Unusual cyclosporin related neurological complications in recipients of liver transplants

In a series of 256 recipients of paediatric liver transplants, from 1984 to 1990, four patients presented with sudden onset seizures not explained by conventional work-up. None had a family or personal history of seizures. Infectious causes were excluded. There were no glucose or electrolyte disturbances. Seizures were not induced by systemic or intracranial hypertension. One child out of four had transient white matter and cortex focal lesions on computed tomography of the brain. One to 10 days before seizures all four children presented with supratherapeutic concentrations of serum cyclosporin that were determined by a non-specific method that measured the parent compound plus its metabolites. The supratherapeutic concentrations were not found with the specific method measuring cyclosporin alone. It is concluded that these seizures may correspond to a toxic effect of cyclosporin, probably due to one or several metabolites, as suggested by the discrepancy between specific and non-specific methods of determination.     

Female fertility, obstetric and gynaecological history in coeliac disease: a case control study

Objectives : The purpose of this study was to investigate the incidence of infertility, abortions and perinatal mortality, age at menarche and menopause in coeliac disease. Method : This was a case control study in which patients and controls, matched for age and sex, were sent questionnaires about their fertility profile and other obstetric and gynaecological problems. All 80 patients and 70 controls replied, but only 68 pairs could be matched for this study. Results : The mean age of menarche in patients was significantly older (13.6 years) than in controls (12.7 years). The mean ages at menopause in patients and controls were 47.6 and 50.1 years, respectively. The mean number of children born to patients was significantly less at 1.9 (SD± 0.9) compared to 2.5 (SD± 1.2) in controls. Before diagnosis the mean number of children born to patients was 1.4 and 1.8 in controls. After diagnosis and treatment, patients had 0.5 children (SD±0.9) compared to 0.7 in controls (SD±1.2). It seems likely that the overall difference in fertility is due to relative infertility prior to diagnosis and its correction by a gluten-free diet. Significantly more conceptions amongst women with coeliac disease (15%) ended in miscarriage prior to diagnosis than amongst controls (6%). After diagnosis and treatment the rate of miscarriage was similar. There were 120 live babies and 7 stillbirths to patients compared with 161 live babies and 1 stillbirth to controls. Conclusions : Patients with CD are subfertile and have an increased incidence of stillbirths and perinatal deaths.     

The changing clinical pattern of Reye's syndrome 1982-1990

OBJECTIVE: To describe trends in the clinical pattern of Reye's syndrome in the British Isles between 1982 and 1990; and to determine the relation between any changes and the June 1986 warnings against the use of aspirin in children. DESIGN: Development, and application to reported cases, of a scoring system designed such that patients showing the typical clinical and pathological features of 'classical' Reye's syndrome scored highly. The relations between 'Reye scores' and a number of explanatory variables were explored using multivariable analysis. SETTING: British Isles. SUBJECTS: 445 cases fulfilling the Reye's syndrome case definition reported to the surveillance scheme between January 1982 and December 1990. MAIN OUTCOME MEASURE: Individual 'Reye score'. RESULTS: Cases with high scores were more likely to have occurred in the 4 1/2 year period before June 1986 compared with the subsequent period (p < 0.006). Numbers of cases in the low and intermediate score categories declined by about 50% after June 1986, whereas those in the high category fell by 79%. High scorers were more likely to have received aspirin (p < 0.0001) and were older than intermediate and low scorers (p < 0.008). No relation was identified between score and season of onset. CONCLUSIONS: The decline in Reye's syndrome after the aspirin warnings cannot be explained entirely, as has been proposed, by improved diagnosis of 'Reye-like' inherited metabolic and other disorders: this would not account for the greater decline of the high scoring subgroup which also contained those cases most likely to resemble 'classical' Reye's syndrome and to have received aspirin. This study provides further evidence for the role of aspirin in a subset of cases meeting the standard diagnostic criteria for Reye's syndrome and supports the need to consider this disorder as a heterogeneous group of conditions including Reye-like inherited metabolic disorders.     

Hepatic inflammation and fibrosis biomarkers are associated with cardiovascular risk factors but not cardiovascular disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study

BackgroundBoth cardiovascular disease and liver disease are particularly common in people with type 2 diabetes and it is possible that the two conditions are inter-related. Non-invasive biomarkers are increasingly used to estimate liver inflammation and fibrosis. In this study the association of these biomarkers with cardiovascular risk factors and disease was explored in a large, representative population of people with type 2 diabetes mellitus.MethodsCytokeratin 18 (CK18, biomarker of hepatic inflammation) and the European Liver Fibrosis panel (ELF, biomarker of hepatic fibrosis) were measured in a random subgroup of 564 adults, aged 60–75 years at recruitment, participating in the Edinburgh Type 2 Diabetes Study (ET2DS). Data on conventional CV risk factors (body-mass index [BMI], waist circumference, blood pressure, total cholesterol, triglycerides, smoking status) and prevalent cardiovascular disease (validated myocardial infarction, angina, stroke and transient ischaemic attack events) were also available.FindingsMedian CK18 was 102 U/L [IQR 76–137, range 29–993] and mean ELF was 8·9 U/L [SD 0·8, range 6·9–11·6]. After adjustment for age and sex, increased CK18 was significantly associated with higher triglyceride levels (r=0·157, p=0·002). Increased ELF score was associated with higher BMI (r=0·202, p<0·001), waist circumference (r=0·139, p=0·008), and diastolic blood pressure (r=–0·045, p=0·025). Despite these associations, neither biomarker was significantly associated with prevalent cardiovascular disease (prevalent cardiovascular disease vs no cardiovascular disease, mean CK18 108·1 U/L [SD 26·2] vs 105·5 [22·6], p=0·473 and mean ELF 8·94 [0·77] vs 8·89 [0·76], p=0·442).InterpretationIn people with type 2 diabetes, non-invasive biomarkers of hepatic inflammation and fibrosis are associated with a number of cardiovascular risk factors but do not appear to associate with pre-existing vascular disease. Further investigation is required to determine whether liver biomarkers predict incident cardiovascular disease in this high risk group.FundingDiabetes UK.     

咖啡因5种主要代谢物的反相高效液相色谱法测定

为保证应用咖啡因代谢探针的正确性,建立了反相高效液相色谱测定尿中咖啡因代谢物的方法。采用日本岛津 Shim Pack CLC-ODS柱(5μm),以甲醇—乙腈—0.05%醋酸(12∶1∶87)为流动相,咖啡因和它的13种代谢物及内标均能良好分离。重点对其中5个主要代谢物AFMU,1U,1X,17U,17X进行了测定。结果表明这5种代谢物回收率均在87%以上,日内和日间误差均小于3%,显示了方法的稳定性。并对120例志愿者尿中5种主要代谢物浓度进行了测定,为进一步评价多种药物代谢酶活性创造条件。     

Phrenic Nerve Paralysis, Vegetative Symptoms and Restrictive Cardiomyopathy in a Case of Poems Syndrome

OBJECTIVE: To study the effectiveness and safety aspects of sodium valproate in the management of painful neuropathy in patients of type 2 diabetes mellitus. MATERIAL AND METHODS: A randomized double‐blind placebo controlled trial of sodium valproate was done in type 2 diabetic patients to assess its efficacy and safety in the management of painful neuropathy. We screened 60 patients but eight patients could not complete the study; hence, the present study was done on 52 patients. Each patient was assessed by clinical examination, pain score by short form of the McGill pain questionnaire (SF‐MPQ) and electrophysiological examination, which included motor and sensory nerve conduction velocity, amplitude and H‐reflex initially and at the end of 1 month of treatment. RESULTS: Significant improvement was noticed in the pain score of patients receiving sodium valproate in comparison to patients receiving placebo at the end of 1 month (P < 0.05). The changes in electrophysiological data were not significant. The drug was well tolerated by all patients except one who developed a raised aspartate transaminase (AST)/alanine transaminase (ALT) level after 15 days of treatment. CONCLUSION: Sodium valproate is a well‐tolerated drug and provides significant subjective improvement in painful diabetic neuropathy. These data provide a basis for future trials of longer duration in a larger group of patients.     

Protection of children against sunburn: a survey of parental practice in Leicester

The incidence of melanoma in the U.K. is increasing more rapidly than that of most other malignant tumours. Sunburn in childhood increases the risk of malignant melanoma in later life and it is herefore essential that protection of children is improved if primary prevention of melanoma is to be effective. We asked 238 parents in Leicester how they protected their children against sunburn, how often their children suffered sunburn, and whether they had heard of malignant melanoma. Although most (80%) had heard of melanoma. 47% did not regularly ensure that their children used a sunblock lotion, and only 34% regularly protected them from the midday sun. Forty-eight percent of parents stated that their children burned at least once a year. New approaches to public education about melanoma may be needed to improve the protection of children against sunburn.