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The effect of bromocriptine on sexual activity was studied in male haemodialysis patients in a single-blind placebo controlled trial with random cross-over. At a dose of 2.5 mg bromocriptine twice day, plasma-prolactin concentrations were consistently reduced, while sexual function as assessed by a questionnaire was markedly improved. At the doses used, side-effects, particularly hypotension, were common, but bromocriptine helped to restore sexual function in dialysed patients.

Ten acromegalics received daily doses of 200-300 micrograms of a long-acting somatostatin analog, SMS 201-995 (Sandostatin, SMS), for an average of 64 weeks. Basal mean GH values of 44 +/- (SE) 7.8 ng/ml had fallen into the normal range at the end of the observation period (mean 64 weeks). This effect was accompanied by a substantial drop in somatomedin-C values. Reduction of pituitary tumor size could be documented in 3 of 6 patients. Whereas SMS did not affect high plasma PRL in 4 microprolactinoma patients, lactotrophs turned sensitive to this agent in mixed GH/PRL tumors. In a comparative study between SMS and bromocriptine, the former normalized circulating GH in 10 of 17 acromegalics in an acute trial, whereas bromocriptine was effective in only 5. A combination of both substances was effective in 2 of 3 patients who were insensitive to single drug administration. Cultures of GH-secreting tumor cells showed a statistically significant hormone decrease in the medium when exposed to SMS. However, in some instances, a diminution of the GH contents of the tumor cells was also observed, presumably as the basis for intracellular breakdown and clinical tumor shrinkage.

The effects were studied of several calcium channel blocking agents on muscle twitch, and possible interactions between these drugs and pancuronium and suxamethonium, using a rat phrenic-hemidiaphragm preparation. Nicardipine, verapamil and diltiazem each caused a concentration-related depression of muscle response. Nicardipine had the most, and diltiazem the least, potent effect. Verapamil and diltiazem 5 and 10 mumol litre-1 caused a concentration-dependent enhancement of suxamethonium-induced neuromuscular blockade, but increased the effect of pancuronium only at 10 mumol litre-1. Nicardipine 10 mumol litre-1 significantly enhanced pancuronium-induced neuromuscular blockade, but not that produced by suxamethonium.

In order to test a possible stimulatory effect of oxytocin and lysine-vasopressin on prolactin (PRL) release six female volunteers received either saline or 1 IU oxytocin (Syntocinon) i.v.. Blood sampling was performed at intervals over 90 minutes. Nine puerperae were treated with oral oxytocin (Sandopart) 50 IU t.i.d. for seven days. Nine other untreated postpartum women served as controls. Blood was collected before delivery and on subsequent postpartum days, and the milk volumes produced were estimated by increases in the babies' weight. In addition, seven volunteers received 5 or IU lysine-vasopressin (Vasopressin) i.m. Blood was withdrawn at regular intervals for 180 minutes, the urine volumes excreted in 30-minute intervals were measured and the clearance of free water calculated. Oxytocin failed to modify basal plasma PRL in the acute trial and in the post-partum women, and milk amounts produced were not influenced by treatment. Vasopressin did not change the PRL plasma profile despite a significant (p less than 0.05) reduction in the excretion of free water. Results indicate that neuropeptides are not implicated in the control of PRL release.

Administration of 2.5 mg bromocriptine (Parlodel), a dopamine agonist, on two occasions to six normal volunteers did not alter the plasma TSH response to an i.v. injection of 100 micrograms TRH, but significantly (P less than 0.01) blunted it after 200 micrograms. Chronic bromocriptine treatment (7.5--50 mg/day) of fifteen acromegalic subjects failed to influence basal plasma TSH or the response pattern to 200 micrograms TRH. The thyroxine Binding Index (TBI) and the levels of T3 and T4 were not modified by treatment. These results indicate that chronic dopaminergic therapy with bromocriptine does not alter thyroid function.

The long-acting somatostatin analogue SMS 201-995 was administered to a six-month-old infant with intractable diarrhea after failure of conventional treatment. During eight weeks of treatment, the secretory component of the diarrhea was positively influenced with a reduction of daily stool weight and stool sodium concentration. Plasma levels of growth hormone were markedly, and levels of insulin, IGF I, gastrin, pancreatic polypeptide, VIP, and neurotensin moderately decreased. Linear growth was also inhibited. The patient unexpectedly died from fulminant colitis at a time, when the dosage had been reduced from 18 to 3.5 micrograms/kg/day. The relationship, if any, between therapy with SMS 201-995 and the colitis remained unclear. It is concluded that SMS 201-995 can be effective in reducing secretory diarrhea in infants. However, further studies are necessary to assess the safety of its administration in this age group.

The possible role of endogenous prolactin (hPRL) in the regulation of renal water, Na and K excretion during sleep was tested in a group of 10 healthy female volunteers. Plasma hPRL and total urinary Na and K excretion were measured at 2- and 4-hourly intervals, respectively, in the control period and after prolactin inhibition with bromocriptin. Despite adequate prolactin suppression, no significant changes were observed in the nyctohemeral excretion rhythms of water, Na and K, suggesting that endogenous prolactin is not instrumental in the control of these parameters.

Systemic administration of the enkephalin analog FK 33.824 was previously shown to inhibit ACTH secretion in man. In this study, the direct action of this analog on cortisol release was studied. The enkephalin analog (1 microM and 10 microM) did not influence basal or ACTH-stimulated cortisol production by cultured isolated adrenocortical cells prepared from the hyperplastic adrenal glands from three patients with Cushing's disease. Naloxone (10 microM) had also no direct effect on cortisol release. It is concluded that the met-enkephalin analog used in this study and naloxone do affect the hypothalamo-pituitary-adrenal axis via a central effect.

The possibility of prolactin-dependent subfertility was investigated in a group of 8 women, with luteal insufficiency exhibiting moderately elevated plasma prolactin (PRL) levels and/or galactorrhea. Another group of 10 normal women volunteers served as the control group. A "luteal index" was elaborated by integration of the area below the curve of plasma progesterone (P) values recorded throughout the postovulatory period. The calculated index for normal women was 177 +/- 35 (SD) expressed as [(ng/ml) x time], and the value of 107 (--2 SD) was adopted as the lower limit of normality (97.5% confidence limit). All 8 patients had luteal indexes (range 20--105) below the established limit. Therapy with bromocriptine (CB 154), 5 mg/day, suppressed PRL to normal levels and prolonged the postovulatory hyperthermic phase in 6 out of 8 women. This was accompanied by an improvement in the luteal index, and 5 women conceived. It is concluded that prolactin may interfere with normal progesterone synthesis by the corpus luteum, as demonstrated by the prompt restoration of fertility by bromocriptine treatment in women with regular cycles and inadequate luteal function.

In rats a chronic uremic syndrome was induced by 5/6 resection and subsequent irradiation of the kidneys. After 5 weeks 45Ca and 89Sr were injected simultaneously, and the different metabolic handling of the two elements was determined applying an open two-compartment model of Calcium kinetics. The uremic animals were compared with two groups of rats which were pairfed, and fed ad libitum, respectively. Besides an elevenfold faster urinary excretion when calculated with Sr, and which was reduced to about one half in the uremic rats, a significant discrimination by bone in favour of Ca was found, with a rather stable factor of 1.2 in the three groups. This is considered to evidence that urinary excretion and bon uptake of Sr are independent processes.

In order to study the mechanism of action of a Met-enkephalin (FK 33824) on the pituitary-adrenal axis eight normal male volunteers were subjected to an ACTH stimulation test. Lysine-vasopressing (LVP), 5 IU, was injected intramuscularly after pretreatment with 0.5 mg FK 33824 i.m. or a placebo. In six of the subjects the opiate was again administered preceding a single injection of 0.25 mg ACTH beta 1-24 i.m. Blood was collected at regular intervals and ACTH and cortisol concentrations analyzed in all samples. LVP induced significant plasma ACTH (P < 0.05) and cortisol (P < 0.001) increases. Pretreatment with FK 33824 completely antagonized the effect of LVP. Furthermore, the cortisol elevation after exogenous ACTH was not modified by previous administration of FK 33824. It is concluded that the Met-enkephalin derivative FK 33824 directly suppresses ACTH release from the pituitary without influencing adrenal synthesis of cortisol.

The somatostatin analogue SMS 201-995 has recently been shown to be effective in suppressing GH secretion in most acromegalic patients. In the present study it was investigated whether PRL release in prolactinoma and acromegalic patients might also be sensitive to SMS 201-995 and whether co-secretion of PRL in acromegaly plays a role in determining the sensitivity of GH secretion to SMS 201-995. The s.c. administration of 50 micrograms SMS 201-995 did not affect high plasma PRL levels in four microprolactinoma patients. Therapy of one of these patients for 3 d with 50 micrograms three times a day also did not affect PRL levels. The single administration of 50 micrograms SMS 201-995 in 22 acromegalic patients lowered plasma GH levels for 2-6 h to less than 5 micrograms/l in 14 patients and to less than 50% of control values in 16 patients. In 18 of these 22 patients the immunohistochemical picture of the pituitary tumour was known. Eleven patients had pure GH-containing tumours and in seven patients there were mixed GH/PRL-containing tumours. In two of these latter patients there was evidence for GH and PRL being secreted by the same tumour cells. The sensitivity of GH secretion to SMS 201-995 did not differ between the patients with pure GH or mixed GH/PRL-containing adenomas. Plasma PRL levels were not affected by SMS 201-995 in the patients with pure GH-secreting tumours, but were significantly suppressed in four of the seven patients with mixed GH/PRL containing tumours. Chronic treatment for 16 weeks of one patient with a mixed GH/PRL-containing tumour with SMS 201-995 (100 micrograms three times a day) resulted in normalization of both the increased GH and PRL levels. It is concluded that SMS 201-995 does not affect tumorous PRL secretion in patients with pure prolactinomas. In acromegalic patients with mixed GH/PRL-containing tumours PRL secretion in some patients is sensitive to SMS 201-995, making these patients good candidates for chronic treatment with the analogue. The simultaneous presence of PRL in the GH-secreting pituitary tumour or the presence of hyperprolactinaemia in acromegalics does not play a role in the sensitivity of GH secretion to the somatostatin analogue.