The effect of water fluoridation on the bone mineral density of young women [Saskatoon study]

Introduction: Osteogenic effects of therapeutic fluoride have been reported; however, the impact of exposure to low level water fluoridation on bone density is not clear. We investigated the effect of long-term exposure to fluoridated water from growth to young adulthood on bone mineral density (BMD). Methods: BMD was measured in 24 healthy women from Regina (fluoride 0.1 mg/L) and 33 from Saskatoon (fluoride 1.0 mg/L), with no differences between groups for height, weight, lifestyle or dietary factors. Results: Saskatoon women had significantly higher mean BMD at total anterior-posterior lumbar spine (APS) and estimated volumetric L3 (VLS), with no difference at total body (TB) or proximal femur (PF). Conclusion: Exposure to water fluoridation during the growing years may have a power impact on axial spine bone density in young women.

Distribution of transferrin saturation in an Australian population: Relevance to the early diagnosis of hemochromatosis

Background & Aims: An elevated transferrin saturation is the earliest phenotypic abnormality in hereditary hemochromatosis. Determination of transferrin saturation remains the most useful noninvasive screening test for affected individuals, but there is debate as to the appropriate screening level. The aims of this study were to estimate the mean transferrin saturation in hemochromatosis heterozygotes and normal individuals and to evaluate potential transferrin saturation screening levels. Methods: Statistical mixture modeling was applied to data from a survey of asymptomatic Australians to estimate the mean transferrin saturation in hemochromatosis heterozygotes and normal individuals. To evaluate potential transferrin saturation screening levels, modeling results were compared with data from identified hemochromatosis heterozygotes and homozygotes. Results: After removal of hemochromatosis homozygotes, two populations of transferrin saturation were identified in asymptomatic Australians (P < 0.01). In men, 88.2% of the truncated sample had a lower mean transferrin saturation of 24.1%, whereas 11.8% had an increased mean transferrin saturation of 37.3%. Similar results were found in women, A transferrin saturation threshold of 45% identified 98% of homozygotes without misidentifying any normal individuals. Conclusions: The results confirm that hemochromatosis heterozygotes form a distinct transferrin saturation subpopulation and support the use of transferrin saturation as an inexpensive screening test for hemochromatosis. In practice, a fasting transferrin saturation of greater than or equal to 45% identifies virtually all affected homozygous subjects without necessitating further investigation of unaffected normal individuals.

Effect of metabolic inhibitors on cyclosporine pharmacokinetics using a population approach

Drugs known to inhibit the metabolism of cyclosporine are administered concomitantly to those who undergo cardiothoracic transplantation. The aim of this study was to examine in quantitative terms the relationship between cyclosporine oral dose rate and the trough concentration (Css(trough)) at steady state in patients who undergo cardiothoracic transplantation and are administered cyclosporine alone or in combination with drugs known to inhibit its metabolism. Dose and whole blood cyclosporine Css(tough) observations measured using the enzyme-multiplied immunoassay technique (EMIT) (396 observations) or the TDx assay (435 observations) were collected as part of routine blood concentration monitoring from 182 patients who underwent cardiothoracic transplantation. Data were analyzed using a linear mixed-effects modeling approach to examine the effect of metabolic inhibitors on dose-rate-Css(trough) ratio. The mean (and 95% confidence interval) dose-rate-Css(trough) ratio for cyclosporine generated from concentrations measured using EMIT was 94 (82.5-105.5) Lh(-1) for patients administered cyclosporine alone, 66.7 (58.1-75.3) Lh(-1) for patients administered concomitant diltiazem, 47.9 (15.4 -80.4) Lh(-1) for patients administered concomitant itraconazole, 21.7 (14.8-28.5) Lh(-1) for patients administered concomitant ketoconazole, and 14.9 (11.8-18.1) Lh(-1) for patients concomitantly administered diltiazem and ketoconazole. For patients administered concomitant cyclosporine, ketoconazole, and diltiazem, the dosage of cyclosporine, if it is administered alone, should be 20% to achieve the same blood concentrations. This will allow safer drug concentration targeting of cyclosporine after cardiothoracic transplantation.

Advice on exercise from a family physician can help sedentary patients to become active

Objectives: To test the effectiveness, in the setting of primary health care, of verbal advice on exercise from a family physician (FP) combined with supporting written information. Design: A controlled trial with subjects allocated to a control group or one of two intervention groups using a balanced design based on day of the week. Setting: Ten general practices in Perth, Western Australia. Subjects: All sedentary patients consulting an FP. Intervention: Verbal advice on exercise from the FP and a pamphlet on exercise mailed to the patient's home address within 2 days of his/her visit to the doctor. Main outcome measure: Level of physical activity at followup. Results: 6,351 adult patients attending an FP practice completed a screening questionnaire, and 763 sedentary adults were recruited to the project. The response to follow-up, via a postal survey at 1, 6, and 12 months after the index consultation was 70%, 60%, and 57%, respectively. At 1 month a subsample of the control and intervention subjects were contacted for a telephone interview to verify self-reported levels of activity (n = 136). Treating all nonresponders as sedentary, at 1 month significantly more subjects in the combined intervention groups reported doing some physical activity (40%) compared with the control group (31%). Similarly, at 6 months, 30% of the control group and 38% of the combined intervention groups were now active. There was very little change at followup at 12 months (31% control and 36% intervention groups, respectively). Conclusion: A simple intervention aimed at the promotion of physical activity to sedentary patients in general practice can help reduce inactivity.

Population pharmacokinetics and pharmacodynamics: An underutilized resource

A meeting was convened in Canberra, Australia, at the request of the Australian Drug Evaluation Committee (ADEC), on December 3-4, 1997 to discuss the role of population pharmacokinetics and pharmacodynamics in drug evaluation and development. The ADEC was particularly concerned about registration of drugs in the pediatric age group. The population approach could be used more often than is currently the case in pharmacokinetic and pharmacodynamic studies to provide valuable information for the safe and effective use of drugs in neonates, infants, and children. The meeting ultimately broadened to include discussion about other subgroups. The main conclusions of the meeting were: 1. The population approach, pharmacokinetic and pharmacodynamic analysis, is a valuable tool both for drug registration purposes and for optimal dosing of drugs in specific groups of patients, 2. Population pharmacokinetic and pharmacodynamic studies are able to fill in the gaps' in registration of drugs, for example, to provide information on optimal pediatric dosing. Such studies provide a basis for enhancing product information to improve rational prescribing, 3. Expertise is required to perform the population studies and expertise, with a clinical perspective, is also required to evaluate such studies if they are to be submitted as part of a drug registration dossier Such expertise is available in the Australasian region and is increasing. Centers of excellence with the appropriate expertise to advise and assist should be encouraged to develop and grow in the region, 4. The use of the population approach by the pharmaceutical industry needs to be encouraged to provide valuable information not obtainable by other techniques. The acceptance of population pharmacokinetic and pharmacodynamic analyses by regulatory agencies also needs to be encouraged, and 5. Development of the population approach to pharmacokinetics and pharmacodynamics is needed from a public health perspective to ensure that all available information is collected and used to improve the way drugs are used. This important endeavor needs funding and support at the local and international levels.

The epidemiology of Parkinson's disease in an Australian population

A prevalence study of Parkinson's disease (PD) was conducted in the rural town of Nambour, Australia. There were 5 cases of PD in a study population of 1207, yielding a crude prevalence ratio of 414 per 100,000 (95% confidence interval; 53-775). We performed a separate case-control study involving 224 patients with FD and 310 controls from South East Queensland and Central West New South Wales, to determine which factors increase the risk for PD in Australia. A positive family history of PD was the strongest risk factor for the development of the disease (odds ratio = 3.4; p < 0.001). In addition, rural residency was a significant risk factor for PD (odds ratio = 1.8, p < 0.001). Hypertension, stroke and well water ingestion were inversely correlated with the development of PD. There was no significant difference between patients and controls for exposure to herbicides and pesticides, head injury, smoking or depression. The high prevalence of PD in Nambour may be explained by rural residency. However, the most significant risk factor for PD was a positive family history. This demonstrates the need for improved understanding of the genetic nature of the disease.

Unsupervised cell nucleus segmentation with active contours

The task of segmenting cell nuclei from cytoplasm in conventional Papanicolaou (Pap) stained cervical cell images is a classical image analysis problem which may prove to be crucial to the development of successful systems which automate the analysis of Pap smears for detection of cancer of the cervix. Although simple thresholding techniques will extract the nucleus in some cases, accurate unsupervised segmentation of very large image databases is elusive. Conventional active contour models as introduced by Kass, Witkin and Terzopoulos (1988) offer a number of advantages in this application, but suffer from the well-known drawbacks of initialisation and minimisation. Here we show that a Viterbi search-based dual active contour algorithm is able to overcome many of these problems and achieve over 99% accurate segmentation on a database of 20 130 Pap stained cell images. (C) 1998 Elsevier Science B.V. All rights reserved.

Insufficiently active Australian college students: Perceived personal, social, and environmental influences

Background. A sustainable pattern of participation in physical activity is important in the maintenance of health and prevention of disease, College students are in transition from an active youth to a more sedentary adult behavior pattern. Methods. We assessed self-reported physical activity and other characteristics in a sample of 2,729 male and female students (median age was 20 years) recruited from representative courses and year levels at four Australian College campuses. They were categorized as sufficiently or insufficiently active, using estimates of energy expenditure (kcal/week) derived from self-reported physical activity, Personal factors (self-efficacy, job status, enjoyment), social factors (social support from family/friends), and environmental factors (awareness of facilities, gym membership) were also assessed. Results. Forty-seven percent of females and 32% of males were insufficiently active. For females, the significant independent predictors of being insufficiently active were lower social support from family and friends, lower enjoyment of activity, and not working. For males, predictors were lower social support from family and friends, lower enjoyment of activity, and being older. Conclusions. Factors associated with physical activity participation (particularly social support from family and friends) can inform physical activity strategies directed at young adults in the college setting. (C) 1999 American Health Foundation and Academic Press.

Inactive Australian college students' preferred activities, sources of assistance, and motivators

Participation in regular physical activity reduces the risk of cardiovascular disease and all-cause mortality as well as providing numerous health benefits.' The steepest decline in physical activity occurs during adolescence (approximately 15 to 18 years of age) and young adulthood (20 to 25 years).(2) Australian population studies have found that levels of physical inactivity are twice as high for those 20 to 29 years old as they are for those under 20 years old.(3,4) As college students move through this period of changing roles within family and peer groups, they may be expected to have specific preferences and expected outcomes for physical activity participation that are different from those they had previously as high school students.(5) Studies of physical activity determinants suggest that while there are some similarities between males and females, there are differences in preferences for specific types of activity.(6) Calfas et al.(5) found that women reported body image factors (weight loss, dissatisfaction with body) to be more motivating, while young men rated strength (muscle gain, muscle tone) and social aspects (organized competition, meeting people) of physical activity more highly than did young women. We examined preferred physical activities, sources of assistance to be more active, and perceived motivators for activity in a sample of inactive college students. Differences between males and females were examined, and the implications for campus-based physical activity promotion strategies are considered.

Population balance model of in vivo neutrophil formation following bone marrow rescue therapy

In this paper, we develop a simple four parameter population balance model of in vivo neutrophil formation following bone marrow rescue therapy. The model is used to predict the number and type of neutrophil progenitors required to abrogate the period of severe neutropenia that normally follows a bone marrow transplant. The estimated total number of 5 billion neutrophil progenitors is consistent with the value extrapolated from a human trial. The model provides a basis for designing ex vivo expansion protocols.

Two-wave-mixing induced self-focusing in an active photorefractive oscillator

We derive a nonlinear wave equation for a signal beam which is coupled to a pump beam by two-wave-mixing in a photorefractive crystal. This equation describes self-focusing of the signal beam. We compare two-wave-mixing induced spatial self-focusing of single-pass experiments in a diffusion-type photorefractive crystal and of a photorefractive oscillator using the same crystal. We observe that the nonlinear refractive index change in the oscillator is decreased while increasing resonator losses.

Active site-directed protein regulation

Regulation of protein function is vital for the control of cellular processes. Proteins are often regulated by allosteric mechanisms, in which effecters bind to regulatory sites distinct from the active sites and alter protein function. Intrasteric regulation, directed at the active site and thus the counterpart of allosteric control, is now emerging as an important regulatory mechanism.