2005;19: 770-77.

CORRIGENDUM

Esculapio Journal of Services Institute of Medical Sciences, Lahore Volume 06, Issue 01, April - June, 2010 In Case Reports, “Concomitant infestation of Meckel’s diverticulum and appendix by pinworm (enterobius vermicularis in a 15 year old male ” By Abreen Imran (Assistant Professor of Pathology/Pakistan Postgraduate Medical Institute, Lahore), And in another case report Volume 05, Issue 04, April - June, 2010 “Chondroid syringoma of the arm: an unusual localization: a case report and preview of the literature” 1. By Abreen Imran (Assistant Professor of Pathology/Pakistan Postgraduate Medical Institute, Lahore), 2. Muhammad saeed Akhtar Khan (Associate Professor of Pathology/Pakistan Postgraduate Medical Institute, Lahore), Page No. 34 should be read authors name in both case reports as follows: Ambreen Anwar Imran and Saeed Akhtar Khan

Esculapio - Volume 07, Issue 01, January-March 2011

Original Article

Lipoprotein Abnormalities And Body Mass Index Differences In Type 2 Diabetic Postmenopausal Women In Tertiary Care Hospitals Of Peshawar Riffat Sultana, Anjum Humayun, Nargis Parveen and Shamim Alam

Objective: To detect serum lipoprotein abnormalities and Body Mass Index differences in type 2 diabetic post menopausal women compared to controls Material & Methods: This case control studywas conducted at Tertiary care hospitals of Peshawar, that is Hayatabad Medical Complex, Khyber Teaching Hospital, and Lady Reading Hospital over a period of two years i.e., from July 2005 to July 2008.One hundred and fifty diagnosed diabetes type 2 post menopausal females compared with fifty non diabetic post menopausal healthy controls were included. Determination of glucose, total cholesterol, high density lipoprotein cholesterol were assessed by enzymatic lab technique (Elitech) using micro lab 200 (Merck), and low density lipoprotein cholesterol was determined by Friedewald formula. Results: The results indicated highly significant difference between the biochemical indices of cases and controls which included elevated levels of LDL-C (p=0. 001), reduced levels of HDL-C (p=0.001) and triglycerides (TG) above the target levels (p=.000). Body Mass Index showed significant change in diabetic postmenopausal females as compared to controls. (p<0.015). Conclusion: Dyslipidemias in post menopausal diabetic females are more prevalent. Lipoprotein abnormalities are a risk factor for cardiovascular diseases which becomes more prevalent with the loss of estrogens and the decrease in High density lipoprotein (HDL) cholesterol levels that occurs concurrently with menopause. Keywords: Dyslipidemia, Type 2 Diabetes Mellitus and Menopause. 5

Introduction

plateau at the age of 50. It is of paramount importance to bring increased awareness of heart disease in women through these studies, because almost 65% of deaths occur in those with no previous symptoms. Women are less likely to be diagnosed correctly, less likely to undergo the correct revascularization procedure, and less likely to survive a major cardiac event than men. Post-menopausal women exhibit a steady increase in the incidence of 6 coronary heart disease with age. Its occurrence is rare before menopause, suggesting that the loss of endogenous estradiol plays an important preventive role in CHD. Age-adjusted risk of CHD in postmenopausal women is increased by two- to three fold, 7 as compared to premenopausal women. Cholesterol, hyperlipidemia is an important risk factor in the development of CHD among women. The Framingham study demonstrated that the total 8 cholesterol increased after menopause. Women during fertile age have a lower risk of cardiac events but this protection fades away after menopause. The response to therapy may also differ in women because of endogenous hormone levels, lower body weight

Diabetes is recognized as the coronary heart disease risk equivalent condition. Dyslipidemia affects 70% to 97% of people with diabetes. It is characterized by a low level of High Density Lipoproteins (HDL), increased levels of Triglycerides and Low Density Lipoproteins (LDL-C) particles of altered composition.1 An increase in the incidence of coronary heart disease risk has commonly been 2 reported in post menopausal women. This difference may be due to the deleterious effects of diabetes on lipids and blood pressure in women. In women, total and low density lipoprotein (LDL) cholesterol increase with age, and this increase is accelerated by menopause, whereas cardio-protective high density lipoprotein (HDL) decreases. These changes lead to increased rates of coronary heart disease, myocardial 3 infarction and stroke in post-menopausal women. The largest health threat to women over age 50 is cardiovascular disease.4 UK Prospective Diabetes study, with the aim to compare fasting lipid among type-2 diabetes mellitus also showed that lipid concentration increases with age, but reached the

Esculapio - Volume 07, Issue 01, January-March 2011 9

and higher fat proportions.

samples were collected for random blood sugar using standard assays. Determination of glucose, total cholesterol, high density lipoprotein cholesterol was done by enzymatic lab technique (Elitech) by micro lab 200 (Merck), and low density lipoprotein cholesterol was determined by Friedewald formula. The diagnosis of Diabetes Mellitus was based on the American Diabetes Association criteria for type 2 diabetes Mellitus (fasting plasma glucose level higher than 126 mg/dl and /or glucose level exceeding 200mg/dl at 2 hours in the 75g oral glucose tolerance test). Anthropometric measurements were made with the participants wearing light weight clothes and no shoes. BMI (Body Mass Index) was calculated for each study subject using the Quetelet's index: BMI=weight (in kg)/height in metres squared (m2). For Asians the normal body mass index is from 18.522.9 kg/m2, Body mass index considered overweight from 23-24.9 kg/m2 and obesity is considered when body mass index is >25 kg/m2. Blood pressure (mmHg) was measured after 5 minutes of rest in a seated position by mercury sphygmomanometer. The blood pressure was recorded from the upper extremity, and elbow was slightly flexed and placed at heart level. The disappearance of sound (phase V) was used for the diastolic blood pressure. Correct cuff and bladder sizes were used. Mean blood pressure was calculated as diastolic plus one third of pulse pressure where pulse pressure was taken as the systolic pressure minus diastolic pressure. Participants were considered to have hypertension if systolic blood pressure (SBP) was >140 mmHg or diastolic blood pressure (DBP) >90 mmHg or if they were taking antihypertensive medication.

Material and Methods Study Design: This was case control study was conducted on post menopausal female's patients with type 2 diabetes mellitus and compared with normal healthy females of the same age group. Sample Size: A sample of 150 subjects was selected, 150 were diagnosed patients of type 2 diabetes and 50 were normal non-diabetic healthy individuals. Place of Study: The study was conducted at Physiology Department, Khyber Medical College Peshawar. Diabetic post menopausal female patients were selected from three tertiary care hospitals of Peshawar i.e. Khyber Teaching Hospital, Lady Reading Hospital and Hayatabad Medical Complex. Controls were selected from the general population of Peshawar. Duration of Study: Two years i.e., from July 2005 to July 2008. Inclusion Criteria: Diagnosed post menopausal female patients of type 2 diabetes between age of 50-60 years Exclusion Criteria: Patients using insulin, having previous history of angina, severe vascular disease, nephropathy or other life threatening diseases, and patients taking corticosteroids or any drugs affecting lipid profile or diabetic status were excluded from the study. Control Group: 50 normal healthy females, randomly selected, between age of 40-50 years. Method of Data Collection: Participants of the study were divided into two groups that are diabetic post menopausal females and age comparable female controls. For laboratory purposes the facility of Pakistan Medical Research Council, Khyber Medical College was availed. The subjects were selected after taking written consent and detailed history and examination according to:

Data Analysis The data was analyzed using SPSS version 16. The meanÂąSD was computed for the comparison of results. The distribution of cases among various criteria was represented by their percentage. The comparison of mean between two groups was tested by Studentâ&#x20AC;&#x2122;s t test. The p-value of highly significance was taken as <0.00, moderately <0.01, marginally as <0.05.

1. Questionnaire Performa 2. Consent form.

Results

Fasting blood sugar and lipid profile was done for all the participants of the study. Participants were asked to come to the laboratory after an overnight fasting for at least 6 to 12 hours. Fasting blood samples were collected for measurement of plasma glucose and lipid profile. The 2HABF (two hours after breakfast)

Participants of the study were divided into two groups i.e. diabetic post menopausal females and age comparable female controls. Table1 illustrates that the mean ages of the diabetic and control groups respectively. were 53.1 and 51.4 years.

Esculapio - Volume 07, Issue 01, January-March 2011

The systolic blood pressure and diastolic blood pressure were significantly higher in post menopausal diabetic females as compared to postmenopausal healthy females. Body Mass Index shows significant change in diabetic postmenopausal females as compared to controls (p<0.015). When lipid profile of healthy females was compared with diabetic females we observed significantly higher levels of TC, LDL-C and TG levels in diabetic females (p < 0.009, p < 0.001 and p < 0.000 respectively). A decreased level of high density lipoprotein cholesterol(HDL-C) was observed in type 2 diabetes post menopausal patients as compared to normotensive control subjects (p<0.001).

healthy lifestyle is the best preventive medicine, which favorably protects the heart and maintains a favorable lipoprotein profile. Lipid abnormalities may be the result of the unbalanced metabolic state of diabetes (i.e. hyperglycemia and insulin resistance) but still there is moderate diabetes-associated dyslipidemia with improved control of hyperglycemia.11 In our study the patients with diabetes were dyslipidemic with high plasma triglyceride and low HDL cholesterol concentrations. Longitudinal epidemiology has pointed to the importance of raised plasma triglycerides and low HDL Cholesterol as a risk factor for coronary disease in diabetic subjects12 and there is supportive evidence for aggressive management of lipid disorders in type 2 diabetes.13

Discussion

Table-1: Clinical characteristics cases and controls

Several potential interacting factors may contribute to the acceleration of coronary heart disease risk in women with diabetes. These include a greater tendency to poor glycemic control, elevations in blood pressure and circulating lipids, and development of obesity.10 First and foremost, a

Controls n=50

Cases n=150

Age (years)

51.9±6.09

53.2±4.92

SBP (mmHg)

122.06±8.06

160.13±13.37

DBP (mmHg)

83.73±6.25

93.33±10.70

Variable

Table-2: Various study parameters in cases and controls Cases (n=150)

Control (n=50)

P-value

Abnormal

136 (90.7%)

38 (76%)

0.015

Normal

14 (9.3%)

12 (25%)

Fasting blood sugar

182.33

85.23

0.000

Random blood sugar

245.38

115.53

0.000

>200 (abnormal)

96 (64%)

18 (36%)

0.009

>150 (normal)

54 (36%)

32 (64%)

>150 (Abnormal)

84 (56%)

11 (22%)

<150 (Normal)

66 (44%)

39 (78%)

< 40 (Abnormal)

47 (1.33%)

4 (8%)

>40 (Normal)

103 (68.7%)

46 (92%)

>160 (Abnormal)

109 (72.7%)

19 (38%)

40-160 (Normal)

41 (27.3%)

31 (62%)

Parameters Body Mass Index (BMI)

Blood Sugar

Total Cholesterol (TC)

Low density lipoprotein cholesterol (LDL-C) 0.001

High density lipoprotein cholesterol (HDL-C) 0.001

Triglyceride (TG)

0.000

Esculapio - Volume 07, Issue 01, January-March 2011

Majority of our patients (72.2%) had hypertriglyceridaemia which is consistent with the 14,15 studies. A 14-year follow-up study of 1,405 post-menopausal women demonstrated that a triglycerides level greater than 4.5 mmol/L was associated with a more than three fold increase in the risk of coronary heart disease related mortality.16 Lipoprotein abnormalities are an independent risk factor for coronary heart disease and there is some evidence that lipoprotein abnormalities increases with age in women.17 Another study has shown that lipoprotein abnormalities was a significant risk factor for coronary artery disease in both pre- and postmenopausal women.18 Diabetes increases the risk of coronary heart disease threefold in women, and puts them at the same risk as men of the same age. Much of this excess risk is due to the excess in other coronary risk factors which occur in 19 diabetics. More women than men develop hypertension as they get older and we know that control of hypertension reduces the risk of both stroke and heart disease. In our study the SBP and DBP were significantly higher in post menopausal diabetic females as compared to postmenopausal healthy females (p< 0.0001 and p < 0.05 respectively). Hypertension is one of the major risk factors for the development of coronary heart disease. The incidence of hypertension increases with age and is higher in men than in women up to the age of about 50. Beyond middle age, however, blood pressure in women exceeds that in men. It has been suggested that menopause may potentiate the age-related increase in systolic pressure, perhaps as a result of reduced arterial compliance. Our study is in agreement with the study done by Staessen et al20 who measured the blood pressure of 315 women and followed them up for a median of 5.2 years. Those women who were postmenopausal had a 4-5 mmHg higher systolic blood pressure than their pre- and peri menopausal counterparts, and also, while there was no change in systolic blood pressure in premenopausal women during follow-up, the systolic blood pressure increased by 4 mmHg in 5 years in the postmenopausal and premenopausal women. In a 21 cross-sectional study, Weiss et al found that postmenopausal women had significantly higher serum cholesterol compared to pre-menopausal women. In the Framingham Study22 women between the ages of 29 and 62 years who were followed-up in a longitudinal study for 18 years demonstrated a significant rise in serum cholesterol levels between

premenopausal and postmenopausal examinations, with the rise taking place within a short time of the onset of the menopause, thus suggesting a causal effect. Type 2 diabetes is becoming ever more common, right along with one of its root causes - obesity. Diabetes should be thought of as a disease of blood vessels as much as a disease of sugar metabolism, as it greatly increases cardiovascular risk. The risk of heart disease in women with diabetes is increased as much as 6-fold.23 Hubert et al indicated that being overweight is a cardiovascular factor; this condition is usually associated with other risk factors rather than constituting an independent factor itself.24 For aging women to maintain an independent lifestyle is more difficult; they are particularly more prone to inactivity and obesity. Obesity and sedentary life style are more common in post-menopausal women than in men of the same age; both are strong risk factors 25 for heart disease and stroke. 26 In the Nurses' Health Study body mass index was strongly associated with death due to CHD, with the risk of CHD over three times higher among women with a body mass index of 29 or higher. Much of this increased risk can be attributed to influences on blood pressure, glucose tolerance and lipid levels. However, the presence of diabetes seems to negate any cardio protection that a woman may have. The findings of the present study are in line with these findings. As women tend to have heart attacks later in life than men, they often have other diseases that mask cardiac symptoms. Coronary heart disease is more often of the silent type in women. Thus, women with heart disease tend to be both under investigated and under treated when actually the female gender is strongly associated with increased risk for heart disease. The one-year post heart attack mortality risk is 41% in women compared to 27% for men. Similarly, in hospitals, mortality rate is 13% for women compared to 7% for men. Our study suggests that, at least in postmenopausal women with an elevated level of serum total cholesterol, one should proceed immediately to lipoprotein analysis for further risk assessment.

Conclusion In conclusion, this study has highlighted that diabetic dyslipidemia in post menopausal females is more prevalent. Lipoprotein abnormalities are a risk factor for cardiovascular diseases which becomes more prevalent with the loss of estrogens and the decrease

Esculapio - Volume 07, Issue 01, January-March 2011

In HDL cholesterol levels that occurs concurrently with menopause. Non-pharmacological intervention should be targeted towards a low-salt, low-fat, high-fibre diet and increased physical activity. Efforts to educate the populace on diabetes, and awareness of heart disease in women including the delayed onset needs to be emphasized at different forum levels of education/

seminar programs. Diabetic women must aggressively manage their risk factors if they are to live a longer, healthier life. Department of Physiology Khyber Girls Medical College Hayatabad, Peshawar

theesculapi@hotmail.com www.sims.edu.pk/esculapio.html

References 1. Ghani HM, Humaira M, Raqeeb A. Patterns of diabetic dyslipidemia and glycemic control at tertiary care hospital Sindh. Medical Channel 2010; 16 (3).Available at URL:http:// www.medicalchannel.pk/pastissues/volume-16/number3/207-patterns-of-diabeticdyslipidemia-and-glycemiccontrol-at-tertiary-carehospital-sindh.html 2. Manson JE, Spelberg A. Risk modification in diabetic patients in prevention of myocardial infarction. Oxford University Press, New York, 1996, pp. 24173. 3. Matthews KA, Meilahn E, Kuller LH. Menopause and risk factors for coronary heart disease. N Engl J Med 1989; 321:641-6. 4. Minino AM, Arias E, Kochanek KD, Murphy SL, Smith BL. Deaths: final data for 2000. Natl Vital Stat Rep 50(15):1-108-45. 5. U.K Prospective Diabetes Study 27, Plasma Lipids and Lipoproteins at diagnosis of NIDDM by age and sex. Diabetes Care 1997,Vol.20 (11):1683-1687. 6. Manolio TA, Wenger NK, Barrett-Connor E. :Cholesterol and heart disease in older persons and women. Ann Epidemiol 1992; 2:161-76. 7. Blumel JE, Castelo-Branco C, Rocangliolo ME, Bifa L,Tacla X, Mamani L. Changes in body mass index around menopause: a population study of Chilean woman. Menopause 2001; 8 (4): 239-44. 8. Grundy SM, Balady GJ, Criqui

10.

11.

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14.

MH. Primary prevention of coronary heart disease: Guidance from the Framingham study. Circulation 1998; 97(18):1876-87. Judd HL, Mebane-Sims I, Legault C, Wasilaskas C, Johnson S, Merino M. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. J Am Med Assoc 1995;273(199):20823. Barr DR, Russ EM, Eder HA. Protein-lipid relationships in human plasma. Am J Med 1951; 11:480-93. Marcus AO. Lipid disorders in patients with type 2 diabetes; Meeting the challenges of early, aggressive treatment. Postgrad Med 2001 Jul;110(1):111-4. Hokanson JE, Austin MA. Plasma triglyceride level as a risk factor for cardiovascular disease independent of high-densitylipoprotein cholesterol: a metaanalysis of population-based prospective studies. J Cardiovasc Risk 1996;3:21-39. Pyorala K, Pedersen TR, Kjekshus J, Faegeman O, Olsson AG, Thorgeirsson G. The S c a n d i n a v i o n S i m va s t a t i n Survival Study(4S). Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study(4S). Diabetes Care1997;20:614-209. M a r w a t M A , Wa z i r Z M . Hypertriglyceridaemia in Diabetes Mellitus. J Ayub Med Coll Abbottabad 2000;12 (4):24-45.

15. Naheed T, Khan A, Masood G. Dyslipidaemias in type 2 diabetes mellitus patients in a teaching hospital of Lahore, Pakistan. Pak J Med Sci 2003;19(4):283-6. 16. Miller Bass K, Newschaffer CJ, Klag MJ, Bush TL. Plasma lipoprotein levels as predictors of cardiovascular death in women. Arch Int Med 1993;153: 2209-16. 17. Sandkamp M, Assman G. Lipoprotein (a) in PROCAM participants and young Myocardial infarction survivors. In:Scanv AM, ed. Lipoprotein(a): 25 years of progress. New York, Academic Press, 1 9 9 0 : 2 0 - 5 9 . 18. Orthgomer K, Mittleman MA, Schenck-gustafsson K, Wamala SP, Eriksson M, Belkie K, et al. Lipoprotein (a) as a determinant of coronary heart disease in young women. Circulation 1997; 95: 329-334. 19. Kannel WB. Metabolic risk factors for coronary heart disease in women; Perspective from the Framingham Study. Am Heart J 1987; 114:413-19. 20. Staessen JA, Ginocchio G, Thijs L, Fagard R. Conventional and ambulatory blood pressure and menopause in a prospective population study. J Human Hypertens 1997; 11:507-14. 21. Weiss NS. Relationship of menopause to serum cholesterol and arterial blood pressure: the United States' Health Examination Survey of adults. Am J Epidemiol 1972; 96:237-41. 22. Hjortland MC, McNamara PM, Kannel WB. Some atherogenic

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disease in women; Perspective concomitants of menopause: the Framingham Study. Am J Epidemiol 1976; 103:304-11. 23. Miller VT. Dyslipoproteinemia in women. Special considerations. Endocrinol Metab Clin North Am 1990 Jun; 19(2):381-98. 24. Huber t HB, Fleinleib M,

McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow up of participants in the Framingham Heart Study. Circulation 1983; 67: 968-977. 25. Lip GYH, Jones AF. Lipoprotein ( a ) a n d va s c u l a r d i s e a s e : thrombogenesis and

atherogenesis. Q J Med 1995; 88:529-39. 26. Manson JE, Willett WC, Stampfer MJ, Colditz GA, HunterDJ, HankinsonSE, et al. Body weight and mortality among women. N Engl J Med 1995; 333:677-85.

Medical News

Novel Protease Inhibitor Active Against Hepatitis C Genotype-1 HCV is the most prevalent and difficult-to-treat HCV subtypes. Standard care is with pegylated interferon alfa and ribavirin, but more than 50% of patients don't respond or relapse. Inhibition of the NS3/NS4A HCV protease has been shown to suppress viral replication, the team randomized 34 treatment-naive patients to monotherapy with placebo or BI201335 at 20 to 240 mg once-daily for 14 days. This was followed by 14 days of use along with pegylated interferon alfa/ribavirin. Active monotherapy induced a rapid, dose-dependent decrease in plasma HCV RNA from baseline in all patients. Subsequently, viral load breakthrough was common. Addition of pegylated interferon alfa/ribavirin led to continuous viral load reductions in most patients. A further 19 treatment-experienced patients also received combination treatment with 48 to 240 mg BI201335 for 28 days. Viral loads fell and breakthroughs were seen in only 3 of these patients. In light of these and other findings, the researchers conclude that the data support "the investigation of different treatment regimens testing doses from 120 mg to 480 mg daily in phase IIb trials."

Original Article

Effect Of Storage Conditions On The Morphological Preservation Of Rabbit Kidney And Liver Tissues Ambereen A Imran, Munazza Hasan, Saeed Akhter Khan and Naseer Ahmed Chaudrhy

Objective: To see the effect of different solutions and storage temperature on morphological preservation of rabbit kidney and liver tissues. Material and Methods: In this experimental study, rabbit kidney and liver slices were stored in Ringer Lactate, Euro Collins and University of Wisconsin solutions (UW solution), for various fixed time intervals. The three solutions were tried at room temperature as well as at 0-4°C. Morphological preservation was assessed by a semi quantitative method. Results: Adequate morphological preservation of both tissues was obtained in all solutions at room temperature for the first 24 hours. Lowering of storage temperature to 0-4°C was highly beneficial to both tissues in all solutions. UW solution is more effective for liver tissue preservation. Conclusion: Anyone of the solutions may be used at room temperature, for preservation of tissue to be submitted for immuno-histochemistry for the first 24 hours. If prolonged storage is required, lowering of temperature is recommended. Keywords: Organ preservation, Ringer lactate, Euro Collins solution, University of Wisconsin solution, morphological preservation, temperature. Introduction Tissue preservation is a major concern in histopathological studies.1 Formalin has long been used as a “routine” tissue preservative and a fixative, but it has numerous drawbacks, the most troublesome of which is its masking of antigenic sites. This interferes with subsequent immuno-histochemical procedures. So the development of alternative preservation techniques is an ongoing challenge to the histopathologist. 3 Fortunately histopathologists are not alone in their efforts to achieve tissue preservation. Transplant surgeons are also on a lookout for solutions which would give optimal organ preservation. This would reduce the constraints on time which could be allowed to elapse between organ procurement and its re-implantation. 4-6 Ringer lactate, Euro Collins solution (EC solution) and University of Wisconsin solution (UW solution) are the most widely used organ preservation solutions.4,5,7 Ringer lactate was amongst the earliest solutions tried.8 Later, EC solution was developed which vastly improved the outlook for the kidney, but unfortunately did not benefit liver preservation.9 After further extensive research, UW solution was developed at the University of Wisconsin. It was a complex multi component solution and provided markedly enhanced preservation of several organs especially liver and pancreas. 10

Another factor found to be significant in tissue and organ storage was the storage temperature. Hypothermic preservation, short of freezing, gave 11, 12 promising results. In this study an attempt has been made to compare the morphological preservation of rabbit kidney and liver tissue in the three above mentioned solutions, both at room temperature and at 0-4°C. The aim was to study the effect of storage conditions on morphological preservation of these tissues and help to determine pragmatic choices made on grounds of cost and logistics.

Material and Methods Rabbits were sacrificed and their kidneys as well as livers were sliced. These slices, 3-4 mm thick, were preserved in three different solutions at room temperature as well as in hypothermic conditions. The solutions were Ringer lactate, EC solution and UW solution. Ringer lactate was purchased from Medisol®, while EC solution was prepared after Abebe et al13 and UW solution was prepared after 14 Baatard et al immediately prior to use. The storage temperature was kept around 25°C for the room temperature groups and at 0-4°C for the hypothermic groups (Table 1). Tissue slices were removed at various fixed time intervals (0 hr, 12 hr, 24 hr, 36 hr, 48 hr, 72 hr, and 96 hr) and processed routinely. Six tissue slices were

included in each group. Sections were stained with haematoxylin and eosin. Morphological preservation was assessed by a semi 2 quantitative method and expressed in percentage. The 0 hr sections served as a control for each group. Observations were recorded by two independent observers. The results were then compared using paired student's t test and slope test.

Table-1: Details of storage conditions Sex Group

Numbers Solution

Percentage Temperature

Ringer Lactate

Room temperature

Ringer Lactate

0-4 C

EC Solution

Room temperature

EC Solution

0-4O C

Results

UW Solution

Room temperature

Satisfactory morphological preservation of both tissues was seen in all solutions at both temperatures for the first 24 hours. Thereafter, the temperature of 0-4° C gave a significantly better preservation. UW

UW Solution

0-4 C

solution was found to give better liver preservation at both temperatures, compared with the other two solutions (Table 2).

Table-2: The effect of lowering of temperature on morphological preservation of rabbit kidney and liver tissues Tissue

Group

Kidney

A B

65 99

45 99

Liver

Kidney Liver

Kidney

Liver

Percentage presevation At 24 hrs At 48 hrs At 96 hrs

Slope

p value

19 95

-0.83

p=0.0000

-0.97

-0.35

-0.98

-0.12

-0.98

-0.42

E-

-0.39

-0.21

-0.61

-0.38

Discussion The current boundaries of tissue preservation have been set in an era of formalin fixation. The dire need of a better tissue preservation medium is obvious to anyone involved in immunohistochemistry and enzyme histochemistry.3 Encouraging results were obtained in the current study. The results showed that if the tissue to be subjected to immunohistochemistry can be transported to a referral centre within 24 hours, Ringer lactate at room temperature can give an adequate degree of preservation. Despite its simple composition Ringer lactate has shown acceptable degree of preservation in other studies.15If transport involves a longer duration of time, lowering the temperature to 0-4° C would be helpful in preserving morphology.

-0.04 P=0.0011

P=0.0000

P=0.0018 P=0.0312

P=0.0093

Improved preservation of tissues at lower 16, 17 temperature is borne out by other studies. This happens because all enzyme activity is temperature dependent. Cooling diminishes metabolic activity, curtails oxygen demand and slows deterioration of energy stores. Also oxygen is more soluble at lower temperatures, allowing that dissolved 18,19 in surrounding fluid to be utilized better. However, a few studies have suggested that a higher storage temperature of 10° C is better for preservation of endothelial cells.20 Another point that deserves mention is that we live in a hot country. Our environmental temperature may soar above 50° C. The temperature in our study was kept at 25° C. The environmental temperature must be kept in mind while deciding whether or not to use

this tool of hypothermia. The results also show that liver tissue has an unmistakable preference for UW solution. This superiority of UW solution in liver preservation is 21 well established. With its components “designed” and “tailored” to cater to the need of the hepatocyte, UW solution remains a solution of choice for liver preservation. The only obstacles to its more widespread use are its high cost, reduced availability 22 and limited shelf life. In conclusion, Ringer lactate at 0-4°C is the best

option for renal tissue preservation. Liver tissue would fare better if stored in UW solution. The maintenance of a temperature of 0-4°C is an important tool in improving preservation of both tissues in all solutions. Department of Pathology Postgraduate Medical Institute, Lahore

thesculapio@hotmail.com www.sims.edu.pk/esculapio.com

References 1. Bertheau P, Cazals-Hatem D, Meignin V, de Roquancourt A, Verola O, Lesourd A. Variability of immuno-histochemical reactivity on stored paraffin slides. J Clin Pathol 1998; 51: 3704. 2. Imran AA, Khan SA, Chaudhry NA, Hasan M, Tayyib M. Morphological evaluation of rabbit renal tissues preserved in Ringer Lactate, Euro Collins and U n ive r s i t y o f W i s c o n s i n solutions. Biomedica 2002; 21-6. 3. Kiernan JA. Preservation and retrieval of antig ens for immunohistochemistry; method and mechanisms.1. Effects of formaldehyde fixation. The Cutting Edge 2005; 1: 5-9. 4. Maathuis MH, Ottens PJ, vanGoor H, Zwaagstra JJ, Wiersema-Buist J, Schuurs TA et al. Static cold storage prese r va t i o n o f i s ch e m i c a l l y damaged kidneys.;a comparison b e t we e n I G L - 1 a n d U W solution. Transpl Int 2008; 21 (5): 473-82 5. Mangus RS, Fridell JA, Vianna RM, Milgrom MA, Chestovich P, Chihara RK et al. Comparison of histidine-tr yptophan-ketoglutarate solution and University of Wisconsin solution in extended criteria liver donors. Liver Transpl 2008 Mar;14 (3):365-73. 6. Guarrera, James V, Karim, Niaz A. Liver preservation: is there anything new yet?. Organ preservation and procurement .

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Current Opinion in Organ Transplantation 200813(2):148154. Imran AA, Khan SA, Chaudrhy NA, Tayyib M. Role of anti microbial agents in delaying changes of autolysis. Ann King Edward Med Coll 2006; 12: 394-5. Benichou J, Halgrimson CG, Weal R, Koep LJ, Starzl TE. Canine and human liver preservation upto 6 to 18 hours by cold infusion. Transplantation 1977; 6: 407-11. Collins GM, Bravo-Shugarman M , Te r a s a k i P I . K i d n e y preservation for transportation. Initial perfusion and 30-hours ice storage. Lancet 1969; ii: 1219-22. Belzer FO, Southard JH. Principles of solid org an preservation by cold storage. Transplantation 1988; 4: 673-6. St Peter SD, Imber CJ, Friend PJ. Liver and kidney preservation by perfusion. Lancet 2002; 359 (9306) : 604-13. Bahde R, Palmes D, Gemsa O, Minin E, Stratmann U, de Groot H et al. Attenuated cold storage injury of rat livers using a modified HTK solution. J Surg Res 2008; 146(1):49-56. Abebe W, Cavallari N, Agrawal DK, Rowley J, Thorpe PE, Hunter WJ. Functional and morphological assessment of rat aorta stored in University of Wisconsin and Euro Collins solutions. Transplantation 1993; 4: 808-16. Baatard R, Pradier F, Dantal J, K aram G, Cantarovich D, Hour mant M. Prospective

15.

16.

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randomized comparison of University of Wisconsin and UW-modified lacking hydroethyl starch cold storage solutions in kidney transplantation. Transplantation 1993; 1: 31-5. Gulec B, Coskun K, Yigitler C, Yigit T, Aydin A, Oner K. Ischaemia-reperfusion injury in the liver during renal transplantation: does perfusion solution play a role? Transplant Proc 2008; 40: 59-62. Fuller BJ, Lee CY. Hypothermic perfusion preservation: the future of organ preservation revisited? Cryobiol 2007; 54: 12945. Mangus RS, Tector AJ, Fridell JA, Kazimi M, Hollinger E, Vianna RM. Comparison of histidine-tr yptophan-ketoglutarate solution and University of Wisconsin solution in intestinal and multi visceral transplantation. Transplantation 2008 Jul 27;86(2):298-302. Ozeki T, Kwon MH, Gu J, Collins MJ, Brassil JM, Miller MB et al. Heart preservation using continuous ex vivo perfusion improves viability and functional recovery. Circ J 2007; 71(1):1539. Pylawka TK, Virdi AS, Cole BJ, Williams JM. Reversal of suppressed metabolism in prolonged cold preser ved cartilage. J Orthop Res 2008; 26 (2): 247-54. Z i e g e r M A , G u p t a M P.

Endothelial cell preservation at 10 degrees C minimizes catalytic iron, oxidative stress and cold induced injury. Cell Transplant 2006; 15: 499-510. 21. Ahmad N, Pratt JR, Potts DJ, Lodge JP. Comparative efficacy

of renal preservation solutions to limit functional impairment after warm ischemic injury. Kidney Int 2006; 69(5):884-93. 22. Abe T, Lynch SV, Balderson GA, Pragalathan S, Pillay PS, Wall DR et al. Comparison of Euro-Collins

Picture Quiz Please examine this x-ray carefully and answer following questions. 1. What abnormality do you see on this x-ray chest? 2. What physical findings may be present in this case? 3. What may be the complications? 4. How will you treat this patient?

See answer on page 47

and University of Wisconsin solutions in adult human cadaveric liver transplantation. J Hepato-biliary Pancreatic Surg 2006; 1: 280-84.

Esculapio - Volume 07, Issue 01, January-March 2011

Original Article

Radiological Feature of Hepatic Cirrhosis in Hepatitis â&#x20AC;&#x153;Câ&#x20AC;? in Pakistan; Our experience at Department of Radiology, Services Institute of Medical Sciences Qamar Sardar, Maliha Fansur, Mamoon Qureshi, Zia Sheikh, Tahir Baig, Nadeem Butt, Khalid Rehman, Tahir Abbas, Tanveer Ahmad, Saleem Cheema, Salman Atiq

Objects: To evaluate the accuracy of liver fibrosis stage by utilizing the techniques of advanced ultrasound performance in patients with chronic liver disease with Hepatitis C. Material and Method: This cross-sectional study was prospectively designed by including 101 consecutive patients with a diagnosis of chronic liver disease including liver cirrhosis between January and December 2010. The ultrasound score was determined from both hepatic lobes and the average scoring was calculated for liver edge, liver surface and liver parenchymal texture. A score of 0 was given when no abnormality was observed; score 1 for mild abnormality; score of 2 for moderate abnormality; and a score of 3 for severe abnormality. Scoring was given for a blunted edge and severe irregular surface or a highly coarse texture only when these characteristics were clearly confirmed by the low frequency probe. Results: Out of 101 subjects, 63.4 % were male and 36.6 % were female with age range of.2370 years (mean age 50.73 years SD +/- 10). 17.8 % subjects were between age group 20-40 years, 67.3 % between age group 41- 60 years and 14.9 % between 61 years and above. Mean duration of illness was 2.86 years (minimum 1 year and maximum 15 years). Mean liver size was 12.261 with SD + 2.7145. Mean portal vein size was 1.662 SD + 2.3247. Mean spleen size was 71.71 SD + 32.226. 62.4 % had splenomegaly, 66.3 % had ascites, 56.4 % had bruising and bleeding, 62.4% had varices. 20.8 % had sharp edge 48.5 % had mildly blunted edge and 30.7 % had blunt edge, 11.9% had smooth edge. 33.7% had mildly irregular edge, 39.6 % had irregular edge and 14.9 % had highly irregular edge. Regarding liver parenchymal structure 13.9 % had fine , 22.8 % had mildly coarse, 48.5 had coarse and 14.9 % had highly coarse liver parenchymal structure.15.8 % of subjects had mild fibrosis (score 0 -2) , 55.4 % had moderate fibrosis (score 3 5) , 28.7 % had severe fibrosis (score 6 -8). Conclusion: US scoring system is clinically useful for differentiating patients with minimal or no fibrosis from those with mild to severe fibrosis. This is also useful for prognostic information and determining the optimal therapeutic options during the follow-up of chronic liver disease. Keywords: Liver fibrosis, hepatitis C, ultrasound. Introduction The liver fibrosis stage in patients with chronic liver diseases due to an infection with hepatitis B virus (HBV) or C virus (HCV) is a pivotal factor regarding both the therapeutic options and for predicting the prognosis. A liver biopsy is considered to be the gold standard for diagnosing the liver fibrosis stage and predicting the outcome of the diseases. Although a percutaneous liver biopsy is relatively safe, it is still associated with a risk of complications, patient discomfort and a high cost. In addition, liver biopsy examinations may lead to false negative results due to inadequate liver tissue sampling. Therefore, there is a need to develop a simple, reliable and non-invasive modality in order to assess the liver fibrosis stage.1 Ultrasound (US) is a non-invasive, inexpensive and

repeatable modality and has been used as the most important and valuable diagnostic tool for detecting hepatocellular carcinoma (HCC)during the follow-up of patients with viral hepatitis.2,3 US is also used for monitoring the response of HCC to treatment. An ultrasound evaluation of the liver fibrosis stage of chronic liver disease has been performed by assessing various ultrasound factors such as the liver size, the bluntness of the liver edge, the coarseness of the liver parenchyma, nodularity of the liver surface, the size of the lymph nodes around the hepatic artery, the irregularity and narrowness of the inferior vena cava, portal vein velocity or spleen size.1,48 However, the conventional definition of the fibrosis stage of the liver based on evaluation of these ultrasound factors is imperfect and lacks accuracy and reliability. 30

Esculapio - Volume 07, Issue 01, January-March 2011

Furthermore, these findings also depend largely on 8 the equipment used. Indeed, a few reports have demonstrated no consistent correlation between the grey scale ultrasound findings and the histological findings, thus claiming that grey scale US is unreliable for grading and staging the degree of liver damage.9 However, recent advances in US technology have improved the diagnostic accuracy for fibrosis in patientswith chronic liver disease. Therefore, we carried out a study to evaluate the accuracy of the liver fibrosis stage by utilizing the techniques of advanced ultrasound performance in 101 patients with chronic liver disease with Hepatitis C.

was observed by a high frequency probe, score 1 was given when a mild abnormality was detected by a high frequency probe while it was undetected by the low frequency probe, a score of 2 was given when a moderate abnormality was detected by the low frequency probe, and a score of 3 was given when a severe abnormality was detected by the low frequency probe. A score of 2 was given for a blunted edge and a score 3 for severe irregular surface or a highly coarse texture when these characteristics were clearly confirmed by the low frequency probe.

Patients and Methods Study setting: Department of radiology Services Institute of Medical Sciences. Study Design: Cross sectional study Study Duration: One year Sample size: 100 subjects with hepatitis C were included in the study. Sampling technique: Non probability convenient sampling Data Collection Procedure: This cross-sectional study was prospectively designed. 101 consecutive patients with a diagnosis of chronic liver disease including liver cirrhosis at SIMS between January and December 2010 were included. The inclusion criteria were as follows: (a) history of chronic liver disease, based on the detection of persistently high levels of aminotransferase; (b) an presence of clinical and/or biochemical signs of decompensated liver diseases (jaundice, ascites or encephalopathy); and (c) no previous histo pathological diagnosis. The patients were studied ultrasonically using a real-time apparatus Toshiba Xario (SSA 660A; Tokyo, Japan) with 3.5 MHz convex array transducer C52 (low frequency probe) and a 512 MHz convex array transducer L125 (high frequency probe). The ultrasound examinations were done by a certified specialist on static B-mode imaging. The US score was determined from the right and left lobes and the average score for each parameter was calculated as follows: (1) liver edge: score 0 for sharp; score 1 for mildly blunted; score 2 for blunted; (2) liver surface: score 0 for smooth; score 1 for mildly irregular; score 2 for irregular; score 3 for highly irregular; and (3) liver parenchymal texture score 0 for fine; score 1 for mildly coarse; score 2 for coarse; score 3 for highly coarse. A score of 0 was given when no abnormality

(A)

(B)

Fig. (A). Transverse sonogram demonstrating various parameters of cirrhosis of liver (mildly blunted liver edge, irregular liver surface and coarse liver parenchymal texture). (B). Magnified view of left hepatic lobe for the confirmation of the average score for sonographic cirrhotic liver parameters. 31

Esculapio - Volume 07, Issue 01, January-March 2011

Data Analysis Procedure:

Table-1: Demographic and clinical profile of cases

Data was entered and analyzed in SPSS ver.17.0. Mean and SD was calculated for numerical variables, age, duration of illness, biochemical value of LFTs,. Frequency tabulation was done for sign and symptoms, and liver edge score and was presented as mild, moderate and severe fibrosis depending upon their cumulative score of liver parenchyma, surface and edge.

with scoring. Variable

Frequency

Percent

Gender of subjects Male

63.4

Gender of subjects

36.6

Age of subjects

Mean 50.73 SD+10.207

Results

20-40 years

17.4

101 subjects those fulfilling the inclusion criteria were included in our study. 63.4 % were male in our study and 36.6 % were female. Minimum age was 23 years and maximum age was 70 years with a mean age of respondents was 50.73 years SD + 10. 17.8 % of the respondents were between age group 20-40 years, 67.3 % of the respondents were between age group 41- 60 years and 14.9 % of the respondents were between age group 61 years and above. Mean duration of illness was 2.86 years with minimum duration of one year and a maximum duration of 15 years. Mean serum bilirubin level was 2.96 SD + 3.7904 with minimum value of .20 to maximum of 19.30. Mean serum AP level was 182.57 SD + 160.976 with minimum value of .20 to maximum of 19.30. Mean serum ALT level was 60.02 SD + 52.961 with minimum value of 10 to maximum of 305. . Mean serum AST level was 60.07 SD + 34.352 with minimum value of 23 to maximum of 228 IU. Mean serum Albumen level was 4.378 SD + 160.976 with minimum value of 1.8 to maximum of 15.0 mg/dl. Mean liver size was 12.261 with SD + 2.7145 with minimum 1.2 and maximum 18.3. Mean portal vein size was 1.662 SD + 2.3247 minimum of 1.0 and maximum of 16.8. Mean spleen size was 71.71 SD + 32.226 with a minimum of 4 and a maximum of 176. 62.4 % had splenomegaly, 66.3 % had Ascites, 56.4 % had bruising and bleeding, 62.4% had varices. 40.6 % had jaundice, 46.5 % had hepatic encephalopathy. 20.8 % had sharp edge 48.5 % had mildly blunted edge and 30.7 % had blunt edge, 11.9% had smooth edge. 33.7% had mildly irregular edge, 39.6 % had irregular edge and 14.9 % had highly irregular edge. Regarding liver parenchymal structure 13.9 % had fine , 22.8 % had mildly coarse, 48.5 had coarse and 14.9 % had highly coarse liver parenchymal structure.15.8 % of subjects had mild fibrosis (score 0 -2) , 55.4 % had moderate fibrosis (score 3 -5) , 28.7 % had severe fibrosis (score 6 -8)

41-60 Years

67.3

61 years and above

14.9

Splenomagaly

62.4

Accites

66.3

Bruising and bleeding

56.4

Varice

62.4

Jaundice

40.6

Hepatic encephlogathy

46.5

Sharp

20.8

Mildly blunted

48.5

Blunt edge

30.7

Smooth

11.9

Mildly Irregular

33.7

Irregular

39.6

Highly irregular

14.9

Mildly Coarse

13.9

Coarse

22.8

Highly Coarse

48.5

Male

14.9

Mild fibrosis (0-2)

15.8

Moderate fibrosis (2-5)

55.4

Sever fibrosis (6-8)

28.7

Discussion

varying degrees of hepatic fibrosis ranging from no fibrosis to cirrhosis. Yoshida et al revealed that the

Sign and symptoms

Liver edge

Liver surface

Fine

Scoring

Chronic liver diseases with viral infection manifest 32

Esculapio - Volume 07, Issue 01, January-March 2011

Annual incidence of hepatocellular carcinoma increased from 0.5% among patients with the stage F0 or F1 fibrosis to 7.9% among the patients with stage F4 fibrosis [13]. It has thus become increasingly apparent that the fibrosis stage is a key factor in defining the prognosis and management of chronic liver diseases with a viral infection. The gold standard in hepatology for the diagnosis of the fibrosis stage has been a histological liver evaluation based on specimens taken either by a needle biopsy or at operation. Recently, non-invasive and reliable assessments for monitoring chronic liver disease 14-16 using the platelet counts aspartate aminotransferase (AST)/alanine aminotransferase 15,16 (ALT) ratio, and serum hyaluronan and type III procollagen amino-terminal peptide17 have been developed. However, none of the currently available tests or modalities can completely replace a histological analysis. Previous studies have assessed several methods for evaluating the fibrosis stage of chronic liver disease using various US parameters. However, there have so far been few studies concerning the accuracy in detecting the signs of 5,18 5 compensated cirrhosis by US Gaiani et al and 19 Hung et al proposed a complex US scoring system using indices of the liver surface, parenchymal echogenecity, the vessel pattern, spleen size etc. to determine the fibrosis stage. In addition, recent advances in ultrasound technology have now made it possible to obtain more precise information about the liver surface, edge and parenchymal texture.8 Our study attempt to assess the US scoring system with a newly developed US equipment based on the conventional parameters of the liver edge, surface and parenchymal texture might obtain sufficiently accurate results in comparison with the histological findings for fibrosis obtained by a liver biopsy. Our study found out 20.8 % had sharp edge 48.5 % had mildly blunted edge and 30.7 % had blunt edge, 11.9% had smooth edge. 33.7% had mildly irregular edge, 39.6 % had irregular edge and 14.9 % had highly irregular edge. The liver parenchymal structure was fine in 13.9 %, 22.8 % had mildly coarse, 48.5 had coarse and 14.9 % had highly coarse liver parenchymal structure.15.8 % of subjects had mild fibrosis (score 0-2) , 55.4 % had moderate fibrosis (score 3 -5) , 28.7 % had severe fibrosis (score 6 -8) With conventional US, the liver surface has been most commonly utilized as a sole indicator for the 5,20,22 diagnosis of cirrhosis. However, numerous

papers have reported that the sole factor of the liver surface can not sufficiently distinguish cirrhosis from chronic hepatitis. Gaiani et al confirmed that the stage of cirrhosis may be underestimated when based on a single specimen and clarified that only two US variables, namely liver surface nodularity and the portal vein mean flow velocity, independently 5 contributed to the diagnosis of cirrhosis. An irregular and nodular liver surface may be easily assessed in patients with decompensated liver cirrhosis, particularly in the case of ascites, and it has been observed in 88% of unselected patients with cirrhosis [20]. Gaiani et al reported the findings of a US scoring system, based on the liver, spleen and portal vein features, which identified cirrhosis in 82.2% of the cases [5]. In our study, 20.8 % had sharp edge 48.5 % had mildly blunted edge and 30.7 % had blunt edge, 11.9% had smooth edge. 33.7% had mildly irregular edge, 39.6 % had irregular edge and 14.9 % had highly irregular edge. Although our study was limited on account of the relatively small number of patients due to the strict inclusion criteria but our scoring system for correctly predicting cirrhosis was found to be very accurate and the score proposed in our study is easy to obtain and can be applied in every ultrasound laboratory by utilizing regular commercially available US equipment. Our scoring system based on three parameters such as the liver edge, surface and parenchymal texture was able to accurately predict the fibrosis stage (correlation coefficient of 0.9524), especially when distinguishing chronic hepatitis from compensated liver cirrhosis.

Conclusion The study demonstrated that US scoring system is clinically useful for differentiating patients who have chronic liver disease with minimal or no fibrosis from those with mild to severe fibrosis. These parameters may also be useful for providing prognostic information and also for determining the optimal therapeutic options during the follow-up of patients with chronic liver disease, especially in patients with chronic hepatitis C. . Department of Radiology SIMS/Services Hospital, Lahore.

theesculapio@hotmail.com www.sims.edu.pk/esculapio.html.

Esculapio - Volume 07, Issue 01, January-March 2011

References 1. Fontana RJ, Lok ASF. Noninvasive monitoring of patients with chronic hepatitis C. Hepatology 2002;36:S57S64. 2. Dohmen K, Shirahama M, Onohara S, Miyamoto Y, Torii Y, Irie K, et al. Differences in survival based on the type of follow-up for the detection of hepatocellular carcinoma: an analysis of 547 patients. Hepatol Res 2000;18:11021. 3. Dohmen K, Shigematsu H, Irie K, Ishibashi H. Trends in clinical characteristics, treatment and prognosis of hepatocellular carcinoma. Hepato-Gastroenterology 2003;50: 18727. 4. Celle G, Savarino V, Picciotto A, Magnolia MR, Scalabrini P, Dodero M. Is hepatic ultrasonography a valid alternative tool to liver biopsy? Report on 507 cases studied with both techniques. Dig Dis Sci 1988;33:46771. 5. Gaiani S, Gramantieri L, Venturoli N, Piscaglia F, Siringo S, D'Errico A, et al. What is the criterion for differentiating chronic hepatitis from compensated cir rhosis? A prospective study comparing ultrasonography and percutaneous liver biopsy. J Hepatol 1997;27:97985. 6. Tüney D, Aribal ME, Ertem D, Kotilolu E, Pehlivanolu E. Diagnosis of liver cirrhosis in children based on colour Doppler ultrasonography with histopathological correlation. Pediatr Radiol 1998;28:85964. 7. Khan KN, Yamasaki M, Yamasaki K, Inoue O, Yatsuhashi H, Koga M, et al. Proposed abdominal sonographic staging to predict severity of liver diseases: analysis

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11.

12.

13.

14.

15.

with peritoneoscopy and histology. Dig Dis Sci 2000;45:55464. Nicolau C, Bianchi L, Vilana R. Gray-scale ultrasound in hepatic cirrhosis and chronic hepatitis: d i a g n o s i s, s c r e e n i n g , a n d intervention. Seminars in US, CT and MRI 2002;23:318. Kutcher R, Smith GS, Sen F, Gelman SF, Mitsudo S, Thung SN, et al. Comparison of sonograms and liver histologic findings in patients with chronic hepatitis C virus infection. J Ultrasound Med 1998;17:3215. Joseph AEA, Saverymuttu SH, Al-Sam S, Cook MG, Maxwell JD. Comparison of liver histology with ultrasonography in assessing diffuse parenchymal liver disease. Clin Radiol 1991;43:2631. Ichida F, Omata M, Tsuji T, Ichida T, Inoue K, Uemura A, et al. New Inuyama classification: new criteria for histological assessment of chronic hepatitis. Hepatol Com 1996;6:1129. Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:151320. Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: National surveillance program of cirrhosis and noncirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med 1999;131:17481. Ono E, Shiratori Y, Okudaira T, Imamura M, Teratani T, Kanai F, et al. Platelet count reflects stage of chronic hepatitis C. Hepatol Res 1999;15:192200 Luo J-C, Hwang S-J, Chang F-Y, Chu C-W, Lai C-R, Wang Y-J, et al. Simple blood tests can predict

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22.

compensated liver cirrhosis in patients with chronic hepatitis C. Hepato-Gastroenterolog y 2002;49:47881. Pohl A, Behling C, Oliver D, Kilani M, Monson P, Hassanein T. Serum aminotransferase levels and platelet counts as predictors of degree of fibrosis in chronic hepatitis C virus infection. Am J Gastroenterol 2001;96:31426. Guéchot J, Laudat A, Loria A, Serfaty L, Poupon R, Giboudeau J. Diagnostic accuracy of hy a l u r o n a n a n d t y p e I I I procollagen amino-terminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluated by ROC curve analysis. Clin Chem 1996;42:55863. R i c h a r d P, B o n n i a u d P, Barthélémy C, Étaix JP, Veyret C, Audigier JC, et al. Valeur de l'ultrasonog raphie dans le diagnostic des cirrhosis. J Radiol 1985;66:5036. Hung C-H, Lu S-N, Wang J-H, Lee C-M, Chen T-M, Tung H-D, et al. Correlation between ultrasonographic and pathologic diagnoses of hepatitis B and C v i r u s - r e l a t e d c i r r h o s i s. J Gastroenterol 2003;38:1537. Di Lelio A, Cestari C, Lomazzi A, Beretta L. Cirrhosis: diagnosis with sonographic study of the liver surface. Radiolog y 1989;172:38992 Ferral H, Male R, Cardiel M, Munoz L, Ferrari FQY. Cirrhosis: diagnosis by liver surface analysis with high-frequency ultrasound. Gastrointest Radiol 1992;17:748. Simonovsk V. The diagnosis of cirrhosis by high resolution ultrasound of the liver surface. Br J Radiol 1999;72:2934.

Esculapio - Volume 07, Issue 01, January-March 2011

Original Article

Cage Loosening In Tuberculosis Of Dorsal Spine Irfan Mehboob, Faisal Nazeer and Waqar Saleem Farooqi

Objective: To investigate the incidence of cage loosening in patients operated for tuberculosis of spine in different teaching hospitals. Material & Methods: This retrospective study was done on 50 individuals who had tuberculosis of dorsal spine with paraplegia and were operated. These patients underwent anterior decompression and cage fixation between 2000 and 2004.Those who had completed 4 years of follow up were included in the study. The diagnosis of loosening of cage was made on xrays which were available at the time of study. Results: Out of 123 cases operated between 2000 and 2004 for tuberculosis of dorsal spine, 50 were available for follow up. These patients were examined clinically and radiographically. Loosening was defined as a zone of osteolysis more than 2 mm around the cage on either view or cage displacement from its operative position more than 4mm.There were 31males and 19 females with age ranging from 21 to 70 years. Cage loosening was seen only in one patient (2%). 49 patients showed good results and were disease free. Conclusion: Cage loosening has not been noticed in our patients who were operated for T.B spine where anterior decomposition and cage fixation was done for treatment purposes. Key Words: Cage loosening, T.B spine. Introduction

may pass through the barrier of coverings of spinal cord and such inflammation may cause irreversible 7 type of paraplegia. Among others Rosenheim, Spiller and Gordon produced histological evidence of involvement of the cord and its coverings by the tuberculosis. In 1900 Menard described the operation of "Drainage Laterale." In 1935 Sir Herbert Seddon described a similar operation in the British Journal of Surgery which called as "costotransversectomy." This is also called Capner's procedure, because Norman Capner claimed that he instructed Herbert Seddon, how to carry out this operation. Medical and surgical 8,9,10 strategies can control the disease in most patients.

Tuberculosis of bones and joints is increasing all over the world and there is a reasonable increase in the incidence of T.B spine.Âš Spinal tuberculosis has existed for at least 5000 years. Incidence of spinal tuberculosis is rapidly increasing in developing countries because of poverty and drug resistance and in Europe and America because of HIV infection.Â˛ Hippocrates (460BC - 370BC) was the first to suggest a possible relationship between spinal deformity and pulmonary disease. Dale champs (1513), a French surgeon, added a very important factor by discovering 3,4 its relationship to paralysis of lower extremities. Hippocrates and Galen (131-21 AD) tried to correct kyphotic deformity due to tuberculosis of spine by manual pressure, traction and mechanical appliances but failed. The orthodox conservative treatment was entirely constitutional in its character and strongly advocated recumbency, immobilization by means of body casts, plaster beds and braces. Spinal tuberculosis has deformed, paralysed and killed many of the human races for the past 7000 years. No race is 5 immune to this disease. This initial trend in the 6 treatment of spinal tuberculosis was towards surgery. As early as 1779, Sir Percival Pott recommended "to reduce the dischargeâ&#x20AC;? meaning to drain the absences, and reduce erosion of the bones. In 1871, Michaud presented an illustrative histological evidence of the concept that tuberculosis infection in Pott's disease

Material and Methods Anterior decompression and cage fixation is a common procedure done for tuberculosis of spine with paraplegia. Out of one hundred and twenty three cases operated between 2000 and 2004, fifty were included in the study. Only those cases were included who had completed 4 years of follow up and were available at the time of study. All those included in the study had fulfilled the strict criteria of inclusion. Only those were included who had TB of dorsal spine between D6 & D12 vertebra and presented with paraplegia of more than one month. The patients with more than one level involved i.e. where disease involved more than two adjacent vertebrae were not

Esculapio - Volume 07, Issue 01, January-March 2011

included in the study. Where disease was associated with co-morbid hepatitis, conditions like diabetes mellitus and debilitating conditions were also excluded. Those who did not take anti-tuberculosis therapy for ten months in the follow up were also excluded. A questionnaire to know the patient satisfaction was also filled at the end of follow up period. The patients follow up was strictly according to criteria. ESR, LFT's and abdominal ultrasound was done to see any complications or side effects of anti tuberculosis therapy. Fresh x-rays were obtained at the time of study. The loosening of the cage was defined as radiological osteolysis of more than 2 mm around the cage or displacement of the cage more than 4 mm on either antero-posterior or lateral view. All x-rays were scrutinized carefully by two orthopedic surgeons and one radiologist. The operating surgeon did not comment on the x-rays to avoid bias. After careful review of the x-rays the data was entered in the computer for record and analysis.

out of thirty was below 10 gm%, while rest of the patients had normal haemoglobin. Patients with less than 10gm% were considered as anemic. In 8 patients (26.7%) out of thirty, total leukocyte count was raised (more than 10x109/liter). In all these cases, polymorph count was high, while lymphocyte count was normal. All patients (100%) had raised ESR. Mean was 71.63 mm/hour. Mantoux test was done in all cases. It was positive in twenty two patients (73.3%). An induration of 10 mm was taken as positive at end of 72 hours. Blood urea, creatinine and LFTS were performed in all patients before and after anti-tuberculous therapy (ATT) and during treatment once a month.

Discussion Although various approaches to the surgical management of spinal tuberculosis have been described, many patients in whom medical management has failed have been treated by debridement with or without grafting or internal 11 fixation. If debridement is supplemented with strut grafts and a prolonged course of chemotherapy is given the resultant deformity can be prevented.12 Graft dislodgement and slippage has been a persistent problem in these cases. Major concern in the treatment of caries spine includes the reduction of bone stock in diseased bone and an appropriate device to mechanically support the vertebral column, 13 weakened by caries. Titanium mesh cages were developed to prevent these problems. Titanium cage appears to be aptly suited for application in patient with severe kyphotic deformity.14 From mechanical point of view, anterior column should be appropriately approached anteriorly without any violation of the middle and posterior columns. The current choice of implant is titanium cage with appropriate and proper fixation to the vertebral endplate. The anterior debridement, bone grafting with stabilization of spine using titanium mesh cage instrumentation has been proved to be a reliable procedure.15 Titanium cage obviates the need for tricortical graft substitutes and avoids their associated risks. The placement of cages has been proven to have a lower hardware related complication rate than those associated with fibular strut grafts or tricortical 16 iliac crest grafts. Titanium mesh cage augmentation is a well established procedure for the surgical treatment of caries spine.16 Clinical improvement was seen in all patients in this study who underwent surgery. The outcome in those patients who presented within 3-4 months of paraplegia was

Results There were 31 males and 19 females with age ranging from 15 to 70 years. Cage loosening were seen only in one patient (2%). 49 patients showed good results and were disease free. Out of 50 patients in follow up study, twenty six (52%) patients were admitted through outpatient department and twenty four (48%) patients through accident and emergency department. Males predominated who were 60% and 40% were females. The ratio between male to female was 1.5:1 Minimum and maximum age of presentation was 15 years and 70 years respectively. The mean age was 32.57 + 14.9 years. The age of 23 patients (46%) was 36-45 years, age of nine patients (18%) was 46-55 years, age of 14 patients (28%) was 26-35 years and the age of 4 patients (8%) was 56-70 years. In the present study, backache was present in all patients (100%). All patients complained of diffuse pain in thoracic region, mild to moderate in intensity, gradual in onset which was more at night. Fever was present in nineteen patients (63.3%). It was mild to moderate in intensity usually not increased beyond 100 ยบ F. In none of patients, it was continuous in nature, persisting for a few hours during the day or night. There was no specific time of fever. Clinically all patients were pale (100%), were unable to walk associated with loss of control on bladder and bowel functions. Routine laboratory investigations were available for 30 patients. Haemoglobin in twelve patients (40%)

Esculapio - Volume 07, Issue 01, January-March 2011 17,18

better than those who came late. In the developing world, we should not be deterred by the duration of paraplegia and should offer such patients at least anterior decompression and titanium cage fixation with chemotherapy19regardless of the duration of paraplegia which is likely to arrest further progression of the deformity even if the paraplegia does not improve due to undue delay.20 Loosening of cage was seen in only one patient in our study.

Conclusion Cage fixation is the preferred surgical treatment in tuberculosis of spine. No statistically significant evidence of cage loosening has been seen in this study. It is recommended to use titanium mesh cage. Department of Orthopaedics SIMS/Services Hospital, Lahore

theesculapio@hotmail.com www.sims.edu.pk/esculapio.html

References 1. Fennelly PK, Martyny WJ, Fulton Ek. Cough generated aerosols of Mycobacterium tuberculosis: a new method to study infectiousness. Am J Respir Crit Care Med 2004; 169: 604-9. 2. Mehboob I. Surgical management of tuberculous spondylitis. Pak J Neurol Surg 2004; 8(1): 40-3. 3. Naveed M, Muhammad A, Qayyum H. Tuberculosis of spine ; pattern of the disease in Pakistan. Professional 2001; 5(2): 221.s 4. Ahmad M, Asif M, Manzoor S. Tuberculous spondylitis. Pak J Neurosurg 1998;4(2):79-81. 5. Daniel N, Lounis N, Ji B. Antituberculosis activity of once weekly rifapentine containing regimens in mice. Long term effectiveness with 6 & 8 months treatment regimens. Am J Respir Crit Cure Med 2000:161:1572-7. 6. Hodgson AR, Stock PE. Anterior spinal fusion for the treatment of tuberculosis of spine. J Bone Joint Surg 1960; 42-A: 295-310. 7. Jost B, Cripton PA, Lund T. Compressive strength of inter body cages in the lumbar spine: the effect of cage shape, posterior instrumentation and bone density. Eur Spine J 1998 ; 7 : 132-141. 8. Dvorak MF, Kwon BK, Fisher CG. Effectiveness of titanium

10.

11.

12.

13.

15.

mesh cylindrical cages in anterior column reconstruction after thoracic and lumbar vertebral body resection. Spine 2005 May 1; 28(9):902-8. Moon MS , Woo Yk , Lee KS. Posterior instrumentation and anterior inter body fusion for tuberculous kyphosis of dorsal and lumbar spines. Spine 1996; 21 (15):1840-1. Hodgson AR, Stock FE. Anterior spinal fusion: a preliminary communication on the radical treatment of Pott's disease and Pott's paraplegia. Br J Surg 1956; 44:266. Ahmad S, Rehman OU. Surgical option in caries spine: new concepts and innovations. J Pak Orthoped Assoc 2005;17(1):1-9. Zhao JZ. Posterior inter body fusion using postero-lateral placement of a single cylindrical threaded cage. Spine 2000; 25(4):425-30. Uchid K, Kobayashi S, Nakajima H, Kokubo Y, Yayama T, Sato R, et al. Anterior expandable strut cage replacement for osteoporotic thoraco-lumbar vertebral collapse. J Neurosurg Spine 2006;4:454-62. Zhang M, Li W. Treatment of multi segmental spinal tuberculosis by using focal debridement and internal fixation with CD rod. Zhonggue Xiu Fu

16.

17.

18.

19.

20.

Chong Jlan Wal Ke Za Zhi 2004; 18:171-3. Laheri VJ, Badhe NP, Dewnany GT. Single stage decomposition, anterior inter body fusion and posterior instrumentation for tuberculous kyphosis of the dorsolumbar spine. Spinal Cord 2001; 39:429-36. Shi PH, Zhang J, Fan SW, Zhao K, Wan SL, Huang Y, et al. Anterior instrumentation for the treatment of tuberculotic spinal deformity. Zhonghua Wai KA Za Zhi 2003;41:292-5. Medical Research Council Working party on Tuberculosis of the Spine. A controlled trial of anterior spinal fusion and debridement in the surgical management of tuberculosis of the spine in patients on standard chemotherapy: a study in Hong Kong. Br J Surg 1974;61:853-66. Parathasarathy R, Sriram K, Santha T. Short course chemotherapy for tuberculosis of the spine: a comparison between ambulant treatment and radical surgery ten year report. J Bone Joint Surg Br 1999;8:464-71. Narotam PK, Pauley SM, Mc Ginn GJ. Titanium mesh cages for cervical spine stabilization after corpectomy : a clinical and radiological study. J Neurosurg 2003; 99:172-80..

Esculapio - Volume 07, Issue 01, January-March 2011

Original Article

A Morphological Study Of Common Carotid Arteries in Atherosclerosis Amjad Naeem and M. Riaz Hussain

Objective: To review the pattern of atherosclerosis in common carotid arteries Material & Methods: The pattern of atherosclerotic lesions was studied in common carotid arteries in 30 human autopsy cases. This study was conducted in the mortuary of King Edward Medical College, Lahore. Both the right and left carotids of all 30 cadavers were opened and reviewed both grossly and microscopically. Results:The fatty streaks were present in 10 cases in the right common carotid artery and 10 cases in the left common carotid artery. The fibrolipid plaques were seen in 9 cases in the right common carotid artery and 9 cases in the left common carotid artery. The complicated lesions were present in 5 cases in the right common carotid artery and 6 cases in the left common carotid artery. In the right common carotid artery 4 cases showed ulceration and one case showed intimal vascularization and haemorrhage alongwith thrombus formation. In the left common carotid artery 4 cases showed ulceration and 2 showed intimal vascularization and haemorrhage alongwith thrombus formation. The calcified lesions were seen in 4 cases in the right common carotid artery and 5 cases in the left common carotid artery. The morphological changes in media and elastic were present in 6 cases in the right common carotid artery and 7 cases in left common carotid artery. Conclusion: This study shows that raised atherosclerotic lesions are reasonably common in our population and stresses the need to conduct larger studies to comment on the relationship with age and sex. Key Words:Atherosclerosis, Carotid arteries, Plaques

Introduction

artery for histological examination. Tissue processing was done. On the average, 7-8 slides were prepared from each block by taking ribbons of tissues . The paraffin sections were stained using Haematoxylin and Eosin stain, Curtis's Picro-ponceau stain, Verhoeff's elastic tissue stain, von kossa's staining technique, periodic acid Schiff (PAS) reaction, Toludine blue stain and Peral's Prussian blue stain.

Depolymerisation of acid-mucopolysaccharides involved in the plaque formation results in the loss of metachormasia of the ground substance. After that the visible fibers crumble and dissolve completely and replaced by lipid droplets and cholesterol.1 In ulcerated atheroma, extensive foma cell are formed that are connected by fibrin mesh.2 Intimal thickening causes hypoxia of mis-zone of media. This provides the stimulus for the ingrowth of capillaries from the adventitial vessels into the thickened intima. Thrombosis may occur on an ulcerating atheroma.3 In atherosclerosis fine granules of calcium appear in the ground substance and the necrotic tissues at the marginal layer of ulcers. The relative attenuation of the media is due to the disintegration of the elastic fiber system in the inner layer of the medial coat.4

Results Gross Appearances The fatty streaks were present in 10 of the 30 cases in the right common carotid artery and 10 of the 30 cases in left common carotid artery. They were distributed along the long axis of the vessel wall. The fibrolipid plaques were seen in 12 cases in the right common carotid and in 12 cases in left common carotid artery. The complicated lesions were present in 3 cases in the right common carotid artery and 4 cases in the left common carotid artery. In the right common carotid artery the ulceration was seen in 2 cases and thrombus formation in one case. In left common carotid artery the ulceration was seen in only 2 cases, intimal vascularization and haemorrhage in one and thrombus formation in one. The calcified

Material And Methods A total of thirty human autopsies were carried out during this study . The autopsies were done in the mortuary of the King Edward Medical College, Lahore. Right and left common carotid arteries were taken out and opened lengthwise. One to four sections were taken from each common carotid 38

Esculapio - Volume 07, Issue 01, January-March 2011

lesions were seen in 3 cases in the right common carotid artery and 4 in left common carotid artery. The number of raised lesions in the right common carotid artery was 1-3 and in the left common carotid artery was 2-3. The size of the largest raised lesion was 3x5mm and that of the smallest raised lesion was 3x3 mm. The raised lesions were distributed irregularly within 1 cm of the beginning of the right common carotid artery and of the ostia in left common carotid in these cases (Table No.1).

lesions. The complicated lesions were present in 5 cases in the right common carotid artery and 6 cases in the left common carotid artery. In the right common carotid artery 4 cases showed ulceration and one case showed intimal vascularization and haemorrhage alongwith thrombus formation. In the left common carotid artery 4 cases showed ulceration and 2 showed intimal vascularization and haemorrhage along with thrombus formation. In ulcerated lesions the lipid contents were less in amount. Foam cells with fibrin were present abundantly. A lymphocytic reaction with granulation tissue was seen in the lesion. In cases showing intimal vascularization and haemorrhage, deposits were also present at the junction of media and atherosclerotic lesions (Fig No. 2). In atherosclerotic lesions showing thrombus formation the fibrin strands were present at the

Microscopic Changes The fatty streaks were present in 10 cases in the right common carotid artery and 10 cases in the left common carotid artery. On histological examination of the fatty streaks the foam cells along with the increase of fluid was present in the intima. Lipid was present both intra-cellularly and extra-cellularly along with the connective tissue changes. The fibrolipid plaques were seen in 9 of the 12 cases found on gross appearance in the right common carotid artery and 9 of the 12 cases found on gross examination in the left common carotid artery. The fibrolipid plaques showed fibrous degeneration and regeneration with mucoid changes (Fig. No.1). There was a meta chromatic change and hyalinization in the atherosclerotic lesion. Number of foam cells were prominent and the number of fibrocytes was also increased. Fat was present in the form of fatty pool and the needle-shaped cholesterol crystal clefts were also demonstrated. Variable number of foam cells was present with the necrotic area at the base of the

Fig-1: Photomicrograph showing regeneration of collagen fibrils in fibrolipid plaque in athersclerotic lesion. Curtisâ&#x20AC;&#x2122;s Picro-Ponceau stain Â´550.

Table-1: Atherosclerotic lesions in common carotid arteries in relation to age and sex (gross findings) (30 cases). Age in years Fatty Streaks R L

Fibrolipid Plaques R L

Calcified Lesions R L

M:F -

1:0

3:33

1:1

3:0

56 - 65

2:2

1:0

2:0

1:0

2:0

66 - 75

1:1

76 - 85

Total

6:4

8:4

2:1

3:1

2:11

3:1

Percentage

20:13.33

26.66:13.33

6.66: 3.33

10:3.33

6.66:3.33

10:3.33

6 - 15

M:F -

16 - 25

26 - 35

3:1

36 - 45

3:3

46 - 55

R=Right, L = Left

M:F -

Complicated Lesions R L

M= Male, F=Female

Esculapio - Volume 07, Issue 01, January-March 2011

severely degenerated. The fragmented internal elastic lamina was separated. The fragmented internal elastic lamina was separated apart and was totally deficient over wide areas at the base of large plaques (Table no. 2).

Fig-2: Photomicrograph of an atherosclerotic lesion showing haemorrhagic area (arrow). Hematoxylin and eosin Â´ 80.

periphery and in between the platelet aggregates (Fig. No. 3). The calcified lesions were seen in 4 cases in the right common carotid artery and 5 cases in the left common carotid artery. The calcified masses were deposited in degenerated debris and hyalinized collagen tissue in the intima. Deposits of calcium were particularly present around the necrotic areas, lipid pool and marginal layers of ulcers in atherosclerotic lesions. The morphological changes in media and elastic were present in 6 cases in the right common carotid artery and 7 cases in left common carotid artery. The medial coat was relatively attenuated below the sclerotic plaque and was one half or less of the thickness of the media in the adjacent part of the artery. The fibres on the inner third of media were

Fig-3: Photomicrograph showing areas of haemorrhage and massive haemosiderin deposition in a thrombotic common carotid artery. Perlâ&#x20AC;&#x2122;s Prussian blue stain Â´350.

Discussion Gross morphology of Atherosclerotic lesions The fatty streaks were distributed along the long axis of the vessel wall. The number of raised lesions in the right common carotid artery was 1-3 and in the left common carotid artery was 3 x 5 mm and that of the smallest raised lesions was 3x3 mm. The raised lesions were distributed irregularly within 1cm of the beginning of the right common carotid artery and of the ostia in left common carotid in these cases.

Table-2: Atherosclerotic lesions in the common carotid arteries in relation to age and sex (microscopic findings) (30 cases). Age in years Fatty Streaks R L

Fibrolipid Plaques R L

Calcified Lesions R L

M:F -

1:0

3:3

1:1

1:0

56 - 65

2:1

1:1

2:1

1:0

2:0

66 - 75

1:1

76 - 85

Total

6:4

6:3

3:2

4.2

3:11

4:1

Percentage

20:13.33

20:10

10:6.666

13.33:6.66

10:3.33

13.33:3.33

6 - 15

M:F -

16 - 25

26 - 35

3:1

36 - 45

3:3

46 - 55

R=Right, L = Left

M:F -

Complicated Lesions R L

M= Male, F=Female

Esculapio - Volume 07, Issue 01, January-March 2011

Microscopic Appearance of Atherosclerotic Lesions On the light microscopy, the fatty streaks showed the presence of foam cells beneath the endothelial lining. There was increase of fluid in the ground substance. In addition to these changes, the connective tissue was arranged in the form of loose mesh with some fibrin deposition.5 It seems likely that lipoproteins are transported across intact endothelial cells by 6 micro-pinocytosis. Lipid was present both intracellularly and extra-cellularly. Foam cells are smooth muscle cells containing lipids. Probably local adherence of the platelets at the endothelium releases Mitogenic Platelet factors into the arterial wall and causes some intimal smooth muscle cells 7 proliferation. In fibrolipid plaques both connective tissue and lipid changes were prominent. These changes were visible as mucoid swelling due to the presence of protein molecules and acid muco poly saccharides. In addition there was a meta chromatic change in the ground substance along with hyalinization. This change has previously been related to the increased amount of the ground substance.2 Alteration in intrinsic composition and molecular size of proteoglycans occurs in atherosclerotic lesion.8 The increase in the number of foam cells in fibrolipid plaques was probably due to increase in the smooth muscle cell proliferation and vacuolated forms.9 In such vacuolated cells the lipid containing inclusions have been associated with the structural elements of smooth muscle cells.10 The accumulation of foam cells has been demonstrated in experimentally induced atherosclerosis.11 The number of fibrocytes is increased during plaque formation. It is associated with increased formation of collagen and elastic fibres. These connective tissue components are probably derived from the proliferating smooth muscle cells in the intima. There was high concentration of fibrin in developing 8 atherosclerotic lesion. It was established that there is an association between accumulation of fibrin and binding of low density lipoproteins (LDL).12 On the other hand it was proposed that the process of smooth muscle cell proliferation is related to the tumour formation initiated by mutation . The lipids were seen in the form of fatty pool and 13,14 needle-shaped cholesterol crystal clefts. LDL is important to the initiation and probably the 15,16 progression of atherosclerotic lesions. In the ulcerated lesions the lipid contents were markedly less

in amount. On the other hand foam cells were extensively present at the base and fibrin was seen 2 intervening these cells. The blood vessels were found in the intima. RBCs and haemosiderin deposits were present at the junction of media and atherosclerotic lesion. It was also explained that neo-vascularization in the intima may lead to haemorrhage because they run 4 the tissue that does not support them adequately. In thrombus formation platelet aggregation at the exposed sub endothelial tissue was seen. The fibrin strands were present at the periphery and in between the platelet aggregates. The collagen rich atherosclerotic lesion initiates thrombosis , because it exposes the blood to powerful platelet aggregating (collagen), and coagulation activating (traumatic surface and lipids) factors that are not found in normal vessel wall. Fibrinogen leads to the platelet ag gregation associated with release of vasoconstrictor, thromboxane A2. This hypercoagulability of platelets again is associated with hyperfibrinogenaemia and thrombosis. Lack of PG12 due to endothelial injury may lead to thrombus formation, because PG12 is powerful anti-aggregating vasodilator.12 Contrary to above mentioned observations it was described that 4 fibrous plaque is fibrinoid or organized thrombus. This study was supported by the observations that calcified granules were presented around the degenerated debris and hyalinized collagen tissue in 17 the intima. They also observed that deposits of calcium were particularly present at the periphery of necrotic areas, lipid pool and marginal layer of ulcers in atherosclerosis. The fibres on the inner third of media were severely degenerated. Internal elastic lamina was fragmented and was totally deficient over wide areas at the base of large plaques due to rigid pressure.1

Conclusion This study shows that raised atherosclerotic lesions are reasonably common in our population and stresses the need to conduct larger studies to comment on the relationship with age and sex.

Department of Pathology Akhtar Saeed Medical and Dental College Lahore

theesculapio@hotmail.com www.sims.edu.pk/esculapio.html 41

Esculapio - Volume 07, Issue 01, January-March 2011

References 1. Barker DJ, Winter PD, Osmond C. Weight in infancy and death from ischaemic heart disease. Lancet 1989; 2:577-80. 2. Oliveria SA, Ellison RC, Moore LL. Parent-child relationships in nutrient intake: the Framingham children's Study. Am J Clin Nutr 1992; 56:593-8. 3. Glagov S, Weisenberg E, Zarins CK. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987; 316:1371-5. 4. Kronmal RA, Mc Clelland RL, Detrano R. Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the MultiEthnic Study of Atherosclerosis (MESA). 5. Chironi g, Simon A, Denarie N. Determinants of progression of coronary artery calcification in asymptomatic men at high cardiovascular risk. Angiol 2002; 53:677-683. 6. Karen L, Margolis, Kay Dunn. Coronary Heart disease in moderately hypercholesterolemic, hypertensive black and non-black patients randomized to pravastatin versus usual care: the Antihypertensive and Lipid Lowering to Prevent heart Attack Trail (ALLAH-LLT). Am Heart J 2009; 158:948-55.

10.

11.

12.

13.

Ross R. Atherosclerosis: the role of endothelial injury, smooth muscle cell proliferation and platelet factors. Triangle 1976; 15:45. Edward, RD Jr, Bhandaru RR, Harold AR. Composition of proteoglycan from human atherosclerotic lesions. Exp Mol Pathol 1987;47:363-376. Gordon RC, Julie HC. Recent advance in molecular pathology: smooth muscle phenotypic changes in arterial wall homeostasis: implications for the pathogenesis of athero-sclerosis. Exp Mol Pathol 1985;42: 139-162. Catherine R. Rahilly-Tierney, Elizabeth VL. Cardiovascular benefit of magnitude of lowdensity lipoprotein cholesterol reduction: a comparison of subgroups by age. Circulation 2009; 120:1491-97. James EC, Mashtaq AK, Gregory C. Cytometric study of cholesteryl ester containing foam cells. II, analysis of aorta from cholestrol fed swine. Exp Mol Pathol 1987;46:52-63. Smith EB, Staples EM, Dietz HS. Role of endothelium in sequestraton of lipoprotein and fibrinogen in aortic lesions, thrombi and graft pseudo-intimsas. Lancet 1979; ii,812. Hoff HF, Heideman CI, Gaubatz

14.

15.

16.

17.

JW. Correlation of apolipoprotein B retention with the structure of atherosclerotic plaques from human aorta. Lab Invest 1978:38:560. Lewis JG, Richard G, Taylor BS. Endothelial surface characteristics in pigeon coronary artery atherosclerosis. Lab Invest 1982; 46:123. Ahmad A. Elesber, Margaret M. Redfield, Charanjit S, Coronary endothelial dysfunction and hyperlipidemia are independently associated with diastolic dysfunction in humans, Am heart J 2007; 153:1081-7. Takemichi, K., Masahiro , I., Hirohilko, H., et al. Comparison among Lipid constituents in Native LDL, ultra water soluble LDL, and Vessel wall and their significance in atherosclerosis. Experimental and molecular Pathology ;1987;47:166-174. Juan J. Ravera, Khurram Nasir, Ronit Katz, Relationship of Thoracic Aortic Calcium to Coronary Calcium and its Progression (from the MultiEthnic Study of Atherosclerosis [MESA]), am J Cardiol 2009; 103:1562-1567.

Esculapio - Volume 07, Issue 01, January-March 2011

Original Article

Causes Of Heart Failure - A Study In Cardiology Department of Pakistan Institute of Medical Sciences (PIMS), Islamabad Muhammad Ismail, Fazlul Aziz Mian, Iqbal S Khan, Asad Riaz, Shahid Nawaz Malik, Naeem Malik, Shafiq Arshad, Akhtar Ali, Mutahir Shah, Jamil Ahmad and Muhammad Nadeem

Objective: To find out causes of heart failure in patients who presented for echocardiography in PIMS Islamabad. Material & Methods: This observational study was carried out in 100 consecutive patients with history of dyspnea and abnormal echocardiography who reported to the Cardiology Department, PIMS, Islamabad. Results: Out of 100 patients, 43 were male and 57 were female. Fifty one percent patients were above the age of 50 years and only 21% were under 30 years of age. Hypertension was present in 51% patients while 22% had diabetes mellitus. Coronary artery disease was present in 26% cases and was the commonest cause of systolic dysfunction. Conclusion: Diastolic dysfunction was the leading cause of heart failure followed by myocardial infarction and rheumatic heart disease. Keywords: Heart failure, Diastolic dysfunction, Systolic dysfunction, Rheumatic heart disease, Hypertension, Coronary artery disease. Introduction

arrhythmias, infections, myocardial ischaemia, anaemia, alcohol excess, poor drug compliance, thyrotoxicosis, pulmonary embolism, pregnancy, iatrogenic causes, for example, postoperative fluid replacement or administration of steroids or nonsteroidal anti-inflammatory drugs.5 A recent United Kingdom (UK) survey of heart failure management in general practice found an average prevalence of 8.3 per 1,000 population. Prevalence was heavily age-dependent, ranging from 0.2 per 1,000 in those aged under 35, to 125 per 1,000 in those aged over 85. 6 The prevalence of asymptomatic left ventricular systolic dysfunction (LVSD) in the general population appears to be 7 ~3%. The syndrome of HF is a common manifestation of the later stages of various cardiovascular diseases, like coronary artery disease, hypertension, valvular disease and primary myocardial disease etc. Coronary artery disease and/or hypertension were implicatedas the cause of heart failure in over 90% of cases in the Framingham study.8 In UK general practice population, about 47% of men have coronary artery disease causing their heart failure, and in 46% of women, hypertension is the cause.6 Nearly half of patients with symptoms of heart failure are found to have a normal left ventricular (LV) ejection fraction (EF). This has been labeled as heart failure with a normal ejection fraction (HFNEF). As recent studies have shown that systolic function is not entirely

Heart failure (HF) is a complex syndrome of perplexing diversity both in its presentation and aetiology. HF is said to exist once heart fails to pump adequate quantity of blood needed for body. Congestive heart failure (CHF) is a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood through the body. Congestive heart failure is often undiagnosed due to a lack of a universally agreed definition and difficulties in diagnosis, particularly 1 when the condition is considered "mild." American College of Cardiology/American Heart Association (ACC/AHA) guidelines2 as well as 3 European Society of Cardiology (ESC) guidelines state that echocardiography is the single most useful test in the diagnosis of heart failure since structural abnormality, systolic dysfunction, diastolic dysfunction, or a combination of these abnormalities need to be documented in patients who present with resting or/and exertional symptoms of heart failure to establish a definitive diagnosis of heart failure. It is important to demonstrate an objective evidence of structural or functional abnormalities to explain patient's symptoms of heart failure since symptoms of heart failure are not specific and more than a third of patients with a clinical diagnosis of heart failure may not actually have heart failure. 4 Precipitating causes of heart failure include 43

Esculapio - Volume 07, Issue 01, January-March 2011

normal in these patients, HFNEF is the preferred term. 9 Morbidity and mortality rates in patients with HFNEF are high but not quite as high as in patients 10 with reduced systolic function. Peripartum cardiomyopathy (PPCM) is an uncommon form of congestive heart failure, afflicting obstetric patients around the time of delivery. It appears to be more common in twin pregnancy. The outcome is variable, 37.5% recovering normal left ventricular function, 12.5% mortality and persistently impaired left ventricular 11 function in the remainder. Left ventricular non compaction (LVNC) is a rare form of cardiomyopathy.12 In heart failure, diastolic dysfunction almost always accompanies systolic dysfunction. Along with systolic dysfunction, diastolic dysfunction plays a significant role in producing clinical features of HF. Diastolic dysfunction is an important independent marker of risk stratification and provides prognostic information independent of systolic HF. There is no decrease in the incidence or severity of rheumatic heart disease over a period of 25 years. The pattern of the disease has changed, with patients who had a previous surgery are now returning with valve dysfunction or related problems.13 Arrhythmias, thromboembolism, hepatic congestion and dysfunction, malabsorption, muscle wasting, pulmonary congestion, respiratory muscle weakness and pulmonary hypertension (rare) are important 16 complications of cardiac failure. Echocardiography represents the "gold standard" in the assessment of LV systolic dysfunction and in the recognition of systolic heart failure. Diastolic dysfunction plays a major role in signs and symptoms of HF and in the risk stratification, and provides

prognostic information independently in HF patients and impaired systolic function.14 Echocardiography offers comprehensive, noninvasive and relatively inexpensive tool for diagnosing cardiac pathology in the elderly. With an organized approach using twodimensional echocardiography and Doppler echocardiography, clinicians can determine the systolic and diastolic left ventricular performance, estimate the cardiac output, pulmonary artery, and ventricular filling pressures, and identify surgically correctable valve disease.15 Prognosis of HF is poor on the whole, with 5 year mortality varying from 26-75%. Heart failure accounts for at least 5% of medical hospital admissions in the UK and up to 16% of patients are back in hospital within 6 months of their first 16 admission. Even with the best therapy, heart failure is associated with an annual mortality of 10%.1 It is the leading cause of hospitalization in people older 17 than 65 years. In Pakistan, heart failure is a common syndrome encountered in clinical practice. No comprehensive nation wide data exists which gives in depth insight about this problem's magnitude, etiology, and clinical outcome. We at Pakistan Institute of Medical Sciences (PIMS) have made an effort in our Echocardiography unit of Cardiology Department to find out causes of heart failure in patients who present for echocardiography in this department. This can form basis for further work in this important field.

Material & Methods This observational study was carried out in Echocardiography unit of Cardiology Department (PIMS) Islamabad. One hundred consecutive

Table-1: Association of age, hypertension, diabetes and CAD with systolic and diastolic heart failure. Study population Systolic dysfunction 21

09%

06%

31-50

30%

34%

>51yrs

61%

60%

Diabetic

18%

40%

Non diabetic

82%

60%

Hypertensive

42%

83%

Non hypertensive

58%

17%

72%

28%

43%

57%

Distribution of Age <31yrs

Prevalence of DM

Prevalence of HTN

Diastolic dysfunction only

Prevalence of CAD CAD Non CAD

Esculapio - Volume 07, Issue 01, January-March 2011

subjects who presented with history of dyspnea and had abnormal echocardiography were included in the study by convenient non-probability sampling.

mixed stenosis and regurgitation. The distribution and grades of diastolic dysfunction in the study population has been depicted in table IV and in patients with systolic dysfunction has been depicted in table V. Rheumatic heart disease is very common in our population. In our study, it was the cause in 25% of the cases of heart failure and affected the younger age groups. The various rheumatic valvular lesions leading to heart failure in our study have been shown in table VI.

Inclusion Criteria: All patients who presented to Echocardiography unit of Cardiology Department in PIMS with dyspnea ranging from NYHA class I to IV. Exclusion Criteria: Patients who had history of lung disease and subjects with normal heart structure and function on echocardiographic study were excluded. Data Collection Technique: One hundred patients with history of dyspnea and abnormal echocardiography were studied. An informed consent was taken from each subject. Cause and severity of the cardiac failure were assessed based on relevant history, thorough physical examination and investigations. Systolic failure was defined as ejection fraction less than 50% determined by M mode echocardiography and Simpson method from 2 D echocardiography. Diastolic failure was graded based on pulse wave Doppler at mitral valve inflow as 'grade 0' when EA ratio was more than 1 but less than 2, and did not change with Valsalva maneuver, 'grade 1'when EA ratio was less than 1, 'grade 2' when EA ratio was again 1 to 2 but reversed with Valsalva maneuver or confirmed with tissue doppler from mitral annulus, 'grade 3' when EA ratio was more than 2 but changed with Valsalva maneuver, and 'grade 4' when EA ratio was more than 2 and did not change with Valsalva maneuver. The data was recorded on a pre designed performa.

Discussion The prevalence of heart failure increased with increasing age in our study which is in accordance with the international data.6 Females were more affected than males. Hypertension was more common (in 51% cases), and it also increased with age. Hypertension was present in 60% of patients

Table-2: Types of heart failure. Type of heart failure

No. of Patients

Pure systolic dysfunction

Systolic and diastolic dysfunction

Pure diastolic dysfunction

Total

100

Table-3: Causes of heart failure in the study population. Causes of cardiac failure

No. of Patients

Pure diastolic failure

Myocardial infarction

Rheumatic heart disease

Results:

Congenital causes

The association of age, hypertension, diabetes and CA with systolic and diastolic heart failure has been shown in table I. Out of 100 patients 43% (n=43) were male and 57 % (n=57) were female. Majority of the patients (51%) were above the age of 50 years and only 21% were under 30 years of age. Fifty one percent of the patients were hypertensive and diabetes was present in 22% of the cases only. Twenty six percent of the cases had history of coronary artery disease. The study population had pure systolic, pure diastolic and mixed heart failure. The distribution is shown in table II. The various causes of heart failure are shown in table III. Of the congenital causes, one patient had compacted LV, one had a PDA leading to heart failure and two patients had bicuspid aortic valves with

Dilated cardiomyopathy

Degenerative aortic valve disease

Peripartum cardiomyopathy

Table-4: Prevalence of grades of diastolic dysfunction in the study population. Grade of diastolic dysfunction

No. of Patients

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Table-5: Diastolic dysfunction in patients with systolic dysfunction. Grade

data, diastolic dysfunction is as common but rheumatic heart disease is much less common than in our population. Diastolic dysfunction can be assessed by Doppler echocardiography only; so 2D echocardiography must be combined with Doppler to assess patients with suspected LV dysfunction. This study was conducted in the echocardiography unit of a cardiology department, and is therefore not representative of the community where most of the patients with dyspnea and LV dysfunction are falsely treated for lung diseases and only few patients have access to health care facility. This study also did not include patients with acute pulmonary edema, whom being very critical could not be transferred to echocardiography unit.

No of Cases Percentage

(18%)

(43%)

(27%)

(12%)

(0%)

Table-6: Valvular lesions in rheumatic HD Valve lesion in rheumatic HD

No. of cases Percentage

Mitral stenosis (MS)

(35%)

Mitral regurgitation (MR)

(30%)

Mixed (MV) Mitral valve

(23%)

(AR) Aortic regurgitation

(4%)

Mixed (AV)

(4%)

Mixed valvular lesions

(4%)

Conclusion: Diastolic dysfunction is the commonest cause of cardiac failure followed by MI and rheumatic heart disease. Hypertension and diabetes are very common in diastolic dysfunction and need to be controlled. CAD is the commonest cause of systolic dysfunction and needs preventive strategies. Public awareness programs should be organized regarding rheumatic fever prophylaxis and treatment.

with diastolic dysfunction. Diabetes mellitus was common in patients with diastolic dysfunction as compared to systolic failure. Coronary artery disease (CAD) was present in one third of the cases and was the commonest cause of systolic dysfunction. According to our study, diastolic dysfunction was the leading cause of heart failure followed by MI and rheumatic heart disease. According to international

Department of Cardiology Pakistan Institute of Medical Sciences, Islamabad

theesculapio@hotmail.com www.sims.edu.pk/esculapio.html

References 1. Stefan N. The failing heart an engine out of fuel. N Engl J Med 356 (11): 1140-51. 2. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2005; 46:e1e82. 3. Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, et al. Task Force for the diagnosis and treatment of chronic heart failure of the European Society of Cardiology.

4. 5. 6.

Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005). Eur Heart J 2005; 26: 111-540. Oh JK. Echocardiography in heart failure: beyond diagnosis. Eur J Echocardiogr 2007;8:414. Watson RD, Gibbs CR, Lip GY. ABC of heart failure, Brit Med J 2000; 22; 320(7229): 2369. Majeed A, Williams J, de Lusignan S. Management of heart failure in primary care after implementation of the National Ser vice Framework for Coronary Heart Disease: a cross-sectional study. Public Health. 2005; 119(2):10511. McKelvie RS, Benedict CR, Yu s u f S. E v i d e n c e b a s e d

8. 9. 10.

11.

cardiolog y: prevention of congestive heart failure and management of asymptomatic left ventricular dysfunction. Brit Med J 1999; 22;318(7195):14002. Lip GY, Gibbs CR, Beevers DG. ABC of heart failure: aetiology. BMJ. 2000 ;320(7227):104-7. Sanderson JE. Heart failure with a normal ejection fraction . Heart 2007; 93:155-8 Hog g K, Swedberg K, McMurray J. Heart failure with preserved left ventricular systolic function; epidemiology, clinical characteristics, and prognosis. J Am Coll Cardiol 2004 ;43(3):31727. Prevalence and outcome of

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peripartum cardiomyopathy in Malaysia.. Int J Clin Pract. 2009;63(5):722-5. Epub 2007 Nov 19. 12. Sandhu R, Finkelhor RS, Gunawardena DR, Bahler RC. Prevalence and characteristics of left ventricular non compaction in a community hospital cohort of patients with systolic dysfunction. Echocardiography. 2008; 25(1):8-12. 13. Deshpande J, Vaideeswar P, Amonkar G, Vasandani S.

Rheumatic heart disease in the past decade: an autopsy analysis. Indian Heart J. 2002; 54(6):676-80 14. Ciampi Q, Villari B. Role of echocardiography in diagnosis and risk stratification in heart failure with left ventricular systolic dysfunction. Cardiovasc Ultrasound. 2007 2;5:34. 15. Sorrell VL, Nanda NC. Role of echocardiog raphy in the diagnostic assessment and etiology of heart failure in the elderly - opacify, quantify, and

rectify. Heart Fail Clin. 2007; 3(4):403-22 16. Cowie MR, Mosterd A, Wood DA. The epidemiology of heart failure. Eur Heart J. 1997; 18(2):208-25. 17. Krumholz HM, Chen YT, Wang Y, Vaccarino V, Radford MJ, Horwitz RI. Predictors of readmission among elderly survivors of admission with heart failure. Am. Heart J. 139 (1 Pt 1): 72-7. PMID 10618565.

Answer Picture Quiz 1. This x-ray chest shows left sided subcutaneous emphysema. There is no lung pathology seen; Commonly it is a complication of chest intubation (also called surgical ephysema) or chest trauma causing rib and lung injury. 2. The main physical findings are palpable and audible crepitus which may extend up to the neck risking the airway. In sever cases a charatrestic swelling is present. 3. In mild to moderate cases no complication develops. In severe cases there may be respiratory distress. 4. Mostly no active management is needed. In severe cases multiple superficial incisions are given to allow air to leak.

Case Report

Bernard-Soulier Syndrome and Dengue Fever: A Rare Association-Case Report Farrukh Iqbal, Bahjat Afreen and Mona Aiziz Gilani

Abstract: A 32-years-old pregnant woman who was a diagnosed case of Bernard-Soulier Syndrome; which is a rare hereditary disorder of qualitative and quantitative platelet defect with tendency to bleed spontaneously, developed dengue fever which resulted in marked thrombocytopenia. She was continuously monitored and managed conservatively. Luckily, she made an uneventful recovery. But this may not be the case always, and constant vigilance is required while treating patients of congenital disorders of platelet function with acquired thrombocytopenia. Keywords: Bernard-Soulier Syndrome (BSS), Dengue Fever (DF), Thrombocytopenia. Introduction â&#x20AC;&#x153;La dystrophie thrombocytaire-hemorragipare congenitaleâ&#x20AC;? was the term given to a congenital bleeding disorder by Bernard and Soulier in 1948. They described constellation of three features: prolonged bleeding time, extremely large platelets and thrombocytopenia in a young male patient who had tendency to severe spontaneous bleeding. It is now called Bernard-Soulier Syndrome (BSS).1 It has an autosomal recessive pattern of inheritance associated with consanguinity. Autosomal dominant 2 inheritance has also been reported in some cases. BSS is quite rare and the reported prevalence is less than 1 in a million with no gender preference. Until now cases have been reported from North America, Japan and Europe.3 The main biochemical defect in BSS is the deficiency of a glycoprotein platelet surface receptor. It is called GP Ib-IX-V complex and is made up of four polypeptides. It has two important roles in primary hemostasis. First, it mediates platelets adhesion to injured vessel wall by binding to von-Willebrand factor. Secondly, it facilitates thrombin at low concentrations to activate platelets. It might also have role in platelet turn over. Hence, its deficiency results in impaired primary hemostasis seen in BSS.4,

Case Report A 32 years old pregnant lady, house wife, who was a known case of Bernard-Soulier Syndrome (BSS) for the past 12 years, presented with complaints of fever for 1 week. Fever was high grade with severe backache and headache. She had no history of bleeding or bruising. Her obstetric history revealed that she was managed with platelet transfusion in her last

pregnancy during labor. Her family history was positive for BSS. On examination, she was febrile and had petechial rash on her arms and legs. She had no lymphadenopathy or hepato-splenomegaly. She was clinically and serologically diagnosed to have dengue hemorrhagic fever. Initially, her platelet count was 70 x 109/ul. It progressively fell down to 15 x 109/ul. She was strictly monitored for any spontaneous bleed. Fortunately, no complications arose. She recovered and platelets started rising as the febrile illness subsided.

Discussion Bernard-Soulier Syndrome is considered quite rare. This low prevalence may also be attributed to underreporting and misdiagnosis. In countries where consanguineous marriages are in practice, BSS may have high prevalence. In Iran, 97 cases of this syndrome have been reported and consanguinity was 6 a common factor in them. There is considerable variability in clinical profiles of BSS, between the individual patients and in the same patient over a period of years. Clinical manifestations vary from no to frequent episodes of epistaxis, mucocutaneous and gastrointestinal hemorrhage, hematuria, menorrhagia and life threatening bleeding during trauma, pregnancy and surgery etc. 7 Laboratory parameters which are characteristic of this syndrome include: (1) prolonged bleeding time. It may be marginally prolonged or as long as greater than 20 minutes. (2) A normal to very low platelet count even less than 30,000/ul. (3) Megakaryocytes on peripheral film, size ranging from 2.5um to 15-20um.2, 8 Defective vWF binding,

Absence of ristocetin induced platelet agglutination and inability to sheer induced platelet aggregation are the other features of this familial syndrome, distinguishing it from other congenital causes of 2 platelet disorders. Because of the variability of clinical manifestations, the course and outcome of a superadded acquired factor of coagulopathy cannot be predicted. As in this case, the patient suffered from dengue fever concurrently without any untoward effects. With a background of familial qualitative platelet disorder, thrombocytopenia induced by dengue virus made her more vulnerable to have spontaneous life threatening bleed therefore, such patients should be managed very carefully. Similarly, risk of hemorrhage is high during elective and emergency surgeries and in labor. Massive blood loss during menses may occur in such 9 patients. Pregnancy may be complicated by intraoperative bleeding, immediate and delayed postpartum hemorrhage, development of maternal antiplatelet anti-bodies leading to fetal intra-cranial hemorrhage and neonatal allo-immune thromb 10 ocytopenia. In patients with this disorder, wrong diagnosis and

wrong treatment is not uncommon. Most frequently BSS is misdiagnosed as ITP and wrongly treated with steroids and splenectomy which have not been documented to have played any pivotal role in the management of such disorder. The patient should be educated about his/her bleeding diathesis, avoidance of even minor trauma and should also avoid the use of anti-platelet drugs. There is no specific drug treatment for BSS; and prevention is the main stay of management. Prevention and control of a bleeding episode usually requires hormonal therapy for menorrhagia, platelet and/or blood transfusion during surgery, labor and life threatening hemorrhage.3 It is the responsibility of treating physician to keep all the above mentioned aspects in mind and show maximum vigilance while treating such patients and discourage consanguinity in such families. Department of Medicine Shaikh Zayed Hospital, Lahore.

theesculapio@hotmail.com www.sims.edu.pk/esculapio.html.

References 1. Bithell TC. Qualitative disorders of platelet function. In: Lee RG, Bithell TC, Foerster J, Athens J W, L u ke n s J N, e d i t o r s. Wintrobe's Clinical Hematology. Philadelphia: Lea & Febiger; 1993. p. 1403-04. 2. Coller BS, French DL. Hereditary qualitative platelet disorders. In: Beutler E, Litchman MA, Coller BS, Kipps TJ, Seligsohn U, editors. Williams Hematology. USA: McGraw Hill; 2001. P. 1560-63 3. Lopez JA, Andrews RK, AfsharKharghan V, Berndt MC. Bernard-Soulier Syndrome. Blood. 1998 June; 91(12): 43974418

4. 5.

Berndt MC, Founier DJ, Castaldi PA. Bernard-Soulier syndrome. Clin Haematol. 1989; 2:585. Belluci-Sessa S, Cean JP. Inherited platelet disorders. In: Hoff brand AV, Lewis SM, Tuddenham EGD, editors. Postg raduate Hematology. Italy: ButterworthHeinemann, 1999. p. 585-86. Toogeh G, Keyhani M, Sharifian R, Safaee R, Emami A, Dalili H. A study of Bernard-Soulier syndrome in Tehran, Iran. Arch Iran Med. 2010 Nov; 13(6):54951. Lanza F. Ber nard Soulier Syndrome (Hemorrhagioparous T hrombocytic Dystrophy). Orphanet J Rare Dis. 2006 Nov;

1:46. Wintrob MM. Clinical Hematology. 10th ed. USA: Lippincott Williams & Wilkins: 1999; p. 1663-66. 9. Hossain N, Farzana T, Khan NH, Shams TS, James AH. Adolescent menorrhagia due to platelet function disorder. J Pak Med Assoc. 2002 Feb; 60(2):1279 10. Peitsidis P, Pafilis I, Otomewo O, Tuddenham EG, Kadir RA. Bernard Soulier Syndrome in pregnancy: a systemic review. Hemophilia. 2010 Jul; 16(4):58491. 8.

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