Results of a double blind study of 89-strontium therapy of skeletal metastases of prostatic carcinoma

Forty-nine patients were treated with either 3×75 MBq ⁸⁹Sr or saline as placebo. Analysis of results 1 to 3 years after therapy revealed the ineffectiveness of ⁸⁹Sr to relieve pain from metastases. Unexpectedly, a higher survival rate was found after Sr application (46% vs 4% after 2 years). Covariate analysis underlines the effect of ⁸⁹Sr therapy on life expectation.     

Arthroscopic synovectomy of rheumatoid shoulder and elbow

Surgical Principles Radical arthroscopic synovectomy of rheumatoid shoulder and elbow. Revised Version from: Operat. Orthop. Traumatol. 4 (1992), 112–129 (German Edition).     

Circadian rhythm and pulsatility of parathyroid hormone secretion in man

OBJECTIVE: We wished to investigate the circadian rhythm and pulsatility of parathyroid hormone (PTH) secretion in man, as conflicting results have been published. DESIGN AND PATIENTS: To investigate the circadian rhythm during daytime, we sampled (a) peripheral blood at hourly intervals in 12 healthy young men from 0900 h until 1700 h. For observation of pulsatility, we sampled (b) peripheral blood at 1-minute intervals for 1 hour in three healthy men and three healthy women (mean 27.7 years, range 21-56 years) and (c) at 1-minute intervals for 30 minutes in 21 patients with surgically confirmed primary hyperparathyroidism (pHPT). MEASUREMENTS: The serum levels of intact PTH were measured by two-site immunoradiometric assay and special care was taken to reduce intra-assay variability, especially at the normal PTH concentration. In series (a), ionized calcium, total calcium and phosphate were also determined. RESULTS: A circadian rhythm during daytime was found for intact PTH in healthy men and women with a nadir at 0930 h and a peak in the afternoon. Ionized calcium and total calcium (protein-adjusted) decreased and phosphate increased in the afternoon. These changes were all statistically significant (P < 0.02). Pulsatility of PTH: Statistical cluster analysis of the data showed no pulsatility either in healthy persons or in patients with primary hyperparathyroidism. In two healthy women and one healthy man slight changes of longer duration were discovered, but no complete pulses. In five patients with primary hyperparathyroidism, larger differences between the highest and lowest concentrations of intact PTH were found, but no complete pulses. CONCLUSIONS: Our data show a significant circadian rhythm during daytime of intact PTH and only minor changes from minute to minute. The alterations in PTH-levels occurred at longer time intervals in healthy persons. In some patients with primary hyperparathyroidism, decreases of PTH-levels were found. The circadian rhythm of PTH may be due to slight changes in calcium or phosphate concentration.     

Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.

The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats.     

P2-purinoceptor-mediated inhibition of noradrenaline release in rat atria.

1. We looked for P2-purinoceptors modulating noradrenaline release in rat heart atria. Segments of the atria were preincubated with [3H]-noradrenaline and then superfused with medium containing desipramine (1 microM) and yohimbine (1 microM) and stimulated electrically, by 30 pulses/1 Hz unless stated otherwise. 2. The adenosine A1-receptor agonist, N6-cyclopentyl-adenosine (CPA; EC50 9.7 nM) and the nucleotides, ATP (EC50 6.6 microM) and adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S; EC50 4.8 microM), decreased the evoked overflow of tritium. The adenosine A2a-agonist, 2-p-(2-carbonylethyl)-phenethylamino-5'-N-ethylcarboxamido-a denosine (CGS-21680; 0.03-0.3 microM) and the P2x-purinoceptor agonist beta, gamma-methylene-L-ATP (30 microM) caused no change. 3. The concentration-response curve of CPA was shifted to the right by the adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropyl-xanthine (DPCPX; 3 nM; apparent pKB value 9.7) but hardly affected by the P2-purinoceptor antagonist, cibacron blue 3GA (30 microM). In contrast, the concentration-response curves of ATP and ATP gamma S were shifted to the right by DPCPX (3 nM; apparent pKB values 9.3 and 9.4, respectively) as well as by cibacron blue 3GA (30 microM; apparent pKB values 5.0 and 5.1, respectively). Combined administration of DPCPX and cibacron blue 3GA caused a much greater shift of the concentration-response curve of ATP than either antagonist alone. The concentration-response curve of ATP was not changed by indomethacin, atropine or the 5'-nucleotidase blocker alpha, beta-methylene-ADP. 4. Cibacron blue 3GA (30 microM) increased the evoked overflow of tritium by about 70%.(ABSTRACT TRUNCATED AT 250 WORDS)