A simple and sensitive fully validated HPLC-UV method for the determination of 5-fluorouracil and its metabolite 5,6-dihydrofluorouracil in plasma

The authors developed a simple and sensitive, fully validated HPLC-UV method for the determination of both 5-FU and its metabolite DHFU in small-volume plasma samples. The analytes were separated on a 4.6 x 250 mm ID Atlantis dC18 5-microm column with isocratic elution at room temperature. Chlorouracil was used as internal standard. The analytes were detected with an UV diode array detector. DHFU was detected at 205 nm, 5-FU at 266 nm, and chlorouracil at both wavelengths. The limits of quantification in plasma were 0.040 mug /mL for 5-FU and 0.075 microg/mL for DHFU. Linearity, accuracy, precision, recovery, dilution, freeze-thaw stability, and stability in the sample compartment were evaluated. The method appeared linear over a range from 0.04 to 15.90 microg/mL for 5-FU and from 0.075 to 3.84 microg/mL for DHFU. The method appeared very suitable for therapeutic drug monitoring and pharmacokinetic studies of 5-FU because of its simple extraction and small sample volume. Problems in earlier published methods with interfering peaks and variable retention times were overcome. The method appeared also to be suitable for detection of uracil and its metabolite dihydrouracil in plasma.     

Food advertising on Australian television: the extent of children's exposure

The objective of this study was to investigate the extent and nature of food advertising during Australian children's television (TV) viewing hours and programs, and to determine whether confectionery and fast food restaurant advertisements were more likely to be broadcast during children's programs than during adults' programs on Sydney television stations. One week (390 h) of Australian advertising data broadcast during children's TV viewing hours over 15 television stations were analysed to determine the proportion of food advertisements and, in turn, the proportion of those advertisements promoting foods high in fat and/or sugar. One week (346 h) of confectionery and fast food restaurant advertisements broadcast over three Sydney television stations were analysed to determine whether these types of advertisements were more likely to be advertised during children's programs than adults' programs. Half of all food advertisements promoted foods high in fat and/or sugar. 'Confectionery' and 'fast food restaurants' were the most advertised food categories during children's TV viewing hours. Confectionery advertisements were three times as likely, and fast food restaurant advertisements twice as likely, to be broadcast during children's programs than adults' programs. It can be concluded that foods most advertised during children's viewing hours are not those foods that contribute to a healthy diet for children. Confectionery and fast food restaurant advertising appears to target children. Australian children need protection from the targeted promotion of unhealthy foods on television, but currently little exists.     

Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting

OBJECTIVE: Alternate day fasting may extend lifespan in rodents and is feasible for short periods in nonobese humans. The aim of this study was to examine the effects of 3 weeks of alternate day fasting on glucose tolerance and skeletal muscle expression of genes involved in fatty acid transport/oxidation, mitochondrial biogenesis, and stress response. RESEARCH METHODS AND PROCEDURES: Glucose and insulin responses to a standard meal were tested in nonobese subjects (eight men and eight women; BMI, 20 to 30 kg/m(2)) at baseline and after 22 days of alternate day fasting (36 hour fast). Muscle biopsies were obtained from a subset of subjects (n = 11) at baseline and on day 21 (12-hour fast). RESULTS: Glucose response to a meal was slightly impaired in women after 3 weeks of treatment (p < 0.01), but insulin response was unchanged. However, men had no change in glucose response and a significant reduction in insulin response (p < 0.03). There were no significant changes in the expression of genes involved in mitochondrial biogenesis or fatty acid transport/oxidation, although a trend toward increased CPT1 expression was observed (p < 0.08). SIRT1 mRNA expression was increased after alternate day fasting (p = 0.01). DISCUSSION: Alternate day fasting may adversely affect glucose tolerance in nonobese women but not in nonobese men. The gene expression results indicate that fatty acid oxidation and mitochondrial biogenesis are unaffected by alternate day fasting. However, the increased expression in SIRT1 suggests that alternate day fasting may improve stress resistance, a commonly observed feature of calorie-restricted rodents.     

Estimating Australia's abortion rates 1985-2003

AIM: To estimate national rates of induced abortion in Australia from 1985 to 2003, using Medicare claim statistics for private patients and hospital morbidity statistics for public patients. DESIGN AND SETTING: Estimates were based on Australian and South Australian data collections relating to abortions. SA hospital morbidity statistics were compared with SA statutory notifications of abortions to estimate the accuracy of these collections. Medicare statistics on abortion procedures performed on private patients in South Australia were then compared with hospital morbidity statistics for private patients. National statistics on abortion derived from Medicare and hospital morbidity statistics were adjusted for inaccuracies found in these sources. MAIN OUTCOME MEASURES: Numbers of induced abortions in Australia for each year from 1985 to 2003; abortion rates per 1000 women aged 15-44 years. RESULTS: Abortion numbers based on Medicare claims by private patients overestimated by 18.7% the number of abortions derived from statutory notifications in South Australia during the period 1988-89 to 1999-00. Hospital morbidity data using principal diagnosis codes relating to medical abortion overestimated statutory notifications by 2.3% (mainly because of readmissions). National statistics were adjusted for these overestimations and for the estimated 14.1% of private patients who would not have submitted Medicare claims (based on surveys of private-clinic patients in New South Wales and Victoria). The estimated Australian abortion rate increased from 17.9 per 1000 women aged 15-44 in 1985 to a peak of 21.9/1000 in 1995, then declined to 19.7/1000 in 2003 (estimated number of abortions, 84,460). CONCLUSION: There are no data currently available for deriving accurate numbers of induced abortions in Australia. Suggestions are made for collection of national statistics.     

Prevention of perinatal transmission of hepatitis B to babies at high risk: an evaluation

We aimed to determine factors associated with successful vaccination coverage and development of infection in high-risk infants born to hepatitis B infected women. Immunisation of 860/932 (92%) of babies was started within 48 h of birth and three doses of vaccination completed for 794/921 (86%). Only 543 (58%) infants were tested and 26 (4.9%) were found to have evidence of current infection. Delayed start of immunisation was significantly associated with unbooked pregnancy, maternal hepatitis B e-markers and year. Current infection in the baby was strongly associated with maternal hepatitis B e-status, ethnicity and year of vaccination. The proportion of infants developing infection declined after 1998, coinciding with the publication of national recommendations and the wider use of the accelerated schedule.     

Acute effects of subclinical epileptiform EEG discharges on cognitive activation

In this prospective, open, clinical comparative study we analyzed impairments of cognitive activation occurring during, immediately before and immediately after epochs with epileptiform EEG discharges of 3 seconds or longer, in an attempt to establish whether cognitive slowing occurs in direct association with an epoch with epileptiform EEG discharges and whether cognitive impairments precede or follow such an epoch. All children were assessed with EEG/video (Brainlab) simultaneously with computerized neuropsychological testing (FePsy): a test for cognitive activation (simple visual and auditory reaction time measurement). Thirty-seven epochs with epileptiform EEG discharges without clinical signs of a seizure (subclinical epileptiform EEG discharges) were evaluated. The results showed a statistically significant and clinically relevant slowing (35% compared to the overall reaction time), occurring during the epoch with epileptiform EEG discharges (repeated measurement analysis of variance p = < .05; df = 3; F-value: 3.293). No statistically significant slowing was found for the periods 'post-discharge' or 'pre-discharge'. Type of discharge was important and effects on cognitive activation were found exclusively for generalized discharges. This effect was, however, also seen in the remaining period, outside the 'peri-discharge' periods and thus seemed to represent a more general effect of the type of epilepsy on cognitive activation. Our results show that the acute effect of short epileptiform EEG discharges (duration 4.14 sec; sd 1.38) may be impressive, causing impairment (slowing) of cognitive activation. This effect was limited to generalized discharges. This effect was not observed for focal discharges, even during longer periods with discharges. However, it is reassuring that this impact on cognitive activation is limited to the actual period in which the discharges occur and does not have 'post-discharge' effects. The risk of accumulating effects that may have longer-lasting repercussions on higher-order cognitive functions therefore seems to be negligible.     

Mean cell spacing abnormalities in the neocortex of patients with schizophrenia

It has been postulated that the prefrontal cortices of schizophrenic patients have significant alterations in their interneuronal (neuropil) space. The present study re-examines this finding based on measurements of mean cell spacing within the cell minicolumn. The population studied consisted of 13 male schizophrenic patients (DSM-IV criteria) and 13 age-matched controls. Photomicrographs of Brodmann's areas 9, 4 (M1), 3b (S1), and 17 (V1) were analyzed with computerized image analysis to measure parameters of minicolumnar morphometry, i.e., columnarity index (CI), minicolumnar width (CW), dispersion of minicolumnar width (V(CW)), and mean interneuronal distance (MCS). The results indicate alterations in the mean cell spacing of schizophrenic patients according to both the lamina and cortical area examined. The lack of variation in the columnarity index argues in favor of a defect postdating the formation of the cell minicolumn.     

Detection of musculoskeletal infection with 18F-FDG PET: review of the current literature

There are several studies on (18)F-FDG PET in the evaluation of musculoskeletal infection; however, a search of the literature failed to identify any large-scale studies. The 7 articles reviewed included 273 cases of suspected musculoskeletal infection evaluated by (18)F-FDG PET. This method was found to be sensitive and specific in the evaluation of chronic and acute osteomyelitis and prosthetic infection. Furthermore, (18)F-FDG PET was accurate in the evaluation of infection at previous surgical sites even within 12 mo of surgery. The current literature suggests that (18)F-FDG PET is a highly accurate method to detect musculoskeletal infection.