Educational booklet reinforces knowledge of osteoporosis and influences intentions to improve bone health in previously diagnosed and treated patients.

We examined individuals' experiences using an educational booklet developed by the Ontario Osteoporosis Strategy. The booklet appeared to motivate individuals to make changes to their existing management of their bone health and served as a reference tool reaffirming current practices and beliefs for others. INTRODUCTION: The purpose of this study was to examine individuals' experiences of the educational booklet and explore the influence of the booklet on individuals' beliefs and actions regarding their bone health. METHODS: Eligible individuals were those who had been prescribed medication to treat low bone mass. One-on-one telephone interviews were conducted over an 18-month period. Participants were interviewed for approximately 1 hour and asked to provide their feedback on the booklet, and to discuss what they were doing with respect to the recommendations made in the booklet. RESULTS: We interviewed 50 participants who ranged in age from 58 to 89. The overall impression of the booklet was positive. Participants described the language in the booklet as clear and easy to understand. Participants stated that they would have appreciated receiving this tool at the onset of their diagnosis. Forty-two participants had already taken action, or expressed an intention to make changes, to their existing routines to improve their bone health. In contrast, eight participants used the booklet to reaffirm current practices and beliefs. For these individuals, the recommendations made in the booklet were consistent with what they had already been doing. CONCLUSION: The booklet can engage patients in discussions about bone health. The booklet appeared to motivate individuals to make changes to their existing routines in an effort to achieve better health outcomes for their bone health. Providing a tool like this to people recently diagnosed with a bone health issue may prove to be beneficial.

Is a 'healthy diet' and a 'calcium-rich diet' the same thing? Qualitative study examining perceptions of a calcium-rich diet in individuals who have received bone health education.

BACKGROUND: In the present study, we aimed to (i) examine perceptions of achieving calcium and vitamin D recommended dietary allowance (RDA) and (ii) determine how participants talked about food in relation to RDA recommendations. METHODS: Participants aged ≥50 years who were prescribed osteoporosis medication and received two modes of bone health education were eligible. Relying on a qualitative description design, we interviewed participants 1 month after they had attended an education session and received a self-management booklet. Calcium and vitamin D intakes were estimated by in-depth questions about diet and supplements and compared with perceptions of achieved RDA levels. Interview transcripts were analysed based on an analytic hierarchical process. RESULTS: Forty-five participants (29 reporting previous fragility fractures) were included. Calcium and vitamin D RDA appeared to be potentially achieved by 64% and 93% of participants, respectively, primarily because of reliance on supplements. Few participants talked about vitamin D in relation to food intake and 49% of participants were unclear about the calcium content of food. Most considered that a healthy diet was equivalent to a calcium-rich diet. We noted no differences in our findings in the subset of individuals with fragility fractures. CONCLUSIONS: Despite reporting a prescription for osteoporosis medication and receiving bone health education, a substantial number of individuals appeared to have sub-optimal calcium levels. This may be attributed to the challenge of achieving RDA with diet alone and the misconception of a healthy diet as a calcium-rich diet.

Food groups and risk of forearm fractures in postmenopausal women in Chengdu, China.

BACKGROUND: Forearm fractures are a major cause of disability in postmenopausal women. However, no prior report on the relationship of dietary patterns and forearm fracture in mainland China is available and the results from Western studies may not be applicable to the Chinese population. OBJECTIVE: To determine whether food groups are associated with the risk of forearm fracture among postmenopausal women in China. Design Case-control study. METHODS: Cases were 209 postmenopausal women aged 50-70 years with new forearm fractures, identified in hospitals in Chengdu. Controls were age- and district-matched subjects randomly selected from the community of Chengdu. Dietary habits and food group intake were measured by a structured food frequency questionnaire. RESULTS: The dietary pattern in Chinese postmenopausal women was of high intakes of cereals, vegetables, fruits, beans or bean products, but lower intakes of meat and milk. The estimated odds ratios (95% confidence intervals) for forearm fracture were 0.53 (0.42-0.67) for each quintile increase in vegetable intake, 0.73 (0.59-0.92) for each quintile increase in cereal intake, and 0.26 (0.14-0.48) in subjects who met World Health Organization (WHO) dietary recommendations for vegetables and fruits. CONCLUSIONS: This is the first report indicating that the levels of vegetable and cereal intake, and that meeting WHO recommendations for vegetable and fruit intake, are associated with a decrease in the risk of forearm fractures in Chinese postmenopausal women.

Henrik Kacser--a neglected author?

All sciences progress by elaborating new concepts and by finding new relationships between the parts of a system of interacting components. Henrik Kacser, with a background in Biophysics and Genetics, was well placed to develop a new and comprehensive analysis of the control of metabolic fluxes and metabolite concentrations; and to demonstrate that changes in the concentration of normal metabolites were as important in Genetics as changes in the composition of metabolites in bringing about a change in trait.

Tea tree oil as an alternative topical decolonization agent for methicillin-resistant Staphylococcus aureus.

The combination of a 4% tea tree oil nasal ointment and 5% tea tree oil body wash was compared with a standard 2% mupirocin nasal ointment and triclosan body wash for the eradication of methicillin-resistant Staphylococcus aureus carriage. The tea tree oil combination appeared to perform better than the standard combination, although the difference was not statistically significant due to the small number of patients.

Development and validation of a calcium intake questionnaire for postmenopausal women in China.

PURPOSE: Develop and evaluate a food frequency questionnaire (FFQ) for assessing calcium intake in Chinese postmenopausal women. METHODS: An interviewer-conducted FFQ that asks respondents about their consumption of 110 calcium-containing foods over the previous week was developed and administered to 21 randomly selected postmenopausal women from Chengdu. This FFQ uses both the traditional weight-estimation method of assessing portion size in China and a new volume-estimation method. Test-retest reliability was assessed by re-administering the questionnaire two weeks later and validity was assessed by comparing the computed daily calcium intake to that obtained by a researcher-conducted 4-day food record. RESULTS: Estimates of calcium intake derived from the volume-estimation method were significantly lower than estimates derived from the traditional weight-estimation method (median calcium intakes = 270 mg/day versus 570 mg/day), but were quite similar to those obtained from the 4-day food record (median calcium intake = 275 mg/day). The test-retest reliability and validity of the volume-estimation method (intraclass correlation coefficient (ICC) = 0.73 and 0.86, respectively) were better than those of the weight-estimation method (ICC = 0.58 and 0.39, respectively). CONCLUSIONS: The reliability and validity of the traditional weight-estimation FFQ method of assessing dietary intake of nutrients in China is poor; this method may significantly overestimate dietary intakes. The proposed volume-estimation FFQ method for assessing calcium intake is a simple, interviewer-conducted method that is both reliable and valid. The calcium intake of postmenopausal women in urban China is much lower than the recommended daily allowance of 800 mg.

Prevalence of rheumatic heart disease among school children in Addis Ababa.

OBJECTIVE: To determine the prevalence of rheumatic heart disease (RHD), and the impact of potential risk factors on its occurrence among school children in Addis Ababa. DESIGN: Cross-sectional survey of school children for the presence or absence of RHD. SETTING: Randomly selected ten government and five private schools from the list of all government and private schools in Addis Ababa teaching grades 7 and 8. SUBJECTS: All school children attending grades 7 and 8 in the randomly selected schools. MAIN OUTCOME MEASURES: Clinical findings suggestive of RHD confirmed by echocardiographic and Doppler studies. RESULTS: Out of the 10,053 school children selected for the study 9,388 (93%) were examined. Sixty of the 9,388 school children examined were subsequently confirmed to have RHD giving an overall prevalence rate of 6.4 per 1000 children. The prevalence for government and private schools representing low and high socio-economic groups were 7.1 and 1 per 1000 children respectively (Fisher's exact = 0.019). Crowding conditions at home, in schools and in the bedrooms were not associated with the risk of RHD (chi 2 = 4.968; p > or = 0.174). CONCLUSION: This study confirmed that the prevalence of RHD, at least in the low socio-economic group is among the highest in the world. This evidence highlights the need for an urgent control programme.

The cross cultural context of obesity: an INCLEN multicentre collaborative study.

Associations between obesity and cardiovascular disease have been documented in the Developed World and have been linked with levels of 'development' in Developing World countries. This study aimed to explore the sociocultural influences on attitudes towards obesity, physical activity and dietary change using a four level conceptual framework (from personal to societal influences). Focus group discussions were conducted in: India, Indonesia, Cameroon, Egypt and Australia. The results of these discussions were analysed to reveal emergent themes. The interpretation of the qualitative data emphasised the need to incorporate influences beyond the individual in efforts to reverse or prevent obesity related disease.

Rheumatic heart disease among school children in Addis Ababa City: awareness and adequacy of its prophylaxis.

One of the objectives of this large scale cross-sectional study of school children of the Addis Ababa city was to assess the status of rheumatic heart disease (RHD) prophylaxis among rheumatic heart disease patients identified during the survey. Awareness about the presence of the illness in those affected and reasons for poor coverage, when detected, were also assessed. Sixty of the 9388 school children surveyed were found to have rheumatic heart disease. On interviewing parents of the children with rheumatic heart disease, ten acknowledged being informed of their children's cardiac illness. Of these parents, 15% (or 9/60) had some idea that their children had heart disease related to some form of infection. However, only two of the nine (22%) children whose parents had some idea about their disease were on regular monthly benzathine penicillin prophylaxis in the previous 12 months preceding the interview. Three (33%) of the nine children had six or fewer injections in the 12 months preceding the interview. The remaining 4 parents (44%) reported that their children took treatment that included injections only at the time of initial diagnosis several years earlier and had not had any follow up since then. Their reasons for not seeking medical care for their children included lack of information on prophylaxis, inability to pay for the treatment and distance of the health facilities. The lack of awareness and the extremely low rate of regular prophylaxis, therefore, highlight the need for an urgent control programme that takes active case detection, treatment access and health education into consideration.

Back pain in Australian military helicopter pilots: a preliminary study.

BACKGROUND: Several studies have highlighted the problem of back pain among helicopter pilots, but few have controlled for potential confounding factors in their analyses, or sought to examine the effects of back pain on operational readiness and flying performance. There have been no previous studies of the prevalence of back pain among Australian military pilots. METHODS: The prevalence, risk factors, and consequences of low back pain were assessed in a cross-sectional survey of 200 Australian military helicopter pilots by self-completion questionnaire. RESULTS: Responses were received from 131 (66%) of available pilots. The overall prevalence of reported back pain was 64% (95% CI 56%-72%), with a further 28% of pilots describing back discomfort while flying. More than half the pilots (55%) indicated that back pain had interfered with their concentration while flying, with 16% reporting that they had hurried flying missions because of pain. A minority of pilots (7%) had refused to fly because of back problems. After adjusting for age, education, BMI, posture and numbers of hours flown, multiple logistic regression modelling indicated that a prior history of back injury was the most significant predictor of back pain among rotary wing pilots (OR 2.63, 95% CI 1.11-6.23). CONCLUSIONS: We conclude that the prevalence of back pain in Australian military helicopter pilots is unacceptably high and may be limiting operational readiness, pilot performance, flying safety, and pilot health. Urgent attention needs to be given to improved ergonomic design in aircraft, and both back pain prevention and back injury rehabilitation programs.

Predictors of mortality in children hospitalized with dysentery in Harare, Zimbabwe.

OBJECTIVES: To document the pattern of complications and identify risk factors for subsequent mortality in a hospitalized paediatric population during a Shigella dysenteriae type 1 epidemic. DESIGN: Hospital based prognostic study. SETTING: Paediatric wards in Harare and Parirenyatwa tertiary referral hospitals. SUBJECTS: All children aged one month to 12 years admitted to the wards with a history of bloody diarrhoea between January 1993 to June 30 1994 were included in the study (n = 312). MAIN OUTCOME MEASURES: Patterns of complications and predictors of mortality. RESULTS: The peak age group of the patients was 12 to 23 months. Ninety five children died giving an overall case fatality rate (CFR) of 30.4% (95% CI, 25.3 to 35.6). One third (n = 107) had haemolytic uraemic syndrome (HUS), among whom the CFR was 43%. Other complications included altered consciousness (35%), seizures (12%), coma (4.5%), severe dehydration (14%), abdominal distention (17%), rectal prolapse (5%) and ileus (6%). In a multivariate analysis, temperature < 36 degrees C (OR 2.12; 95% CI, 1.33 to 3.39), severe dehydration (OR, 1.70; 95% CI, 1.15 to 2.53), hyperkalemia (> 5.5 mmol/L) (OR, 1.74; 95% CI, 1.01 to 1.97), hyponatremia (< 120 mmol/L) (OR, 1.57; 95% CI, 1.17 to 2.11), urea (> 8 mmol/L) (OR, 1.74; 95% CI, 1.29 to 2.36), and abdominal distention (OR, 1.67; 95% CI, 1.16 to 2.41) were found to be predictors of mortality. CONCLUSION: Some of the major clinical and laboratory features allowing the early identification of children at increased risk of dying during dysentery outbreaks have been delineated. The high fatality associated with complicated dysentery highlights the need for preventive strategies which are sustainable in the region.

Management of childhood gastroenteritis in the community.

OBJECTIVE: To examine general practitioners' (GPs') management of childhood gastroenteritis and their perceptions about barriers to optimal management in the community. DESIGN: Cross-sectional postal survey in which GPs' self-reported practices were assessed by a paediatric gastroenterologist for compliance with published guidelines. SETTING: Hunter region of NSW, mid 1994. PARTICIPANTS: All 422 urban and rural GPs practising in the Hunter region were sent questionnaires; 289 (243 urban and 46 rural) GPs responded. RESULTS: Nearly all GPs (97%) recommended clear fluids in the management of childhood gastroenteritis, with 195 (67%) recommending oral electrolyte solution. Management practices were assessed as: optimal, 170 GPs (59%); acceptable, 33 GPs (11%); inappropriate or potentially dangerous, 38 GPs (13%); and too vague to classify, 48 GPs (17%). Multiple logistic regression analysis showed that better management strategies were associated with being younger and practising in rural areas. GPs perceived the main barriers to effective management of gastroenteritis were: inadequate parenting skills, 131 GPs (45%); lack of parental understanding about the illness, 118 GPs (41%); other social problems, 67 GPs (23%); parental anxiety, 57 GPs (20%); and conflicting advice given by others, 42 GPs (15%). Only 33 GPs (11%) identified the taste and 16 (6%) the cost of oral electrolyte solution as major barriers. CONCLUSIONS: Most GPs reported management of gastroenteritis was acceptable, although not necessarily optimal. GPs need to ensure that parents fully understand the nature of their child's illness and their recommendations for management at home.

Whose diet has changed?

The same questions about diet were asked in two community-based surveys conducted in the Hunter Region of New South Wales in 1983 and 1994. There were substantial changes in diet over the period; for example, the proportion of respondents who reported using low-fat or skim milk increased from 25 per cent to 51 per cent, the proportion eating meat fewer than five times a week doubled from 21 per cent to 42 per cent and the proportion eating fewer than three eggs per week increased from 55 per cent to 80 per cent. In both surveys, women reported eating a healthier diet than men, and older people and those of higher socioeconomic status reported better diets than younger people or people with less education or lower status occupations. The surprising finding was that over the 11-year period the changes in patterns of food consumption were remarkably similar across all strata of the population. The conclusions are that wide-spread dietary change is possible. However, the changes in the last decade related mainly to reducing the risk of cardiovascular disease; similar behavioural changes to reduce the risk of diet-related cancer are required.

Dietary trends: estimates from food supply and survey data.

OBJECTIVE: To illustrate methodological issues involved in estimating dietary trends in populations using data obtained from various sources in Australia in the 1980s and 1990s. METHODS: Estimates of absolute and relative change in consumption of selected food items were calculated using national data published annually on the national food supply for 1982-83 to 1992-93 and responses to food frequency questions in two population based risk factor surveys in 1983 and 1994 in the Hunter Region of New South Wales, Australia. The validity of estimated food quantities obtained from these inexpensive sources at the beginning of the period was assessed by comparison with data from a national dietary survey conducted in 1983 using 24 h recall. RESULTS: Trend estimates from the food supply data and risk factor survey data were in good agreement for increases in consumption of fresh fruit, vegetables and breakfast food and decreases in butter, margarine, sugar and alcohol. Estimates for trends in milk, eggs and bread consumption, however, were inconsistent. CONCLUSIONS: Both data sources can be used for monitoring progress towards national nutrition goals based on selected food items provided that some limitations are recognized. While data collection methods should be consistent over time they also need to allow for changes in the food supply (for example the introduction of new varieties such as low-fat dairy products). From time to time the trends derived from these inexpensive data sources should be compared with data derived from more detailed and quantitative estimates of dietary intake.

In vitro evaluation of temozolomide combined with X-irradiation.

The in vitro cytotoxicity of 8-carbamoyl-3-methylimidazo [5,1-d]-1,2,3,5-tetrazine-4(3H)-one (temozolomide) with concurrent X-irradiation was examined in a human glioblastoma cell line (U373MG) as a potential radio-chemotherapeutic treatment for malignant glioma. The combination was also examined in a human colorectal adenocarcinoma (Mawi) which had 100-fold greater O6-alkylguanine-DNA alkyltransferase (AGT) activity, a DNA-repair protein which confers resistance to temozolomide. A comparison of IC50 values indicated U373MG to be over 32-fold more sensitive to temozolomide than Mawi, but slightly more resistant to X-irradiation (p < 0.035; unpaired two-tailed t-test). Temozolomide and X-irradiation proved largely additive in U373MG by isobologram analysis (50% iso-effect) and the addition of 10 microM temozolomide to 1-2 Gy of X-irradiation increased cell kill by 2.5- to 3.0-fold. However, the combination was antagonistic in Mawi: an effect attributed to AGT induction by X-irradiation as the antagonism was removed by co-incubation with the AGT inhibitor O6-benzylguanine (O6-BG 1 microM; 24 h). O6-BG did not affect the radiation dose-response curve, but significantly increased temozolomide cytotoxicity (p < 0.015). In conclusion, the combination of temozolomide with radiation is at best additive, but could nonetheless by of considerable therapeutic benefit in glioma, particularly if administered for prolonged periods. If AGT induction compromises the efficacy of this therapy, it may be circumvented with an appropriate inhibitor such as O6-BG.

Effect of single and multiple administration of an O6-benzylguanine/temozolomide combination: an evaluation in a human melanoma xenograft model.

The purpose of the present study was to examine the effect of O6-benzylguanine (O6-BG) on the antitumour activity and toxicity of 8-carbamoyl-3-methylimidazo [5, 1-d]-1,2,3,5-tetrazine-4(3H)-one (temozolomide) in a human malignant melanoma xenograft model following single and multiple administration of the combination. O6-BG irreversibly inactivates the DNA-repair protein O6-alkylguanine-DNA alkyltransferase (AGT), which confers resistance to temozolomide. Preadministration of O6-BG (35 mg/kg, i.p.) 1 h prior to temozolomide (i.p.) was examined using single and daily x5 dosing regimens in athymic mice bearing subcutaneous A375P xenografts. The AGT activity of A375P tumors was 95 +/- 8 fmol/mg protein (mean +/- SE, n = 4). O6-BG alone completely suppressed xenograft AGT activity within 1 h of administration but had no effect upon tumor growth. O6-BG did not significantly increase the tumor growth delay induced by a single 200-mg/ kg dose of temozolomide (P > 0.05, two-tailed Mann-Whitney test) but did increase the associated mean body weight loss (P < 0.025). In contrast, when the same dose of temozolomide was divided into five equal fractions (40 mg/kg) and given with O6-BG on 5 consecutive days, a comparable increase in toxicity was accompanied by a very significant increase in tumor growth delay (P < 0.0025), equivalent to that produced by a 3-fold greater dose of temozolomide alone. O6-BG with temozolomide also produced a greater antitumour effect than an equitoxic dose of temozolomide alone on this schedule (P < 0.005). These data indicate that the enhancement of temozolomide antitumour activity by O6-BG preadministration is dependent upon the schedule of drug administration, with multiple dosing of O6-BG + temozolomide producing the greatest effect. The results also suggest that prolonged administration of the combination can lead to an increase in the therapeutic index of temozolomide.

Feed us nutrition: final year medical students' perceptions of nutrition medical education.

BACKGROUND: Nutrition is recognised as an integral aspect of Australian medical education. Since medical students will learn more of a subject they consider important, there is a need for their perceptions of nutrition to be investigated. AIMS: To identify final year medical students' perceptions about nutrition and its inclusion in their medical course, and to compare priority nutrition topics identified with those previously identified by Faculty and General Practitioners (GPs) who teach in the undergraduate curriculum. METHODS: A cross-sectional survey of all final year medical students attending the University of Newcastle was conducted, using a distributed questionnaire, comprising three sections: demographics, perceptions about nutrition and its inclusion in the medical course, and a listing of 38 major nutrition topics. Main outcome measures were: interest in nutrition, and whether it should be included in the undergraduate medical curriculum; rated importance of listed nutrition topics; comparison between students and Faculty and GPs. Frequency distributions and Chi square analyses were used to compare group responses. RESULTS: Seventy-one per cent of the students were interested in nutrition and 94% believed it should be included in the medical curriculum. More than 60% of the students nominated 21 of the 38 topics, essential or important. Thirteen of these topics were also highly rated by Faculty and GPs, although Faculty and GPs rated more topics as essential or important. CONCLUSIONS: Newcastle medical students are interested in nutrition and believe it should be included in their medical curriculum. This may be due to their clinical exposure and the educational milieu of the University of Newcastle Medical School. Exposure to nutrition in their undergraduate education appears to be an important determinant for priority designated nutrition topics.

3-aminobenzamide and/or O6-benzylguanine evaluated as an adjuvant to temozolomide or BCNU treatment in cell lines of variable mismatch repair status and O6-alkylguanine-DNA alkyltransferase activity.

O6-benzylguanine (O6-BG) and 3-aminobenzamide (3-AB) inhibit the DNA repair proteins O6-alkylguanine-DNA alkyltransferase (AGT) and poly(ADP-ribose) polymerase (PARP) respectively. The effect of O6-BG and/or 3-AB on temozolomide and 1,3-bis(2-chloroethyl)-nitrosourea (BCNU) cytotoxicity, was assessed in seven human tumour cell lines: six with an AGT activity of > 80 fmol mg-1 protein (Mer+) and one with an AGT activity of < 3 fmol mg-1 protein (Mer-). Three of the Mer+ cell lines (LS174T, DLD1 and HCT116) were considered to exhibit resistance to methylation by a mismatch repair deficiency (MMR-), each being known to exhibit microsatellite instability, and DLD1 and HCT116 having well-characterised defects in DNA mismatch binding. Potentiation was defined as the ratio between an IC50 achieved without and with a particular inhibitor treatment. Temozolomide or BCNU cytotoxicity was not potentiated by either inhibitor in the Mer- cell line. Preincubation with O6-BG (100 microM for 1 h) was found to potentiate the cytotoxicity of temozolomide by 1.35- to 1.57-old in Mer+/MMR+ cells, but had no significant effect in Mer+/MMR- cells. In comparison, O6-BG pretreatment enhanced BCNU cytotoxicity by 1.94- to 2.57-fold in all Mer+ cell lines. Post-incubation with 3-AB (2 mM, 48 h) potentiated temozolomide by 1.35- to 1.59-fold in Mer+/MMR+ cells, and when combined with O6-BG pretreatment produced an effect which was at least additive, enhancing cytotoxicity by 1.97- to 2.16-fold. 3-AB treatment also produced marked potentiation (2.20- to 3.12-fold) of temozolomide cytotoxicity in Mer+/MMR- cells. In contrast, 3-AB produced marginal potentiation of BCNU cytotoxicity in only three cell lines (1.19- to 1.35-fold), and did not enhance the cytotoxicity of BCNU with O6-BG treatment in any cell line. These data suggest that the combination of an AGT and PARP inhibitor may have a therapeutic role in potentiating temozolomide activity, but that the inhibition of poly(ADP-ribosyl)ation has little effect on the cytotoxicity of BCNU.

Dominance--one hundred and fifteen years after Mendel's paper.

In The Molecular Basis of Dominance, Kacser & Burns (1981) demonstrated that dominance in diploids and polyploids, and pleiotropy in all organisms, were biochemical phenomena; they were the consequences of the response of a metabolic system to a genetically specified change in the activity of any one enzyme within the system. Epistasis was similarly explicable when each of at least two enzyme activities suffered a change. The significance of this achievement by Kacser & Burns (1981) for biochemistry, genetics, molecular biology, medicine and bio-technology is best seen against the background of 115 years of attempts to explain the origins of dominance.