The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.     

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-- >T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.      

A comparison of findings on parents' and teachers' questionnaires, and detailed ophthalmic and psychological assessments.

BACKGROUND: Questionnaires are important tools used to gain information about health and level of function in different domains. AIMS AND METHODS: To determine the degree of agreement between questionnaires, administered to parents and teachers, and ophthalmic and psychological examinations in a cohort of 309 low birth weight children (<1701 g) at age 10-13 years. RESULTS: A total of 90.9% of cases showed agreement between the question on distance vision and clinical assessment, and agreement for the near vision question was 83%. However, the correlation on an individual basis was only fair (kappa = 0.46, distance vision) to poor (kappa = 0.2, near vision). The overall agreement for the questions on cognitive ability was better than the correlation, whereas the questions on reading and mathematical ability showed low agreement and low correlation. CONCLUSION: Questionnaire assessment of vision and cognitive ability is more suitable for studying the outcome of a large population than for identifying deficits in individuals.     

Endoscopic closure of fetal membrane defects: comparing iatrogenic versus spontaneous rupture cases.

OBJECTIVE: Currently, physicians manage preterm premature rupture of membranes (PPROM) by expectant management or termination of the gestation. A therapy aimed at sealing membranes would be optimal to maintain the pregnancy and achieve a normal neonate. Our objective was to compare an endoscopic technique for intrauterine closure of fetal membrane defects after both iatrogenic and spontaneous rupture of membranes. METHODS: Our technique was performed on four patients experiencing PPROM spontaneously and four patients after genetic amniocentesis. Intrauterine endoscopy allowed direct visualization of membrane defects. Rapid sequential injections of platelets, fibrin glue and powdered collagen slurry were administered at the site of the defect and of trocar placement. Sonography for amniotic fluid index, nitrazine and fern testing and pad count were performed after each procedure at three intervals: immediately post-procedure, and after 24 and 48 h. RESULTS: Eight patients underwent endoscopic intrauterine sealing of ruptured membranes between 16 and 24 weeks of gestation: four were spontaneous ruptures and four were ruptures post-amniocentesis. In the post-amniocentesis group, three patients delivered viable infants at 26, 32 and 34 weeks. In one patient, the membranes ruptured again 12 h after the sealing procedure and she decided to undergo termination of pregnancy. Of the four spontaneous rupture patients, two experienced preterm labor and delivery within 2 days of the procedure. One patient was diagnosed with fetal demise 12 h post-procedure, and one patient delivered a neonate at 31 weeks of gestation with severe respiratory distress syndrome. CONCLUSIONS: This technique for sealing ruptured membranes is effective after amniocentesis, but may not be of benefit with spontaneous rupture.