Pathology Commons^™

Mycobacterium Tuberculosis Lineage 4 Comprises Globally Distributed And Geographically Restricted Sublineages, David Stucki, Daniela Brites, Leïla Jeljeli, Mireia Coscolla, Gunturu Revathi

Pathology, East Africa

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most …

Medical Interns', Residents' And Attending Physicians' Attitudes Towards Integrative Medicine And Recommended Treatments For Patients With Psoriasis, Jennifer L. Pacyon

PCOM Psychology Dissertations

Background: Psoriasis is a multifactorial disease that effect approximately 7.5 million Americans. There are a variety of traditional treatments for psoriasis (e.g. topical medications, biologics) that for many, are effective in combating the disease. However, traditional treatments often have aversive side effects and may not be appropriate for every patient (e.g. pregnant women). Additionally, the efficacy of these medications are variable leaving some looking for adjunctive treatment options. There is increasing evidence to support the use of adjunctive treatments for psoriatic patients (e.g. psychotherapy, mindfulness). However, research is variable in regards to medical professionals’ attitudes towards integrative medicine (IM) as …

Results From The Survey Of Antibiotic Resistance (Soar) 2011-14 In The Democratic Republic Of Congo, Ivory Coast, Republic Of Senegal And Kenya, A. Kacou-Ndouba, Gunturu Revathi, P. Mwathi, A. Seck, A. Diop, M. J. Kabedi-Bajani, W. Mwiti, M. J. Anguibi-Pokou, I. Morrissey, D. Torumkuney

Pathology, East Africa

Objectives: To assess antibiotic susceptibility of community-acquired respiratory tract isolates from Ivory Coast, Kenya, Democratic Republic of Congo (DRC) and Senegal in 2011–14.

Methods: Bacterial isolates were collected and MICs determined using Etest^® for all antibiotics except erythromycin, for which testing was by disc diffusion. Susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. For macrolide interpretation, CLSI breakpoints were adjusted for incubation in CO₂.

Results: Susceptibility to penicillin (using CLSI oral or EUCAST breakpoints) was low among isolates of Streptococcus pneumoniae from the DRC and Kenya (17.4% and 19%, respectively) but higher among isolates from …

Adding A Single Low-Dose Of Primaquine (0.25 Mg/Kg) To Artemether-Lumefantrine Did Not Compromise Treatment Outcome Of Uncomplicated Plasmodium Falciparum Malaria In Tanzania: A Randomized, Single-Blinded Clinical Trial, Richard Mwaiswelo, Billy Ngasala, Irina Jovel, Berit Aydin‑Schmidt, Roland Gosling, Zul Premji, Bruno Mmbando, Anders Björkman, Andreas Mårtensson

Pathology, East Africa

Background: The World Health Organization (WHO) recently recommended the addition of a single low-dose of the gametocytocidal drug primaquine (PQ) to artemisinin-based combination therapy (ACT) in low transmission set‑ tings as a component of pre-elimination or elimination programmes. However, it is unclear whether that influences the ACT cure rate. The study assessed treatment outcome of artemether-lumefantrine (AL) plus a single PQ dose (0.25 mg/kg) versus standard AL regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania.

Methods: A randomized, single-blinded, clinical trial was conducted in Yombo, Bagamoyo district, Tanzania. Acute uncomplicated P. falciparum malaria patients aged ≥1 year, …

Safety Of A Single Low-Dose Of Primaquine In Addition To Standard Artemether-Lumefantrine Regimen For Treatment Of Acute Uncomplicated Plasmodium Falciparum Malaria In Tanzania, Richard Mwaiswelo, Billy Ngasala, Irina Jovel, Roland Gosling, Zul Premji, Eugenie Poirot, Bruno Mmbando, Anders Björkman, Andreas Mårtensson

Pathology, East Africa

Background: This study assessed the safety of the new World Health Organization (WHO) recommendation of adding a single low-dose of primaquine (PQ) to standard artemisinin-based combination therapy (ACT), regardless of individual glucose-6-phosphate dehydrogenase (G6PD) status, for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania.

Methods: Men and non-pregnant, non-lactating women aged ≥1 year with uncomplicated P. falciparum malaria were enrolled and randomized to either standard artemether-lumefantrine (AL) regimen alone or with a 0.25 mg/kg single-dose of PQ. PQ was administered concomitantly with the first AL dose. All drug doses were supervised. Safety was evaluated between days 0 and 28. …

Activation Of Signal Transduction Pathways During Hepatic Oncogenesis, W Chung, M Kim, S De La Monte, L Longato, R Carlson, B L. Slagle, X Dong, J R. Wands

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Understanding the molecular pathogenesis of hepatocellular carcinoma (HCC) is essential to identify therapeutic targets. A hepatitis B virus (HBV) related double transgenic murine model was developed. METHODS: Liver specific expression of HBV X protein (HBx) and insulin receptor substrate 1 (IRS1) was achieved and transgenic mice were followed from birth to age 21 months. Liver and tumor tissue were assessed for histologic changes as well as activation of signal transduction pathways by qRT-PCR and multiplex ELISA protein assays. RESULTS: Overexpression of HBx and IRS1 stimulates liver cell proliferation in the double transgenic mice. Only the male mice …

Tmsb4y Is A Candidate Tumor Suppressor On The Y Chromosome And Is Deleted In Male Breast Cancer., Hong Yuen Wong, Grace M Wang, Sarah Croessmann, Daniel J Zabransky, Anita Aggarwal, Min-Ling Liu, + 10 More

Pathology Faculty Publications

Male breast cancer comprises less than 1% of breast cancer diagnoses. Although estrogen exposure has been causally linked to the development of female breast cancers, the etiology of male breast cancer is unclear. Here, we show via fluorescence in situ hybridization (FISH) and droplet digital PCR (ddPCR) that the Y chromosome was clonally lost at a frequency of ~16% (5/31) in two independent cohorts of male breast cancer patients. We also show somatic loss of the Y chromosome gene TMSB4Y in a male breast tumor, confirming prior reports of loss at this locus in male breast cancers. To further understand …

Effect Of Raised Body Fat On Vitamin D, Leptin And Bone Mass, Syeda Sadia Fatima, Saad Farooq, Maaida Asif Tauni, Omar Irfan, Faiza Alam

Department of Biological & Biomedical Sciences

Objective: To estimate leptin, vitamin D and bone mineral density levels in individuals with high fat mass, and to assess any correlation.Methods: The cross-sectional study was conducted at the Basic Medical Sciences Institute, Jinnah Post Graduate Medical Centre, Karachi, and Aga Khan University, Karachi, from August 2012 to July 2014, and comprised healthy male volunteers between the ages of 18-60 years. Body fat percentage was determined using bioelectrical impedance analysis and the participants were classified as: Group A (15-21.9); Group B (22-27.9); and Group C ( > 28). Bone mineral density was calculated by ultrasound bone densitometer (T-score between +1 and …

Labrad : Vol 41, Issue 3 - December 2015, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Overview on Approach to Inherited Bleeding Disorders
• Diagnostic Approach to Haemoglobinopathies
• Transient Abnormal Myelopoiesis
• Urinary Tract Infections (UTI) in Children
• Role of Histopathology in the Diagnosis of Paediatric Renal Tumours
• Role of Histopathology in the Diagnosis of Paediatric Bone and Soft Tissue Small Round Cell Tumours
• Evaluation of Inborn Errors of Metabolism (IEM) In a Nutshell
• An Update on Blood Lead Levels in Children
• Clinical Utility of Immature Platelet Fraction – An advanced 25 Parameter in Laboratory Hematology
• Meeting Report: “Les Confluences” The Society for the Study 30 of Inborn errors of Metabolism (SSIEM) Annual Symposium 2015 in Lyon, France

Intraventricular Sialidase Administration Enhances Gm1 Ganglioside Expression And Is Partially Neuroprotective In A Mouse Model Of Parkinson's Disease., Jay S Schneider, Thomas N Seyfried, Hyo-S Choi, Sarah Kidd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Preclinical and clinical studies have previously shown that systemic administration of GM1 ganglioside has neuroprotective and neurorestorative properties in Parkinson's disease (PD) models and in PD patients. However, the clinical development of GM1 for PD has been hampered by its animal origin (GM1 used in previous studies was extracted from bovine brains), limited bioavailability, and limited blood brain barrier penetrance following systemic administration.

OBJECTIVE: To assess an alternative therapeutic approach to systemic administration of brain-derived GM1 to enhance GM1 levels in the brain via enzymatic conversion of polysialogangliosides into GM1 and to assess the neuroprotective potential of this approach. …

Ependymal Tumors With Oligodendroglioma Like Clear Cells: Experience From A Tertiary Care Hospital In Pakistan, Fauzan Alam Hashmi, Muhammad Faheem Khan, Saad Akhtar Khan, Muhammad Waqas, Muhammad Ehsan Bari, Arsalan Ahmed

Section of Neurosurgery

Background: Ependymal tumors with oligodendroglioma like clear cells have never been reported from Pakistan. We aimed to see the features and outcomes of this rare entity.
Methods: It was retrospective cohort conducted at the Department of Neurosurgery, Aga Khan University from 2003 to 2013. The medical records and radiology of patients with proven histopathology were reviewed. Analysis was done on SPSS 20.
Results: Eleven cases of ependymal tumors with clear cells were found, which equated to 1.5% of the total tumor burden in 11 years. The median age was 49 years. Most common presenting symptom was headache 54.5%. Out of …

Spectrum Of Histopathological Findings In Postmenopausal Bleeding, Muhammad Usman Tariq, Romana Idress, Ahmed Raheem, Naila Kayani

Department of Pathology and Laboratory Medicine

Objective:To determine the frequencies of histopathological findings in endometrial and endocervical biopsy samples with clinical history of Postmenopausal Bleeding (PMB). Study Design:Descriptive cross-sectional study. Place and Duration of Study:Section of Histopathology, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from February 2012 to January 2013. Methodology:Atotal of 157 consecutive endometrial and endocervical biopsy specimens with history of postmenopausal bleeding were included. After microscopic examination, frequencies of histological findings in different age groups were generated. Chi-square and independent sample t-tests were applied to see whether the difference was significant which was set at p < 0.05. Results:One hundred and twenty-one (77.1%) specimens showed benign pathologies while 36 (22.9%) were malignant. Endometrial polyp was seen in 67 (42.7%) cases followed by endometrial carcinomas in 25 (15.9%), endometrial hyperplasia in 21 (13.4%), cervical carcinoma in 12 (7.6%) and cervical polyps in 9 (5.7%) cases. Ahighly significant increase in the percentage of malignant and pre-malignant lesions was seen with increasing age group (p < 0.001). Mean age of patients with type-2 endometrial carcinoma was higher than type-1 endometrial carcinoma but statistical significance was not observed (70.2 ±6.5 vs. 61.8 ±9.1 years respectively, p=0.069). Conclusion:Although benign pathologies were more common in postmenopausal bleeding but the collective proportion of endometrial and cervical malignancies and pre-malignant conditions was quite high. Therefore, PMB should be urgently evaluated for cause and early commencement of treatment

Neuroinflammatory Paradigms In Lysosomal Storage Diseases., Megan Bosch, Tammy Kielian

Journal Articles: Pathology and Microbiology

Lysosomal storage diseases (LSDs) include approximately 70 distinct disorders that collectively account for 14% of all inherited metabolic diseases. LSDs are caused by mutations in various enzymes/proteins that disrupt lysosomal function, which impairs macromolecule degradation following endosome-lysosome and phagosome-lysosome fusion and autophagy, ultimately disrupting cellular homeostasis. LSDs are pathologically typified by lysosomal inclusions composed of a heterogeneous mixture of various proteins and lipids that can be found throughout the body. However, in many cases the CNS is dramatically affected, which may result from heightened neuronal vulnerability based on their post-mitotic state. Besides intrinsic neuronal defects, another emerging factor common to …

Primary Sclerosing Epithelioid Fibrosarcoma Of Kidney With Variant Histomorphologic Features: Report Of 2 Cases And Review Of The Literature., Dilek Ertoy Baydar, Kemal Kosemehmetoglu, Oguz Aydin, Julia A. Bridge, Berrin Buyukeren, Fazil Tuncay Aki

Journal Articles: Pathology and Microbiology

The authors present two cases of primary sclerosing epithelioid fibrosarcoma (SEF) of the kidney. Both patients had a mass in the upper part of the left kidney without any primary extrarenal neoplastic lesions. Grossly, the tumors were solid masses both measuring 7.5 cm in the greatest diameter. Histologically, one of the lesions exhibited a predominantly lobular growth of round or oval small uniform epithelioid cells in variable cellularity. Circular zones of crowded tumor cells alternating with hypocellular collagenous tissue in a concentric fashion around entrapped native renal tubules were distinctive. The second case was distinctive with significant cytological atypia in …

Neurofibromatosis Type 2 Patient Presenting With Medulloblastoma, Jan Kalimullah, Abdul Malik Amir Humza Sohail, Rai Shahjehan, Sabeehuddin Siddique, Muhammad Ehsan Bari

Section of Neurosurgery

Background: Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome with a frequency of 1 in 25,000 live births and a penetrance of almost 100% by the sixth decade of life. The main tumors occurring in NF2 patients are bilateral vestibular schwannomas, other peripheral, cranial and spinal nerve schwannomas, intracranial and intraspinal meningiomas, ependymomas, and gliomas.
Case description: We report the case of a 6-year-old boy who presented with a 1-month history of nausea and recurrent vomiting. Physical examination was positive for ataxic gait and left-sided facial nerve palsy. Family history was positive for NF2 in the patient's father and …

Diagnostic Options And Challenges For Dengue And Chikungunya Viruses., Stacey K. Mardekian, Amity L. Roberts, Phd, D(Abmm)

Department of Medical Genetics Faculty Papers

Dengue virus (DENV) and Chikungunya virus (CHIKV) are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas. These two viruses also cause similar clinical presentations, especially in the initial stages of infection, with neither virus possessing any specific distinguishing clinical features. Because the outcomes and management strategies for these two viruses are vastly different, early and accurate diagnosis is imperative. Diagnosis is also important for surveillance, outbreak control, and research related to vaccine and drug development. Available diagnostic tests are aimed at detection of the virus, its antigenic components, or the host immune antibody …

Aleukemic Myeloid Sarcoma Of The Breast, Muhammad Shariq Shaikh, Naila Kayani

Department of Pathology and Laboratory Medicine

Myeloid sarcoma is a solid collection of leukemic blast cells outside bone marrow. It is seen infrequently in association with overt Acute Myeloid Leukemia (AML), however, it invariably transforms into this aggressive condition. A28-year woman presented with a lump in left breast for last 2 years. Morphological and immunophenotypic results of breast mass were consistent with myeloid sarcoma. Bone marrow aspirate and biopsy were normal, however, patient died after one and a half years of diagnosis. Myeloid sarcoma at any extramedullary site heralds development of overt acute myeloid leukemia and should be appropriately managed at the time of diagnosis

A Rare Haemoglobin Variant Identified As K Woolwich In A Pakistani Male, Sidra Asad Ali, Natasha Bahadur Ali

Department of Pathology and Laboratory Medicine

Haemoglobin (Hb) K Woolwich is a rare Hb variant which was first described in a family from West Indies and its occurrence was later reported mainly in Black families from many African countries. We report a case of a young male who came for evaluation of anemia. His complete blood count showed hypochromic, microcytic anemia and his serum ferritin was low. Hb electrophoresis done as part of initial workup showed an abnormal band which moved faster than HbA. For further evaluation, Hb analysis by high performance liquid chromatography was subsequently performed and revealed Hb K Woolwich. This is a rare …

Establishing Quality Control Values For Hematology Parameters: An Insight, Muhammad Shariq Shaikh

Department of Pathology and Laboratory Medicine

No abstract provided.

Clinical Significance Of The Integrin Α6Β4 In Human Malignancies, Rachel L Stewart, Kathleen L O'Connor

Pathology and Laboratory Medicine Faculty Publications

Integrin α6β4 is a cellular adhesion molecule that binds to laminins in the extracellular matrix and nucleates the formation of hemidesmosomes. During carcinoma progression, integrin α6β4 is released from hemidesmosomes, where it can then signal to facilitate multiple aspects of tumor progression including sustaining proliferative signaling, tumor invasion and metastasis, evasion of apoptosis, and stimulation of angiogenesis. The integrin achieves these ends by cooperating with growth factor receptors including EGFR, ErbB-2, and c-Met to amplify downstream pathways such as PI3K, AKT, MAPK, and the Rho family small GTPases. Furthermore, it dramatically alters the transcriptome …