Fibrosing colonopathy in cystic fibrosis: results of a case-control study.

Fibrosing colonopathy was first described in cystic fibrosis (CF) children in 1994. We have done a nested case-control study to identify possible associations with this condition. A case ascertainment within the UK CF population to identify any cases that occurred between January, 1984, and April, 1994, found 14 cases, all under 14 years and confirmed by independent histopathological review. All had presented since April, 1993; 12 were boys and six had received some or all of their care in Liverpool. Each case was matched, by date of birth, with four controls from the UK CF Registry. Information was obtained about cases and controls from their case records and by a structured interview with the families. In the 12 months before surgery, there was an association between the occurrence of fibrosing colonopathy and use of high-strength pancreatic enzyme preparations. This association was dose related. Odds ratio per extra 1000 high-strength capsules was 1.45 (95% CI 1.14-1.84). For use of protease, the odds ratio per million extra units per kg was 1.55 (1.19-2.03). For usage of individual high-strength products at any time during the 12 months before surgery some differences were observed; for Creon 25000 the odds ratio was 0.38 (0.10-1.42), for Nutrizym 22 43.4 (2.51-751), and for Pancrease HL 8.4 (1.95-36.1). These last two confidence intervals are extremely wide and compatible with these two products having the same odds ratios. Laxative use was independently predictive (odds ratio 2.42 [1.20-4.94]). We conclude that there is a dose-related association between high-strength pancreatic enzyme preparations and fibrosing colonopathy.

Herpes simplex encephalitis: long term magnetic resonance imaging and neuropsychological profile.

The first comprehensive in vivo documentation of the long term profile of pathological and spared tissue is described in a group of 10 patients with a diagnosis of herpes simplex encephalitis, who were left with memory difficulties as a major residual sequel of their condition. With a dedicated MRI protocol, which included high resolution images of temporal lobe and limbic system areas, data are provided on structures that have recently gained importance as anatomical substrates for amnesia. The major features of the lesion profile were: (1) unilateral or bilateral hippocampal damage never occurred in isolation, and was often accompanied by damage to the parahippocampus, the amygdala, specific temporal lobe gyri, and the temporal poles; (2) the insula was always abnormal; (3) neocortical temporal lobe damage was usually unilateral or asymmetric. It never occurred in isolation, and was invariably associated with more medial pathological changes; (4) anterior and inferior temporal lobe gyri were damaged more often and more severely than posterior and superior temporal lobe gyri; (5) pronounced abnormality was often present in the substantia innominata (region of the basal forebrain/anterior perforated substance); (6) there was evidence of significant abnormality in the fornix; (7) there was evidence of damage to the mammillary bodies; (8) thalamic nuclei were affected in around 50% of cases, with damage usually unilateral; (9) frontal lobe damage was present in a few patients, and affected medial areas more than dorsolateral areas; (10) there was some involvement of the striatum, although this was usually unilateral and mild; (11) there was usually limited involvement of the cingulate gyrus and of the parietal and occipital lobes; (12) the cerebellum and brain stem were never damaged. Lesion covariance analysis indicated a close relation between the presence of abnormalities in temporal lobe and limbic-diencephalic regions. Unlike severe head injury, lesions in the temporal pole were not associated with the presence of lesions in the orbitofrontal cortex. Long term neuropsychological impairments were characterised by a dense amnesia in 60% of cases, and a less serve but noticeable anterograde memory impairment in the others. Naming and problem solving deficits were found in a small number of cases. Only two patients were able to return to open employment. Severity of amnesia showed a significant relation with severity of damage to medical limbic system structures such as the hippocampus, with bilateral damage being particularly important. By contrast, there was a minimal relation between memory loss and severity of damage to the thalamus, to lateral temporal lobe areas, or to the frontal lobes.

Use of prescription drugs in the first trimester and congenital malformations.

A prospective survey of prenatal use of prescription drugs in Tasmania yielded detailed information on drug exposure, delivery and outcome for 56,037 births from 1982 to 1989. First trimester drug use was reported by 30.9% of women, and 17.9% used only supplements of vitamins and/or minerals; 40% used alcohol during the first trimester, and 28.8% smoked cigarettes. There were 1,035 (1.85%) congenital malformations, of which 885 (85.5%) were major. The malformation rate was not significantly different in the following exposure categories: supplements only (1.62%); other pharmaceuticals (1.92%); smokers (1.88%); alcohol users (1.89%); and maternal age 35 or more years (1.95%). Adjusting for alcohol use, smoking, maternal age and diabetes mellitus, significant associations [expressed as adjusted odds ratio and 95% confidence intervals (CI)] were found between aspirin and hypospadias (3.5, 95% CI 1.4 to 8.8); dicyclomine and phocomelia (4.4, 95% CI 1.0 to 19.5); and between oral contraceptive use and pes cavus (9.7, 95% CI 2.3 to 40.4). Although significant, these associations were based on very few cases and no direct supporting evidence could be found from other data sources.