Chromatin remodeling and human disease.

In the past few years, there has been a nascent convergence of scientific understanding of inherited human diseases with epigenetics. Identified epigenetic processes involved in human disease include covalent DNA modifications, covalent histone modifications, and histone relocation. Each of these processes influences chromatin structure and thereby regulates gene expression and DNA methylation, replication, recombination, and repair.

Genes involved in breast cancer metastasis to bone.

Metastasis to bone occurs frequently in advanced breast cancer and is accompanied by debilitating skeletal complications. Current treatments are palliative and new therapies that specifically prevent the spread of breast cancer to bone are urgently required. While our understanding of interactions between breast cancer cells and bone cells has greatly improved, we still know little about the molecular determinants that regulate specific homing of breast cancer cells to the bone.

A conserved domain in the NH2 terminus important for assembly and functional expression of pacemaker channels.

Pacemaker channels are formed by co-assembly of hyperpolarization-activated cyclic nucleotide-gated (HCN) subunits. Previously, we suggested that the NH(2) termini of the mouse HCN2 isoform were important for subunit co-assembly and functional channel expression. Using an alignment strategy together with yeast two-hybrid assays, patch clamp electrophysiology, and confocal imaging, we have now identified a domain within the NH(2) terminus of the HCN2 subunit that is responsible for interactions between NH(2) termini and promoting the trafficking of functional channels to the plasma membrane.

Estrogen-dependent growth of a rat pituitary tumor involves, but does not require, a high level of vascular endothelial growth factor.

Long-term (10-week) treatment of Fischer 344 (F344) rats with the synthetic estrogen diethylstilbestrol (DES) increases the level of vascular endothelial growth factor (VEGF) in the pituitary. This is concurrent with the development of a large tumor of the pituitary of F344 rats. A role for VEGF in estrogen-dependent pituitary tumor growth is also supported by the fact that pituitary VEGF level is not increased by estrogen treatment in rats of the tumor-resistant Brown Norway (BN) strain.

Variation in patient management based on ECG interpretation by emergency medicine and internal medicine residents.

This study was performed to determine the impact of electrocardiogram (ECG) interpretation on urgent patient care decisions by internal medicine (IM) and emergency medicine (EM) resident physicians. Six clinical scenarios and ECGs were given to 31 IM residents and 31 EM residents at a university medical center. Based on the ECG interpretation, the residents were asked to select the best patient management from a list of choices.

Post hoc mortality analysis of the efficacy trial of diaspirin cross-linked hemoglobin in the treatment of severe traumatic hemorrhagic shock.

Background: The efficacy trial of diaspirin cross-linked hemoglobin (DCLHb) in traumatic hemorrhagic shock demonstrated an unexpected mortality imbalance, prompting a three-step review to better understand the cause of this finding.

Methods: Patients were enrolled in this DCLHb hemorrhagic shock study using 28-day mortality as the primary endpoint. Mortality data were primarily analyzed using the TRISS method and a nonblinded clinical review, followed by an independent Pennsylvania Trauma Outcome Study (PTOS)-derived probability of survival analyses.

Vibrio vulnificus and Vibrio parahaemolyticus in U.S. retail shell oysters: a national survey from June 1998 to July 1999.

From June 1998 to July 1999, 370 lots of oysters in the shell were sampled at 275 different establishments (71%, restaurants or oyster bars; 27%, retail seafood markets: and 2%, wholesale seafood markets) in coastal and inland markets throughout the United States. The oysters were harvested from the Gulf (49%). Pacific (14%), Mid-Atlantic (18%), and North Atlantic (11%) Coasts of the United States and from Canada (8%).

A safety assessment of diaspirin cross-linked hemoglobin (DCLHb) in the treatment of hemorrhagic, hypovolemic shock.

Objective: To determine the safety and possible efficacy of diaspirin cross-linked hemoglobin (DCLHb) in the treatment of patients in Class II-IV hemorrhagic, hypovolemic shock.

Design: Multicenter, randomized, normal saline-controlled, dose-escalation study.

Setting: Eleven hospitals in the U.

Setting-based practice variation in the management of simple febrile seizure.

Objective: To identify provider-based differences in the ED assessment and management of children presenting with uncomplicated, first-time febrile seizures.

Methods: Multicenter, retrospective cohort study of seven EDs in-the Chicago area: two tertiary academic pediatric EDs (PEDs) and five community-based general EDs (GEDs). The visits of all patients with a discharge diagnosis including the term "seizure" were identified from a 30-month period.

A proposed consent process in studies that use an exception to informed consent.

Federal regulations allow an exception to informed consent when it is not feasible to obtain informed consent in certain emergency research circumstances. A multicenter, randomized, single-blinded, normal saline procedure-controlled efficacy trial of diaspirin cross-linked hemoglobin (DCLHb) in acute traumatic hemorrhagic shock was conducted. The study intended to include 850 of the most severely injured trauma patients with hemorrhage and persistent hypoperfusion as demonstrated by vital signs suggestive of vascular collapse or a base deficit that signified prolonged hypoperfusion.

The informed consent process and the use of the exception to informed consent in the clinical trial of diaspirin cross-linked hemoglobin (DCLHb) in severe traumatic hemorrhagic shock. DCLHb Traumatic Hemorrhagic Shock study group.

Unlabelled: In the clinical trial of diaspirin cross-linked hemoglobin (DCLHb), optimal therapy required the immediate enrollment of patients with severe, uncompensated, traumatic hemorrhagic shock. When it was not feasible to obtain prospective consent, an exception to informed consent was used according to FDA regulation 21 CFR 50.24.

Diaspirin cross-linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock: a randomized controlled efficacy trial.

Context: Severe, uncompensated, traumatic hemorrhagic shock causes significant morbidity and mortality, but resuscitation with an oxygen-carrying fluid might improve patient outcomes.

Objective: To determine if the infusion of up to 1000 mL of diaspirin cross-linked hemoglobin (DCLHb) during the initial hospital resuscitation could reduce 28-day mortality in traumatic hemorrhagic shock patients.

Design And Setting: Multicenter, randomized, controlled, single-blinded efficacy trial conducted between February 1997 and January 1998 at 18 US trauma centers selected for their high volume of critically injured trauma patients, but 1 did not enroll patients.

Nocturnal and daytime panic attacks--comparison of sleep architecture, heart rate variability, and response to sodium lactate challenge.

Background: The purpose of this study was to determine if nocturnal panic patients have greater autonomic dysregulation than patients with daytime panic.

Methods: Three groups were studied: patients who suffer from panic attacks during sleep (n = 12), those who suffer from daytime panic attacks only (n = 12), and control subjects (n = 12). Each subject underwent 24-hour holter monitoring for heart rate variability (HRV), an overnight sleep recording, and sodium lactate challenge during wakefulness.

ST segment elevation and the prediction of hospital life-threatening complications: the role of right ventricular and posterior leads.

Unlabelled: Accurate prognosis in suspected acute myocardial infarction (AMI) is essential for appropriate use of thrombolytic therapy and primary angioplasty. However, previous models may be limited because the 12-lead electrocardiogram (ECG) does not examine the right ventricular (RV) and posterior myocardium. We evaluated ST segment elevation (STSE) in posterior (V7-V9) and RV (V4R-V6R) leads to determine their predictive value for hospital life-threatening complications (HLTCs).

Change in nutritional status of patients on peritoneal dialysis.

Objective: To document the prevalence of undernutrition/overnutrition in patients on peritoneal dialysis (PD) and to examine whether nutritional status (NS) changes with time on this form of dialysis.

Design: Retrospective observational study. Patients had been on PD >2 years.

The role of CD45 and CD45-associated molecules in T cell activation.

CD45 (lymphocyte common antigen) is a receptor-linked protein tyrosine phosphatase that is expressed on all leucocytes, and which plays a crucial role in the function of these cells. On T cells the extracellular domain of CD45 is expressed in several different isoforms, and the particular isoform(s) expressed depends on the particular subpopulation of cell, their state of maturation, and whether or not they have previously been exposed to antigen. It has been established that the expression of CD45 is essential for the activation of T cells via the TCR, and that different CD45 isoforms display a different ability to support T cell activation.

Value of posterior and right ventricular leads in comparison to the standard 12-lead electrocardiogram in evaluation of ST-segment elevation in suspected acute myocardial infarction.

In this multicenter prospective trial, we studied posterior (V7 to V9) and right ventricular (V4R to V6R) leads to assess their accuracy compared with standard 12-lead electrocardiograms (ECGs) for the diagnosis of acute myocardial infarction (AMI). Patients aged >34 years with suspected AMI received posterior and right ventricular leads immediately after the initial 12-lead ECG. ST elevation of 0.

Circadian rhythms and psychiatric disorders in the elderly.

This article reviews changes in circadian rhythms that have been reported to occur in the elderly psychiatric population. Data relating to circadian changes in normal aging are included where relevant. Information was obtained from: (1) a computerized MEDLINE search from 1975 to May 1996; (2) a review of bibliographies of papers obtained through the computerized search; and (3) texts on chronobiology.

A pharmacoeconomic evaluation of intravenous fosphenytoin (Cerebyx) versus intravenous phenytoin (Dilantin) in hospital emergency departments.

The cost of emergency department services has become a major concern for patients, providers, and payers. Solid economic information is needed to provide a rationale for the selection of therapeutic options and the provision of care that is both clinically and financially prudent. To assess the full cost of care for patients with seizures who are treated in an acute care setting, a modified activity-based cost-accounting model was developed.