Pathology Commons^™

Labrad : Vol 39, Issue 1 - September 2013, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Immunophenotyping by Flowcytometry
• Chronic Lymphocytic Leukaemia: Diagnosis and Prognostic Factors
• Tumour Markers
• Role of Chemical Pathology in Screening and Diagnosis of Multiple Myeloma
• 1p/19q Deletion: Favourable Prognostic Marker for Oligodendroglioma
• EGFR Mutation Screening Test for Lung Cancer Patients
• Clinical Utility of BCR-ABL1 Kinase Domain Mutational Analysis
• Molecular Cytogenetic Testing for Acute Myeloid Leukaemia
• Diffuse Large B-Cell Lymphoma (DLBCL) Subgroups have Different Phenotype

Sessile Serrated Adenomas In The Proximal Colon Are Likely To Be Flat, Large And Occur In Smokers, Tarun Rustagi, Priya Rangasamy, Matthew Myers, Melinda Sanders, Haleh Vaziri, George Y. Wu, John W. Birk, Petr Protiva, Joseph C. Anderson

Dartmouth Scholarship

Aim: To examine the epidemiology and the morphology of the proximal sessile serrated adenomas (SSAs).

Methods: We conducted a retrospective study to identify patients with SSAs using a university-based hospital pathology database query from January 2007 to April 2011. Data collected included: age, gender, ethnicity, body mass index, diabetes, smoking, family history of colorectal cancer, aspirin, and statin use. We collected data on morphology of SSAs including site (proximal or distal), size, and endoscopic appearance (flat or protuberant). We also compared proximal SSAs to proximal tubular adenomas detected during same time period.

A Dysfunctional Tricarboxylic Acid Cycle Enhances Fitness Of Staphylococcus Epidermidis During Β-Lactam Stress., Vinai Chittezham Thomas, Lauren C. Kinkead, Ashley Janssen, Carolyn R. Schaeffer, Keith M. Woods, Jill K. Lindgren, Jonathan M. Peaster, Sujata S. Chaudhari, Marat Sadykov, Joselyn Jones, Sameh M. Mohamadi Abdelghani, Matthew C. Zimmerman, Kenneth W. Bayles, Greg A. Somerville, Paul D. Fey

Journal Articles: Pathology and Microbiology

A recent controversial hypothesis suggested that the bactericidal action of antibiotics is due to the generation of endogenous reactive oxygen species (ROS), a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To test this hypothesis, we assessed the ability of oxacillin to induce ROS production and cell death in Staphylococcus epidermidis strain 1457 and an isogenic citric acid cycle mutant. Our results confirm a contributory role for TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward β-lactam antibiotics and also revealed a propensity for clinical isolates to accumulate TCA cycle dysfunctions presumably as a way to tolerate these …

Illuminating The Dark Side--Vitamin D Status In Different Localities Of Karachi, Romaina Iqbal, Lena Jafri, Ali Haroon, Aysha Habib Khan

Department of Medicine

This study was conducted to determine the association between place of residence (grouped into neighbourhoods), and 25-hydroxy D (25[OH]D) levels of individuals of Karachi. Addresses of 4788 individuals tested for 25[OH]D at the clinical laboratory of the Aga Khan University (AKU), Karachi, from January 2007 to June 2008 were reviewed. The neighbourhoods were categorized into ten, based on locality attributes. A high overall prevalence (74%) of vitamin D deficiency (VDD) was observed. There was a significant difference (p-value < 0.01) between mean log 25[OH]D levels amongst neighbourhoods grouped according to distinct housing structure attributes and localities. A high frequency of VDD in all the studied localities of an urban city warrant dietary vitamin D supplementation and food fortification.

Hippocampal Sclerosis Of Aging, A Prevalent And High-Morbidity Brain Disease, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Bernard J. Wilfred, Wang-Xia Wang, Janna H. Neltner, Michael Baker, David W. Fardo, Richard J. Kryscio, Stephen W. Scheff, Gregory A. Jicha, Kurt A. Jellinger, Linda J. Van Eldik, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5-30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is …

Population Genetics And Drug Resistance Markers: An Essential For Malaria Surveillance In Pakistan, Afsheen Raza, Mohammad Asim Beg

Department of Pathology and Laboratory Medicine

Plasmodium (P.) vivax is the prevalent malarial species accounting for 70% of malaria cases in Pakistan. However, baseline epidemiological data on P. vivax population structure and drug resistance are lacking from Pakistan. For population structure studies, molecular genetic markers, circumsporozoite protein (csp) and merozoite surface protein-1 (msp-1) are considered useful as these play an important role in P. vivax survival under immune and environmental pressure. Furthermore, these genes have also been identified as suitable candidates for vaccine development. While efforts for effective vaccine are underway, anti-malarial agents remain the mainstay for control. Evidence of resistance against commonly used anti-malarial agents, …

Sentinel Node Localisation Using Pre-Operative Lymphoscintigraphy And Intraoperative Gamma Probe In Early Oral Cavity Cancer, Mubasher Ikram, Shabbir Akhtar, Montasir Junaid, Tariq Dhari, Maseeh-Uz Zaman, Riffat Hussain, Zubair Ahmad

Section of Otolaryngology, Head & Neck Surgery

Objectives: To assess the diagnostic value of sentinel lymph node localisation using pre-operative lymphoscintigraphy and intra-operative gamma probe radio localisation in Pakistani patients suffering from early stage squamous cell carcinoma of the oral cavity.
Methods: The prospective case series was conducted between September 2007 and April 2010 at the Aga Khan University Hospital, Karachi. It comprised patients with T1and T2 oral cavity cancer with clinically and radiologically negative neck. Pre-operative lymphoscintigraphy was performed one day before surgery and intra-operative gamma probe was used to detect sentinel node. Final histo-pathological evaluation was taken as the gold standard.
Results: The study comprised …

Orrahood, Marvin David, 1923-2000 (Mss 465), Manuscripts & Folklife Archives

Manuscript Collection Finding Aids

Finding aid only Manuscripts Collection 465. Correspondence, primarily professional, or Dr. Marvin David Orrahood, a pathologist practicing in Owensboro, Kentucky. Includes Parts I-IV of a family history and genealogy, "The Family of Marvin David Orrahood II and Aline Joyce Orrahood," and a list of Owensboro physicians (Click on "Additional Files" below for scans).

Presumed Familial Late-Onset Medullary Thyroid Cancer In A Patient With A Germline Point Mutation, C. 2304 G->T, In Ret Proto-Oncogene Codon 768: Specific Mutation May Guide Timing Of Prophylactic Total Thyroidectomy In Affected Family Members, Susan Gerber, Md, Madalina Tuluc, Md, Phd, Serge Jabbour, Md, Facp, Face

Department of Medicine Faculty Papers

Medullary thyroid carcinoma (MTC) accounts for 15% of thyroid cancers. It arises in the C-cells of the thyroid, and is often metastatic at presentation. Approximately 75% of MTC cases are sporadic. Heritable MTC is subdivided into three categories: MEN2A, familial medullary thyroid carcinoma (FMTC), and MEN2B. Determination of the particular mutation may guide the timing of prophylactic total thyroidectomy in family members who carry the mutation.

Ectopic Cushing's Syndrome From Acth-Producing Pheochromocytoma, Susan Gerber, Md, Lawrence C. Kenyon, Md, Phd, Mary Kate Mccullen, Serge Jabbour, Md, Facp, Face

Department of Medicine Faculty Papers

ACTH-dependent Cushing’s syndrome results from excessive ACTH secretion from a pituitary gland adenoma (Cushing’s disease) in 80% of cases. Much less commonly, ectopic ACTH production occurs outside the pituitary gland, with the majority of those cases caused by bronchial carcinoids. A small number are due to excessive ACTH secretion by a pheochromocytoma.

Database-Guided Discovery Of Potent Peptides To Combat Hiv-1 Or Superbugs., Guangshun Wang

Journal Articles: Pathology and Microbiology

Antimicrobial peptides (AMPs), small host defense proteins, are indispensable for the protection of multicellular organisms such as plants and animals from infection. The number of AMPs discovered per year increased steadily since the 1980s. Over 2,000 natural AMPs from bacteria, protozoa, fungi, plants, and animals have been registered into the antimicrobial peptide database (APD). The majority of these AMPs (>86%) possess 11-50 amino acids with a net charge from 0 to +7 and hydrophobic percentages between 31-70%. This article summarizes peptide discovery on the basis of the APD. The major methods are the linguistic model, database screening, de novo …

Neuropathogenic Escherichia Coli K1 Does Not Exhibit Proteolytic Activities To Exert Its Pathogenicity, Junaid Iqbal, Mehak Rajan, Ruqaiyyah Siddiqu, Naveed Ahmed Khan

Department of Biological & Biomedical Sciences

Background: Proteases are well-known virulence factors that promote survival, pathogenesis and immune evasion of many pathogens. Several lines of evidence suggest that the blood-brain barrier permeability is a prerequisite in microbial invasion of the central nervous system. Because proteases are frequently associated with vascular permeability by targeting junctional proteins, here it is hypothesized that neuropathogenic Escherichia coli K1 exhibit proteolytic activities to exert its pathogenicity.
Methods: Zymographic assays were performed using collagen and gelatin as substrates. The lysates of whole E. coli K1 strain E44, or E. coli K-12 strain HB101 were tested for proteolytic activities. The conditioned media were …

Qcm Aptasensor For Rapid And Specific Detection Of Avian Influenza Virus, Luke Brockman

Graduate Theses and Dissertations

There has been a need for rapid detection of avian influenza virus (AIV) H5N1 due to it being a potential pandemic threat. Most of the current methods, including culture isolation and PCR, are very sensitive and specific but require specialized laboratories and trained personnel in order to complete the tests and are time-consuming. The goal of this study was to design a biosensor that would be able to rapidly detect AIV H5N1 using aptamers as biosensing material and a quartz crystal microbalance (QCM) for transducing method. Specific DNA aptamers against AIV H5N1 were immobilized, through biotin and streptavidin conjugation, onto …

Malignant Vascular Tumours Associatedwith The Breast: A Study Of 7 Cases, Azizun-Nisa, Zeeshanuddin, Naila Kayani

Department of Pathology and Laboratory Medicine

Angiosarcomas account for less than 0.05% of the malignant neoplasms of the breast. We present here 7 cases of malignant vascular neoplasms of the breast, including 2 cases of postmastectomy Stewart-Treves syndrome. In this case series, most of the patients were young. Tumour was bilateral at presentation in one case. The size of the tumours ranged from 1.6 cm to 11 cm. Although breast angiosarcomas are rare neoplasms, with the increasing use of radiation therapy for breast cancer patients, post-radiation skin lesions should not be ignored.

The Line Between Addiction And Medication: Alcohol, Anesthesia, And Analgesia, Priya Joshi, B.S., Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

Alcohol is a particularly dangerous addiction because its consumption is legal even in excess, despite its harmful effects. Because alcohol has a multitude of targets in the central nervous system that are modified during chronic exposure, medications with overlapping targets such as anesthetics and analgesics must be modified when given to alcoholics. Unfortunately, as relatively little is known about the mechanism of addiction, it is difficult to predict how medications will be affected by central adaptation to chronic alcohol exposure. This review summarizes the consequences of alcohol exposure with particular attention to the GABA_Areceptor, and discusses the reasons …

Transfusion Related Acute Lung Injury, Nadia Abidi, Jay Herman, Md, Julie Karp, Md

Department of Pathology Honors Program Student Research Symposium

A 74 year old woman presented with hematemesis. Her medical history was significant for pulmonary embolism treated with warfarin anticoagulation, fibromyalgia treated with NSAIDs/steroids, and a prior bleeding event from a gastric ulcer. On admission she was stable with a hemoglobin of 8.7 g/dL and a therapeutic INR of 3.19. A type and screen determined a blood type of AB positive. In anticipation of endoscopy, the patient received one unit of red blood cells and four units of type AB plasma. Following transfusion, her INR was 1.83. The patient received an additional four units of type AB plasma to further …

Morphologic And Endoscopic Evaluation Of Collagenous Gastritis, Annie Ashok, Ashlie L. Burkart, Md, Cm

Department of Pathology Honors Program Student Research Symposium

Collagenous gastritis (CG) is a rare gastrointestinal condition of unknown etiology and pathogenesis characterized by the presence of a gastric subepithelial collagen band of variable thickness. While little is known about the disease, children and young adults often present with anemia, abdominal pain, and nodular gastric mucosa on endoscopy. In contrast, adults often present with chronic watery diarrhea and normal gastric mucosa on endoscopy. Disease associations (usually in adult cases) include celiac disease, collagenous colitis, collagenous sprue, and lymphocytic colitis. This study aims to further characterize the clinical, endoscopic and morphologic spectrum of CG.

Lumbar Chordoma: A Primary Bone Tumor, Andrew N. Fleischman, Bs, Brian O'Hara, Md

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

• Primary malignant bone tumor of embryonic notochord remnants
• 1-4% of primary bone tumors, <0.1 per 100,000
• Location: Sacral (50%), Skull base (35%), Vertebral column (15%)
• Classic, chondroid (5-15%), and dedifferentiated (5%) variants
• Most commonly in late middle age (50s to 60s)
• Low-grade, slow growing tumor
• But locally aggressive, high rate of local recurrence (20% in 1^st year)
• Local recurrence is most important predictor of mortality
• Metastasis only occurs very late in disease
• Median survival of about 6 years, less than 12 months with mets
• 5 year survival of 70%, 10 year survival of 40%
• Primary therapy- aggressive surgical resection (if possible) …

An Unexpected Immunohistochemical Profile In An Ovarian Lesion, Kate Fritton, Joanna Chan, Md

Department of Pathology Honors Program Student Research Symposium

A 27 year old female presented with pelvic pain and a palpable pelvic mass. Upon histological examination, the cystic mass contained a multi-cellular lining with nuclear grooves. Negative inhibin staining ruled out a follicular cyst and granulosa cell tumor while pan-cytokeratin positivity suggested an epithelial lesion. The lesion stained positive for thrombomodulin, ultimately suggesting a diagnosis of a Brenner cell tumor, although CD56 positivity in the tumor questions the known immunohistochemical profile of Brenner cell tumors. This unusual result opens the door to future research into the role CD56 in the diagnosis of ovarian neoplasms.

Myeloid Sarcoma: Extramedullary Relapse After Allogeneic Bone Marrow Transplant For Chronic Myelogenous Leukemia, Maria Gubbiotti, Alina Dulau Florea, Md, Renu Bajaj, Phd

Department of Pathology Honors Program Student Research Symposium

Myeloid sarcoma (MS) is an extramedullary tumor of myeloid precursor cells, which can precede or occur concomitantly with acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms. Although MS can involve any organ, it is more common in the central nervous system (CNS) and gonads, sites known as “pharmacologic sanctuaries” where leukemic cells can survive despite systemic chemotherapy. Less often, this tumor can be the manner of relapse after allogeneic bone marrow transplantation.

The diagnosis is based on morphology and immunophenotype by either flow cytometry or immunohistochemistry of paraffin-embedded tissue, and confirmed by FISH or molecular studies. Myeloid sarcomas usually express …