Transmission of lymphocytic choriomeningitis virus by organ transplantation.

Background: In December 2003 and April 2005, signs and symptoms suggestive of infection developed in two groups of recipients of solid-organ transplants. Each cluster was investigated because diagnostic evaluations were unrevealing, and in each a common donor was recognized.

Methods: We examined clinical specimens from the two donors and eight recipients, using viral culture, electron microscopy, serologic testing, molecular analysis, and histopathological examination with immunohistochemical staining to identify a cause.

Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer's disease.

The cascade of Alzheimer's disease (AD) neurodegeneration is associated with persistent oxidative stress, mitochondrial dysfunction, impaired energy metabolism, and activation of pro-death signaling pathways. More recently, studies with human postmortem brain tissue linked many of the characteristic molecular and pathological features of AD to reduced expression of the insulin and insulin-like growth factor (IGF) genes and their corresponding receptors. We now demonstrate using an in vivo model of intracerebral Streptozotocin (ic-STZ), that chemical depletion of insulin and IGF signaling mechanisms combined with oxidative injury is sufficient to cause AD-type neurodegeneration.

Pulmonary hemodynamic responses to brain natriuretic peptide and sildenafil in patients with pulmonary arterial hypertension.

Study Objectives: Brain natriuretic peptide (BNP) blunts hypoxic pulmonary hypertension in animal models, but its acute hemodynamic effects in patients with pulmonary arterial hypertension (PAH) are not known. The aim of this study was to determine if human B-type natriuretic peptide is a safe and efficacious pulmonary vasodilator in patients with PAH and if the pulmonary hemodynamic effects are potentiated by phosphodiesterase inhibition.

Design: Open-label study.

Vaccination with protein-transduced dendritic cells elicits a sustained response to hepatitis C viral antigens.

Background & Aims: Professional antigen-presenting dendritic cells are capable of eliciting a vigorous antiviral response in naive T cells. The administration of antigen-loaded dendritic cells offers a potential approach to induce high-level immunity against hepatitis C virus.

Methods: The dendritic cell population in mice was expanded in vivo by hydrodynamic delivery of naked DNA that encoded the secreted form of human fms-like tyrosine kinase 3 ligand.

Incidence of and risk factors for medical malpractice lawsuits among Mohs surgeons.

Background: Despite rising medical malpractice costs, little is known about the factors associated with claims filed against Mohs surgeons.

Objective: We sought to define the scope of medical malpractice claims filed against Mohs surgeons and to identify salient factors associated with the filing and disposition of those claims.

Methods: A comprehensive survey was mailed to 599 physicians with US addresses listed in the 2003 directory of the American College of Mohs Micrographic Surgery and Cutaneous Oncology.

Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine.

Reduced glucose utilization and energy metabolism occur early in the course of Alzheimer's disease (AD) and correlate with impaired cognition. Glucose utilization and energy metabolism are regulated by insulin and insulin-like growth factor I (IGF-I), and correspondingly, studies have shown that cognitive impairment may be improved by glucose or insulin administration. Recently, we demonstrated significantly reduced levels of insulin and IGF-I polypeptide genes and their corresponding receptors in advanced AD relative to aged control brains.

The influence of white noise on sleep in subjects exposed to ICU noise.

Background And Purpose: There is disagreement in the literature about the importance of sleep disruption from intensive care unit (ICU) environmental noise. Previous reports have assumed that sleep disruption is produced by high-peak noise. This study aimed to determine whether peak noise or the change in noise level from baseline is more important in inducing sleep disruption.

"Islands of Risk": subgroups of adolescents at risk for HIV.

Objective: To use cluster analysis to determine profiles of adolescents at risk for HIV.

Methods: Adolescents 15-21 years old (N = 1153) with a history of unprotected sex were assessed in five domains of risk (unprotected sex, alcohol/marijuana use, other drug use, mental health crises, and arrest/school dropout) as well as demographic, contextual, and behavioral variables.

Results: Cluster analysis revealed separate three-cluster solutions for males and females.

PI3K/Akt-dependent regulation of the transcription factor myocyte enhancer factor-2 in insulin-like growth factor-1- and membrane depolarization-mediated survival of cerebellar granule neurons.

Survival signals such as insulin-like growth factor-1 (IGF-1) or membrane depolarization convey their neuronal protective effects through the activation of signaling networks and nuclear factors. In cerebellar granule neurons, IGF-1 mediates survival primarily through the PI3K/Akt pathway. The function of the transcription factor myocyte enhancer factor-2 (MEF2) is required for mediating membrane depolarization-dependent neuronal survival.

Extent and impact of industry sponsorship conflicts of interest in dermatology research.

Background: Many published clinical trials are authored by investigators with financial conflicts of interest. The general medical literature documents the pervasive extent and sometimes problematic impact of these conflicts. Accordingly, there is renewed discussion about author disclosure and clinical trial registry to minimize publication bias from financial conflicts of interest.

The evolution of trauma care at a level I trauma center.

Background: My colleagues and I compared trauma patient demographics and outcomes between two time periods in the last 10 years in our Level I trauma center to evaluate the impact of the marked evolution in trauma care and determine additional opportunities for improvement.

Methods: Our trauma registry was queried for adult trauma patients admitted from 1991 to 1993 (EARLY) and 1999 to 2001 (LATE). The EARLY period predated creation and maturation of a dedicated trauma service and Level I trauma center verification.

Cyclin-dependent kinase 5 mediates neurotoxin-induced degradation of the transcription factor myocyte enhancer factor 2.

Regulation of the process of neuronal death plays a central role both during development of the CNS and in adult brain. The transcription factor myocyte enhancer factor 2 (MEF2) plays a critical role in neuronal survival. Cyclin-dependent kinase 5 (Cdk5) mediates neurotoxic effects by phosphorylating and inhibiting MEF2.

Hepatitis C virus core protein stimulates hepatocyte growth: correlation with upregulation of wnt-1 expression.

Hepatitis C virus (HCV) core protein has been implicated in the development of human hepatocellular carcinoma (HCC). Here we report that expression of HCV core protein by transient transfection increased cell proliferation, DNA synthesis, and cell cycle progression in Huh-7 cells, a human HCC-derived cell line. Culture supernatant from transfected cells also harbored a growth-promoting effect.

Low utility of endoscopy for suspected upper gastrointestinal bleeding occurring in hospitalized patients.

Objectives: To determine the clinical utility of upper endoscopy in patients who have upper gastrointestinal bleeding after hospitalization.

Methods: Patients were studied who underwent upper endoscopy for an indication of suspected upper gastrointestinal bleeding that developed more than 48 hours after hospitalization. Demographic, clinical, and endoscopic data were extracted by chart review.

Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes?

The neurodegeneration that occurs in sporadic Alzheimer's disease (AD) is consistently associated with a number of characteristic histopathological, molecular, and biochemical abnormalities, including cell loss, abundant neurofibrillary tangles and dystrophic neurites, amyloid-beta deposits, increased activation of pro-death genes and signaling pathways, impaired energy metabolism/mitochondrial function, and evidence of chronic oxidative stress. The general inability to convincingly link these phenomena has resulted in the emergence and propagation of various heavily debated theories that focus on the role of one particular element in the pathogenesis of all other abnormalities. However, the accumulating evidence that reduced glucose utilization and deficient energy metabolism occur early in the course of disease, suggests a role for impaired insulin signaling in the pathogenesis of AD.

Modulation of macrophage phenotype by soluble product(s) released from neutrophils.

The regulation of macrophage phenotype by neutrophils was studied in the s.c. polyvinyl alcohol sponge wound model in mice made neutropenic by anti-Gr-1 Ab, as well as in cell culture.

Effect of mutating the two cysteines required for HBe antigenicity on hepatitis B virus DNA replication and virion secretion.

Hepatitis B virus (HBV) variants with impaired expression of e antigen (HBeAg) frequently arise at the chronic stage of infection, as exemplified by precore and core promoter mutants. Since an intramolecular disulfide bond maintains the secondary structure of HBeAg, we explored effect of missense mutations of either cysteine codon. Consistent with earlier reports, substitution of each cysteine rendered HBeAg nearly undetectable.

Rotavirus vaccines: an update.

Purpose Of Review: Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and has a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease.

Recent Findings: Rotavirus disease prevention efforts suffered a great setback in 1999 with the withdrawal of the RRV-TV vaccine less than a year after its introduction.

Health-related quality of life among children presenting to a pediatric sleep disorders clinic.

The present study is a retrospective review of a clinical database that assessed the association between childhood sleep disturbances and health-related quality of life (HRQOL). The sample consists of 80 caretakers of children ages 5 to 18 years referred to a pediatric sleep disorders clinic. Caretakers completed the Child Health Questionnaire-Parent Form (CHQ-PF50) and the Children's Sleep Habits Questionnaire (CSHQ).

Type 1 interferon augments DNA-based vaccination against hepatitis C virus core protein.

Eradication of chronic hepatitis C virus (HCV) infection depends upon a broad-based cellular immune response. Genetic immunization stimulates such a response, but the resultant activity is generally weak. Type 1 interferons (IFNs), which are known for their direct anti-viral and anti-proliferative properties, possess vigorous immunomodulatory properties.

Transcriptional regulation of TNF-alpha production in neutropenia.

Neutropenia has been shown to markedly increase plasma TNF-alpha concentration after LPS injection and to enhance LPS-induced mortality. Experiments reported here demonstrate that the 15-fold higher plasma TNF-alpha concentration elicited by LPS in neutropenic vs. nonneutropenic unanesthetized mice correlated with increased hepatic and splenic, but not pulmonary, TNF-alpha mRNA.

Expression of uncoupling protein-2 in human colon cancer.

Purpose: Cancer cell survival depends on adaptive mechanisms that include modulation of oxidative stress. One such mechanism may be via up-regulation of uncoupling protein-2 (UCP2), a mitochondrial inner membrane anion carrier recently found to provide cytoprotection in nontumor cells by acting as a sensor and negative regulator of reactive oxygen species production. We hypothesized that UCP2 expression may be increased in colon cancer as part of tumor adaptation.