Pathology Commons^™

A Brief Report Of Immunohistochemical Markers To Identify Aggressive Hepatoblastoma., Vivekanand Singh, Michelle Manalang, Meenal Singh, Udayan Apte

Manuscripts, Articles, Book Chapters and Other Papers

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although survival of patients has improved significantly over the last 2 decades, a significant number of patients do not respond to standard chemotherapy. We conducted a pilot study to understand if there was immunophenotypic difference between tumors that respond well to chemotherapy versus that do not. We selected 10 cases of HB from children presenting at our hospital. All patients had initial tissue diagnosis, underwent chemotherapy followed by surgical resection. The cases were divided into 2 groups: aggressive group with 5 cases (all of which had a poor response …

Intestinal Carriage Of Third-Generation Cephalosporin-Resistant And Extended-Spectrum Β-Lactamase-Producing Enterobacteriaceae In Healthy Us Children., Shamim Islam, Rangaraj Selvarangan, Neena Kanwar, Rendie Mchenry, James D. Chappell, Natasha Halasa, Mary E. Wikswo, Daniel C. Payne, Parvin H. Azimi, L Clifford Mcdonald, Oscar G. Gomez-Duarte

Manuscripts, Articles, Book Chapters and Other Papers

Background: The epidemiology of antibiotic-resistant Enterobacteriaceae intestinal carriage in healthy US children has not been well characterized.

Methods: Children between 14 days and 14 years of age were enrolled during well-child visits in Oakland, California, Kansas City, Kansas, and Nashville, Tennessee, between December 2013 and March 2015. Data on recent antibiotic use by the child and travel and hospitalization history of all members of each child's household were obtained with a risk-factor survey. Stool specimens collected from the subjects were screened for extended-spectrum β-lactamase-producing (ESBL-P) bacteria using CHROMagar ESBL medium. Putative ESBL-P Escherichia coli and Klebsiella colonies underwent phenotypic confirmation …

Review Of Karyotypic Data From Low Grade Glial Brain Tumors, Specifically Pilocytic Astrocytomas, And Correlation Of Genetic Aberrations With Tumor Recurrence., Linda D. Cooley, Scott C. Smith, Lisa Warren, Melissa Gener, Kevin Ginn, John Herriges

Posters

Abstract: Brain tumors are the most common solid tumor of childhood. Approximately 50% of pediatric CNS tumors are low grade gliomas (WHO grade I or II) and Pilocytic astrocytoma (PA) is the most common accounting for 33% of all gliomas in children 0-14 years and ~18% of all childhood brain tumors. Prognosis with this slow-growing tumor is excellent; 10 year overall survival of ~95%. However, event free survival averages ~50%. Patient age and extent of tumor resection are key prognostic factors; tumor location and size impact resection and outcome. Histopathological features indicate PA is a benign tumor and rarely are …

Non O1, Non O139 Vibrio Cholerae Bacteraemia In An Infant; Case Report And Literature Review, Mirza Zain Baig, Umme Hani Abdullah, Yusra Shafquat, Khadija Nuzhat Humayun, Afia Zafar

Medical College Documents

Non 01, Non O139 Vibrio cholerae bacteraemia is a rare but potentially fatal occurrence. There have been very few incidents of this infection from around the world. The treatment regimen of antibiotics also varies in literature. We present a case of bacteraemia caused by Non O1, Non O139 Vibrio cholerae along with associated risk factors, disease manifestations, laboratory diagnosis and treatment regimen. This serves to add additional information regarding symptoms and signs of this infection along with management of patient. Knowledge regarding this topic shall be highly useful to professionals if further cases are detected. In the discussion section, a …

Diagnostic Dilemma Of Patients With Methylmalonic Aciduria: Experience From A Tertiary Care Centre In Pakistan, Hafsa Majid, Aysha Habib Khan, Lena Jafri, Azeema Jamil, Nasir Yousufzai, Midhat Fatima, Zeba Zulfiqar Ali, Bushra Afroze

Department of Pathology and Laboratory Medicine

Objective: To determine the frequency of disorders leading to methylmalonic acidurias.
Methods: This cross-sectional study was conducted from January 2013 to April 2016 at the Aga Khan University Hospital, Karachi, and comprised patients diagnosed with methylmalonic acidurias based on urine organic acid analysis. Clinical history and biochemical data was collected from the biochemical genetics laboratory requisition forms. Organic acid chromatograms of all the subjects were critically reviewed by a biochemical pathologist and a metabolic physician. For assessing the clinical outcome, medical charts of the patients were reviewed. SPSS 19 was used for data analysis.
Results: Of the 1,778 patients 50(2.81%) …

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 …

Reducing Discard Blood Draw Volumes From Subcutaneously Implanted Ports (Port) In Patients With End Stage Renal Disease (Esrd), Uttam Garg, Tyson Moore, Renita Trujillo, Penny Monachino, Amy Wiebold, Angela Ferguson, Gabor Oroszi, Vimal Chadha

Posters

Background
•To monitor clinical status, dialysis and transplant patients with ESRD frequently require blood draws.
•To preserve their veins and to avoid frequent intravenous access, these patients, especially young children, require PORT placement.
•The PORT is flushed with saline and filled with heparinized saline to prevent blood clotting between blood draws.
•To avoid contamination from PORT fluids, a fixed amount of blood is withdrawn and discarded before the blood sample is drawn for laboratory analyses. Currently, the recommended discard blood volume is 5 mL (five times the reservoir volume of most PORTs and attached catheters.)
•The volume of discarded blood …

Significant Loss Of Blood Amino Acids And Free Carnitine In Newborns Receiving Continuous Renal Replacement Therapy (Crrt), Uttam Garg, Marita Thompson, Bradley A. Warady, Vimal Chadha

Posters

Background

•Newborns with acute kidney injury (AKI) or end-stage kidney disease (ESKD) often receive prolonged CRRT when the early initiation of peritoneal dialysis is either contraindicated or unable to be performed. •These patients often receive total parenteral nutrition (TPN) to meet their nutritional goals. •Little to no information exists on the loss of blood amino acids (AA) and carnitine during CRRT in these patients. •The objective of this study was to determine the amino acids and carnitine losses in newborns receiving prolonged CRRT and TPN. Material and Methods

•Three newborns who received prolonged (> 2 weeks) CRRT and TPN were …

High Heterotrophic Counts In Potable Water And Antimicrobial Resistance Among Indicator Organisms In Two Peri-Urban Communities Of Karachi, Pakistan, Sadia Shakoor, Imran Ahmed, Saima Mukhtiar, Israr Ahmed, Farzeen Hirani, Shazia Sultana, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objective: Fecal contamination of potable water leads to unsafe water supply. Although many urban areas of large metropolitan cities receive safe water, peri-urban areas are often not monitored by public health authorities and water supply and quality remain unknown. We assessed microbiological quality and rates of antimicrobial resistance in viable indicator bacteria in two peri-urban communities of Karachi, Pakistan. Water samples were collected over 5 months (October 2015 to February 2016) from these peri-urban communities and samples were processed for microbiological quality as per Standing Committee of Analysts, United Kingdom and World Health Organization guidelines and criteria for drinking water. …

Precision Newborn Screening For Lysosomal Disorders, Melissa M. Minter Baerg, Stephanie D. Stoway, Jeremy Hart, Lea Mott, Dawn S. Peck, Stephanie L. Nett, Jason S. Eckerman, Jean M. Lacey, Coleman T. Turgeon, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Silvia Tortorelli, Dietrich Matern, Lars Mørkrid, Piero Rinaldo

Pathology and Laboratory Medicine Faculty Publications

Purpose: The implementation of newborn screening for lysosomal disorders has uncovered overall poor specificity, psychosocial harm experienced by caregivers, and costly follow-up testing of false-positive cases. We report an informatics solution proven to minimize these issues.

Methods: The Kentucky Department for Public Health outsourced testing for mucopolysaccharidosis type I (MPS I) and Pompe disease, conditions recently added to the recommended uniform screening panel, plus Krabbe disease, which was added by legislative mandate. A total of 55,161 specimens were collected from infants born over 1 year starting from February 2016. Testing by tandem mass spectrometry was integrated with multivariate pattern recognition …

Experience With The Quantitative Lyta Gene Real-Time Polymerase Chain Reaction For The Detection Of Streptococcus Pneumoniae From Pediatric Whole Blood In Pakistan, Furqan Kabir, Sahrish Muneer, Adil Kalam, Ana Sami, Shahida Qureshi, Aneeta Hotwani, Atif Riaz, Syed Mohiuddin, Mohammad Tahir Yousafzai, Sara Hussain, Syed Asad Ali, Sadia Shakoor

Department of Paediatrics and Child Health

Background: We present our experience with optimization and diagnostic use of quantitative real-time polymerase chain reaction (PCR) targeting the lytA gene of Streptococcus pneumoniae for the detection of S. pneumoniae in whole blood of children ≥5 CFU/10 μl or 1 copy of DNA/2 μl of blood.
Methods: This assay was applied on 1912 whole blood specimens collected from children pneumonia, of which 35 specimens were lytA positive. The bacterial loads were determined through categorization of load into five different categories, i.e., very high load, high load, moderate load, low load, and very low load.
Results: Of the 35 lytA-positive …

Antibiotic Prophylaxis Is Associated With Subsequent Resistant Infections In Children With An Initial Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae Infection., Sibani Das, Amanda L. Adler, Arianna Miles-Jay, Matthew P. Kronman, Xuan Qin, Scott J. Weissman, C A. Burnham, Alexis Elward, Jason G. Newland, Rangaraj Selvarangan, Kaede V. Sullivan, Theoklis Zaoutis, Danielle M. Zerr

Manuscripts, Articles, Book Chapters and Other Papers

The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged species, resistance determinants, and fumC-fimH (E. coli) or tonB (Klebsiella pneumoniae) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 …

Selective Screening For Organic Acidurias And Amino Acidopathies In Pakistani Children, Noreen Abbas Sherazi, Aysha Habib Khan, Lena Jafri, Azeema Jamil, Nasir Ali Khan, Bushra Afroze

Department of Pathology and Laboratory Medicine

Objective: To determine the frequency of organic acidurais (OA) and amino acidopathies (AA) in selected high-risk patients screened in two years.
Study Design: Retrospective Observational study.
Place and Duration of Study: The Aga Khan University Hospital (AKUH), Karachi, from January 2013 to December 2014.
Methodology: Patients with OA and AA were included in the study and patients with IMDs other than OA and AA were excluded. Amino acids and organic acids were analyzed on high performance liquid chromatography and gas chromatography-mass spectrometry respectively. Clinical data and chromatograms of patients screened for IMDs were reviewed by chemical pathologist and metabolic physician. …

Forensic And Clinical Diagnosis In "Shaken Baby Syndrome", Between Child Abuse And Iatrogenic Abuse, Roxana M. Duncea, Irina Apostol, Relu G. Calota, Vladimir Belis

Journal of Mind and Medical Sciences

“Shaken baby syndrome” in child abuse cases is a challenge for pediatrician and forensic experts, often a diagnosis of exclusion, with overwhelming moral and legal implications. Diagnosis is based on: subdural bleeding, rupture of retinal vessels, traumatic diffuse axonal injury with diffuse brain encephalopathy in the absence of external traumatic injuries and anamnesis data of an accidentally head injury.

Microscopic findings in diffuse axonal injuries were initially considered as a specific traumatic effect due to unrestricted movement and accelerated rotation of the head. Immunohistochemistry of beta amyloid protein precursor is gold standard method for identifying pathological diffuse axonal lesions, which …

An Expanded Role For Nurses In Laboratory Utilization, Marilyn S. Hamilton, Rangaraj Selvarangan, Michele Fix, Lynn E. Shriver

Posters

Introduction: The majority of laboratory testing errors occur in the pre-analytical stage, including specimen collection. Children provide special challenges including small blood volumes, small veins, and an inability to cooperate. We describe collaboration between laboratorians and nursing staff to improve specimen collection and the reliability of test results.

Methods: We identified three areas for improvement: 1) Volume of blood for culture, 2) Urine collection, and 3) Appropriate blood collection through a line. Base line data was established. Guidelines for specimen collection were updated. Nurse members of the Laboratory Utilization Committee developed educational tools.

Results: Nursing education was effective at improving …

Hematuria Without Microalbuminuria, Angela Ferguson, Vimal Chadha, Amy Wiebold, Uttam Garg

Posters

Background

Microabubiminuria is a condition in which small amounts of albumin are excreted in the urine without overt nephropathy. Based on the

American Diabetic Association classification, microalbuminuria is defined as urinary excretion of albumin of 30–300 mg per 24 hours or 20–200 mcg/min or 30–300 mcg/mg creatinine. Various conditions such as diabetes, hypertension, and impaired renal tubular reabsorption can lead to microalbuminuria. Microalbuminuria is an indicator and predictor of the development of overt nephropathy. If identified and treated early, overt nephropathy can be prevented and averted. Proteinuria and hematuria are the two most common urinary abnormalities encountered during routine urinalysis. …

Reference Intervals For Thyroid Stimulating Hormone And Free Thyroxine Derived From Neonates Undergoing Routine Screening For Congenital Hypothyroidism At A University Teaching Hospital In Nairobi, Kenya: A Cross Sectional Study, Geoffrey Omuse, Ali Kassim, Francis Kiigu, Ra'ana Hussain, Mary Limbe

Pathology, East Africa

Background: In order to accurately interpret neonatal thyroid function tests (TFTs), it is necessary to have population specific reference intervals (RIs) as there is significant variation across different populations possibly due to genetic, environmental or analytical issues. Despite the importance of RIs, globally there are very few publications on RIs for neonatal TFTs primarily due to ethical and technical issues surrounding recruitment of neonates for a prospective study. To the best of our knowledge, this is the first report from Africa on neonatal RIs for TFTs.

Methods: We used hospital based data largely derived from neonates attending the wellness clinic …

Rapid Detection Of In Vitro Antituberculous Drug Resistance Among Smear-Positive Respiratory Samples Using Microcolony Detection-Based Direct Drug Susceptibility Testing Method, Irim Iftikhar, Seema Irfan, Joveria Farooqi, Zahida Azizullah, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: With the rise in multidrug-resistant tuberculosis, there is a search for newer techniques that will rapidly detect drug-resistant Mycobacterium tuberculosis. Although molecular techniques can detect resistance, culture is still considered gold standard, especially in resource-limited settings where quick, cheap, and easy techniques are needed. The aim of the study was to evaluate microcolony method thin layer agar (TLA) for quick detection of resistance against the first- and second-line antituberculous drugs in clinical isolates. This was a cross-sectional study performed at Aga Khan University Hospital.
Material and Methods: A total of 87 Z-N stain smear-positive pulmonary samples were received and …

Yap And The Hippo Pathway In Pediatric Cancer., Atif Ahmed, Abdalla D. Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada

Manuscripts, Articles, Book Chapters and Other Papers

The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation …

Pediatric Ovarian Growing Teratoma Syndrome., Rebecca M. Rentea, Aaron Varghese, Atif Ahmed, Alexander Kats, Michelle Manalang, Tazim Dowlut-Mcelroy, Richard J. Hendrickson

Manuscripts, Articles, Book Chapters and Other Papers

Ovarian immature teratoma is a germ cell tumor that comprises less than 1% of ovarian cancers and is treated with surgical debulking and chemotherapy depending on stage. Growing teratoma syndrome (GTS) is the phenomenon of the growth of mature teratoma elements with normal tumor markers during or following chemotherapy for treatment of a malignant germ cell tumor. These tumors are associated with significant morbidity and mortality due to invasive and compressive growth as well as potential for malignant transformation. Current treatment modality is surgical resection. We discuss a 12-year-old female who presented following resection of a pure ovarian immature teratoma …

Simplified Antibiotic Regimens For Treatment Of Clinical Severe Infection In The Outpatient Setting When Referral Is Not Possible For Young Infants In Pakistan (Simplified Antibiotic Therapy Trial [Satt]): A Randomised, Open-Label, Equivalence Trial, Fatima Mir, Imran Nisar, Shiyam S. Tikmani, Benazir Baloch, Sadia Shakoor, Fyezah Jehan, Imran Ahmed, Simon Cousens, Anita K M Zaidi

Department of Paediatrics and Child Health

Background: Parenteral antibiotic therapy for young infants (aged 0–59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection.
Methods: We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0–59 days) who either presented at a primary health-care …

Stars In Cytoplasm: Pediatric Neuroblastoma, Monazza Chaudhary, Shahzad Sarwar, Natasha Bahadur Ali

Section of Haematology/Oncology

We report a case of a 2-year-old female child who presented with abdominal distention and fever. On examination, there was a palpable mass in the right hypochondrium. Computed tomography of the abdomen revealed a large mass in the right suprarenal area. Biopsy of the mass revealed malignant round blue cell neoplasm. Bone marrow examination showed diffuse infiltration with atypical mononuclear cells and cytogenetic studies showed positivity for NMyc translocation.

Functional Validation Of Novel Compound Heterozygous Variants In B3gat3 Resulting In Severe Osteopenia And Fractures: Expanding The Disease Phenotype., Florian Job, Shuji Mizumoto, Laurie Smith, Natario Couser, Ashley Brazil, Howard Saal, Melanie Patterson, Margaret Gibson, Sarah E. Soden, Neil A. Miller, Isabelle Thiffault, Carol J. Saunders, Shuhei Yamada, Katrin Hoffmann, Kazuyuki Sugahara, Emily G. Farrow

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: A new disease class of syndromes, described as linkeropathies, which are derived from defects in the glycosaminoglycan-linker region as well as glycosaminoglycan-side chains of proteoglycans is increasingly being recognized as a cause of human disease. Proteoglycans are an essential component of the extracellular matrix. Defects in the enzymatic process of proteoglycan synthesis broadly occur due to the incorrect addition of side chains. Previously, homozygous missense variants within the B3GAT3 gene encoding beta 1,3 glucuronyltransferase 3(GlcAT-I) responsible for the biosynthesis of glycosaminoglycans have been described in 7 individuals.

CASE PRESENTATION: In this study, a 4-year-old patient with a severe phenotype …

Biallelic Mutations In Tbcd, Encoding The Tubulin Folding Cofactor D, Perturb Microtubule Dynamics And Cause Early-Onset Encephalopathy., Elisabetta Flex, Marcello Niceta, Serena Cecchetti, Isabelle Thiffault, Margaret G. Au, Alessandro Capuano, Emanuela Piermarini, Anna A. Ivanova, Joshua W. Francis, Giovanni Chillemi, Balasubramanian Chandramouli, Giovanna Carpentieri, Charlotte A. Haaxma, Andrea Ciolfi, Simone Pizzi, Ganka V. Douglas, Kara Levine, Antonella Sferra, Maria Lisa Dentici, Rolph R. Pfundt, Jean-Baptist Lepichon, Emily G. Farrow, Frank Baas, Fiorella Piemonte, Bruno Dallapiccola, John M. Graham, Carol J. Saunders, Enrico Bertini, Richard A. Kahn, David A. Koolen, Marco Tartaglia

Manuscripts, Articles, Book Chapters and Other Papers

Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin …

Reference Intervals For Thyroid Stimulating Hormone And Free Thyroxine Derived From Neonates Undergoing Routine Screening For Congenital Hypothyroidism At A University Teaching Hospital In Nairobi, Kenya: A Cross Sectional Study, Geoffrey Omuse, Ali Kassim, Francis Kiigu, Syeda Hussain, Mary Limbe

Pathology, East Africa

Background: In order to accurately interpret neonatal thyroid function tests (TFTs), it is necessary to have population specific reference intervals (RIs) as there is significant variation across different populations possibly due to genetic, environmental or analytical issues. Despite the importance of RIs, globally there are very few publications on RIs for neonatal TFTs primarily due to ethical and technical issues surrounding recruitment of neonates for a prospective study. To the best of our knowledge, this is the first report from Africa on neonatal RIs for TFTs.

Methods: We used hospital based data largely derived from neonates attending the wellness clinic …

Pathogen-Specific Burdens Of Community Diarrhoea In Developing Countries: A Multisite Birth Cohort Study (Mal-Ed), Sadia Shakoor, Shahida Qureshi, Furqan Kabir, Anita K. M. Zaidi, Zulfiqar Ahmed Bhutta, Imran Ahmed, Didar Alam, Syed Asad Ali, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Pathology and Laboratory Medicine

Background: Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community.
Methods: We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through …

Cyclooxygenase-2, Prostaglandin E2, And Prostanoid Receptor Ep2 In Fluid Flow Shear Stress-Mediated Injury In The Solitary Kidney., Tarak Srivastava, Uri S. Alon, Patricia A. Cudmore, Belal Tarakji, Alexander Kats, Robert E. Garola, R Scott Duncan, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Lynda F. Bonewald, Ashraf El-Meanawy, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Hyperfiltration subjects podocytes to increased tensile stress and fluid flow shear stress (FFSS). We showed a 1.5- to 2.0-fold increase in FFSS in uninephrectomized animals and altered podocyte actin cytoskeleton and increased synthesis of prostaglandin E2 (PGE2) following in vitro application of FFSS. We hypothesized that increased FFSS mediates cellular changes through specific receptors of PGE2. Presently, we studied the effect of FFSS on cultured podocytes and decapsulated isolated glomeruli in vitro, and on solitary kidney in uninephrectomized sv129 mice. In cultured podocytes, FFSS resulted in increased gene and protein expression of cyclooxygenase (COX)-2 but not COX-1, prostanoid receptor EP2 …

Lps And Pan-Induced Podocyte Injury In An In Vitro Model Of Minimal Change Disease: Changes In Tlr Profile., Tarak Srivastava, Mukut Sharma, Kok-Hooi Yew, Ram Sharma, R Scott Duncan, Moin A. Saleem, Ellen T. Mccarthy, Alexander Kats, Patricia A. Cudmore, Uri S. Alon, Christopher J. Harrison

Manuscripts, Articles, Book Chapters and Other Papers

Minimal change disease (MCD), the most common idiopathic nephrotic syndrome in children, is characterized by proteinuria and loss of glomerular visceral epithelial cell (podocyte) ultrastructure. Lipopolysaccharide (LPS) and puromycin aminonucleoside (PAN) are used to study podocyte injury in models of MCD in vivo and in vitro. We hypothesized that LPS and PAN influence components of the innate immune system in podocytes such as the Toll-Like Receptor (TLRs), TLR adapter molecules, and associated cytokines. Our results show that cultured human podocytes constitutively express TLRs 1-6 and TLR-10, but not TLRs 7-9. LPS (25 μg/ml) or PAN (60 μg/ml) caused comparable derangement …

Effectiveness Of Sequential V. Standard Triple Therapy For Treatment Of Helicobacter Pylori Infection In Children In Nairobi, Kenya, Ahmed Laving, Rose Kamenwa, Shahin Sayed, Andrew Nyerere Kimang'a, Gunturu Revathi

Paediatrics and Child Health, East Africa

Background: Once the diagnosis of Helicobacter pylori is confirmed, treatment requires at least two antibiotics and an acid inhibitor for a minimum of seven days. Unfortunately, treatment failures are being frequently reported. Treatment regimens that include sequential administration of antibiotics with acid inhibitors have been developed to try and increase the rate of eradication.

Objective: To determine the effectiveness of a novel 10-day sequential therapy compared with the standard 10-day triple therapy for treatment of H. pylori infection in children.

Methods: A double-blinded, randomised, controlled trial was conducted. Children under the age of 16 years with recurrent abdominal pain associated …

Atypical Clinical And Diagnostic Features In Ménétrier's Disease In A Child, Michael Chung, Jaime Pittenger, Deborah Flomenhoft, Jeffrey Bennett, Eun Young Lee, Harohalli Shashidhar

Internal Medicine Faculty Publications

Ménétrier's disease is one of the rarest protein-losing gastropathies in childhood. It is characterized clinically by non-specific gastrointestinal symptoms and edema, biochemically by hypoalbuminemia, and pathologically by enlarged gastric folds. In adults, this disease can be devastating with significant morbidity and mortality. In childhood, it is a self-limiting, transient and benign illness. Its treatment is largely supportive with total parenteral nutrition (TPN) while oral intake is encouraged. Acute onset of vomiting in healthy school age children can be initially explained by acute viral gastroenteritis. However, persistent vomiting associated with hematemesis and severe abdominal pain should warrant further work-up. This case …