Pathology Commons^™

Efficacy And Safety Of The Six-Dose Regimen Of Artemether-Lumefantrine In Pediatrics With Uncomplicated Plasmodium Falciparum Malaria: A Pooled Analysis Of Individual Patient Data, M. Makanga, Zul Premji, C. Falade, J. Karbwang, E.A. Mueller, K. Andriano, P. Hunt, P.I. De Palacios

Pathology, East Africa

Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5-25 kg. A total of 544 patients with uncomplicated P. falciparum malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis. Analysis of day 28 cure rate based on the intention-to-treat and evaluable populations yielded corrected cure rates for the six-dose regimen of 93% and 96% compared with 61% and 76%, respectively, for the four-dose regimen (P < 0.0001 for both comparisons). Similarly high cure rates were achieved with the six-dose regimen in non-immune infants weighing as little as 5 kg. The six- and four-dose regimens were equally well tolerated. The main finding of this analysis is that the six-dose regimen of coartemether is safe and more efficacious than the four-dose regimen in children. Copyright © 2006 by The American Society of Tropical Medicine and Hygiene.

Significance Of Cytogenetic Abnormalities In Acute Myeloid Leukaemia, Mahadev S. Harani, Salman Adil, Ghulam Nabi Kakepoto, Zahida Khilji, Usman Shaikh, Mohammad Khurshid

Department of Pathology and Laboratory Medicine

Objective: To evaluate the role of karyotype in acute myeloid leukaemia (AML) as a predictor of response to induction chemotherapy.
Methods: A cross-sectional study was carried out at the department of Pathology and Oncology, Aga Khan University Karachi from January 2003 to January 2005. Newly diagnosed patients with denovo AML admitted to the hospital were included in the study. Diagnosis of AML was based on FAB criteria, immunophenotyping and cytogenetic studies. They were treated according to standard protocols (combination of anthracycline and cytarabine -3+7) and those who had acute promyelocytic leukaemia additionally received all- trans retinoic acid (ATRA). …

Relationship Between Antipyretic Effects And Cytokine Levels In Uncomplicated Falciparum Malaria During Different Treatment Regimes, Elisabeth Hugosson, Scott M. Montgomery, Zul Premji, Marita Troye-Blomberg, Anders Bjorkman

Pathology, East Africa

We have previously shown that both chloroquine and paracetamol (acetaminophen) have antipyretic activity during treatment of acute uncomplicated Plasmodium falciparum malaria in children 1-4 years old. Here, we studied if this effect was accompanied by changes in plasma cytokine levels. The 104 children were treated with either chloroquine or sulfadoxine/pyrimethamine (SP) alone, SP + chloroquine or SP + paracetamol for 4 days. Cytokine levels were determined days 0, 2 and 3, body temperature every sixth hour until 72 h and parasitemia once daily for 4 days. At admission, body temperature correlated with levels of IL-10, IFN-γ and IL-6, and parasitemia …

Screening For Cystic Fibrosis: The Importance Of Using The Correct Tools, Uzma Shah, Tariq Moatter

Department of Pathology and Laboratory Medicine

Background: Cystic Fibrosis (CF) is a potentially lethal genetic disorder. The most frequent mutation worldwide in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene is designated as the Delta F508 mutation. This mutation was found in only 33% of Pakistani patients studied. Since the common Pakistani mutations remain to be identified, appropriate screening tools are required to identify disease. Sweat chloride determinations remain the gold standard for diagnosing CF. This study was done to emphasize the importance of using the correct tests.
Methods: The study was conducted at the Aga Khan University Hospital. The CFTR delta F508 mutation was tested …

Blood And Body Fluid Exposure And Risk To Health Care Workers, Afia Zafar

Department of Pathology and Laboratory Medicine

No abstract provided.

M. Leprae Inhibits Apoptosis In Thp-1 Cells By Downregulation Of Bad And Bak And Upregulation Of Mcl-1 Gene Expression, Zahra Hasan, Mussarat Ashraf, Ali Tayyebi, Rabia Hussain

Department of Pathology and Laboratory Medicine

Background: Virulent Mycobacterium leprae interfere with host defense mechanisms such as cytokine activation and apoptosis. The mitochondrial pathway of apoptosis is regulated by the Bcl-2 family of proteins. Expression of Fas ligand and apoptotic proteins is found in leprosy lesions and M. leprae has been shown to activate pro-apoptotic Bcl-2 genes, Bak and Bax. However, the mechanism by which M. leprae modulates apoptosis is as yet unclear. We investigated expression of apoptotic genes in THP-1 monocytes in response to infection by M. leprae and non-pathogenic M. bovis BCG.
Results: M. leprae did not induce apoptosis in THP-1 cells, while BCG …

Waldenstrom's Macroglobulinemia Terminating In Acute Myeloid Leukemia, Safoorah Khalid, Salman Adil, Mohammad Khurshid

Department of Pathology and Laboratory Medicine

Waldenstrom's macroglobulinemia (WM) is a rare condition, accounting for approximately 2% of haematologic malignancies. The most common causes of death in these patients are progression of the malignant lymphoproliferative process, infection and cardiac failure. Acute leukemia is a rare event in the clinical course of WM. A number of case reports have documented the development of terminal acute leukemia in patients with WM following prolonged chemotherapy.

Role Of Ict Malaria Immunochromatographic Test For Rapid Diagnosis Of Malaria, Mahadev S. Harani, M.Asim Beg, Lubna Khaleeq,, Salman Adil, Ghulam Nabi Kakepoto, Mohammad Khurshid

Department of Pathology and Laboratory Medicine

Objective: To evaluate the sensitivity and specificity of immunochromatographic test (ICT) malaria p.f/p.v using microscopy as the gold standard diagnosis. Methods: Five hundred and sixty patients of both sexes and all age groups with clinical suspicion of malaria were studied. Venous blood was collected for microscopy and ICT. Thick and thin films prepared and stained with Leishman's stain were examined. ICT malaria test was performed and interpreted according to manufacturer's instructions. Data was analyzed using Epi-6.
Results: A total of 560 cases were studied, 339 males and 221 females with age ranges between 2 to 73 years. …

Fludarabine Induced Autoimmune Haemolytic Anaemia In A Patient With Chronic Lymphocytic Leukaemia, Naveen Naz Syed, Mohammad Khurshid

Department of Pathology and Laboratory Medicine

Autoimmune haemolytic anaemia following fludarabine is an uncommon complication and previously treated patients are at higher risk. We describe a case of 57- year old lady with chronic lymphocytic leukaemia; she received intermittent courses of alkylating agents and purine analogue, fludarabine. Reintroduction of fludarabine for her relapsing disease induced autoimmune haemolytic anaemia. Numbers of cases have been reported regarding autoimmune haemolytic anaemia following fludarabine administration, but none have been published from our part of the world. Normally T-cell suppresses autoreactive lymphocytes that can produce autoantibodies. Suppression of T-cells by fludarabine, in addition to the underlying disease process appears to be …

Clinico-Pathologic Features Of Chronic Myeloid Leukemia And Risk Stratification According To Sokal Score, Naveen Naz Syed, Mikal Usman, Gulnaz Khaliq, Salman Adil, Mohammad Khurshid

Department of Pathology and Laboratory Medicine

To compile the clinical and haematological parameters of chronic myeloid leukemia (CML) and risk stratification according to Sokal score in our population. A descriptive analysis. The Aga Khan University Hospital, during the period from August 1997 to August 2005. All patients with diagnosis of chronic myeloid leukemia treated as outpatient in haematology clinic, or admitted in haem-oncology wards in The Aga Khan University Hospital were included. Records were retrospectively analyzed for clinicopathologic features. Risk groups were assigned as per Sokal scoring. During the 8 years study period, 245 patients with chronic myeloid leukemia were analyzed, the median age of presentation …

Extra Pulmonary Uptake Of Tc-99m-Maa Perfusion Lung Scan As A Result Of Right To Left Intra Cardiac Shunt, Riffat Hussain, Maseeh-Uz-Zaman, Sohail Abrar Khan, M Nadeem Ahmad

Department of Pathology and Laboratory Medicine

Extra pulmonary accumulation of Tc-99m-macroaggregate of albumin (MAA) is rarely seen on perfusion lung scan, and has been reported in less than 4% of a study population of nearly 380 patients1. It occurs when the agent bypasses the lungs due to a right to left (R-L) cardiac or pulmonary shunt, when it is shunted to the portal vein before reaching the right atrium and ventricle of the heart, and when the agent is degraded to a submicron particle size.2 When a pharmaceutical problem is excluded, extra-pulmonary uptake implies unusual hemodynamics with a shunt.

Validity Of Frozen Section In The Diagnosis Of Breast Lumps: 5 Years Experience At The Aga Khan University Hospital., Naila Kayani, Nuzhat Sultana

Department of Pathology and Laboratory Medicine

Abstract

Objective: To determine the accuracy of frozen section in the diagnosis of breast lump. Methods: Frozen section diagnosis given in consecutive breast biopsies performed in 5 years in our laboratory was evaluated against the final pathology report of permanent sections. Results: The Aga Khan University Hospital Lab receives more than 400 cases per year for frozen section. Three hundred and nineteen consecutive frozen sections of breast lumps examined from 1999-2003 were considered for analysis. Age of patients ranged between 22 and 90 years (mean age 49 years). In 316 cases (99%) there was no difference between the frozen section …

Role Of Rapid Urease Test And Histopathology In The Diagnosis Of Helicobacter Pylori Infection In A Developing Country, Javed Yakoob, Wasim Jafri, Shahab Abid, Zaigham Abbas, Saeed Hamid, Muhammad Islam, Kashif Anis, Hasnain Ali Shah, Hizbullah Shaikh

Section of Gastroenterology

Background

The aim of this study was to determine the effect of commonly self-prescribed proton pump inhibitors (PPI) on the results of rapid urease test and histology for the diagnosis of H. pylori infection.

Methods

One hundred-nine consecutive patients with dyspeptic symptoms attending the endoscopy suite were enrolled in this study. Antrum biopsy specimens were collected at endoscopy for the rapid urease test (Pronto Dry, Medical Instrument Corp, France) and histopathology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and like-hood ratio of a positive and negative of Pronto Dry test were compared against histology. The gold standard …

Metanephric Adenoma: A Rare Benign Renal Tumour, Nausheen Yaqoob, Jai Pal Paryani, Naila Kayani, Mohammad Zafar Rafique, Raziuddin Biyabani

Department of Pathology and Laboratory Medicine

Metanephric adenoma is a rare benign renal tumour. We are reporting one histologically proven such case in a 23 year old male from Afghanistan. He presented with severe right flank pain since 3 weeks. Nephrectomy was done and histopathology was consistent with the diagnosis of metanephric adenoma. This novel renal mass has been reported to have benign clinical course despite its symptomatic presentation and large tumour size. There is no distinguishing radiological feature with can differentiate it from malignant tumours. So far, a uniformly benign clinical course has been associated with Metanephric adenoma, but given its relatively recent identification and …

Heterotopic Glial Tissue In Tonsil: A Case Report, Nausheen Yaqoob, Zubair Ahmed, Akhtar Husain

Department of Pathology and Laboratory Medicine

We describe a six month old boy with a mass in the left tonsil. It was present since birth and was enlarging progressively. It was completely excised. Histopathology showed a choristoma of neural origin composed of glial cells--astrocytes in a fibrillary background, and a choroid plexus. Immunohistochemistry confirmed the findings.

Lymphoepithelioma-Like Carcinoma Of Urinary Bladder: (Lelca), Nausheen Yaqoob, Naila Kayani, Jaipal Piryani, Mohammad Nasir Sulaiman, Sheema H. Hasan

Department of Pathology and Laboratory Medicine

Lymphoepithelioma-like carcinoma of the bladder (LELCA) is an uncommon neoplasm of the urinary bladder and up till now only 49 cases have been reported in the English literature. It is imperative to distinguish between lymphoepithelioma-like carcinoma and malignant lymphoma as primary bladder lymphoma is extremely rare. We report a case of a 55 year old lady who presented with the complaint of burning micturition and gross hematuria for the past 5 months. There were no other known comorbids. Pelvic ultrasound was normal. Cystoscopy showed a 4x4 cm sessile mass in the bladder. Histopathological examination was consistent with the diagnosis of …

To Compare The Total Cholesterol And Hdl-Cholesterol Before And After Ultra-Centrifugation In Lipemic Samples, Jawaid Jabbar, Imran Siddiqui, Syed Qaiser Raza, Ayaz Baig

Department of Pathology and Laboratory Medicine

Objective: It is an everyday routine in laboratories to encounter interference in the analysis of lipids. These likely interferences (hemolysis, icterus and lipemia) are countered by asking physicians and patients to send fresh and properly collected samples. At the Aga Khan University (AKU) Laboratory, we receive 2-3 lipemic/turbid samples per day. Previously it was our departmental policy to advise these patients to go for lipoprotein electrophoresis, which though accurate was time consuming and not cost effective. We therefore studied ultra centrifugation/airfuge as an alternate method to clear lipid interference and provide accurate, reliable and cost effective results.
Methods: Daily 2-3 …

Ductal Carcinoma In Situ (Dcis) In Karachi, Naila Kayani, Yasmin Bhurgri

Department of Pathology and Laboratory Medicine

Objective:
To study the frequency of ductal carcinoma in situ (DCIS) in a large pathology series. DCIS is a proliferation of non-invasive, malignant epithelial cells within the ductolobular system of the breast. It is a heterogeneous entity with several morphologic variants that differ in gross appearance, growth pattern, cytologic features, mammography, and malignant potential.
Methods:
The data of The Aga Khan University' Pathology Department, diagnosed on the basis of histopathology, during a 6-year period (1st January 1998 to 31st December 2003) was reviewed, all cases of DCIS studied, and data was analyzed with the help of analytical software SPSS.
Results: …

Trefoil Factor 2 (Tff2) Deficiency In Murine Digestive Tract Influences The Immune System, M. Baus- Loncar, J. Schmid, El-Nasir Lalani, I. Rosewell, R. A. Goodlad, H. G.W. Stamp, N. Blin, T. Kayademir

Department of Pathology and Laboratory Medicine

Background & Aims:

The gastrointestinal trefoil factor family (TFF1, TFF2, TFF3) peptides are considered to play an important role in maintaining the integrity of the mucosa. The physiological role of TFF2 in the protection of the GI tract was investigated in TFF2 deficiency.

Methods:

TFF2-/- mice were generated and differential expression of various genes was assessed by using a mouse expression microarray, quantitative real time PCR, Northern blots or immunohistochemistry.

Results:

On an mRNA level we found 128 differentially expressed genes. We observed modulation of a number of crucial genes involved in innate and adaptive immunity in the TFF2-/- mice. …

Psychomotor Skills For The Undergraduate Medical Curriculum In A Developing Country--Pakistan, Rashida Ahmed, Zoon Naqvi, Ineke Wolfhagen

Department of Pathology and Laboratory Medicine

Objective: To identify essential psychomotor skills for all the medical graduates of an undergraduate programme in Pakistan.
Materials and Methods: Twenty-five physicians practising in a tertiary care centre and ninety primary care physicians used a Likert's scale, ranging from "very essential" to"not required at all", to mark 99 psychomotor skills in the undergraduate medical curriculum in Pakistan.
Results: Overall the opinions of both the groups about the essential skills matched except for a few areas.
Conclusion: This study provides baseline data about psychomotor skills that a medical graduate in developing countries should be able to perform. Further studies will be …

Ovarian Primary Neuroendocrine Carcinoma Of Non-Small Cell Type: Report Of An Extremely Rare Neoplasm, Zubair Ahmed, Kanwal Aftab, Naila Kayani

Department of Pathology and Laboratory Medicine

Paraffin block sections of a uterus and ovarian mass from a 31 year old female were sent for second opinion to the Pathology Laboratory of Aga Khan University. Histologic examination and immunohistochemical features gave a diagnosis of primary neuroendocrine carcinoma of non-small cell type admixed with benign mucinous cystadenoma. This is a rare tumour with only eight being reported in literature.

Expression Of Hepatocyte Growth Factor And Its Receptor C-Met, Correlates With Severity Of Pathological Injury In Experimental Alcoholic Liver Disease., El-Nasir Lalani, Richard Poulsom, Gordon Stamp, Franz Fogt, Peter Thomas, Amin A. Nanji

Department of Pathology and Laboratory Medicine

Expression of hepatocyte growth factor (HGF) and its receptor, c-met is up-regulated in various forms of liver injury. This study evaluated the relationship between HGF and c-met expression and pathological changes in experimental alcoholic liver disease. Rats (5 per group) were fed ethanol and a diet containing saturated fat corn oil or fish oil by intragastric infusion. Dextrose isocalorically replaced ethanol in controls. In a second set of experiments, Kupffer cells, endothelial cells and hepatocytes were isolated from rats in each group. Pathological evaluation and analysis of HGF and c-met expression were performed in liver and the different cell types. …

Efficacy And Safety Of Artemether-Lumefantrine (Coartem®) Tablets (Six-Dose Regimen) In African Infants And Children With Acute, Uncomplicated Falciparum Malaria, C. Falade, M. Makanga, Zul Premji, C.E. Ortmann, M. Stockmeyer, P. Ibarra De Palacios

Pathology, East Africa

Approximately one million children die from malaria each year. A recently approved artemisinin-based tablet, Coartem (co-artemether), comprising artemether 120 mg plus lumefantrine 20 mg, given in four doses, provides effective antimalarial treatment for children in many sub-Saharan countries. However, this regimen is considered insufficient for non-immune infants and in areas where multidrug-resistant Plasmodium falciparum predominates. This open-label study assessed the efficacy and safety of co-artemether administered to 310 African children weighing 5-25 kg, with acute, uncomplicated falciparum malaria. Six doses of co-artemether were given over 3 days, with follow-up at 7, 14 and 28 days. Treatment rapidly cleared parasitemia and …

Plasma Zinc Concentrations Are Depressed During The Acute Phase Response In Children With Falciparum Malaria, C. Duggan, W.B. Macleod, N.F. Krebs, J.L. Westcott, W.W. Fawzi, Zul Premji, V. Mwanakasale, J.L. Simon, K. Yeboah-Antwi, D.H. Hamer

Pathology, East Africa

Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (<9.2 μmol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = -0.24, P < 0.0001) and the degree of parasitemia (r = -0.19, P < 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response. © 2005 American Society for Nutritional Sciences.

Habitat Characterization And Spatial Distribution Of Anopheles Sp. Mosquito Larvae In Dar Es Salaam (Tanzania) During An Extended Dry Period, M.A. Sattler, D. Mtasiwa, M. Kiama, Zul Premji, M. Tanner, G.F. Killeen, C. Lengeler

Pathology, East Africa

Introduction: By 2030, more than 50% of the African population will live in urban areas. Controlling malaria reduces the disease burden and further improves economic development. As a complement to treated nets and prompt access to treatment, measures targeted against the larval stage of Anopheles sp. mosquitoes are a promising strategy for urban areas. However, a precise knowledge of the geographic location and potentially of ecological characteristics of breeding sites is of major importance for such interventions.

Methods: In total 151 km2 of central Dar es Salaam, the biggest city of Tanzania, were systematically searched for open mosquito breeding sites. …

Familial Homocystinuria, F Bilwan, Na Syed, M Usman, Mohammad Khurshid

Department of Pathology and Laboratory Medicine

Two cases of siblings diagnosed as cases of familial homocystinuria are reported. Both the cases have classical presentation of familial homocystinuria including history of dislocation of lens of the right eye. Brother had history of psychomotor retardation while sister had a significant history of deep vein thrombosis. Levels of plasma homocysteine were elevated and urinary homocysteine was positive in both the cases.

Vi Antigen Expression In Salmonella Enterica Serovar Typhi Clinical Isolates From Pakistan, John Wain, Deborah House, Afia Zafar, Stephen Baker, Satheesh Nair, Claire Kidgell, Zulfiqar Bhutta, Gordon Dougan, Rumina Hasan

Department of Pathology and Laboratory Medicine

The accurate identification of Salmonella enterica subsp. enterica serovar Typhi variants that fail to express the capsular polysaccharide, Vi, is an important and much discussed issue for medical microbiology. We have tested a multiplex PCR method which shows the presence or absence of the genetic locus required for Vi expression. Of 2,222 Salmonella serovar Typhi clinical isolates collected from patients' blood over a 4-year period in a region of Pakistan where typhoid is endemic, 12 tested negative for Vi expression by serological agglutination. However, only 1 of these 12 was Vi negative by the multiplex PCR method. This result was …

The Pervasive Triad Of Food Security, Gender Inequity And Women's Health: Exploratory Research From Sub-Saharan Africa, A.A. Hyder, S. Maman, J.E. Nyoni, S.A. Khasiani, N. Teoh, Zul Premji, S. Sohani

Pathology, East Africa

Objectives: This study was designed to explore the interactions between food securing activities, health and gender equity from the perspective of rural east African women. The specific objectives were to document the critical interaction among these three issues - food security, gender inequity, women's health within the context of sub-Saharan Africa; to describe the nature of this triad from the perspective of women farmers in Africa; and to propose a framework for linking available interventions to the vicious nature of this triad.

Setting: In-depth interviews and focus group discussions were conducted with rural women farmers in Kwale District, Kenya and …

Frequency Of Irregular Red Cell Alloantibodies In Patients With Thalassemia Major: A Bicenter Study, Fareena Bilwani, Ghulam Nabi, Salman Adil, Mohammad Usman, Farrukh Hassan, Mohammad Khurshid

Department of Pathology and Laboratory Medicine

Objective: To provide frequency and distribution pattern of various types of irregular red cell alloantibodies in patients with thalassemia major.
Methods: This is a descriptive study conducted at two centers from January to December 2001. Purposive sampling was done and all patients diagnosed to have thalassemia major were included in the study. Antibody identification was carried out on serum employing commercial two-cell panel using standardized blood bank methods. If patients were found to have an irregular red cell alloantibody then the antibody identification was performed using 16 panel cells. Results: A total of ninety-seven patients were included …

Frequency And Sensitivity Pattern Of Extended Spectrum Beta Lactamase Producing Isolates In A Tertiary Care Hospital Laboratory Of Pakistan, Kauser Jabeen, Afia Zafar, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objective: To determine frequency, distribution and sensitivity pattern of Extended-Spectrum ß Lactamase (EBSL) producing organism at a tertiary care hospital in Pakistan.
Methods: All members of enterobacteriacae isolated between April and August 2002 were studied. Isolates were speciated according to standard biochemical tests. Susceptibility testing was performed by Kirby-Bauer method. ESBL was detected using double disc method using cefotaxime versus cefotaxime plus clavulanate according to NCCLS. Statistical analysis was performed by SPSS version 10. Test of significance were calculated using chi-square test.
Results: During the study period, 1137/2840 (40%) of the isolates tested were found to be ESBL producing. …