The importance of seizure-inducing factors in youth

Of over forty known epileptogenic mechanisms, some eight involve transient conditions, the regulation of which necessarily involves the understanding cooperation of the patient/parents. Tension states, alterations of the wake-sleep cycle, fatigue and sleep deprivation, CNS stimulation by sensory or drug means, and shifts of the water and acid-base balances constitute the bulk of such seizure-inducing factors. The relative lack of CNS homeostatic control, due to immature development of the blood-brain barrier and cerebral maturation, serve to exaggerate these problems in childhood. In a referred group of 150 refractory epileptic children, the seizure-inducing mechanisms were found to be important (50% reduction of seizure incidence) in 20% and to be of "crucial" importance (complete control) in an additional 14%. These results indicate the importance of such mechanisms in selected children with epilepsy, who were only marginally or inadequately controlled by drug therapy. Reviews of the literature have suggested that this more comprehensive approach to the therapeutic management of epilepsy has not been adequately exploited.     

Dysregulation of the Hypothalamus-Pituitary-Adrenal Axis in Male and Female, Genetically Obese (ob/ob) Mice

The autosomal, recessive obesity of ob/ob mice is associated with hypercorticosteronemia and amelioration of most symptoms of obesity following adrenalectomy. Increased adrenocorticotropic hormone (ACTH) secretion has been hypothesized on the basis of several reports of higher pituitary ACTH content in ob/ob mice compared to lean littermates. However, the only measurement of ACTH blood concentration found lower levels in ob/ob mice than in leans suggesting that hypercorticosteronemia might result solely from an enhanced adrenal response to ACTH and also suggesting that the ob/ob's elevated pituitary ACTH content might be due to decreased ACTH secretion rather than increased ACTH synthesis. In our study, basal serum ACTH levels were higher in ob/ob males and females compared to sex-matched lean littermates. Anterior pituitary ACTH synthesis was also elevated as indicated by increased content of ACTH and proopiomelanocortin mRNA in obese mice of both sexes; however hypothalamic corticotropin-releasing factor content was not different in lean and obese mice. Basal serum ACTH and corticosterone (CS) levels showed normal circadian rhythm in both phenotypes and sexes, but the circadian increase in CS level was much greater in obese mice than in leans despite equal serum ACTH increases in the two phenotypes. Ether stress at both peak and trough of the circadian rhythm also stimulated much larger serum CS increases in obese mice even though ACTH increases were again equal in the two phenotypes. Taken together, these results strongly indicate that ob/ob mice have increased synthesis and secretion of pituitary ACTH despite the presence of chronically elevated serum CS. This hyperactivity of the hypothalamo-pituitary-adrenal axis appears to be most pronounced in ob/ob females since pituitary ACTH content was equal in obese males and females despite much higher circulating CS levels in the females. Furthermore, the results also indicate an enhanced response to ACTH by the adrenal cortex of the obese mouse. Thus, ob/ob mice exhibit abnormal hypothalamo-pituitary-adrenal axis function with hyperactivity occurring at the level of pituitary ACTH synthesis/secretion as well as at the level of adrenocortical response to ACTH.     

Effects of dexamethasone and transient malnutrition on rabbits infected with aerosolized Mycobacterium tuberculosis CDC1551

Malnutrition is common in the developing world, where tuberculosis is often endemic. Rabbits infected with aerosolized Mycobacterium tuberculosis that subsequently became inadvertently and transiently malnourished had compromised cell-mediated immunity comparable to that of the rabbits immunosuppressed with dexamethasone. They had significant leukopenia and reduced delayed-type hypersensitivity responses. Malnutrition dampened cell-mediated immunity and would interfere with diagnostic tests that rely on intact CD4 T-cell responses.     

Irradiation of the heart during tangential breast treatment: a study within the START trial

Radiotherapy to the breast is often given as a component of the treatment for women with breast cancer. It has been shown to increase overall survival although an increase in cardiac mortality has also been noted. This study was undertaken as part of the START trial quality assurance programme to record and evaluate the cardiac dose using modern radiotherapy techniques. Departments randomizing patients into the START trial and who had CT facilities for planning breast patients were invited to take part. 62 patients were included. CT slices were taken at the level of the maximum heart depth and on the treatment field central axis. Each patient was planned in the normal way and the distributions were analysed by the quality assurance team at Mount Vernon Hospital. The maximum heart position was found to be inferior to the central axis used for breast planning for the majority of patients; mean position 2.3 cm inferior with a mean maximum heart depth of 0.55 cm. For 45% of patients the maximum heart dose was less than 50% of the prescribed dose. The study showed that the volume of irradiated cardiac tissue has decreased compared with earlier studies, and also highlighted the need to scan away from the central axis if the dose to cardiac tissue is to be assessed.     

Evaluating geographic imputation approaches for zip code level data: an application to a study of pediatric diabetes

Background  

There is increasing interest in the study of place effects on health, facilitated in part by geographic information systems. Incomplete or missing address information reduces geocoding success. Several geographic imputation methods have been suggested to overcome this limitation. Accuracy evaluation of these methods can be focused at the level of individuals and at higher group-levels (e.g., spatial distribution).