Effects of porcine calcitonin on human platelet fuction.

The effects of different doses of porcine calcitonin (pCT) were tested in vitro and in vivo. In vitro, pCT at a concentration ranging from 0.1 to 5 M. R. C. Units/ml induced a dose-dependent inhibition of ADP (1.2 microM) and collagen- (2 micrograms/ml) induced platelet aggregation, showing a prevalent action on the second wave of ADP-induced aggregation and causing prolongation of the lag time and reduction of both maximum aggregation and slope in collagen-induced aggregation. 45Ca uptake by platelets in the presence of the ionophore A23187 and 14C-serotonin release were also inhibited in a dose-related fashion, using concentrations ranging from 1 to 10 M. R. C. Units of pCT. The in vivo tests, performed before and after a 7-day treatment with 2 different doses of pCT (1 and 160 M. R. C. Units/daily, i. m.) confirmed the inhibitory effect of pCT on ADP- and collagen-induced platelet aggregation. It should be stressed that the effect of 1 unit was stronger than that of 160 units. It is therefore postulated that in vitro and in vivo effects of pCT on platelet functions probably depend on different mechanisms of action.

Calcium metabolism in multiple myeloma.

45Calcium metabolism and circulating levels of iPTH (N-terminal fragment) and iCT were investigated in normocalcemic patients with multiple myeloma (12) in an attempt to ascertain early changes in calcium metabolism, which may occur before hypercalcemia develops. The same parameters were also investigated in patients with senile osteoporosis (11), corticosteroid-induced osteoporosis (6), Paget's disease (6) and controls without bone disorders (13). In the myeloma group, the exchangeable calcium pool (7,678 +/- 321 mg) was significantly higher (P less than 0.01) than in the control group (4,405 +/- 374 mg), the senile osteoporosis group (4,108 +/- 407 mg) and the corticosteroid-induced osteoporosis group (3,015 +/- 161 mg) and nearly as high as in the Paget's disease group (8,876 +/- 1,173 mg). Calcium pool turnover rate was higher in the myeloma group than in controls, as were bone anabolism and bone catabolism, although differences were not statistically significant. There were no statistically significant differences among the groups in the plasma iPTH or iCT, although the mean value of the latter was higher in the myeloma group than in controls (86 +/- 24 vs. 47 +/- 13 pg/ml). These data suggest that an increase in the exchangeable calcium pool and in turnover rate may occur early in the course of multiple myeloma, preceding the development of hypercalcemia. The role of some homeostatic mechanisms in maintaining normal plasma calcium levels in multiple myeloma despite increased bone calcium resorption is discussed.

[Evaluation of the effects of some non-steroid anti-inflammatory agents on the gastric mucosa]. / Valutazione degli effetti di alcuni farmaci anti-inflammatori non steroidei sulla mucosa gastrica

300 mg/day phenylbutazone, 210 mg/day indomethacin, and 600 mg/day pyrasanone were administered for 14 days to three randomised groups of patients respectively, consisting of a total of 76 subjects with various forms of non-infectious inflammation (osteoarthritis, fibrositis, rheumatoid arthritis, gout, phlebitis), in a double-blind trila designed to determine the activity of the three drugs and their tolerance. In 36 cases, gastroscopy was performed before and after the treatment. On the basis of doses that were equivalent as far as their anti-inflammatory effect was concerned, epigastric pain and pyrosis were noted in about 31% of the series, though no significant difference could be made out between the three drugs. Gastroscopic evidence of erythema (8 cases), multiple erosion (2 cases), pomphoid gastritis (1 case), and duodenal ulcer (1 case) was obtained in subjects treated with phenylbutazone or indomethacin, and of erythema only (1 case) after pyrasanone. No relation could be established between the clinical symptoms and the gastroscopic findings.

Plasma immunoreactive N-terminal parathyroid hormone and cyclic AMP and cyclic GMP urinary levels in man after I. M. administration of two different doses of porcine calcitonin.

The effects of acute porcine calcitonin (pCT) administration were studied in 11 healthy volunteers with no metabolic disease. Each subject was given, intramuscularly, 1 MRC unit of pCT in glycine vehicle, 160 units of pCT in gelatine vehicle, and placebo, according to a crossover design. The following parameters were studied: blood calcium, phosphorus and immunoreactive parathyroid hormone (iPTH); urine calcium, phosphorus, cyclic AMP and GMP. Both the pCT preparations produced, at the same time after administration, a hypocalcemic effect (P less than 0.01) which was not dose related, without any modification of urinary calcium excretion, implying that both doses are able to inhibit completely bone destruction. Despite the blood calcium decrease, no significant modifications in plasma iPTH levels were observed. pCT administration did not modify the urinary excretion of cyclic AMP, while it increased the urinary levels of cyclic GMP, particularly at the higher dose employed. Blood phosphorus decrease and urinary phosphate excretion increase were observed only after the administration of 160 MRC units of pCT. These observations suggest that the effects on urinary cyclic GMP and on blood and urine phosphorus are not mediated by PTH but could be the result of a direct action of calcitonin seen only when high doses are employed. In conclusion, one MRC unit of pCT is sufficient to inhibit bone resorption.

Adriamycin cardiotoxicity: a survey of 1273 patients.

Valuable information was collected on the medical history and clinical course of 1273 patients entered in clinical trials with Adriamycin (ADR) carried out in 12 European cancer centers. A coded patient form was used for the data collection carried out in each center by a qualified physician following a guideline which was discussed and accepted by all of the participants. The aim of the study was to define the incidence, characteristics, and possible co-factors of the cardiomyopathy (CMP) in patients treated with combination chemotherapy regimens including ADR. The mean total dose of ADR was 268 mg/m2 (range, 15--1251 mg/m2), and 5.1% of the patients received a total dose of greater than 550 mg/m2. A "definite" ADR-related CMP was observed in 1.7% of the cases; another 3% of the cases were reported as "possible" ADR-CMP since the role played by the drug could not be clearly defined. "Definite" ADR-CMP was fatal in eight patients (0.6%) while "possible" ADR-CMP was fatal in 13 patients (1.0%). Among the possible co-factors examined, the following ones were found to be significantly associated with the occurrence of a "definite" ADR-CMP: (a) total dose of ADR; (b) vincristine when given both before and concomitantly with ADR; (c) bleomycin when given before ADR; and (d) radiotherapy to the mediastinum when given concomitantly with ADR. Furthermore, none of 182 patients receiving ADR by slow infusion developed a "definite" ADR-CMP, while 2% of the patients treated by bolus injection did so. The occurrence of a "possible" ADR-CMP was found to be significantly associated with two pre-existing pathologic conditions (electrocardiogram [ECG] abnormalities and hypertension) but not with the treatment-related co-factors for the "definite" ADR-CMP mentioned above. Other variables examined, such as sex, age, cancer type, baseline liver function, and cyclophosphamide treatment, did not seem to influence the risk of ADR-CMP. Data on ECG changes occurring during ADR treatment were also reported and their incidence was found to be strictly related to the frequency of the ECG monitoring.