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Biomedical subjects

R Hesp

Publications and source records attributed to R Hesp.

At least 19 recordsLinked to original sources
PubMed1995

Gastrointestinal calcium absorption and dietary calcium load: relationships with bone remodelling in vertebral osteoporosis.

Patients with vertebral osteoporosis have a wide range of bone loss rates, bone remodelling rates and capacities for gastrointestinal (GI) calcium absorption. To test the hypothesis that variations in GI absorptive capacity determine rates of bone loss or remodelling, we have sought relationships between calcium absorption or vitamin D metabolite levels on the one hand and rates of cancellous and cortical bone loss (measured by serial quantitative computed tomography in the radius; n = 25) or indices of bone remodelling in tetracycline-prelabelled transiliac biopsies (n = 41) on the other, in a sequential untreated group. Calcium absorption (net and true) was measured in 18-day balances and by a two-isotope deconvolution method (fractional absorption and maximum absorption rate, MAR). There was no significant seasonal effect on any of these four measures of calcium absorption (variance ratio, F = 0.52-1.61, p > 0.1) or on 1,25-dihydroxyvitamin D levels (F = 0.13, p > 0.1; range 11-69 pg/ml), notwithstanding the expected seasonal effect on 25-hydroxyvitamin D levels (mean 18.7 ng/ml, zenith mid July, semi-amplitude 7.5 ng/ml; F = 6.82, p < 0.01). Neither this metabolite nor 1,25-dihydroxyvitamin D correlated with any index of calcium absorption (p > 0.1). No measure of calcium absorption (or intake) had a significant relationship with radial cortical or cancellous bone loss (p all > 0.1) but cancellous bone loss was associated with the rate of endogenous calcium excretion (r = 0.50, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1994

The effects of two different periods of weight-reduction on selected performance parameters in elite lightweight oarswomen.

Six successful members of the British Women's Lightweight Rowing Team were assessed before and after two-month (1990) and four-month (1991) periods of weight-reduction controlled by reduced caloric intake, while engaged in their normal physical training. Fat free mass (FFM) was calculated from body weight (BW) by utilising total body potassium measurements. Maximal oxygen intake (VO2max), respiratory anaerobic threshold (Tvent), upper body anaerobic peak power (PP) and mean power (MP) outputs, and knee flexor (KF) and extensor (KE) isokinetic peak torques were among the physiological parameters assessed. No statistical differences were noted between the data obtained prior to the two weight-reduction periods, and both periods resulted in lower BW (p < 0.001) and FFM (p < 0.05); approximately 50% of the lost BW was FFM. At the end of the two-month weight-reduction period Tvent (p < 0.02) and KF (p < 0.02) decreased. In contrast, a similar BW loss during the four-month period was associated with higher VO2max (p < 0.01) and PP (p < 0.05) compared with values prior to weight reduction. Comparisons between the percentage changes pre to post BW loss showed that the longer weight-reduction period was associated with significantly improved VO2max (p < 0.01), Tvent (p < 0.005), PP (p < 0.05) and KF (p < 0.05). We conclude: a) the proportion (50%) of weight lost as FFM in the present elite rowers is higher than the suggested optimal figure of 22%, and b) compared to four months, 6-7% of BW loss over two months may adversely influence fitness-related parameters in international lightweight oarswomen.

Adipose Tissue↗
PubMed1993

Temporal variations in iliac trabecular bone formation in vertebral osteoporosis.

The histologic heterogeneity of osteoporosis relative to normal controls has attracted great interest. There has been controversy as to whether patients with high turnover osteoporosis may convert to a normal or low turnover form, and vice versa. We have studied 44 patients over 12 years by dynamic histomorphometry and 85Sr kinetics+calcium balance performed within 60 days in 20 patients (Group 1) and 75-808 days apart in the remainder (Group 2). In the first group, the histologic tissue level bone formation rate (BFR/BV or BFR/BS) was predictive of the 85Sr measurements of bone formation (r = 0.66 P < 0.01). There was no statistically significant correlation in Group 2 and the regression coefficients were significantly different (P = 0.01). Periodic regression was used to determine if seasonal changes were responsible for this loss of correlation; none was found that was of statistical significance. No systematic changes with time in bone formation were found in Group 2 during the period of observation; nor were consistent secular changes detected when the data for both groups were examined according to procedure date. In conclusion, bone formation may change with time in postmenopausal osteoporosis. Evidence that these changes are systematic was not found and this has implications for the design of treatment studies.

Aged↗
PubMed1993

Human parathyroid peptide treatment of vertebral osteoporosis.

Previous studies have shown that treatment with daily injections of human parathyroid peptide (hPTH) 1-34 increase axial cancellous bone mass partially at the expense of peripheral cortical bone. In the present work the same hPTH 1-34 regime given for 12 months has been combined with oestrogen or nandrolone therapy to control peripheral bone resorption. Spinal and iliac cancellous (but not cortical) bone increased by 40%-50% above initial values while no perceptible changes occurred in radial cortical or cancellous bone. The evidence of radiokinetic and histomorphometric studies performed before and in the last months of treatment suggested that bone remodeling had proceeded through a transient anabolic phase with increased activation, but that activation had become normal after 11-12 months in the cancellous bone of the ilium whereas it continued to be raised elsewhere in the skeleton. It is concluded that in combination with oestrogens, hPTH peptides given daily injections hold great promise for the treatment of patients with osteoporosis who have already lost substantial amounts of spinal cancellous bone.

Absorptiometry, Photon↗
PubMed1993

Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency.

The effects of 6 months' treatment with recombinant human growth hormone (rhGH) on serum lipids and lipoproteins were assessed in 24 adult patients with GH deficiency in a double-blind, placebo-controlled trial. Compared with age-, weight-, and sex-matched controls, the patients had significantly higher serum concentrations of total cholesterol (P = .002), low-density lipoprotein (LDL) cholesterol (P < .001), apolipoprotein B ([apoB] P = .011), and triglyceride (P = .017), and lower concentrations of high-density lipoprotein (HDL) cholesterol (P < .001). The prevalence of elevated serum cholesterol, triglyceride, LDL cholesterol, and apo B levels was 39%, 26%, 39%, and 25%, respectively; 75% of patients had decreased concentrations of HDL cholesterol. Treatment with rhGH (0.07 U/kg daily) resulted in decreases in total cholesterol level (5.8 +/- 0.3 to 5.1 +/- 0.3 mmol.L-1 over 6 months; P = .01 compared with placebo), LDL cholesterol level (4.22 +/- 0.25 to 3.19 +/- 0.23 mmol.L-1; P = .0003), LDL:HDL cholesterol ratio (5.57 +/- 0.47 to 3.29 +/- 0.33; P = .03), apo B level (1.07 +/- 0.06 to 0.84 +/- 0.07 g.L-1; P = .003), and apo B: A-1 ratio (0.73 +/- 0.05 to 0.69 +/- 0.05; P = .01). HDL cholesterol and apo A-1 levels did not change following rhGH treatment. The changes in lipid and lipoprotein levels were not significantly related to changes in insulin, thyroid hormones, insulin-like growth factor-1 (IGF-1), or indices of adiposity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Physical activity as a determinant of bone conservation in the radial diaphysis in rheumatoid arthritis.

OBJECTIVES: To determine if increasing physical activity is protective of diaphysial (cortical) bone mass METHODS: Fifteen patients attending two rheumatology clinics who had developed seropositive or classical rheumatoid arthritis up to 26 months previously were studied prospectively for two to three years. Rates of loss (or gain) in bone mass in the radial diaphysis and the trabecular bone of the distal radius were measured by quantitative computed tomography, and in the spine by dual photon absorptiometry. Physical activity was assessed by the Framingham physical activity index. Disease activity was followed at three-monthly clinic visits at which the haemoglobin, erythrocyte sedimentation rate, and platelet count were measured. The urinary hydroxyproline to creatinine ratio and plasma osteocalcin were measured at the beginning and end of the observation period. RESULTS: Eleven patients required treatment with disease modifying drugs but none was given corticosteroids. Those whose physical activity did not improve lost radial diaphysial bone at about 4% annually. There was, however, a statistically significant inverse relation, accounting for 48.5% of the variance, between bone loss at this site and improvement in physical activity as assessed by the Framingham index. The other two sites showed much weaker associations. Adjusting for indices of disease activity hardly affected the first relation. Three biochemical indices related to bone turnover showed weak tendencies to decrease with increasing physical activity. CONCLUSIONS: Peripheral cortical bone, distant from inflamed joints, is conserved more successfully in patients who achieve higher levels of physical rehabilitation. This may have implications for avoiding long bone fractures later in the disease.

Absorptiometry, Photon↗
PubMed1993

Biochemical prediction of changes in spinal bone mass in juvenile chronic (or rheumatoid) arthritis treated with glucocorticoids.

OBJECTIVE: To identify biochemical predictors of spinal bone mineral growth and the development of spinal osteoporosis in children with juvenile chronic arthritis (JCA) treated with glucocorticoids. METHODS: Bone mass measurements were made at 3 monthly intervals for one year in 31 children. At each visit, blood and urine were obtained for assessment of laboratory indices related to the acute phase response and bone remodelling rates. Assessments were also made of joint inflammation (simple joint count). RESULTS: Plasma albumin and C-reactive protein (CRP) concentrations contributed independently of height velocity to the prediction of lumbar spinal bone mineral growth, but only when averaged over the year of observation. The simple joint count did not usefully predict spinal bone mineral changes in the individual patient, nor did any measured index normally related to bone turnover (plasma osteocalcin, 25 (OH) vitamin D, urinary hydroxyproline). Mean values of the simple joint count were predicted by mean CRP and CRP trends. Joint count trends were predicted by hemoglobin trends. None of these relationships, although statistically significant, was strong enough to predict individual outcomes precisely. CONCLUSIONS: Failure of spinal bone mineral growth is related to failure of growth in height and weight but also to biochemical markers for the activation of the acute phase response. Failure of bone growth to correlate with increased hydroxyprolinuria or plasma osteocalcin concentrations may be attributed to the confounding effect of glucocorticoid treatment on plasma osteocalcin levels in children whose bone resorption is little changed from normal levels despite their reduced growth. Biochemical measurements are weak substitutes for bone densitometry in monitoring spinal growth in these children.

Adolescent↗
PubMed1993

Deflazacort in juvenile chronic arthritis.

Vertebral crush fracture associated with glucocorticoid therapy causes major morbidity in juvenile chronic arthritis (JCA). Deflazacort (DFZ) may have an advantage over prednisone (PRED) because of its alleged bone sparing properties. Of 34 children with JCA receiving more than 5 mg PRED/day, 31 completed a 1-year, double blind, randomized, comparative trial of DFZ and PRED. Patient characteristics at trial entry were well matched. DFZ and PRED were prescribed in equivalent amounts. DFZ achieved similar disease control to PRED, and was not associated with untoward effects. Joint counts, hematological indices and biochemical values did not differ between treatment groups initially or during the trial. Bone density trends (velocities) in the lumbar spine were measured using dual photon absorptiometry at 3-monthly intervals and trends in bone and soft tissue growth calculated. Lumbar spine bone growth correlated with indices of somatic growth, with wide ranges in each group. Co-variance analysis showed a significant advantage (p < 0.007) of DFZ over PRED when spinal bone density was compared to body surface area and weight. Children taking DFZ showed less weight gain but similar height gain to children taking PRED. Children with poor or no somatic growth showed significant lumbar bone loss only in the PRED group. Of the children originally treated with PRED; 11 were switched to DFZ after completing the double blind study. Data for 26 children treated with DFZ for 1 year were thus available and confirmed a significantly greater rate of spinal bone growth relative to somatic growth, p < 0.002.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1992

Bone remodelling does not decline after menopause in vertebral fracture osteoporosis.

There is considerable current interest in whether activators of bone remodelling, such as IL-1 and other cytokines, are involved in the pathogenesis of osteoporosis. We have therefore studied indices relating to remodelling activation in 50 patients with postmenopausal vertebral osteoporosis and 12 with hip fracture osteoporosis in comparison with 25 age- and sex-matched controls. Because of uncertainty regarding the accuracy of current biochemical markers of bone formation with respect to the estimation of whole body rates of bone formation, a 85Sr-based radioisotopic method was used. This method was previously validated by comparison with data obtained after double in vivo labelling of transiliac biopsies taken nearly simultaneously. Bone resorption was estimated from urinary hydroxyproline data. Controls selected for their continued good health showed a progressive and statistically highly significant decline in indices of bone formation with time after menopause. No such decline was seen in the vertebral fracture patients (P less than 0.005). There were no hip fracture patients within 10 years of menopause so this statistical test could not be applied appropriately to them. The hydroxyproline data were consistent with the suggestion arising from the bone formation data that remodelling declines progressively after menopause in the controls but not in the vertebral fracture patients. The data also suggested that these two fracture groups were in more negative calcium balance than the controls, this being particularly marked in the hip fracture cases. Plasma osteocalcin data correlated moderately well with the kinetic measurements of bone formation. It is concluded that vertebral fracture osteoporosis is associated with prolongation of menopausal levels of bone remodelling which is inappropriate by comparison with healthy controls.

Age Factors↗
PubMed1992

Basal metabolic rate in adults with growth hormone deficiency and in patients with acromegaly: relationship with lean body mass, plasma insulin level and leucocyte sodium pump activity.

1. The relationship of lean body mass, plasma insulin concentration and leucocyte active sodium transport with basal metabolic rate was investigated in 24 adults with growth hormone deficiency before and after treatment with recombinant human growth hormone and in 10 patients with untreated acromegaly. 2. Based on total-body potassium determined by whole-body 40K counting, patients with acromegaly had increased lean body mass, whereas lack of growth hormone was associated with decreased lean body mass. 3. By indirect calorimetry, patients with acromegaly had increased basal metabolic rates and patients with growth hormone deficiency had decreased values when expressed as percentages of values predicted from the WHO/FAO/UNU equations. Basal metabolic rate expressed in terms of lean body mass was similar in acromegaly and growth hormone deficiency, but was higher than normal in both patient groups. 4. The leucocyte ouabain-sensitive sodium efflux rate constant was decreased in both patients with acromegaly and patients with growth hormone deficiency, and there was no correlation with basal energy expenditure, fasting plasma insulin level or serum growth hormone level. 5. There was no increase in the sodium efflux rate constant in patients with growth hormone deficiency after 1 month on treatment with recombinant human growth hormone. 6. Apparent differences in basal metabolic rate in growth hormone deficiency and acromegaly are due to changes in lean body mass. Both adults with growth hormone deficiency and patients with acromegaly have increased energy expenditure, probably owing to changes in fuel metabolism which are not reflected in the leucocyte sodium pump activity.

Acromegaly↗
PubMed1992

Whole-body and site-specific bone remodelling in patients with previous femoral fractures: relationships between reduced physical activity, reduced bone mass and increased bone resorption.

1. A new tracer method is described for the non-invasive measurement of bone formation in the proximal femur. The method is based on our previously described whole-body method using 85Sr as the tracer (Reeve, J., Hesp, R. & Wootton, R. Calcif. Tissue Res. 1976; 22, 191-206). It allows correction to be made for long-term exchange processes within the skeleton. 2. The method has been applied in a study of regional and whole-body bone formation in 12 rehabilitated patients who had previously suffered a fracture of the proximal femur. Twelve healthy control subjects were studied, who were selected for their good health and continued physical activity. The aim was to explore the relationship between bone formation and physical activity. 3. Bone formation was similar in the two groups, both regionally and in the whole body. Based on analyses of four cadaver specimens, bone formation in the proximal femur was about one and two-thirds times that in the whole skeleton when related to mass of calcium in the region of interest. 4. Whole-body bone resorption, estimated from five measurements per subject of hydroxyproline excretion in relation to creatinine excretion, was significantly higher in the fracture patients (P < 0.01, Wilcoxon's test). 5. Estimates of current physical activity (and immediate pre-fracture physical activity) were made with a newly devised questionnaire. Historical levels of physical activity (at ages 15-45 years) were determined with Astrom's questionnaire. No bone formation index correlated with any index of physical activity. Urinary hydroxyproline excretion correlated inversely both with current physical activity and historical physical activity (for both regression coefficients P < 0.01). 6. The results are discussed in the light of our current understanding of the control of bone remodelling by the discrete basic multicellular units of bone. The opportunity to study regional bone resorption by the additional use of serial dual X-ray absorptiometry of the same region will in future allow the direct monitoring of the effects of therapeutic interventions which have been designed to prevent contralateral hip fracture.

Aged↗
PubMed1992

Validation of a method of treating menorrhagia by endometrial ablation.

Menstrual blood loss was measured by intravenous injection of radioactive iron (59Fe) and whole-body counting in 19 women complaining of menorrhagia due to dysfunctional bleeding. Fifteen patients were then treated by radiofrequency endometrial ablation, after which blood loss was re-measured. The majority of the patients were bleeding excessively before treatment (mean 281 (SD 156) ml per cycle averaged over two cycles, range 49-665 ml, n = 19). In the 15 treated patients, average blood loss was reduced to 52 (SD 39) ml per cycle and the mean reduction in blood loss was highly significant (P < 0.001). These quantitative data correlate well with the patients' subjective reports.

Adult↗
PubMed1992

Regulation of iron absorption in iron loaded subjects with end stage renal disease: effects of treatment with recombinant human erythropoietin and reduction of iron stores.

The effects on iron absorption of variation in erythroid activity, haemoglobin and iron stores were studied in six anaemic dialysis-dependent subjects in whom iron stores were increased from previous red cell transfusions. Gastrointestinal mucosal uptake and whole body retention of oral iron were measured at the beginning of the study, after starting treatment with recombinant erythropoietin (but before significant increase in haemoglobin), after partial correction of anaemia, after further reduction of iron stores by repeated phlebotomy, and when erythropoiesis decreased from the discontinuation of treatment with erythropoietin. Between successive measurements, valid comparisons were made in five subjects. Correction of anaemia decreased whole body retention of iron through decreased mucosal uptake (P = 0.032). Further reduction in iron stores through repeated phlebotomy whilst the increase in haemoglobin was maintained by treatment with erythropoietin, tended to increase whole body retention of iron through an increase in mucosal transfer (P = 0.010). With initial enhancement of erythropoiesis in anaemic iron-loaded subjects there was no change in any measured component of iron absorption. However, after correction of anaemia and reduction of iron stores, a decrease in erythropoiesis was associated with decreased whole body iron retention in all subjects through decreased mucosal transfer (P = 0.028). The data suggest that anaemia upregulates mucosal iron uptake, and that erythroid activity upregulates mucosal transfer but that this latter effect may be counter-balanced by iron overload which downregulates mucosal transfer.

Adult↗
PubMed1992

Histology of skeletal muscle in adults with GH deficiency: comparison with normal muscle and response to GH treatment.

The histology of needle biopsy specimens of skeletal muscle from the vastus lateralis was quantitatively assessed in a group of adults with growth hormone (GH) deficiency, most of whom had hypopituitarism treated with conventional pituitary hormone replacement. The mean age of the 21 patients (16 males and 5 females) was 39 +/- 2 (SEM). Comparisons were made with age- and sex-matched controls following six months double-blind, placebo-controlled treatment with recombinant human GH (rhGH) in the GH-deficient patients. Before treatment, needle muscle biopsies from patients with GH deficiency showed mean type I and II fibre areas of 5,153 +/- 273 and 4,828 +/- 312 microns 2 respectively, which did not differ from the controls (4,482 +/- 306 and 4,699 +/- 310 microns 2). Percentages of type I fibres were similar in the two groups (47.2 +/- 2.5% in GH deficiency and 45.3 +/- 2.2% in controls). No difference in the variability of type I or II fibre areas was demonstrated between the groups. Correlations between the relative contribution to total fibre area by type I fibres (mean fibre area x percent) and maximal oxygen uptake (p = 0.006), and between type II fibres and quadriceps force (p = 0.035) were noted in GH-deficient adults before treatment. Following rhGH treatment, no change was noted in mean fibre areas, variability of fibre areas, or percentage of either fibre type.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Iliac trabecular bone formation predicts radial trabecular bone density changes in type 1 osteoporosis.

In 28 patients with idiopathic or postmenopausal type 1 (spinal crush fracture) osteoporosis, resorption indices and dynamic measurements of trabecular bone formation based on in vivo tetracycline labeling in 7.5 mm transiliac biopsies have been compared with trends in radial cortical and trabecular bone density measured with computed tomography. Positive correlations were observed between trabecular bone density trends in the radius and indices of bone formation in the ilium. These were improved when one of the two resorption indices was included with a formation index in bivariate regressions. Marked interindividual variations in radial bone density trends were also seen in cortical bone. These correlated poorly with trends in trabecular bone. Weak negative relationships between cortical bone trends and indices relating to bone formation and resorption were observed, but a positive association was seen with single-labeled surfaces on iliac trabeculae. If, as has been suggested, there are periodic variations in bone formation, the results suggest that axial and peripheral trabecular bone density trends are synchronized in osteoporosis, perhaps in response to systemic factors, such as circulating hormones.

Aged↗
PubMed1991

hPTH 1-34 treatment of osteoporosis with added hormone replacement therapy: biochemical, kinetic and histological responses.

Twelve patients with vertebral fracture osteoporosis were recruited into a trial of treatment with hPTH 1-34 by daily injection for 1 year combined (from the 5th month) with an anti-resorptive agent (oestrogen, n = 9; nandrolone, n = 3). Treatment outcomes were monitored by biochemical and radiotracer measurements together with histomorphometry of transiliac biopsies before and at the end of treatment following double in vivo pre-labelling with demethylchlortetracycline. Indices of whole body bone formation, obtained from the analysis of 85Sr data, showed substantial increases (P less than 0.005) for all three indices measured) while biochemical (hydroxyproline) and kinetic measurements of bone resorption showed modest and equivocal changes only. As a result calcium balance improved. Gastrointestinal calcium absorption showed a tendency to improve, while urine calcium decreased; but these changes were statistically not significant except for radiocalcium absorption in the oestrogen treated subgroup. Histomorphometry revealed substantial increases in cancellous bone volume as reported previously with hPTH 1-34 given alone. However, iliac (as distinct from whole body) indices related to bone formation and resorption appeared to have returned towards pre-treatment values by the time of the second biopsy under the influence of the anti-resorptive agent given with the hPTH 1-34. It is confirmed that hPTH 1-34 therapy can increase iliac cancellous bone mass (as well as spinal cancellous bone mass as reported earlier) without a long-term increment in whole body bone resorption, providing the hPTH is combined with an anti-resorptive agent.

Aged↗
PubMed1991

Cardiovascular effects of growth hormone treatment in growth-hormone-deficient adults: stimulation of the renin-aldosterone system.

1. In adult humans with growth hormone deficiency, treatment with growth hormone has recently been shown to have major anabolic effects and to improve exercise performance. The cardiovascular effects of growth hormone in adults with growth hormone deficiency were examined in 24 patients treated with recombinant human growth hormone (0.07 units/kg at night) in a double-blind, placebo-controlled trial lasting 6 months. 2. Compared with placebo, resting M-mode echocardiography showed increases in left ventricular end-diastolic dimension and stroke volume in the group treated with recombinant human growth hormone. No differences were noted between the groups with respect to left ventricular end-systolic dimension, fractional shortening, wall thicknesses or mean arterial blood pressure. Left ventricular myocardial mass increased in the group given recombinant human growth hormone. 3. The supine plasma renin activity was increased and remained elevated over the 6 months, whereas the plasma aldosterone concentration was unchanged, after treatment with recombinant human growth hormone. Clinical signs of sodium retention were evident during the first 3 months of treatment with recombinant human growth hormone. 4. We conclude that treatment with recombinant human growth hormone in adults with growth hormone deficiency resulted in small increases in left ventricular pre-load, due to the sodium-retaining action of growth hormone. Activation of the renin-aldosterone system was involved in such changes. Myocardial hypertrophy was observed without changes in mean arterial pressure, reflecting the anabolic action of growth hormone.

Adult↗