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Biomedical subjects

W Kirch

Publications and source records attributed to W Kirch.

At least 163 records · Page 9Linked to original sources

Ranitidine increases the bioavailability of nitrendipine in patients with arterial hypertension.

1. In a randomized placebo-controlled study, 12 hypertensive patients were treated po for one week with 20 mg nitrendipine once daily plus placebo, twice daily and later with the same dose of nitrendipine plus 300 mg ranitidine (150 mg twice a day). 2. When ranitidine was coadministered, plasma nitrendipine levels (0-24 h) were significantly increased (P < 0.001), although no significant increase in peak plasma nitrendipine level (Cmax) was observed due to the wide range of variation of this parameter (Cmax) in hypertensive patients. 3. Ranitidine coadministration increased the area under the curve for 24-h (AUC0-24) plasma concentration vs time, from 49.07 +/- 6.28 micrograms.h/l to 82.35 +/- 2.57 micrograms.h/l (P < 0.01). This significant increase caused a reduction in total body clearance from 2008.33 +/- 246.33 to 1284.00 +/- 182.16 ml/min (P < 0.002). 4. Nitrendipine bioavailability was increased by 89% when ranitidine was coadministered but the kinetic effect of this drug interaction is unlikely to be of clinical relevance since no adverse effects were observed in patients evaluated after ranitidine association.

Adult↗

Neuropsychological impairment in auto-immune disease.

Estimations of the prevalence of central nervous system involvement in patients with systemic lupus erythematosus (SLE) vary from 25 to 75%. In order to assess possible deficits in memory, attention, and/or reaction time, a battery of neuropsychological tests was administered to 15 patients with SLE and to two matched groups of control subjects; eight patients on corticosteroids and 15 healthy controls. The test battery included the Multiple Choice Word Fluency Test (MWT-B), Benton Visual Memory Scale, Syndrome Short Test (SKT; attention and memory), Attention and Concentration Test (d2), Wechsler Adult Intelligence Scale (WAIS) subtests for Comprehension, Digit Span, Block Design, a Computer Controlled Reaction Time task (CCRT), and a Learning and Memory Test (LGT-3). Results revealed a statistically significant short-term memory deficit (for all six relevant subtests used) and a marked delayed simple reaction time in SLE patients as compared with scores in healthy subjects. An attention deficit as well as the expected difference between the estimated premorbid and actual level of intelligence could not be demonstrated. With three exceptions (SKT-9 figural recognition, Benton Visual Memory, and LGT-3 figural recognition), patients treated with corticosteroids did not differ from healthy controls. They also did not differ from SLE patients in any of the parameters tested. It therefore appears that the demonstrated deficit in short-term memory and reaction time in SLE patients may not only be due to the neuropsychiatric manifestation of SLE but possibly also result from medication side-effects.

Adult↗

Modulation of the immune response to stress in patients with systemic lupus erythematosus: review of recent studies.

Physical and psychological stress in healthy subjects leads to characteristic alterations of plasma hormone concentrations and the lymphocyte subset distribution. After short-term bicycle ergometry or acoustic stress, and after a 2-h-long neuropsychological examination, a rise in B- and T-suppressor/cytotoxic lymphocytes and a decrease in T-helper lymphocytes has been shown to occur. This cell mobilization was accompanied by an elevation in plasma catecholamines. Although the rise in catecholamine levels was similar in patients with systemic lupus erythematosus (SLE) and in healthy subjects, the alterations in the lymphocyte subsets were less pronounced in SLE patients after bicycle ergometry as well as after psychological testing than in healthy subjects, patients with sarcoidosis, and patients without collagenosis under treatment with corticosteroids. Differences between short-term physical exercise and the acoustic stress test on the one hand, and the 2-h-long neuropsychological test on the other, were observed only for the absolute lymphocyte count. After short-term stress, a rise in the leukocyte and lymphocyte count was noted, whereas after long-term testing, only an increase in leukocytes and a decrease in lymphocytes could be found. In conclusion, sympathomimetic stimulation by bicycle ergometry or by psychological stress led to a characteristic cell mobilization in all the groups investigated. The extent of cell mobilization was attenuated in SLE patients despite the fact that comparable increases of plasma catecholamines were observed.

Adult↗

Modulation of lymphocyte subsets due to psychological stress in patients with rheumatoid arthritis.

The influence of a 1-hour neuropsychological stress test on the distribution of lymphocyte subpopulations and on plasma catecholamine levels was investigated in 18 patients with rheumatoid arthritis (RA) and 14 sex- and age-matched controls. Despite significant increases in lymphocyte counts in both groups, lymphocyte subsets did not change accordingly. A wide scattering of catecholamine levels in plasma before and after stress was observed. Plasma levels of lymphokines such as interleukin (IL)-1 beta and IL-6 could not be detected in RA patients. Enzyme immunoassay of markers of lymphocyte activation such as HLA-DR and cell-bound IL-2 receptor showed only a significant elevation of HLA-DR marked cells in RA patients at baseline. Significantly higher amounts of the soluble IL-2 receptor were detected in patients with RA before the stress test, but stress testing did not alter this parameter. In conclusion, lymphocyte activation in RA and a defect in the expression of IL-2 receptor on the cell surface of lymphocytes were confirmed in the present study.

Arthritis, Rheumatoid↗

[Indirect azygos-vein-continuation syndrome with aneurysm of the inferior vena cava].

Nausea and emesis after exercise were leading symptoms in a 28 year old patient with indirect vena azygos continuation syndrome. This anomaly was verified by sonography, abdominal CT and by venography. The CT examination revealed initially structures of malignant appearance low to the renal position by angiography. This appeared to be distended collaterals. Therapeutic intervention aims primarily to the prevention of complications such as thrombosis of the distal venous flow or venous insufficiency of the lower extremities. Prophylactically we suggest low dose heparin and compression stockings.

Adult↗

[Effectiveness of pravastatin and bezafibrate in primary hypercholesterolemia].

The efficacy and safety of pravastatin and bezafibrate (in retard form) were compared in a randomised double-blind trial comprising 96 patients (48 men, 48 women; mean age 52.5 [20-68] years) with primary hypercholesterolaemia types IIa and IIb. After four weeks' treatment 6 out of 38 patients (400 mg/d bezafibrate) and 27 out of 58 patients (20 mg/d pravastatin) reached a LDL cholesterol level of 190 mg/dl or less. In the other 31 patients of the pravastatin group the dose was raised to 40 mg/d. During the twelve-week course of pravastatin total cholesterol concentration fell from a mean of 364 +/- 75 mg/dl (initial value) to 281 +/- 61 mg/dl (P less than 0.01), while LDL-cholesterol fell from 288 +/- 81 mg/dl to 206 +/- 64 mg/dl (P less than 0.01) and triglyceride concentration from 168 +/- 83 mg/dl to 148 +/- 80 mg/dl (P less than 0.05). During the twelve-week course of treatment with 400 mg bezafibrate total cholesterol concentration fell from a mean of 363 +/- 91 mg/dl to 325 +/- 73 mg/dl (P less than 0.01), LDL-cholesterol level fell from 284 +/- 88 mg/dl to 242 +/- 70 mg/dl (P less than 0.01) and the triglyceride concentration from 173 +/- 91 mg/dl to 121 +/- 83 mg/dl (P less than 0.01). HDL cholesterol concentration rose by 9% in the bezafibrate group and by 8.4% in the pravastatin group (P less than 0.05). Except in the case of HDL-cholesterol, the falls were significantly different in the two treatment groups: pravastatin was superior to bezafibrate in terms of the reductions in both total and LDL-cholesterol (P less than 0.01 for each). However, bezafibrate produced a greater fall in serum triglycerides (P less than 0.05). No serious side effects were associated with either drug.

Adult↗

Negative chronotropic effects of nizatidine.

Twelve healthy volunteers were given one week's oral treatment with each of 300 mg nizatidine, 40 mg famotidine, and placebo once daily in a randomised, placebo controlled, double blind study. Three hours after administration, nizatidine led to a significant reduction in the mean (SD) resting heart rate compared with placebo (63.6 (6.4) beats/minute on placebo to 55.9 (7.2) beats/minute on nizatidine (p less than 0.05)), whereas famotidine did not influence the heart rate significantly. Both drugs, however, increased significantly the pre-ejection period and the ratio of pre-ejection period to left ventricular ejection time on mechanocardiography and led to a significant decrease in cardiac output on impedance cardiography. The exercise heart rate on nizatidine as well as the resting heart rate on concurrent administration of nizatidine and the beta receptor blocking agent atenolol were subsequently investigated in the same volunteers. Nizatidine slightly inhibited exercise tachycardia by 4.4% (p less than 0.05). When compared with placebo, the mean resting heart rate was decreased on atenolol alone by a mean of 10.6 beats/minute (p less than 0.01) and fell further on co-administration with nizatidine to a total of 16.1 beats/minute (p less than 0.05 versus atenolol alone). In conclusion, the effect of nizatidine in reducing the heart rate needs careful evaluation in elderly patients with heart failure or those also taking beta blockers. In contrast to famotidine, long term treatment with 300 mg nizatidine a day has mainly negative chronotropic effects.

Adult↗

Infective endocarditis at a hospital of the University of Kiel, 1958-1987.

The clinical courses of 214 patients with infective endocarditis treated between 1958 and 1987 at the First Medical Hospital of the University of Kiel (FRG) were analyzed retrospectively. A decrease in the incidence of endocarditis occurred during the 30-year observation period. The mean age of patients was 48 years, and men were more frequently affected than women. In the course of the investigation, a rise in isolated aortic valve disease was noted, whereas the number of patients with isolated involvement of the mitral valve and combined mitral-aortic valvular defects declined. Streptococci (57%) were the most frequent pathogens isolated; as opposed to their increase, the percentages of Staphylococcus aureus and enterococci decreased. Otolaryngological, dentogenic and urogenital diseases were most frequently held to be responsible for the development of infective endocarditis. Prior cardiosurgical interventions became increasingly significant as a cause of the disease. In this connection, a rising percentage of endocarditis cases was linked with prosthetically replaced heart valves. Complications and concomitant symptoms of endocarditis included the development of heart failure, cerebral embolism and encephalitis, splenomegaly, and renal inflammation. Finally, the marked decrease in mortality contrasted with a simultaneous rise in the number of endocarditis cases achieving full recovery.

Adolescent↗

Pharmacodynamic action and pharmacokinetics of moxonidine after single oral administration in hypertension patients.

Moxonidine is a new centrally acting alpha 2-adrenoceptor agonist that differs from others by a lower incidence of side effects in hypertensive patients. The effects of moxonidine and placebo on blood pressure, pulse rate, plasma catecholamines, plasma renin activity, sedation, and salivary flow were evaluated in eight hypertensive patients by an intraindividual comparison. Moxonidine induced a significant decrease in blood pressure that corresponded with its plasma concentrations. The maximum antihypertensive effect appears to be delayed when compared with the peak plasma level. Plasma norepinephrine, epinephrine, and plasma renin activity were significantly reduced by moxonidine, and blood pressure reduction corresponded with decrease of plasma norepinephrine. Heart rate, sedation, and salivary flow were not different using moxonidine compared with placebo. Only one patient mentioned dry mouth. No further relevant adverse effects were seen in the patients. This study demonstrates a significant decrease of blood pressure, plasma renin activity, norepinephrine, and epinephrine with a single dose of 0.25 mg moxonidine, but no significant effect on pulse rate, salivation, and sedation.

Adult↗

The effects of frusemide and probenecid on the pharmacokinetics of phenprocoumon.

We have studied the pharmacokinetics of phenprocoumon with and without co-administration of frusemide and probenecid in two groups of 17 healthy volunteers. Frusemide 40 mg b.i.d. for 7 days did not interact with phenprocoumon to a significant extent. Probenecid 500 mg q.i.d. for 7 days significantly accelerated the overall elimination of phenprocoumon, as indicated by a decrease in AUC from 295 to 157 micrograms.h.ml-1, and a reduction in the fraction of the dose excreted by the kidneys. The data are consistent with inhibition of the glucuronidation of phenprocoumon by probenecid. Its accelerated elimination may be a consequence of the increased formation of hydroxylated metabolites.

Administration, Oral↗

Pharmacokinetics after a single oral dose of bopindolol in patients with cirrhosis.

The plasma concentration-time curve of the hydrolysis product of bopindolol has been investigated in 14 patients with cirrhosis and in 15 healthy volunteers given a single oral dose of 2 mg bopindolol. Cirrhosis was confirmed by history and clinical examination or liver biopsy. The time to maximum concentration, maximum concentration and AUC of hydrolyzed bopindolol were similar in the patients and controls. However, the elimination half-life was 6.0 h in controls and 9.5 h in cirrhotics. Antipyrine clearance was markedly decreased in patients with cirrhosis, but no correlation was found with the pharmacokinetic parameters of hydrolysed bopindolol. Although the AUC was not significantly altered in patients with cirrhosis, the longer half-life of hydrolysed bopindolol suggests impairment of its disposition in liver disease, which could lead to significant accumulation of drug during chronic dosing.

Administration, Oral↗

Interaction of tertatolol with rifampicin and ranitidine pharmacokinetics and antihypertensive activity.

The interaction of the new beta-receptor antagonist tertatolol with rifampicin and ranitidine was investigated in ten patients with arterial hypertension (WHO stages I-II). They were treated orally with a single dose of tertatolol 5 mg alone and, after randomized allocation, with ranitidine 150 mg twice daily or rifampicin 600 mg once daily for 1 week each (tertatolol 5 mg was concurrently administered on the seventh day of the treatment phases). Following each therapeutic phase, circadian blood pressure values as well as kinetic parameters were obtained. On treatment with tertatolol alone, maximum plasma concentrations were 123.7 +/- 32.4 ng/ml (mean +/- SD) and were reached after 1.95 +/- 1.77 hours. The tertatolol elimination half-life was 9.0 +/- 7.1 hours. Coadministration of ranitidine did not significantly alter the kinetic parameters and antihypertensive effect of tertatolol. Rifampicin, however, decreased the maximum plasma levels of tertatolol to 80.6 +/- 18.5 ng/ml and markedly shortened the elimination half-life to 3.4 +/- 2.6 hours (p less than 0.01 compared with tertatolol alone). Urinary excretion of parent tertatolol and unchanged 4-hydroxy tertatolol was decreased under rifampicin, and a tendency to a reduction in the effect of tertatolol on circadian blood pressure values was observed. Twenty-four hours after administration, the heart rate in those patients on tertatolol alone (68 +/- 6 beats/min) was lower than in those on tertatolol plus rifampicin (74 +/- 7 beats/min). In conclusion, a pronounced pharmacokinetic interaction, with a limited consequence in terms of pharmacodynamic effects, was found in the present study when tertatolol was administered with rifampicin, but not with ranitidine.

Adrenergic beta-Antagonists↗

Hemodynamic effects of different H2-receptor antagonists.

In a randomized, placebo-controlled, double-blind study, 10 healthy volunteers were treated orally once a day for 1 week each with placebo, 800 mg cimetidine, 300 mg ranitidine, and 40 mg famotidine. On the seventh treatment day, heart rate, blood pressure, systolic time intervals, and impedance cardiography were measured before the morning dose and at 2, 6, 12, and 24 hours after the morning dose. Heart rate and blood pressure were not markedly altered by any of the H2-receptor antagonists compared with the findings for placebo. Cimetidine and ranitidine did not markedly alter parameters of systolic time interval and impedance cardiography compared with placebo in contrast to famotidine, which significantly decreased stroke volume, cardiac output, and the Heather Index in impedance cardiography (p less than 0.05) and also significantly increased the ratio of the preejection period to the left ventricular ejection time in systolic time interval (p less than 0.05) 2 hours after the morning dose. Six hours after administration, most of these alterations could no longer be detected. The observed changes in hemodynamic parameters confirm that famotidine exerts negative effects on cardiac performance, whereas such influences could not be shown for cimetidine and ranitidine.

Adult↗