Type I diabetes may be an autoimmune disorder, although the evidence is largely circumstantial. The natural history of the disease after diagnosis includes partial remission in most patients, but only about 3 percent achieve transient insulin independence. beta Cell function, as indicated by the plasma concentration of C-peptide, is lost over 6 to 30 months and islet cell antibodies disappeared over 1 to 2 years. This article describes a pilot study in which 41 patients were treated with the immunosuppressive agent cyclosporine for 2 to 12 months. Of 30 patients treated within 6 weeks of diagnosis, 16 became insulin independent with concentrations of plasma C-peptide in the normal range and decreasing titers of islet cell antibodies. Of 11 patients who entered the study 8 to 44 weeks after diagnosis, two achieved this state. These results indicate that a controlled trial of the effects of cyclosporine in type I diabetes should be conducted.

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The efficacy of cyclosporin A (CyA) in severe psoriasis was analysed in 457 adult patients included in five European multicentre dose-finding studies. Initial CyA doses were 1.25 mg/kg/day in 33 patients, 2.5-3 mg/kg/day in 285 and 5 mg/kg/day in 139. After 3 months of treatment, the reduction of the Psoriasis Area and Severity Index (PASI) score was 35 +/- 6% with 1.25 mg/kg/day of CyA, 57 +/- 2% with 2.5 mg or 3 mg/kg/day and 86 +/- 2% with 5 mg/kg/day (P less than 0.001). The rates of success, defined by a PASI score reduction greater than or equal to 75% or a score less than or equal to 8, were 24%, 52% and 88%, respectively. There were no differences in age, initial severity or duration of psoriasis. The improvement was maintained for 9 months or more in the majority of patients receiving continuous CyA therapy.

1 Eight double-blind, randomized, placebo-controlled, single-dose, cross-over studies were carried out to evaluate the usefulness of testing the acute analgesic effect of drugs in out-patients with non-migrainous headache. 2 The reference compounds were either (1) aspirin, (2) a combination of aminopyrine, caffeine and butalbarbital (Optalidon®), and (3) a combination of (2) with dihydroergotamine (Tonopane).3 The test compounds were (1) proquazone, (2) fluproquazone and (3) and (4), new formulations of Optalidon® and Tonopan® in which the aminopyrine was replaced by propyphenazone. They were all found to be active. 4 A significant, dose-response relationship was established for aspirin (250, 500 and 1000 mg). 5 It is concluded that the non-migrainous headache model is a practical, reproducible and sensitive method for the investigation of the acute efficacy of analgesics.

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Serum creatinine and blood pressure were measured in patients who had severe psoriasis and who were treated with cyclosporin A (CyA) in initial doses of 1.25 mg (n = 34), 2.5 or 3 mg (n = 314), or 5 (n = 215) mg/kg/day. Of the 563 patients involved, 201 were treated for more than 3 months, and 100 received CyA continuously for 12 months or more. Sixty-eight additional patients were included as controls and received placebo (n = 42) or etretinate (n = 26). At doses of 2.5 and 5 mg/kg/day, CyA induced slight but significant dose-dependent increases in serum creatinine and blood pressure. Creatinine increases of 50% or more over baseline values were detected in 4% of the patients receiving 2.5 mg/kg/day and in 13% of those receiving 5 mg/kg/day. After an initial rise during the first weeks of treatment, mean creatinine level remained stable over 1 year provided that the CyA dose was reduced whenever creatinine levels increased by 30% or more over baseline. The incidence of hypertension was 10.6% and did not vary whether the CyA dose was 2.5 or 5 mg/kg/day. The first elevated blood pressures were recorded early after starting CyA therapy (median: 1 month). However, 3 months after stopping treatment, the increases in creatinine as well as in blood pressure were reversible and the levels did not significantly differ from baseline values.

No abstract

A method for the evaluation of the efficacy of mild analgesic drugs in outpatients with nonmigrainous headache is described. During the 3-hour drug evaluation period, patients were required to record at hourly intervals their pain intensity using both a verbal rating and a visual analog scale, their pain relief, and the occurrance of side effects. The results obtained in six studies consisted of comparisons of reference compounds aspirin (1000 mg) and two analgesic combinations (containing aminophenazone, caffeine, and butalbital); test medications aspirin (500 mg), codeine (30 mg), proquazone (300 mg), and new formulations of the two analgesic combinations (aminophenazone replaced by propyphenazone); and, in every study, placebo. In a seventh study, the analgesic effects of three doses aspirin (250, 500, and 1000 mg) were compared with that of placebo. Every study was conducted under double-blind, complete crossover conditions, and between 24 and 36 patients were used in each study. Using parametric and nonparametric statistical analyses, the reference compounds and the majority of the test medications exhibited significant analgesic properties. Also, a highly significant dose--response effect was demonstrated for aspirin. It is concluded that the headache model is a practicable, reliable, and sensisive method for the evaluation of the effectiveness of mild analgesic drugs.