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Biomedical subjects

Cyrus Cooper

Publications and source records attributed to Cyrus Cooper.

At least 91 records · Page 5Linked to original sources
PubMed2003

Maternal protein deficiency affects mesenchymal stem cell activity in the developing offspring.

Epidemiological studies suggest that environmental influences such as maternal nutrition, programme skeletal growth during intrauterine and early postnatal life. However, the mechanism whereby the skeletal growth trajectory is modified remains unclear. We have addressed this using a rat model of maternal protein insufficiency to investigate the cellular mechanisms involved in the programming of bone development. The aims of this study were to determine whether colony formation (colony forming unit-fibroblastic, CFU-F), proliferation, and differentiation of bone marrow stromal cells from offspring of female rats maintained on normal (18% casein) or low (9% casein) protein was altered and, whether their responses to growth hormone (GH), 1,25(OH)(2)D3, and IGF-1 differed. Dams were fed an 18% casein (control) diet or 9% casein (low protein) diet from conception until the end of pregnancy. Offspring were then fed a normal protein diet until harvest at 8, 12, and 16 weeks after birth. At 8 weeks, total CFU-F and alkaline phosphatase-positive CFU-F were significantly (P < 0.01) reduced in the low protein group compared to controls. At 12 weeks, no significant differences were observed in colony formation. Modulation of osteoblast proliferation and differentiation by IGF-1 and GH was observed (P < 0.01) in the control group at 8 weeks and the low protein group at 12 weeks. Alkaline phosphatase specific activity was significantly decreased at 8 weeks (P < 0.001) in the low protein group. At 12 and 16 weeks this was reversed, with significantly increased specific activity in the low protein group. These results suggest that normal proliferation and differentiation of mesenchymal stem cells were delayed by maternal protein restriction during early life. Furthermore, these results suggest that, with skeletal maturity, "catch-up" or a physiological shift in bone cell activity was present in the low protein group. These alterations in mesenchymal stem cell function by the early environment may represent an important candidate mechanism for the programming of osteoporosis and associated consequences in later life.

Animals↗
PubMed2003

Characteristics of a prevalent vertebral deformity predict subsequent vertebral fracture: results from the European Prospective Osteoporosis Study (EPOS).

The presence of a prevalent vertebral deformity increases the risk of a future vertebral fracture. The aim of this study was to determine whether certain characteristics of the prevalent deformity, including its shape and location in the spine, influenced this effect. The 3100 men and 3500 women who took part in this analysis were recruited from population registers for participation in the European Prospective Osteoporosis Study (EPOS). Subjects had lateral thoracic and lumbar spine x-rays at baseline, and again after a mean interval of 3.8 years. Prevalent morphometric vertebral deformities on the baseline film were identified by the McCloskey-Kanis method. Incident fractures were defined as vertebrae that also satisfied the McCloskey-Kanis criterion for prevalent deformities on the follow-up film, and in addition had at least one height (anterior, mid, or posterior) which had reduced by at least 20% between films. Poisson regression was used to assess the association between various characteristics of the prevalent deformity and the risk of an incident vertebral fracture, with generalised estimating equations used to allow for the fact that each subject contributed several vertebrae to the analysis. The risk of an incident fracture increased with the number of prevalent deformities: relative risk (RR) for one prevalent deformity 3.2 (95% confidence interval (CI); 2.1, 4.8); 9.8 (95% CI;6.1, 15.8) for 2; and 23.3 (95% CI;15.3, 35.4) for 3 or more. Relative risks differed significantly according to the shape of the prevalent deformity, ranging from 5.9 (95% CI; 4.1, 8.6) if the anterior and mid heights were reduced to 1.6 (95% CI;0.8, 3.2) if the posterior and mid heights were reduced. Risks varied also according to the severity of the deformity. There were fivefold differences in relative risk of incident fracture depending on the location of the prevalent deformity within the spine. Compared to vertebrae in subjects with no deformities at baseline, the relative risk of an incident fracture within three vertebrae of a prevalent deformity was greater (7.7 (95% CI;5.6, 10.5)) than the risk in more distant vertebrae (4.0 (95% CI;2.6, 6.0)). In summary, the risk of a subsequent vertebral fracture in individuals with preexisting deformities is importantly influenced by the characteristics of these deformities.

Age Factors↗
PubMed2003

Inflammatory bowel disease and the risk of fracture.

BACKGROUND & AIMS: Although patients with inflammatory bowel disease (IBD) have reduced bone mass, there is controversy whether there is an increased risk of fracture. This study examines the risk of fracture and its predictors in patients with IBD. METHODS: In a primary care- based nested case-control study, 231,778 fracture cases and 231,778 age- and sex-matched controls were recruited. A history of IBD was assessed from medical records. RESULTS: The prevalence of IBD was 156 and 282 per 100,000 for Crohn's disease (CD) and ulcerative colitis (UC), respectively. Patients with IBD had an increased risk of vertebral fracture (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.13-2.61) and hip fracture (OR, 1.59; 95% CI, 1.14-2.23). The risk of hip fracture was greater in patients with CD (OR, 1.86; 95% CI, 1.08-3.21) compared with UC (OR, 1.40; 95% CI, 0.92-2.13). Disease severity, assessed by the number of symptoms, predicted fracture even after adjusting for corticosteroid use (OR, 1.46; 95% CI, 1.04-2.04). Only 13% of patients with IBD who had already sustained a fracture were on any form of antifracture treatment. CONCLUSIONS: Patients with IBD have a higher risk of fracture due to both disease activity and use of oral corticosteroids. However, few of these patients are receiving optimal bone-sparing therapy, highlighting the importance of increasing awareness of osteoporosis in those managing these patients.

Adrenal Cortex Hormones↗
PubMed2003

Is grip strength a useful single marker of frailty?

BACKGROUND: chronological age is widely used as a marker of frailty in clinical practice. However there can be wide variation in frailty between individuals of a similar age. Grip strength is a powerful predictor of disability, morbidity and mortality which has been used in a number of frailty scores but not as a single marker of frailty. OBJECTIVE: to investigate the potential of grip strength as a single marker of frailty in older people of similar chronological age. DESIGN: cross-sectional study with prospective collection of mortality data. SETTING: North Hertfordshire, UK. SUBJECTS: 717 men and women, aged 64-74, born and still living in North Hertfordshire, who took part in a previous study to investigate the relationship between size at birth and ageing processes in later life. METHODS: the number of significant associations between grip strength and the ageing markers was compared with numbers between chronological age and the ageing markers. RESULTS: in men, lower grip strength correlated significantly with ten ageing markers compared to chronological age which was significantly associated with seven. In women, there were six significant relationships for grip compared to three for age. The greater number of relationships between grip strength and ageing markers was not explained by the association between grip strength and age, and remained after adjustment for adult size. CONCLUSIONS: grip strength was associated with more markers of frailty than chronological age within the narrow age range studied. Grip strength may prove a more useful single marker of frailty for older people of similar age than chronological age alone. Its validity in a clinical setting needs to be tested.

Aged↗
PubMed2003

Assessment of the risk of fracture in patients with gastrointestinal disease.

Osteoporotic fractures are a common problem and associated with significant morbidity, mortality and costs. There is now increasing evidence that patients with coeliac disease are at an increased risk of osteoporotic fracture. With the advent of new therapeutic agents to reduce the risk of fracture, it is important to identify people at highest risk. The best predictors of future fracture include a previous osteoporotic fracture, low bone density, active inflammatory bowel disease, the use of oral corticosteroids and an increased risk of falling.

Accidental Falls↗
PubMed2003

Systemic nocardiosis in a splenectomized patient with systemic lupus erythematosus: successful treatment using linezolid.

A splenectomized patient with systemic lupus erythematosus, who had previously been treated with high doses of corticosteroids, presented with headaches and symptoms of a respiratory tract infection. A magnetic resonance imaging scan of the brain revealed a ring-enhancing lesion, and Nocardia asteroides was isolated from a stereotactic biopsy specimen. After adverse reactions to a number of antibiotics, infection control was finally achieved by the new oxazolidinone drug, linezolid. Nocardiosis should be considered as a differential diagnosis in all immunocompromised patients who develop an obscure infection; delay in diagnosis and subsequent initiation of appropriate treatment often results in a fatal outcome. Linezolid is a new option for the treatment of nocardiosis and is effective when given orally.

Journal Article↗
PubMed2003

Temporal analysis of rat growth plates: cessation of growth with age despite presence of a physis.

Despite the continued presence of growth plates in aged rats, longitudinal growth no longer occurs. The aims of this study were to understand the reasons for the cessation of growth. We studied the growth plates of femurs and tibiae in Wistar rats aged 62-80 weeks and compared these with the corresponding growth plates from rats aged 2-16 weeks. During skeletal growth, the heights of the plates, especially that of the hypertrophic zone, reflected the rate of bone growth. During the period of decelerating growth, it was the loss of large hydrated chondrocytes that contributed most to the overall decrease in the heights of the growth plates. In the old rats we identified four categories of growth plate morphology that were not present in the growth plates of younger rats: (a). formation of a bone band parallel to the metaphyseal edge of the growth plate, which effectively sealed that edge; (b). extensive areas of acellularity, which were resistant to resorption and/or remodeling; (c). extensive remodeling and bone formation within cellular regions of the growth plate; and (d). direct bone formation by former growth plate chondrocytes. These processes, together with a loss of synchrony across the plate, would prevent further longitudinal expansion of the growth plate despite continued sporadic proliferation of chondrocytes.

Acid Phosphatase↗
PubMed2003

Efficacy and safety of oral weekly ibandronate in the treatment of postmenopausal osteoporosis.

Adherence to oral daily bisphosphonate regimens in postmenopausal osteoporosis is currently suboptimal. Less frequent dosing regimens are likely to improve patient adherence and thus, potentially, patient outcomes. A multicenter, randomized, double-blind, noninferiority study was conducted in 235 women (53-80 yr old; time since menopause >/==" BORDER="0"> 3 yr) with postmenopausal osteoporosis [lumbar spine (L1-L4) bone mineral density (BMD) T-score </= -2] to demonstrate the noninferiority of an oral weekly (20 mg) ibandronate regimen compared with an oral daily (2.5 mg) ibandronate regimen. All patients received daily calcium (500 mg) and vitamin D (400 IU). The primary analysis was the relative change in lumbar spine (L1-L4) BMD from baseline after 48 wk in the per- protocol population. Daily and weekly ibandronate significantly increased spinal BMD by 3.47 and 3.53%, respectively, and provided substantial and similar decreases in biochemical markers of bone turnover. In the primary analysis, noninferiority of the weekly regimen to the daily regimen was demonstrated, with the boundary of the one-sided confidence interval, -0.96%, within both the -1.65% prespecified margin and a more stringent margin of -1.10%. These results demonstrate that oral weekly ibandronate provides the same efficacy and safety as oral daily ibandronate in women with postmenopausal osteoporosis.

Administration, Oral↗
PubMed2003

Analysis of environmental factors in familial versus sporadic Paget's disease of bone--the New England Registry for Paget's Disease of Bone.

UNLABELLED: A registry for Paget's Disease (PD) was created to study the environmental and familial features of this disorder. This study examines the first 202 people enrolled. Those with a family history of PD (20%) suffered earlier deformity and fracture, and tended to have grandparents born abroad. These findings suggest heritage is important in PD; the role of environment remains unclear. INTRODUCTION: The New England Registry for Paget's Disease of Bone is a database that was created to explore the distribution and determinants of disease frequency. METHODS: Using a case-series design, we explored the association of environmental factors in expression of the disease, comparing those patients with familial Paget's disease to those with sporadic Paget's disease (PD). RESULTS AND CONCLUSIONS: Analysis of the first 202 patients enrolled in the registry revealed a positive family history (FH) in 41 (20%). Significant findings in this cohort included an earlier age of onset (51 years FH+ versus 59 years FH-, p < 0.05), a trend to a higher incidence of bone deformity (49% versus 33%, p < 0.1), and an increased fracture rate (27% versus 11%, p < 0.05). Persons with a FH of PD were less likely to record the United States or Canada as their grandparents' birthplace (p < 0.01), and sibships tended to be larger (p < 0.05). A history of measles infection, childhood exposure to pets, milk ingestion, year of immigration to the United States, birth order, level of education, and functional status did not distinguish the two groups. The database confirms the high prevalence of familial PD and supports the theory that heritable factors are important in the pathogenesis of this focal disorder of bone metabolism.

Age of Onset↗
PubMed2003

Impact of ergonomic intervention on back pain among nurses.

OBJECTIVES: This study assessed the impact of ergonomic intervention on rates of low-back pain among hospital nurses. METHODS: Altogether 1239 female nurses from two hospitals in southern England completed a baseline postal questionnaire about low-back pain and associated risk factors. Between 18 and 28 months after the baseline survey, major intervention was implemented at one hospital to minimize unassisted patient handling and high-risk nursing tasks. At the other, no intervention was initiated, and efforts to improve patient handling were more limited. Thirty-two months after the baseline survey, a second postal survey was carried out in both hospitals (1,167 respondents) to reassess the prevalence of symptoms and risk factors. RESULTS: After adjustment for nonoccupational risk factors, prevalent low-back pain at baseline was associated with low job satisfaction and the performance of patient-handling activities without mechanical aids. After the intervention, the prevalence of occupational risk factors was somewhat lower, but similar improvements occurred at the comparison hospital. At the intervention site the prevalence of symptoms increased slightly (from 27% to 30%), whereas at the comparison site there was no change, the prevalence remaining constant at 27%. Calculations based on the association of risk factors with symptoms at baseline and the observed changes in their prevalence indicated that the change in risk factors was insufficient to produce a substantial reduction in back pain. CONCLUSIONS: These findings cast doubt on the means by which many hospitals are attempting to improve the ergonomics of nursing activities. More effective methods of implementing changes in work systems are needed.

Adult↗
PubMed2003

Predictors of hip joint replacement in new attenders in primary care with hip pain.

BACKGROUND: Studies investigating the factors associated with need for total hip replacement should ideally be based on prospective investigation of new attenders in primary care. AIM: To determine the incidence of listing for total hip replacement, and its predictors, among attenders in primary care with a new episode of hip pain. DESIGN OF STUDY: Prospective multicentre cohort study. SETTING: One hundred and ninety-five patients (mean age = 63 years, 68% female) with new episode of hip pain, attending primary care between November 1994 and October 1997. At the first visit, patients were evaluated for indices of pain and disability, range of hip movement, and radiographic changes of osteoarthritis. METHOD: General practitioner participants were recruited from the membership of the Primary Care Rheumatology Society to recruit all consecutive attenders with a new episode of hip pain. Annual follow-up was carried out to determine which patients were being 'put on a waiting list' for total hip replacement. RESULTS: Seven per cent of patients were put on a waiting list for total hip replacement within 12 months and 23% of patients within four years. At presentation, pain duration, pain severity, (including the need to use a stick) and restriction of internal rotation were the major clinical predictors of being put on a waiting list. Radiographic predictors of osteoarthritis performed similarly to the clinical measures. A simple scoring system based on both radiographic severity and two of the clinical measures was derived that identified groups at high likelihood of being put on a waiting list (sensitivity = 76%) with a low false-positive rate (specificity = 95%). CONCLUSION: New primary care attenders with pain are frequently accepted for total hip replacement soon after their first attendance--a decision that can be predicted by simple clinical measures.

Arthroplasty, Replacement, Hip↗
PubMed2002

Birth weight, childhood size, and muscle strength in adult life: evidence from a birth cohort study.

Environmental influences during gestation may have long-term effects on adult muscle strength. It is not known how early in adult life such effects are manifest and whether they are modified by childhood body size. The authors examined the relation between birth weight and hand grip strength in a prospective national birth cohort of 1,371 men and 1,404 women from the Medical Research Council National Survey of Health and Development who were aged 53 years in 1999. A positive relation between birth weight and adult grip strength remained after adjustment first for adult height and weight and then additionally for childhood height and weight (p = 0.006 for men and p = 0.01 for women). The effects of birth weight on grip strength did not vary by childhood or current body size and were not confounded by social class. To the authors' knowledge, this is the first study to show that birth weight has an important influence on muscle strength in midlife independent of later body size and social class. It suggests that birth weight is related to the number of muscle fibers established by birth and that even in middle age compensating hypertrophy may be inadequate. As the inevitable loss of muscle fibers proceeds in old age, a deficit in the number of fibers could threaten quality of life and independence.

Birth Weight↗
PubMed2002

The clinical grading of Raynaud's phenomenon and vibration-induced white finger: relationship between finger blanching and difficulties in using the upper limb.

OBJECTIVES: To investigate the association between functional difficulties in using the upper limb and extent and frequency of finger blanching, and the merits of these markers in grading the severity of Raynaud's phenomenon (RP) and vibration-induced white finger (VWF). METHODS: A questionnaire was mailed to a randomly selected community sample of 22,194 working-aged adults. Information was collected on cold-induced finger blanching--including the extent and frequency of attacks in the past year, and on difficulty in using the upper limb in several everyday activities (e.g. doing up buttons, opening a tight screwtop jar, and pouring from a jug). Associations were examined by logistic regression with the resultant odds ratios converted into prevalence ratios (PRs) and 95% confidence intervals (95% CI). RESULTS: Among 12,907 respondents were 1,359 who reported finger blanching and provided details of its extent and frequency. Of these, 7.4% reported frequent attacks (50 or more over the year), and 12% reported extensive blanching (affecting nine or ten digits). After adjustment for potential confounders, subjects with finger blanching reported an excess of difficulties in using the limb. Thus, in men with blanching the PR for difficulty with buttons was 4.7 (95% CI 3.9-5.8), and that for pouring from a jug was 3.8 (3.0-4.9) in comparison with men who had never had blanching. Similar associations were found in women and in those men with exposure to hand-transmitted vibration. The risk of reporting difficulties increased markedly with frequency of blanching--up to four- or fivefold in those with 50 or more attacks in the past year compared with those who had none; but differences by extent were less marked, with PRs < or = 1.6 in those with nine to ten digits affected compared with one to two digits. CONCLUSIONS: RP and VWF are both associated with difficulties in using the upper limb in everyday tasks. Further investigation of potential reporting biases is warranted, but if the associations are causal, frequency of attacks influences impairment more than extent of disease. More account may need to be taken of frequency of blanching episodes in assessing and in compensating subjects with VWF.

Adolescent↗
PubMed2002

The relationship between endogenous estrogen, sex hormone-binding globulin, and bone loss in female residents of a rural Japanese community: the Taiji Study.

The aim of this study was to clarify the relationship between endogenous estrogen, sex hormone-binding globulin (SHBG), and bone loss in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 participants-50 women in each of four age decades-were randomly selected, and baseline bone mineral density (BMD) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total estradiol (total E2) and SHBG were measured, and SHBG-unbound E2 (UBE2) was calculated using SHBG and the percent SHBG-unbound fraction ratio. BMD was measured again 3 years later, in 1996. Participants with ovariectomy or hysterectomy were excluded, and the remaining participants were categorized into four groups: premenopausal ( n = 38), perimenopausal ( n = 14), postmenopausal group 1 (5 years or less since menopause; n = 18), and postmenopausal group 2 (6 years or more since menopause; n = 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for UBE2 showed the same pattern across the groups. After the multiple regression analysis of BMD at follow-up and endogenous estrogens, in premenopausal women, there were no significant associations between BMD at follow-up and serum total E2 and UBE2. In perimenopausal women, however, serum total E2 and UBE2 were significantly correlated with trochanteric BMD at follow-up ( P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Ward's triangle BMD at follow-up ( P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle). Concerning the association between BMD at follow-up and SHBG, in the premenopausal group, serum levels of SHBG were negatively correlated with BMD at the femoral neck ( P < 0.05). In regard to partial regression coefficients for the change rates of BMD over 3 years and serum estrogens and SHBG concentrations, in perimenopausal women, UBE2 was correlated with the change rate of BMD at Ward's triangle ( P < 0.05), and in postmenopausal group 1, serum levels of SHBG were significantly negatively related to change in BMD at the trochanter ( P < 0.01). No other relationships with change in BMD were observed at any sites. These findings suggest that serum E2, UBE2, and SHBG levels differentially predict BMD levels in groups of differing menstrual status. It would, however, be difficult to predict bone loss in middle-aged and elderly Japanese women over a 3-year period using these indices alone.

Adult↗
PubMed2002

Null mutation in human ciliary neurotrophic factor gene confers higher body mass index in males.

Ciliary neurotrophic factor (CNTF) administration reduces weight in leptin-resistant mice via the signalling pathway normally activated by leptin. A G>A null mutation in the CNTF gene results in complete absence of protein. We hypothesised that absence of CNTF could lead to diminished initiation of anorectic pathways, with consequent increase in body mass. In 575 Caucasian men aged 59-73 years, the A/A genotype (frequency 1.9%) was associated with a 10 kg increase in weight (P=0.03, 2 df) and 3 kg/m(2) greater BMI (P=0.02, 2 df). There was no effect in women. The CNTF G>A null mutation therefore confers a moderate effect on obesity in males of A/A genotype, who represent 1% of the general population.

Aged↗
PubMed2002

Prenatal and childhood influences on osteoporosis.

Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most effort in fracture prevention has been directed at retarding the rate of age-related bone loss, and reducing the frequency and severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. The normal patterns of skeletal growth have been well characterized in cross-sectional and longitudinal studies. It has been confirmed that boys have higher bone mineral content, but not volumetric bone density, than girls. Furthermore, in both genders there is a dissociation between the peak velocities for height gain and bone mineral accrual. Puberty is the period during which volumetric density appears to increase in both axial and appendicular sites. Many factors influence the accumulation of bone mineral during childhood and adolescence, including heredity, gender, diet, physical activity, endocrine status and sporadic risk factors such as cigarette smoking. Measures for maximizing bone mineral acquisition, particularly through encouraging physical activity and adequate dietary calcium intake, are likely to affect the risk of fracture in later generations. In addition to these modifiable factors during childhood, evidence has also accrued that the risk of fracture might be programmed during intrauterine life. Epidemiological studies have demonstrated a relationship between birthweight, weight in infancy and adult bone mass. This appears to be mediated through modulation of the set-point for basal activity of pituitary-dependent endocrine systems such as the hypothalamic - pitutiary - adrenal (HPA) and growth hormone/insulin-like growth factor I (GH/IGF-I) axes. Maternal smoking, diet and physical activity levels appear to modulate bone mineral acquisition during intrauterine life; furthermore, both low birth size and poor childhood growth are directly linked to the later risk of hip fracture. The optimization of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations.

Adolescent↗