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J Beilby

Publications and source records attributed to J Beilby.

At least 19 recordsLinked to original sources
PubMed2004

Effects of endogenous estrogen on renal calcium and phosphate handling in elderly women.

High postmenopausal endogenous estrogen concentrations are an important determinant of preservation of bone mass and reduced fracture in elderly women. Calcium supplementation can also reduce bone loss in these patients, suggesting an interaction between estrogen deficiency and calcium balance. Potential mechanisms of estrogen on calcium transport include direct effects on the bone, the kidney, and the bowel. Previous studies have demonstrated effects of estrogen on renal phosphate handling. We have used a cross-sectional, population-based analysis of biochemical data obtained from ambulant elderly women to determine the association of endogenous estradiol with urine calcium and phosphorus excretion. The subjects were 293 postmenopausal women >70 yr old. Factors associated with renal calcium and phosphate excretion were measured, including the filtered calcium and phosphate load, parathyroid hormone (PTH), estradiol, and sex hormone-binding globulin (SHBG). The free estradiol concentration (FE) was calculated from a previously described formula. A high plasma estradiol concentration (r(2) = 0.023, P = 0.01) and a high FE (r(2) = 0.045, P = 0.001) were associated with reduced renal calcium excretion. The estradiol and FE effect on renal calcium excretion remained significant after adjusting for calcium filtered at the glomerulus and serum PTH. A high FE was associated with a reduced renal phosphate threshold in univariate analysis (r(2) = 0.023, P = 0.010). The effect remained significant after adjustment for serum PTH. The size of the effect of the FE was of the same order of magnitude as the effect of PTH on reducing renal calcium excretion and increasing renal phosphate excretion. These data support in vitro and animal data demonstrating an effect of estradiol on renal calcium and phosphate handling and indicate that, in elderly postmenopausal women, the effect is of a similar magnitude to the well-recognized effects of PTH on these physiologically regulated parameters.

Aged↗
PubMed2004

Prediction of incident osteoporotic fractures in elderly women using the free estradiol index.

A decline in postmenopausal estrogen concentration accelerates postmenopausal bone loss. We have examined the predictive power of endogenous estrogen production, DXA hip bone density (BMD), and heel quantitative ultrasound (QUS) on incident clinical fracture in a prospective 3-year population based, randomised controlled trial of calcium supplementation. Baseline blood testing on 1499 women mean (SD) age 75 (3) years for estradiol and sex hormone binding globulin measurements and ankle QUS measurements (Lunar Achilles) was undertaken. Bone density was measured using DXA (Hologic 4500A) at 1 year. Incident clinical fractures were confirmed by X-ray. At 3 years, 10% had sustained more than one incident fracture. The fracture group had significantly lower levels of free estradiol index (FEI) (0.40+/-0.44 versus 0.49+/-0.54 pmol/nmol), hip BMD (0.776+/-0.129 versus 0.815+/-0.124 g/cm(2)) and measures of QUS (BUA 98+/-8 versus 101+/-8 db/Hz, SOS 1504+/-22 versus 1514 +/-26 m/s; stiffness 67+/-11 versus 71+/-11 % mean young adult), respectively, than the non-fracture group. After adjustment for age, weight, use of topical estrogen, calcium supplementation and prevalent fracture, incident fracture was predicted by free estradiol index (HR per SD: 1.43:95%CI: 1.08-1.91, P=0.013). After adjustment for BMD, SOS or stiffness, the free estradiol index no longer predicted fracture. When examined separately, the presence of a vertebral or an appendicular fracture was associated with an 18% lower free estradiol index compared with no fracture. The risk of vertebral fracture increased with decreased free estradiol index (HR per SD reduction: 1.63:95% CI: 0.91-2.92); the risk of appendicular fracture also increased with decreased free estradiol index (HR per SD reduction: 1.45:95% CI: 1.05-2.01) after adjustment for age, weight, use of topical estrogen, calcium supplementation and prevalent fracture. After further adjustment for hip BMD or QUS measures, the effect of free estradiol index was no longer significant for vertebral or appendicular fractures. Therefore, a low free estradiol index increases the probability of having an incident fracture as a result of decreased BMD. These data confirm the importance of postmenopausal estrogen concentration in the pathogenesis of osteoporosis in elderly women.

Administration, Topical↗
PubMed2004

Keeping women doctors in the country.

Women are disproportionately poorly represented in the rural Australian medical workforce and appropriate retention policies should recognise the factors contributing to a positive rural experience for female doctors. This study describes the professional, social and family experiences of 10 female general practitioners (GPs) working in rural South Australia. Variety of work, the opportunity to provide continuity of care and being valued by the community were important factors in rural recruitment and retention. Successful retention of a female rural medical workforce also required flexible on-call and after-hours arrangements, provision of additional support and employment opportunities for non-medical spouses and partners; and provision of appropriate child care services to rural medical families. To date, there have been few initiatives specifically addressing the concerns of female rural medical practitioners. An advisory body of rural women doctors and community representatives can provide practical guidance regarding the opportunities available for rural communities to effectively support their women doctors.

Journal Article↗
PubMed2004

Reduced breast cancer risk with increasing serum folate in a case-control study of the C677T genotype of the methylenetetrahydrofolate reductase gene.

Breast cancer risk may be associated with folate status or the C677T genotype of the methylenetetrahydrofolate reductase (MTHFR) gene. We compared serum folate concentrations and C677T genotype in 141 breast cancer patients and 109 age-matched controls. Serum folate was significantly lower in cases compared to controls (geometric means, 5.7 versus 6.6 microg/l; P=0.005). Breast cancer risk was not associated with C677T genotype. After adjusting for age of menarche, parity, alcohol intake and total fat intake we observed reductions in odds ratios for breast cancer risk comparing the highest with the lowest quartiles of serum folate concentrations of 0.23 (95% confidence interval (CI) 0.09, 0.54) for the entire group, 0.27 (CI 0.09, 0.80) for the wild-type and 0.08 (CI 0.01, 0.52) for the heterozygous C677T genotype. We conclude that for the whole group, and the wild-type and heterozygous C677T genotypes, increased serum concentrations of folate were associated with reduced risks of breast cancer.

Adult↗
PubMed2003

Localization of a non-melanoma skin cancer susceptibility region within the major histocompatibility complex by association analysis using microsatellite markers.

The major histocompatibility complex (MHC) is known to have a role in the development of non-melanoma skin cancer (NMSC), although the genes and mechanisms involved have yet to be determined. To identify the susceptibility locus for NMSC within the MHC, we used a collection of well-defined polymorphic microsatellite markers from the Human leucocyte antigen (HLA) region for an association analysis of 150 cases with NMSC and 200 healthy controls selected from the Busselton population in Western Australia. High-resolution mapping was undertaken using a total of 40 highly polymorphic markers located at regular intervals across the HLA region (3.6Mb). Polymerase chain reaction (PCR) analysis was initially performed on pooled DNA markers to detect those markers that showed different allele profiles. Statistically significant differences in allelic frequencies (differentiating alleles) were found between cases and controls at three polymorphic microsatellite loci within a 470-kb genomic susceptibility region ranging between 6 kb centromeric of the HLA-B gene and intron 5 of the DDR gene. Interestingly, this genome region corresponded completely with the psoriasis-susceptibility locus. The three differentiating alleles and another four markers outside the susceptibility region were then PCR tested by individual genotyping of cases and controls. The newly identified susceptibility locus for NMSC within the MHC was found to be significantly different between the cases and controls by comparisons of allele frequencies at the three differentiating loci estimated from DNA pools and then confirmed by individual genotyping. This is the first study using high density microsatellite markers to localize a NMSC susceptibility region within the human genome.

Australia↗
PubMed2003

Depressive disorders and unprotected casual anal sex among Australian homosexually active men in primary care.

OBJECTIVE: To examine the relationship between depressive disorders and unprotected anal intercourse with casual partners, among homosexually active men attending for primary care. METHODS: The first 460 homosexually active men enrolling in an Australian integrated primary care programme were screened for current depressive disorders using the Primary Care Evaluation of Mental Disorders (PRIME-MD) and completed questionnaires on their sexual behaviour in the prior 6 months. One hundred and sixty-two (35%) were HIV positive, 283 (62%) were HIV negative and 15 (3%) were untested. RESULTS: The prevalence of major depressive episode (MDE), as measured by the PRIME-MD, on enrollment was 28% (129/460), while the prevalence of dysthymic disorder (DD) was 26% (121/460). These include 84 men (18%) who met the criteria for both disorders ('double depression'). Neither disorder was associated with HIV status. Men with MDE were less likely to have been sexually active than the remainder of the cohort (90/129 [70%] vs. 291/331 [88%]; OR: 0.32 [95% CI: 0.19-0.52]; P<0.0001). Men with DD alone, however, were significantly more likely than men with neither disorder to report having had unprotected anal intercourse with a casual partner (11/38 [29%] vs. 43/292 [15%]; OR: 2.36 [95%CI: 1.09-5.10]; P=0.035). CONCLUSIONS: Depressive disorders were highly prevalent in this cohort and independent of HIV status. MDE was associated with reduced sexual activity. Among men without MDE, the presence of DD was independently associated with an increased likelihood of reporting unsafe anal sex with a casual partner in the prior 6 months.

Adult↗
PubMed2002

Pregnancy outcome following women's participation in a randomised controlled trial of acupuncture to treat nausea and vomiting in early pregnancy.

OBJECTIVES: Recent studies have concluded that acupuncture is safe in the hands of a qualified practitioner. This study assessed the risk of adverse effects of acupuncture administered during pregnancy. METHODS: 593 women with nausea and vomiting in early pregnancy volunteered to participate in a randomised controlled trial, conducted at the Women's and Children's Hospital, in South Australia. Patients were given either traditional acupuncture, formula acupuncture, sham acupuncture or no acupuncture. OUTCOME MEASURES: Data were collected on perinatal outcome, congenital abnormalities, pregnancy complications and the newborn. RESULTS: No differences were found between study groups in the incidence of perinatal outcome, congenital abnormalities, pregnancy complications and other infant outcomes. CONCLUSION: Our findings suggest that no serious adverse effects arise from acupuncture administered in early pregnancy.

Acupuncture Therapy↗
PubMed2002

A polymorphism in the methylenetetrahydrofolate reductase gene predisposes to colorectal cancers with microsatellite instability.

BACKGROUND: The enzyme methylenetetrahydrofolate reductase (MTHFR) catalyses the formation of folate intermediates that are vital to methylation reactions. A polymorphic variant (TT) has been linked to reduced levels of plasma folate, aberrant DNA methylation in leucocytes, and increased risk of colorectal cancer (CRC) under conditions of low folate intake. The cystathionine beta-synthase (CBS) enzyme reduces homocysteine levels and thus may protect against CRC. The CBS gene has a variant, 844ins68, that has been linked with increased activity. These variants may be involved in the development of the subgroup of CRC displaying aberrant DNA methylation and frequently associated with microsatellite instability (MSI). AIM: To investigate the frequencies of the TT and 844ins68 genotypes in CRC patients with MSI+ tumours compared with those with MSI- tumours and a control population. SUBJECTS: Patients with CRC (n=501) and healthy control subjects (n=1207) were studied. CRC cases were classified as MSI+ (n=75) or MSI- (n=426) based on deletions within the BAT-26 mononucleotide repeat. METHODS: Subjects were genotyped for MTHFR using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and PCR-restriction fragment length polymorphism (PCR-RFLP) techniques, and for CBS using PCR. RESULTS: The MTHFR TT genotype was more frequent in older CRC patients (>or=70 y) compared with equivalent aged controls (p=0.03), was associated with a significantly later age of diagnosis in patients with proximal colon tumours (p=0.02), and was almost twice as frequent in MSI+ than in MSI- tumours (p=0.05). Compared with normal controls, the 844ins68 variant of CBS was less frequent in patients with proximal tumours (p=0.02). CONCLUSIONS: The TT genotype of MTHFR is associated with an increased risk of CRC in older populations, possibly due to age related disturbances in folate metabolism. The TT genotype appears to predispose to CRC that is MSI+. This may reflect the involvement of aberrant DNA methylation frequently associated with MSI+. The 844ins68 CBS polymorphism may protect against proximal tumours.

Adult↗
PubMed2002

Pre-exercise oral creatine ingestion does not improve prolonged intermittent sprint exercise in humans.

BACKGROUND: This investigation determined whether pre-exercise oral Cr ingestion could enhance prolonged intermittent sprint exercise performance. METHODS EXPERIMENTAL DESIGN: a randomised, double-blind crossover design was employed. SETTING: testing was performed at the Western Australian Institute of Sport and participants were monitored and treated by both scientific and medical personnel. PARTICIPANTS: eight active, but not well-trained males with a background in multiple-sprint based sports acted as subjects for this investigation. INTERVENTIONS: subjects ingested either 15 g Cr.H2O or placebo 120 min and 60 min prior to the start of an 80-min maximal sprint cycling task (10 sets of multiple 6-sec sprints with varying active recoveries). Subjects were retested 14 days later, being required to ingest the alternate supplement and repeat the exercise test. MEASURES: performance variables (work done and peak power) were obtained throughout the exercise challenge. Muscle biopsies (vastus lateralis) were raised to a peak of 2348+/-223 micromol x l(-1) prior to the commencement of exercise after Cr ingestion. There were no significant changes in any cycling performance parameters following Cr ingestion, although blood La- was significantly lower (p<0.05) than placebo at all time points during were taken preexercise as well as immediately and 3 min post-exercise in order to determine concentrations of ATP, PCr, Cr, La- and glycogen. Venous blood was drawn prior to and on four occasions during the exercise test, and analysed for Cr, NH3+, La- and pH. RESULTS: Serum Cr concentrations exercise, and plasma NH3+ accumulation was also significantly reduced (p<0.05) in the Cr condition, but only in the second half of the 80-min exercise test. Muscle ATP and TCr levels as well as postexercise PCr replenishment were unaffected following Cr administration. CONCLUSIONS: The data suggest that although the pre-exercise ingestion of a large Cr dose was shown to have some impact on blood borne metabolites, it does not improve maximal prolonged intermittent sprint exercise performance, possibly due to an insufficient time allowed for uptake of serum Cr by skeletal muscle to occur. Therefore, this form of loading does not provide an alternative method of Cr supplementation to the traditional five-day supplementation regimes established by previous research.

Adult↗
PubMed2001

Combined effect of cyclosporine and sirolimus on improving the longevity of recombinant adenovirus-mediated transgene expression in the retina.

OBJECTIVES: To reevaluate the longevity and intraocular safety of recombinant adenovirus (rAd)-mediated gene delivery after subretinal injection, and to prolong transgene expression through the combination of 2 synergistic immunosuppressants. METHODS: An rAd vector carrying green fluorescent protein (GFP) gene was delivered subretinally in the rat eye. The GFP expression was monitored in real time by fundus fluorescent photography. Intraocular safety was examined by observation of changes of retinal pigmentation, cell infiltration in virus-contacted area, immunophenotyping for CD4(+) and CD8(+) cytotoxic T lymphocytes, and CD68(+) macrophages, histologic findings, and dark-adapted electroretinography. Two synergistic immunosuppressants, cyclosporine and sirolimus, were used alone or in combination to prolong transgene expression by temporary immunosuppression. RESULTS: The GFP expression peaked on day 4, dramatically decreased on day 10, and was not detectable on day 14. The decreased GFP expression was coincident with cell infiltration in virus-contacted area. Immunostaining showed that the infiltrating cells were CD4(+) and CD8(+) cytotoxic T lymphocytes and CD68(+) macrophages. Clumped retinal pigmentation and decreased b wave of dark-adapted electroretinogram were observed at 3 to 4 weeks after injection. Histologic examination confirmed rAd-induced retinal degeneration. Transient immunosuppression by cyclosporine and sirolimus, either alone or in combination, improved transgene expression, with the combination being the most efficient. The combined immunosuppression attenuated but did not retard the rAd-induced retinal damage. CONCLUSIONS: Transgene expression mediated by rAd after subretinal delivery is short-term and toxic to the retina. Combination of cyclosporine and sirolimus may act as an immunosuppressive adjunct to prolong rAd-mediated gene transfer. CLINICAL RELEVANCE: The intraocular safety of rAd should be carefully considered before clinical trials are performed.

Adenoviridae↗
PubMed2001

Effect of creatine loading on long-term sprint exercise performance and metabolism.

PURPOSE: This study examined whether creatine (Cr) supplementation could enhance long-term repeated-sprint exercise performance of approximately 80 min in duration. METHODS: Fourteen active, but not well-trained, male subjects initially performed 10 sets of either 5 or 6 x 6 s maximal bike sprints, with varying recoveries (24, 54, or 84 s between sprints) over a period of 80 min. Work done (kJ) and peak power (W) were recorded for each sprint, and venous blood was collected preexercise and on four occasions during the exercise challenge. Muscle biopsies (vastus lateralis) were obtained preexercise as well as 0 min and 3 min postexercise. Subjects were then administered either 20 g.d-1 Cr.H2O (N = 7) or placebo (N = 7) for 5 d. Urine samples were collected for each 24 h of the supplementation period. Subjects were then retested using the same procedures as in test 1. RESULTS: Total work done increased significantly (P < 0.05) from 251.7 +/- 18.4 kJ presupplementation to 266.9 +/- 19.3 kJ (6% increase) after Cr ingestion. No change was observed for the placebo group (254.0 +/- 10.4 kJ to 252.3 +/- 9.3 kJ). Work done also improved significantly (P < 0.05) during 6 x 6 s sets with 54-s and 84-s recoveries and approached significance (P = 0.052) in 5 x 6 s sets with 24-s recovery in the Cr condition. Peak power was significantly increased (P < 0.05) in all types of exercise sets after Cr loading. No differences were observed for any performance variables in the placebo group. Resting muscle Cr and PCr concentrations were significantly elevated (P < 0.05) after 5 d of Cr supplementation (Cr: 48.9%; PCr: 12.5%). Phosphocreatine levels were also significantly higher (P < 0.05) immediately and 3 min after the completion of exercise in the Cr condition. CONCLUSION: The results of this study indicate that Cr ingestion (20 g.day-1 x 5 d) improved exercise performance during 80 min of repeated-sprint exercise, possibly due to an increased TCr store and improved PCr replenishment rate.

Administration, Oral↗
PubMed2000

The impact of nausea and vomiting on women: a burden of early pregnancy.

Nausea and vomiting are troublesome symptoms occurring in the first trimester of pregnancy. The aim of this study was to describe the impact these symptoms have on women in early pregnancy by interviewing, using a structured questionnaire, 593 pregnant women presenting with nausea and vomiting in the first trimester of pregnancy. The women were asked to complete the Rhodes index of nausea and vomiting and the MOS 36 Short Form Health Survey (SF-36). Symptoms of nausea and vomiting started early in pregnancy. Nausea was the most troublesome symptom experienced by women, both in its duration and intensity. Low scores for the SF-36 were found for all items, particularly physical functioning, energy and social functioning. The women described substantial effects on working, household duties and parenting activities. Findings from this study suggest nausea and vomiting in early pregnancy has a profound impact on women's general sense of well-being and day to day life activities.

Activities of Daily Living↗
PubMed2000

Pharmacokinetics of retinyl palmitate and retinol after intramuscular retinyl palmitate administration in severe malaria.

Retinol (vitamin A alcohol) is an accepted adjunctive treatment in infections such as measles. There is also indirect evidence from in vitro, animal and human studies that retinol supplementation may be beneficial in severe malaria. There have, however, been no studies that have examined the pharmacokinetics of acute retinol supplementation in severe illness. To establish whether mobilization of intramuscular retinyl palmitate (RP) and its availability as retinol are adequate in complicated falciparum malaria, we administered a single dose of 400000 i.u. of RP to six Vietnamese adults with severe malaria. Another 28 patients were not given RP. All patients had blood samples taken over 96 h for RP and retinol assay using HPLC, and received conventional anti-malarial and supportive therapy. Admission serum retinol concentrations were below the lower limit of the reference range (<1.0 micromol/l) in 74% of the 34 patients. In supplemented patients, analysis of serum RP between 0 and 96 h using a multi-compartmental model revealed a median (range) delay in mobilization of 6.9 h (0.7-15.1 h), a bioavailability of 55% (19-100%) and an elimination half-life of 13.5 h (4.2-23.7 h). The area under the serum retinol curve expressed as an absolute or percentage change from baseline was greater in supplemented than in unsupplemented patients (P<0.05). The separation in median serum retinol concentrations in the two groups was maximal at 48 h. The model-derived retinol half-life [1.5 (0.7-15.8) h] suggested rapid uptake, metabolism and/or excretion. In conclusion, there is variable RP bioavailability in severe malaria, but a significant if delayed increase in serum retinol over that associated with recovery from the infection. In severe infections, RP supplementation appears simple, well tolerated and of potential benefit once anti-microbial and supportive therapy have been established.

Adult↗
PubMed1998

Vitamin A and cancer prevention I: observations in workers previously exposed to asbestos at Wittenoom, Western Australia.

Our aim was to describe a vitamin A-based cancer prevention program for former asbestos workers and to check for possible harmful effects by comparing rates of disease and death in study subjects with subjects who chose not to join. All subjects had been occupationally exposed to crocidolite at Wittenoom Gorge between 1943 and 1966; 1,677 subjects indicated interest in the program and 1,203 joined between June 1990 and May 1995. Comparison subjects consisted of 996 former workers known to be alive in Western Australia in 1990 who did not join the program. Program subjects were provided with annual supplies of vitamin A (either synthetic beta-carotene or retinol), help in quitting smoking and dietary advice. The comparison group received only mail contact. Both groups were followed up to December 1994 for vital status and cancer information, and rates of cancer and death from various causes were compared. Mortality in both groups was higher than expected (standardised mortality ratio 1.23 in program subjects and 1.67 in comparison subjects). After adjustment for age, smoking and asbestos exposure, the relative rates in participants compared with non-participants was below I for all examined cancers and causes of death. For mesothelioma and lung cancer, group differences increased with time from entry, whereas other differences dissipated with time. No significant side effects were reported. In conclusion, program participants had significantly lower mortality than non-participants, but the rates of the 2 groups converged with time.

Adult↗
PubMed1998

Vitamin A and cancer prevention II: comparison of the effects of retinol and beta-carotene.

Former blue asbestos workers known to be at high risk of asbestos-related diseases, particularly malignant mesothelioma and lung cancer, were enrolled in a chemo-prevention program using vitamin A. Our aims were to compare rates of disease and death in subjects randomly assigned to beta-carotene or retinol. Subjects were assigned randomly to take 30 mg/day beta-carotene (512 subjects) or 25,000 IU/day retinol (512 subjects) and followed up through death and cancer registries from the start of the study in June 1990 till May 1995. Comparison between groups was by Cox regression in both intention-to-treat analyses and efficacy analyses based on treatment actually taken. Median follow-up time was 232 weeks. Four cases of lung cancer and 3 cases of mesothelioma were observed in subjects randomised to retinol and 6 cases of lung cancer and 12 cases of mesothelioma in subjects randomised to beta-carotene. The relative rate of mesothelioma (the most common single cause of death in our study) for those on retinol compared with those on beta-carotene was 0.24 (95% CI 0.07-0.86). In the retinol group, there was also a significantly lower rate for death from all causes but a higher rate of ischaemic heart disease mortality. Similar results were found with efficacy analyses. Our results confirm other findings of a lack of any benefit from administration of large doses of synthetic beta-carotene. The finding of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation.

Adult↗