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Biomedical subjects

C Cooper

Publications and source records attributed to C Cooper.

At least 289 records · Page 16Linked to original sources
PubMed1997

Quality of life as outcome in the treatment of osteoporosis: the development of a questionnaire for quality of life by the European Foundation for Osteoporosis.

The morbidity of osteoporosis is caused by fractures. Vertebral fractures lead to pain and disability and a decrease in quality of life. A Working Party of the European Foundation for Osteoporosis has developed a specific questionnaire for patients with established vertebral osteoporosis. This questionnaire is intended for use in clinical trials. The questionnaire consists of questions and visual analogue scales in the following domains: pain, activities of daily living, jobs around the house, mobility, leisure and social activities, general health perception and mood. The questionnaire has been translated from English into French, German, Italian, Hebrew, Swedish and Dutch. The questionnaire is currently being validated in a multicentre study involving patients with stable osteoporosis and control subjects. Preliminary results indicate that the reproducibility is sufficient and that the questionnaire is able to discriminate between patients with vertebral osteoporosis and control subjects.

Activities of Daily Living↗
PubMed1997

Influence of hormonal and reproductive factors on the risk of vertebral deformity in European women. European Vertebral Osteoporosis Study Group.

The aim of this study was to determine whether variation in the level of selected hormonal and reproductive variables might explain variation in the occurrence of vertebral deformity across Europe. A population-based cross-sectional survey method was used. A total of 7530 women aged 50-79 years and over were recruited from 30 European centres. Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs which were taken according to a standard protocol. After adjusting for age, centre, body mass index and smoking, those in the highest quintile of menarche (age > or = 16 years) had an increased risk of vertebral deformity (odds ratio [OR] = 1.48; 95% confidence interval [CI] 1.16, 1.88). Increased menopausal age (> 52.5 years) was associated with a reduced risk of deformity (OR = 0.78; 95% CI 0.60, 1.00), while use of the oral contraceptive pill was also protective (OR = 0.76; 95% CI 0.58, 0.99). There was a smaller protective effect associated with one or more years use of hormone replacement therapy, though the confidence limits clearly embraced unity. There was no apparent effect of parity or breast-feeding on the risk of deformity. We conclude that oestrogen status is an important determinant of vertebral deformity. Ever use of the oral contraceptive pill was associated with a 25% reduction in risk of deformity though the effect may be a result of the higher-dosage oestrogen pills used in the past. Parity and breast-feeding do not appear to be important and would appear to have little potential for identification of women at high risk of vertebral deformity.

Age Factors↗
PubMed1997

Polymorphisms of the vitamin D receptor, infant growth, and adult bone mass.

Family and twin studies have demonstrated a strong genetic component to the development of peak bone mass. Early fetal and infant environment has also been shown to influence bone mass through an effect on skeletal size and mineral content. We report a retrospective study that has examined whether early infant growth is regulated by genetic factors shown to be associated with bone mass. We have determined the vitamin D receptor (VDR) gene alleles for 66 women (mean age 65.5 years) on whom detailed birth records were available. There was a statistically significant trend (P = 0.04) for VDR genotype against weight at the age of 1 year, with the "tt" homozygote group having 7% higher weight. We conclude that early fetal or infant environment may interact with an individual's underlying genotype to program early skeletal growth, and that this may track through later life to influence adult characteristics. Further prospective studies are required, however, to fully clarify the precise environmental and genetic mechanisms underlying these findings.

Absorptiometry, Photon↗
PubMed1997

The relationship between childhood growth, bone mass, and muscle strength in male and female adolescents.

In this population-based study, the relationship between childhood weight and height, and adolescent bone mass and muscle strength have been studied in 39 girls and 48 boys. Total body and femoral neck bone mass measurements (bone mineral content, BMC and bone mineral density, BMD) were made by dual X-ray absorptiometry. Quadriceps muscle strength was measured. Mean age at the time of measurement was 15.1 years for girls and boys. Results were individually linked to data on childhood (birth to 6 years of age) weight and height, taken from community health records. Childhood weight was found to be predictive of adolescent total body BMC (TBMC). However, this was not the case when correlating childhood weight and total body BMD (TBMD), suggesting that growth determines the size of the skeleton, whereas the density within that bone envelope is to a greater extent governed by other factors. Further, in a multiple regression model we found that the combined effect of childhood weight and height was significantly correlated with adolescent quadriceps muscle strength.

Absorptiometry, Photon↗
PubMed1997

Upper gastrointestinal adverse events and cyclical etidronate.

PURPOSE: Recently, there have been several published case reports of esophagitis associated with the use of aminobisphosphonates. The objective of this study was to evaluate the upper gastrointestinal (GI) safety of cyclical etidronate, an alkylbisphosphonate, in routine clinical practice. PATIENTS AND METHODS: Information was obtained from 550 general practices in the United Kingdom that provide the medical records to the General Practice Research Database. A group of 7977 cyclical etidronate takers and 2 age-, gender-, and practice-matched control groups (1 with osteoporosis and 1 without) were analyzed. RESULTS: For cyclical etidronate takers, the average age was 71.6 years and total follow-up was 10,328 person-years. The risk of upper GI events (inflammation or ulcer of esophagus, stomach, or duodenum) was comparable between patients taking etidronate and the two control groups. The adjusted relative risk of upper GI events was 0.92 (95% confidence interval [CI] 0.78 to 1.09) for etidronate takers compared with osteoporosis controls and 1.12 (CI 0.91 to 1.37) compared to nonosteoporosis controls. For esophagitis and esophageal ulcers, the relative risks were 0.83 (CI 0.64 to 1.08) and 0.97 (CI 0.71 to 1.31) respectively. The incidence of upper GI events during nonsteroidal anti-inflammatory drug (NSAID), aspirin, or corticosteroid use was similar across the three groups. The upper GI risks of etidronate NSAID users were 0.71 (CI 0.45 to 1.11) and 2.06 (CI 0.98 to 4.35) compared with NSAID users in the two control groups. CONCLUSIONS: These results support the GI tolerability and safety profile of cyclical etidronate in routine clinical practice. Concomitant use of cyclical etidronate with NSAIDs, aspirin, or corticosteroids did not increase the incidence of upper GI events.

Aged↗
PubMed1997

Perimenopausal bone density screening--will it help prevent osteoporosis?

OBJECTIVE: To estimate the potential efficacy and cost-effectiveness of hormone replacement therapy (HRT) in the prevention of osteoporotic fractures, with and without the assistance of perimenopausal bone mineral density (BMD) screening. METHOD: Residual lifetime fracture experience of a hypothetical cohort of 100,000. British women aged 45 years at baseline, modelled using prevailing UK mortality and fracture rates. Appropriate fracture risk gradients were used to estimate the distribution of future fragility fractures (distal forearm, proximal femur and clinically diagnosed vertebral fractures) according to quarters of baseline bone density measured at fracture specific sites. We assumed that 72% of the population could be contacted and would attend for HRT counselling, with or without bone densitometry, that 10 years of continuous HRT use would reduce fracture rates by 50%, and that compliance with HRT might vary between 10% and 50%. Universal recommendation of HRT was compared to selective treatment protocols offering HRT to those women whose BMD fell below the 25th, 50th or 75th percentile of BMD at the lumbar spine, femoral neck or distal forearm, measured either singly or in combination. RESULTS: The proportion of future fractures averted was closely related to compliance with therapy, but for any given level of compliance, universal treatment always achieved the greatest reduction in fractures. If compliance was 10% universal HRT was also the most cost-effective strategy, but if compliance was higher or if the unit cost of HRT increased, selective strategies were often more cost-effective. The sensitivity of BMD screening in identifying women at risk of future fracture could be increased by relaxing the BMD decision threshold, or expanding the number of skeletal sites measured, or both. However increments in test sensitivity were always accompanied by reductions in specificity. CONCLUSIONS: If BMD measurement does not influence compliance, then universal treatment with HRT is likely to prevent more fractures, at a similar or lower average cost per fracture averted, than selective therapy. However, if BMD screening leads to increased compliance, or if more expensive forms of treatment were used, then our model suggests a favourable impact of screening on the numbers and/or net cost of fractures prevented.

Aged↗
PubMed1997

Outbreak of sporotrichosis among tree nursery workers.

In spring 1994, an outbreak of sporotrichosis occurred at a tree nursery in Florida; 9 (14%) of 65 workers involved in production of sphagnum moss topiaries developed lymphocutaneous sporotrichosis. A cohort study of all 65 employees was conducted to identify risk factors for sporotrichosis, and an environmental investigation was done. The risk of sporotrichosis increased significantly with the duration of working with sphagnum moss (P < .05), in particular with filling topiaries (P < .05), and with having less gardening experience (P < .05). Wearing gloves was protective (P < .005). Sporothrix schenckii was cultured from patients and sphagnum moss used in topiary production. Use of restriction fragment length polymorphism revealed an identical pattern for patient isolates that was different from the patterns of environmental isolates. Physicians should be aware of sporotrichosis in patients with ulcerative skin lesions who have a history of occupational or recreational exposure to sphagnum moss.

Adult↗
PubMed1997

The SYT protein involved in the t(X;18) synovial sarcoma translocation is a transcriptional activator localised in nuclear bodies.

The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in the fusion of the SYT gene on chromosome 18 to either of two closely related genes SSX1 and SSX2 on chromosome X. The resulting chimaeric genes express SYT-SSX1 or SYT-SSX2 fusion proteins in which the C-terminal amino acids of SYT are replaced by amino acids from the C-terminus of the SSX proteins. Using green fluorescent protein fusions we demonstrate that the SYT, SSX and the SYT-SSX proteins are nuclear proteins. We demonstrate that whilst the SSX1 protein has a uniform nuclear distribution the SYT protein has a speckled distribution in the cell nucleus, and this distribution is retained with the SYT-SSX2 fusion protein. Since the SYT speckles do not co-localise with PML-containing bodies (PODs) or spliceosomes it is possible that they represent a novel nuclear structure. Transfection of constructs expressing GAL4 fusion proteins demonstrate that the SYT domains present in the SYT-SSX fusion proteins can activate transcription of a luciferase reporter. It is proposed that the t(X;18) translocation results in the generation of an SYT-SSX transcriptional co-activator in which the addition of the C-terminal SSX domain to SYT provides a new interacting domain that redirects the SYT activation domain to different target promoters.

Cell Nucleus↗
PubMed1997

Prion protein expression in Chinese hamster ovary cells using a glutamine synthetase selection and amplification system.

Syrian hamster prion protein (PrPC) and a truncated Syrian hamster prion protein lacking the glycosylphosphatidylinositol (GPI) anchor C-terminal signal sequence (GPI-) were expressed in Chinese hamster ovary cells using a glutamine synthetase selection and amplification system. The CHO cell clones expressing the GPI- PrP secreted the majority of the protein into the media, whereas most of the PrP produced by clones expressing the full-length protein with the GPI anchor was located on the cell surface, as demonstrated by its release upon treatment with phosphatidylinositol-specific phospholipase C (PIPLC). A cell clone that expressed the highest levels of full length PrP was subcloned to obtain clone 30C3-1. PrP from clone 30C3-1 was shown to be sensitive to proteolysis by proteinase K and to react with monoclonal and polyclonal antibodies that recognize native PrPC. The recombinant PrP migrated as a diffuse band of 19-40 kDa but removal of the N-linked oligosaccharides with peptide N-glycosidase F (PNGase F) revealed three protein species of 19, 17 and 15 kDa. The 19 kDa band corresponding to deglycosylated full-length PrP was quantified and found to be expressed at a level approximately 14-fold higher than that of PrPC found in Syrian hamster brain.

Animals↗
PubMed1997

Retinal vascular network architecture in low-birth-weight men.

BACKGROUND: Low birth weight is associated with hypertension and increased cardiovascular mortality, but the mechanism of this association is not known. Hypertension is accompanied by abnormalities of the microvasculature including rarefaction. OBJECTIVE: To test the hypothesis that low birth weight is associated with an alteration in microvascular architecture. DESIGN: A stratified random sample of 100 men aged 64-74 years was selected from a cohort of men whose birth weights were known. They were of relatively high or low birth weight ('high' > or = 3700 g, 'low' < or = 3200 g) and high or low systolic blood pressure (high > or = 160 mmHg, low < or = 140 mmHg). METHODS: Retinal arteriolar geometry was defined in terms of arteriolar bifurcation angles and junction exponents (a measure of the relative diameters of parent and daughter vessels), measured from photographic diapositives using operator-directed image analysis. RESULTS: Members of low-birth-weight groups had significantly narrower bifurcation angles than did members of high-birth-weight groups (74 +/- 1 degree versus 78 +/- 1 degree, P= 0.017 by analysis of variance). There was no significant difference between angles in members of groups with high and low blood pressures. Neither birth weight nor blood pressure grouping affected junction exponents. CONCLUSIONS: Narrower bifurcation angles are associated with increased circulatory energy costs and may be related to a lower than normal microvascular density. Our finding of differences in retinal microvascular architecture might reflect a persistent alteration in vascular architecture as a result of an impairment of foetal development and could provide a mechanistic link between low birth weight and subsequently increased cardiovascular risk.

Aged↗
PubMed1997

Multicenter evaluation of proposed standardized procedure for antifungal susceptibility testing of filamentous fungi.

A multicenter study was conducted to expand the generation and analysis of data that supports the proposal of a reference method for the antifungal susceptibility testing of filamentous fungi. Broth microdilution MICs of amphotericin B and itraconazole were determined in 11 centers against 30 coded duplicate pairs of Aspergillus spp., Fusarium spp., Pseudallescheria boydii, and Rhizopus arrhizus. The effect of inoculum density (approximately 10(3) and 10(4) CFU/ml), incubation time (24, 48, and 72 h), and procedure of MIC determination (conventional and colorimetric [Alamar Blue] evaluation of growth inhibition) on intra- and interlaboratory agreement was analyzed. Based on intra- (97 to 100%) and interlaboratory (94 to 95%) agreement for both drugs, the overall optimal testing conditions identified were determination of colorimetric MICs after 48 to 72 h of incubation with an inoculum density of approximately 10(4) CFU/ml. These testing conditions are proposed as guidelines for a reference broth microdilution method.

Antifungal Agents↗
PubMed1997

Growth in infancy and bone mass in later life.

OBJECTIVE: To examine the association between weight in infancy and bone mass during the seventh decade of life in a population based cohort for which detailed birth and childhood records were preserved. METHODS: 189 women and 224 men who were aged 63-73 years and were born in East Hertfordshire underwent bone densitometry by dual energy x ray absorptiometry. Measurements were also made of serum osteocalcin and urinary excretion of type 1 collagen cross linked N-telopeptide. RESULTS: There were statistically significant associations between weight at 1 year and bone mineral content (but not bone mineral density) at the spine (P < 0.02) and femoral neck (P < 0.01) among women, and spine (P < 0.03) among men. Although serum osteocalcin was negatively correlated with bone mineral density at both sites among men and women, infant weight was not significantly associated with either biochemical marker of bone turnover. CONCLUSIONS: These data confirm our previous observations that growth in infancy is associated with skeletal size in adulthood, and suggest that skeletal growth may be programmed during intrauterine or early postnatal life.

Aged↗
PubMed1997

Acetabular dysplasia and osteoarthritis of the hip in elderly white women.

OBJECTIVES: To examine the association of acetabular dysplasia and osteoarthritis (OA) of the hip among elderly white women. METHODS: Pelvic radiographs from a sample of 165 white women aged 65 and above with radiographic hip OA and 88 white women aged 65 and above without radiographic changes of hip OA were read for evidence of acetabular dysplasia by a single trained investigator. Acetabular dysplasia was assessed using measurements of the centre edge angle and the acetabular depth, which are both reduced in this condition. Odds ratios for the association between acetabular dysplasia and hip OA were estimated using logistic regression analysis. RESULTS: Fourteen (3.4%) hips had a centre edge angle < 25 degrees, 46 (11.2%) hips had an acetabular depth of < 9 mm, and 54 (13.2%) hips had acetabular dysplasia defined as either of the above. Hips with OA had a small, but not statistically significant, increased prevalence of abnormal centre edge angle (odds ratio: 1.43; 95% confidence intervals: 0.46, 4.46), abnormal acetabular depth (1.47; 0.78, 2.77) and acetabular dysplasia (1.33; 0.74, 2.40). CONCLUSION: These results do not support the hypothesis that mild acetabular dysplasia accounts for a substantial proportion of hip OA in elderly white women. A study with a much larger sample size would be required to rule out a weak association between dysplasia and hip OA of the magnitude actually observed in our study.

Acetabulum↗
PubMed1997

Prenatal factors influencing long-term outcome.

Animal studies have shown that undernutrition before birth programmes persisting changes in a range of metabolic, physiological and structural parameters. Studies in humans have shown that men and women who had birth weights at the lower end of the normal range, who were thin or short at birth, or who were small in relation to placental size, have increased rates of coronary heart disease. This article suggests how fetal undernutrition at different stages of gestation may be linked to these patterns of early growth. Adaptations by the fetus to undernutrition are associated with changes in the concentrations of fetal placental hormones. Persisting changes in the level of hormone secretion and tissue sensitivity may link fetal undernutrition with adult disease.

Adult↗