Pathology Commons^™

Increase In Isolation Of Extended Spectrum Beta Lactamase Producing Multidrug Resistant Non Typhoidal Salmonellae In Pakistan., Kauser Jabeen, Afia Zafar, Seema Irfan, Erum Khan, Vikram Mehraj, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background:Increasing resistance to quinolones and ceftriaxone in non typhoidal Salmonellae is a global concern. Resistance to quinolone and 3rd generation cephalosporin amongst non typhoidal Salmonellae (NTS) from Pakistan has been reported in this study.

Methods:

Retrospective analysis of laboratory data was conducted (1990-2006). NTS were isolated and identified from clinical samples using standard microbiological techniques. Antimicrobial susceptibility testing was performed by Kirby Bauer. Extended spectrum beta lactamase production (ESBL) was detected using combined disc method. Ciprofloxacin sensitivity was detected by nalidixic acid screening method. Minimum inhibitory concentration (MIC) of ciprofloxacin was determined by agar dilution method. Statistical analysis was …

Trends In Salmonella Enteric Serovar Typhi In Nairobi, Kenya From 2004 To 2006, Doris M. Mengo1, Sam Kariuki, Ann W. T. Muigai, Gunturu Revathi

Pathology, East Africa

Background: Typhoid fever is a global health problem. The World Health Organization (WHO) estimates that the current annual global burden of typhoid is approximately 22 million new cases, 5% of which are fatal.

Methodology: To assess the trends in antibiotic resistance in 100 Salmonella enterica serovar Typhi strains were isolated from the blood of patients in Nairobi, Kenya, from 2004 to 2006. All isolates were tested against ampicilin, chloramphenic, nalidixic acid, ciprofloxacin, cotrimoxazole, cefuroxime, cefriaxone, amoxycillin/clavulanic acid, tetracycline and gentamycin. Susceptibility and resistance were determined using MIC and disk diffusion tests.

Results: From 2004 to 2006 a total of 100 …

Increased Isolation Of Esbl Producing Klebsiella Pneumoniae With Emergence Of Carbapenem Resistant Isolates In Pakistan: Report From A Tertiary Care Hospital, Erum Khan, Muslima Ejaz, Afia Zafar, Kauser Jabeen, Sadia Shakoor, Raunaq Inayat, Rumina Hasan

Department of Pathology and Laboratory Medicine

OBJECTIVE: To report trends of extended spectrum beta lactamase (ESBL), multidrug resistant (MDR) ESBL and emergence of carbapenem resistant ESBL producing isolates of K. pneumoniae from Pakistan.

METHODS: Retrospective analysis of laboratory data was conducted (2002-2007). K. pneumoniae were isolated and identified from clinical samples using standard microbiological techniques. Antimicrobial susceptibility testing was performed by Kirby Bauer. ESBL was detected using combined disc method. Statistical analysis was performed using SPSS version 13.

RESULTS: 15914 K. pneumoniae isolates (2002-2007) were analyzed. Significant increase in ESBL and MDR ESBL producing K. pneumoniae (p = or < 0.0001) was observed. We found significant association of ESBL positive K. pneumoniae with age less than 10 years, males and blood isolates (p = 0.001). 0.4% (n=23) of ESBL positive isolates were carbapenem resistant.

CONCLUSIONS: Increase in ESBL and carbapenem resistant …

Microrna In Situ Hybridization In The Human Entorhinal And Transentorhinal Cortex, Peter T. Nelson, James Dimayuga, Bernard R. Wilfred

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) play key roles in gene expression regulation in both healthy and disease brains. To better understand those roles, it is necessary to characterize the miRNAs that are expressed in particular cell types under a range of conditions. In situ hybridization (ISH) can demonstrate cell- and lamina-specific patterns of miRNA expression that would be lost in tissue-level expression profiling. In the present study, ISH was performed with special focus on the human entorhinal cortex (EC) and transentorhinal cortex (TEC). The TEC is the area of the cerebral cortex that first develops neurofibrillary tangles in Alzheimer's disease (AD). However, the …

Anti-Argonaute Rip-Chip Shows That Mirna Transfections Alter Global Patterns Of Mrna Recruitment To Microribonucleoprotein Complexes, Wang-Xia Wang, Bernard R. Wilfred, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) play key roles in gene expression regulation by guiding Argonaute (AGO)-containing microribonucleoprotein (miRNP) effector complexes to target polynucleotides. There are still uncertainties about how miRNAs interact with mRNAs. Here we employed a biochemical approach to isolate AGO-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with a previously described anti-AGO antibody. Co-immunoprecipitated (co-IPed) RNAs were subjected to downstream Affymetrix Human Gene 1.0 ST microarray analysis. During rigorous validation, the "RIP-Chip" assay identified target mRNAs specifically associated with AGO complexes. RIP-Chip was performed after transfecting brain-enriched miRNAs (miR-107, miR-124, miR-128, and miR-320) and nonphysiologic control miRNA to identify …

Nuclear Expression Of Klf6 Tumor Suppressor Factor Is Highly Associated With Overexpression Of Erbb2 Oncoprotein In Ductal Breast Carcinomas, Ricardo C. Gehrau, Diego S. D'Astolfo, Catherine I. Dumur, Jose L. Bocco, Nicolas P. Koritschoner

Pathology Publications

Background

Krüppel-like factor 6 (KLF6) is an evolutionarily conserved and ubiquitously expressed protein that belongs to the mammalian Sp1/KLF family of transcriptional regulators. Though KLF6 is a transcription factor and harbors a nuclear localization signal it is not systematically located in the nucleus but it was detected in the cytoplasm of several tissues and cell lines. Hence, it is still not fully settled whether the tumor suppressor function of KLF6 is directly associated with its ability to regulate target genes.

Methodology/Principal Findings

In this study we analyzed KLF6 expression and sub-cellular distribution by immunohistochemistry in several normal and tumor tissues …

I-Kappa-Kinase-2 (Ikk-2) Inhibition Potentiates Vincristine Cytotoxicity In Non-Hodgkin's Lymphoma, Ayad Al-Katib, Alan A. Arnold, Amro Aboukameel, Angela Sosin, Peter Smith, Anwar N. Mohamed, Frances W. Beck, Ramzi M. Mohammad

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

IKK-2 is an important regulator of the nuclear factor-κB (NF-κB) which has been implicated in survival, proliferation and apoptosis resistance of lymphoma cells. In this study, we investigated whether inhibition of IKK-2 impacts cell growth or cytotoxicity of selected conventional chemotherapeutic agents in non-Hodgkin's lymphoma.

Two established model systems were used; Follicular (WSU-FSCCL) and Diffuse Large Cell (WSU-DLCL2) Lymphoma, both of which constitutively express p-IκB. A novel, selective small molecule inhibitor of IKK-2, ML120B (N-[6-chloro-7-methoxy-9H-β-carbolin-8-yl]-2-methylnicotinamide) was used to perturb NF-κB in lymphoma cells. The growth inhibitory effect of ML120B (M) alone and in combination with cyclophosphamide monohydrate (C), …

Utility Of Immunohistochemical Markers In Differentiating Benign From Malignant Follicular-Derived Thyroid Nodules, Husain A. Saleh, Bo Jin, John Barnwell, Opada Alzohaili

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Thyroid nodules are common among adults though only a small percentage is malignant, which can histologically mimic benign nodules. Accurate diagnosis of these thyroid nodules is critical for the proper clinical management.

Methods

We investigated immunoexpression in 98 surgically removed benign thyroid nodules including 52 hyperplastic nodules (HN) and 46 follicular/Hurthle cell adenomas (FA), and 54 malignant tumors including 22 follicular carcinoma (FC), 20 classic papillary carcinoma (PTC), and 12 follicular variant papillary carcinoma (FVPC).

Results

The staining results showed that malignant tumors express galectin-3, HBME-1, CK19 and Ret oncoprotein significantly more than benign nodules. The sensitivity of …

Pulmonary Carcinosarcoma Initially Presenting As Invasive Aspergillosis: A Case Report Of Previously Unreported Combination, Ariyo O. Olobatoke, Doina David, Wasif Hafeez, Thien Van, Husain A. Saleh

Wayne State University Associated BioMed Central Scholarship

Abstract

Carcinosarcoma of the lung is a malignant tumor composed of a mixture of carcinoma and sarcoma elements. The carcinomatous component is most commonly squamous followed by adenocarcinoma. The sarcomatous component commonly comprises the bulk of the tumor and shows poorly differentiated spindle cell features. Foci of differentiated sarcomatous elements such as chondrosarcoma and osteosarcoma may be seen. Aspergillus pneumonia is the most common form of invasive aspergillosis and occurs mainly in patients with malignancy, immunocompromizing or debilitating diseases. Patients with Aspergillus pneumonia present with fever, cough, chest pain and occasionally hemoptysis. Tissue examination is the most reliable method for …

Nuclear Factor-Kappa B Localization And Function Within Intrauterine Tissues From Term And Preterm Labor And Cultured Fetal Membranes, Sonali Vora, Asad Abbas, Chong J. Kim, Taryn Ls Summerfield, Juan P. Kusanovic, Jay D. Iams, Roberto Romero, Douglas A. Kniss, William E. Ackerman Iv

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The objective of this study was to quantify the nuclear localization and DNA binding activity of p65, the major transactivating nuclear factor-kappa B (NF-kappaB) subunit, in full-thickness fetal membranes (FM) and myometrium in the absence or presence of term or preterm labor.

Methods

Paired full-thickness FM and myometrial samples were collected from women in the following cohorts: preterm no labor (PNL, N = 22), spontaneous preterm labor (PTL, N = 21), term no labor (TNL, N = 23), and spontaneous term labor (STL, N = 21). NF-kappaB p65 localization was assessed by immunohistochemistry, and DNA binding activity was …

Mir-107 Is Reduced In Alzheimer's Disease Brain Neocortex: Validation Study, Peter T. Nelson, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

MiR-107 is a microRNA (miRNA) that we reported previously to have decreased expression in the temporal cortical gray matter early in the progression of Alzheimer's disease (AD). Here we study a new group of well-characterized human temporal cortex samples (N=19). MiR-107 expression was assessed, normalized to miR-124 and let-7a. Correlation was observed between decreased miR-107 expression and increased neuritic plaque counts (P< 0.05) and neurofibrillary tangle counts (P< 0.02) in adjacent brain tissue. Adjusted miR-107 and BACE1 mRNA levels tended to correlate negatively (trend with regression P< 0.07). In sum, miR-107 expression tends to be lower relative to other miRNAs as AD progresses.

Understanding Caretakers' Dilemma In Deciding Whether Or Not To Adhere With Referral Advice After Pre-Referral Treatment With Rectal Artesunate, D.O. Simba, D.C. Kakoko, M. Warsame, Zul Premji, M.F. Gomes, G. Tomson, E. Johansson

Pathology, East Africa

Background: Malaria kills. A single rectal dose of artesunate before referral can reduce mortality and prevent permanent disability. However, the success of this intervention depends on caretakers' adherence to referral advice for follow-up care. This paper explores the dilemma facing caretakers when they are in the process of deciding whether or not to transit their child to a health facility after pre-referral treatment with rectal artesunate.

Methods: Four focus group discussions were held in each of three purposively selected villages in Mtwara rural district of Tanzania. Data were analysed manually using latent qualitative content analysis.

Results: The theme «Caretakers dilemma …

Who Gets Prompt Access To Artemisinin-Based Combination Therapy? A Prospective Community-Based Study In Children From Rural Kilosa, Tanzania, D.O. Simba, M. Warsame, D. Kakoko, Z. Mrango, G. Tomson, Zul Premji, M. Petzold

Pathology, East Africa

Background: Effective and timely case management remains one of the fundamental pillars for control of malaria. Tanzania introduced artemisinin-combination therapy [ACT] for uncomplicated malaria; however, the policy change is challenged by limited availability of ACTs due to high cost. This study aimed to determine factors influencing prompt access to ACTs among febrile children in rural Kilosa, Tanzania.

Methods and Findings: In a community-based study, 1,235 randomly selected children under five were followed up weekly for six months, in 2008. Using a structured questionnaire, children's caretakers were asked about the child's febrile history in the last seven days, and treatment …

Carcinosarcoma Of The Esophagus, Ziaur Rehman, Inam Pal, Zubair Ahmad, Asim Qureshi

Section of General Surgery

Carcinosarcoma of the esophagus is a rare neoplasm characterized histologically by presence of carcinomatous and sarcomatous elements. Case report of carcinosarcoma of the esophagogastric junction whose morphological and immunohistochemical features makes it quite distinctive from other tumours is presented. It was an ulcerated lesion diagnosed in an elderly Afghan lady located 34 cms from the incisor teeth. The patient was a smoker.

Helicobacter Pylori: Prevalence And Antibiotic Susceptibility Among Kenyans, Andrew Nyerere Kimang’A, Gunturu Revathi, Samuel Kariuki, Shahin Sayed, Smita Devani

Pathology, East Africa

Background. Helicobacter pylori infection in Kenya is staggeringly high. Evidence links infection of the gastric mucosa by H. pylori with subsequent development of gastric pathologies.

Aim. We investigated the prevalence of H. pylori in dyspeptic patients, its relationship with gastric pathologies, and associated antibiotic susceptibility profiles, and compared two media to find the appropriate medium that enhances growth and expedites culture and isolation.

Methods. Rapid urease and histological tests were used to screen for H. pylori. Culture was performed to test sensitivity and evaluate media. Selective and nutritional supplements were added to culture media (Colombia blood agar and brainheart infusion …

Labrad : Vol 35, Issue 1 - January - February 2010, Aga Khan University Hospital, Karachi

LABRAD

• Assessment of Osteoporosis Risk by NTx- A Biochemical Marker
• Antibodies Against Cyclic Citrullinated Peptides (Anti-CCP) Assay in Rheumatoid Arthritis
• A Disintegrin and Metallopeptidase with Thrombospondin Type 1 Motif, 13 (ADAMTS-13)
• Soluble Transferrin Receptor (sTfR)
• Diagnosis of Cryptococcal Meningitis
• Infections in Thalassaemia
• CDX-2, A Reliable Diagnostic Marker for Carcinomas of Colorectal Origin
• Radiopaque Metallic Marker Insertion in Breast Cancers Prior to Neoadjuvant/Preoperative Chemotherapy
• Meeting Reports: 10TH International Radiological Conference 2009
• Continuing Medical Education Seminar Organised by Clinical Laboratory at AKUH

Bone Marrow Examination Findings At Aga Khan University Hospital, Nairobi, Nancy Okinda, Riyat Malkit

Pathology, East Africa

Objective: To establish the bone marrow examination findings and determine the indication for bone marrow examination.

Design: A retrospective audit.

Setting: Aga Khan University Hospital, Nairobi.

Subjects: All bone marrow aspirates done at Aga Khan University for the period comprising February 2003 to February 2006 were retrieved and analysed.

Results: A total of 356 patient’s case histories including bone marrow examination results were analysed. Ages of the patients ranged from 18 months to 91 years. Males were 180 (50.6%) and females were 176 (49.4%). Nutritional anaemia as a group was the most common haematological disorder found on bone marrow …

Population Pharmacokinetics And Pharmacodynamics Of Artemether And Lumefantrine During Combination Treatment In Children With Uncomplicated Falciparum Malaria In Tanzania, S.F. Hietala, A. Martensson, B. Ngasala, S. Dahlstrom, N. Lindegardh, A. Annerberg, Zul Premji, A. Farnert, P. Gil, A. Bjorkman, M. Ashton

Pathology, East Africa

The combination of artemether (ARM) and lumefantrine is currently the first-line treatment of uncomplicated falciparum malaria in mainland Tanzania. While the exposure to lumefantrine has been associated with the probability of adequate clinical and parasitological cure, increasing exposure to artemether and the active metabolite dihydroartemisinin (DHA) has been shown to decrease the parasite clearance time. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine in African children with uncomplicated malaria. In addition to drug concentrations and parasitemias from 50 Tanzanian children with falciparum malaria, peripheral parasite densities from 11 asymptomatic children were …

Population Genetic Analysis Of Large Sequence Polymorphisms In Plasmodium Falciparum Blood-Stage Antigens, A.D. Ahouidi, A.K. Bei, D.E. Neafsey, O. Sarr, S. Volkman, D. Milner, J. Cox-Singh, M.U. Ferreira, O. Ndir, Zul Premji, S. Mboup, M.T. Duraisingh

Pathology, East Africa

Plasmodium falciparum, the causative agent of human malaria, invades host erythrocytes using several proteins on the surface of the invasive merozoite, which have been proposed as potential vaccine candidates. Members of the multi-gene PfRh family are surface antigens that have been shown to play a central role in directing merozoites to alternative erythrocyte receptors for invasion. Recently, we identified a large structural polymorphism, a 0.58 Kb deletion, in the C-terminal region of the PfRh2b gene, present at a high frequency in parasite populations from Senegal. We hypothesize that this region is a target of humoral immunity. Here, by analyzing 371 …

Treatment Of Asymptomatic Carriers With Artemether-Lumefantrine: An Opportunity To Reduce The Burden Of Malaria?, B. Ogutu, A.B. Tiono, M. Makanga, Zul Premji, A.D. Gbadoe, D. Ubben, A.C. Marrast, O. Gaye

Pathology, East Africa

Background: Increased investment and commitment to malaria prevention and treatment strategies across Africa has produced impressive reductions in the incidence of this disease. Nevertheless, it is clear that further interventions will be necessary to meet the international target of a reversal in the incidence of malaria by 2015. This article discusses the prospective role of an innovative malaria control strategy - the community-based treatment of asymptomatic carriers of Plasmodium falciparum, with artemisinin-based combination therapy (ACT). The potential of this intervention was considered by key scientists in the field at an Advisory Board meeting held in Basel, in April 2009. …