Clinical Pharmacology in Sarcoidosis: How to Use and Monitor Sarcoidosis Medications.

When sarcoidosis needs treatment, pharmacotherapy is usually required. Although glucocorticoids work reliably and relatively quickly for sarcoidosis, these drugs are associated with numerous significant side effects. Such side effects are common in sarcoidosis patients, as the disease frequently has a chronic course and glucocorticoid treatment courses are often prolonged.

Examining the clinical impact of rapid multiplex polymerase chain reaction-based diagnostic testing for bloodstream infections in a national cohort of the Veterans Health Administration.

Study Objective: Bloodstream infections (BSIs) are a significant cause of mortality. Use of a rapid multiplex polymerase chain reaction-based blood culture identification panel (BCID) may improve antimicrobial utilization and clinical outcomes by shortening the time to appropriate therapy and de-escalating antibiotics among patients on overly broad-spectrum empiric therapy. The effect of BCID on clinical outcomes across varying institutional antimicrobial stewardship program (ASP) practices is unclear.

Effect of Vancomycin-Associated Acute Kidney Injury on Incidence of 30-Day Readmissions among Hospitalized Veterans Affairs Patients with Skin and Skin Structure Infections.

Among hospitalized adults who received vancomycin for their skin and skin structure infection (SSSI), patients who experienced acute kidney injury (AKI) had considerably higher 30-day readmission rates. Nearly half of the observed 30-day readmissions were due to non-SSSI-related reasons, which is consistent with the persistent organ dysfunction observed among patients with AKI.

Comparing drug interaction frequencies of various hepatitis C treatment regimens among monoinfected patients.

Introduction And Objectives: Four regimens are recommended for treating hepatitis C (HCV) genotype 1 infection. Study aims were to (1) compare frequencies of contraindicated drug interactions (XDDIs) when each HCV regimen is added to medication profiles of HCV-monoinfected patients, (2) quantify the proportion of patients with XDDIs to all four regimens and (3) determine covariates independently associated with having a XDDI to all four regimens.

Materials And Methods: A cross-sectional study was performed within Upstate New York Veterans Healthcare Administration.

The Offender Job Search Self-Efficacy Scale: Development and initial validation.

The purpose of this study was to develop the Offender Job Search Self-Efficacy Scale (OFJSSE) for the specific job search needs of the criminal justice population. Participants were 249 male inmates within 2 years of release from a state correctional facility in the southern region of the United States who identified mostly as Caucasian (56.2%), single (62.

Relationship Between Single Tablet Antiretroviral Regimen and Adherence to Antiretroviral and Non-Antiretroviral Medications Among Veterans' Affairs Patients with Human Immunodeficiency Virus.

Several antiretrovirals (ART) have been coformulated as single tablet regimens (STR). Study objectives were to compare ART and non-ART adherence between STR and multiple tablet regimens (MTR) recipients, determine whether STR independently predicts ART adherence, and determine whether ART adherence influences non-ART adherence. A retrospective cohort study was performed among Upstate New York Veterans' Healthcare Administration (VISN-2) patients from 2000 to 2013.

Development and Validation of Prognostic Indices for Recovery of Physical Functioning Following Stroke: Part 2.

Objective: To develop a prognostic index for achievement of modified independence (Functional Independence Measure grade VI) after completion of either comprehensive or consultative rehabilitation after stroke.

Design: Retrospective cohort study.

Setting: Veterans Affairs Medical Centers (VAMCs) throughout the United States.

Development and Validation of Prognostic Indices for Recovery of Physical Functioning Following Stroke: Part 1.

Objective: To develop a prognostic index using Functional Independence Measure grades and stages that would enable clinicians to determine the likelihood of achieving a level of minimum assistance with physical functioning after a stroke. Grades define varying levels of physical function, and stages define varying levels of cognitive functioning.

Design: Retrospective cohort study.

Factors influencing receipt of outpatient rehabilitation services among veterans following lower extremity amputation.

Objective: To determine patient-, treatment-, and facility-level characteristics associated with receiving outpatient rehabilitation services after lower extremity amputation within the Veterans Affairs (VA) system.

Design: Observational study.

Setting: All Veterans Affairs Medical Centers (VAMCs).

Robust induction of PGHS-2 by IL-1 in orbital fibroblasts results from low levels of IL-1 receptor antagonist expression.

Human orbital fibroblasts are more susceptible to some actions of proinflammatory cytokines than are fibroblasts from other anatomic regions. These cells produce high levels of PGE(2) when activated by cytokines. Here we report that they express high levels of prostaglandin-endoperoxide H synthase (PGHS)-2, the inflammatory cyclooxygenase, when treated with IL-1beta.

Nitric oxide modulates capillary formation at the endothelial cell-tumor cell interface.

Nitric oxide synthase expression has been documented in lung tumors, but a potential role for nitric oxide (NO) in induction of capillary formation remains to be elucidated. The purpose of this report was to characterize the direct effects of NO at the level of the tumor-endothelium interface with respect to angiogenesis. A Transwell two-compartment culture system, human endothelial cells (EC), and two human non-small cell lung cancer (CA) lines that constitutively produce NO were used to simulate the EC-tumor cell interface.

Prostaglandin endoperoxide H synthase expression in human thyroid epithelial cells.

KAT-50, an established human thyrocyte cell line, expresses constitutively high levels of prostaglandin endoperoxide H synthase-2 (PGHS-2), the inflammatory cyclooxygenase. Here, we examine primary human thyrocytes. We find that they, too, express PGHS-2 mRNA and protein under control culture conditions.

Thyroxine promotes association of mitogen-activated protein kinase and nuclear thyroid hormone receptor (TR) and causes serine phosphorylation of TR.

Activated nongenomically by l-thyroxine (T(4)), mitogen-activated protein kinase (MAPK) complexed in 10-20 min with endogenous nuclear thyroid hormone receptor (TRbeta1 or TR) in nuclear fractions of 293T cells, resulting in serine phosphorylation of TR. Treatment of cells with the MAPK kinase inhibitor, PD 98059, prevented both T(4)-induced nuclear MAPK-TR co-immunoprecipitation and serine phosphorylation of TR. T(4) treatment caused dissociation of TR and SMRT (silencing mediator of retinoid and thyroid hormone receptor), an effect also inhibited by PD 98059 and presumptively a result of association of nuclear MAPK with TR.

Leukoregulin upregulation of prostaglandin endoperoxide H synthase-2 expression in human orbital fibroblasts.

Human orbital fibroblasts from patients with severe thyroid-associated ophthalmopathy are particularly susceptible to the actions of a variety of proinflammatory molecules. In this study, we demonstrate that the inductions of prostaglandin endoperoxide H synthase-2 (PGHS-2), interleukin (IL)-1alpha, and IL-1beta by leukoregulin, a product of activated T lymphocytes, are far more robust in orbital fibroblasts than those observed in dermal fibroblasts. These actions of leukoregulin are mediated through an intermediate induction of IL-1alpha.

Expression of hyaluronan synthase messenger ribonucleic acids and their induction by interleukin-1beta in human orbital fibroblasts: potential insight into the molecular pathogenesis of thyroid-associated ophthalmopathy.

The disordered accumulation of hyaluronan, a nonsulfated glycosaminoglycan, is a hallmark feature of the tissue remodeling observed in thyroid-associated ophthalmopathy (TAO). Orbital fibroblasts have been shown to exhibit substantial up-regulation of hyaluronan synthesis when activated with proinflammatory cytokines such as interleukin-1beta (IL-1beta). Recently, three members of the hyaluronan synthase (HAS) gene family were cloned.

CD40 expression in human thyroid tissue: evidence for involvement of multiple cell types in autoimmune and neoplastic diseases.

CD40, a member of the tumor necrosis factor-alpha (TNF-alpha) receptor family of surface molecules, is expressed by a variety of cell types. It is a crucial activational molecule displayed by lymphocytes and other bone marrow-derived cells and recently has also been found on nonlymphoid cells such as fibroblasts, endothelia, and epithelial cells in culture. While its role in lymphocyte signaling and activation has been examined in great detail, the function of CD40 expression on nonlymphoid cells, especially in vivo, is not yet understood.

HMC-1 mast cells activate human orbital fibroblasts in coculture: evidence for up-regulation of prostaglandin E2 and hyaluronan synthesis.

The purpose of this study was to determine the effects of mast cell coculture on human orbital fibroblasts. Thyroid-associated ophthalmopathy is characterized by infiltration of lymphocytes and mast cells and connective tissue activation in the orbit, leading to a disordered accumulation of hyaluronan and intense inflammation. Here, we report that HMC-1, an established human mast cell line, can activate human orbital fibroblasts to produce increased levels of prostaglandin E2 (PGE2) and hyaluronan when cocultured.

Prostaglandin-endoperoxide H synthase-2 expression in human thyroid epithelium. Evidence for constitutive expression in vivo and in cultured KAT-50 cells.

Prostaglandin-endoperoxide H synthase (PGHS) (EC 1.14.99.

Activation of human orbital fibroblasts through CD40 engagement results in a dramatic induction of hyaluronan synthesis and prostaglandin endoperoxide H synthase-2 expression. Insights into potential pathogenic mechanisms of thyroid-associated ophthalmopathy.

Human orbital fibroblasts play a putative role in the pathogenesis of thyroid-associated ophthalmopathy (TAO). We hypothesize that the hyaluronan accumulation and inflammation in TAO derive from enhanced biosynthetic activities of orbital fibroblasts. CD40, a member of the tumor necrosis factor-alpha receptor superfamily, is a critical signaling molecule expressed by B lymphocytes.

Human thyroid fibroblasts exhibit a distinctive phenotype in culture: characteristic ganglioside profile and functional CD40 expression.

Fibroblasts from different regions of the human body exhibit substantial phenotypic diversity, some of which relates to the capacity for cross-talk with cells of the immune system. We examine, for the first time, thyroid fibroblast biology in culture. Thyroid explants were placed in culture, and fibroblasts were outgrown and serially passaged.

Recurrent bacterial peritonitis caused by Neisseria cinerea in a chronic ambulatory peritoneal dialysis (CAPD) patient.

We present an unusual case of recurrent (chronic ambulatory peritoneal dialysis) CAPD-associated peritonitis caused by Neisseria cinerea. Using DNA restriction fragment length polymorphism (RFLP) analysis, we determined that the recurrent infection was caused by reinfection with a different N. cinerea strain rather than relapse with the index strain and that the probable origin of the reinfecting organism was the patient's upper respiratory tract.

Nitrovasodilator repletion increases TNF-alpha-induced pulmonary edema.

We tested the hypothesis that nitrovasodilator repletion enhances tumor necrosis factor-alpha (TNF-alpha) -induced pulmonary edema. Lungs were isolated from control guinea pigs or 4 h after the intraperitoneal injection of TNF-alpha (1.60 x 10(5) U/kg).

Tumor necrosis factor-alpha decreases pulmonary artery endothelial nitrovasodilator via protein kinase C.

We postulated that tumor necrosis factor-alpha (TNF) decreases endothelium-derived nitrovasodilator(s) via a protein kinase C (PKC)-dependent pathway. Calf pulmonary artery endothelial monolayers (PAEM) were treated with TNF (10, 100, and 1,000 U/ml) for 15 min or 18 h during an 18-h incubation. At the end of the incubation, the cell lysate and supernatant were harvested.