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Biomedical subjects

R Hesp

Publications and source records attributed to R Hesp.

At least 37 records · Page 2Linked to original sources

Different training patterns and bone mineral density of the femoral shaft in elite, female athletes.

The effects of sporting activity and of menstrual status on the bone mineral content of the femoral mid-shaft were investigated. The cohort consisted of 67 elite, female athletes comprising 21 runners, 36 rowers, and 10 dancers. Twenty five of these athletes were amenorrhoeic, 27 eumenorrhoeic, and 15 were taking the oral contraceptive. The bone mineral content was also measured in 13 eumenorrhoeic, sedentary women. The mean (95% confidence interval) bone mineral content in the runners was 1.51 (1.47 to 1.55) g/cm2, which was significantly higher than in the rowers, dancers, and sedentary controls whose values were 1.43 (1.40 to 1.47), 1.39 (1.33 to 1.45), and 1.40 (1.34 to 1.45) g/cm2 respectively. There was no significant difference in the bone mineral content between the amenorrhoeic, eumenorrhoeic, and oral contraceptive taking athletes. These results may have implications for devising exercise strategies to reduce the possibility of fractures in later life.

Adult↗

Quantitative measurement of faecal blood loss: comparison of radioisotopic and chemical analyses.

Blood loss in faeces was assessed by three different methods in five patients with recurrent iron deficiency. In short term (12 day) studies chemical analysis of complete stool collections for haemderived porphyrins (HemoQuant) gave results closely correlated with those obtained by measuring stool loss of 51Cr-labelled red blood cells. Whole body counting for 59Fe was relatively insensitive to small blood losses but allowed losses to be followed up over longer periods. Chemical analysis of faecal porphyrins thus provides a satisfactory alternative to radioisotopic techniques in short term quantitation of faecal blood loss, while longer term whole body counting of 59Fe may still be appropriate in a few patients for the detection and quantification of intermittent blood losses.

Adult↗

Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength.

The effect of recombinant DNA human growth hormone (rhGH) treatment in adults with growth hormone (GH) deficiency was studied in 24 patients in a double-blind placebo-controlled trial. The dose was 0.07 U/kg body wt daily. After 6 mo of treatment, significant increases were noted in the rhGH group for total cross-sectional area of thigh muscle (+11.2 +/- 3.1 vs. -0.5 +/- 3.0 cm2; P = 0.015 vs. placebo) and quadriceps muscle (+4.1 +/- 0.8 vs. +0.4 +/- 1.2 cm2; P = 0.031) measured by computerized tomography. Strong correlations were noted between lean body mass (measured as total body potassium) and total thigh muscle area in normal and GH-deficient adults both before and after rhGH treatment. Strength of hip flexors (+1.25 +/- 0.27 vs. +0.25 +/- 0.12 z-scores; P = 0.004) and limb girdle muscles increased (P = 0.02) in the rhGH group. We conclude that 1) rhGH increases lean tissue and skeletal muscle mass in adults with human GH deficiency, 2) this suggests a role for GH in the regulation of body composition of adult humans, 3) the increase in strength of limb girdle muscles after rhGH treatment suggests that adults with GH deficiency may have a proximal myopathy, and 4) the failure to demonstrate an increase in strength in other muscle groups may require the study of larger numbers of patients.

Adolescent↗

Growth hormone treatment in growth hormone-deficient adults. II. Effects on exercise performance.

Growth hormone (GH) treatment in adults with GH deficiency increases lean body mass and thigh muscle cross-sectional area. The functional significance of this was examined by incremental cycle ergometry in 24 GH-deficient adults treated in a double-blind placebo-controlled trial with recombinant DNA human GH (rhGH) for 6 mo (0.07 U/kg body wt daily). Compared with placebo, the rhGH group increased mean maximal O2 uptake (VO2max) (+406 +/- 71 vs. +133 +/- 84 ml/min; P = 0.016) and maximal power output (+24.6 +/- 4.3 vs. +9.7 +/- 4.8 W; P = 0.047), without differences in maximal heart rate or ventilation. Forced expiratory volume in 1 s, vital capacity, and corrected CO gas transfer were within normal limits and did not change with treatment. Mean predicted VO2max, based on height and age, increased from 78.9 to 96.0% in the rhGH group (compared with 78.5 and 85.0% for placebo; P = 0.036). The anaerobic ventilatory threshold increased in the rhGH group (+159 +/- 39 vs. +1 +/- 51 ml/min; P = 0.02). The improvement in VO2max was noted when expressed per kilogram body weight but not lean body mass or thigh muscle area. We conclude that rhGH treatment in adults with GH deficiency improves and normalizes maximal exercise performance and improves submaximal exercise performance and that these changes are related to increases in lean body mass and muscle mass. Improved cardiac output may also contribute to the effect of rhGH on exercise performance.

Adolescent↗

Randomized, double-blind trial of deflazacort versus prednisone in juvenile chronic (or rheumatoid) arthritis: a relatively bone-sparing effect of deflazacort.

Thirty-four children with juvenile chronic (rheumatoid) arthritis were recruited to a randomized, double-blind study of deflazacort (an oxazolone derivative of prednisone) vs prednisone. All had been receiving glucocorticoid therapy for at least 1 year and required at least 5 mg/d of prednisolone (usually as 10 mg every 2 days). Thirty-one children completed the study. Bone density trends were measured in the spine by dual photon absorptiometry and in the forearm by single photon quantitative computed tomography at 3-monthly intervals. Trends (velocities) in bone and soft tissue growth were calculated. In the spine, bone growth correlated well with indices of soft tissue growth, but covariance analysis showed a significant advantage (P less than .007) of deflazacort when spinal bone mineral growth was compared to body surface area and weight. In part this was due to a temporary interruption in weight by children receiving deflazacort, whose gain in height was comparable with that of the prednisone group. Some children in both groups improved clinically and showed catch-up growth; in these children relative spinal bone mineral growth velocities were about twice those observed for height and weight. It is concluded that during the first year of deflazacort, their spinal bone mineral content at a level that was appropriate for their height and weight. Further observations are required to establish whether this advantage can be maintained subsequently. The anti-inflammatory effects of the two glucocorticoids appeared similar.

Adolescent↗

Treatment of type 1 Gaucher's disease affecting bone with aminohydroxypropylidene bisphosphonate (pamidronate).

Two patients with Type 1 (adult) Gaucher's disease and major skeletal involvement with multiple fractures have been treated with the second generation bisphosphonate pamidronate for extensive periods. There was evidence of an immediate reduction in bone resorption, with increased calcium absorption (delayed in Patient 1), improved calcium balance and maintained or improved bone density indices in the axial and peripheral skeleton. There was no evidence of immediate relapse on treatment cessation. No toxic effects of pamidronate treatment were identified and subjective skeletal pain diminished in both patients. Histomorphometry of transiliac bone biopsies obtained before the start of treatment, after double in vivo tetracycline labelling, represents one of the earliest reports of the quantitative findings in iliac bone invaded by Gaucher cells.

Adult↗

Treatment of osteoporosis with human parathyroid peptide and observations on effect of sodium fluoride.

OBJECTIVE: To evaluate the need for a randomised study of treatment of spinal osteoporosis with human parathyroid peptide in the secondary prevention of crush fractures; to study the effect of human parathyroid hormone peptide 1-34 plus sex hormones on vertebral body cancellous bone; and, separately, to determine the effect of relatively low doses of sodium fluoride plus calcium on spinal bone mineral density. DESIGN: Open study of patients with primary or postmenopausal osteoporosis. All patients had serial bone densitometry of the spine by quantitative computed tomography and dual photon absorptiometry as well as serial densitometry of the radial midshaft (cortical) and radial distal (trabecular) bone by quantitative computed tomography. Changes in the spinal bone not forming the spongiosa of the vertebral bodies ("cortical" bone) were determined from the difference between the two axial measurements, after correction to the same units of measurement. SETTING: Northwick Park Hospital and Medical Research Council Clinical Research Centre. PATIENTS: 24 Patients who fulfilled the conventional criteria for type 1 (vertebral) osteoporosis not secondary to recognised causes other than sex hormone deficiency and with at least one crush or wedge vertebral fracture and a spinal bone density (quantitative computed tomography) less than 80 mg/cm3 or two or more fractures. Twelve patients received human parathyroid peptide and 12 sodium fluoride; they were not randomised. MAIN OUTCOME MEASURES: Trends in axial and peripheral bone mass values determined by linear, time dependent regression analyses. RESULTS: The patients receiving the peptide showed a substantial increase in vertebral spongiosa (mean 25.6 mg/cm2 two years after the start of treatment). No significant changes were seen in spinal cortical or radial bone density. The patients receiving sodium fluoride showed roughly equal increases in cancellous and cortical bone over the same period (mean increase in vertebral spongiosa 16.1 mg/cm3). No significant changes were seen in radial bone. CONCLUSIONS: Treatment of postmenopausal women with human parathyroid peptide selectively increases spinal cancellous bone density by amounts that may prove useful in secondary prevention. Peptide treatment should now be tested in a randomised study in which the important end point is prevention of fractures as the usefulness of sodium fluoride in this context is doubtful.

Bone Density↗

Rapid periarticular bone loss in rheumatoid arthritis. Possible promotion by normal circulating concentrations of parathyroid hormone or calcitriol (1,25-dihydroxyvitamin D3).

For approximately 2 years, bone loss was measured in women with early stages of rheumatoid arthritis (RA) and in control subjects, using serial computed tomography and dual photon absorptiometry. Rapid trabecular bone loss from the distal radius was observed in the RA patients but not the controls. The bone loss correlated with initial plasma levels of parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol) concentrations. It has been suggested that these humoral factors may interact with cytokines or other mediators produced in the adjacent wrist joint. Losses of the cortical bone of the radial midshaft and the lumbar spine were modest and were comparable in the 2 groups. Indices relating to both bone formation and bone resorption predicted bone loss at these 2 sites, but changes in the parathyroid hormone and calcitriol concentrations did not.

Absorptiometry, Photon↗

High indices of remodelling in iliac trabecular bone predict reduced forearm cortical bone mass indices in patients with proximal femoral fractures.

To investigate whether high bone turnover could be a predictor of cortical bone loss and a candidate risk factor for fractures of the proximal femur, 33 7.5-mm transiliac biopsies taken at fracture fixation from 48 patients who participated in a study of potential risk factors have been quantitated. Twenty-four of the 33 patients made good recoveries and about 6 weeks postoperatively consented to bone densitometry of the forearm midshaft. Forearm bone density correlated negatively (r = 0.77, P = 0.001) with the surface of trabecular bone covered with osteoid, which in osteoporotic patients with crush fractures of the vertebrae was previously shown to relate both to rates of bone formation and resorption. An important minority of these femoral fracture patients appeared to be suffering from high rates of iliac trabecular bone resorption. Thus, high bone remodelling activity could lead to excessive cortical thinning. This has pathogenetic implications which may be clinically important.

Aged↗

The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency.

In a double-blind, placebo-controlled trial, we studied the effects of six months of growth hormone replacement in 24 adults with growth hormone deficiency. Most of the patients had acquired growth hormone deficiency during adulthood as a consequence of treatment for pituitary tumors, and all were receiving appropriate thyroid, adrenal, and gonadal hormone replacement. The daily dose of recombinant human growth hormone (rhGH) was 0.07 U per kilogram of body weight, given subcutaneously at bedtime. The mean (+/- SE) plasma concentration of insulin-like growth factor I increased from 0.41 +/- 0.05 to 1.53 +/- 0.16 U per liter during rhGH treatment. Treatment with rhGH had no effect on body weight. The mean lean body mass, however, increased by 5.5 +/- 1.1 kg (P less than 0.0001), and the fat mass decreased by 5.7 +/- 0.9 kg (P less than 0.0001) in the group treated with growth hormone; neither changed significantly in the placebo group. The basal metabolic rate, measured at base line and after one and six months of rhGH administration, increased significantly; the respective values were 32.4 +/- 1.4, 37.2 +/- 2.2, and 34.4 +/- 1.6 kcal per kilogram of lean body mass per day (P less than 0.001 for both comparisons). Fasting plasma cholesterol levels were lower (P less than 0.05) in the rhGH-treated group than in the placebo group, whereas plasma triglyceride values were similar in the two groups throughout the study. We conclude that growth hormone has a role in the regulation of body composition in adults, probably through its anabolic and lipolytic actions.

Adult↗

The effect of a high protein diet on leucine and alanine turnover in acid maltase deficiency.

Leucine and alanine production rate was measured in 5 patients with acid maltase deficiency in the postabsorptive state, following 6 months on a normal diet with placebo and 6 months on an isocaloric high protein diet (16-22% protein). Whole body leucine production rate, a measure of protein degradation, expressed in terms of lean body mass was significantly greater than in five control subjects. Following the high protein diet, leucine production rate was decreased in four of the five patients but this was not statistically significant. Alanine production rate expressed in terms of lean body mass was significantly greater than in control subjects. After the high protein diet, alanine production rate and concentration were significantly decreased (p less than 0.05). There were no significant improvements in any of the clinically relevant variables measured in these patients. It is possible that a larger increase in protein intake over a longer time period may have a clinical effect.

Adult↗

Dietary intake of calcium and postmenopausal bone loss.

The use of calcium supplements to prevent postmenopausal bone loss and hence osteoporosis is widespread, but the evidence for their efficacy, either alone or in combination with other treatments, is contradictory. Skeletal measurements and dietary intake of calcium were determined in 59 healthy postmenopausal women, most of whom were within five years of the menopause. No correlation was found between current intake of calcium and either total calcium in the body or the density of trabecular or cortical bone in the forearm or vertebral trabecular bone. Dietary intake of calcium did not influence the rate of postmenopausal bone loss in the 54 women who completed 12 months of active or placebo treatment. Even when extremes of calcium intake were examined no difference was found in bone measurements between the women with the highest and lowest intakes. The results of this study suggest that the bone density of women in the early menopause is not influenced by current dietary intake of calcium.

Adult↗

Muscle and bone in paraplegic patients, and the effect of functional electrical stimulation.

1. Four paraplegic men volunteered for an exercise programme in which their paralysed quadriceps muscles were stimulated by means of computer-regulated electrical impulses applied through external electrodes. The first exercise regimen consisted of leg raising against a graded load, and during the second regimen exercise took the form of cycling on a modified bicycle ergometer. Each subject exercised five times weekly for 10 weeks during the first regimen and 32 weeks during the second regimen. 2. Whole-body protein turnover determined by L-[1-13C]leucine during feeding remained constant during both exercise regimens, when expressed either in terms of body weight or fat-free mass derived from measurements of total body potassium. 3. Quadriceps muscle protein synthetic rate increased during the study, from 0.0712 to 0.0985%/h (P less than 0.05), as did quadriceps muscle area assessed by computed tomography. 4. Bone mineral content for lumbar vertebrae was normal in all four patients, but for the femoral mid-shaft bone mineral content averaged only 66% of normal for three of the patients. Trabecular bone density in the distal tibia ranged from normal to 2% of normal for the men with the shortest and longest periods of disability, respectively. No changes in bone mineral content or bone density occurred during the exercise period.

Adult↗

Reversible trabecular bone density loss following induced hypo-oestrogenism with the GnRH analogue buserelin in premenopausal women.

Thirteen premenopausal women who each received 400 micrograms three times daily of intranasal buserelin for 6 months as treatment for endometriosis participated in this study. Cortical bone mineral content (BMC) in the mid-shaft of the right femur measured by dual photon densitometry, and trabecular bone density (TBD) in the lumbar vertebrae (L2-4) measured by quantitative computed tomography, were evaluated prior to, at the end of 6 months' buserelin treatment and after 6 months off treatment. Significant hypo-oestrogenism (P less than 0.001) was sustained during the period on treatment. The significant reduction in the mean lumbar vertebral TBD of 5.9% (P less than 0.02) observed at the end of treatment with buserelin was regained within 6 months following resumption of ovarian activity. There was a marginally significant (P = 0.07) reduction of only 0.9% in the mean femoral cortical BMC at the end of treatment. Six months after the end of treatment cortical BMC values were not significantly different from the pretreatment values. There was no significant correlation between the degree of hypo-oestrogenism and the corresponding change in vertebral TBD, (r = 0.20; P less than 0.10).

Adult↗

Skeletal blood flow, iliac histomorphometry, and strontium kinetics in osteoporosis: a relationship between blood flow and corrected apposition rate.

In 20 untreated patients with idiopathic or postmenopausal osteoporosis, kinetic studies of skeletal blood flow (using 18F) and bone turnover (using 85Sr) were combined with dynamic histomorphometry performed on transiliac biopsies taken within 6 weeks of each other. In 8 patients the combined studies were repeated after treatment. A further 5 patients were studied only while receiving treatment. As expected, skeletal blood flow measured by 18F correlated with an index of 85Sr uptake into the exchangeable pools of bone. Additionally and independently, skeletal blood flow correlated with an index of the work rate of the osteoblasts in each multicellular unit of bone (the corrected apposition rate of Parfitt). These correlations were statistically significant in both the untreated patients (P less than 0.05) and the whole group (P less than 0.001). Further indices related to bone turnover at the level of the skeleton as a whole were significantly associated with skeletal blood flow only in the combined group.

Aged↗

Estimation of whole body bone resorption rate: a comparison of urinary total hydroxyproline excretion with two radioisotopic tracer methods in osteoporosis.

In 37 female patients with primary osteoporosis, urinary hydroxyproline excretion, determined in 18 24-h consecutive complete urine collections was compared with two radioisotopic measurements of bone resorption rate measured simultaneously using 85Sr. A somewhat better fit was obtained when the kinetically determined bone resorption rate was corrected for long-term exchange processes within bone. Regression analysis showed that the intercept of the regression of hydroxyproline excretion on resorption rate, corrected or uncorrected for exchange, was significantly higher than zero at about 100 mumol/day. This is consistent with a substantial fraction of urinary hydroxyproline arising from non-bony sources. Fifteen paired studies were analysed and the results suggested that intra-individual variability in these relationships (when studies were separated by a year or more) were similar to inter-individual variability. We calculated the precision with which an estimate of bone resorption could be determined based on the calculated regressions. As a means of non-invasive quantitation of whole body bone resorption rate, the excretion rate of hydroxyproline, measured over 5 days, for example, appeared competitive with isotopic methods making no correction for exchange and relatively little worse than our exchange corrected method.

Aged↗