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Hines, TX, United States

Johnson-Welch S.F.,University of Texas Southwestern Medical Center | Weinberg A.,University of Texas Southwestern Medical Center | Seikaly M.,Ut Southwestern Medical Center
Pediatric Transplantation | Year: 2012

PTLD of the CNS is a rare complication of solid organ transplantation, and there are only case reports/series available in the literature. Current literature suggests that CNS PTLD carries a worse prognosis than PTLD outside the CNS, and most are of B-cell lineage, predominately monomorphic, and are associated with EBV infection. Because this disorder is so rare, there is no standard chemotherapy for pediatric patients with CNS PTLD and reported therapies for EBV-associated CNS PTLD are heterogeneous with mixed results. Since outcomes of CNS PTLD are historically poor, we attempted to develop a novel therapeutic treatment regimen. Based on a review of the literature and with the help of a multidisciplinary team, we created a regimen of chemotherapy that included dexamethasone and high-dose methotrexate in addition to intravenous and intraventricular Rituximab in two pediatric patients. The intraventricular chemotherapy succeeded in shrinking the tumor in both of our patients; however, as shown in the second case, the clinical outcome depends on the location of the tumor. Systemic and intraventricular therapies hold promise in the management of EBV-associated CNS PTLD; however the rarity of this entity prevents the development of well-designed studies necessary for the establishment of an evidence-based treatment standard. © 2012 John Wiley & Sons A/S.

Gattineni J.,University of Texas Southwestern Medical Center | Gattineni J.,Ut Southwestern Medical Center | Baum M.,University of Texas Southwestern Medical Center
Pediatric Nephrology | Year: 2012

Regulation of phosphate homeostasis is critical for many biological processes, and both hypophosphatemia and hyperphosphatemia can have adverse clinical consequences. Only a very small percentage (1%) of total body phosphate is present in the extracellular fluid, which is measured by routine laboratory assays and does not reflect total body phosphate stores. Phosphate is absorbed from the gastrointestinal tract via the transcellular route [sodium phosphate cotransporter 2b (NaPi2b)] and across the paracellular pathway. Approximately 85% of the filtered phosphate is reabsorbed from the kidney, predominantly in the proximal tubule, by NaPi2a and NaPi2c, which are present on the brush border membrane. Renal phosphate transport is tightly regulated. Dietary phosphate intake, parathyroid hormone (PTH), 1,25 (OH)2 vitamin D3, and fibroblast growth factor 23 (FGF23) are the principal regulators of phosphate reabsorption from the kidney. Recent advances in genetic techniques and animal models have identified many genetic disorders of phosphate homeostasis. Mutations in NaPi2a and NaPi2c; and hormonal dysregulation of PTH, FGF23, and Klotho, are primarily responsible for most genetic disorders of phosphate transport. The main focus of this educational review article is to discuss the genetic and clinical features of phosphate regulation disorders and provide understanding and treatment options. © IPNA 2011.

Griffiths C.,Wingate University | Pass S.,Texas Tech University Health Sciences Center | Yarbrough W.,VA North Texas Healthcare System | Yarbrough W.,Ut Southwestern Medical Center
Hospital Pharmacy | Year: 2014

Introduction: Pneumonia is a common cause of morbidity and mortality in the critically ill. Clinicians use a range of duration for antibiotic treatment from 7 to 14 days or longer. Failure to de-escalate antimicrobial therapy in a timely manner may lead to increased antimicrobial resistance, increased risk of side effects, and increased cost. Objective: To investigate potential methods to improve treatment of pneumonia for patients in 4 intensive care units (ICUs). Methods: A retrospective descriptive chart review was conducted at the Veterans Affairs North Texas Health Care System (VANTHCS). Veterans aged 18 to 90 years admitted to the ICU with a diagnosis of pneumonia were included. Descriptive statistics were used to interpret the data. Current management was reviewed to identify markers such as length of antibiotic therapy, ICU length of stay, and inpatient mortality. Secondary objectives included appropriateness and accuracy of the empiric regimen. Results: Of the 1,854 Veterans admitted, 107 met inclusion criteria. Antibiotic choices for positive cultures were appropriate in 45 out of 46 (98%) patients, with an average length of therapy of 8.6 ± 6.3 days. De-escalation of antibiotics based on sensitivity data occurred in 73% of positive cultures. Conclusions: Pneumonia in the VANTHCS ICUs is initially treated with empiric antibiotics. Empiric antibiotic therapy for pneumonia was appropriate and accurate over this time period. Opportunities exist for de-escalation in patients with or without positive cultures. The procalcitonin assay is now being utilized at VANTHCS to optimize patient care © 2014 Thomas Land Publishers, Inc.

Rocca-Serra P.,University of Oxford | Ruttenberg A.,Science Commons | O'Connor M.J.,Stanford University | Whetzel P.L.,Stanford University | And 7 more authors.
Applied Ontology | Year: 2011

When developing the Ontology of Biomedical Investigations (OBI), the process of adding classes with similar patterns of logical definition is time consuming, error prone, and requires an editor to have some expertise in OWL. Moreover, the process is poorly suited for a large number of domain experts who have limited experience with ontology development, and this can hinder contributions. We have developed a procedure to ease this task and allow such domain experts to add terms to the ontology in a way that both effectively includes complex logical definitions, yet requires minimal manual intervention by the OBI developers. The procedure is based on editing a Quick Term Template in a spreadsheet format that is subsequently converted into an OWL file. This procedure promises to be a robust and scalable approach for ontology enrichment as evidenced by encouraging results obtained when evaluated with an early version of the MappingMaster Protégé plugin. © 2011 - IOS Press and the authors. All rights reserved.

Quinn C.T.,Ut Southwestern Medical Center | Johnson V.L.,New York Medical College | Kim H.-Y.,New England Research Institutes, Inc. | Trachtenberg F.,New England Research Institutes, Inc. | And 7 more authors.
British Journal of Haematology | Year: 2011

Little is known about the effects of thalassaemia on the kidney. Characterization of underlying renal function abnormalities in thalassaemia is timely because the newer iron chelator, deferasirox, can be nephrotoxic. We aimed to determine the prevalence and correlates of renal abnormalities in thalassaemia patients, treated before deferasirox was widely available, using 24-h collections of urine. We calculated creatinine clearance and urine calcium-to-creatinine ratio and measured urinary β2-microglobulin, albumin, and protein. We used multivariate modelling to identify clinical, therapeutic, and laboratory predictors of renal dysfunction. One-third of thalassaemia patients who were not regularly transfused had abnormally high creatinine clearance. Regular transfusions were associated with a decrease in clearance (P=0·004). Almost one-third of patients with thalassaemia had hypercalciuria, and regular transfusions were associated with an increase in the frequency and degree of hypercalciuria (P<0·0001). Albuminuria was found in over half of patients, but was not consistently associated with transfusion therapy. In summary, renal hyperfiltration, hypercalciuria, and albuminuria are common in thalassaemia. Higher transfusion intensity is associated with lower creatinine clearance but more frequent hypercalciuria. The transfusion effect needs to be better understood. Awareness of underlying renal dysfunction in thalassaemia can inform decisions now about the use and monitoring of iron chelation. © 2011 Blackwell Publishing Ltd.

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