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Biomedical subjects

W Kirch

Publications and source records attributed to W Kirch.

At least 181 records · Page 10Linked to original sources
PubMed1990

[Cytostatic and immunosuppressive treatment of ocular Behçet syndrome].

Ocular symptoms of Behçet's syndrome in 16 patients and the results of cytostatic and immunosuppressive therapy with cyclosporin A (6 patients), chlorambucil (6 patients), and a combination of cyclophosphamide and procarbacin (4 patients) are described. The clinical course and therapeutic outcome were compared to the patients' visual acuity and the duration of the disease prior to institution of cytostatic therapy. Average follow-up was 4.6 years, maximum 9 years. The principal ocular symptom in all patients was hemorrhagic, occlusive periphlebitis. Other symptoms, in descending order of frequency, were chorioretinitis, iridocyclitis, complicated cataract, secondary glaucoma and exudative retinal detachment. The patients in whom cytostatic therapy was instituted no later than 6 months after onset of the disease showed an improvement in or stabilization of visual acuity, as well as a clear reduction in signs of intraocular inflammation and frequency of recurrence. No improvement in visual acuity or ocular symptoms was achieved in cases where the disease was very advanced, despite cytostatic-immunosuppressive therapy. The results support early institution of immunosuppressive therapy in cases with Behçet's syndrome where severe, irreversible damage has not yet occurred and in which vision is threatened in both eyes. However, due consideration must be given to the potential risks of immunosuppressive therapy, in particular the risk of a malignant tumor.

Acyclovir↗
PubMed1990

Hemodynamic effects of brefanolol and propranolol assessed by noninvasive methods in patients with arterial hypertension.

In a placebo-controlled, randomized, cross-over study, 16 patients (10 males, 6 females; 50.6 +/- 10.4 years; body weight of 74.5 +/- 8.9 kg; mean +/- SD) with arterial hypertension (WHO stages I and II) were administered single oral doses of placebo, 80 mg of propranolol, as well as 50 and 100 mg of brefanolol (a beta-adrenergic blocking agent with vasodilating properties) in order to determine the resulting hemodynamic effects. Blood pressure, heart rate, and various hemodynamic parameters were assessed noninvasively by mechano- and impedance cardiography as well as by venous occlusion plethysmography before and 2, 4, 6, 10, and 24 h after drug administration. Treatment with propranolol resulted in the typical hemodynamic changes induced by a beta-adrenergic blocking agent characterized by a significant reduction in blood pressure, heart rate, cardiac output, stroke volume, and an increase in total peripheral resistance. A dose of 100 mg of brefanolol also led to comparable hemodynamic effects. Similar significant decreases in blood pressure, heart rate, and cardiac output also occurred with 50 mg of brefanolol, but stroke volume and reactive hyperemia increased. Thus, in this phase of drug development, dose titration with 50 and 100 mg of brefanolol indicates that the lower dose gives rise to a more balanced relationship between its beta-adrenergic blocking and vasodilating properties.

Adrenergic beta-Antagonists↗
PubMed1990

Parathyroid hormone and cirrhosis of the liver.

Fifty patients with liver cirrhosis (36 alcoholic, 1 drug-induced, 7 posthepatitic, and 6 cryptogenic) and normal renal function were investigated to determine whether PTH levels in serum, measured using the common midregion human PTH-(44-68) RIA, are elevated in such patients and whether this is related to impaired liver function rather than to the effect of secondary hyperparathyroidism. Their data were compared with those from 25 control subjects. The median PTH level of 462 +/- 18 ng/L (+/- SEM) was significantly increased (P less than 0.01) in cirrhotics compared with that of 236 +/- 13 ng/L in the control group. Significant correlations were found between PTH levels and parameters of liver function such as prothrombin time (r = -0.40; P less than 0.01), albumin as a percentage of total protein (r = -0.48; P less than 0.01), bilirubin (r = 0.35; P less than 0.05), albumin (r = -0.34; p less than 0.05), and cholesterol (r = -0.32; P less than 0.05), but not for antipyrine clearance, suggesting increasing PTH with decreasing liver function. The median calcium level (2.26 +/- 0.03 mmol/L), corrected for changes in albumin, was near the lower limit of the normal range (2.25-2.60), but corrected calcium and PTH were positively correlated (r = 0.33; P less than 0.05), indicating that the elevation is not reactive to calcium depletion. A negative correlation existed between PTH and 25-hydroxy-cholecalciferol (r = -0.49; P less than 0.05), the main circulating metabolite of vitamin D. Normal values in an immunoradiometric assay that detects the whole sequence of human PTH-(1-84) suggest that fragments rather than the intact hormone are responsible for PTH elevations in cirrhosis. The positive correlation between midregion PTH and corrected calcium is probably an artifact of the correction formula. In conclusion, midregion PTH fragments are increased in patients with liver cirrhosis. The reason for this elevation may well be the impaired liver function rather than secondary hyperparathyroidism.

Calcifediol↗
PubMed1990

Efficacy and tolerability of the new calcium antagonist isradipine in essential hypertension.

The antihypertensive efficacy and tolerability of the new calcium antagonist isradipine was assessed in 86 hypertensive patients who had pretreatment diastolic blood pressures (DBP) greater than or equal to 105 mm Hg and who were randomly allocated to a double-blind comparison of three different dosage regimens: 1.25 mg, 2.5 mg, and 5 mg b.i.d., and placebo. A 2-week run-in period was followed by a 4-week course of treatment. Isradipine reduced systolic and diastolic blood pressures dose-dependently; the normalization rate (DBP less than or equal to 90 mm Hg) was 5% with placebo and 29, 55, and 64% with isradipine 1.25, 2.5, and 5 mg b.i.d., respectively. The proportion of patients experiencing at least a 10 mm Hg reduction in sitting DBP was 29, 67, 86, and 91%, respectively. All three dosages proved to be significantly effective compared to placebo. Neither heart rate nor blood pressure regulation in orthostasis were influenced. The main side effects were headache, dizziness, and flushing; isradipine 1.25 and 2.5 mg b.i.d. were well tolerated (not significantly different from placebo). In conclusion, isradipine 2.5 mg b.i.d. appears to be the potential dose of first choice, exhibiting a favorable benefit-risk profile.

Blood Pressure↗
PubMed1989

[Probenecid affects liver metabolism].

The effect of probenecid on the pharmacokinetics of phenprocoumon (PPC) given as a single oral or intravenous dose, on the vitamin-K-dependent protein-C-antigen, and on the pharmacokinetics of antipyrine and 6 beta-hydroxycortisol was determined in 14 healthy volunteers. Probenecid caused a 75% decrease in urinary excretion of PPC and PPC-glucuronide and shortened the plasma half-life of PPC significantly (by about 35%). The results after oral and intravenous administration of PPC did not differ significantly. Plasma protein-C-antigen concentrations following intravenous PPC were significantly increased by probenecid. The plasma half-life of antipyrine after 7 days of probenecid therapy was significantly diminished. Accordingly, urinary excretion of 6 beta-hydroxycortisol was significantly increased. These data appear for the first time to reveal enzyme-inducing properties of probenecid, which may be responsible for the shortening of PPC plasma half-life when probenecid is given simultaneously. In addition, the influence of probenecid on plasma protein-C-antigen concentrations may indicate further effects of probenecid on liver metabolism.

4-Hydroxycoumarins↗
PubMed1989

[Effect of acoustic stress on immunoregulatory cells in female patients with systemic lupus erythematodes (SLE), patients with sarcoidosis and normal comparative subjects].

14 patients with systemic lupus erythematosus (SLE), 12 with sarcoidosis and two age- and sex-matched groups of healthy subjects were exposed to a 10-minute acoustic stress test. Healthy subjects and patients with sarcoidosis showed significant increases in leukocyte and lymphocyte counts (p less than 0.01), relative elevations of B and Tsc lymphocytes (p less than 0.01) and a relative reduction of Th lymphocytes (p less than 0.01). Patients with SLE showed the same characteristic alterations (p less than 0.01) but the degree of this cell mobilization was significantly less pronounced as compared with the healthy subjects (p less than 0.01). No dependence was found between corticosteroid therapy or disease activity and the cellular reaction in SLE patients. In SLE patients there thus seemed to be an attenuated immune response due to stress which may play an etiopathogenetic role in this disease.

Acoustic Stimulation↗
PubMed1989

Elimination and haemodynamic effects of nitrendipine in patients with chronic renal failure.

In sixteen patients with arterial hypertension and differing degrees of renal function the pharmacokinetics and haemodynamic effects of nitrendipine have been studied after treatment for 7 days. The AUC (0-24) and the elimination half-life of nitrendipine were significantly increased; the AUC (0-24) in patients with renal failure (median creatinine clearance 27.1 ml x min-1) was 196 ng x ml-1 x h compared to 97.8 ng x ml-1 x h in control subjects (median creatinine clearance 94.4 ml x min-1). The corresponding elimination half-lives were 13.5 h in renal failure and 4.4 h in the controls. The haemodynamic effects of nitrendipine were not enhanced in the patients.

Aged↗
PubMed1989

Negative effects of famotidine on cardiac performance assessed by noninvasive hemodynamic measurements.

In a randomized placebo-controlled study 12 healthy volunteers were treated for 1 wk each with 10 mg of nifedipine four times daily plus placebo or the same dose of nifedipine concurrently with 40 mg of famotidine once a day. Famotidine did not significantly alter pharmacokinetic parameters of nifedipine. Determination of systolic time intervals showed that the preejection period and the ratio of the preejection period and the left ventricular ejection time were significantly reduced by administration of nifedipine plus placebo. Coadministration of famotidine and nifedipine, however, led to a significant increase of these parameters. In an additional double-blind study, a significant rise of the preejection period and of the ratio was detected after administration of famotidine alone. In impedance cardiography stroke volume and cardiac output were significantly reduced by famotidine. Heart rate and blood pressure values were not altered by the H2-antagonist. For the first time, to our knowledge, the observed changes of hemodynamic parameters appear to indicate that famotidine may exert negative effects on cardiac performance which, in our opinion, could be of clinical relevance in elderly subjects or in patients with heart failure.

Adult↗
PubMed1989

Digitoxin in patients with hepatorenal insufficiency after repeated oral administration.

Following chronic oral administration of digitoxin 0.1 mg day-1 the pharmacokinetics of this glycoside were studied in seven patients with hepatorenal insufficiency and were compared with those of seven healthy volunteers. Liver cirrhosis of the patients was confirmed by liver biopsy. Mean creatinine clearance of the healthy subjects was 129.7 +/- 3.3 ml min-1 (mean +/- SEM), that of the patients was 25.6 +/- 20.4 ml min-1. Mean antipyrine clearance (parameter of oxidative liver function) was 49.7 +/- 6.0 ml min-1 in the volunteers and 22.0 +/- 2.9 ml min-1 in the patients. Plasma protein binding of digitoxin (PPB) was 95.0 +/- 1.1% in the patients and 96.7 +/- 0.6% in the healthy subjects (n.s.). Total body clearance of digitoxin (Cltot) was 0.0728 +/- 0.0120 ml min-1 kg-1 in the patients and 0.0615 +/- 0.0027 ml min-1 kg-1 in normals (n.s.]. Mean steady state plasma levels (Css) of the patients were 18.3 +/- 4.7 ng ml-1 and 15.8 +/- 1.3 ng ml-1 in the normals (n.s.). Our data obtained from chronic oral administration do not indicate a reduced total body clearance of digitoxin in patients with hepatorenal insufficiency.

Administration, Oral↗
PubMed1989

The influence of prostaglandin inhibition by indomethacin on blood pressure and renal function in hypertensive patients treated with cilazapril.

1. In a placebo-controlled double-blind cross-over study lasting 6 weeks, twenty patients with essential hypertension were treated with placebo for 2 weeks followed by oral cilazapril 2.5 mg once a day or oral indomethacin 50 mg twice daily for 2 weeks. Afterwards they received the combination of both drugs for a further 2 weeks. 2. Cilazapril significantly lowered systolic and diastolic blood pressure for a period of 24 h post administration. 3. Indomethacin significantly attenuated the antihypertensive activity of cilazapril. This was more pronounced in those patients who were treated for the initial 2 weeks with indomethacin plus placebo (and subsequently with cilazapril in addition) than in the subjects who first received cilazapril plus placebo and then the combination. 4. Correspondingly the decrease of plasma renin activity (PRA) and urinary prostaglandin excretion (PGE2) was more pronounced in those patients treated initially with indomethacin. 5. The effect of indomethacin on the antihypertensive effect of cilazapril appears to depend upon the sequence of drug administration.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Changes of immunoregulatory cells induced by acoustic stress in patients with systemic lupus erythematosus, sarcoidosis, and in healthy controls.

In order to determine whether the characteristically attenuated cell mobilization after physical stress in patients with systemic lupus erythematosus (SLE) or sarcoidosis is disease specific or the result of lower tolerance for such stress, SLE and sarcoidosis patients as well as healthy volunteers were subjected to an acoustic stress model, independent of physical capacity. After a 10-min period of intermittent acoustic stress, healthy subjects showed significant increases in leucocyte and lymphocyte counts, marked relative elevations of B and T suppressor cytotoxic lymphocytes (P less than 0.01), and a relative reduction in T helper lymphocytes (P less than 0.01). By contrast, this degree of change was significantly less pronounced in the 14 female SLE patients studied (P less than 0.01) as compared with the healthy controls, but not in the 12 sarcoidosis patients tested. No dependence was found between the severity of disease or administration of corticosteroid therapy and cell mobilization. It is yet to be determined whether the attenuated response of SLE patients to stress is a consequence of pathophysiological mechanisms or plays an aetiopathogenic role in the course of the disease.

Adult↗
PubMed1989

Effects of felodipine on plasma digoxin levels and haemodynamics in patients with heart failure.

The interaction between felodipine and digoxin was studied after a single oral dose and at steady state in 14 patients with congestive heart failure. Felodipine (10 mg) was randomly given as an extended release (FER) tablet in a double-blind, placebo-controlled, cross-over fashion. In addition, felodipine (10 mg) was given openly as a plain tablet, following the double-blind period. Each period lasted for 7 d. Felodipine ER did not alter the pharmacokinetics of digoxin when given as a single dose or at steady state compared with placebo. At steady state the felodipine plain tablet resulted in an 11% increase (P less than 0.05) in peak plasma concentrations of digoxin. Systolic time intervals as noninvasively measured haemodynamic parameters were not significantly altered following the felodipine ER period, while the felodipine plain tablet significantly decreased the pre-ejection/left ventricular ejection time ratio compared to placebo.

Aged↗
PubMed1989

[Mechano- and impedance cardiography parameters in patients with heart failure in administration of a calcium antagonist. The significance of the Heather index].

By means of impedance- and mechanocardiography the effect of the calcium-channel blocker nisoldipine on the circadian course of hemodynamic parameters was measured in a placebo-controlled randomized double-blind study in 18 patients with heart failure (NYHA II). A significant effect of nisoldipine on left ventricular function was observed after 2 h but not any more 6 h following the administration of the drug. This effect was expressed by a reduction of the pre-ejection period (PEPc) and PEP/LVET in the systolic time intervals (STI) and a rise in stroke volume (delta V) and cardiac output (CO), as well as an increase of the Heather-index in impedance cardiography (ICG). In ICG the Heather-index proved to be a more reliable parameter of left ventricular function than the calculation of stroke volume and cardiac output, respectively. This is probably due to the fact that the distance between the electrode (L) is not considered for the Heather-index, while it has to be taken into account for determining stroke volume and cardiac output. When performing impedance cardiography in the elderly, the distance between the electrodes may be a source of error because of a lack of cooperation, possible underlying corpulance, or due to a restricted motility of the chest or the vertebral column. In these patients the Heather-index should be preferred to the calculation of stroke volume and cardiac output, whereas in healthy subjects the latter parameters seem to be of sufficient validity.

Aged↗