Medical Specialties Commons^™

Glomus Tumor Of Trachea In An Adult Male, Sidra Arshad, Zubair Ahmad, Nasir Ud Din

Department of Pathology and Laboratory Medicine

Glomus tumors most commonly occur in distal extremities, particularly in the subungual region. The origin of these tumors is modified smooth muscle cells of glomus bodies. Trachea is one of the rare sites where normal glomus bodies may be sparse or absent, so occurrence of glomus tumor in trachea is very rare. Only 30 cases have been reported in the literature so far. In this case report, the authors describe a very rare and in fact first case of glomus tumor of trachea in a 45-year male Pakistani patient.

Diagnostic Accuracy Of Anti-Endomysial Antibody In Celiac Disease, Arslaan Javaeed, Walayat Shah, Saaniya Khan Gauri, Rizwan Akhtar

Department of Pathology and Laboratory Medicine

The objective of the study was to determine the diagnostic accuracy of anti-EMA antibody in comparison to histopathological findings in patients suspected of CD. This cross-sectional study was conducted at Gastroenterology Department, Fatima Memorial Hospital, Lahore, from March to October 2014. One hundred and twenty-one patients aged between 5 - 60 years of either gender were recruited in the study. Every patient went through serological testing and biopsy specimens were obtained from second part of the duodenum. Histopathological evaluation was done according to the Modified Marsh classification. The overall sensitivity of anti-EMAcame out to be 85.7% which varied with the …

Cerebral Aspergillosis And Pulmonary Tuberculosis In A Child With Chronic Granulomatous Disease, Muhammad Waqas, Sidra Zafar, Tooba Rehman, Muhammed Riyaz, Muhammad Ehsan Bari, Romana Idress

Section of Neurosurgery

Background: Chronic granulomatous disease (CGD) is an immune disorder that affects phagocytes. It is characterized by recurrent or persistent bacterial and fungal infections. Reports of tuberculosis (TB) in patients with CGD are rare. In developing countries, where TB is endemic, possibility of other chronic infections is often overlooked by physicians.
Case description: We report the case of a 4-year-old boy who had recurrent respiratory infections and episodes of headache. He was put on antituberculosis (ATT) drugs without microbiological or pathological evidence 2 months prior to presentation. The child did not improve and was brought to our hospital where a computed …

Induction Process Of Trainees In Pathology Residency, Imran Siddiqui, Natasha Bahadur Ali

Department of Pathology and Laboratory Medicine

This article describes the evolution of the induction process of pathology residency at The Aga Khan University hospital. The Department of Postgraduate Medical Education was established in 1985. The induction process is an exhaustive exercise that includes an admission test held simultaneously in Karachi, Hyderabad, Lahore, and Rawalpindi, followed by an interview of the shortlisted candidates. The pathology residency program was started 25 years ago and since then the induction process has undergone major changes with the course of time.

How Diet Intervention Via Modulation Of Dna Damage Response Through Micrornas May Have An Effect On Cancer Prevention And Aging, An In Silico Study, Felicia Carotenuto, Maria C. Albertini, Dario Coletti, Alessandra Vilmercati, Luigi Campanella, Zbigniew Darzynkiewicz, Laura Teodori

NYMC Faculty Publications

The DNA damage response (DDR) is a molecular mechanism that cells have evolved to sense DNA damage (DD) to promote DNA repair, or to lead to apoptosis, or cellular senescence if the damage is too extensive. Recent evidence indicates that microRNAs (miRs) play a critical role in the regulation of DDR. Dietary bioactive compounds through miRs may affect activity of numerous genes. Among the most studied bioactive compounds modulating expression of miRs are epi-gallocatechin-3-gallate, curcumin, resveratrol and n3-polyunsaturated fatty acids. To compare the impact of these dietary compounds on DD/DDR network modulation, we performed a literature search and an in …

Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr

Theses & Dissertations

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …

Assessment Of Wt1 Expression As A Marker Of Treatment Outcome In Karyotype Normal Acute Myeloid Leukemia Patients In Pakistan, Zeeshan Ansar Ahmed, Muhammad Shariq Shaikh, Tariq Moatter

Department of Pathology and Laboratory Medicine

Currently, there is an effort to predict relapse by follow-up monitoring of MRD and subsequently to begin the treatment of the patients during their clinical and hematological remission prior to overt hematological relapse. Expression of WT1 in AM Lis known to be independently associated with significant inferior response to therapy and short survival outcome. Follow-up monitoring of WT1 gene expression during or after therapy would be a valuable predictive marker for early recurrence or relapse of AMLdisease. This pilot study evaluated newly diagnosed and post-induction or consolidation chemotherapy of AMLpatients who were registered with the Oncology Clinics of the Aga …

Adenoid Cystic Carcinoma Of Breast: Clinicopathologic Study Of Seven Cases, Raabia Nizamuddin, Nasir Ud Din, Romana Idress, Naila Kayani

Department of Pathology and Laboratory Medicine

Adenoid cystic carcinoma (ACC) of the breast is a rare type of tumor. Our objective was to determine the clinicopathologic features of breast ACC. We reviewed slides of breast ACC reported during 12 years. Seven cases were identified. Age ranged from 38 to 59 years (mean = 47 years). Mean tumor size was 2.3 cm (range 1.2 to 4 cm). Histologically, dominant cribriform pattern was seen in 4 cases, solid in 2 and tubular in one case. Mitotic figures ranged from 2 to 22/10 HPFs. Grades I and II were seen in 3 cases each while 1 was grade III. …

Cll Metabolism Is Regulated By Prognostic Factors, Modulated By Stroma And Abrogated By Pi3k Inhibition, Hima Vangapandu

Dissertations and Theses (Open Access)

Metabolism of chronic lymphocytic leukemia (CLL), a disease characterized by the relentless accumulation of mature B cells has been little explored. Bone marrow stromal cells provide a survival benefit to CLL cells, in part through PI3K/AKT pathway. Compared with proliferative B-cell lines, metabolic fluxes of oxygen and lactate were low in quiescent malignant B lymphocytes from CLL patients. Glycolysis (extracellular acidification rate, ECAR) was consistently low in CLL samples, but oxygen consumption (OCR) varied considerably. Higher OCR was associated with poor prognostic factors such as ZAP 70 positivity, unmutated IgVH, high β2M levels, and higher Rai stage. Co-culture with the …

Isolation Frequency And Susceptibility Pattern Of Non-O1 And Non-O139 Vibrio Cholerae In A Tertiary Health Care Laboratory, 1999-2012, S Irfan, N Fasih, N K. Ghanchi, Erum Khan

Department of Pathology and Laboratory Medicine

In the past decade the importance of non-O1 and non-O139 strains of Vibrio cholerae has been highlighted globally. This study aimed to evaluate the frequency and antimicrobial susceptibility profile of non-O1 and non-O139 V. cholerae in Pakistan. Data of stool specimens yielding growth of non-O1 and non-O139 V. cholerae isolated at a national referral laboratory from 1999 to 2012 were retrospectively analysed and evaluated for resistance to ampicillin, tetracycline, chloramphenicol, co-trimoxazole and ofloxacin. A total of 95 800 stool samples submitted over 1999-2012 yielded 3668 strains of V. cholerae, of which 6% were non-O1 and non-O139 V. cholerae. A high …

Assessment Of Red Blood Cell Distribution Width As A Prognostic Marker In Chronic Lymphocytic Leukemia, Monika Podhorecka, Dorota Halicka, Agnieszka Szymczyk, Arkadiusz Macheta, Sylwia Chocholska, Zbigniew Darzynkiewicz

NYMC Faculty Publications

Red blood cell distribution width (RDW) is a quantitative measure of the variability in size of circulating erythrocytes. It was recently reported that RDW is a prognostic factor for infection diseases, cardiovascular and pulmonary diseases, as well as some neoplasms. Moreover, RDW is remarkably strong predictor of longevity, including all causes of death, for adults aged 45 years and older. To explain this occurrence it was proposed that persistent IGFs/mTOR signaling is one of the factors that play a role in affecting the RDW and mortality.The above observations induced us to analyze the prognostic role of RDW in chronic lymphocytic …

Moving Towards Effective Therapeutic Strategies For Neuronal Ceroid Lipofuscinosis., Ryan D. Geraets, Seung Yon Koh, Michelle L. Hastings, Tammy Kielian, David A. Pearce, Jill M. Weimer

Journal Articles: Pathology and Microbiology

The Neuronal Ceroid Lipofuscinoses (NCLs) are a family of autosomal recessive neurodegenerative disorders that annually affect 1:100,000 live births worldwide. This family of diseases results from mutations in one of 14 different genes that share common clinical and pathological etiologies. Clinically, the diseases are subcategorized into infantile, late-infantile, juvenile and adult forms based on their age of onset. Though the disease phenotypes may vary in their age and order of presentation, all typically include progressive visual deterioration and blindness, cognitive impairment, motor deficits and seizures. Pathological hallmarks of NCLs include the accumulation of storage material or ceroid in the lysosome, …

A Patient With Constitutional Ring 1 Chromosome Characterized By Snp Array Cgh, Sheila Saliganan, Joanna Lee, Sainan Wei

Pathology and Laboratory Medicine Faculty Publications

We present a male patient with constitutional ring 1 chromosome and subsequent 6 Mb deletion at 1q43q44. The patient displays overlapping clinical features with reported patients with ring 1 chromosome and 1q43q44 microdeletion syndrome. To our knowledge, this is the first patient with ring 1 chromosome characterized by comparative genomic hybridization.

Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg

Senior Honors Theses

The intimin gene in the Locus of Enterocyte Effacement (LEE) island of pathogenicity is the primary attachment mechanism in Citrobacter rodentium. Intimin is a bacterial adhesin (protein) that attaches to obtain a niche/nutrient and thrive within the intestine. Intimin was deleted within C. rodentium to study colonization and pathogenesis in the murine intestine. Additionally, C. rodentium is an attaching/effacing pathogen, and a useful murine model in understanding Enterohemorrhagic Escherichia coli (EHEC) infection in humans. E. coli and C. rodentium cause gastroenteritis in humans and mice, respectively. C. rodentium is a murine pathogen commonly used to model gastrointestinal disease because …

Investigating The Role Of The Basic Helix-Loop-Helix Transcription Factor Mist1 In Pancreatic Diseases, Anju Karki

Open Access Dissertations

Acinar cells of the exocrine pancreas are dedicated to synthesize, package and secrete immense quantities of pro-digestive enzymes to maintain proper metabolic homeostasis for the organism. Dysregulation of enzyme secretion in acinar cells can give rise to exocrine diseases including acute pancreatitis (AP), a disease that targets acinar cells, leading to acinar-ductal metaplasia (ADM), inflammation and fibrosis—events that can transition into the earliest stages of pancreatic ductal adenocarcinoma (PDAC). The focus of this thesis is to interrogate transcriptional regulatory networks that are susceptible to AP and the role that these networks play in acinar cell and exocrine pancreas responses. The …

Labrad : Vol 42, Issue 1 - April 2016, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Biochemical Bone Profiles Available at Clinical Laboratoryof 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)
• Renal Osteodystrophy: A Disturbed Metabolic Aspect of Renal Failure
• Update on Microbiological Diagnosis of Bone and Joint Disorders
• Classification of Tumours of Bone : An Update Based on the 2013 World Health Organization Classification of Tumours of Soft Tissue and Bone
• Recent Developments in Benign Bone Tumours
• Role of Clinical and Radiological Correlation in Orthopaedic Pathology
• CME Seminar on ‘World Osteoporosis Day’

A Novel Comparative Pattern Analysis Approach Identifies Chronic Alcohol Mediated Dysregulation Of Transcriptomic Dynamics During Liver Regeneration., Lakshmi Kuttippurathu, Egle Juskeviciute, Rachael P Dippold, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Liver regeneration is inhibited by chronic ethanol consumption and this impaired repair response may contribute to the risk for alcoholic liver disease. We developed and applied a novel data analysis approach to assess the effect of chronic ethanol intake in the mechanisms responsible for liver regeneration. We performed a time series transcriptomic profiling study of the regeneration response after 2/3(rd) partial hepatectomy (PHx) in ethanol-fed and isocaloric control rats.

RESULTS: We developed a novel data analysis approach focusing on comparative pattern counts (COMPACT) to exhaustively identify the dominant and subtle differential expression patterns. Approximately 6500 genes were differentially regulated …

Acute Promyelocytic Leukemia Co-Existing With Jak2 V617f Positive Myeloproliferative Neoplasm: A Case Report, Aleksandra Mamorska-Dyga, Jingjing Wu, Pallavi Khattar, Faisal Ronny, Humayun Islam, Karen Seiter, Delong Liu

NYMC Faculty Publications

The V617F mutation of Janus-associated kinase 2 (JAK2) is commonly seen in myeloproliferative neoplasms (MPN). Transformation of JAK2 positive MPNs to acute leukemia has been reported. We here report a case of acute promyelocytic leukemia which was later confirmed to have a co-existing JAK2 V617F positive MPN. In addition, the patient was found to have FLT3-TKD mutation, which, together with PML/RARa, could play a role in the MPN transformation to APL.

Cd34(+) Therapy-Related Acute Promyelocytic Leukemia In A Patient Previously Treated For Breast Cancer, John Savooji, Fouzia Shakil, Humayun Islam, Delong Liu, Karen Seiter

NYMC Faculty Publications

Therapy-related acute myeloid leukemia (AML) is a long term complication of chemotherapy for a variety of cancers. In most cases, the marrow demonstrates high risk cytogenetics and the prognosis is poor. In a minority of patients "good risk" cytogenetics, including t(15;17)(q22;q12), are seen and the patient's prognosis is similar to those who have de novo disease. Currently we present a patient who developed therapy-related acute promyelocytic leukemia (APL) after chemoradiotherapy for breast cancer. This case was especially atypical because the leukemic cells were CD34(+), which is an unusual immunophenotype for APL. Recognition that this patient had APL, rather than the …

Establishment Of Prostate Cancer Spheres From A Prostate Cancer Cell Line After Phenethyl Isothiocyanate Treatment And Discovery Of Androgen-Dependent Reversible Differentiation Between Sphere And Neuroendocrine Cells, Yamei Chen, Shundong Cang, Liying Han, Christina Liu, Patrick Yang, Zeeshan Solangi, Quanyi Lu, Delong Liu, Jenwei Chiao

NYMC Faculty Publications

Prostate cancer can transform from androgen-responsive to an androgen-independent phenotype. The mechanism responsible for the transformation remains unclear. We studied the effects of an epigenetic modulator, phenethyl isothiocyanate (PEITC), on the androgen-responsive LNCaP cells. After treatment with PEITC, floating spheres were formed with characteristics of prostate cancer stem cells (PCSC). These spheres were capable of self-renewal in media with and without androgen. They have been maintained in both types of media as long term cultures. Upon androgen deprivation, the adherent spheres differentiated to neuroendocrine cells (NEC) with decreased proliferation, expression of androgen receptor, and PSA. NEC reverse differentiated to spheres …

Post-Chemotherapy Neuroblastoma-Like Differentiation In Ewing Sarcoma Of Humerus: Report Of A Rare Case With Review Of Literature, Nasir Ud Din, Amna Qasim, Zubair Ahmad, Sheema H Hasan

Department of Pathology and Laboratory Medicine

A 21-year patient initially presented with a fracture of the humerus following minor trauma. A bone scan and biopsy were done due to the suspicion of pathological fracture and the biopsy confirmed the diagnosis of Ewing Sarcoma (EWS). Two months after initial presentation, chemotherapy was started and 5 cycles were given over a span of 6 months. Surgical resection of the tumor was then performed. The post-chemotherapy resection specimen, on histological examination, showed the presence of areas of neuroblastoma-like differentiation in otherwise morphologically classic EWS. Cytogenetic analysis by FISH revealed EWSR1 gene rearrangement. Four similar cases have been reported earlier …

The Effects Of Acidified Pepsin On Porcine Vocal Fold Tissue: Developing A Porcine Model Of Laryngopharyngeal Reflux Disease, Abigail Cox Durkes

Open Access Dissertations

Approximately 7.5 million Americans are affected by a voice disorder. In the last year, 7.2% of people missed one or more days of work due to a voice problem. For professional voice users, such as teachers, the rate increases to 20% and an annual cost of $2.5 billion. Voice disorders are complex and multi-faceted, as well as difficult to diagnose and treat. Prospective animal studies are necessary to study the pathophysiology of voice disorders, optimize our understanding of laryngeal pathology, and improve treatment outcomes. The pig provides a unique opportunity to test hypotheses relating to laryngeal disease because porcine vocal …

Primary Angiosarcoma Of Breast, Saroona Haroon, Naveen Faridi, Faisal Rashid Lodhi

Department of Pathology and Laboratory Medicine

Primary breast sarcomas, except for phyllodes tumour, are very rare entities, accounting for < 0.1% of all malignant neoplasms. Angiosarcoma of breast is infrequent malignancy and differential diagnosis from other sarcomatous and angiomatous breast tumours holds importance. Two cases of primary angiosarcoma of breast were encountered. One involved a 32 years lady who was treated by wide local excision and six cycles of chemotherapy. The other occurred in a 54 years old lady who was treated with mastectomy, did not receive any radiation or chemotherapy and was later lost to follow-up. Neither of the patient had history of previous breast surgery, chemotherapy or radiotherapy.

Spectrum Of Microbial Diseases And Resistance Patterns At A Private Teaching Hospital In Kenya: Implications For Clinical Practice, Daniel Maina, Geoffrey Omuse, Gunturu Revathi, Rodney Adam

Pathology, East Africa

Background: Accurate local prevalence of microbial diseases and microbial resistance data are vital for optimal treatment of patients. However, there are few reports of these data from developing countries, especially from sub-Saharan Africa. The status of Aga Khan University Hospital Nairobi as an internationally accredited hospital and a laboratory with an electronic medical record system has made it possible to analyze local prevalence and antimicrobial susceptibility data and compare it with other published data.

Methods: We have analyzed the spectrum of microbial agents and resistance patterns seen at a 300 bed tertiary private teaching hospital in Kenya using microbial identity …

Multiplatform Molecular Profiling Identifies Potentially Targetable Biomarkers In Malignant Phyllodes Tumors Of The Breast., Zoran Gatalica, Semir Vranic, Anatole Ghazalpour, Joanne Xiu, Idris Tolgay Ocal, John Mcgill, Ryan P Bender, Erin Discianno, Aaron Schlum, Souzan Sanati, Juan P. Palazzo, Sandeep Reddy, Barbara Pockaj

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including …

Membranoproliferative Glomerulonephritis Recurrence After Kidney Transplantation: Using The New Classification., Sami Alasfar, Naima Carter-Monroe, Avi Z Rosenberg, Robert A Montgomery, Nada Alachkar

Pathology Faculty Publications

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is an uncommon glomerular disorder that may lead to end stage renal disease (ESRD). With new understanding of the disease pathogenesis, the classical classification as MPGN types I, II, III has changed. Data on post-transplant MPGN, in particular with the newly refined classification, is limited. We present our center's experience of MPGN after kidney transplantation using the new classification.

METHODS: This is a retrospective study of 34 patients with ESRD due to MPGN who received 40 kidney transplants between 1994 and 2014. We reviewed the available biopsies' data using the new classification. We assessed post transplantation …

Gene 33/Mig6 Inhibits Hexavalent Chromium-Induced Dna Damage And Cell Transformation In Human Lung Epithelial Cells, Soyoung Park, Cen Li, Hong Zhao, Zbigniew Darzynkiewicz, Dazhong Xu

NYMC Faculty Publications

Hexavalent Chromium [Cr(VI)] compounds are human lung carcinogens and environmental/occupational hazards. The molecular mechanisms of Cr(VI) carcinogenesis appear to be complex and are poorly defined. In this study, we investigated the potential role of Gene 33 (ERRFI1, Mig6), a multifunctional adaptor protein, in Cr(VI)-mediated lung carcinogenesis. We show that the level of Gene 33 protein is suppressed by both acute and chronic Cr(VI) treatments in a dose- and time-dependent fashion in BEAS-2B lung epithelial cells. The inhibition also occurs in A549 lung bronchial carcinoma cells. Cr(VI) suppresses Gene 33 expression mainly through post-transcriptional mechanisms, although the mRNA level of gene …

The Effects Of Allergies And Anaphylaxis On The Body And Mind: A Survey Of Opinions And Knowledge On These Disorders, Kathryn E. O'Brien

Honors Program: Student Scholarship & Creative Works

Despite common knowledge, allergies and anaphylaxis are considered disabilities. As such, these disorders affect the daily lives of those who have them, including one's mental health. In this paper, all the nuances of allergies and anaphylaxis will be discussed as the etiology and scientific aspects of allergies, anaphylaxis, and hypersensitivity are distinguished from one another. Furthermore, the findings are reported from two surveys; an assessment of how well educated and prepared teachers are for students with allergies and whether other students with food allergies have had similar experiences to the author's and those described in research by other studies concerning …

Type Vi Choledochal Cyst—An Unusual Presentation Of Jaundice, L. Nambiar, E. Siskind, A. W. Shen, C. Fan, G. Grimaldi, C. Choy, J. Madariaga, J. Nicastro, E. P. Molmenti, G. Coppa, +1 Additional Author

Journal Articles

No abstract provided.

The Application Of Digital Pathology To Improve Accuracy In Glomerular Enumeration In Renal Biopsies., Avi Z Rosenberg, Matthew Palmer, Lino Merlino, Jonathan P Troost, Adil Gasim, Serena Bagnasco, Carmen Avila-Casado, Duncan Johnstone, Jeffrey B Hodgin, Catherine Conway, Brenda W Gillespie, Cynthia C Nast, Laura Barisoni, Stephen M Hewitt

Pathology Faculty Publications

BACKGROUND: In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment.

DESIGN: We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE) digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging. Glomerular number and the percentage of globally sclerotic glomeruli are …