Ondansetron is significantly more effective than metoclopramide in preventing acute nausea and vomiting. In the delayed phase, the results of both drugs were disappointing, although metoclopramide's effect on delayed nausea was superior. Patients preferred ondansetron.

The effects on gallbladder motility of long term treatment with the somatostatin analog SMS 201-995 (SMS) were studied in five patients with acromegaly treated for 6-32 months with 200-300 micrograms SMS daily. SMS (100 micrograms) or placebo was injected sc 45 min before a standard breakfast. Gallbladder volume (ultrasonography), plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) were measured until 120 min after the meal. SMS completely suppressed the postprandial gallbladder contraction, despite a blunted, though still statistically significant, increase in plasma CCK from 1.6 +/- 0.2 pmol/L to an average of 3.7 +/- 1.7 pmol/L (P less than 0.01). The postprandial plasma PP peak after placebo was replaced by a slight but statistically significant decrease after SMS (P less than 0.05). A statistically significant correlation between the plasma CCK values and corresponding gallbladder volumes was seen only after placebo injection, not in the SMS study. We conclude that during long term treatment of acromegalics with SMS, an injection of 100 micrograms, sc, completely abolishes gallbladder contraction for at least 2 h after a standard breakfast, despite blunted, but still significant, CCK release. The data suggest a decreased sensitivity of the gallbladder to endogenous CCK during long term treatment with SMS. Careful control of patients with respect to the formation of gallstones is recommended.

Since octreotide (SMS 201–995, Sandostatin; Sandoz Pharmaceuticals) is a potent inhibitor of pancreatic exocrine secretion and gallbladder contraction, long-term treatment with this drug may theoretically result in impaired pancreatic function and gallstones. However, we observed excellent pancreatic exocrine function – as assessed by the PABA/PAS test – in acromegalics who received octreotide treatment for more than 6 months. Plasma cholecystokinin showed a significant, although blunted, postprandial response, which exceeded the threshold for gallbladder contraction in healthy controls. Remarkably, postprandial gallbladder contraction was completely abolished for at least 2 h during octreotide treatment. In contrast to other studies, none of 16 acromegalic patients on long-term octreotide treatment developed gallstones. Although the incidence of gallstones in patients on long-term octreotide treatment may be increased, the risk seems to be variable.

Serum samples from 13 patients with active acromegaly on long-term sc treatment with octreotide (SMS 201-995, 1-36 months, mean daily dose 285 \ g=m\ g) were taken 12 h after the injection of their regular evening doses. Octreotide assay was performed using 125I \ x=r eq-\ Tyr-SMS and a polyclonal rabbit anti-serum. For assessment of antibody formation both serum coated charcoal adsorption (adsorption of free octreotide) and polyethylene glycol precipitation (precipitation of IgG complexes) were used. The mean binding percentage in the patients proved to be similar to that of 5 healthy volunteers (p>0.10). No specific binding was detected, whatever method used. No correlation was found between the binding percentages and octreotide serum levels, duration of octreotide treatment or daily octreotide dose (p>0.10). These results strongly suggest that clinically relevant endogenous antibody formation is not a frequent event during long-term sc treatment of acromegalic patients with octreotide.The long-acting somatostatin analogue octreotide (SMS 201-995, SMS) is a potent inhibitor of growth hormone secretion. In the treatment of acromegaly it normalizes GH levels in many patients without rebound hypersécrétion and reverses most anom¬ alous GH responses (1-8). Pituitary tumour reduc¬ tion has been reported, even leading to recovery from ophthalmoplegia (3,9). Some patients are treated now for more than five years with intermittent subcutaneous octreotide in¬ jection without important local or systemic adverse reactions. The octapeptide has a potential risk of inducing antibody formation, being structurally different from native somatostatin. Antibody for¬ mation could impair the effect of octreotide treat¬ ment, cross-react with the native somatostatin, and interfere with the measurement of plasma octreo¬ tide. So far no study on this subject in acromegaly has been published. In 7 patients with peptide-secreting pancreatic tumours treated with the ana¬ logue, no evidence of humoral immune responses against the octapeptide could be demonstrated (10). In the latter study, however, dextran-coated charcoal was used to detect the presence of anti-SMS antibodies. This technique could have erro¬ neously underestimated SMS-binding owing to dis¬ sociation of less avidly bound SMS. Therefore, in addition to this procedure we used polyethylene glycol (PEG) precipitation to demonstrate possible SMS-binding in patients with active acromegaly to ascertain whether formation of endogenous anti¬ bodies to the peptide occurred during chronic sub¬ cutaneous treatment with this somatostatin ana¬ logue. Subjects and MethodsWe investigated 13 patients with active acromegaly (2 men, 11 women, age 26-68 years) on chronic treatment with octreotide. All but one had been treated with sc in¬ jections for 1-36 months, 2 to 3 times daily. The mean daily dose was 285-ng, ranging from 200-600 ng-One patient (No. 13) was treated with continuous sc octreotide administration by pump infusion (300 ng per day). Serum

No abstract

The development of transient hypothyroidism and goiter in a patient with a metastasized malignant melanoma during treatment with recombinant interleukin-2 (rIL-2) and dacarbazine is reported. Signs of autoimmune thyroiditis became apparent 2 weeks after the start of treatment and disappeared after treatment stopped. It is likely that rIL-2 was responsible by interfering with preexisting autoimmune thyroid disease. The possible mechanisms are discussed here. Patients with positive antithyroid microsomal antibody titers are prime candidates for rIL-2-induced thyroiditis.

No abstract

Abstract. Twelve patients with active acromegaly were treated with the long-acting somatostatin analogue SMS 201-995 (SMS), at a dose of 50 μg sc twice daily in the first 2 weeks of treatment and 100 μg sc thereafter. Four h after the first injection of SMS, GH levels became normal in 8 of the 12 patients. Basal glucose levels were significantly lower at the 28th day of treatment. This glucose lowering effect was stronger in the diabetic than in the nondiabetic patients. The post-prandial rise of insulin levels was reversed by SMS, leading to a more pronounced postprandial rise of glucose, whereas the postprandial secretion of glucagon was also reversed by SMS. The rise of glucose levels during oral glucose loading was similar before and during SMS, despite a strong inhibitory effect of the drug on the insulin rise after glucose loading. Basal TSH levels were not influenced by SMS, the TRHinduced TSH response, however, was significantly blunted. Although the basal PRL levels were significantly reduced by SMS, the TRH-induced PRL rise was similar before and during administration of the analogue. Paradoxical GH responses to TRH disappeared in 7 out of 8 patients during SMS. Paradoxical GH responses to GnRH, however, persisted in 4 out of 4 patients. Paradoxical responses of GH after glucose loading disappeared in 2 out of 2 patients. The GH response after GHRH administration was strongly suppressed by SMS. During long-term treatment (up to 2 years), the GH level obtained within 5 h after the last injection of SMS remained normal in the patients whose GH levels normalized at the first day of treatment. There was a good response of the disease to this treatment, and no serious adverse reactions were observed. We conclude that SMS normalizes most anomalous growth hormone kinetics in acromegaly. The drug offers a new tool in the treatment of this disease.