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Biomedical subjects

P Charles

Publications and source records attributed to P Charles.

At least 19 recordsLinked to original sources
PubMed2000

Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish Osteoporosis Prevention Study.

OBJECTIVES: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. METHODS: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual bleeding were recruited from a random sample of the background population. Mean age was 50. 8+/-2.8 years, and the number of person years followed was 9335.3. There were two main study arms: a randomised arm (randomised to HRT; n=502, or not; n=504) and a non-randomised arm (on HRT; n=221, or not; n=789 by own choice). First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women. RESULTS: After five years, a total of 156 fractures were sustained by 140 women. There were 51 forearm fractures in 51 women. By intention-to-treat analysis (n=2016), overall fracture risk was borderline statistically significantly reduced (RR=0.73, 95% CI: 0.50-1.05), and forearm fracture risk was significantly reduced (RR=0.45, 95% CI: 0.22-0.90) with HRT. Restricting the analysis to women who had adhered to their initial allocation of either HRT (n=395) or no HRT (n=977) showed a significant reduction in both the overall fracture risk (RR=0.61, 95% CI: 0.39-0.97) and the risk of forearm fractures (RR=0.24, 95% CI: 0.09-0.69). Compliance with HRT was 65% after five years. CONCLUSIONS: It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention.

Age Factors↗
PubMed2000

Negative regulation of central nervous system myelination by polysialylated-neural cell adhesion molecule.

Many factors have been shown to promote myelination, but few have been shown to be inhibitory. Here, we show that polysialylated-neural cell adhesion molecule (PSA-NCAM) can negatively regulate myelin formation. During development, PSA-NCAM is first expressed on all growing fibers; then, axonal expression is down-regulated and myelin deposition occurs only on PSA-NCAM-negative axons. Similarly, in cocultures of oligodendrocytes and neurons, PSA-NCAM expression on axons is initially high, but decreases as myelination proceeds. Importantly, if expression of PSA-NCAM is prematurely decreased in cultures, by either antibody-mediated internalization or enzymatic removal of the PSA moieties with endoneuraminidase N (endo-N), myelination increases 4- to 5-fold. In the optic nerve, premature cleavage of PSA moieties by intravitreous injection of endo-N also induces a transient increase in the number of myelinated internodes, but does not interfere with the onset of myelination. Previously, we showed that axonal electrical activity strongly induced myelination, which could be prevented by tetrodotoxin (TTX), an action potential blocker. Interestingly, removal of PSA moieties does not reverse the inhibition of myelination by TTX. Together, this suggests that myelination is tightly controlled by both positive (electrical activity) and negative (PSA-NCAM expression) regulatory signals.

Animals↗
PubMed2000

Determinants of bone mass and bone geometry in adolescent and young adult women.

Bone mass and bone geometry are considered to have independent effects on bone strength. The purpose of this study was to obtain data on bone mass and geometry in young female populations and how they are influenced by body size and lifestyle factors. In a cross-sectional, observational study in six European countries, 1116 healthy Caucasian girls aged 11-15 and 526 women aged 20-23 participated. Their radius was scanned at the ultradistal site and at a site approximately 30% of the radius length from the distal end with dual energy X-ray absorptiometry (DXA). The following parameters were assessed from the scans: bone mineral content (BMC), bone mineral density (BMD), cortical wall thickness (CWT), middistal diameter (D), cortical index (CI = 2CWT/D), and the Breaking Bending Resistance Index (BBRI = (D4 - [D-CWT]4)/D). Calcium intake was assessed by 3-day food records and physical activity by questionnaire. Body size parameters were measured by anthropometry. All parameters showed an increasing trend with pubertal stage and age, except for physical activity and calcium intake. BMC and BMD were relatively more dependent on body weight and age at menarche, whereas variation in D and the mechanical index BBRI was better explained by differences in height and grip strength. CI and CWT were relatively independent of variation in body size, whereas BMC and BBRI especially were explained for a substantial proportion (25-33% in the young adults) by body size parameters. Dietary intake of calcium and level of physical activity seem to contribute little to variation in bone parameters.

Adolescent↗
PubMed2000

Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement.

The aims of this study were to investigate myopathy in relation to vitamin D status, and to study the muscular effects of vitamin D treatment on vitamin D-deficient individuals. Further, hypovitaminosis D myopathy was investigated in relation to alkaline phosphatase (ALP), the most commonly used marker for hypovitaminosis D osteopathy. Eight patients with osteomalacia had an isokinetic dynamometer test of all major muscle groups before and after 3 months of vitamin D treatment. The most pronounced improvements in muscle power were seen in the weight-bearing antigravity muscles of the lower limbs. A cross-sectional study was performed among 55 vitamin D-deficient veiled Arab women living in Denmark and 22 Danish controls. An isometric dynamometer model was used for determination of quadriceps muscle power. Both maximal voluntary contraction (MVC) and electrically stimulated values (single twitch, maximal production rate (MPR), and maximal relaxation rate (MRR)) were determined. The women underwent high-dose vitamin D treatment and were retested after 3 and 6 months. Prior to vitamin D treatment all parameters of muscle function in the group of vitamin D-deficient Arab women were significantly reduced compared with Danish controls. MVC: 259.4 +/- 11.0 N (Newton) versus 392.6 +/- 11. 4 N (P < 10(-6)), single twitch: 47.0 +/- 1.8 N versus 74.6 +/- 2.2 N (P < 10(-5)), MPR 8.9 +/- 0.3 N/10 ms versus 14.3 +/- 0.4 N/10 ms (P < 10(-6)), MRR 4.5 +/- 0.2 N/10 ms versus 6.2 +/- 0.2 N/10 ms (P < 10(-6)). Muscle function was affected to a similar degree in women with and without bone involvement (as indicated by elevated ALP). After 3 months of vitamin D treatment all muscle-related parameters improved significantly. After 6 months only MVC was reduced compared with Danish controls (320.7 +/- 14.3 N (P < 0.02)), whereas all other measurements were normalized. Hypovitaminosis D myopathy is a prominent symptom of vitamin D deficiency, and severely impaired muscle function may be present even before biochemical signs of bone disease develop. Full normalization of hypovitaminosis D myopathy demands high-dose vitamin D treatment for 6 months or more. Our findings indicate that serum levels of ALP cannot be used in the screening for hypovitaminosis D myopathy. Assessment of s-25OHD is the only reliable test.

Alkaline Phosphatase↗
PubMed2000

Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited.

OBJECTIVES: Sunlight exposure of the skin is known to be the most important source of vitamin D. The aims of this study were: (i) to estimate vitamin D status amongst sunlight-deprived individuals (veiled Arab women, veiled ethnic Danish Moslem women and Danish controls); and (ii) through food intake analysis to estimate the oral intake of vitamin D necessary to keep a normal vitamin D status in sunlight-deprived individuals. DESIGN: Cross-sectional study amongst randomly selected Moslem women of Arab origin living in Denmark. Age-matched Danish women were included as controls. To control for racial differences, a group of veiled ethnic Danish Moslem women (all Caucasians) was included. SETTING: Primary Health Care Centre, City Vest and Department of Endocrinology and Metabolism C, University Hospital of Aarhus, Aarhus Amtssygehus, Aarhus, Denmark. SUBJECTS: Sixty-nine Arab women (60 veiled, nine non-veiled) and 44 age-matched Danish controls were randomly selected amongst patients contacting the primary health care centre for reasons other than vitamin D deficiency. Ten ethnic Danish Moslem women were included through a direct contact with their community. MAIN OUTCOME MEASURES: Serum levels of 25-hydroxyvitamin D were used as estimates of vitamin D status. Intact parathyroid hormone (PTH) was used to control for secondary hyperparathyroidism. Alkaline phosphatase and bone-specific alkaline phosphatase were used as markers for osteomalacic bone involvement. Oral intake of vitamin D and calcium were estimated through a historical food intake interview performed by a trained clinical dietician. RESULTS: Veiled Arab women displayed extremely low values of 25-hydroxyvitamin D: 7.1 +/- 1.1 nmol L-1, compared with 17.5 +/- 2. 3 (P < 0.002) in ethnic Danish Moslems and 47.1 +/- 4.6 (P < 10-17) in Danish controls. PTH was increased amongst veiled Arab women: 15. 6 +/- 1.8 pmol L-1, compared with 5.7 +/- 1.4 in ethnic Danish Moslems and 2.7 +/- 0.3 (P < 10-6) in Danish controls. The vitamin D intake (including food supplementation) was very low amongst Arab women: 1.04 microg day-1, compared with 13.53 amongst ethnic Danish Moslems and 7.49 amongst Danish controls (P < 0.0005). CONCLUSIONS: Severe vitamin D deficiency is prevalent amongst sunlight-deprived individuals living in Denmark. In veiled Arab women, vitamin D deficiency is the result of a combination of limitations in sunlight exposure and a low oral intake of vitamin D. The oral intake of vitamin D amongst veiled ethnic Danish Moslems was, however, very high, at 13.53 microgram (approximately 600 IU), but they were still vitamin D-deficient. Our results suggest that the daily oral intake of vitamin D in sunlight-deprived individuals should exceed 600 IU; most probably it should be 1000 IU day-1 to secure a normal level of 25-hydroxyvitamin D. This finding is in contrast with the commonly used RDA (recommended daily allowance) for adults in Europe: 200 IU day-1.

Adult↗
PubMed2000

Bremsstrahlung from thick targets and a diagnostic for electron energy distributions

The bremsstrahlung from solid material caused by runaway electrons may blur severely the bremsstrahlung that is recorded from gases or plasmas in order to determine the energy distribution of their hot electrons. The expressions for these emissions are presented in order to compare their characteristics. Explanations are then given for an irregular feature observed at the tip of the spectrum for solid targets. More importantly, a type of diagnostics of energy distribution functions is proposed, based on analysis of the bremsstrahlung emissivity from thick targets. It can be implemented on experimental setups by purposely inserting a well-defined solid target into the electron trajectories, and it is applied as an example to the electron beam of microwave tubes. These diagnostics could also be taken advantage of to study runaway electrons hitting vessel walls.

Journal Article↗
PubMed2000

[Pivotal role of axonal adhesion molecules in central nervous system myelination].

Close relationship between neurons and oligodendrocytes seems to be of the greatest importance during oligodendrocyte maturation and myelin formation within central nervous system. Two major factors are likely to play the decisive role in CNS myelination--adhesion molecules and electrical activity. It has been shown, both in vitro and in vivo, that blocking or stimulating electrical activity may inhibit or induce myelination respectively. The fact that even in culture oligodendrocytes myelinate solely axons and not other cellular processes present within CNS as well as the finding that normal myelin sheath compaction is encountered only around axons suggest that close interaction between oligodendrocytes and neurons is required for normal myelin formation. Adhesion molecules are most likely involved in this interaction by not only bringing the axon and the glial cell close to each other but also by transducing signals to initiate myelination. The neural cell adhesion molecule (NCAM) is a candidate molecule that could regulate axon/glial cell interaction. It is abundantly present in all growing fiber tracts of the developing CNS. Since its polysialylated from (PSA-NCAM) has been shown to disappear from axonal surface as myelination progresses and that its removal increases 4 to 5 fold myelination, it is thought to be a negative factor for myelin formation. These observations may have important implications in therapeutic strategies in demyelinating disorders like multiple sclerosis.

Axonal Transport↗
PubMed1999

[Effect of specific physiotherapy on chronic pain, functional level and quality of life in osteoporosis. A prospective randomized single-blind placebo-controlled study].

Patients suffering from osteoporotic vertebral fractures are handicapped by pain and reduced quality of life. Our aim was to investigate the effect of a short training program for osteoporotic patients with regard to pain level, use of analgetics and quality of life. We performed a prospective randomized single-blinded placebo-controlled study. The training program included general training of balance and muscle strength and stabilization of the back. The participants were randomised to 10 weeks of ambulatory training. Controls and training participants were tested weekly by registration of pain level and analgetic intake. Questionnaires on daily level of function and quality of life were given at the start and after five and 10 weeks. After three months both groups filled out the questionnaires at home. The training group had a significant reduction in pain score and use of analgetics. The distribution of functional score improved during training. Quality of life score improved significantly throughout the study and after three months. In conclusion, this ambulatory training program is effective for training osteoporotic patients with moderately severe pain and the training should be continued.

Aged↗
PubMed1999

Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis.

Treatment with a chimeric mAb to TNF-alpha has been shown to suppress inflammation and improve patient well-being in rheumatoid arthritis (RA), but the mechanisms of action of such treatment have not been fully explored. Here we show that in vivo administration of anti-TNF-alpha Ab, using a longitudinal analysis, results in the rapid down-regulation of a spectrum of cytokines, cytokine inhibitors, and acute-phase proteins. Marked diurnal variation in the serum levels of some of these were detected. These results were consistent with the concept of a cytokine-dependent cytokine cascade, and the degree of clinical benefit noted after anti-TNF-alpha therapy is probably due to the reduction in many proinflammatory mediators apart from TNF-alpha, such as IL-6, which reached normal levels within 24 h. Serum levels of cytokine inhibitors such as soluble p75 and p55 TNFR were reduced as was IL-1 receptor antagonist. Reductions in acute-phase proteins occurred after serum IL-6 fell and included serum amyloid A, haptoglobin, and fibrinogen. The latter reduction could be of importance, as it is a risk factor for atherosclerosis, which is augmented in RA patients.

Acute-Phase Proteins↗
PubMed1999

The Danish Osteoporosis Prevention Study (DOPS): project design and inclusion of 2000 normal perimenopausal women.

OBJECTIVE: In 1990 we initiated a 20 year, partly randomised study (Danish Osteoporosis Prevention Study, DOPS) in order to (a) evaluate clinical, biochemical and osteodensitometric variables as predictors of low bone mass and future osteoporotic fractures, and (b) test the hypothesis, that hormone replacement therapy (HRT) initiated shortly after menopause reduces the risk of later osteoporotic fractures. This report describes study design and baseline characteristics of the DOPS-cohort. METHODS: The study design is pragmatic, attempting to mimic the normal clinical situation. Several HRT alternatives are available according to clinical need. It was considered futile, impractical and unethical to use placebo for 20 years. Instead the study focus on hard endpoints (fractures) confirmed by independent persons (peripheral fractures) or by methods which allow investigator blinding (spinal X-rays). Statistical evaluation will focus on intention to treat analyses evaluating the decision of HRT and it's feasibility. With a compliance of 60% we will have sufficient statistical power (88%) to detect a fracture reduction of 40% in the treatments group. Clinical risk factors, current daily intakes of macronutrients, vitamins and minerals, anthropometric variables, biochemical variables (including bone markers and 25-hydroxyvitamin D), regional bone mineral density (BMD) and total body composition were assessed in all participants at entry and at various follow up intervals. RESULTS: 2016 study participants were recruited by direct mailing to a random sample of 45-58 years old women. In the randomised arm 501 were allocated to HRT and 505 to no treatment. In the non-randomised arm 219 preferred HRT and 791 preferred no treatment. Post-randomisation analysis revealed a slight but significant difference in age (50.01 versus 50.44 years) but no difference in menopausal age, prevalence of hysterectomy, educational level, BMI, serum bone alkaline phosphatase, serum osteocalcin, urine hydroxyproline or serum 25-hydroxyvitamin D. In the non-randomised arm women preferring HRT were closer to menopause, had a higher prevalence of hysterectomy, were better educated, were leaner, and had lower bone turnover than the women, who refused HRT. CONCLUSION: It is possible to include a sufficient number of perimenopausal women in a randomised 20 year study on the antifracture effect of HRT.

Body Composition↗
PubMed1999

[Attitude of general practitioners to the importance of gender and diet in disease prevention].

Three hundred and seventy-four general practitioners (GPs) in Denmark filled in a questionnaire on attitudes to include information on gender and diet in the strategy for prevention of coronary heart disease, cancer, osteoporosis, and overweight/underweight. Risk factors for disease in general were ranked as follows: smoking, alcohol, stress, diet, physical exercise, heredity and hygiene. The patients' lack of motivation, insufficient time for each patient, and inadequate knowledge about nutrition were stated as barriers to dietary counselling. The GPs stated that the gender of the patient was important only to the counselling on osteoporosis. Lack of time and insufficient knowledge were perceived as barriers for including gender specific issues in prevention. It is concluded that GPs consider dietary counselling important but lack time and knowledge. The results point at a need for better pre- and postgraduate training in nutrition, and for a better reimbursement system for time spent on prevention.

Attitude of Health Personnel↗
PubMed1999

[Prevention in general practice. Are female and male patients treated the same way? A questionnaire study].

Three hundred and seventy-four general practitioners (GPs) in Denmark filled in a questionnaire on practices regarding prevention of coronary heart disease (CHD), cancer, osteoporosis, and overweight/underweight. Half of the GPs were questioned about the issue of prevention based upon female case stories and the other half on male case stories with identical wording. The GPs more often in relation to: Prevention of CHD gave dietary counselling and recommended weight loss to slightly overweight male than female patients. Prevention of cancers gave dietary counselling and recommended weight loss and increase of exercise to female than to male patients. Prevention of osteoporosis recommended a supplement of calcium and vitamin D to female than to male patients. Treatment of underweight recommended weight gain and discussion of psycho-social issues to underweight female than male patients. In conclusion, GPs distinguish between men and women in relation to prevention strategies in general practice. There is a need for well-described prevention and action strategies with relevant gender differentiation for use in general practice.

Adult↗
PubMed1999

Calcium intake is weakly but consistently negatively associated with iron status in girls and women in six European countries.

Several studies indicate that intake of calcium can inhibit iron absorption especially when taken simultaneously. In the CALEUR study, a cross-sectional study among girls (mean 13.5 y) and young women (mean 22.0 y) in six European countries, the association between calcium intake and iron status was studied. In 1,080 girls and 524 women, detailed information on calcium intake was collected by means of a 3-d food record, and serum ferritin, serum iron, serum transferrin and transferrin saturation were measured as indicators of iron status. The mean levels of serum iron, ferritin and transferrin were 15.8 +/- 6.1 mmol/L, 34.5 +/- 19.1 microg/L and 3. 47 +/- 0.47 g/L, respectively, in girls and 16.9 +/- 7.5 mmol/L, 40. 2 +/- 30.5 and microg/L, 3.59 +/- 0.60 g/L, respectively, in women. A consistent inverse association between calcium intake and serum ferritin was found, after adjusting the linear regression model for iron intake, age, menarche, protein, tea and vitamin C intake and country, irrespective of whether calcium was ingested simultaneously with iron. The adjusted overall regression coefficients for girls and women were -0.57 +/- 0.20 and -1.36 +/- 0.46 per 100 mg/d increase in calcium intake, respectively. Only in girls, transferrin saturation as a measure for short-term iron status was inversely associated with calcium intake (adjusted overall coefficient -0.18 +/- 0.08). However, analysis per country separately showed no consistency. We conclude that dietary calcium intake is weakly inversely associated with blood iron status, irrespective of whether calcium was ingested simultaneously with iron.

Adolescent↗
PubMed1999

Dietary calcium and bone density in adolescent girls and young women in Europe.

The objective of this study was to investigate the association between dietary calcium intake and radial bone density among young women, over the whole range of intake and at different levels of calcium intake. The study design was a cross-sectional, observational multicenter investigation in six European countries. One thousand one hundred and sixteen healthy Caucasian girls aged 11-15 years and 526 women aged 20-23 years participated, after having been selected from larger population samples to represent a large range in calcium intake. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry at the ultradistal and middistal radius. Calcium intake was assessed with 3-day food records. Other potential determinants of BMD were measured by anthropometry or questionnaires. Mean calcium intake among the girls varied between 609 mg/day in Italy and 1267 mg/day in Finland; intakes for women were in a similar range. After adjustment for height, weight, and age at menarche for the women, and adjustment for age, height, weight, Tanner stage, and bone area for the girls, radial BMD at both sites did not significantly vary among quartiles of calcium intakes for both age groups. In multivariate linear regression, calcium was weakly positively associated with BMD at both sites in the girls (per 100 mg of calcium: beta = 0.57 mg/cm2, p = 0.03 for middistal BMD and beta = 0.56 mg/cm2, p = 0.01 for ultradistal BMD). For middistal BMD, the association was observed predominantly in pre-menarcheal girls. The associations were no longer statistically significant after full adjustment for all determinants of BMD, except again in pre-menarcheal girls. Radial BMD in the women was not associated with calcium intake, except after full adjustment for determinants of BMD, when ultradistal BMD became inversely associated with calcium intake (per 100 mg beta = -1.02, p = 0.03); this finding was due to results in one of the countries and not found in other countries. There was no evidence for a different relation between calcium and BMD at different levels of intake; although there was a positive association at calcium intake levels < 600 mg/day, the interaction was not significant and there was no consistent trend over intake categories. These results do not support the hypothesis that dietary calcium is a determinant of peak BMD in European women, for a wide range of intake. This study does not provide evidence that Recommended Dietary Allowances for calcium should be increased.

Adolescent↗
PubMed1998

Positive effects of physiotherapy on chronic pain and performance in osteoporosis.

The aim of this placebo-controlled, randomized, single-masked study was to establish the effects of a 10-week ambulatory exercise programme for osteoporotic patients on pain, use of analgesics, functional status, quality of life, balance and muscle strength. Fifty-three ambulatory postmenopausal women with at least one spinal crush fracture and pains within the last 3 years were randomized for physiotherapeutic training twice a week for 10 weeks or no training. The training included general training of balance and muscle strength, with stabilization of the lumbar spine. The participants were tested at baseline, week 5 and week 10 with a balance test, muscle strength test and questionnaires on pain, use of analgesics, functional status and quality of life. Twelve weeks after the supervised training had finished (week 22) they answered the same questionnaires. The study groups were comparable at baseline. The training group had a significant reduction in use of analgesics (p = 0.02) and pain level (p = 0.01) during the training period. Distribution of functional score improved; the improvement was reduced at week 22. Quality of life score improved significantly throughout the study (p = 0.0008), even after week 22. Balance improved non-significantly (p = 0.08). Quadriceps muscle strength improved significantly after 5 weeks (p = 0.04). Back extensor muscle strength improved almost significantly (p = 0.09). In conclusion, this training programme for osteoporotic patients improved balance and level of daily function and decreased experience of pain and use of analgesics. Quality of life was improved even beyond the active training period.

Aged↗