Medical Specialties Commons^™

Human West Nile Virus Disease Outbreak In Pakistan, 2015–2016, E. Khan, Kelli L. Barr, Joveria Farooqi, Dhani Prakoso, Alizae Abbas, Zain Y. Khan, Shanze Ashi, Kehkashan Imtiaz, Z Aziz, Faisal Malik

Department of Pathology and Laboratory Medicine

Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological …

Emergence Of An Extensively Drug-Resistant Salmonella Enterica Serovar Typhi Clone Harboring A Promiscuous Plasmid Encoding Resistance To Fluoroquinolones And Third-Generation Cephalosporins, Rumina Hasan, Sadia Shakoor, Farah Naz Qamar, Dania Khalid Saeed, Ghazala Shaheen, Shahida Qureshi, Mohammad Tahir Yousafzai, Muhammad Khalid Salim, Zahra Hasan, Elizabeth J. Klemma, Andrew J. Page, Kim Judge, Vanessa K. Wong, Timothy J. Dallman, Satheesh Nair, Stephen Baker, Gordon Dougan

Department of Pathology and Laboratory Medicine

Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S. Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant …

Breast Cancer Knowledge, Perceptions And Practices In A Rural Community In Coastal Kenya, Shahin Sayed, Anthony Ngugi, Megan R. Mahoney, Jaameeta Kurji, Zohray M. Talib, Sarah B. Macfarlane, Theresa A. Wynn, Mansoor Saleh, Amyn B Lakhani, Esther Nderitu, Felix Agoi, Zul Premji, Jo Anne Zujewski, Zahir Moloo

Pathology, East Africa

Background: Data on breast healthcare knowledge, perceptions and practice among women in rural Kenya is limited. Furthermore, the role of the male head of household in influencing a woman’s breast health seeking behavior is also not known. The aim of this study was to assess the knowledge, perceptions and practice of breast cancer among women, male heads of households, opinion leaders and healthcare providers within a rural community in Kenya. Our secondary objective was to explore the role of male heads of households in influencing a woman’s breast health seeking behavior.

Methods: This was a mixed method cross-sectional study, conducted …

Treated Hypothyroidism Is Associated With Cerebrovascular Disease But Not Alzheimer's Disease Pathology In Older Adults, Willa D. Brenowitz, Fang Han, Walter A. Kukull, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

Thyroid hormone (TH) disease is common among older adults and is associated with cognitive impairment. However, pathologic correlates are not well understood. We studied pathologic and clinical factors associated with hypothyroidism, the most common form of TH disease, in research subjects seen annually for clinical evaluations at U.S. Alzheimer’s Disease Centers. Thyroid disease and treatment status were assessed during clinician interviews. Among autopsied subjects, there were 555 participants with treated hypothyroidism and 2,146 with no known thyroid disease; hypothyroidism was associated with severe atherosclerosis (OR=1.35 95% CI: 1.02, 1.79) but not Alzheimer’s disease (AD) pathologies (amyloid plaques or neurofibrillary tangles). …

Frequency Of Macroprolactin In Hyperprolactinemia, Aysha Habib Khan, Noreen Abbas Sherazi, Mirza Zain Baig

Department of Pathology and Laboratory Medicine

Objective: To determine the frequency of Macroprolactin (MaPRL) in patients with increased total prolactin and its clinical and financial impact.
Study Design: Cross-sectional study.
Place and Duration of Study: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from March to May 2015. Methodology: Patients with high total prolactin were screened by polyethylene glycol (PEG) precipitation for determination of MaPRL. Clinical history, imaging work-ups, and cost incurred in further investigations were collected by telephonic interview after verbal consent. Patients were stratified into true hyperprolactinemia and macroprolactinemia after PEG treatment, based on monomeric prolactin …

Genomic And Cellular Studies Establish The Pathogenesis And Cellular Mechanisms Of Disease-Causing Mutations In Families With Autosomal Recessive Disorders, Nesreen Khalid Ahmad Al Jezawi

Dissertations

The majority of the reported genetic disorders in the UAE population are of the autosomal recessive type, which is mainly due to high rates of consanguinity within the UAE national population, and within a significant proportion of other UAE expatriate communities; such as Arabs and Pakistanis. It is estimated that more than 50% of all marriages among Emiratis occur between biologically related couples, with first cousin marriages being the highest. That could be attributed to sociocultural values in the region. Successful management of genetic diseases can be achieved by the implementation of effective preventative programs that could help reduce the …

Infection Of A Ventricular Septal Defect Patch With Acremonium Species, Nosheen Nasir, Kauser Jabeen, Joveria Farooqi, Binish Arif Sultan, Afia Zafar, Aamir Hameed Khan, Muneer Amanullah, Farheen Ali

Section of Internal Medicine

A ventricular septal defect (VSD) patch infection with Acremonium species isolated from vegetation and blood culture is described. Antifungal treatment was discontinued after 3 months and patient developed relapse. Surgery with prolonged oral voriconazole was instituted with recovery. We emphasize importance of surgery and prolonged therapy to treat such infections.

Direct Detection Of Shigella In Stool Specimens By Use Of A Metagenomic Approach, Jie Liu, Mathieu Almeida, Furqan Kabir, Sadia Shakoor, Shahida Qureshi, Anita K. M. Zaidi, Shan Li, Boubou Tamboura, Samba O. Sow, Inacio Mandomando

Department of Paediatrics and Child Health

The underestimation of Shigella species as a cause of childhood diarrhea disease has become increasingly apparent with quantitative PCR (qPCR)-based diagnostic methods versus culture. We sought to confirm qPCR-based detection of Shigella via a metagenomics approach. Three groups of samples were selected from diarrheal cases from the Global Enteric Multicenter Study: nine Shigella culture-positive and qPCR-positive (culture⁺ qPCR⁺) samples, nine culture-negative but qPCR-positive (culture^- qPCR⁺) samples, and nine culture-negative and qPCR-negative (culture^- qPCR^-) samples. Fecal DNA was sequenced using paired-end Illumina HiSeq, whereby 3.26 × 10⁸ ± 5.6 × 10 …

Mammographic Breast Density And Breast Cancer Molecular Subtypes: The Kenyan-African Aspect, Asim Jamal, Maeve Mullooly, Shahin Sayed, Rose Ndumia, Innocent Abayo, James Orwa, Ronald Wasike, Zahir Moloo, Gretchen L. Gierach

Internal Medicine, East Africa

Introduction: Data examiningmammographic breast density (MBD) among patients in Sub-Saharan Africa are sparse.We evaluated how MBD relates to breast cancer characteristics in Kenyan women undergoing diagnostic mammography.

Methods: This crosssectional study included women with pathologically confirmed breast cancers (𝑛 = 123). Pretreatment mammograms of the unaffectedbreast were assessed to estimate absolute dense area (cm2), nondense area (cm2), and percent density (PD). Relationships between density measurements and clinical characteristics were evaluated using analysis of covariance.

Results: Median PD and dense area were 24.9% and 85.3 cm2. Higher PD and dense area were observed in younger women (𝑃 < 0.01). Higher dense and nondense areas were observed in obese women (𝑃-trend < 0.01). Estrogen receptor (ER) positive patients (73%) had higher PD and dense area than ER-negative patients (𝑃 ≤ 0.02). Triple negative breast cancer (TNBC) patients (17%) had lower PD and dense area (𝑃 ≤ 0.01) compared with non-TNBCs. No associations were observed between MBD and tumor size and grade.

Conclusions: Our findings show …

Lipoblastoma: A Clinicopathologic Review Of 23 Cases From A Major Tertiary Care Center Plus Detailed Review Of Literature, Jamshid Abdul Ghafar, Zubair Ahmad, Muhammad Usman Tariq, Naila Kayani Naila Kayani, Nasir Ud Din

Department of Pathology and Laboratory Medicine

Objective: Lipoblastoma is a rare neoplasm that occurs mostly in infants and children. Although benign, it has a tendency for local recurrence.
Results: Clinical and pathological features of 23 cases of lipoblastoma described. Patients’ age ranged from 8 months to 18 years with mean and median age 4.1 and 2.5 years, respectively. Male:female ratio was 2.8:1. Most common sites were lower extremities (9 cases), followed by abdominal cavity and retroperitoneum (4 cases), and scrotum/groin (3 cases). Grossly, 22 tumors were well circumscribed and multi nodular. All cases showed lobules composed of adi‑ pocytes and lipoblasts with intervening fbrous septa and …

Methylation In Mycobacterium Tuberculosis Is Lineage Specific With Associated Mutations Present Globally, Jody Phelan, Paola Florez De Sessions, Leopold Tientcheu, Joao Perdigao, Diana Machado, Rumina Hasan, Zahra Hasan, Indra L. Bergval, Richard Anthony, Ruth Mcnerney

Department of Pathology and Laboratory Medicine

DNA methylation is an epigenetic modification of the genome involved in regulating crucial cellular processes, including transcription and chromosome stability. Advances in PacBio sequencing technologies can be used to robustly reveal methylation sites. The methylome of the Mycobacterium tuberculosis complex is poorly understood but may be involved in virulence, hypoxic survival and the emergence of drug resistance. In the most extensive study to date, we characterise the methylome across the 4 major lineages of M. tuberculosis and 2 lineages of M. africanum, the leading causes of tuberculosis disease in humans. We reveal lineage-specific methylated motifs and strain-specific mutations that are …

Cabot Rings And Marked Anisopoikilocytosis In Imerslund-Gräsbeck Syndrome., Derrick L. Goubeaux, Weijie Li

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Automated Real-Time Collection Of Pathogen-Specific Diagnostic Data: Syndromic Infectious Disease Epidemiology, L. Meyers, C. C. Ginocchio, A. N. Faucett, F. S. Nolte, P. H. Gesteland, A. Leber, D. Janowiak, V. Donovan, S. Juretschko, M. A. Poritz, +23 Additional Authors

Journal Articles

© Lindsay Meyers, Christine C Ginocchio, Aimie N Faucett, Frederick S Nolte, Per H Gesteland, Amy Leber, Diane Janowiak,. Background: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. Objective: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test …

Experimental Intravascular Hemolysis Induces Hemodynamic And Pathological Pulmonary Hypertension: Association With Accelerated Purine Metabolism, Victor P. Bilan, Frank Schneider, Enrico M. Novelli, Eric E. Kelley, Sruti Shiva, Mark T. Gladwin, Edwin K. Jackson, Stevan P. Tofovic

Faculty & Staff Scholarship

Pulmonary hypertension (PH) is emerging as a serious complication associated with hemolytic disorders, and plexiform lesions (PXL) have been reported in patients with sickle cell disease (SCD). We hypothesized that repetitive hemolysis per se induces PH and angioproliferative vasculopathy and evaluated a new mechanism for hemolysis-associated PH (HA-PH) that involves the release of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) from erythrocytes. In healthy rats, repetitive admin- istration of hemolyzed autologous blood (HAB) for 10 days produced reversible pulmonary parenchymal injury and vascular remodeling and PH. Moreover, the combination of a single dose of Sugen-5416 (SU, 200mg/kg) and 10-day …

Wdr5 Supports Colon Cancer Cells By Promoting Methylation Of H3k4 And Suppressing Dna Damage, Beth K. Neilsen, Binita Chakraborty, Jamie L. Mccall, Danielle E. Frodyma, Richard L. Sleightholm, Kurt W. Fisher, Robert E. Lewis

Faculty & Staff Scholarship

Background: KMT2/MLL proteins are commonly overexpressed or mutated in cancer and have been shown to support cancer maintenance. These proteins are responsible for methylating histone 3 at lysine 4 and promoting transcription and DNA synthesis; however, they are inactive outside of a multi-protein complex that requires WDR5. WDR5 has been implicated in cancer for its role in the COMPASS complex and its interaction with Myc; however, the role of WDR5 in colon cancer has not yet been elucidated.

Methods: WDR5 expression was evaluated using RT-qPCR and western blot analysis. Cell viability and colony forming assays were utilized to evaluate the …

Subclinical Atherosclerosis, Cardiovascular Health, And Disease Risk: Is There A Case For The Cardiovascular Health Index In The Primary Prevention Population?, Sarah S. Singh, Courtney S. Pilkerton, Carl D. Shrader Jr, Stephanie J. Frisbee

Faculty & Staff Scholarship

Background: Current primary prevention guidelines for cardiovascular disease (CVD) prioritize risk identification, risk stratification using clinical and risk scores, and risk reduction with lifestyle interventions and pharmacotherapy. Subclinical atherosclerosis is an early indicator of atherosclerotic burden and its timely recognition can slow or prevent progression to CVD. Thus, individuals with subclinical atherosclerosis are a priority for primary prevention. This study takes a practical approach to answering a challenge commonly faced by primary care practitioners: in patients with no known CVD, how can individuals likely to have subclinical atherosclerosis be easily identified using existing clinical data and/or information provided by the …

Mucinous Adenocarcinoma Of The Scalp: Primary Cutaneous Neoplasm Versus Underlying Metastatic Disease, Ciara A. Brown, Michael C. Lynch, Cristiane M. Ueno

Faculty & Staff Scholarship

Primary cutaneous mucinous carcinoma (PCMC) is a rare mucin-pro- ducing malignancy derived from epithelial glandular structures. The literature re- garding this topic is mostly in the form of case reports and case series. PCMC tends to present in the elderly with predilection for the head and neck and on initial assessment it can be easily mistaken for a simple inclusion cyst. Although PCMC is often indolent in nature, in rare instances it can metastasize and should remain a differential diagnosis in a selected population. The significance in identifying PCMC is reliably differentiating it from metastatic mucinous adenocarcinoma. We present a …

The Effect Of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors On Nonfasting Remnant Cholesterol In A Real World Population, Anthony P. Morise, Jennifer Tennant, Sari D. Holmes, Danyel H. Tacker

Faculty & Staff Scholarship

Background. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have demonstrated significant effects on low-density lipoprotein (LDL) cholesterol and nonhigh density lipoprotein (HDL) cholesterol. To date, there have been limited reports on the effect of PCSK9 inhibitors on remnant cholesterol. Objectives. Assess the effect of PCSK9 inhibitors on nonfasting remnant cholesterol in a real world population. Identify whether pretreatment triglyceride levels are associated with PCSK9 inhibition success as indicated by changes in remnant cholesterol levels. Methods. Patients in our adult lipid clinic (n = 109) receiving PCSK9 inhibition for atherosclerotic cardiovascular disease or familial hypercholesterolemia who had available pre- and post- …

Hyperspectral Imaging And K-Means Classification For Histologic Evaluation Of Ductal Carcinoma In Situ, Yasser Khouj, Jeremy Dawson, James Coad, Linda Vona-Davis

Faculty & Staff Scholarship

Hyperspectral imaging (HSI) is a non-invasive optical imaging modality that shows the potential to aid pathologists in breast cancer diagnoses cases. In this study, breast cancer tissues from different patients were imaged by a hyperspectral system to detect spectral differences between normal and breast cancer tissues. Tissue samples mounted on slides were identified from 10 different patients. Samples from each patient included both normal and ductal carcinoma tissue, both stained with hematoxylin and eosin stain and unstained. Slides were imaged using a snapshot HSI system, and the spec- tral reflectance differences were evaluated. Analysis of the spectral reflectance values indicated …

Total Sulfane Sulfur Bioavailability Reflects Ethnic And Gender Disparities In Cardiovascular Disease, Saurabh Rajpal, Pavan Katikaneni, Matthew Deshotels, Sibile Pardue, John Glawe, Xinggui Shen, Nuri Akkus, Kalgi Modi, Ruchi Bhandari, Paari Dominic, Pratap Reddy, Gopi K. Kolluru, Christopher G. Kevil

Faculty & Staff Scholarship

Hydrogen sulfide (H2S) has emerged as an important physiological and pathophysiological signaling molecule in the cardiovascular system influencing vascular tone, cytoprotective responses, redox reactions, vascular adap- tation, and mitochondrial respiration. However, bioavailable levels of H2S in its various biochemical metabolite forms during clinical cardiovascular disease remain poorly understood. We performed a case-controlled study to quantify and compare the bioavailability of various biochemical forms of H2S in patients with and without cardiovascular disease (CVD). In our study, we used the reverse-phase high performance liquid chromatography monobromobimane assay to analytically measure bioavailable pools of H2S. Single nucleotide polymorphisms (SNPs) were also identified …

Cytogenomic Identification And Long-Read Single Molecule Real-Time (Smrt) Sequencing Of A Bardet-Biedl Syndrome 9 (Bbs9) Deletion, J. Reiner, L. Pisani, W. Qiao, R. Singh, Y. Yang, L. Shi, W. A. Khan, R. Sebra, N. Cohen, S. A. Scott, +3 Additional Authors

Journal Articles

No abstract provided.

Pleural Effusion In A 7-Year-Old Child - With Unique Cells, N. Gupta, K. Das

Journal Articles

No abstract provided.

The Path Report Volume 2 Issue 3, Pathology Department, New York Medical College

The Path Report

No abstract provided.

Metabolic And Transcriptional Modules Independently Diversify Plasma Cell Lifespan And Function, Wing Y. Lam, Arijita Jash, Cong-Hui Yao, Lucas D'Souza, Rachel Wong, Ryan M. Nunley, Gordon P. Meares, Gary J. Patti, Deepta Bhattacharya

Faculty & Staff Scholarship

Plasma cell survival and the consequent duration of immunity vary widely with infection or vaccination. Using fluorescent glucose analog uptake, we defined multiple developmentally independent mouse plasma cell populations with varying life- spans. Long-lived plasma cells imported more fluo- rescent glucose analog, expressed higher surface levels of the amino acid transporter CD98, and had more autophagosome mass than did short-lived cells. Low amino acid concentrations triggered re- ductions in both antibody secretion and mitochon- drial respiration, especially by short-lived plasma cells. To explain these observations, we found that glutamine was used for both mitochondrial respira- tion and anaplerotic reactions, yielding …

Overexpression Of Β1 Integrin Contributes To Polarity Reversal And A Poor Prognosis Of Breast Invasive Micropapillary Carcinoma, B. Liu, X. Zheng, F. Meng, Y. Han, Y. Song, F. Liu, S. Li, L. Zhang, X. Zhang, L. Fu, +1 Additional Author

Journal Articles

© Liu et al. Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive breast cancer. Polarity reversal exemplified by cluster growth is hypothesized to contribute to the invasiveness and metastasis of IMPC. In this study, we demonstrate that levels of β1 integrin and Rac1 expression were greater in breast IMPC than in invasive breast carcinoma of no specific type and paraneoplastic benign breast tissue. We show that silencing β1 integrin expression using the β1 integrin inhibitor AIIB2 partially restored polarity in IMPC primary cell clusters and downregulated Rac1. Thus, overexpression of β1 integrin upregulates Rac1. Univariate analysis showed …

A Primary Breast Cancer With Distinct Foci Of Estrogen Receptor-Alpha Positive And Negative Cells Derived From The Same Clonal Origin As Revealed By Whole Exome Sequencing, K. Kyker-Snowman, B. Erlanger Avigdor, M. Nasim, A. Cimino-Mathews, S. J. Wheelan, P. Argani, B. H. Park

Journal Articles

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Background/purpose: Tumor heterogeneity is a now well-recognized phenomenon that can affect the classification, prognosis and treatment of human cancers. Heterogeneity is often described in primary breast cancers based upon histologic subtypes, hormone- and HER2-receptor status, and immunolabeling for various markers, which can be seen within a single tumor as mixed cellular populations, or as separate discrete foci. Experimental design/methods: Here, we present a case report of a patient’s primary breast cancer that had two separate but adjacent histologic components, one that was estrogen receptor (ER) positive, and the other ER …

Stromal Infiltration Of Tumor-Associated Macrophages Conferring Poor Prognosis Of Patients With Basal-Like Breast Carcinoma, M. Yang, Z. Li, M. Ren, S. Li, L. Zhang, X. Zhang, F. Liu

Journal Articles

© Ivyspring International Publisher. Aims: Tumor associated macrophages (TAMs) play a critical role in the initiation and progression of breast cancer. However, their prognostic significance in the molecular subtype of basal-like breast cancer (BLBC) is poorly understood. The aim of this study was to investigate the extent and patterns of TAMs in BLBC and their associations with clinicopathological features and patient survival. Methods and Results: We evaluated TAMs in 200 cases of BLBC by immunohistochemistry using the M2 macrophage marker CD163 and the pan-macrophage marker CD68 in tumor nest and stroma, and assessed their prognostic significance. The study demonstrated that …

Phosphoglycerate Mutase 1 Is Highly Expressed In C6 Glioma Cells And Human Astrocytoma, Z. Liu, J. Ding, C. Du, N. Xu, E. Wang, J. Li, Y. Wang, J. Yu

Journal Articles

No abstract provided.

Oligomerization Of Bacterially Expressed H1n1 Recombinant Hemagglutinin Contributes To Protection Against Viral Challenge, Tess E. Kuenstling, Anthony R. Sambol, Steven H. Hinrichs, Marilynn A. Larson

Journal Articles: Pathology and Microbiology

Vaccination is the most effective intervention to prevent influenza and control the spread of the virus. Alternatives are needed to the traditional egg-based vaccine strategy for a more rapid response to new outbreaks. Two different hemagglutinin (HA) fragments (rHA1_1-326 and rHA1_53-269) derived from influenza A virus subtype H1N1 were expressed in Escherichia coli and characterized by immunoblot, gel filtration, hemagglutination, and competitive binding assays. rHA1_1-326 included neutralizing epitopes and the trimerization domain, whereas rHA1_53-269 included only the head of HA with the neutralizing epitopes. Mice were immunized with rHA1_1-326 or rHA1_53-269, and …

Searching For Novel Biomarkers Using A Mouse Model Of Cln3-Batten Disease, Derek Timm, Jacob T. Cain, Ryan D. Geraets, Katherine A. White, Seung Yon Koh, Tammy Kielian, David A. Pearce, Michelle L. Hastings, Jill M. Weimer

Journal Articles: Pathology and Microbiology

CLN3-Batten disease is a rare, autosomal recessive disorder involving seizures, visual, motor and cognitive decline, and premature death. The Cln3Δex7/8 mouse model recapitulates several phenotypic characteristics of the most common 1.02kb disease-associated deletion. Identification of reproducible biomarker(s) to facilitate longitudinal monitoring of disease progression and provide readouts for therapeutic response has remained elusive. One factor that has complicated the identification of suitable biomarkers in this mouse model has been that variations in animal husbandry appear to significantly influence readouts. In the current study, we cross-compared a number of biological parameters in blood from Cln3Δex7/8 mice and control, non-disease mice on …