Tropical medicine in and out of the tropics.
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Biomedical subjects
Publications and source records attributed to N Day.
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Experimental diabetic neuropathy, whether chemically induced or present in several spontaneously diabetic animal models, is characterized by sorbitol accumulation and myo-inositol depletion and usually also by enhanced turnover of the monoesterified moieties of polyphosphoinositides, particularly phosphatidylinositol-4,5-bisphosphate (PIP2). This study examined the relationship of these alterations by assessing the effects of myo-inositol and the aldose reductase inhibitor, sorbinil, supplied as dietary supplements, on sorbitol and myo-inositol concentrations and incorporation of 32P into polyphosphoinositides in sciatic nerve from rats killed 8 weeks after induction of diabetes with streptozotocin. Nerves from diabetic rats killed after 8 weeks of disease exhibited 52% to 76% greater PIP2 labeling, markedly elevated sorbitol levels, and 30% less myo-inositol when compared with age-matched normal rats. Incorporation of isotope into PIP2 in nerves from animals fed a myo-inositol supplement, added to either a high-sucrose diet or standard rat chow beginning immediately after induction of diabetes, remained substantially elevated, whereas myo-inositol levels were corrected to normal. Essentially the same results were obtained when rats were fed the myo-inositol-containing diet beginning 4 weeks after streptozotocin injection. In contrast, PIP2 labeling in nerves from diabetic rats that received the sorbinil-supplemented diet for either 4 or 8 weeks was not different from that in controls. myo-Inositol levels in these animals were also restored to normal, whereas sorbitol levels remained elevated, albeit reduced by approximately 30%. These results indicate that myo-inositol administration is unable to completely counteract the impact of diabetes on the turnover of monoesterified phosphate groups in PIP2. In contrast, sorbinil can correct this abnormality, but this beneficial effect is not dependent on the presence of normal sorbitol concentrations.
Electromyographic recordings show that, for adult brown trout swum up to their critical swimming speed (Ucrit) in a flume at neutral pH, white muscle recruitment occurred when speeds approached 1 body length s-1 (BL s-1) and continued to Ucrit (approximately 2 BL s-1) at both winter (5 °C) and summer (15 °C) acclimation temperatures. However, in the majority of fish swum up to Ucrit at sublethal acidic pH, continuous white muscle recruitment did not occur, although all swam above 1 BL s-1. Any observed electrical activity of the white muscle in these individuals was, at best, intermittent. Consequently, the mean Ucrit of these fish was approximately half that of fish swum at neutral pH. In all fish at sublethal pH, red muscle activity was observed for the whole duration of the exercise period, showing that swimming speeds greater than 1 BL s-1 were achieved largely aerobically. Fish that were chased around a tank at sublethal pH appeared lethargic in their escape response, exhibiting little or no burst swimming. Other observed effects of exposure to sublethal pH, which may have affected swimming capacity, included increases in the resting levels of blood and muscle ammonia, reduced muscle glycogen stores and reduced muscle ion concentrations.
Recently, we completed a second biostatistical study of urinary tract tumors (UTT) in areas with Balkan endemic nephropathy (BEN) in the Vratza district, Bulgaria, during the period 1975 to 1991. We confirmed the positive correlation between the incidence of urinary tract tumors (UTT) and BEN demonstrated in our first population-based case control 1977 study. A UTT incidence of 98.9 per 100,000 men and 74.7 per 100,000 women was found in villages most affected by BEN when compared with 11.0 and 6.7 for men and women, respectively, in nonendemic villages. The relative risk (RR) of UTT in BEN villages showed tumors of kidney pelvis and ureters-29 in men and 35 in women and urinary bladder tumors-4 in men and 11 in women. The percentage of food and blood samples containing nephrotoxic and carcinogenic mycotoxin Ochratoxin A (OTA) correlated with the origin of the samples. The most contaminated samples were found in BEN villages and households, and the urinary excretion of OTA was higher in the group of BEN/UTT patients. The UTT DNA's were studied by the 32P-postlabeling method for the presence of OTA-DNA adducts. Some OTA-DNA adducts characteristic for endemic UTT and absent in control nonendemic UTT and nontumorous tissues were described for the first time.
OBJECTIVE: To test the hypothesis that sleep disruptions would be evident in 3-year-old children with a history of prenatal marijuana exposure. DESIGN: A prospective study using stratified random sampling beginning in the fourth month of pregnancy. Marijuana and other substance use were assessed by interviews at multiple time points. Offspring were followed up through age 3 years with multidomain assessments at fixed time points, including electroencephalographic sleep studies in the newborn period and at age 3 years. SETTING: Primary care, prenatal clinic at a university hospital. SUBJECTS: The sample included 18 children with prenatal marijuana exposure (mean [+/- SD] age, 39.0 +/- 4.4 months) and 20 control children (mean [+/- SD] age, 39.7 +/- 4.4 months). The two groups were similar in relationship to maternal age, race, income, education, or maternal use of alcohol, nicotine, and other substances in the first trimester. MAIN OUTCOME MEASURE: Sleep variables from polysomnographic recordings at age 3 years. RESULTS: Children with prenatal marijuana exposure showed more nocturnal arousals (mean [+/- SD], 8.2 +/- 5.3 vs 3.2 +/- 4.6; P < .003), more awake time after sleep onset (mean [+/- SD], 27.4 +/- 20.0 vs 13.7 +/- 12.4 min; P < .03), and lower sleep efficiency (mean [+/- SD], 91.0 +/- 3.8 vs 94.4 +/- 2.1; P < .03) than did control children. CONCLUSION: Prenatal marijuana exposure was associated with disturbed nocturnal sleep at age 3 years.
Although mortality from coronary heart disease (CHD) in Australia has fallen dramatically since the 1960s, it still remains the major cause of death in Australia and poses a significant burden on the economy. Even though a number of studies have concluded that prevention has been the main determinant of the declines in CHD, a disproportionate amount of health-care expenditure is devoted to treatment rather than prevention. This paper reviews the international literature on the economic appraisal (costs and benefits) of alternative interventions for the treatment and prevention of CHD with the view of assessing whether there is sufficient evidence to justify a reallocation of resources away from treatment to prevention. First, few studies on the economic evaluation of CHD prevention and treatment programs have been undertaken in Australia, with most being from the United States and Europe. Second, assumptions about the specification, measurement and valuation of costs, and the epidemiological evidence on program effectiveness have varied. Third, health promotion and prevention programs are not necessarily more cost-effective than drug or surgical treatments for CHD. Individual interventions must be judged on their own merits. There is a need for a systematic evaluation of interventions for CHD using primary Australian data to better inform decision making on resource-allocation priorities. Such an evaluation should incorporate economic evaluation techniques.
Interval cancer rates are a major determinant of the success of a screening programme. In the Swedish two county study, on which the United Kingdom programme is based, a 39% reduction in mortality was observed in screened women aged 50-64. Using data from the Swedish study, the relationship between interval cancer incidence and the likely future effect on breast cancer mortality was quantified. In East Anglia, as elsewhere in the United Kingdom, interval cancers rates are nearly double those obtained in Sweden: interval cancer rates in the first, second, and third years respectively, after a negative screen were 24%, 59%, and 79% of the expected underlying incidence in the absence of screening. The corresponding figures from the two county study were 17%, 30%, and 56%. From these it was estimated that the mortality reduction in East Anglia will be 21%, which is lower than the 35% observed in invited women in this age group in the Swedish two county study and the 25% specified in the Health of the Nation target. In a rereading exercise, using screening mammograms from women who were screen normal, who had screen detected cancers, or who subsequently developed interval cancers, four out of five radiologists recommended recall for around 70% of the original mammograms (classed as screen normal at time of screening) from 33 interval cancers. This suggests that sensitivity is a contributory factor to the higher interval cancer rates in East Anglia.
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Screening for dementia in populations presents particular difficulties for researchers. In the absence of gold standards for diagnosis, the methods used must be determined by the purposes of the study. In two-stage epidemiological study the screening wave and the diagnostic instrument should be considered together in relation to a third proxy gold standard such as progression of the disorder to moderate and greater severity and neuropathological diagnosis. This provides a measure of the predictive performance of the original screening method and its diagnostic phase. To reduce the variance of estimates of prevalence and incidence it is suggested that the screening interview be a subset of the diagnostic interview.
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A case-referent study of birth defects was nested in a prevalence survey of adverse reproductive outcomes carried out among 8867 floriculture workers in Bogotá, Colombia. A total of 535 children born to these workers and reported by their parents as malformed and 1070 children selected at random as referents were invited to a medical examination including consultation with a geneticist and a clinical teratologist and a review of the medical records. Seventy-six percent of both groups attended the examination. Of 403 children reported as malformed, a birth defect was confirmed for only 154 (38%). On the other hand, of the 817 children reported as normal, 735 (90%) were normal, but 68 had a birth defect and 14 had other conditions. A case-referent analysis was then carried out including 222 children with birth defects and 443 referents. An increased risk was found only for birthmarks, and specifically for hemangiomas, for children with parents exposed to pesticides in the floriculture industry.
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We assessed fetal morbidity and mortality in women with systemic sclerosis (SSc). Women with a history of SSc and a concomitant pregnancy completed a detailed questionnaire about the pregnancy. These 48 subjects were age-matched and race-matched to 2 other groups of women (a rheumatoid arthritis group and a control group from the same neighborhood), all of whom had been pregnant at least once. There were no differences in the frequencies of miscarriage or perinatal death in the SSc group compared with the 2 control groups. Preterm births occurred slightly more frequently in both SSc patients and rheumatoid arthritis patients compared with the neighborhood control subjects. There were significantly more small full-term infants born to women with SSc. Interestingly, the increase in preterm births and small full-term babies occurred with equal frequency prior to and after the onset of disease. Although close monitoring for premature birth and intrauterine growth retardation is necessary, we conclude that an uneventful, healthy pregnancy is possible for women with SSc. Those with early, rapidly progressive, diffuse skin thickening should avoid becoming pregnant since, intrinsically, they are at higher risk of developing renal crisis.
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