T Tr re ea at tm me en nt t o of f s st te er ro oi id d--d de ep pe en nd de en nt t b br ro on nc ch hi ia al l a as st th hm ma a w wi it thWe performed a double-blind, placebo-controlled, randomized, parallel group trial on the effect of cyclosporin on pulmonary function, asthma severity and tapering of prednisone in 34 steroid-dependent asthmatics (mean oral prednisone dose: 16 mg·day -1 ). The study consisted of: 1) baseline period (12 weeks); 2) experimental period divided into two parts: Part I (12 weeks) cyclosporin or placebo treatment; Part II (22 weeks) cyclosporin or placebo treatment and oral prednisone reduction; and 3) follow-up observation (8 weeks). Asthma symptoms score, pulmonary function tests (daily peak expiratory flow (PEF) and bi-weekly forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal midexpiratory flow (MEF50), biochemical profile and blood cyclosporin levels were monitored throughout the study.Following cyclosporin administration, a slight beneficial effect on some subjective parameters of asthma severity was observed. At the same time, no beneficial effect on pulmonary function was noted. The time trends analysis of mean daily prednisone doses between the treatment groups revealed a statistically significant difference indicating that, during prednisone reduction, cyclosporin seemed to be slightly more efficient than placebo in reducing the requirement for systemic corticosteroid, even though the steroid reduction was accompanied by slight impairment of some pulmonary function. However, there was no significant difference in the final dose reduction between the treatment groups.These data and the known toxicity of the drug suggest a limited place for cyclosporin treatment in steroid-dependent bronchial asthma.

SummaryIn a placebo-controlled trial healthy volunteers and patients with hyperlipoproteinemias types II and IV received orally vitamin E at doses of 300 mg and 600 mg daily for 2 weeks. Serum tocopherol levels increased two-fold, but serum concentrations of total lipids, cholesterol, triglycerides, ceruloplasmin and transferrin remained unchanged. Dietary supplementation with vitamin E suppressed elevated concentrations of plasma lipid peroxides and this effect was correlated with an increase in serum antioxidant activity. In patients a mild platelet suppressant effect of vitamin E (600 mg daily) was observed.Feeding an atherogenic diet to rabbits for a week resulted in elevation of plasma lipid peroxides and a 90% decrease in arterial generation of prostacyclin. Enrichment of the atherogenic diet with 100 mg vitamin E daily prevented the increase in plasma lipid peroxides and protected the prostacyclin generating system in arteries. Thus, in hyperlipoproteinemias vitamin E corrects certain abnormalities of lipid metabolism which might predispose to atherosclerosis.

We used cyclosporin to treat 12 adult patients with severe bronchial asthma who had been on systemic steroids for an average of 16 years. During the baseline period, lasting 4-6 months, therapy with high doses of inhaled beclamethasone, aminophylline and salbutamol was standardized and a minimum necessary dose of systemic steroids was established. After 9 months' treatment with low-dose cyclosporin (average whole-blood trough levels of 105 ng/ml), in six patients the daily dose of oral prednisone could be reduced from mean 30 mg to mean 11 mg, while daily symptom scores and peak expiratory flows improved significantly. This was accompanied by a reduction in exacerbations of asthma. However, in six other patients attempts to taper the steroid doses were unsuccessful, and cyclosporin was stopped after 4 to 7 months. These preliminary results suggest that cyclosporin might be of benefit in some patients with steroid-dependent asthma.

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IntroductionUp to 5% of all pituitary tumors are hereditary e.g. due to MEN1 or aryl hydrocarbon receptor-interacting protein (AIP) genes mutations.ObjectivesThe study was aimed at the assessment of the frequency and characteristics of AIP-mutation related tumors in patients with apparently sporadic pituitary macroadenomas in the Polish population.Materials and methodsThe study included 131 patients (57 males, 74 females; median age 42 years) diagnosed with pituitary macroadenomas, and with a negative family history of familial isolated pituitary adenoma (FIPA) or multiple endocrine neoplasia type 1 (MEN1) syndromes. Sanger sequencing was used for the assessment of AIP gene variants. The study was approved by the Ethics Board of JUMC.ResultsAIP variants were identified in five of the 131 included subjects (3.8%): one diagnosed with Cushing’s disease, two with acromegaly, and two with non-secreting adenomas. Patients harboring hereditary AIP gene alterations did not differ from the rest of the study group in median age at diagnosis (41.0 vs. 42.5 years, P=0.8), median largest tumor diameter (25 vs. 24 mm, P=0.6), gender distribution (60.0% vs. 56.3% females, P=0.8), secreting tumor frequency (60.0% vs. 67.5%, P=0.7), or acromegaly diagnosis frequency (40.0% vs.37.3%, P=0.9).ConclusionsIn our series of apparently sporadic pituitary macroadenomas, AIP gene variant carriers did not differ substantially from patients with negative genetic testing. A risk factor-centred approach to AIP genetic screening may result in missing germline variants. Considering the clinical impact of such genetic variants and their relatively low penetrance, it is, however, doubtful if general genetic screening benefits the whole cohort of pituitary macroadenoma patients and their families.