Publications

OBJECTIVES

This study examined factors associated with emergency department use among homeless and marginally housed persons.

METHODS

Interviews were conducted with 2578 homeless and marginally housed persons, and factors associated with different patterns of emergency department use were assessed in multivariate models.

RESULTS

Findings showed that 40.4% of respondents had 1 or more emergency department encounters in the previous year; 7.9% exhibited high rates of use (more than 3 visits) and accounted for 54.5% of all visits. Factors associated with high use rates included less stable housing, victimization, arrests, physical and mental illness, and substance abuse. Predisposing and need factors appeared to drive emergency department use.

CONCLUSIONS

Efforts to reduce emergency department use among the homeless should be targeted toward addressing underlying risk factors among those exhibiting high rates of use.

Between March and October 2000, 157 suspected cases of leptospirosis hospitalized with complications of Weil's syndrome and a mortality of 8% were identified in Salvador, Brazil. We conducted a population-based case-control study to identify risk factors for acquisition of leptospirosis in neighborhoods with high endemicity during the rainy season-associated urban epidemic. Sixty-six (65%) of 101 laboratory-confirmed cases and 125 age and sex-matched healthy neighborhood controls were interviewed. Residence in proximity to an open sewer (matched odds ratio [OR] = 5.15, 95% confidence interval [CI] = 1.80-14.74), peri-domiciliary sighting of rats (OR = 4.49, 95% CI = 1.57-12.83), sighting groups of five or more rats (OR = 3.90, 95% CI = 1.35-11.27), and workplace exposure to contaminated environmental sources (OR = 3.71, 95% CI = 1.35-10.17) were found to be independent risk factors for acquiring disease. Some of these risk factors are amenable to focused interventions, which include provision of closed drainage systems for sewage and reduction of rodent populations in the peri-domicilary environment. Environmental control of transmission may help to greatly reduce the incidence of severe leptospirosis.

INTRODUCTION

Thoracic spinal cord stimulation (SCS) has been used to treat angina pectoris and to produce cardiac autonomic control. We studied the effect of thoracic SCS on sinus node and AV nodal function to test the hypothesis that SCS modulated autonomic regulation of the electrophysiology of these structures.

METHODS AND RESULTS

The effects of thoracic SCS on sinus cycle length and AH interval were studied in 47 dogs in five experimental groups: group 1: intact autonomic nerves; group 2: bilateral ansae subclaviae transection and efferent stellate stimulation; group 3: ansae transection, bilateral vagi transection, and efferent stellate stimulation; group 4: bilateral vagi transection and efferent vagal stimulation; and group 5: bilateral vagal stimulation and bilateral ansae subclaviae transection. Under fluoroscopic guidance, the spinal stimulator electrode was advanced to the T1-T2 position and threshold determined by adjusting the output to produce muscle contraction. Parameters were measured at baseline prior to SCS and during SCS, at 90% threshold. Ansae subclaviae and vagi nerves were isolated using standard approaches. Stellate and vagal stimulation were each performed using a constant current stimulator and at three different frequencies. Sinus cycle length and AH intervals (the latter at constant right atrial pacing of 400 msec) were measured with and without SCS at baseline and at each level of nerve stimulation. Nitric oxide was measured using the coronary sinus overflow method, from a luminal balloon catheter placed deep in the coronary sinus. SCS resulted in an increase in sinus cycle length from 507 +/- 23 msec to 544 +/- 22 msec (P = 0.02) and AH interval from 71 +/- 4 msec to 74 +/- 4 msec (P = 0.03). Ansae subclaviae transection had no effect on this increase, while vagal transection eliminated the increase in sinus cycle length and AH with SCS. The increase in these parameters with SCS was maintained during both stellate stimulation (group 2) and vagal stimulation (group 5) across all three levels of neural stimulation.

CONCLUSION

SCS appears to enhance parasympathetic activity, mediated via the vagus. This may have implications for use of thoracic SCS to treat chronic angina and perhaps prevent sudden cardiac death.

The translocation of proteins across the bacterial cell membrane is carried out by highly conserved components of the Sec system. Most bacterial species have a single copy of the genes encoding SecA and SecY, which are essential for viability. However, Streptococcus gordonii strain M99 encodes SecA and SecY homologues that are not required for viability or for the translocation of most exported proteins. The genes (secA2 and secY2) reside in a region of the chromosome required for the export of GspB, a 286 kDa cell wall-anchored protein. Loss of GspB surface expression is associated with a significant reduction in the binding of M99 to human platelets, suggesting that it may be an adhesin. Genetic analyses indicate that M99 has a second, canonical SecA homologue that is essential for viability. At least two other Gram-positive species, Streptococcus pneumoniae and Staphylococcus aureus, encode two sets of SecA and SecY homologues. One set is more similar to SecA and SecY of Escherichia coli, whereas the other set is more similar to SecA2 and SecY2 of strain M99. The conserved organization of genes in the secY2-secA2 loci suggests that, in each of these Gram-positive species, SecA2 and SecY2 may constitute a specialized system for the transport of a very large serine-rich repeat protein.

The objective of this prospective, analytic study was to identify predictors and describe the demographic and clinical correlates of head computed tomography (CT) evaluation in patients with poisoning or drug overdose and altered mental status. Forty-three patients that were evaluated by head CT and 109 that were not evaluated by head CT were entered into the study at a poison control center. None of the 43 scanned patients had any acute findings on head CT. A logistic regression model yielded 4 predictors that were statistically associated with the ordering of a head CT scan: Glasgow Coma Scale (GCS) < or = 8 (odds ratio [OR]: 2.3; 95% confidence interval [CI] 1.03-5.7); age > or = 41 years (OR 5.3; 95% CI 2.2-13); use of drugs or abuse by history (OR 2.8; 95% CI 1.04-7.6); and witnessed seizure activity (OR 4.8; 95% CI 1.3-17.9). We also tested 2 additional models to identify predictors of hospital admission, 1 with and 1 without CT scan included as a covariate. In the first model, only GCS

An understanding of the epidemiology of ALI/ARDS and the effects of treatment have been hampered by the lack of a uniform definition of the syndrome. Various definitions have been proposed, and these are reviewed with particular attention to how changes in definition have affected our understanding of the natural history and treatment options for the condition.

The requirement for cytotoxic T lymphocytes during allograft rejection is controversial. We have demonstrated that CD8+ T cells are not essential for allograft rejection or for the induction of apoptosis in two experimental models of transplantation. To determine candidate cells types which may play a role in the events leading to graft rejection, the cellular composition of rejecting allografts was determined. We demonstrate that substantial numbers of NK cells, of recipient origin, infiltrate allografts as early as 12 h after transplantation. These NK cells produce cytokines and express cytotoxic mediators such as granzyme B and FasL. It is unknown which NK cell receptors are expressed and activated during transplantation. NK cells express multiple cell surface receptors, including MHC class I binding inhibitory receptors, which deliver a negative signal, and activation receptors, which stimulate cytokine secretion and cytotoxicity of NK cells. To begin to understand NK cell activation in the context of transplantation, we have recently cloned a novel rat immunoglobulin-like surface receptor from a rejecting liver allograft. Sequence analysis demonstrates that this putative activation receptor contains 71% identity to human NKp30 at the DNA level, suggesting that it is the rat homologue (rNKp30). Characterization of NK activation receptors may lead to better understanding of the interactions between the innate and adaptive immune responses in transplantation.

Cytochromes P450 (P450s) are hemoprotein enzymes committed to the metabolism of chemically diverse endo- and xenobiotics. They are anchored to the endoplasmic reticulum (ER) membrane with the bulk of their catalytic domain exposed to the cytosol, and thus they constitute excellent examples of integral monotopic ER proteins. Physiologically they are known to turn over asynchronously, but the determinants that trigger their proteolytic disposal and the pathways for such cellular disposal are not well defined. We recently showed that CYP3A4, the dominant human liver drug-metabolizing enzyme, and its rat liver orthologs undergo ubiquitin-dependent 26S proteasomal degradation not only after suicide inactivation, but also when CYP3A4 is expressed in Saccharomyces cerevisiae, presumably in its "native" form. The latter findings, obtained by the use of strains either with compromised proteasomal degradation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) or deficient in ubiquitin-conjugating enzymes (Ubc; UBC), revealed that this native monotopic P450 enzyme, in common with the polytopic HMGR, required the function of certain HRD (HMGR degradation) and UBC genes. In this study, we examined the degradation of CYP2C11, a male rat liver-specific P450, by heterologous expression in S. cerevisiae under comparable conditions. We report that unlike CYP3A4 and HMGR, the degradation of CYP2C11 in S. cerevisiae is independent of either HRD or UBC gene function, but it is largely dependent on vacuolar (lysosomal) proteolysis. These findings with two monotopic ER hemoproteins, CYP2C11 and CYP3A4, and the polytopic ER protein HMGR attest to the remarkable mechanistic diversity of cellular proteolytic disposal of ER proteins.