Publications
Department of Medicine faculty members published more than 3,000 peer-reviewed articles in 2022.
2007
This study aimed to investigate whether HIV and HIV-related factors are associated with spontaneously resolved hepatitis C virus (HCV) infection and levels of hepatitis C viremia. Among 351 anti-HCV(+) injection drug users, with and without HIV infection, multivariate methods were used to evaluate whether HIV status and HIV viral load, CD4 T-cell count, and concurrent HIV antiretroviral therapy were associated with (1) spontaneously resolved HCV infection and (2) HCV RNA levels. In 186 HIV patients, decreased HCV resolution was independently associated with Black race and modestly associated with CD4 T-cell count <200 cells/ml. Among 310 patients with persistent HCV infection, higher HCV RNA levels were independently associated with HIV status but not with other HIV-related factors. HIV may be associated with persistent HCV infection in patients with low CD4 T-cell counts. Moreover, HIV is associated with increased HCV viral load, which may attenuate response to HCV antiviral treatment in coinfected patients.
View on PubMed2007
Cardiac fibroblasts are critical for the maintenance of extracellular matrix deposition and turnover in the normal heart and are key mediators of inflammatory and fibrotic myocardial remodeling in the injured and failing heart. Sphingosine kinase (SphK) activation is a well-recognized determinant of cell fate in cardiac myocytes and other cells, but SphK responses have not previously been studied in cardiac fibroblasts. Initially we found that total SphK activity is over 10-fold higher in cardiac fibroblasts than in adult mouse cardiac myocytes. SphK is composed of two major isoforms, SphK-1 and SphK-2. In fibroblasts isolated from SphK-1 knockout mice, SphK activity was greatly reduced indicating that SphK-1 is the major isoform expressed in these cells. To determine whether SphK regulates cell proliferation and the proinflammatory protein inducible nitric oxide synthase (iNOS), we exposed cultured cardiac fibroblasts to the cytokine interleukin-1beta (IL-1beta) and/or hypoxia. Both hypoxia and IL-1beta alone and in combination enhanced fibroblast SphK activity. In wild-type fibroblasts, hypoxia induced proliferation, but in SphK-1 null fibroblasts this response was blunted even in the presence of serum. In contrast, we found that iNOS expression and NO production were enhanced in SphK-1 null fibroblasts during hypoxia. In wild-type fibroblasts, IL-1beta was only a weak inducer of iNOS and of NO accumulation and hypoxia alone had no significant effect on iNOS activation. However, IL-1beta in combination with hypoxia extensively stimulated iNOS and NO production, and this stimulation was enhanced in SphK-1 null fibroblasts. We conclude that activation of endogenous SphK-1 serves a dual regulatory function: it is required for optimal cardiac fibroblast proliferation but is a negative modulator of proinflammatory responses during hypoxia.
View on PubMed2007
2007
2007
In wild-type FVB mice, leukocyte recruitment to lipopolysaccharide was sexually dimorphic, with a greater number of leukocytes recruited in females. In male beta(2)-adrenergic receptor knock out mice (bred on a congenic FVB background) the number of leukocytes recruited was increased approximately 4-fold, while in females there was no change, eliminating sexual dimorphism in leukocyte migration. While there were significantly fewer recruited CD62L(+) and CD11a(+) leukocytes in wild-type males, only in male beta-adrenergic receptor knock out mice was there an increase in the number of recruited CD11a(+) leukocytes, again eliminating sexual dimorphism. Thus, leukocyte migration and CD11a(+) adhesion molecule expression in male, but not in female, leukocytes is beta-adrenergic receptor-dependent. Our findings provide support for a role of beta(2)-adrenergic receptor mechanisms in the inflammatory response, and suggest that beta(2)-adrenergic receptor on male leukocytes contributes to sexual dimorphism in the effect of stress on inflammatory diseases.
View on PubMed2007
BACKGROUND
Delirium occurs in up to 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. Recently published reports have suggested that the standard drug for delirium, haloperidol, a typical antipsychotic that may cause adverse extrapyramidal symptoms among patients, may be replaced by atypical antipsychotics such as risperidone, olanzapine or quetiapine, that are as effective as haloperidol in controlling delirium, but that have a lower incidence of extrapyramidal adverse effects.
OBJECTIVES
To compare the efficacy and incidence of adverse effects of haloperidol with risperidone, olanzapine, and quetiapine in the treatment of delirium.
SEARCH STRATEGY
The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 August 2006 using the search terms:haloperidol or haldol or risperidone or risperdal* or quetiapine or seroquel* or olanzapine or zyprexa* or aminotriazole or sertindole or leponex* or zeldox* or ziprasidone.
SELECTION CRITERIA
Types of studies included unconfounded, randomised trials with concealed allocation of subjects. For inclusion trials had to have assessed patients pre- and post-treatment. Where cross-over studies are included, only data from the first part of the study were examined. Interrupted time series were excluded. Length of trial and number of measurements did not influence the selection of trials for study. Where indicated, individual patient data were requested for further examination.
DATA COLLECTION AND ANALYSIS
Two reviewers extracted data from included trials. Data were pooled where possible, and analysed using appropriate statistical methods. Odds ratios of average differences were calculated. Only 'intention to treat' data were included. Analysis included haloperidol treated patients, compared with placebo.
MAIN RESULTS
Three studies were found that satisfied selection criteria. These studies compared haloperidol with risperidone, olanzapine, and placebo in the management of delirium and in the incidence of adverse drug reactions. Decrease in delirium scores were not significantly different comparing the effect of low dose haloperidol (< 3.0 mg per day) with the atypical antipsychotics olanzapine and risperidone (Odds ratio 0.63 (95% CI 10.29 - 1.38; p = 0.25). Low dose haloperidol did not have a higher incidence of adverse effects than the atypical antipsychotics. High dose haloperidol (> 4.5 mg per day) in one study was associated with an increased incidence of extrapyramidal adverse effects, compared with olanzapine. Low dose haloperidol decreased the severity and duration of delirium in post-operative patients, although not the incidence of delirium, compared to placebo controls in one study. There were no controlled trials comparing quetiapine with haloperidol.
AUTHORS' CONCLUSIONS
There is no evidence that haloperidol in low dosage has different efficacy in comparison with the atypical antipsychotics olanzapine and risperidone in the management of delirium or has a greater frequency of adverse drug effects than these drugs. High dose haloperidol was associated with a greater incidence of side effects, mainly parkinsonism, than the atypical antipsychotics. Low dose haloperidol may be effective in decreasing the degree and duration of delirium in post-operative patients, compared with placebo. These conclusions must be tempered by the observation that they are based on small studies of limited scope, and therefore will require further corroborating evidence before they can be translated into specific recommendation for the treatment of delirium.
View on PubMed2007
2007
BACKGROUND
Depression and inflammation independently predict adverse cardiovascular outcomes in patients with coronary heart disease (CHD). Depression has been associated with elevated levels of inflammation in otherwise healthy patients without known CHD. However, studies investigating the link between depression and inflammation in patients with established CHD have produced inconclusive results.
METHODS
We sought to examine the association of major depression with inflammation in 984 outpatients with established CHD from the Heart and Soul Study. We assessed current major depression with the Computerized Diagnostic Interview Schedule and collected venous blood samples for measurement of five inflammatory biomarkers (white blood cell count, CD40 ligand, C-reactive protein [CRP], fibrinogen, and interleukin-6 [IL-6]). We used multivariate analysis of variance to examine the association of current depression with inflammatory markers, adjusted for potential confounding variables.
RESULTS
Of the 984 participants, 217 (22%) had current major depression. Depression was not associated with increased levels of any inflammatory marker. Contrary to our hypothesis, depression was associated with lower levels of CRP (p = .09), fibrinogen (p = .006), and IL-6 (p = .007) in both unadjusted and adjusted models.
CONCLUSIONS
We found no evidence that current depression is associated with greater inflammation in outpatients with CHD. Inflammation is unlikely to explain the adverse cardiovascular outcomes associated with depression in patients with established CHD.
View on PubMed2007