Pathology Commons^™

Expression Of The Androgen Receptor, Pakt, And Ppten In Breast Cancer And Their Potential In Prognostication, Aisha Sultana, Romana Idress, Zulfiqar Ali Naqvi, Iqbal Azam, Shaista Khan, Anwar Ali Siddiqui, El Nasir Lalani

Department of Pathology and Laboratory Medicine

BACKGROUND: Importance of androgen receptor (AR) as an independent prognostic marker in Pakistani women with breast cancer (BCa) remains unexplored. Our aim was to identify the expression and potential prognostic value of AR, its upstream regulator (pAkt) and target gene (pPTEN) in invasive BCa.
METHODS: This study used a cohort of 200 Pakistani women with invasive BCa diagnosed during 2002-2011. Expression of AR, pAkt and pPTEN was determined on formalin fixed paraffin embedded tissue sections by immunohistochemistry. The association of AR, pAkt and pPTEN with clinicopathological parameters was determined. Survival analyses were undertaken on patients with ≥ 5 years of …

Ovarian Sex Cord Stromal Tumours In Children And Young Girls - A More Than Two Decade Clinicopathological Experience In A Developing Country, Pakistan, Saroona Haroon, Romana Idrees, Aleena Zia, Aisha Memon, Saira Fatima, Naila Kayani

Department of Pathology and Laboratory Medicine

Background: Ovarian sex-cord stromal tumours (SCST) are rare, and relatively infrequent in children. These have to be distinguished from more common germ cell tumors in children and also from benign epithelial neoplasms.
Objectives: The purpose of our study was to report the clinical and pathological findings in young patients with these tumours in our population.
Material and Methods: The present observational cross-sectional study included all subjects SCST, in Aga Khan University Hospital Histopathology Laboratory, Karachi, Pakistan, from January 1992 till July 2013.
Results: Of the total of 513 SCSTs presented during the study period, 39 fulfilled inclusion criteria and were …

Pleomorphic Lobular Carcinoma Of The Male Breast With Axillary Lymph Node Involvement: A Case Report And Review Of Literature, Muhammad Nauman Zahir, Khurram Minhas, Munira Shabbir-Moosajee

Department of Pathology and Laboratory Medicine

Background: Carcinoma of the male breast is responsible for less than 1% of all malignancies in men but the incidence is rising. Invasive ductal carcinoma is the most common histological subtype while invasive lobular carcinoma is responsible for only 1.5% of the total cases of which pleomorpic lobular carcinoma is an extremely rare variant. We report the case of a gentleman with node positive, pleomorphic lobular carcinoma of the breast.
Case Presentation: An elderly gentleman with a past history of type 2 diabetes and long term ethanol use presented to us with a self-discovered palpable lump in the left breast. …

Environmental And Occupational Factors Associated With Chronic Myeloid Leukemia: A Case-Control Study, R. Kasmani, N.A. Othieno-Abinya, M.T. Singh Riyat, G.W. Kiarie, Peter Wanzala

Pathology, East Africa

Background: The relationship between chronic myeloid leukemia (CML) and a broad range of exposures to occupational and environmental factors known to cause leukemia in general is limited. CML is by and large incurable and treatment is just palliative and life prolonging, with high case fatality rate, even in the best centers. Furthermore treatment is very expensive. Identification of leukemogenic factors is therefore important if this can lead to simple public health interventions.

Objective: The objective was to determine key environmental and occupational exposure factors that may be associated with CML.

Methods: This was a case-control study involving CML …

Low Prevalence Of Methicillin Resistant As Determined By An Automated Identification System In Two Private Hospitals In Nairobi, Kenya: A Cross Sectional Study, Geoffrey Omuse, Beatrice Kabera, Gunturu Revathi

Pathology, East Africa

Background: Staphylococcus aureus (S.aureus) is a major cause of both healthcare and community acquired infections. In developing countries, manual phenotypic tests are the mainstay for the identification of staphylococci with the tube and slide coagulase tests being relied upon as confirmatory tests for S. aureus. The subjectivity associated with interpretation of these tests may result in misidentification of coagulase negative staphylococci as S.aureus. Given that antibiotic resistance is more prevalent in CONS, this may result in over estimation of methicillin resistant S.aureus (MRSA) prevalence.

Methods: A review of susceptibility data from all non-duplicate S.aureus isolates generated between March 2011 and …

Insulin Regulates Glucose Consumption And Lactate Production Through Reactive Oxygen Species And Pyruvate Kinase M2., Qi Li, Xue Liu, Yu Yin, Ji-Tai Zheng, Cheng-Fei Jiang, Jing Wang, Hua Shen, Chong-Yong Li, Min Wang, Ling-Zhi Liu, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Although insulin is known to regulate glucose metabolism and closely associate with liver cancer, the molecular mechanisms still remain to be elucidated. In this study, we attempt to understand the mechanism of insulin in promotion of liver cancer metabolism. We found that insulin increased pyruvate kinase M2 (PKM2) expression through reactive oxygen species (ROS) for regulating glucose consumption and lactate production, key process of glycolysis in hepatocellular carcinoma HepG2 and Bel7402 cells. Interestingly, insulin-induced ROS was found responsible for the suppression of miR-145 and miR-128, and forced expression of either miR-145 or miR-128 was sufficient to abolish insulin-induced PKM2 expression. …

Network Analysis Of Circular Permutations In Multidomain Proteins Reveals Functional Linkages For Uncharacterized Proteins., Donald Adjeroh, Yue Jiang, Bing-Hua Jiang, Jie Lin

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Various studies have implicated different multidomain proteins in cancer. However, there has been little or no detailed study on the role of circular multidomain proteins in the general problem of cancer or on specific cancer types. This work represents an initial attempt at investigating the potential for predicting linkages between known cancer-associated proteins with uncharacterized or hypothetical multidomain proteins, based primarily on circular permutation (CP) relationships. First, we propose an efficient algorithm for rapid identification of both exact and approximate CPs in multidomain proteins. Using the circular relations identified, we construct networks between multidomain proteins, based on which we perform …

Aetiology Of Acute Febrile Episodes In Children Attending Korogwe District Hospital In North-Eastern Tanzania, C. Mahende, B. Ngasala, J. Lusingu, A. Butichi, P. Lushino, M. Lemnge, Zul Premji

Pathology, East Africa

Introduction: Although the burden of malaria in many parts of Tanzania has declined, the proportion of children with fever has not changed. This situation underscores the need to explore the possible causes of febrile episodes in patients presenting with symptoms at the Korogwe District Hospital (KDH).

Methods: A hospital based cross-sectional study was conducted at KDH, north-eastern Tanzania. Patients aged 2 to 59 months presenting at the outpatient department with an acute medical condition and fever (measured axillary temperature ≥37.5°C) were enrolled. Blood samples were examined for malaria parasites, human immunodeficiency virus (HIV) and bacterial infections. A urine culture was …

Using Verbal Autopsy To Measure Causes Of Death: The Comparative Performance Of Existing Methods, C.J.L. Mahende, R. Lozano, A.D. Flaxman, P. Serina, D. Phillips, A. Stewart, S.L. James, A. Vahdatpour, C. Atkinson, M.K. Freeman, S.L. Ohno, R. Black, S.M. Ali, A.H. Baqui, L. Dandona, E. Dantzer, G.L. Darmstadt, V. Das, U. Dhingra, A. Dutta, W. Fawzi, S. Gomez, B. Hernandez, R. Joshi, H.D. Kalter, A. Kumar, V. Kumar, M. Lucero, S. Mehta, Zul Premji, D. Ramirez-Villalobos, H. Remolador, I. Riley, M. Romero, M. Said, D. Sanvictores, S. Sazawal, V. Tallo, A. D. Lopez

Pathology, East Africa

Background: Monitoring progress with disease and injury reduction in many populations will require widespread use of verbal autopsy (VA). Multiple methods have been developed for assigning cause of death from a VA but their application is restricted by uncertainty about their reliability.

Methods: We investigated the validity of five automated VA methods for assigning cause of death: InterVA-4, Random Forest (RF), Simplified Symptom Pattern (SSP), Tariff method (Tariff), and King-Lu (KL), in addition to physician review of VA forms (PCVA), based on 12,535 cases from diverse populations for which the true cause of death had been reliably established. For adults, …

A Review Of 74 Patients With Newly Diagnosed Multiple Myeloma At A Tertiary Referral Hospital In Nairobi, Kenya, G. Kiraka, Mbayah Etabale, Riyat Malkit

Pathology, East Africa

Introduction: Multiple myeloma is a neoplastic disorder characterized by clonal proliferation of plasma cells. We aimed to carry out a retrospective audit to describe clinical and laboratory features of patients newly diagnosed with multiple myeloma.

Materials and Methods: Records of all patients initially diagnosed with multiple myeloma at the haematology clinic of Aga Khan University Hospital, Nairobi, from January 1, 1999 to December 31, 2011 were reviewed. Diagnosis of multiple myeloma was based on (1) increased numbers of abnormal, atypical or immature plasma cells in a bone marrow aspirate or trephine, (2) presence of monoclonal protein or free light chains …

Applying Consensus Criteria To The Evaluation Of Patients With Suspected Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, E. Mulwa-Babu, Riyat Malkit, D. Parech

Pathology, East Africa

We describe a series of 5 patients in whom the application of consensus criteria for the diagnosis of chronic lymphocytic leukemia (CLL) led to a revised diagnosis. These patients had been recruited in a wider study describing the occurrence of CLL in Kenya. This case series highlights some of the pitfalls of making a diagnosis of CLL without incorporating all criteria.

Harnessing Microbiome And Probiotic Research In Sub-Saharan Africa: Recommendations From An African Workshop, Gregor Reid, Nicholas Nduti, Wilbert Sybesma, Remco Kort, Tobias R. Kollmann, Rodney Adam, Hamadi Boga, Eric M. Brown, Alexandra Einerhand, Hani El-Nezami, Gregory B. Gloor, Irene I. Kavere, Johanna Lindahl, Amee Manges, Wondu Mamo, Rocio Martin, Amy Mcmillan, Jael Obiero, Pamela A. Ochieng’, Arnold Onyango, Stephen Rulisa, Eeva Salminen, Seppo Salminen, Antony Sije, Jonathan R. Swann, William Van Treuren, Daniel Waweru, Steve J. Kemp

Pathology, East Africa

To augment capacity-building for microbiome and probiotic research in Africa, a workshop was held in Nairobi, Kenya, at which researchers discussed human, animal, insect, and agricultural microbiome and probiotics/prebiotics topics. Five recommendations were made to promote future basic and translational research that benefits Africans.

Clinical And Laboratory Features Distinguishing Juvenile Polymyositis And Muscular Dystrophy, Gulnara Mamyrova, James D. Katz, Robert V. Jones, Ira N. Targoff, Peter A. Lachenbruch, Olcay Y. Jones, Frederick W. Miller, Lisa G. Rider

Pathology Faculty Publications

OBJECTIVE:

To differentiate juvenile polymyositis (PM) and muscular dystrophy, both of which may present with chronic muscle weakness and inflammation.

METHODS:

We studied 39 patients with probable or definite juvenile PM and 9 patients with muscular dystrophies who were initially misdiagnosed as having juvenile PM. Differences in demographic, clinical, and laboratory results; outcomes; and treatment responses were evaluated by Fisher's exact and rank sum tests. Random forests classification analysis and logistic regression were performed to examine significant differences in multivariable models.

RESULTS:

Clinical features and serum muscle enzyme levels were similar between juvenile PM and dystrophy patients, except 89% of …

Labrad : Vol 39, Issue 2 - December 2013, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Diagnosis of Inborn Errors of Metabolism in Pakistan
• Inherited Metabolic Disorders-Presenting as Metabolic Emergencies
• Role of Biochemical Genetics Laboratary in Evaluation of IEM
• Amino Acid Chromatography for the Diagnosis of Inborn Error of Metabolism
• Polymorphism in Methylenetetrahydrofolate Reductase (MTHFR) Gene
• Diagnosis of Tyrosinemia Type I
• Congential Hypothyroidism
• Congential Adrenal Hyperplasia, An Insight of Laboratory
• Inaugration Ceremony of Section of biochemical Genetics Laboratory

Transfusion Medicine Illustrated: Transfusion Interference By Cold Agglutinins., Melissa R. George, Jay Herman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

First Report Of Ndm-1-Producing Acinetobacter Baumannii In East Africa, Gunturu Revathi, Kristopher L. Siu, Po-Liang Lu, Li-Yueh Huang

Pathology, East Africa

Background: The emergence of carbapenem-resistant Acinetobacter baumannii (CRAB) was observed in a Kenyan hospital from 2009 to 2010. Further investigation of the dissemination of CRAB isolates and the molecular characterization of associated resistance determinants were therefore performed.

Methods: Antibiotic susceptibilities were determined by broth microdilution and Etest. Metallo-blactamases were detected by Etest method. Clonal relationships were studied by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). b-Lactam and aminoglycoside resistance determinants and the clonal relatedness to widespread European clones were studied by PCR and sequencing.

Results: Sixteen CRAB isolates from 10 patients possessed six pulsotypes; half of the isolates …

Development Of A Conditional Mesd (Mesoderm Development) Allele For Functional Analysis Of The Low-Density Lipoprotein Receptor-Related Family In Defined Tissues, Andrew V. Taibi, Janet K. Lighthouse, Richard C. Grady, Kenneth R. Shroyer, Bernadette Holdener

Department of Biomedical Engineering Faculty Publications

The Low-density lipoprotein receptor-Related Protein (LRP) family members are essential for diverse processes ranging from the regulation of gastrulation to the modulation of lipid homeostasis. Receptors in this family bind and internalize a diverse array of ligands in the extracellular matrix (ECM). As a consequence, LRPs regulate a wide variety of cellular functions including, but not limited to lipid metabolism, membrane composition, cell motility, and cell signaling. Not surprisingly, mutations in single human LRPs are associated with defects in cholesterol metabolism and development of atherosclerosis, abnormalities in bone density, or aberrant eye vasculature, and may be a contributing factor in …

Clinical Reasoning And Dual Mental Processing In Diagnostic Competence., M. Tariq, Syed Ahsan Ali

Department of Medicine

No abstract provided.

A Study On The Geophylogeny Of Clinical And Environmental Vibrio Cholerae In Kenya, J. Kiiru, A. Mutreja, A. A. Mohamed, R. W. Kimani, J. Mwituria, R. O. Sanaya, J. Muyodi, Gunturu Revathi, J. Parkhill, N. Thomson, G. Dougan, S. Kariuki

Pathology, East Africa

Cholera remains a significant public health challenge in many sub-Saharan countries including Kenya. We have performed a combination of phylogenetic and phenotypic analysis based on whole genome DNA sequences derived from 40 environmental and 57 clinical V. cholerae from different regions of Kenya isolated between 2005 and 2010. Some environmental and all clinical isolates mapped back onto wave three of the monophyletic seventh pandemic V. cholerae El Tor phylogeny but other environmental isolates were phylogenetically very distinct. Thus, the genomes of the Kenyan V. cholerae O1 El Tor isolates are clonally related to other El Tor V. cholerae isolated elsewhere …

Comparison Of Hpv Dna Testing In Cervical Exfoliated Cells And Tissue Biopsies Among Hiv-Positive Women In Kenya, Hugo De Vuyst, Michael Chung, Lacopo Baussano, Nelly R. Mugo, Vanessa Tenet, Folkert J. Van Kemenade, Farzana S. Rana, Samah R. Sakr, Chris J.L.M. Meijer, Peter J.F. Snijders, Silvia Franceschi

Pathology, East Africa

HIV-positive women are infected with human papillomavirus (HPV) (especially with multiple types), and develop cervical intraepithelial neoplasia (CIN) and cervical cancer more frequently than HIV-negative women. We compared HPV DNA prevalence obtained using a GP5+/6+ PCR assay in cervical exfoliated cells to that in biopsies among 468 HIV-positive women from Nairobi, Kenya. HPV prevalence was higher in cells than biopsies and the difference was greatest in 94 women with a combination normal cytology/normal biopsy (prevalence ratio, PR = 3.7; 95% confidence interval, CI: 2.4-5.7). PR diminished with the increase in lesion severity (PR in 58 women with high-grade squamous intraepithelial …