Low-dose cyclosporine for the treatment of Crohn's disease. The Canadian Crohn's Relapse Prevention Trial Investigators

BACKGROUND: Long-term corticosteroid therapy for Crohn's disease is associated with important types of morbidity, such as osteoporosis. Safe and effective alternative treatments are required. Although a short-term benefit of cyclosporine in active Crohn's disease has been suggested, the long-term safety and efficacy of this treatment have not been established. METHODS: We conducted a randomized, double-blind, placebo-controlled evaluation of the effect of 18 months of low-dose cyclosporine treatment on the course of Crohn's disease. Adult patients whose disease had been active within the previous two years were randomly assigned to receive cyclosporine (151 patients) or placebo (154 patients) in addition to their usual therapy. Randomization was stratified according to center and score on the Crohn's Disease Activity Index (193 patients had scores of 150 or less, and 112 had scores greater than 150). The primary outcome measure was clinically important worsening of Crohn's disease, defined as a 100-point increase in the Crohn's Disease Activity Index from the patient's base-line value. Secondary outcomes were the use of prednisone and 5-amino-salicylates, mean score on the Crohn's Disease Activity Index and mean quality-of-life score, and the need for surgery. RESULTS: The condition of more patients worsened with cyclosporine than with placebo (91 of 151, or 60.3 percent, vs. 80 of 154, or 51.9 percent; P = 0.10). The median time to worsening of disease in patients receiving cyclosporine was 338 days, as compared with 492 days in patients receiving placebo (P = 0.25; relative risk, 1.22; 95 percent confidence interval, 0.86 to 1.72). Analyses of the mean Crohn's Disease Activity Index and quality-of-life scores and of the use of prednisone and 5-aminosalicylates also failed to demonstrate benefit. CONCLUSIONS: In our patient population, the addition of low-dose cyclosporine to conventional treatment for Crohn's disease did not improve symptoms or reduce requirements for other forms of therapy.     

Analysis of medication off-odors using an electronic nose

Bearing in mind a growing interest in the quality of educational processes the authors stressed the need for addressing this issue in the field of occupational medicine. They discussed major principles of the internal system of quality assessment and the possibility of adopting two instruments for evaluating (controling) the quality of teaching and learning: a questionnaire for self-assessment of acquired/transmitted competences and a test for assessing the progress in acquiring knowledge and skills necessary to solve problems.     

Intraoperative discovery of neuroblastoma in an infant with pulmonary atresia

There have been 28 previously reported cases of neuroblastoma associated with congenital heart disease. Because many of these have been defects of the conotruncal region, it has been proposed that abnormal neural crest cell migration or maturation may be a factor that links these normally disparate pathologic conditions. Most neuroblastomas in these cases have been detected at autopsy or by radiologic studies conducted in the evaluation of the cardiac anomalies. Recently, we discovered an occult posterior mediastinal neuroblastoma in a patient undergoing a unifocalization procedure for tetralogy of Fallot with pulmonary atresia and major aortopulmonary collaterals. The tumor was resected, and the patient has demonstrated no evidence of residual or metastatic neuroblastoma.     

Language dysfunction in children with Rolandic epilepsy

Rolandic epilepsy is regarded as the classic example of benign focal epilepsy. However, neuropsychological deficits have been noted in affected children. As Rolandic discharges are mainly distributed over the centrotemporal region, specific interference with language function might be suspected. Therefore, we conducted a standardized neuropsychological assessment in children with Rolandic epilepsy which covered all important aspects of language processing. We measured intelligence Quotient, verbal memory, auditory discrimination, vocabulary, grammar and literacy in 20 children with an active Rolandic focus. Information about performance at school was obtained from teachers by means of a questionnaire. Patients with Rolandic epilepsy failed five of the twelve standardized language tests significantly more often than the normative population and consequently showed impairment of the following functions: reading, spelling, auditory verbal learning, auditory discrimination with background noise and expressive grammar. Thirteen of the 20 children showed language dysfunction with difficulties in two or more of the twelve standardized language tests. In eight of these 13 children the Full Scale Intelligence Quotient was within average range, indicating a specific language deficit. Language dysfunction was closely associated with learning difficulties at school. This study documents a consistent pattern of language dysfunction in children with Rolandic epilepsy which suggests interictal dysfunction of perisylvian language areas.     

The successful induction of molting in the adult male lobster (Homarus americanus) with a slow-release form of ecdysterone

In an initial, and then a confirmatory experiment, adult, male lobsters were injected with solvent, ecdysterone (E, 2.0 mug/g live weight) or ecdysterone acetate (EAc, 2.5 or 5.0 mug/g live weight) emulsions in Freund's incomplete adjuvant (FIA). Control lobsters underwent no molts and only one death in the two cases. The E treated animals all died (average: exp. 1, 19.2 +/-2.1 days; exp. 2, 25.3 +/- 8 days). After the lobsters were treated twice with 2.5 mug EAc/g live weight, in the first experiment, four out of five molted and one died; in the second experiment six out of eight molted, one died and one remained refractory. The high EAc dose resulted in five deaths, one molt and two pseudomolts after one treatment. It is concluded that the use of the oil emulsion and EAc sufficiently slowed the release of free ecdysterone to allow complete premolt development in the lobster.     

A dose-response study of anorectic drug effects on food intake, self-stimulation, and stimulation-escape

The DNA polymerase of Ustilago maydis is stimulated by a DNA binding protein from the same organism. Analysis of this stimulation shows that there is an increase in affinity for both substrates of the reaction. The apparent Km for deoxynucleoside triphosphates is decreased 3 fold, and that for denatured DNA by 4 fold. In both cases the maximum velocity (Vmax) is increased 1.2 to 1.4 fold. It is suggested that the variability in the affinity of the enzyme for deoxynucleoside triphosphates mediated by the binding protein may provide the basis for the UV sensitivity of pyrimidine auxotrophs in this organism.