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Biomedical subjects

J Witek

Publications and source records attributed to J Witek.

At least 19 recordsLinked to original sources

Increased CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells.

Why HIV-specific CD8(+) T cells ultimately fail to clear or control HIV infection is not known. We show here that HIV-specific CD8(+) T cells exhibit increased sensitivity to CD95/Fas-induced apoptosis. This apoptosis is 3-fold higher compared to CMV-specific CD8(+) T cells from the same patients. HIV-specific CD8(+) T cells express the CD45RA(-)CD62L(-) but lack the CD45RA(+)CD62L(-) T cell effector memory (T(EM)) phenotype. This skewing is not found in CMV- and EBV-specific CD8(+) T cells in HIV-infected individuals. CD95/Fas-induced apoptosis is much higher in the CD45RA(-)CD62L(-) T(EM) cells. However, cytotoxicity and IFNgamma production by HIV-specific CD8(+) T cells is not impaired. Our data suggest that the survival and differentiation of HIV-specific CD8(+) T cells may be compromised by CD95/Fas apoptosis induced by FasL-expressing HIV-infected cells.

Adult↗

Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy.

CONTEXT: Despite suppressive treatment with highly active antiretroviral therapy (HAART), replication-competent virus can still be isolated from peripheral blood mononuclear cells and genital cells of many individuals receiving suppressive HAART. OBJECTIVE: To determine whether free virion RNA can be detected in the blood plasma and/or genital tract fluids from patients receiving suppressive HAART. DESIGN: Prospective cohort study conducted from November 1998 to May 1999. SETTING: Academic medical center. PATIENTS: Human immunodeficiency virus 1-infected individuals (20 men and 2 women) shown in our laboratories to have fewer than 50 copies/mL of HIV-1 RNA in peripheral blood plasma while taking suppressive HAART. MAIN OUTCOME MEASURES: Free virion RNA levels in peripheral blood plasma and genital fluids, quantified using an ultrasensitive reverse transcriptase polymerase chain reaction able to quantify cell-free virion RNA to a lower limit of 5 copies/mL and qualitatively detect viral RNA below this level. RESULTS: In all 22 patients, residual viral RNA could be detected in the peripheral blood plasma (mean level, 17 copies/mL). The presence of viral RNA suggests that ongoing viral replication is occurring, albeit at low levels, in each patient evaluated. Viral RNA levels were lower in most patients' genital fluids compared with blood plasma and in 12 patients were undetectable. CONCLUSIONS: These data suggest that low-level replication of HIV-1 in patients taking suppressive HAART may be demonstrated not only in peripheral blood mononuclear cells but also in peripheral plasma as cell-free virion RNA. Complete ablation of viral replication may require intensification of antiretroviral therapies beyond standard suppressive HAART.

Anti-HIV Agents↗

Acute and long-term treatment of hypertension with nifedipine in the elderly.

The acute hypotensive effect of nifedipine was evaluated, and the possibility of its long-term use in hypertensives over 60 years of age was studied. Sublingual nifedipine in a dose of 20 mg was given to 28 patients, mean age 73.1 yrs, and blood pressure, heart rate, and plasma drug concentration were monitored at 15 min, and every 30 min thereafter for 3 hrs. Systolic and diastolic blood pressure decreased at 15 min by 22.1 and 7.0 mmHg, respectively, reaching a maximal decrease two hours after drug administration. The decrease in blood pressure level did not correlate with nifedipine plasma concentration, but only with the initial systolic blood pressure. Long-term treatment with nifedipine was initiated in 60 patients, with 45 patients completing the study. Mean age was 66.2 years. An initial dose of 30 mg daily had to be increased to 60-80 mg in one-third of the patients. Monotherapy was not satisfactory in some patients. Blood pressure gradually decreased from 173/99 to 148/85 mmHg at three months, and to 141/84 mmHg at six months. Drug tolerance was fairly good. Nifedipine was withdrawn due to a considerable increase in heart rate in three patients and skin allergy in one. The most frequent adverse symptoms were: rash, headache, and leg oedema. Laboratory tests revealed no changes in urea and creatinine, and an increase in fasting glycaemia. Lipid parameters did not change significantly. These data proved that a single dose of 20 mg of nifedipine produced therapeutic plasma concentration of the drug and good hypotensive effect, positively correlating with initial systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Sublingual↗

[Diagnostic problems in patients with superior vena cava syndrome].

Diagnostical difficulties were shown in 275 patients with the superior vena cava syndrome (SVCS) evaluated in the years 1970-1982. Men consisted 84 percent of the group. In 68 percent the symptoms preceded hospitalization by less than one month. 31 percent of the patients were treated without histopathological verification. In 83 percent the cause of the SVCS was lung cancer. Only in 10 patients (5.3%) non-malignant causes were present. Basing on analysis of their material the authors conclude that it it possible to make a diagnosis of SVCS etiology in the majority of the patients. This is mandatory because the etiology of this syndrome is variable, and the therapy may produce unwarranted and unjustified side effects in many cases.

Adult↗

[Nifedipine level in the blood and its immediate hypotensive effect after its sublingual administration to aged patients].

In 28 aged patients (means = 73.1 years) with arterial hypertension nifedipine has been administered sublingually in a single dose of 20 mg and the hypotensive effect of that drug under the control of its concentration in the blood serum was evaluated. The nifedipine concentration was determined by the use of gas chromatography with electron capture detector. The mean drug concentration increased from 38.1 ng/ml to 82.3 ng/l during the 2nd hour of observation. After 3 hours the lowering of the nifedipine concentration and the decrease of its hypotensive effect was observed. After 15 min from the drug application the systolic pressure lowered by the average 22.1 mmHg whereas the diastolic pressure was 7.0 mmHg lower. The most significant pressure decrease (mean of systolic pressure 52.7 mmHg) 7.03 kPa and that of diastolic pressure 23.2 mmHg (3.1 kPa) occurred after 2 and 1.5 hours. The decrease of pressures after nifedipine correlated with the start-point value of systolic pressure. The frequency of the heart action in the whole group did not altered significantly, however, in individual cases both the acceleration of that action (34 per min) or acceleration (42 systoles per min) was noted. Slight typical side-effects were noted in 5 treated patients. A single-dose sublingual 20 mg nifedipine (Cordafen--Polfa) administration enabled in all the subjects the obtaining of therapeutic drug level in the blood and in the aged patients with hypertension may be regarded as efficacious antihypertensive treatment.

Administration, Sublingual↗

Trends and patterns in lung cancer incidence in four cities of Eastern Europe, 1971-1980.

The trends of age-adjusted and age-specific lung cancer incidence rates showed over the period of 1971-1980 substantial differences in four selected towns of Eastern Europe. The downward age-adjusted trends in males coincided in Berlin with the possible beginning of their downturn in the whole country, while their decline in both sexes in Bratislava could be related to the change of demographis factors. In the other two towns studied--Cracow and Tallinn--the substantial increase of lung cancer incidence in males corresponded with the similar evolution in both respective countries (Poland and Estonia). The rising trends in females in both mentioned towns could be more or less compared with their dramatic increase in some developed countries. The rising trends of age-specific rates in younger age groups of males do not indicate meanwhile the positive influence of low-tar or filter-tipped cigarettes on lung cancer incidence in males observed recently in some countries.

Adult↗

Pharmacokinetic investigations of Craviten. I. Spectrofluorometric determination of the drug in biological material.

A spectrofluorometric method for the quantitative determination of Craviten in serum, tissues and urine is described. The fluoroscence spectrum of that compound in acetic acid solution at excitation and emission wavelengths 270/380 nm respectively, is determined. A linear relationship between fluorescence and concentration exists over the range 0.25-10 microgram/ml and concentration of the drug as small as 0.15 microgram/ml may be determined.

Animals↗

Pharmacokinetic investigations of Craviten. II. Dose-dependent elimination kinetics in rats following rapid intravenous injection.

Serum and urine levels of iv administered Craviten were determined. Comparison of the decline of the same absolute and relative serum concentrations of the drug and the variation of pharmacokinetic parameters with the dose leads to the conclusion, that the elimination of Craviten in rats cannot be described by first-order kinetics. The amount of the drug found in urine indicates, that the fraction of Craviten eliminated in the intact form is about 1.27 per cent of the iv administered dose.

Animals↗