T cell responses to recall antigens, alloantigen, and mitogen of HIV-infected patients receiving long-term combined antiretroviral therapy

The effect of highly active antiretroviral therapy (HAART) on T cell responses in 30 HIV-infected patients was studied. Lymphocyte proliferation in response to influenza A virus, HIV-1 p24, gp160, allogeneic leukocytes, and mitogen, as well as influenza-specific cytotoxic T lymphocyte (CTL) responses, were measured. AIDS patients had decreased T cell-proliferative responses to influenza and alloantigen compared with asymptomatic patients. Absence of positive proliferative responses of HIV-infected patients to HIV-1 antigens was not associated with increased interleukin 10 production. Correlation was observed between influenza-specific CTL response and T cell proliferation, as well as CD4+ T lymphocyte counts, indicating the importance of CD4+ helper T cells for generating antiviral CTL responses. Finally, these results show that HAART-treated asymptomatic patients, but not AIDS patients, have T cell responses comparable to those of control individuals. It remains to be determined whether immune-based therapy will contribute any additional benefit to patients who received HAART.     

Treatment of silastic catheter-induced central vein septic thrombophlebitis

Two patients with surgically implanted right atrial silastic catheters for home hyperalimentation developed central vein septic thrombophlebitis. Initial treatment including removal of the catheter and antibiotic therapy was unsuccessful and both patients had persistent fever and bacteremia. A clinical and microbiologic response occurred when anticoagulation therapy with heparin was added to the treatment regimen. Although a surgical approach has been emphasized in patients with peripheral vein suppurative thrombophlebitis, anticoagulation therapy may be a useful alternative in the treatment of patients with central vein infection.     

Effect of oral nitroglycerin and cold stress on myocardial perfusion in areas subtended by stenosed and nonstenosed coronary arteries

Physical obstruction and coronary vasoconstriction mediated by adrenergic stress are believed to be responsible for episodes of myocardial hypoperfusion and angina. Nitroglycerin relieves symptoms by reducing preload and dilating epicardial vessels. The net perfusion change and relation to stenosis severity of nitroglycerin and adrenergic stress have been debated. This study aimed to evaluate whether oral nitroglycerin and adrenergic stress alters perfusion in myocardial segments subtended by stenosed and nonstenosed coronary arteries. Myocardial perfusion was quantified (using N-13-ammonia positron emission tomography [PET]) at rest, after oral nitroglycerin 400 microg, and after cold stress in 25 patients with coronary artery disease (62 +/- 9 years, 21 men) and in 30 controls (34 +/- 9 years, 22 men). Myocardial perfusion was quantified in areas supplied by stenosed (>70%) and nonstenosed (<30%) coronary arteries. The cold pressor test did not significantly alter myocardial perfusion in any of the groups. However, when normalized for rate-pressure product, the response in stenosed areas showed a significantly more pronounced reduction compared with nonstenosed areas (0.78 +/- 0.18 vs 0.64 +/- 0.19 ml/g/min, p <0.005 and 0.86 +/- 0.19 vs 0.73 +/- 0.24 ml/g/min, p <0.05, p <0.05) for intergroup comparison. In both stenosed areas and nonstenosed areas nitroglycerin increased perfusion (0.51 +/- 0.14 vs 0.60 +/- 0.17 ml/g/min, p <0.05 and 0.56 +/- 0.14 vs 0.61 +/- 0.17 ml/g/min, p <0.05). Nitroglycerin did not alter myocardial perfusion in the control group. There was a negative correlation between the cold pressor test response and stenosis severity (r(2) = 0.17, p <0.046), whereas this was not the case for nitroglycerin. In patients with coronary artery disease, myocardial segments supplied by stenosed coronary arteries showed an altered perfusion response to adrenergic stress. Oral nitroglycerin increased myocardial perfusion irrespective of the presence of a stenosis.     

Hepatic encephalopathy influences high-affinity uptake of transmitter glutamate and aspartate into the hippocampal formation

The present work was carried out to study the influence of ammonia and factors from sera and cerebrospinal fluid (CSF) from patients with different degrees of chronic liver diseases on [³H]D-aspartate (Asp) and [³H]L-glutamate (Glu) high-affinity uptake into the rat hippocampal formation. For comparison, high-affinity uptake of Glu and Asp was determined in human hippocampal brain tissue obtained at autopsy from cirrhotic patients dying in hepatic coma and from control brains free from neurological, psychiatric, or hepatic diseases. Sera and CSF from patients with chronic liver failure and hepatic encephalopathy (HE) were seen to reduce dramatically Glu and Asp uptake into rat hippocampal dendritic layers. A close inverse relationship was found to exist between the level of ammonia in the sera and the inhibition of uptake, both phenomena correlating highly with the extent of liver failure. The present findings, obtained after dilution of sera from patients with HE while maintaining initial ammonium levels, elucidate, however, that ammonia alone cannot account for the reduction in Glu/Asp uptake capacity. The inhibition of Asp uptake into human hippocampal formation of patients dying in hepatic coma was even more pronounced when compared to that found in rat hippocampus incubated in sera and CSF from patients. Glu/Asp uptake into brain tissue is supposed to be an important factor in the pathogenesis of HE accompanying liver dysfunctions.     

In vivo antagonism with zidovudine plus stavudine combination therapy

Human immunodeficiency virus (HIV)-infected subjects receiving zidovudine were randomized either to add stavudine (d4T) or didanosine (ddI) to their current regimen or to switch to ddI or d4T monotherapy. After 16 weeks of therapy, the mean reduction in HIV RNA from baseline was 0.14 log(10) copies/mL in patients receiving d4T or zidovudine plus d4T. In subjects receiving ddI or ddI plus zidovudine, reductions were 0.39 and 0.56 log(10), respectively. CD4 cell counts remained stable or showed modest increases in all arms except the zidovudine plus d4T arm. Patients receiving zidovudine plus d4T showed progressive declines in CD4 cell counts with a median of 22 cells/mm(3) below baseline by 16 weeks. Examination of intracellular levels of d4T-triphosphate in 6 subjects was consistent with previous in vitro studies demonstrating pharmacologic antagonism between zidovudine and d4T. Analysis of these data suggests that zidovudine and d4T should not be prescribed in combination and that ddI provides greater antiviral activity than d4T in zidovudine-treated patients.     

Preferential uptake of a water-soluble phthalocyanine by atherosclerotic plaques in rabbits

This study is the first demonstration of preferential accumulation of a water soluble phthalocyanine dye in atheromatous plaques in the rabbit. Two groups of rabbits with diet-induced atheromatous plaques were killed 4 and 24 h following intravenous administration of copper phthalocyanine tetrasulfonate. Uptake of the dye by plaque-containing and normal appearing aortae was evaluated macroscopically and quantitatively by extraction of the dye from the tissues. The concentration of the dye in the atheromatous plaques was 2.6 and 1.7 times higher than in the normal vessel wall at 4 and 24 h, respectively. The concentration of the dye in normal appearing aortae in the 2 study groups was similar to that of aortae of control rabbits which were fed a normal diet and exposed to the dye for the same time periods. We conclude that copper phthalocyanine accumulates preferentially in atheromatous plaques in rabbits. These findings provide a basis for the utilization of phthalocyanines for plaque identification and for photodynamic therapy of atherosclerosis.     

Impact of Impaired Coronary Flow Reserve and Insulin Resistance on Myocardial Energy Metabolism in Patients With Syndrome X

To evaluate the role of a decreased coronary flow reserve in the genesis of angina pectoris in patients with syndrome X, we studied myocardial hemodynamics and metabolism at rest, during pace stress, and in the recovery period after pacing in 18 consecutive patients with syndrome X and in 10 control subjects. By means of positron emission tomography or the intracoronary flow-wire method, patients were subclassified as having microvascular angina (MA, n = 8) when coronary flow reserve was reduced (<2.5) or no microvascular angina (non-MA, n = 10) when coronary flow reserve was preserved (≥2.5). At rest, coronary sinus blood flow was increased in MA patients. During pace stress, coronary sinus blood flow increased by 39 ± 6% in MA patients versus 67 ± 12% in non-MA patients and 69 ± 7% in controls (p <0.05). Patients with non-MA revealed fasting hyperinsulinemia, increased arterial concentration of free fatty acids, and a similar tendency for

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-hydroxybutyrate. Oxygen extraction and carbon dioxide release did not differ between groups. Net myocardial lactate release was not observed in any patient during pace stress and myocardial energy metabolism was preserved in all patients with syndrome X. During pacing, myocardial uptake of free fatty acids and

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-hydroxybutyrate was increased in non-MA patients. Myocardial uptake of free fatty acids correlated positively and myocardial glucose and lactate uptake correlated inversely with arterial concentrations of free fatty acids in all subjects. Metabolic evidence of myocardial ischemia is uncommon in patients with syndrome X, irrespective of a globally reduced coronary flow reserve. Although patients with syndrome X can be subclassified according to presence of a microvascular or a metabolic disorder, angina pectoris and ST-segment depressions coexist with a preserved global myocardial energy efficiency in all patients.We studied myocardial metabolism in patients with syndrome X subclassified depending on whether coronary flow reserve was reduced. None of the patients had metabolic evidence suggestive of myocardial ischemia, and myocardial energy metabolism remained preserved in all patients, including those with a reduced coronary glow reserve.     

Altered left ventricular volume and ejection fraction responses to supine dynamic exercise in athletes

Two-dimensional echocardiography was used to determine the responses of left ventricular volumes, ejection fraction and segmental left ventricular motion to supine dynamic exercise in 22 professional athletes, comparing these responses with those in 22 age- and gender-matched healthy untrained individuals. End-systolic volume was significantly greater at rest and during exercise in the athletes (50 +/- 6 versus 29 +/- 4 ml and 40 +/- 5 versus 17 +/- 4 ml, respectively, p less than 0.001 for both). It decreased during exercise in all the untrained subjects, but did not change or increased in nine athletes (41%). End-diastolic volume was greater in the athletes at rest (143 +/- 12 versus 98 +/- 9 ml) and during exercise (157 +/- 14 versus 121 +/- 13 ml, p less than 0.01 for both). It increased in all the untrained subjects, but decreased or did not change in six athletes (27%). Ejection fraction was significantly lower in the athletes at rest and during exercise (65 +/- 4% versus 70 +/- 5% and 73 +/- 5% versus 86 +/- 5%, p less than 0.01 and 0.001, respectively); the values augmented normally in all the untrained subjects, but increased only by less than 5% units, did not change or decreased in nine athletes (41%). Eight athletes (36.5%) failed to demonstrate the expected symmetric hyperkinetic wall motion changes during exercise, which were seen in all the untrained subjects. No correlation was found between atypical responses to exercise and electrocardiographic patterns.(ABSTRACT TRUNCATED AT 250 WORDS)