Medical Specialties Commons^™

Temporal Trends Of Molecular Markers Associated With Artemether- Lumefantrine Tolerance/Resistance In Bagamoyo District, Tanzania, M. Malmberg, B. Ngasala, P.E. Ferreira, E. Larsson, I. Jovel, A. Hjalmarsson, M. Petzold, Zul Premji, J.P. Gil, A. Bjorkman, A. Martensson

Pathology, East Africa

Background: Development and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy (ACT) constitutes a major threat to recent global malaria control achievements. Surveillance of molecular markers could act as an early warning system of ACT-resistance before clinical treatment failures are apparent. The aim of this study was to analyse temporal trends of established genotypes associated with artemether-lumefantrine tolerance/resistance before and after its deployment as first-line treatment for uncomplicated malaria in Tanzania 2006.

Methods: Single nucleotide polymorphisms in the P. falciparum multidrug resistance gene 1 (pfmdr1) N86Y, Y184F, D1246Y and P. falciparum chloroquine transporter gene (pfcrt) K76T were analysed from …

Exploration Of In Vivo Efficacy Of Artemether-Lumefantrine Against Uncomplicated Plasmodium Falciparum Malaria In Under Fives In Tabora Region, Tanzania, D. Joseph, A.M. Kabanywanyi, R. Hulser, Zul Premji, O.M.S. Minzi, K. Mugittu

Pathology, East Africa

Background: Tanzania adopted artemether-lumefantrine (AL) as first-line drug for uncomplicated malaria in 2006. Recently, there was an anecdotal report on high malaria recurrence rate following AL treatment in in the (urban and peri-urban), western part of Tanzania. The current report is an exploratory study to carefully and systematically assess AL efficacy in the area.

Methods: Between June and August 2011, a total of 1,126 patients were screened for malaria, 33 had malaria, of which 20 patients met inclusion criteria and were enrolled and treated with standard dose of AL as recommended in the WHO protocol. Treated patients were followed …

Research Brief: "Psychopathology, Iraq And Afghanistan Service, And Suicide Among Veterans Health Administration Patients", Institute For Veterans And Military Families At Syracuse University

Institute for Veterans and Military Families

This brief is about the connections between being a OIF/OEF veteran who receives care from the VHA and suicide mortality. In policy and practice, mental health screenings for OIF/OEF veterans should be implemented in non-VHA healthcare settings and families of OIF/OEF veterans should encourage veterans to seek treatment if they exhibit signs of a mental health condition. The VHA should implement policies that promote its healthcare to veterans in order to decrease suicide risks among veterans and should also offer more mental health screenings for recently returned veterans. Suggestions for future research include looking at risks for suicide after traumatic …

Fluoroquinolone And Macrolide Co-Resistance In Clinical Isolates Of Campylobacter Species: A 15-Year Study In Karachi, Pakistan, Seema Irfan, A Ahmad, D Guhar, E Khan, Fasial Malik, Syed Mahmood, Afia Zafar

Department of Pathology and Laboratory Medicine

Fluoroquinolone and macrolide antibiotics are generally considered as first-line drugs for the treatment of severe campylobacteriosis. This study was conducted to analyse the trend of erythromycin and ofloxacin resistance among Campylobacter spp. isolated from stool specimens over a period of 15 years (1992-2007) at The Aga Khan University clinical laboratory in Karachi, Pakistan. A total of 83 396 stool specimens were processed, with a 14% isolation rate for enteric pathogens. The isolation rate of Campylobacter spp. was low during 1992-93 (6%-13%), peaked in 1996 (46%), then ranged from 20% to 40%. We report a rising trend in ofloxacin resistance, re-emergence …

Neuropsychological Outcomes In Adults Commencing Highly Active Anti-Retroviral Treatment In South Africa: A Prospective Study, John Joska, John Joska, Jennifer Westgarth-Taylor, Jacqueline Hoare, Kevin Thomas, Robert Paul, Landon Myer, Dan Stein

Psychology Faculty Works

BackgroundInfection with HIV may result in significant neuropsychological impairment, especially in late stage disease. To date, there have been no cohort studies of the impact of highly active anti-retroviral treatment (HAART) in South Africa where clade C HIV is predominant.MethodsParticipants in the current study were recruited from a larger study of HIV-associated neurocognitive disorders (HAND) and included a group of individuals commencing HAART (n = 82). Baseline and one-year neuropsychological function was assessed using a detailed battery, and summary global deficit scores (GDS) obtained. Associations with change in GDS were calculated.ResultsParticipants had a median CD4 cell count of 166 at …

Labrad : Vol 38, Issue 2 - December 2012, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Automation in Microbiology Specimen Processing and Inoculation
• Use of Automated Urine Analyzer for Urinanalysis
• Automation in Blood Culture
• Vitek 2 System: An Automated System for Antimicrobial Susceptibility Testing
• TB Diagnosis-A New Horizon
• Serological and Molecular Diagnosis of Malaria
• Diagnosis of Leishmaniasis
• Rapid Detection of Dengue NS1 Antigen by ELISA in Suspected Dengue Patients
• Saline Infusion Hysterosonography to Evaluate Abnormal Uterine Bleeding
• Workshop on “Diagnosis of Fungal Infections in Clinical Laboratory”

Histologic Findings In Biopsies/Resection Specimens From The Small Intestine With Special Emphasis On Celiac Disease: Experience From A Developing Country In South Asia, Huma Arshad, Zubair Ahmad

Department of Pathology and Laboratory Medicine

Biopsies from the small intestine especially the duodenum are now being performed much more frequently than in the past. The most frequent reason for performing duodenal biopsies is to evaluate for malabsorption. In the last few years, increased awareness has resulted in more biopsies sent for evaluation of malabsorption, especially celiac disease (CD). In the duodenum, features of malabsorption (increased intraepithelial lymphocytes, villous shortening, and atrophy) were the most common histologic finding seen in 63.4% of cases. Serum tTG levels were available for correlation in 52.8% of cases. In patients with confirmed CD, 53.4% were MARSH IIIb, and 29.5% were …

Ccpa Regulates Arginine Biosynthesis In Staphylococcus Aureus Through Repression Of Proline Catabolism., Austin S. Nuxoll, Steven M. Halouska, Marat Sadykov, Mark L. Hanke, Kenneth W. Bayles, Tammy Kielian, Robert Powers, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of community-associated and nosocomial infections. Imperative to the success of S. aureus is the ability to adapt and utilize nutrients that are readily available. Genomic sequencing suggests that S. aureus has the genes required for synthesis of all twenty amino acids. However, in vitro experimentation demonstrates that staphylococci have multiple amino acid auxotrophies, including arginine. Although S. aureus possesses the highly conserved anabolic pathway that synthesizes arginine via glutamate, we demonstrate here that inactivation of ccpA facilitates the synthesis of arginine via the urea cycle utilizing proline as a substrate. Mutations within putA, rocD, …

Allogeneic Stem Cell Transplantation In Acute Myeloid Leukemia, Natasha Bahadur Ali, Salman Adil, Mohammad Usman Shaikh, Nehal Masood

Department of Pathology and Laboratory Medicine

We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients). Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

Aplastic Anemia Post Liver Transplant Due To Graft-Versus-Host Disease, Ping Gong, Md, Jerald Z. Gong, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Poster presented at: American society for clinical pathology (ASCP) conference 2012, Boston MA, USA.

Introduction:

The patient was a 64-year-old male presented with a 2 day history of increasing fevers and altered mental status. He underwent orthotopic liver transplant for cryptogenic cirrhosis, probably secondary to non-alcoholic steatohepatitis, 45 days before. The head and neck imaging showed pancytopenia with WBC 0.6 x 109 /L., hemoglobin 6.8 g/dl and platelet 29 x 109 /L.

Macrolide And Fluoroquinolone Resistance In Helicobacter Pylori Isolates: An Experience At A Tertiary Care Centre In Pakistan, Sana Rajper, Erum Khan, Zubair Ahmad, Syed Muhammad Zaheer Alam, Adil Akbar, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objective:
To assess fluoroquinolone and clarithromycin susceptibility pattern along with the types of genomic mutations involved in the resistance of Helicobacter pylori isolates.
Methods:
The cross-sectional study was conducted at the Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi, from June 2009 to July 2010, and comprised 162 gastric biopsy samples which were tested with GenoTypeHelicoDR (Hain Lifescience GmbH, Germany), a reverse hybridisation multiplex polymerase chain reaction (PCR) line probe assay (LiPA). Also, 23S rRNA (ribosomal ribonucleic acid) gene was analysed with three-point mutations at A2146G, A2146C and A2147G for clarithromycin, and gyrA gene was analyzed at two …

Multifocal Venous Thrombosis In Behcet’S Disease, Lena Jafri, Nosheen Nasir, Aysha Almas

Department of Pathology and Laboratory Medicine

Behcet's disease is a multisystem inflammatory vascular disorder with a chronic course characterized by recurrent oral and genital ulcers, eye lesion, arthritis and skin lesions. It has a typically waxing and waning course. The cause and pathogenesis of the disease are unclear and specific treatment is not available. A 39 years old man presented with rash, ocular manifestation and left leg swelling. He was found to have deep venous thrombosis of left leg along with recurrent cerebral venous thrombosis. He was a known case of Behcet's disease since 3 years and had been on anticoagulants since then.

Diagnostic Utility Of Anti-Citrullinated Protein Antibody And Its Comparison With Rheumatoid Factor In Rheumatoid Arthritis, Aysha Habib, Lena Jafri, M. Ahraz Hussain, Saliha Ishaq

Department of Pathology and Laboratory Medicine

Objective: To assess the diagnostic utility of anti-citrullinated protein antibody (anti-CCP) in rheumatoid arthritis (RA) and compare it with rheumatoid factor (RF). Study Design: Analytical study. Place and Duration of Study: Section of Chemical Pathology, Department of Pathology and Microbiology and Medicine, the Aga Khan University, Karachi, from January to May 2010. Methodology: A review of medical records of patients presenting to the clinics with complaints of muscular or joint pains and who were tested for their serum anti-CCP was done. Inclusion criteria were presence of clinical synovitis in at least one joint and an absence of alternative diagnosis. Patients …

Prevalence And Determinants Of Human Papillomavirus Infection And Cervical Lesions In Hiv-Positive Women In Kenya, H De Vuyst, N R. Mugo, M H. Chung, K P. Mckenzie, E Nyongesa-Malava, V Tenet, J W. Njoroge, S R. Sakr, C Jlm Meijer, P Jf Snijders, Farzana Rana, S Franceschi

Pathology, East Africa

Background: We assessed the association of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) with various characteristics, CD4 count and use of combination antiretroviral therapy (cART) among HIV-positive women.

Methods: Cross-sectional study of 498 HIV-positive women who underwent HPV PCR-based testing, cytology, and systematic cervical biopsy.

Results: In all, 68.7% of women were HPV-positive, 52.6% had high-risk (hr) HPV, and 40.2% multiple type infections. High-risk human papillomavirus-positivity did not vary significantly by age but it was negatively associated with education level. The most frequent types in 113 CIN2/3 were HPV16 (26.5%), HPV35 (19.5%), and HPV58 (12.4%). …

An Autopsy Case Of Alveolar Capillary Dysplasia, Yu Shi, John Farber

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Poster presented at College of American Pathologist 2012 in San Diego California.

Patient:

Chief Complaint: A full term, newborn girl developed respiratory distress shortly after birth.

Intraabdominal Cysts Turn Out To Be Distended Large Bowel - An Electively Terminated Fetus With Isolated Imperforate Anus, Yu Shi, Maria Giraldo-Isaza, John Farber

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Patient:

Clinical History: A 19-week male fetus of a 36-year old G7P4 mother was found by ultrasound to have intrabdominal "cysts" and oligo-anhydramnios. At 15 weeks of pregnancy, by ultrasound examination, two intraabdominal cysts measuring 1.1x0.7x0.4 cm and 1.4x1.0x1.0 cm were noted. At 19 week gestation, the ultrasound was performed again showing anhydromaio, ascites, a normal appearing bladder, and multiple cystic structures in the abdomen most likely consistent with dilation of bowel (Figure 1A, B). The mother was consulted and opted to proceed with KCL injection and induction of labor. The nonviable fetus was delivered at 19 5/7 week gestation. …

Sarcopenia, Obesity, And Natural Killer Cell Immune Senescence In Aging: Altered Cytokine Levels As A Common Mechanism, Charles T. Lutz, Lebris S. Quinn

Pathology and Laboratory Medicine Faculty Publications

Human aging is characterized by both physical and physiological frailty. A key feature of frailty, sarcopenia is the age-associated decline in skeletal muscle mass, strength, and endurance that characterize even the healthy elderly. Increases in adiposity, particularly in visceral adipose tissue, are almost universal in aging individuals and can contribute to sarcopenia and insulin resistance by increasing levels of inflammatory cytokines known collectively as adipokines. Aging also is associated with declines in adaptive and innate immunity, known as immune senescence, which are risk factors for cancer and all-cause mortality. The cytokine interleukin-15 (IL-15) is highly expressed in skeletal muscle tissue …

Line Probe Assay For Detection Of Rifampicin And Isoniazid Resistant Tuberculosis In Pakistan, Joveria Qais Farooqi, Erum Khan, Syed Muhammed Zaheer Alam, Asho Ali, Zahra Hasan, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objective:
To assess the efficacy of a line-probe assay delta (LiPA) as rapid diagnostic test for early detection of drug-resistant tuberculosis compared to conventional susceptibility methods in Pakistan.
Methods:
Resistance to rifampicin (RIF) and isoniazid (INH) in 108 smear-positive pulmonary tuberculosis samples was detected using a line-probe assay [GenoType MTBDRplus (Hain Lifescience, GmbH, Nehren, Germany)] at the clinical microbiology laboratory of Aga Khan University Hospital in May, 2009. Results were compared with susceptibilities performed while using agar proportion.
Results:
In comparison to the agar proportion method, the detection rate and specificity of resistance using MTBDR plus was 92.5% and 98.2% …

Low Levels Of Β-Lactam Antibiotics Induce Extracellular Dna Release And Biofilm Formation In Staphylococcus Aureus., Jeffrey B. Kaplan, Era A. Izano, Prerna Gopal, Michael T. Karwacki, Sangho Kim, Jeffrey L. Bose, Kenneth W. Bayles, Alexander R. Horswill

Journal Articles: Pathology and Microbiology

UNLABELLED: Subminimal inhibitory concentrations of antibiotics have been shown to induce bacterial biofilm formation. Few studies have investigated antibiotic-induced biofilm formation in Staphylococcus aureus, an important human pathogen. Our goal was to measure S. aureus biofilm formation in the presence of low levels of β-lactam antibiotics. Fifteen phylogenetically diverse methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains were employed. Methicillin, ampicillin, amoxicillin, and cloxacillin were added to cultures at concentrations ranging from 0× to 1× MIC. Biofilm formation was measured in 96-well microtiter plates using a crystal violet binding assay. Autoaggregation was measured using a visual test tube …

Contribution Of The Staphylococcus Aureus Atl Am And Gl Murein Hydrolase Activities In Cell Division, Autolysis, And Biofilm Formation., Jeffrey L. Bose, Mckenzie K. Lehman, Paul D. Fey, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

The most prominent murein hydrolase of Staphylococcus aureus, AtlA, is a bifunctional enzyme that undergoes proteolytic cleavage to yield two catalytically active proteins, an amidase (AM) and a glucosaminidase (GL). Although the bifunctional nature of AtlA has long been recognized, most studies have focused on the combined functions of this protein in cell wall metabolism and biofilm development. In this study, we generated mutant derivatives of the clinical S. aureus isolate, UAMS-1, in which one or both of the AM and GL domains of AtlA have been deleted. Examination of these strains revealed that each mutant exhibited growth rates comparable …

The Importance Of Amino Acid Composition In Natural Amps: An Evolutional, Structural, And Functional Perspective., Biswajit Mishra, Guangshun Wang

Journal Articles: Pathology and Microbiology

No abstract provided.

Labrad : Vol 38, Issue 1 - July 2012, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• How to Investigate a Bleeding Disorder
• Nucleic Acid Testing at AKUH
• Lab Diagnosis of von Willebrand Disease
• Scoring Systems in Diagnosis of Disseminated Intravascular Coagulation
• Plasma and Platelet Transfusions in Liver Diseases
• Ristocetin Cofactor Activity
• All You Need to Know About Thrombophilia Screening
• Signifi cance of Antiphospholipid Antibodies
• Homocysteine as a Risk Factor of Thrombosis
• Report on 4th Biennial Course in Chemical Pathology

Giant Cell Reparative Granuloma Of Temporal Bone: Case Report Of A 62-Year-Old Male, Muhammad Waqas, Naeem Sultan Ali, Muhammad Zubair Tahir, Syed Ather Enam, Zeeshan-Ud-Din, Mubasher Ikram

Section of Otolaryngology, Head & Neck Surgery

Giant cell reparative granuloma (GCRG) is an uncommon non‑neoplastic reactive tumor which occurs almost exclusively within the mandible and maxilla. GCRG of the temporal bone is a rare condition. It has been found to affect predominantly adolescents and adults (age: 10‑25 years). We report a case of a 62‑year‑old male with GCRG of left temporal bone who presented to us with progressive left temporal swelling for 3 months. It was associated with hearing loss. There was no history of trauma. A non‑contrast computed tomography scan brain showed a locally destructive lesion involving squamous temporal bone closely related to the left …

Three Linked Vasculopathic Processes Characterize Kawasaki Disease: A Light And Transmission Electron Microscopic Study, Jan M. Orenstein, Stanford T. Shulman, Linda M. Fox, Susan C. Baker, Masato Takahashi, Tricia R. Bhatti, Pierre A. Russo, Gary W. Mierau, Jean Pierre De Chadarévian, Elizabeth J. Perlman, Cynthia Trevenen, Alexandre T. Rotta, Mitra B. Kalelkar, Anne H. Rowley

Pathology Faculty Publications

Background

Kawasaki disease is recognized as the most common cause of acquired heart disease in children in the developed world. Clinical, epidemiologic, and pathologic evidence supports an infectious agent, likely entering through the lung. Pathologic studies proposing an acute coronary arteritis followed by healing fail to account for the complex vasculopathy and clinical course.

Methodology/Principal Findings

Specimens from 32 autopsies, 8 cardiac transplants, and an excised coronary aneurysm were studied by light (n=41) and transmission electron microscopy (n=7). Three characteristic vasculopathic processes were identified in coronary (CA) and non-coronary arteries: acute self-limited necrotizing arteritis (NA), subacute/chronic (SA/C) vasculitis, and luminal …

Differential Effects Of Interleukin-17 Receptor Signaling On Innate And Adaptive Immunity During Central Nervous System Bacterial Infection., Debbie Vidlak, Tammy Kielian

Journal Articles: Pathology and Microbiology

Although IL-17A (commonly referred to as IL-17) has been implicated in the pathogenesis of central nervous system (CNS) autoimmune disease, its role during CNS bacterial infections remains unclear. To evaluate the broader impact of IL-17 family members in the context of CNS infection, we utilized IL-17 receptor (IL-17R) knockout (KO) mice that lack the ability to respond to IL-17, IL-17F and IL-17E (IL-25). In this article, we demonstrate that IL-17R signaling regulates bacterial clearance as well as natural killer T (NKT) cell and gamma-delta (γδ) T cell infiltrates during Staphylococcus aureus-induced brain abscess formation. Specifically, when compared with wild-type (WT) …

Clinical Significance Of Maternal Anti-Cw Antibodies: A Review Of Three Cases And Literature, Shabneez Malik, Bushra Moiz

Department of Pathology and Laboratory Medicine

Anti Cw antibody is a low frequency immunoglobulin (IgG) against red cell antigen- Cw. It is clinically significant and may cause haemolytic disease of the newborn. Due to its low frequency, it is not included in routine antenatal antibody screening panel. The incidence of Anti Cw antibodies has not been reported in our population. Here, we describe the clinical and laboratory spectra of three pregnant women having low titres anti Cw antibodies. Fortunately, haemolytic disease of the newborn was not encountered in any case.

Proline-Rich Tyrosine Kinase 2 (Pyk2) Regulates Igf-I-Induced Cell Motility And Invasion Of Urothelial Carcinoma Cells, Marco Genua, Shi-Qiong Xu, Simone Buraschi, Stephen C. Peiper, Leonard G. Gomella, Antonio Belfiore, Renato V. Iozzo, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The insulin-like growth factor receptor I (IGF-IR) plays an essential role in transformation by promoting cell growth and protecting cancer cells from apoptosis. We have recently demonstrated that the IGF-IR is overexpressed in invasive bladder cancer tissues and promotes motility and invasion of urothelial carcinoma cells. These effects require IGF-I-induced Akt- and MAPK-dependent activation of paxillin. The latter co-localizes with focal adhesion kinases (FAK) at dynamic focal adhesions and is critical for promoting motility of urothelial cancer cells. FAK and its homolog Proline-rich tyrosine kinase 2 (Pyk2) modulate paxillin activation; however, their role in regulating IGF-IR-dependent signaling and motility in …

Deciphering Mechanisms Of Staphylococcal Biofilm Evasion Of Host Immunity., Mark L. Hanke, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilms are adherent communities of bacteria contained within a complex matrix. Although host immune responses to planktonic staphylococcal species have been relatively well-characterized, less is known regarding immunity to staphylococcal biofilms and how they modulate anti-bacterial effector mechanisms when organized in this protective milieu. Previously, staphylococcal biofilms were thought to escape immune recognition on the basis of their chronic and indolent nature. Instead, we have proposed that staphylococcal biofilms skew the host immune response away from a proinflammatory bactericidal phenotype toward an anti-inflammatory, pro-fibrotic response that favors bacterial persistence. This possibility is supported by recent studies from our laboratory using …

Environmental Friendly Synthesis, Characterization Of Surface Modifiable Starch Encapsulated Gold Nanoparticles With Bactericidal And Catalytic Activity, Dillon Pender

Mahurin Honors College Capstone Experience/Thesis Projects

In the present study, we report the green synthesis of gold nanoparticles (GNPs), using potato starch as a reducing as well as a stabilizing agent in an aqueous buffer medium. The resulting starch-GNPs (St-GNPs) were near spherical in shape with an average diameter of 15 ± 5 nm. In this approach, St-GNPs were characterized and investigated for their antibacterial properties against both gram negative (Escherichia coli) and gram positive (Staphylococcus epidermidis) bacteria. These St-GNPs were found to possess significant dose dependent antibacterial activity against bacteria. Also, St-GNPs showed a significant catalytic activity and can easily be …

Interactions Of Nitric Oxide And Superoxide Pathways In Hyperglycemic Endothelial Cells, Steven Clay Rogers

Graduate Theses and Dissertations

Cardiovascular complications arising from diabetic hyperglycemia represents one of the leading causes of death and greatest public health challenges of modern societies. Despite state-of-the-art glucose control, diabetic patients remain at a markedly increased risk of cardiovascular disease. The loss of endothelial function (the development of diabetic endothelial dysfunction) has been implicated in the development of numerous diabetic cardiovascular diseases. The endothelial cell produces many vasoactive substances, hormones and cytoprotective biological factors. Endothelial cells are also involved in and affected by the initiation of inflammatory responses through the release and interaction of cytokines and other immune system molecules. Therefore, regulation of …