Beating the bug.
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Computer-Assisted Instruction↗
Biomedical subjects
Deborah King
Publications and source records attributed to Deborah King.
Intracellular cytokines may model immunoregulation of abacavir hypersensitivity in HIV-infected subjects.
BACKGROUND: The clinical treatment of patients with HIV and adverse drug events may be enhanced by an understanding of the underlying mechanisms. About 4% of patients with HIV receiving the potent antiretroviral drug abacavir develop a hypersensitivity reaction. This idiosyncratic reaction appears to have an immunologic component that has yet to be defined. Given that the T-cell type 2 cytokine IL-4 may be overproduced by patients with allergy or other immunologic dysregulation, an index cytokine profile could help elucidate the character of a drug-specific hypersensitivity reaction. OBJECTIVE: Quantitation of the production of the type 2 IL-4 and the counterregulatory type 1 cytokine IFN-gamma in patients with abacavir-related hypersensitivity. METHODS: Intracellular cytokines were enumerated in blood T cells by flow cytometry. Subjects were grouped for evaluation as patients with a hypersensitive response after abacavir treatment, patients initiating abacavir who also were evaluated again after 1 month on abacavir, patients on abacavir for 6 months without hypersensitivity, and HIV-naive control individuals. RESULTS: There was a significant association between increased IL-4 production by CD4 and CD8 T lymphocytes and hypersensitivity reactions to abacavir. Lymphocytes from hypersensitive subjects expressed CD28 and the anti-HIV chemokine macrophage inflammatory protein 1beta with a frequency comparable with HIV-naive control cells, suggesting the possibility that the activated T cells from patients with hypersensitivity are functional. CONCLUSION: The expansion of type 0 and type 2 T cells phenotyped by IL-4 production may correlate with abacavir-associated hypersensitivity. The data suggest a cytokine bias that may facilitate B-cell differentiation and downregulate T-cell cytotoxic responses.
Anti-HIV Agents↗
Characteristics of triple and quadruple toe-loops performed during the Salt Lake City 2002 Winter Olympics.
The purpose of this study was to compare triple (T) and quadruple (Q) toe-loop figure skating jumps and quantify basic characteristics of these jumps to provide information to coaches that will assist them in teaching quadruple toe-loops to elite figure skaters. High-speed video was taken during men's practice and competition sessions at the 2002 Salt Lake City Winter Olympics; three-dimensional analyses of selected triple and quadruple jumps were completed. The most significant difference between triple and quadruple toe-loops was an increase in rotational velocity in the air. Additionally, increased vertical velocity at take-off and subsequent time in the air were also observed. Three main conclusions were developed: 1) The timing of rotation of the hips and shoulders was different for quadruple toe-loops compared to triples with the differences being observed before toe-pick; 2) Increases in rotational velocity occurred primarily as a result of the skaters assuming different body positions from take-off through landing which resulted in tighter rotating positions for longer durations of the jump; 3) Greater vertical velocity was gained during the propulsive phase due to the extension of the legs during the press off the ice.
Adult↗
Left ventricular diastolic dysfunction: risks, identification, and treatment.
Risk factors of cardiovascular disease, such as hypertension, diabetes, and myocardial infarction, if left untreated, will increase the risk of the development of chronic heart failure. Much is known about the pathophysiology and effective treatments of chronic heart failure from left ventricular systolic dysfunction; however, little clinical trial evidence exists concerning benefits of treating patients with chronic heart failure and preserved systolic function, also known as left ventricular diastolic dysfunction. Rather, an understanding of the pathophysiology and patient signs and symptoms has usually dictated choice of treatments. With the results of ongoing trials, as well as the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM)-Preserved and the Digitalis Investigation Group (DIG) trials, clinical evidence is accumulating to support effective treatments in patients with left ventricular diastolic dysfunction. The focus of this review is to discuss the risks of, identification of, and rationale for therapeutic choices being employed for treating left ventricular diastolic dysfunction and implications from studies that may support these choices.
Adrenergic beta-Antagonists↗
Cardiovascular implications of thiazolidinedione therapy.
The incidence of obesity and type 2 diabetes mellitus (DM2) in the United States has been increasing dramatically over the past 15 years, and is now at epidemic proportions. DM2 is the clinical manifestation of a long-term metabolic process that is initiated by cells' decreased sensitivity to the actions of insulin. Many outcome studies have identified DM2 as a strong and independent risk factor for the development of cardiovascular complications such as hypertension, arteriosclerosis, and heart failure. The goals of therapy in treating DM2 are to improve the long-term outlook for these patients. However, in selecting a therapeutic regimen for patients, clinicians should be aware that potentially severe adverse events may occur at a rate not previously identified in phase 3 studies. Certain therapies used to treat DM2, by effectively increasing the sensitivity of insulin, have also been reported to cause adverse effects, which can precipitate symptomatic heart failure. The purpose of this column is to discuss the therapeutic options available for treating patients with DM2, the potential pathophysiology of the adverse events of symptomatic heart failure, encouragement of use of the US Food and Drug Administration MedWatch program for reporting adverse events associated with medication therapy, and review of newer treatment guidelines for use of insulin-sensitizing agents in patients with chronic heart failure.
Cardiovascular Diseases↗
Evidence for Gag p24-specific CD4 T cells with reduced susceptibility to R5 HIV-1 infection in a UK cohort of HIV-exposed-seronegative subjects.
AIM: To characterize HIV-1 Gag p24-specific CD4 cell responses in HIV-exposed-seronegative (ES) individuals. METHODOLOGY: Twelve ES individuals, of diverse ethnicity and wild type for the CCR5 Delta-32 mutation, were identified. Controls were HIV-negative blood donors. Gag p24-specific and total Vbeta+ CD4 cells that expressed MIP-1beta, IFN-gamma and IL-2 were enumerated by intracytoplasmic cytokine staining. beta-Chemokine expression was correlated with susceptibility to R5 HIV-1 infection, as measured by polymerase chain reaction for integrated HIV-1 and by p24 enzyme-linked immunosorbent assay. RESULTS: Similar numbers of mitogen-stimulated and Vbeta+ MIP-1beta+, IFN-gamma+ and IL-2+ T cells were found in ES and HIV-negative control subjects. However, all ES subjects tested had an HIV Gag p24-specific MIP-1beta+, IFN-gamma+ and IL-2+ CD4 T-cell response that was rare in controls. p24-Specific cells of all ES but no control subjects could be expanded by in-vitro Ag/IL-2 stimulation, and when re-stimulated with an overlapping peptide series showed evidence of a broad CD4 cell memory response directed against multiple regions of Gag p24. Mitogen-stimulated ES CD4 cells were as susceptible to HIV infection as those from control subjects, but p24-specific IFN-gamma+ CD4 cells of six out of seven ES subjects tested were less susceptible to R5 HIV-1 infection than the counterpart fraction depleted of p24-specific IFN-gamma+ cells. The addition of blocking anti-beta-chemokine antibodies did not promote R5 HIV-1 infection of p24-specific IFN-gamma+ cells. CONCLUSION: Specific CD4 cell immunity, characterized by a broadly directed memory Gag-p24 CD4 cell response and reduced susceptibility of specific CD4 cells to R5 HIV-1 infection, is a likely correlate of non-transmission.
Adult↗
Obesity Hypertension in the Atherosclerosis Risk in Communities Cohort: Implications of Obesity Guidelines.
An estimated 55% of the U.S. adults are overweight or obese (body mass index [BMI] equals 25 kg/m2). Overweight individuals have a threefold increased risk for the development of hypertension compared to lean individuals. The National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI) guidelines for treatment of overweight and obese adults recommend weight reduction strategies including pharmacologic treatment with antiobesity agents approved by the FDA. Treatment is recommended for obese individuals and for overweight persons with other risk factors for cardiovascular disease (CVD) including hypertension. This analysis of the Atherosclerosis Risk In Communities (ARIC) cohort for overweight/ obese hypertensive participants indicate that 64% of the hypertensive participants in ARIC deserve consideration for treatment with antiobesity agents according to the current NHLBI guidelines. Thus far there are no long term morbidity and mortality clinical trials to determine the safety of antiobesity agents currently approved by the FDA. The authors caution health care providers in the use of these agents in the obese patient with hypertension. (c)1999 by Le Jacq Communications, Inc.
Journal Article↗