Medical Specialties Commons^™

Outcome Of Match Related Allogeneic Stem Cell Transplantation Procedures Performed From 2004 Till 2011, Natasha Ali, Salman Naseem Adil, Mohammad Usman Shaikh, Munira Moosajee, Nehal Masood

Department of Pathology and Laboratory Medicine

We present our initial experience of allogeneic stem cell transplant procedure performed between April 2004 and August 2011 for various haematological disorders. All patients with non-malignant and malignant haematological disorders with HLA matched donors were selected after pre-transplant workup. Ninety seven patients underwent the procedure. Most common indications for transplant were aplastic anaemia in n=34 (35%), followed by beta-Thalassemia major in n=21 (21.6%) and chronic myeloid leukemia in n=11 patients (11.3%). Primary graft failure present was present in 2.06%. Incidence of graft versus host disease (GvHD) in our patients was 34%. After median follow-up of five years the overall survival …

Resistance Patterns Of Mycobacterium Tuberculosis Isolates From Pulmonary Tuberculosis Patients In Nairobi, Perpetual Wangui Ndung’U, Samuel Kariuki, Zipporah Ng’Ang’A, Gunturu Revathi

Pathology, East Africa

Introduction: In Kenya, which ranks thirteenth of 27 high tuberculosis burden countries, diagnosis is based on Ziehl-Neelsen staining alone and patients are treated without information on sensitivity patterns. This study aimed to determine resistance patterns of Mycobacterium tuberculosis isolated from pulmonary samples.

Methodology: Pulmonary tuberculosis patients in Nairobi were randomly sampled after informed consent and recruited into the study using a structured questionnaire. Specimens were cultured in liquid and solid media, and drug susceptibility tests were performed for first-line drugs including (isoniazid, rifampin, streptomycin, ethambutol and pyrazinamide).

Results: Eighty-six (30%) of 286 isolates were resistant to at least one of …

Lung Carcinoma In The Era Of Personalized Medicine: The Role Of Cytology., Maureen F Zakowski, Marluce Bibbo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In 2004, three groups working independently [1–3] , almost simultaneously, reported remarkable findings: that activating mutations in the epidermal growth factor receptor (EGFR) were common in certain lung carcinomas and that these mutations correlated with the response of those lung tumors to therapy with gefitinib and erlotinib, both EGFR tyrosine kinase inhibitors (TKIs). This was the first time driver mutations in lung cancer that responded to targeted therapy had been identified, marking the beginning of a new era of personalized medicine in lung cancer. Prior to the discovery of these mutations, patients had been treated with EGFR TKIs but predicting …

Clinical Spectrum And Severity Of Hemolytic Anemia In Glucose 6-Phosphate Dehydrogenase-Deficient Children Receiving Dapsone, Allan Pamba, Naomi D. Richardson, Nick Carter, Stephan Duparc, Zul Premji, Alfred B. Tiono, Lucio Luzzatto

Pathology, East Africa

Drug-induced acute hemolytic anemia led to the discovery of G6PD deficiency. However, most clinical data are from isolated case reports. In 2 clinical trials of antimalarial preparations containing dapsone (4,4′-diaminodiphenylsulfone; 2.5 mg/kg once daily for 3 days), 95 G6PD-deficient hemizygous boys, 24 G6PD-deficient homozygous girls, and 200 girls heterozygous for G6PD deficiency received this agent. In the first 2 groups, there was a maximum decrease in hemoglobin averaging -2.64 g/dL (range -6.70 to +0.30 g/dL), which was significantly greater than for the comparator group receiving artemether-lumefantrine (adjusted difference -1.46 g/dL; 95% confidence interval -1.76, -1.15). Hemoglobin concentrations were decreased by …

Adherence To Artemether/Lumefantrine Treatment In Children Under Real-Life Situations In Rural Tanzania, D.O. Simba, D. Kakoko, G. Tomson, Zul Premji, M. Petzold, M. Mahindi, L.L. Gustafsson

Pathology, East Africa

A follow-up study was conducted to determine the magnitude of and factors related to adherence to artemether/lumefantrine (ALu) treatment in rural settings in Tanzania. Children in five villages of Kilosa District treated at health facilities were followed-up at their homes on Day 7 after the first dose of ALu. For those found to be positive using a rapid diagnostic test for malaria and treated with ALu, their caretakers were interviewed on drug administration habits. In addition, capillary blood samples were collected on Day 7 to determine lumefantrine concentrations. The majority of children (392/444; 88.3%) were reported to have received all …

De Novo Design Of Antiviral And Antibacterial Peptides With Varying Loop Structures, Guangshun Wang, Karen W. Buckheit, Biswajit Mishra, Tamara Lushnikova, Robert W. Buckheit Jr.

Journal Articles: Pathology and Microbiology

No abstract provided.

Major Families Of Multiresistant Plasmids From Geographically And Epidemiologically Diverse Staphylococci., Julia E.S. Shearer, Joy Wireman, Jessica Hostetler, Heather Forberger, Jon Borman, John Gill, Susan Sanchez, Alexander Mankin, Jacqueline Lamarre, Jodi A. Lindsay, Kenneth W. Bayles, Ainsley Nicholson, Frances O'Brien, Slade O. Jensen, Neville Firth, Ronald A. Skurray, Anne O. Summers

Journal Articles: Pathology and Microbiology

Staphylococci are increasingly aggressive human pathogens suggesting that active evolution is spreading novel virulence and resistance phenotypes. Large staphylococcal plasmids commonly carry antibiotic resistances and virulence loci, but relatively few have been completely sequenced. We determined the plasmid content of 280 staphylococci isolated in diverse geographical regions from the 1940s to the 2000s and found that 79% of strains carried at least one large plasmid >20 kb and that 75% of these large plasmids were 20-30 kb. Using restriction fragment length polymorphism (RFLP) analysis, we grouped 43% of all large plasmids into three major families, showing remarkably conserved intercontinental spread …

Proliferating Tricholemmal Tumour: Clinicopathological Aspects Of A Case., Adeel Khoja, Yan B, Lee Sj, Cheong E. C, Tan K B

Department of Medicine

We report the case of a 49-year-old man who presented with an enlarging mass over his occipital scalp. The clinical impression was either a squamous cell carcinoma or an unusual adnexal tumour. A wide excision was performed with skin grafting. Gross examination revealed a large exophytic tumour mass measuring 10 cm. Histopathological examination showed a circumscribed, well-differentiated squamoproliferative lesion with a lobulated architecture. Clear cell features, pilar-type keratinisation, microcalcifications and the presence of mucinous degeneration were noted. A diagnosis of proliferating tricholemmal tumour was made. This entity incorporates a spectrum of lesions, ranging from the mostly benign proliferating tricholemmal cyst …

Switches, Excitable Responses And Oscillations In The Ring1b/Bmi1 Ubiquitination System., Lan K Nguyen, Javier Muñoz-García, Helene Maccario, Aaron Ciechanover, Walter Kolch, Boris N Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots …

Differential Combination Of Cytokine And Interferon- Gamma +874 T/A Polymorphisms Determines Disease Severity In Pulmonary Tuberculosis., Ambreen Ansari, Zahra Hasan, Ghaffar Dawood, Rabia Hussain

Department of Pathology and Laboratory Medicine

Background:Mycobacterium tuberculosis infects nearly 1/3 of the world population and this reservoir forms the largest pool from which new cases arise. Among the cytokines, IFN-gamma is a key determinant in protection against tuberculosis. Single nucleotide polymorphisms (SNPs) in IFN-gamma gene (+874 T/A) which determine TT high ((hi)), AA low ((lo)) and TA intermediate ((int)) responder phenotypes have shown variable associations with tuberculosis disease outcome in different ethnic populations. The objective of the current study was to analyze IFN-gamma gene combinations with other IFN-gamma regulating cytokine genes (IL-10, TNF -alpha, IL-6) to see the effect of gene- combinations on disease …

Nuclease Modulates Biofilm Formation In Community-Associated Methicillin-Resistant Staphylococcus Aureus., Megan R. Kiedrowski, Jeffrey S. Kavanaugh, Cheryl L. Malone, Joe M. Mootz, Jovanka M. Voyich, Mark S. Smeltzer, Kenneth W. Bayles, Alexander R. Horswill

Journal Articles: Pathology and Microbiology

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging contributor to biofilm-related infections. We recently reported that strains lacking sigma factor B (sigB) in the USA300 lineage of CA-MRSA are unable to develop a biofilm. Interestingly, when spent media from a USA300 sigB mutant was incubated with other S. aureus strains, biofilm formation was inhibited. Following fractionation and mass spectrometry analysis, the major anti-biofilm factor identified in the spent media was secreted thermonuclease (Nuc). Considering reports that extracellular DNA (eDNA) is an important component of the biofilm matrix, we investigated the regulation and role of Nuc in USA300. The expression of …

Brca1 Status In Pakistani Breast Cancer Patients With Moderate Family History, Tariq Moatter, Muniba Aban, Shaista Khan, Iqbal Azam, Shahid Pervez

Department of Pathology and Laboratory Medicine

OBJECTIVE: To determine BRCA1 status in breast carcinoma patients of Pakistani origin.

STUDY DESIGN: Observational study.

PLACE AND DURATION OF STUDY: The Oncology Clinics of the Aga Khan University Hospital, Karachi, between May 2005 and December 2009.

METHODOLOGY: Fifty three breast cancer patients based on clinical and laboratory diagnosis were recruited for this study. Moderate family history was defined as having a close relative (mother, daughter, sister) diagnosed with breast cancer under 45 years. Peripheral blood samples were collected from each patient in a 5 ml tube containing EDTA as anticoagulant. Subsequent to DNA extraction, mutational analysis of BRCA1 exons …

Early Exposure To Paraquat Sensitizes Dopaminergic Neurons To Subsequent Silencing Of Pink1 Gene Expression In Mice., Hongxia Zhou, Cao Huang, Jianbin Tong, Xugang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Environmental exposure, genetic modification, and aging are considered risky for Parkinson's disease (PD). How these risk factors cooperate to induce progressive neurodegeneration in PD remains largely unknown. Paraquat is an herbicide commonly used for weed and grass control. Exposure to paraquat is associated with the increased incidence of PD. In contrast to familial PD, most sporadic PD cases do not have genetic mutation, but may suffer from partial dysfunction of neuron-protective genes as aging. Using conditional transgenic RNAi, we showed that temporal silencing of PINK1 expression in adult mice increased striatal dopamine, the phenotype that could not be induced by …

Ccl2/Mcp-I Genotype-Phenotype Relationship In Latent Tuberculosis Infection, Rabia Hussain, Ambreen Ansari, Najeeha Talat, Zahra Hasan, Ghaffar Dawood

Department of Pathology and Laboratory Medicine

Among the known biomarkers, chemokines, secreted by activated macrophages and T cells, attract groups of immune cells to the site of infection and may determine the clinical outcome. Association studies of CCL-2/MCP-1 -2518 A/G functional SNP linked to high and low phenotypes with tuberculosis disease susceptibility have shown conflicting results in tuberculosis. Some of these differences could be due the variability of latent infection and recent exposure in the control groups. We have therefore carried out a detailed analysis of CCL-2 genotype SNP -2518 (A/G transition) with plasma CCL-2 levels and related these levels to tuberculin skin test positivity in …

Specific Sequence Determinants Of Mir-15/107 Microrna Gene Group Targets, Peter T. Nelson, Wang-Xia Wang, Guogen Mao, Bernard R. Wilfred, Kevin Xie, Mary H. Jennings, Zhen Gao, Xiaowei Wang

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) target mRNAs in human cells via complex mechanisms that are still incompletely understood. Using anti-Argonaute (anti-AGO) antibody co-immunoprecipitation, followed by microarray analyses and downstream bioinformatics, 'RIP-Chip' experiments enable direct analyses of miRNA targets. RIP-Chip studies (and parallel assessments of total input mRNA) were performed in cultured H4 cells after transfection with miRNAs corresponding to the miR-15/107 gene group (miR-103, miR-107, miR-16 and miR-195), and five control miRNAs. Three biological replicates were run for each condition with a total of 54 separate human Affymetrix Human Gene 1.0 ST array replicates. Computational analyses queried for determinants of miRNA:mRNA binding. The …

Characterization Of Invasive And Colonizing Isolates Of Streptococcus Agalactiae In East African Adults, Charlotte Huber, Francis Mcodimba, Valentin Pflueger, Claudia Daubenberger, Gunturu Revathi

Pathology, East Africa

Ninety-five colonizing isolates and 74 invasive isolates of Streptococcus agalactiae from Kenyan adults were characterized by using capsular serotyping and multilocus sequence typing. Twenty-two sequence types clustering into five clonal complexes were found. Data support the view that S. agalactiae isolates belonging to a limited number of clonal complexes are invasive in adults worldwide.

Atypical Clinical And Diagnostic Features In Ménétrier's Disease In A Child, Michael Chung, Jaime Pittenger, Deborah Flomenhoft, Jeffrey Bennett, Eun Young Lee, Harohalli Shashidhar

Internal Medicine Faculty Publications

Ménétrier's disease is one of the rarest protein-losing gastropathies in childhood. It is characterized clinically by non-specific gastrointestinal symptoms and edema, biochemically by hypoalbuminemia, and pathologically by enlarged gastric folds. In adults, this disease can be devastating with significant morbidity and mortality. In childhood, it is a self-limiting, transient and benign illness. Its treatment is largely supportive with total parenteral nutrition (TPN) while oral intake is encouraged. Acute onset of vomiting in healthy school age children can be initially explained by acute viral gastroenteritis. However, persistent vomiting associated with hematemesis and severe abdominal pain should warrant further work-up. This case …

Labrad : Vol 37, Issue 2 - September 2011, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Biochemical Bone Profiles Available at Clinical Laboratory of Aga Khan University Hospital
• Ionized Calcium Determination in Clinical Labortory
• Parathyroid Hormone Disorders and Issues of Testing
• Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR)
• LABRAD Quiz
• Renal Osteodystrophy: A Disturbed Metabolic Aspect of Renal Failure
• Osteopenia and Osteoporosis in Beta Thalassemia Major
• Role of β2 Microglobulin in Multiple Myeloma
• Update on Microbiological Diagnosis of Bone and Joint Disorders
• Bone Sarcomas: Role of Histopathology in Diagnosis

A Non-Randomized, Observational Trial Of Short-Term Pre-Operative Endocrine Therapy In Er Positive Breast Cancer To Investigate Changes In Genomic Expression Using The Oncotype Dx® Recurrence Score®, Aaron D. Bleznak Md, Facs, Elizabeth A. Dellers Md, B G. Porter, Sharon R. Kimmel Phd, Mha, Heiwon Chung Md, Facs, Carl N. Yoshizawa, Emily Burke, D S. Davison, Calvin Chao

Department of Pathology & Laboratory Medicine

No abstract provided.

Presence Of Rd149 Deletions In M. Tuberculosis Central Asian Strain 1 Isolates Affect Growth And Tnfalpha Induction In Thp-1 Monocytes., Akber Kanji, Zahra Hasan, Mehnaz Tanveer, Raunaq Mahboob, Sana Jafri, Rumina Hasan

Department of Pathology and Laboratory Medicine

Central Asian Strain 1 (CAS1) is the prevalent Mycobacterium tuberculosis genogroup in South Asia. CAS1 strains carry deletions in RD149 and RD152 regions. Significance of these deletions is as yet unknown. We compared CAS1 strains with RD149 and concurrent RD149-RD152 deletions with CAS1 strains without deletions and with the laboratory reference strain, M. tuberculosis H37Rv for growth and for induction of TNFα, IL6, CCL2 and IL10 in THP-1 cells. Growth of CAS1 strains with deletions was slower in broth (RD149; p = 0.024 and RD149-RD152; p = 0.025) than that of strains without deletions. CAS1 strains with RD149 deletion strains …

Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery To The Distal Lung., Jeffrey A Kazzaz, Marlene S Strayer, Jichuan Wu, Daniel J Malone, Hshi-Chi Koo, Thomas H Shaffer, Jonathan M Davis, David S Strayer, Marla R Wolfson

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

WE COMPARED LUNG DELIVERY METHODS OF RECOMBINANT ADENOVIRUS (RAD): (1) rAd suspended in saline, (2) rAd suspended in saline followed by a pulse-chase of a perfluorochemical (PFC) liquid mixture, and (3) a PFC-rAd suspension. Cell uptake, distribution, and temporal expression of rAd were examined using A549 cells, a murine model using luciferase bioluminescence, and histological analyses. Relative to saline, a 4X increase in transduction efficiency was observed in A549 cells exposed to PFC-rAd for 2-4 h. rAd transgene expression was improved in alveolar epithelial cells, and the level and distribution of luciferase expression when delivered in PFC-rAd suspensions consistently peaked …

A Conserved Tissue-Specific Homeodomain-Less Isoform Of Meis1 Is Downregulated In Colorectal Cancer., Richard C Crist, Jacquelyn J Roth, Scott A Waldman, Arthur M Buchberg

Department of Microbiology and Immunology Faculty Papers

Colorectal cancer is one of the most common cancers in developed nations and is the result of both environmental and genetic factors. Many of the genetic lesions observed in colorectal cancer alter expression of homeobox genes, which encode homeodomain transcription factors. The MEIS1 homeobox gene is known to be involved in several hematological malignancies and solid tumors and recent evidence suggests that expression of the MEIS1 transcript is altered in colorectal cancer. Despite this potential connection, little is known about the role of the gene in the intestines. We probed murine gastrointestinal tissue samples with an N-terminal Meis1 antibody, revealing …

Tlr4 Mutation Reduces Microglial Activation, Increases Aβ Deposits And Exacerbates Cognitive Deficits In A Mouse Model Of Alzheimer's Disease, Min Song, Jingji Jin, Jinghong Kou, Abhinandan Pattanayak, Jamaal Rehman, Hong-Duck Kim, Ken-Ichiro Fukuchi

NYMC Faculty Publications

BACKGROUND: Amyloid plaques, a pathological hallmark of Alzheimer's disease (AD), are accompanied by activated microglia. The role of activated microglia in the pathogenesis of AD remains controversial: either clearing Aβ deposits by phagocytosis or releasing proinflammatory cytokines and cytotoxic substances. Microglia can be activated via toll-like receptors (TLRs), a class of pattern-recognition receptors in the innate immune system. We previously demonstrated that an AD mouse model homozygous for a loss-of-function mutation of TLR4 had increases in Aβ deposits and buffer-soluble Aβ in the brain as compared with a TLR4 wild-type AD mouse model at 14-16 months of age. However, it …

Primary Non-Functioning Paraganglioma Of Liver: A Rare Tumour At An Unusual Location, Muhammad Rizwan Khan, Rushna Raza, Abdul Jabbar, Arsalan Ahmed

Section of General Surgery

Pheochromocytomas are rare tumours, 22% of which are extra-adrenal and are known as paragangliomas. We report a case of a young male with non-functioning paraganglioma of the liver; a very uncommon primary site. A CT scan with contrast showed a huge, highly vascular mass lesion in the right lobe of the liver and a core biopsy confirmed it to be a paraganglioma. Whole body study with iodine-131-meta-iodobenzylguanidine (MIBG) tracer highlighted the liver tumour but was negative for any other active lesions depicting that the tumour was confined to the liver. The lesion was completely resected by extended right hepatectomy and …

Analysis Of Chlamydia Pneumoniae And Ad-Like Pathology In The Brains Of Balb/C Mice Following Direct Intracranial Infection With Chlamydia Pneumoniae, Jessica Rachel Barton

PCOM Biomedical Studies Student Scholarship

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disorder and the most common form of dementia. The pathology in the central nervous system (CNS) impairs memory and cognition, hindering the capabilities and the quality of life of the individual. This project continues studying the role of infection and Alzheimer’s disease and contributes to the overall understanding of the possible causes of this disease. In this study, BALB/c mice were infected, via direct intracranial injection, with a respiratory isolate (AR-39) of Chlamydia pneumoniae. Their brains were analyzed at 7 and 14 days post-infection, using immunohistochemistry, for the presence of C. …

Hiv-1 Circulating Recombinant Form In Nepal, Aniqa Shahid, Sameer M. Dixit, V. L. Gurbacharya, Dibesh Karmacharya, Syeda K. Ali

Department of Pathology and Laboratory Medicine

No abstract provided.

Cytological Diagnosis Of Typical Carcinoid On Bronchoscopic Brush Smears In An Hiv-Positive Patient, Neeta Kumar, Shahin Sayed, Swati Das

Internal Medicine, East Africa

We report a case of typical carcinoid of the lung in a 60-year-old human immunodeficiency virus (HIV)-positive man diagnosed on brush cytology smears. Bronchial carcinoids are rare tumors, accounting for 1% to 2% of all lung tumors. Although the exact incidence in HIV-infected individuals is not known, the paucity of their documentation in the literature indicates that they may be equally rare. Cytological diagnosis on brush smears is rarely documented as the tumor is covered with mucosa and cellular yield is often not good. In this case, bronchial brushings showed distinctive cytological features of typical carcinoid. The awareness of its …

Comparison Of Chromogenic Urinary Tract Infection Medium With Cysteine Lactose Electrolyte Deficient Media In A Resource Limited Setting, Saba Qaiser, Muhammad Zeeshan, Kausar Jabeen, Tanwir Ahsan, Afia Zafar

Department of Pathology and Laboratory Medicine

OBJECTIVES: To compare the chromogenic UTI medium (CUM) with cysteine lactose electrolyte deficient medium (CLED) in terms of isolation of uropathogens, turnaround time and cost.

METHODS: A total of 251 urine samples were selected and inoculated on both CLED and CUM, growth was observed after 24 and 48 hours of incubation. Isolates were identified by colony's colour and biochemical tests. Turnaround time for identification and cost was calculated till final identification of microorganisms.

RESULTS: A discrepancy in isolation was observed in seven samples with growth on CUM in 24 hours while in 48 hours on CLED. There was 100% agreement …

Relationship Between The Quetelet’S Index, Homa-Ir Index And Prostate Size In Patients With Benign Prostatic Hyperplasia At St.Mary’S Hospital In, Timothy Onyuma

Master of Medicine in Anatomic Pathology

Introduction: Benign prostatic hyperplasia is a highly prevalent disease and is considered an inevitable correlate of ageing. Several theories have been advanced in a bid to explain its pathogenesis, the most popular ones relating to sex steroid hormones (1). Currently facets of the metabolic syndrome of which two principal components are insulin resistance and high BMI have been postulated to be related to growth of the prostate (2). Insulin resistance is assessed by the HOMA-IR index. Some studies have demonstrated an association between these indices and the size of the prostate (3). While others have not (4). We set out …

Malignant Lymphoma Subtypes In A Private Hospital In Nairobi: A Retrospective Cross-Sectional Study, Omar A. Sherman

Master of Medicine in Anatomic Pathology

Introduction: Lymphoma diagnosis integrates clinical, morphological, immunophenotypical and molecular genetic features as evident from the World Health Organization (WHO) classification of lymphoid malignancies.(1, 2) Although it is standard practice for histopathology laboratories in developed countries to confirm and further sub classify lymphomas using immunohistochemistry and other molecular techniques, the same is not true for developing countries like Kenya. The reasons that prevent the performance of these tests are the prohibitive costs and inadequate trained personnel. Objectives: The aims of this study were to retrospectively classify lymphomas diagnosed at The Aga Khan University Hospital (AKUHN) Laboratory based on the WHO classification …