Aggravation of gentamicin induced nephrotoxicity by ciprofloxacin

To evaluate histopathological changes of gentamicin induced nephrotoxicity in rabbits receiving the combination of ciprofloxacin and gentamicin compared with rabbits receiving gentamicin alone. Laboratory based Randomized controlled trial. Study was conducted in the department of Histopathology with the collaboration of the department of Pharmacology, Army Medical College Rawalpindi and National University of Sciences and Technology [NUST] Islamabad. Eighteen rabbits were used in this study. They were divided randomly into three groups. Each group contained six rabbits. Group 1 [control] was injected subcutaneously with 0.9% NaCl. The second group of animals was injected with gentamicin. The third group of animals was injected with the same dose of gentamicin and additionally ciprofloxacin. The findings were entered and analyzed with the help of histopathological [HP] score calculated by summing up the histological parameters through Microsoft excel and Graph pad Instat 3. Necrosis, congestion and inflammatory infiltrate were graded as absent, mild, moderate and severe. The score assigned was from 0 to 4 accordingly. Highest tubular necrosis grade [grade 3] and maximum inflammatory changes [moderate grade] were observed in 50% of rabbits of group 3, receiving combination of gentamicin and ciprofloxacin. p-values were significant <0.01. Combined administration of ciprofloxacin along with gentamicin in rabbits enhances adverse histopathological effects of gentamicin induced nephrotoxicity

Histomorphology of umbilical vessels at regions of low and high altitudes in Pakistan

Objective: To compare the kistomorphological characteristics of human umbilical cord ar high altitde [HA] area i.e. Skardu with those at low altillrde [LA] i.e. Rawalpindi in Pakistan. Materials and methods: This cross sectional cornparalive study was conducted in Anatomy department at Army Medical Gollcgt Rawalpindi, from October 2002 to April 2003. Eighty umbilical cords, forty each from normal cases a: LA and HA! were Included. The full depth samples of umbilcal cord were taken and stained wtth H and E. Dclailed hisromarphology of umbilical cord was studied and thickness of vessel walls via5 measured. Results: Mean thickness ol umbilical artcrics in two gmups was 630.73 5 10.27 Llrn and 534.58 c 8.17 prr., while r-rlcan ihickness of urnbilical vein in same groups was 365.55 + 10.49 urn arid 318.3+ 8.64 Jim respotlively. Tne qlianlitative difference belwccn mean lhickness of unibilical artcries and veins, in LA and HA grnups was statistically significant. Conclusion: Tht thickness d umbilical cord as well as umbilical vessels, was signi1ican:ly less in HA group as compared to LA group.

Diagnostic accuracy of pipelle biopsy in endometrial pathologies

To evaluate the diagnostic accuracy of Pipelle biopsy as compared to endometrium of hysterectomy specimen [gold standard] in various gynaecological abnormalities pertaining to endometrium. This validation study was carried out in the Department of Histopathology, Army Medical College in collaboration with Department of Gynaecology, Military Hospital Rawalpindi from Feb 2008 to Jan 2009. Consenting 100 patients undergoing hysterectomy for various indications at Military Hospital Rawalpindi during the study period fitting the inclusion criteria were incorporated. The preoperative Pipelle and subsequent hysterectomy samples were both delivered to the laboratory in 10% formal saline. Pipelle samples were embedded as such. From the hysterectomy specimen, three representative sections were taken from endomyometrium. Both the samples were processed in automated tissue processor. Paraffin blocks of Pipelle and gold standard were made in paraffin embedding machine. Through rotary microtome, 3-5 micrometer thickness sections were made. Sections were stained by haematoxylin and eosin in autostainer and then mounted. The slides were then examined by resident histopathologist and final diagnosis was given by consultant histopathologist. Endometrial hyperplasia without atypia was a frequent pathology detected on Pipelle accounting for 16% of all cases. Diagnostic accuracy of Pipelle sampling in chronic endometritis, endometrial hyperplasia

comparative analysis of coronary adventitial T-lymphocytes-an autopsy study

Recent clinical and histopathologic data suggests that inflammation plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. The intima has received much attention as a site of inflammation, while the adventitia has remained relatively unexplored. The aim of the present study was to investigate the frequency of inflammatory activity in the cap and shoulder region of unruptured, atherosclerotic lesions in coronary arteries and to correlate these findings with distribution of inflammatory cells in adventitia. The study was carried out in Histopathology Department, Army Medical College, Rawalpindi and National University of Sciences and Technology [NUST], from August 2008 to July 2009. Sixty-seven autopsy cases performed at Military Hospital Rawalpindi, Pakistan were selected. The cases were divided into study group and control group. Case group [n=35] included those where cause of death was ischemic heart disease. Those coronary arteries were taken as control [n=32] where atherosclerotic changes were found by chance [death without history of ischemic heart disease]. Plaques in each group were assessed by light microscopy and by immunohistochemistry. The ages of the deceased ranged from 38 to 49 years. Within study group, adventitial lymphocytes exhibited strong correlation with erosion, thrombus formation in culprit plaque [p=0.001]. No correlation was found between adventitial T-lymphocytes and erosion of plaque [p=0.700] in control group. In 72% of culprit plaques moderate staining for T-lymphocytes was observed in adventitia as well as intima. In control group, most of the cases contained scattered cells. Few cases of stable plaques revealed lymphocytes as clusters, both in adventitia and in intima. Adventitial inflammation may play a pivotal role for atherosclerotic lesion histology and atheroma instability. With the help of these autopsy findings, we hope to be able to reduce the incidence of culprit plaques related to inflammatory reaction in patients of ischemic heart disease

Site specific response to high cholesterol diet in aorta of rabbit

To compare the development of atherosclerotic changes in different parts of aorta in rabbits fed on high cholesterol diet. Experimental study. The Anatomy department of Army Medical College, Rawalpindi; from March 2009 to February 2010. Twenty adult Newzealand white rabbits were randomly allocated to two equal study groups. Group I was given regular lab diet and group II wras fed 2% high ch olesterol diet. After six weeks, aorta was excised from each animal. Cross sections were taken from each aortic part for microscopic examination. Rest of aorta was opened longitudinally and stained with Sudan IV for gross estimation of lesion. In contrast to group I, atherosclerotic changes developed in all the animals of group II but of varying intensity and site specificity. In cholesterol-fed rabbits, sudanophilic lesion score was significantly higher in arch versus descending thoracic or abdominal parts. Intimal thickening and intima to media ratio maximally increased in ascending part, followed by arch and then substantially decreased with increasing distance from heart. Ascending aorta and arch are the most atherosclerosis-susceptible aortic sites in cholesterol-fed rabbits

Assessment of atherosclerotic plaque vulnerability of coronary arteries in cases of sudden cardiac death

To study the plaque vulnerability in coronary arteries taken from autopsy specimens, of individuals dying of ischemic heart disease in our setup and to compare it with atheroma of those who died of non-cardiac causes. Case control study. Study was carried out in the department of Pathology [Histopathology], Army Medical College, Rawalpindi and National University of Sciences and Technology [NUST], from June 2008 to June 2009. Sixty coronary arteries having atherosclerosis, from autopsies of patients who died of sudden cardiac death were divided into case and control groups. Case group included thirty coronary arteries having atherosclerosis from autopsies of patients of whose death was attributable to Ischemic Heart Disease [IHD]. Control group included thirty coronary arteries where atherosclerotic changes were found by chance [death not attributable to ischemic heart disease]. Plaques were assessed for fibrous cap thickness, foam cells; mean percentage of inflammatory cells on Haemotoxylin and Eosin [H and E] stained slides whereas immunohistochemical [IHC] markers for T-Cells were done by IHC stain method. In present study, foam cells are significantly more in study group than in control group [P=0.007]. Fibrous cap thickness fulfilling the criteria of vulnerable plaque was more in study group as compared to control group [P<0.001]. The present study demonstrated that there was insignificant difference [P=0.152], in the mean percentage of inflammatory cells in case group and control group. An overall significant association was found between vulnerable plaque and death due to ischemic heart disease [P<0.001]. Patients dying of ischemic heart disease have more vulnerable plaque in their coronary arteries as compared to those dying from non ischemic cause. Although this is an autopsy study but the significance of in this study can be very important to guide cardiologists to identify patients at high risk of acute coronary syndrome and use new diagnostic modalities like intravascular ultrasonography and therapeutic strategies like genomic and proteomic techniques. This will help the early detection and treatment of such cases and may ultimately reduce the incidence of sudden cardiac death

Spectrum of atherosclerotic changes in deceased dying of non-cardiac cause

To study the pattern of coronary atherosclerosis in deceased of sudden death, dying of non cardiac cause. This descriptive study was carried out in the department of Histopathology, Army Medical College, Rawalpindi, from January 2009 to January 2010. Fifty autopsy specimens from 20 to 50 years old who died of non cardiac causes and had no history of cardiac disease. Coronary arteries were removed and examined for atherosclerotic plaques. Fifty autopsy specimens of coronary atherosclerosis who had died of non cardiac cause were included in the study. All were males with a median age of 38 years, with range between 20- 55 years. Analysis in different age groups revealed that advanced atherosclerotic plaques, progressed with age reaching a maximum of 62% by the age of 31-40 years, and in the same age group number of severe atherosclerosis seen was also high [16%]. This study showed that the frequency of atherosclerotic plaque was more after third decade. The study showed that in patients with sudden cardiac death due to non ischemic causes there is high frequency of atherosclerosis in coronary arteries in people of age group of 31-40 years. Although this is an autopsy study but the significance finding found in this study can be very important to guide the clinicians in reducing the traditional risk factors of coronary atherosclerosis. This will help the early detection and treatment of such cases and may ultimately reduce the incidence of sudden cardiac death

Correlation of steatosis with fibrosis and necro-inflammation in chronic hepatitis C infection in the absence of confounding factors

To assess the frequency and degree of hepatic steatosis in patients of chronic hepatitis C infection and determine its correlation with stages of fibrosis and necro-inflammatory grades. Cross-sectional study. The study was carried out in the Department of Pathology [Histopathology], Army Medical College, Rawalpindi, from March 2006 to March 2007. Patients who had undergone a liver biopsy for evaluation of hepatitis C virus infection were included in the study. Demographic characteristics and laboratory data were collected at the time of biopsy. First hundred biopsy specimens meeting the inclusion criteria were assessed for steatosis, necro-inflammation and fibrosis. Steatosis was present in 46 patients and graded as mild [41.3%], moderate [54.3%] and severe [4.3%]. An overall significant correlation was found between grades of steatosis with stage of fibrosis [p < 0.0001] but no correlation was found with necro-inflammatory grades. Only focal necrosis revealed weak correlation with grades of steatosis [p < 0.003]. These results suggest a possible role of the hepatitis C virus itself in the pathogenesis of steatosis and indicate its close relationship with fibrosis and focal degeneration in chronic hepatitis C. Necro-inflammation seen in liver biopsy is host immune reaction to hepatitis C virus and is not related to steatosis

Effects of amlodipine besylate on spermatogenesis in sprague dawley rats

To determine the effects of chronic treatment with amlodipine besylate on spermatogenesis in Sprague Dawley rats. Quasi experimental study. The study carried out in the department of Physiology, Army Medical College Rawalpindi in collaboration with the department of Pathology, Army Medical College and National Institute of Health, Islamabad during April 2007 and March 2008. Thirty male Sprague Dawley rats were divided into two groups; each comprising of 15 rats. Group A was given vehicle whereas group B was given amlodipine besylate [norvasc] by oral and gavage for 50 days along with standard rat diet. Testes were removed 24 h after the last experimental day and sectioned. The sections were stained by hematoxylin and eosin and examined microscopically. Results were analyzed on SPSS version 13. There were significant differences in mean tubular diameter and height of germinal epithelium of testes between amlodipine and vehicle treated rats. Long term treatment with amlodipine besylate [norvasc] results in suppression of spermatogenesis in male rats

Comparative analysis of estrogen, progesterone, C-ERBB-2 receptor status of age matched male and female breast carcinoma

To assess the estrogen receptor [ER], progesterone receptor [PR] status and Her-2/neu oncogene mutation in male breast carcinomas and to compare these prognostic markers with age matched female patients. This is a comparative descriptive study carried out in the department of Pathology [Histopathology], Army Medical College, Rawalpindi, with necessary collaboration with Armed Forces Institute of Pathology [AFIP], from January 2007 to January 2009. Twenty male patients were divided in different age groups and age group matched 20 female breast carcinoma cases were selected. Request forms and haematoxylin and eosin [H and E] stained slides were assessed for age of the patients, type and grade of the tumor. Tumors were graded according to the Nottingham Modification of Bloom-Richardson classification and Immunohistochemical scoring for ER and PR was done by H Scoring method. The c-erbB-2 scoring was done according to DAKO Scoring system. Forty [20 males and 20 females] patients of breast carcinoma were included in the study. Majority were having invasive ductal carcinoma. The predominant histological grade was grade-II. Statistically significant correlation, was found between the intensities of ER and PR in male patients as compared to female patients [p value =0.001] except in age group 26-35 where it was more in females [p value =0.001]. There was no significant difference in the c-erbB-2 scoring of both groups [p value >0.05]. Male breast cancers display distinct immunophenotypic features than in females, implying a different pathogenesis in the evolution and progression of this disease. This recognition may provide better-focused treatment strategies and improved survival

Histomorphology of terminal villi of human placenta at low and high altitude with emphasis on blood capillaries

This cross sectional study is designed to compare the histomorphological characteristics of human placenta at high altitude [HA] i.e. Skardu [8500 ft] with those at low altitude [LA] i.e. Rawalpindi [1800 ft]. Cross sectional comparative study. Place and duration of study: The study was conducted in the anatomy department of Army Medical College Rawalpindi, from October 2002 to April 2003. Eighty placentae, 40 each from normal cases at LA and HA, were included. Three full depth samples of placental tissue were taken. Histological study was done in Haematoxylin and eosin [H and E] and Periodic acid Schiff [PAS] stained sections. Detailed morphology of terminal villi was studied and number of capillaries was counted. The core of terminal villus in LA group contained few capillaries with considerable amount of stroma while in HA group it contained abundant dilated capillaries with very little stroma. Mean number of capillaries in LA and HA groups were 201.45 +/- 2.692 and 216.97 +/- 2.828 respectively. The capillaries in terminal villi were dilated and there number was significantly more in high altitude group probably showing adaptive changes in response to hypoxia

Histopathological study of benign Melanocytic naevi

To study the histological spectrum and types of benign melanocytic naevi and to observe unusual/atypical histological features in these lesions. An observational study with prospective data. 1st June 1997 to 30th June 1998 at department of Pathology PNS Shifa, Karachi. A total of 50 consecutive cases of melanocytic naevi were studied. Skin biopsies were taken by the Dermatologist from the patients with a primary clinical diagnosis of naevus/mole. Relevant data was recorded. Majority of cases 24[48%] were in the third decade with female preponderance [56%]. Commonest site was the face [66%]. Thirty percent cases showed lentiginous proliferation. Acanthosis was observed in 26% cases and effacement in 12%. Twelve percent cases showed mild patchy infiltration by the inflammatory cells. Foreign body reaction along with inflammation was seen in 8% cases. Nuclear pleomorphism with slight variation in size, shape and staining was observed in 8% of the lesions. No architectural disarray or other atypical histological features fulfilling the criteria of dysplastic naevus or malignancy were observed. Face was the most common site and intradermal naevus was the commonest lesion. Few histological features like lentiginous proliferation, multinucleated naevus cells, foreign body reaction, fatty infiltration, linear fibrosis and acanthosis were observed. However no cytological features for dysplasia or malignancy were present

Effects of free mobility verses restricted mobility on the degenerative changes induced by immobilization on the femoral articular cartilage of Rabbit knee

To produce degenerative changes by immobilization of rabbit Stifle [knee] joint in extension and then to see the subsequent effects of either free or restricted mobility on the femoral articular cartilage. An experimental study. This study was conducted from April 2006 to April 2007 at Army Medical College, Rawalpindi and National Institute of Health Sciences, Islamabad. In this study forty adult New Zealand white rabbits were divided into five groups. Groups I and II served as control and were euthanized at 4 and 8 weeks respectively. The left knee joints of the three study groups [III, IV and V] were immobilized in extension by plaster of Paris cast for 4 weeks. After the removal of cast free [IV] and restricted mobility [V] groups were remobilized for another 4 weeks. Following euthanasia, femoral articular cartilages were dissected and examined both macroscopically and microscopically. To evaluate the degenerative changes thickness of articular cartilage, chondrocytes number and semi quantitative Mankin's scoring was done. Immobilization in extension for four weeks produced significant degenerative changes that were evident on both gross and microscopic analysis. Animals in free mobility group showed surface irregularities, superficial ulceration, fibrillation and deep clefts reaching radial zone along with reduction in the staining of matrix. Restricted mobility group when compared with the free mobility group showed significant decrease in Mankin's score and also significant increase in cellularity. The thickness of the articular cartilage in restricted mobility group was although greater than free mobility group but statistically significant difference was not found [p value=.055]. Most peculiar feature of restricted mobility group was proliferation of chondrocytes with formation of clones and intense metachromasia around the clones, a tendency towards intrinsic repair. Early motion and free mobility exposed the injured articular cartilage to increased loads when normal activity was allowed. Moreover rest and restricted mobility for 4 weeks following immobilization allowed some restoration of structure of articular cartilage

Liver biopsy in chronic hepatitis C: An assessment of inter and intra-observer's variability

To evaluate the inter and intraobserver variability in the histological grading and staging according to modified Knodell scoring system. A cross-sectional comparative study. Histopathology department Army Medical College, Rawalpindi, Pakistan from June 2006 to December 2006, at the Slides and original reports of already reported chronic hepatitis C cases were retrieved from the case files. A total of 52 liver biopsies of patients were reevaluated by two pathologists. The inter and intraobserver reproducibility for grade of necroinflammation and stage of fibrosis were calculated by using kappa statistics. For grades of necroinflammation a substantial level of interobserver [kappa=0.802] and intra-observer [kappa= 0.749] reproducibility was found. Disagreement in the interobserver results was detected in 11.5% cases, with difference of only one grade in all the cases. Disagreement in the intraobserver diagnosis was noted in 15.4% cases, again with the difference of only one grade of necroinflammation. Similarly for the stage of fibrosis, a substantial level of interobserver [kappa= 0.66] and intra-observer [kappa=0.77] reproducibility was present. Main disagreement for interobserver results was of stage 2 and 3 fibrosis. For intraobserver stage of fibrosis, disagreement was found in 9 cases [17.3%]. There was disagreement in 6 of the 9 cases with fibrosis stage 3, where original histological stage was reported 4. There were 3 [5.8%] cases where presence of steatosis was missed [all in non-tabulated form of reports]. Substantial level of inter and intra-observer agreement can be achieved, both for the necroinflammatory grade and stage of fibrosis, if the scoring system of chronic hepatitis is strictly followed

accuracy of references in manuscripts selected for publication in Pakistan Armed Forces Medical Journal [PAFMJ]

To assess the accuracy of references cited in manuscripts accepted for publication in an issue of a scientific journal and to categorize these errors. An observational study. The study was conducted in the library of Army Medical College, Rawalpindi during September 2007. A total of 288 references listed in the references section of twenty manuscripts were examined. Journal references were compared with either the original articles or [s] obtained through MEDLINE and Pakmedinet. Book references were checked against the original book or bibliographical information obtained through Publisher`s catalogues and online catalogues of libraries. The total number of errors in the references were counted and categorized. Seventy [24.3%] of the 288 assessed references had no errors, while a single error occurred in 51[17.7%] and more than six errors were found in 22[7.64%] references. The author element was the most frequent error category, where 103[43.64%] references from journal and 26[63.41%] references from books contained the errors The primary responsibility of ensuring accuracy of references lies with the authors. However the continuous process of removing errors by reviewers and editorial team can reduce the error rate in the references