Severity and persistence of asthma and mental health: a birth cohort study.

BACKGROUND: The goal of the current study was to investigate asthma and mental health among youth in the community, and to consider the role of asthma severity and persistence in this link. Method Data were drawn from the Raine Study, a population-based birth cohort study in Western Australia. Logistic regression models and generalized estimating equations were used to examine the relationship between asthma at age 5 years and the range of internalizing and externalizing mental health problems at ages 5-17 years. Analyses were stratified by asthma severity and persistence, and adjusted for a range of potential confounders. RESULTS: More severe and persistent asthma at age 5 was associated with significantly increased odds of affective, anxiety, somatic, oppositional defiant and conduct problems at ages 5-17. Mild asthma and remitted asthma were not associated with heightened vulnerability to mental disorders. CONCLUSIONS: Our results suggest that youth with symptomatic asthma are more likely to suffer from a wide range of mental health problems, and that the likelihood of mental health problems appears to increase as a function of asthma severity. Youth with poorly controlled and/or more severe and persistent asthma may be considered a vulnerable group who might benefit from mental health screening in clinical, school and community settings.

Associations between aggressive behaviour scores and cardiovascular risk factors in childhood.

OBJECTIVE: To examine the influence of aggressive behaviour scores on cardiovascular disease (CVD) risk factors throughout childhood. METHODS: This study utilized cross-sectional and longitudinal data from the Western Australian Pregnancy Cohort (Raine) Study (n = 2900). Aggressive behaviour scores were derived from the Child Behavior Checklist/4-18(CBCL), Youth Self-Report/11-18 (YSR) and Teacher Report Form/6-18 (TRF). CVD risk factors included body mass index (BMI), blood pressure, fasting lipids and homeostasis model of insulin resistance (HOMA-IR). RESULTS: Girls with higher aggressive behaviour scores had higher BMI from 10 years of age (P ≤ 0.001), higher BMI trajectories throughout childhood (P = 0.0003) and at 14 years higher HOMA-IR (P = 0.008). At the 14-year survey, this equated to a difference of 1.7 kg/m2 in the predicted BMI between the extreme CBCL scores in girls (top 5% (CBCL ≥ 17) vs. CBCL score = 0). Boys with higher aggressive behaviour scores had higher BMI at 5 years (P = 0.002), lower diastolic pressure at 14 years (P = 0.002) and lower systolic blood pressure trajectories throughout childhood (P = 0.016). CONCLUSION: Aggressive behaviour influences BMI from early childhood in girls but not boys. If this association is causal, childhood offers the opportunity for early behavioural intervention for obesity prevention.

Maternal and umbilical cord androgen concentrations do not predict digit ratio (2D:4D) in girls: a prospective cohort study.

Digit ratio (2D:4D) is widely used as a marker of prenatal androgen exposure. However, there are no published prospective studies where prenatal androgen exposure has been measured and correlated with digit ratio in adult life. We aimed to establish the prospective relationship between prenatal androgen exposure in the second and third trimesters of pregnancy (as measured by maternal circulating androgen concentrations and umbilical cord androgen concentrations) and digit ratio in adolescent girls. Androgen concentrations (testosterone, free androgen index, androstenedione, DHEAS) and sex hormone binding globulin (SHBG) were measured in stored plasma samples from pregnant mothers at 18 (n=118) and 34/36 (n=114) weeks of gestation and in cord blood (n=82) from the Western Australian Pregnancy (Raine) Cohort Study (www.rainestudy.org.au). Digit ratio was measured in 244 female offspring from this cohort at age 14-16 years. Only one borderline statistically significant correlation between maternal circulating androstenedione levels at 18 weeks of gestation and left hand digit ratio was seen. No other statistically significant relationship between maternal androgen concentrations or umbilical cord androgen concentrations and digit ratio in adolescence were observed. These findings suggest that variation in 2D:4D in girls is not established as a result of testosterone concentrations in the second and third trimesters. We conclude that prenatal androgen exposure as measured by maternal circulating androgen concentrations at 18 and 34/36 weeks of gestation or in the umbilical cord at birth may not predict digit ratio in girls.

Neighbourhood socioeconomic status and maternal factors at birth as moderators of the association between birth characteristics and school attainment: a population study of children attending government schools in Western Australia.

BACKGROUND: This article investigates whether reading and writing skills among children of equivalent perinatal characteristics differ by neighbourhood socioeconomic status and maternal factors. METHODS: Notifications of births for all non-Aboriginal singletons born in 1990-7 in Western Australia subsequently attending government primary schools were linked to the State literacy tests in grade three and with information on socioeconomic status of the school and the residential area. Using multilevel modelling, the associations between birth characteristics (gestational age, intrauterine growth, birth order and Apgar score at 5 minutes) and literacy attainment in grade three were examined in models that included socioeconomic and demographic factors of the child, mother and community. RESULTS: Higher percentages of optimal head circumference and birth length and term birth were positively and independently associated with literacy scores. A higher percentage of optimal birth weight was associated with higher reading scores especially for children born to mothers residing in educationally advantaged areas. First birth was positively associated with reading and writing attainment: this association was stronger for children born to single mothers and additional advantage in writing was also associated with first birth in children living in disadvantaged areas. CONCLUSIONS: These findings suggest that having suboptimal growth in utero or an older sibling at birth increases vulnerability to poor literacy attainment especially among children born to single mothers or those in disadvantaged neighbourhoods. These data provide evidence for advocating lifestyles compatible with optimum fetal growth and socioeconomic conditions conducive to healthy lifestyles, particularly during pregnancy.

Preparation and properties of an alpha-1-protease inhibitor concentrate with high specific activity.

BACKGROUND AND OBJECTIVES: Because the current demand for alpha-1-protease inhibitor (A1PI) exceeds the available supply, we aimed to develop a process for purification of A1PI from plasma which would achieve the highest possible degree of purity, specific activity and yield. MATERIALS AND METHODS: A1PI was purified from Cohn fraction IV-1,4 using ethanol precipitation and Q-Sepharose chromatography. Ceramic hydroxyapatite chromatography was used as a final purification step. Two independent virus-inactivation procedures (chemical and vapour heating) were applied. RESULTS: The resulting A1PI had an unprecedented high specific activity. In addition, the process led to the discovery of a new isoform of A1PI in isoelectric focusing gels. CONCLUSION: The high specific activity of the A1PI preparation achieved with this process should allow a reduction of the A1PI total protein load necessary to achieve clinically relevant effects.

Phase II study of weekly 24-hour intra-arterial high-dose infusion of 5-fluorouracil and folinic acid for liver metastases from colorectal carcinomas.

BACKGROUND: A multicenter phase II trial was initiated in order to evaluate the weekly, high-dose 24-hour infusion of 5-fluorouracil (5-FU) plus folinic acid (FA) in patients with unresectable colorectal cancer hepatic metastases. PATIENTS AND METHODS: A weekly hepatic arterial infusion (HAI) of FA 500 mg/m2 followed by a 24-hour infusion of 5-FU 2,600 mg/m2 (later reduced to 2,200 mg/m2) was given via a surgically implanted intra-arterial port system. One treatment cycle consisted of six weekly applications followed by a two-week rest period. Toxicity was assessed according to the WHO criteria. Chemotherapy was continued until disease progression or complete response occurred. RESULTS: A total of 50 patients (40 chemonaive, 10 pre-treated) entered this trial. An objective tumor response occurred in 28 patients (56%), while 13 patients (26%) had stable disease. The median progression free survival was 12 months, and the median survival 22.3 months. Due to a high rate of gastrointestinal side-effects in the initial phase of the trial, the dosage of 5-FU was reduced to 2,200 mg/m2 for all subsequent patients. Diarrhea and nausea led to a dose reduction in 40% of applications and 24% of patients, respectively. One patient died of cardiac insufficiency unrelated to chemotherapy before response evaluation. CONCLUSIONS: This HAI approach using high-dose 5-FU was relatively well tolerated when 2,200 mg/m2 instead of 2,600 mg/m2 was used. The activity of this regimen is promising and warrants further evaluation and modification.

Australian medical patents granted in the United States in 1984-1999.

OBJECTIVE: To describe all medical patents granted in the United States to Australian-resident inventors between 1984 and 1999. DATA SOURCES: All patent data originated from the US Patent and Trademark Office. Data for 1984-1994 were compiled by CHI Research Inc, and data for 1995-1999 were obtained from the Community of Science website. MAIN OUTCOME MEASURES: Number of medical patents granted in the US to Australian-resident inventors; assignees (owners) of these medical patents; proportion of these medical patents related to biotechnology. RESULTS: From 1984 to 1999, 7835 utility patents were granted in the US to Australian-resident inventors. Of these, 1308 patents (17%) were identified as medical patents; 489 (37%) of these were biotechnology patents. Medical patents account for an increasing proportion of all US patents granted to Australian inventors, increasing from 10% in 1984 to 25% in 1999. Biotechnology accounted for an increasing proportion of medical patents, rising from 10% to 55% between 1984 and 1999. More than half the medical patents are owned by commercial interests, and 33% by only 14 organisations, six of which are universities and their affiliated institutions. CONCLUSION: Only a few organisations account for most of the patenting of medical technology. The inventors and their organisations listed on medical patents could be canvassed when developing government policy and targeted for support in commercialising their medical technology.

Should there be more teaching of critical thinking in Australian general practice?

For clinicians such as GPs, critical thinking includes critical appraisal of scientific evidence and the context of their clinical practice, and critical introspection. Largely due to a lack of rigorous research, there is no evidence that teaching critical thinking or appraisal, at undergraduate or postgraduate levels, improves GPs' clinical performance or their patients' health. Before conducting such research, a systematic review of the available literature (largely in education and psychology) is warranted to assess the efficacy of teaching critical thinking in non-medical environments. Critical thinking is being taught in Australian medical schools and will be introduced in the RACGP Training Program. However, it will be a while before this will have an impact in GPs' surgeries. The challenge will be to design an attractive CME program relevant to GPs while simultaneously evaluating its efficacy.

Tumor promoters in commercial indoor-plant cultivars of the Euphorbiaceae.

Certain decorative indoor-plant cultivars are derived from toxic wild plant species. Native members of the Euphorbiaceae (spurge) contain highly irritating and tumor-promoting diterpene esters. Plant breeders and gardeners are constantly searching for less toxic cultivars of the popular Euphorbiaceae indoor plants. In this investigation, 22 commercial cultivars of Euphorbiaceae indoor plants were examined for tumor promoter contents by high-performance liquid chromatography (HPLC). Cultivars of E. milii (E. lomii hybrids), and in particular E. leuconeura, contained ingenol derivatives, whereas cultivars of E. pulcherrima and Codiaeum variegatum were devoid of these compounds. Tumor-promoting activity was assessed by induction of a luciferase reporter gene, which was placed under the control of an Epstein-Barr virus early antigen promoter. The response was closely correlated with ingenol ester content; the latex of the two E. leuconeura cultivars tested gave the strongest response. The HPLC and bioassay methods used in this study provide a basis for the development of nontoxic indoor-plant cultivars and perhaps for consumer-oriented labeling.

Tumor promoting diterpenes from Euphorbia leuconeura L.

Diterpene esters of the phorbol and ingenol types are known to be highly active tumor promoting agents that typically occur in members of the Euphorbiaceae. In the present work, Euphorbia leuconeura, a rare indoor plant, is analyzed for its tumor promoting potential. Latex as well as total leaf extracts exhibited Epstein-Barr-virus (EBV) inducing activity comparable to 12-O-tetradecanoyl-phorbol-13-O-acetate, a well known tumor promoter. The activity of individual fractions correlated with their ingenol ester content. Three ingenol esters with EBV inducing activity could be isolated and identified. They belong to the milliamine type of diterpene esters that contain aromatic peptidyl groups. Two of them (milliamines L and M) are already known from E. milii. The third compound is identified as an isomer of milliamine F with a novel 3,20-diester arrangement. The data show a close relationship between E. leuconeura and the more popular indoor plant E. milii whose latex is also used as a powerful molluscicide.

Prevalence of abdominal aortic aneurysms in men with diabetes.

OBJECTIVE: To assess the prevalence of abdominal aortic aneurysm (AAA) in men with diabetes aged 60 years and over. DESIGN: Prospective screening study. PATIENTS: 303 eligible participants among the first 1000 recruited to a large, community-based study of diabetes. MAIN OUTCOME MEASURES: Aortic diameter > or = 30 mm on screening ultrasonography, or previous surgery for AAA. RESULTS: AAA was diagnosed in three of the 303 men screened, and four others had previously had surgery for AAA. The aorta was not visualised in three obese men. Only one AAA required surgery (> or = 50 mm diameter). The overall prevalence of AAA was 2.3% (7/300), lower than that reported previously in the general population. Multivariate logistic regression analysis showed statistically significant associations with fasting triglyceride levels, and a history of intermittent claudication. CONCLUSIONS: Although a small number of men with diabetes aged 60 or more have undiagnosed AAA, the prevalence does not appear to be high enough to warrant targeted ultrasound screening.

Falling incidence of amputations for peripheral occlusive arterial disease in Western Australia between 1980 and 1992.

OBJECTIVES: To assess temporal trends in the incidence of surgical procedures for peripheral occlusive arterial disease (POAD) and associated changes in outcome as measured by the rate of major lower limb amputations for POAD. DESIGN: A retrospective descriptive population-based study was conducted of the geographically isolated population of Western Australia between 1980 and 1992. METHODS: Vascular procedures with an accompanying diagnosis of POAD were identified in a computerised system of name-identified records of all discharges from hospital for the population. These procedures were detected using relevant codes from the International Classification of Diseases and Procedures. Records of angioplasty and thrombolysis procedures were augmented by searches of hospital-based registers of invasive radiological procedures. The data for the remaining procedures were validated by a review of a random sample of medical records. RESULTS: Over the 13 years of the study, rates of major amputations fell significantly for women under 70 years of age and for men under 80 years from 1983. At the same time there was a significant fall in non-amputation vascular surgery for individuals under the age of 60. In addition, rather than an overall rise in surgery there was shift away from sympathectomy and thromboendarterectomy to angioplasty and bypass surgery. Furthermore, an increasing proportion of all major amputations had a prior attempt at arterial reconstruction. CONCLUSION: These observations suggest the decrease in major amputations for POAD may reflect a fall in the incidence of POAD, possibly aided by more effective surgery, rather than increased rates of vascular surgery.

The effect of hormone replacement therapy on prognostic indices in women with breast cancer.

OBJECTIVE: To examine the effect of hormone replacement therapy (HRT) on breast cancer biology. PATIENTS: Four hundred and sixty Western Australian women with breast cancer who were 40 years or over at the time of their breast cancer surgery. DESIGN AND SETTING: A questionnaire was sent to women seeking information on the use of HRT before breast cancer surgery. To qualify as HRT users, HRT had to have been used continuously for six months or more up to within two weeks of surgery. MAIN OUTCOME MEASURES: Biochemical indices of oestrogen receptor, progesterone receptor, cathepsin D and protein levels, and pathological indices of tumour size, tumour differentiation and lymph node involvement for users and nonusers of HRT. RESULTS: Eighty-seven per cent of questionnaires were recovered and 39 HRT users and 258 non-users were analysed. Twenty-five HRT users used a combination of oestrogen and progestogen and 14 used oestrogen only. Twenty-six had used HRT for more than two years and 13 for two years or less at the time of breast cancer diagnosis. There were no significant differences in the tumour indices between these two groups. The mean level of oestrogen receptors appeared to be lower in oestrogen-only users than in combination HRT users and non-users. The mean cathepsin D level was significantly higher in oestrogen-only users than in non-users. The percentage of all HRT users with involved lymph nodes (23%) was significantly lower than the percentage of non-users (44%). CONCLUSION: Oestrogen-only HRT may have a detrimental effect on tumour biology. The use of a progestogen in combination with oestrogen may offer some protection. On the other hand, HRT users had less lymph node involvement with tumour. This may reflect early detection with increased surveillance in women using HRT.

ApcMin, a mutation in the murine Apc gene, predisposes to mammary carcinomas and focal alveolar hyperplasias.

ApcMin (Min, multiple intestinal neoplasia) is a point mutation in the murine homolog of the APC gene. Min/+ mice develop multiple intestinal adenomas, as do humans carrying germ-line mutations in APC. Female mice carrying Min are also prone to develop mammary tumors. Min/+ mammary glands are more sensitive to chemical carcinogenesis than are +/+ mammary glands. Transplantation of mammary cells from Min/+ or +/+ donors into +/+ hosts demonstrates that the propensity to develop mammary tumors is intrinsic to the Min/+ mammary cells. Long-term grafts of Min/+ mammary glands also gave rise to focal alveolar hyperplasias, indicating that the presence of the Min mutation also has a role in the development of these lesions.

Compact holographic camera without vibration insulation using a 670-nm semiconductor laser.

A compact camera for holography and holographic interferometry is presented. Owing to its simple and rigid construction, vibration insulation is not necessary. The use of a semiconductor laser with a wavelength of 670 nm permits the use of common holographic recording materials. The only optical components of this camera are a beam splitter and a deflection mirror. As an example of the application of this camera, holographic surface contouring is demonstrated.

Co-ordinate control of synthesis of mitochondrial and non-mitochondrial hemoproteins: a binding site for the HAP1 (CYP1) protein in the UAS region of the yeast catalase T gene (CTT1).

Control of expression of the Saccharomyces cerevisiae CTT1 (catalase T) gene by the HAP1 (CYP1) gene, a mediator of heme control of mitochondrial cytochromes, was studied. Expression of a CTT1-lacZ fusion in a hap1 mutant showed that the CTT1 promoter is under HAP1 control. As demonstrated by a gel retardation assay, the HAP1 protein binds to a heme control region of the CTT1 gene. This binding in vitro is stimulated by hemin. The HAP1-binding sequence was localized by using DNA fragments spanning different regions, by DNase I footprinting and by methylation interference of DNA-protein binding. The binding site was compared to the HAP1-binding sequences previously characterized in detail (UAS1CYC1, UASCYC7). There is strikingly little similarity between the three sequences, which have only four of those 23 bp in common which are protected from DNase I digestion. However, the pattern of major and minor groove contacts in the complex is quite similar in all three cases. The results obtained show that there is true co-ordinate control of expression of mitochondrial cytochromes and at least some extra-mitochondrial hemoproteins. Heme acts as a metabolic signal in this coordination, which is mediated by the HAP1 protein.