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Biomedical subjects

G Jones

Publications and source records attributed to G Jones.

At least 55 records · Page 3Linked to original sources
PubMed2003

A randomized controlled trial of phytoestrogen supplementation, growth and bone turnover in adolescent males.

OBJECTIVE: To assess the effect of phytoestrogens on bone turnover and growth in adolescent boys. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Single school in northwest Tasmania. PARTICIPANTS: Adolescent boys (treatment n=69, placebo n=59, mean age 16.8 y). INTERVENTIONS: Six weeks of isoflavone supplementation (Novasoy, 50 mg daily of isoflavone equivalents). Bone turnover markers (bone specific alkaline phosphatase (BAP) and pyridinoline creatinine ratio (PYR)) were measured at baseline and follow-up. RESULTS: Despite marked increases in urinary genistein and daidzein in the treatment arm (both P<0.001), there were no significant differences in BAP, PYR or short-term height or weight change. This applied to both intention-to-treat and per protocol analysis. Neither was there a significant correlation between urinary genistein and daidzein levels and BAP or PYR. CONCLUSIONS: Phytoestrogen supplementation to the level of usual Japanese dietary intake has no measurable effect on bone turnover in adolescent boys. Longer-term studies of bone density may be desirable but it is unlikely that there will be a large effect in either girls or boys given the lower endogenous oestrogen levels in boys.

Adolescent↗
PubMed2003

Oral administration of type II collagen suppresses pro-inflammatory mediator production by synoviocytes in rats with adjuvant arthritis.

The objective of this study was to investigate the effect of the oral administration of type II collagen (CII) on pro-inflammatory mediator production by synoviocytes in rats with adjuvant arthritis (AA). Sprague-Dawley rats were fed with bovine CII either before immunization with Complete Freund's adjuvant (CFA) or after initiation of arthritis. Hind paw secondary swelling was measured and synoviocytes were harvested. Sera from portal vein of oral tolerized rats were collected and in vitro synoviocytes culture or synoviocytes-Peyer's Patches (PP) cells coculture system were developed. Interleukin (IL)-1 activity was measured by a mouse thymocyte activation assayed by MTT dye reduction and tumour necrosis factor (TNF) activity was measured by an L929 cytotoxicity bioassay. Nitric oxide (NO) and malondialdehyde (MDA) levels were measured by biochemical methods. We found that feeding with CII (5, 50 and 500 micro g/kg) for 7 days before immunization significantly suppressed hind paw secondary swelling measured at day 16, 20, 24 and 28 (all P < 0.01) and pro-inflammatory mediator (IL-1, TNF, NO and MDA) production by synoviocytes (all P < 0.01) in rats with AA. Feeding with CII (5, 50 and 500 micro g/kg) for 7 days after initiation of arthritis had a similar effect. CII (1, 10, 100 micro g/ml) had no effect on IL-1 and TNF production by synoviocytes in vitro, but CII 10 micro g/ml suppressed IL-1 and TNF production by synoviocytes-PP cells coculture system (P < 0.01), which was antagonized by anti-TGF-beta antibody (10 micro g/ml) (P < 0.01). Portal serum (1 : 10) from oral tolerized rats suppressed IL-1 and TNF production by synoviocytes (P < 0.01), which was also antagonized by anti-TGF-beta antibody (10 micro g/ml) (P < 0.01). We conclude that oral administration of CII had prophylactic and therapeutic effects on AA and over-production of IL-1, TNF, NO and MDA by synoviocytes was suppressed. Bystander active suppression may be the main mechanism of oral CII in the suppression of synoviocyte function.

Administration, Oral↗
PubMed2003

The effect of treatment on radiological progression in rheumatoid arthritis: a systematic review of randomized placebo-controlled trials.

OBJECTIVE: To undertake a systematic review of randomized placebo-controlled trials to assess and rank the efficacy of pharmacological interventions in preventing radiological progression of rheumatoid arthritis. METHODS: The two outcome measures were the weighted standardized mean difference and the odds of progression of X-ray scores pooled as close to 12 months as possible to minimize heterogeneity. RESULTS: A total of 38 trials were identified. Of these, 13 were excluded, leaving data on 3907 subjects. Infliximab, cyclosporin, sulphasalazine, leflunomide, methotrexate, parenteral gold, corticosteroids, auranofin and interleukin 1 receptor antagonist were statistically better than placebo in terms of change in erosion scores. All agents were equivalent statistically, with the exception of infliximab (which was superior to the last five agents). There were similar findings for the odds of progression, with the exception of auranofin (P=0.06) and the infliximab-methotrexate comparison (P=0.07). Other agents did not reach statistical significance in either outcome measure. With the exception of the antimalarials, the magnitude of the effect was consistent with the effect seen in short-term disease activity trials. CONCLUSION: There is published evidence which supports the efficacy of nine agents in decreasing radiological progression in rheumatoid arthritis.

Antirheumatic Agents↗
PubMed2003

Interpreting change scores on the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40).

OBJECTIVES: To determine the amount of change over time on the five dimensions of the 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) that are subjectively meaningful to patients. Minimally important differences (MID), effect sizes (ES) and standardized response means (SRM) are calculated for respondents who indicate only a little change over the time of the study whilst mean change scores, ES and SRM statistics are calculated for those who indicated much change. DESIGN: Postal survey. Copies of the ALSAQ-40 were completed on two occasions three months apart. Respondents were also asked to indicate how much change they had experienced since baseline on each of the five domains of the questionnaire. SETTING: All patient members of the Motor Neurone Disease Association for England, Wales and Northern Ireland. SUBJECTS: Seven hundred and sixty-four patient members returned questionnaires at baseline and follow-up. RESULTS: For those reporting minor change since baseline results varied across dimensions. For example a MID was reflected in a change of 6.67 (SD 16.52) points for the Communication dimension, whilst for the Emotional functioning dimension the change was 2.67 (SD 15.45) points. Similarly ESs and SRMs varied considerably across dimensions. Mean change over time, ES and SRM statistics for those who reported that their health was much worse at follow-up were substantially larger: for example, mean changes ranged from 6.87 (SD 15.87) to 13.79 (SD 22.60). CONCLUSIONS: Results indicate the minimum magnitude of change that is subjectively meaningful to patients. Results indicate that smaller changes than have been suggested previously as significant have a subjectively meaningful adverse effect upon patients.

Adult↗
PubMed2003

Adipose thyrotrophin receptor expression is elevated in Graves' and thyroid eye diseases ex vivo and indicates adipogenesis in progress in vivo.

The thyrotrophin receptor (TSHR) provides an autoantigenic link between the thyroid and orbit in Graves' (GD) and thyroid eye diseases (TED). We measured TSHR transcripts in different fat depots to determine whether TSHR expression levels are influenced by the autoimmune/inflammatory process and/or thyroid hormone status, using quantitative real-time PCR. Nine intact or fractionated adipose samples, from patients with GD and/or TED, were analysed ex vivo. Eight expressed the TSHR, at levels approaching the thyroid, and one was at the limit of detection. Thirteen/fifteen orbital and abdominal fat samples from patients free of GD and TED, measured ex vivo, were negative for TSHR transcripts and two were at the limit of detection. All preadipocyte samples induced to differentiate in vitro expressed the TSHR. To investigate the influence of thyroid hormone status on adipose TSHR expression, we induced hyper- and hypothyroidism in BALBc mice by administering tri-iodothyronine and propylthiouracil respectively. In euthyroid animals, whole fat samples were at the limit of detection and were not altered by thyroid hormone status. The results show that adipose TSHR expression ex vivo indicates adipogenesis in progress in vivo and is associated with the autoimmune/inflammatory process in GD and TED but is not restricted to the orbit or influenced by thyroid hormone status.

Adipose Tissue↗
PubMed2002

Symptomatic fracture incidence in southern Tasmania: does living in the country reduce your fracture risk?

There are limited data describing urban-rural differences in fracture incidence and the overall effect remains controversial. The aim of this study was to compare symptomatic fracture incidence occurring in geographically defined rural (n = 34619) and urban (n = 194974) populations of Southern Tasmania from July 1, 1997 to June 30, 1999. Fractures were ascertained by reviewing reports from all the radiology providers within the area. In the 2-year study time frame there were 3644 fractures in males and 2657 fractures in females. Fracture incidence was significantly higher in urban compared with rural populations in both sexes (male: RR 1.60, 95% CI 1.47-1.75; female: RR 1.77, 95% CI 1.58-1.98). This higher urban fracture incidence was present across all age groups and all fracture types with the exception of knee and pelvis fractures in males (although not all were statistically significant). In addition, urban men >50 years old had a higher fracture incidence than rural women >50 years old (RR 1.25, 95% CI 1.05-1.50), suggesting that in later life the factors responsible for the urban-rural difference are able to offset completely the effect of gender. While some of the reduced fracture incidence in the rural population may be explained by urban drift and underreporting of minor fractures such as foot fractures, the overall pattern of higher fracture risk was very consistent, suggesting a real difference in whole-of-life symptomatic fracture incidence. Further research at an individual level is required to determine what factors account for these large urban-rural differences, as they imply a substantial potential for fracture prevention.

Adult↗
PubMed2002

Falsely elevated serum tobramycin levels in a patient receiving nebulised tobramycin.

It is common when treating patients with respiratory exacerbations of cystic fibrosis to use both nebulised and intravenous antibiotics. Aminoglycoside drug levels are often measured from finger-prick blood samples. We describe a case of a 14-year-old girl treated simultaneously with IV and nebulised tobramycin in whom drug levels, measured from finger prick blood samples, were erroneously high due to finger contamination by the nebulised drug. Special precautions or direct venepuncture is essential when assessing antibiotic levels in such patients.

Administration, Inhalation↗
PubMed2002

Characterisation, mutation detection, and association analysis of alternative promoters and 5' UTRs of the human dopamine D3 receptor gene in schizophrenia.

The dopamine D(3) receptor gene (DRD3) is a candidate for a number of psychiatric conditions including schizophrenia, bipolar disorder and alcohol and drug abuse. Previous studies have reported associations between polymorphisms in DRD3 and these disorders, but these findings may have reflected linkage disequilibrium with pathogenic variants that are further upstream. We have isolated and sequenced approximately 9 kb of genomic sequence upstream of the human DRD3 translational start site. Using 5' RACE, we have identified within this region three additional exons and two putative promoter regions which show promoter activity in three different cell lines. A 5' UTR identified only in lymphoblasts is spread over three exons and is 353 bp long. A second 5' UTR, found in adult and fetal brain, lymphocytes, kidney and placenta is spread over two exons and is 516 bp long. A 260-bp sequence within this 9 kb corresponds to a previously reported EST, but corresponding mRNA could not be found in the tissues above. The EST, 5' UTRs and putative promoter regions have been analysed for polymorphisms, revealing 10 single nucleotide polymorphisms, seven of which were tested for association in a large sample of unrelated patients with schizophrenia and matched controls. No associations were observed with schizophrenia. In addition we failed to replicate previous findings of association with homozygosity of the Ser9Gly variant. The results from this study imply that neither the coding nor the regulatory region of DRD3 plays a major role in predisposition to schizophrenia.

5' Untranslated Regions↗
PubMed2002

Uterine artery resistance and anxiety in the second trimester of pregnancy.

OBJECTIVE: To investigate the association between maternal anxiety and uterine artery resistance index (RI) at 20 weeks of gestation. METHODS: Uterine artery blood flow was assessed using color Doppler ultrasound and maternal anxiety was measured using the Hospital Anxiety and Depression (HAD) scale in 96 healthy primigravid women attending consecutively for their routine 20-week anomaly scan. RESULTS: The mean uterine artery RI was 0.54 (95% confidence interval, 0.52-0.56) and the median HAD anxiety score was 6 (range, 0-20). There was no association between RI and anxiety scores (r = 0.09, P = 0.36). Women scoring as definite cases of anxiety did not have a significantly elevated uterine artery RI or increased frequency of waveform notching compared to women with doubtful or no anxiety. CONCLUSIONS: The data of this study do not suggest a significant association between maternal anxiety and uterine artery RI at 20 weeks of gestation in healthy primigravid women with normally developing pregnancies. A prospective cohort study would be useful to determine the nature of the relationship between maternal anxiety, alteration in uterine artery blood flow and abnormal pregnancy outcome.

Anxiety↗
PubMed2002

Clinical risk factors but not bone density are associated with prevalent fractures in prepubertal children.

OBJECTIVE: The aim of this study was to investigate the association of clinical risk factors and bone density with prevalent fractures in prepubertal children. METHODS: Bone mineral density (BMD) in lumbar spine, femoral neck and total body bone was assessed by dual-energy X-ray absorptiometry. Clinical data on risk factors were collected by measurement and questionnaires. RESULTS: Of 324 children, 32 (10%) had a prevalent fracture (upper limb 69%). Most fractures were due to low-energy falls at home (69%). Children with fractures were older (P = 0.04), had higher levels of sports participation (P = 0.03), lower levels of breastfeeding (P = 0.05) and tended towards higher usage of inhaled corticosteroids in the previous year (P = 0.05). However, both BMD and apparent BMD did not differ between those with and without prevalent fracture. No differences were observed in the proportion of maternal fractures, maternal smoking during pregnancy, asthma history and oral prednisolone in last year (all P > 0.05). A final model incorporating age, weight, height, breastfeeding history, sports participation and inhaled corticosteroid usage accounted for 10% of the variability in the odds of fracture (P = 0.03). CONCLUSION: These results suggest that BMD may be less important than clinical risk factors for total fracture risk in prepubertal children. However, sample size limitations mean that further investigation in larger populations with less heterogeneity in fracture types is warranted.

Absorptiometry, Photon↗
PubMed2002

Symptomatic fracture incidence in those under 50 years of age in southern Tasmania.

OBJECTIVE: To document symptomatic fracture incidence in those aged under 50 years of age. METHODS: Fractures were ascertained from X-ray reports containing the word 'fracture' from all radiology providers for the geographically defined population of southern Tasmania (n = 165 175) for the period 1 July 1997 to 30 June 1999. RESULTS: In the 2-year study frame there were 2943 fractures in 164 730 person years in males and 1348 fractures in 165 620 person years in females. This represents a fracture incidence of 1787 per 100 000 person years in males and 819 per 100 000 person years in females. Peak fracture incidence was 10-14 years in females and 15-19 years in males although different fracture types had varying peak incidence suggesting different fracture-specific causes. The most common fractures were those of the hand (24%), forearm (17%), wrist (10%) and foot (9%). All fractures (including vertebral) were more common in males with relative risks ranging from 1.34 to 4.50. The estimated probability of at least one fracture between birth and 50 years of age was 59% for males and 34% for females. CONCLUSION: There are threefold as many fractures in this age group compared to those due to osteoporosis in the elderly in any given year. More research priority needs to be given to understanding the causes of these fractures so that preventive strategies can be formulated.

Adolescent↗
PubMed2002

The relationship of circulating insulin-like growth factor 1, its binding protein-3, prostate-specific antigen and C-reactive protein with disease stage in prostate cancer.

OBJECTIVE: To assess the relationships among circulating insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), prostate-specific antigen (PSA) and C-reactive protein (an indicator of inflammatory systemic response) in patients with prostate disease and cancer of different stages. PATIENTS AND METHODS: Circulating IGF-1, IGFBP-3, PSA and C-reactive protein concentrations were measured in patients with BPH (17) or stages T1/T2 (15), T3/T4 (16) and metastatic prostate cancer (12 patients). RESULTS: IGF-1 and IGFBP-3 concentrations were similar between patients with BPH and those with cancer, and there was no difference between the groups with cancer. In the latter patients there was a significant correlation between age and IGFBP-3 concentrations (r = -0.400, P = 0.008) but not with IGF-1 concentrations. Controlling for age, there were significant partial correlations between C-reactive protein and IGF-1 (r = -0.412, P = 0.008) and IGFBP-3 (r = -0.277, P = 0.05). CONCLUSIONS: These results indicate that circulating IGF-1 and IGFBP-3 concentrations do not change with disease stage in prostate cancer, but that they decrease with an increase in the systemic inflammatory response.

Aged↗
PubMed2002

HLA haplotypes and susceptibility to rheumatoid arthritis. More than class II genes.

Our aim was to examine, using microsatellite (ms) markers, the contribution of the telomeric part of the HLA region to rheumatoid arthritis (RA) predisposition in the Spanish population. We have looked at the distribution of DQB1, DRBI and five ms loci (D6S1014, D6S273, D6STNFa, MIB and C1-2-5) within the HLA region in 147 Spanish RA patients and 202 control subjects. A total of 19 conserved ms configurations were observed, twelve of them in linkage disequilibrium with particular DQB1-DRB1 haplotypes. Interestingly, haplotype c1 (DQB1*0201-DRB1*0301-D6S1014*143-D6S273*139-D6STNFa*99-MIB*350-C1-2-5*196) was significantly associated with RA predisposition. As part of this haplotype, the MIB*350 allele was found to be a risk factor independently of the RA-predisposing haplotypes. The present results along with data from others prove the existence of a second predisposing locus located inside the MHC region, and suggest that might be located within the TNFa-HLA-B region.

Arthritis, Rheumatoid↗
PubMed2002

A comparison of three scoring systems for mortality risk among retrieved intensive care patients.

AIMS: To assess the impact of two paediatric intensive care unit retrieval teams on the performance of three mortality risk scoring systems: pre-ICU PRISM, PIM, and PRISM II. METHODS: A total of 928 critically ill children retrieved for intensive care from district general hospitals in the south east of England (crude mortality 7.8%) were studied. RESULTS: Risk stratification was similar between the two retrieval teams for scores utilising data primarily prior to ICU admission (pre-ICU PRISM, PIM), despite differences in case mix. The fewer variables required for calculation of PIM resulted in complete data collection in 88% of patients, compared to pre-ICU PRISM (24%) and PRISM II (60%). Overall, all scoring systems discriminated well between survival and non-survival (area under receiver operating characteristic curve 0.83-0.87), with no differences between the two hospitals. There was a tendency towards better discrimination in all scores for children compared to infants and neonates, and a poor discrimination for respiratory disease using pre-ICU PRISM and PRISM II but not PIM. All showed suboptimal calibration, primarily as a consequence of mortality over prediction among the medium (10-30%) mortality risk bands. CONCLUSIONS: PIM appears to offer advantages over the other two scores in terms of being less affected by the retrieval process and easier to collect. Recalibration of all scoring systems is needed.

Child↗
PubMed2002

Investigation of chromosome 2q in osteoarthritis of the hand: no significant linkage in a Tasmanian population.

BACKGROUND: Previous studies have suggested a strong genetic component to osteoarthritis (OA), especially that of the hand, and three linkage studies have suggested the existence of susceptibility loci in disparate regions of chromosome 2q. OBJECTIVE: To examine for linkage to 2q in a Tasmanian population of women and men with familial hand OA. METHODS: Hand OA (distal interphalangeal, carpometacarpal, and Heberden's nodes) was assessed by a combination of hand photographs and radiographs. A non-parametric linkage (NPL) analysis was performed on chromosome 2q of 69 members in 22 families with severe distal interphalangeal joint OA using Genehunter. A quantitative trait linkage analysis of a larger group of 456 members in 68 families was also performed using SOLAR. RESULTS: The maximum non-parametric linkage score was 1.05 (p=0.15) at marker IL1R1, close to the centromere. All components of hand OA scores had significant heritability in this dataset (28%-35%, all p<0.001). Despite this, the quantitative trait analysis (after adjustment for age and, where appropriate, sex) yielded maximum LOD scores of 0.90 for Heberden's nodes (both sexes combined), and 1.19 for carpometacarpal OA score (women only). CONCLUSIONS: These results do not provide confirmation of linkage on chromosome 2q in the larger white population with hand OA. They suggest that there are regional variations in the genetic cause of hand OA and that other loci not on 2q may be important in this disease.

Adult↗