Abacavir hypersensitivity reaction in primary HIV infection

OBJECTIVE: To evaluate risk factors associated with the abacavir hypersensitivity reaction during primary HIV infection (PHI). DESIGN: Acute HIV Infection and Early Disease Research Program protocol (AIEDRP) AI-02-001 provided antiretroviral therapy including abacavir. This retrospective analysis evaluated variables potentially associated with hypersensitivity in the cohort enrolled in AI-02-001 at the University of Washington Primary Infection Clinic. METHODS: Cases of suspected hypersensitivity were identified prospectively and reviewed retrospectively using a standardized case definition. Controls were the remaining cohort without hypersensitivity. Univariate analyses were performed by linear logistic regression. RESULTS: Nine (18%) of 50 individuals treated with abacavir developed suspected hypersensitivity. Two of nine cases and no controls were HLA-B5701 positive. When antiretroviral medications were started, cases had lower mean CD8 T-cell percentage and plasma HIV RNA value. After 2 weeks on abacavir, cases had a lower mean HIV RNA value and a trend towards greater decrease in RNA. Cases began abacavir a median of 103 days after HIV acquisition compared to 48 days for controls. There was no significant in vitro abacavir-specific lymphoproliferation or IFN-gamma production in peripheral blood mononuclear cells from individuals following the suspected hypersensitivity reaction. CONCLUSIONS: Abacavir use during PHI may be associated with increased risk of hypersensitivity. As in chronic infection, HLA-B5701 is associated with the abacavir hypersensitivity reaction in PHI. Although levels of CD8 T cells and HIV RNA may be risk factors for hypersensitivity, the observed association may be due to correlation with HLA-B5701. The interesting temporal association of hypersensitivity with initiation of abacavir later in PHI merits future investigation.     

Left ventricular ejection fraction and volumes on rest gated 201Tl perfusion SPECT: comparison with two-dimensional echocardiography

BACKGROUND: Rest gated 201Tl images are considered to be of poor count statistics due to lower energy and low photon flux of 201Tl in addition to increased attenuation and low dose that can be administered. We compared the left ventricular ejection fraction (LVEF), end diastolic (EDV) and end systolic volume (ESV) obtained on 4 h gated rest 201Tl myocardial perfusion single photon emission computed tomography (SPECT) with those obtained by two-dimensional echocardiography (2-D ECHO) in patients with known or suspected coronary artery disease (CAD). METHODS: Eighty-two consecutive patients who underwent gated 201Tl stress-rest myocardial perfusion SPECT and 2-D ECHO were studied. The gated thallium images were processed with Siemens e-soft autocardiac processor and LVEF, EDV and ESV were evaluated using Emory Cardiac Toolbox. The same parameters were also assessed on the 2-D ECHO using the modified Simpson method for comparison. RESULTS: Out of 82 rest gated images, one study was excluded because of poor count statistics. In 81 (99%) patients there was good linear correlation with 2-D ECHO values and rest gated 201Tl SPECT images for EDV, ESV and LVEF. Pearson's correlation co-efficient (r value) for EDV, ESV and LVEF between the two methods was 0.78, 0.79 and 0.88, respectively. A Bland-Altman plot showed close agreement with LVEF but not for EDV and ESV. CONCLUSION: These results suggest that the 4 h rest gated 201Tl study gives a reliable value for the LVEF compared to 2-D ECHO and can be used in routine clinical practice.     

Thrombotic thrombocytopenic purpura in a patient with very early pregnancy: clinical presentation and autopsy findings

Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy leading to microvascular occlusion resulting in ischemic dysfunction of various organs. Pregnancy has been thought to precipitate it during second and third trimester, but its reports in first trimester are extremely rare. We report the clinical protocol of a young lady with 5-week period of gestation, who presented with fever, seizures and altered sensorium, and succumbed to her illness during an episode of seizure. Complete autopsy findings are also presented in detail.     

Discriminative stimulus (DS) properties of nicotine in the C57BL/6 mouse.

Previous research conducted in this and other laboratories has examined the role of genetic factors in determining sensitivity to (-)-nicotine in a variety of behavioral and physiological measures in the rat. More recent research further indicates that genetic factors can also influence the level of sensitivity to (-)-nicotine when serving as a discriminative stimulus (DS) in different rat strains. However, there has been little work examining the influence of genotype on the discriminative stimulus (DS) properties of (-)-nicotine in mice, a species that has played a major role in understanding the relationship between genetics and (-)-nicotine pharmacological effects. To further our understanding of the role of genetics and the ability of (-)-nicotine to exert DS control of behavior in the mouse, a group of C57BL/6 mice was trained to discriminate 0.4 mg/kg (-)-nicotine from saline using a two-lever operant procedure. (-)-Nicotine's discriminative stimulus in C57BL/6 mice appears to be similar to that generated in the rat. Results from behavioral tests with other drugs indicated that d-amphetamine exhibited a partial generalization, while (+)-nicotine fully generalized with nicotine. Tests of antagonism with mecamylamine and scopolamine further showed the cholinergic specificity of the (-)-nicotine DS in the mouse; mecamylamine but not scopolamine completely antagonized the (-)-nicotine DS. This work lays the groundwork for future comparisons of different mouse strain's sensitivities to (-)-nicotine's discriminative stimulus as well as using this behavioral model to search for new nicotinic receptor agonists and antagonists.     

The relation between body size and normalized small solute clearances in continuous ambulatory peritoneal dialysis.

The normalized peritoneal clearances of small solutes depend on the ratio of their concentration in dialysate and plasma (D/P) and the drain volume (Dv) corrected for some measure of body size such as body water (V) or body surface area (BSA). The clearance formulas (D/P) x (Dv/V) and (D/ P) x (Dv/BSA) can be used to examine why large individuals tend to be underdialyzed. Large people have low normalized drain volumes (Dv/V, Dv/BSA). It is not known whether size affects the D/P ratios. The purpose of this study was to examine the relationship between normalized peritoneal clearances (Kt/Vurea, CCr per 1.73 m2 BSA) and four size indicators (weight, height, V, BSA) in 301 patients on continuous ambulatory peritoneal dialysis (four daily exchanges with 2-L exchange volume) who underwent 613 clearance studies. Highly significant (P < 0.001) nonlinear relationships were found between Kt/Vurea and weight (r2 = 0.371), height (r2 = 0.289), BSA (r2 = 0.436), and V (r2 = 0.527); and between CCr and weight (r2 = 0.178), height (r2 = 0.115), BSA (r2 = 0.199), and V (r2 = 0.151). There were also significant negative correlations between the normalized drain volumes (Dv/V and Dv/BSA) and all four indicators of body size. Raw (not normalized) peritoneal clearances and drain volumes correlated positively with size. However, D/P(urea) or D/P(creatinine) did not vary with any size indicator except for a weak association between D/P(creatinine) and V (r = 0.089, P = 0.028). This association was not confirmed when V was used to stratify subjects into quartiles, and group differences for D/P(creatinine were tested by one-way ANOVA. This study shows that the exclusive cause of the low normalized peritoneal clearances in large subjects on continuous ambulatory peritoneal dialysis is a low normalized drain volume. No evidence was found to indicate that body size influences the D/P ratio of small solutes. The portion of the variance in normalized clearance explained by size varies by size indicator and solute (urea versus creatinine).