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Biomedical subjects

D H Marshall

Publications and source records attributed to D H Marshall.

At least 37 records · Page 2Linked to original sources

Bisphosphonate space measurement in Paget's disease of bone treated with APD.

The bisphosphonate space (BPS) is a quantitative measurement of skeletal uptake of 99mTc-HMDP. We measured BPS in 36 patients with Paget's disease of bone, both before and 6 months after treatment with intravenous APD (disodium pamidronate) infusions. BPS fell after treatment, but proportionally less than serum alkaline phosphatase (ALP) and fasting urinary hydroxyproline/creatinine (HYPRO). There was no dose-response relationship between the dose of APD given and the percentage reduction in ALP and HYPRO at 6 months. Log dose of APD/pretreatment BPS, however, predicted the percentage reduction in ALP and HYPRO very well, and from the respective regression equations it was possible to predict the dose of APD needed to achieve normal values of ALP and HYPRO. In the 10 patients who achieved a normal ALP and 9 patients a normal HYPRO after more than 6 months treatment with APD (range 7-18 months), the predicted dose of APD agreed closely with the actual dose. In conclusion, our data support the idea that log dose APD/pretreatment BPS is a valid predictor of biochemical response in Paget's disease.

Alkaline Phosphatase↗

Comparison of low-dose intramuscular and intravenous salcatonin in the treatment of primary hyperparathyroidism.

The treatment of hypercalcaemia with low-dose salcatonin (100 U/d), administered either as a single intramuscular bolus or as a continuous intravenous infusion for five days, was examined in two groups of 10 patients with primary hyperparathyroidism, in a randomized open parallel study. Both the peak (0.31 +/- 0.035 mmol/L v 0.13 +/- 0.034 mmol/L) and overall (0.073 +/- 0.016 mmol/L v 0.018 +/- 0.016 mmol/L) hypocalcaemic responses were greater in the infusion group. The peak reduction in serum calcium occurred on day 2 of treatment after which there was a progressive attenuation of response. All the differences between the two methods of administration wer due to renal rather than bony effects of salcatonin. Possible causes of progressive resistance to treatment included reductions in sodium excretion and serum phosphate. It is concluded that low-dose salcatonin administered as a continuous infusion was more effective than the same dose given as a bolus. The kidney played a pivotal role both in the cause of the hypercalcaemia and in the response to treatment, including the rapid development of resistance which limits the use of salmon calcitonin in primary hyperparathyroidism to short-term reduction of serum calcium.

Alkaline Phosphatase↗

Early detection of hearing impairment: what role is there for behavioural methods in the neonatal period?

A survey of the use of behavioural methods for neonatal hearing screening in 1985 (1) concluded that the future for automated methods was quite promising. Since then several studies have assessed the two main automated behavioural tests: the Auditory Response Cradle (ARC) and the Crib-o-Gram (COG). As a screen targeted at neonatal intensive care unit (NICU) babies and other high risk groups (at present the most cost-effective form of neonatal hearing screening), the ARC is shown to have low sensitivity, even for severe hearing impairments, and the COG has an unacceptably low specificity. Any future for behavioural testing during this period must therefore rely on new implementations flowing out of a fundamental understanding of (a) the way in which neonates respond to sound and (b) the ways in which a behavioural test might complement screening with Auditory Brainstem Responses (ABR) or Evoked Oto-acoustic Emissions (EOAE). A clearer understanding of the relative benefits of detecting different degrees of hearing impairment at birth in both the NICU population and the unrestricted population is urgently needed. To determine what role should be played by specific screening programmes such benefits need to be balanced against the total costs of screening assessment and rehabilitation, in which false positives (low specificity) play a large part.

Acoustic Stimulation↗

Prediction of hearing thresholds in children using an automated toy discrimination test.

A previous paper described the development of the prototype of a semi-automated, sensitive and accurate version of the McCormick Toy Discrimination Test. In this report we describe a further development of the hardware, and demonstrate that results obtained from the automated test provide a basis for estimating the mean elevation of pure-tone threshold in the child's better ear. The correlation between speech and pure-tone results is high. The average of the better ear pure-tone thresholds at 0.5, 1 and 4 kHz can be predicted from the word-discrimination threshold obtained with the toy test, with a 95% confidence interval of +/- 11 dB.

Adolescent↗

The evolution of acute renal failure, 1956-1988.

A total of 1347 patients with severe acute renal failure, treated at a single centre between 1956 and 1988, are reviewed. Only patients with an acute uraemic episode requiring dialysis and/or with serum creatinine levels above 600 mumols/l were included. The age of patients increased from median 41.25 years in the 1950s to 60.5 years in the period 1980 to 1988. The case-mix also altered with a decline in obstetric and traumatic disease, both of which carried an excellent prognosis, and an increase in the number of elderly patients with complicated medical and surgical conditions. Survival significantly decreased with increasing age and in the presence of complicating factors such as sepsis or malignancy. Despite these changes, there has been a progressive improvement in survival from 48.8 per cent in 1956-1959 to 57.9 per cent in 1985-1988. Survival for medical and surgical cases has improved from 38.5 per cent in 1956-1959 to 57.9 per cent in 1985-1988 (overall survival for non-obstetric cases was 44.2 per cent), due to improved prognosis for acute renal failure in general and acute renal failure due to intrinsic renal disease in particular.

Acute Kidney Injury↗

Spinal osteoporosis in men.

In 94 men with crush fracture, 40 were found to have primary osteoporosis. Cross-sectional measurements of a number of variables related to bone in these 40 patients were compared to the values in various groups of healthy men aged 20-96. In healthy men, metacarpal and femoral cortical area/total area, bone volume, osteoid surfaces, seam and trabecular width, plasma dihydroepiandrosterone and estrone, and radiocalcium absorption fell with age, whereas eroded surfaces, trabecular number, urine hydroxyproline and calcium/creatinine ratios, plasma alkaline phosphatase, estradiol, androstenedione, cortisol and testosterone remained constant with age. As compared with healthy men, men with primary osteoporosis had reduced femoral cortical area/total area (P less than 0.05), and Singh grade (P less than 0.001) and in seven there was a history of forearm or femoral fracture. On iliac crest biopsy, bone volume (P less than 0.001) and trabecular number (P less than 0.01) were decreased. Plasma alkaline phosphatase (P less than 0.02) was increased but urine hydroxyproline and calcium excretion were not significantly raised. Calcium balance was negative due to failure of absorption to match urinary calcium loss and radiocalcium absorption (P less than 0.01) and plasma 1,25-dihydroxyvitamin D (P less than 0.05) were reduced.

Adult↗

Osteoporosis in hypogonadal men: role of decreased plasma 1,25-dihydroxyvitamin D, calcium malabsorption, and low bone formation.

To investigate the pathogenesis of osteoporosis in male hypogonadism we have investigated a heterogeneous group of 13 men with hypogonadism: 7 men (median age 60, range 31-79) with two or more vertebral crush fractures and 6 men (median age 61.5, range 28-76) without vertebral fractures. The group with crush fractures had trabecular and cortical osteoporosis as assessed by Singh grade, iliac crest trabecular bone volume, and metacarpal cortical area/total area. This was accompanied by an altered trabecular architecture with a reduction in number of trabeculae but no change in trabecular width, which contrasts with age-related bone loss in men where there is no reduction in trabecular number but thinning of trabeculae. The fracture group had significantly lower plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations than the nonfracture group, and this was associated with malabsorption of calcium. Irrespective of the presence or absence of osteoporosis, treatment with testosterone led to a significant increase in total and free plasma 1,25(OH)2D and an improvement in calcium absorption measured with radiocalcium and by balance techniques. In addition, urine biochemistry, metabolic balance studies, and bone biopsy suggest that skeletal retention of calcium and bone formation are increased by testosterone treatment. We conclude that male hypogonadism causes both cortical and trabecular osteoporosis and altered trabecular architecture. A major risk factor for the development of osteoporosis is reduction in plasma 1,25(OH)2D, leading to malabsorption of calcium and reduced bone formation.

Adult↗

Are scintigrams of the spine useful in vertebral osteoporosis?

To determine whether technetium diphosphonate scintigraphy could be used to date vertebral crush fractures, serial scintigrams and radiographs were obtained on two groups of 27 osteoporotic patients. Although radiologically crushed vertebrae were significantly associated with areas of increased isotope uptake on the scintigrams (p less than 0.001), this did not depend on the age of the crush fracture. Some radiologically uncrushed vertebrae, particularly in the lumbar spine, also showed increased isotope uptake.

Adult↗

A comparison of the effect of sorbitol and glucose on calcium absorption in postmenopausal women.

It has been suggested that the oral administration of sorbitol promotes calcium absorption, while glucose has no effect. We have therefore compared the effect of oral sorbitol and glucose on the absorption of radiocalcium from low and high carrier loads in healthy postmenopausal women. In a control group of 20 women given neither sorbitol nor glucose, the mean +/- SEM fractional radiocalcium absorption rate from a low carrier load was 0.65 +/- 0.05 (fraction of dose/h). In a second group of 10 women the fractional absorption rate from the low carrier load was lower (p less than 0.05) with 10 g sorbitol (0.48 +/- 0.05) than with 10 g glucose (0.65 +/- 0.08). Fractional absorption of radiocalcium from a high carrier load measured in a third group of seven women using two isotopes (oral 45Ca, IV 47Ca) was also lower (p less than 0.001) with 10 g sorbitol (0.22 +/- 0.01, fraction/3 h) than with 10 g glucose (0.29 +/- 0.02). The results suggest that calcium absorption from a low carrier load is unaltered by glucose but that absorption of calcium from both low and high carrier loads is lower with sorbitol than with glucose.

Aged↗

A stochastic model of age-related bone loss and fractures.

A stochastic model of age-related bone loss capable of predicting age-specific incidence of fractures has been implemented by Monte Carlo simulation. Each simulation involves aging a large cohort of individuals from 20 to 100 years. Every individual is randomly allocated a particular amount of bone as a young adult, an age of onset of bone loss, and parameter values that determine the subsequent bone loss. Fracture risk is assumed to be zero when the amount of bone is above a global threshold level, increasing progressively as the amount of bone falls below the threshold. From the individual fracture risks, a fracture subpopulation is identified and age-specific incidence evaluated numerically. By adjusting the model parameters, predicted and observed incidences of femoral neck fracture can be closely matched in both sexes by use of a linear function to describe age-related bone loss. For fracture of the distal radius, a close match can be achieved in women by use of an exponential function to describe the bone loss phase. In men, the incidence is independent of age; trauma, rather than the amount of bone in the forearm, appears to be the main determinant of fracture risk.

Adult↗

Studies on the prevalence and epidemiology of urinary stone disease in men in Leeds.

A postal survey among 2% of men in Leeds showed that the prevalence of urinary stone disease is 3.8%. The prevalence of upper urinary tract and spontaneously passed stones increases progressively from 0.7% in social class 5 to 5.0% in social class 1 but that of bladder stones (0.7% in the group as a whole) is independent of social class. There is an initial peak of upper urinary tract and spontaneously passed stones commencing at age 20 and having a projected prevalence at age 90 of 5.7% and a second peak of bladder stones, commencing about age 50, with a projected prevalence of 1.9%. The prevalence of stone disease increases according to the order: single less than divorced/separated less than married less than widowed men. A family history of stones tends to be higher amongst relatives of stone-formers than amongst the corresponding relatives of control subjects, the male/female ratio being 2:1. The occurrence of urinary stones is significantly associated with that of gallstones, high blood pressure, backache, arthritis and gout but not with that of peptic ulcer, diabetes, thyroid disease or bronchitis.

Adult↗

Dose-dependent response of FSH, flushes and urinary calcium to oestrogen.

The reduction of gonadotrophin levels, urinary calcium and hot flushes in post-menopausal patients by ethinyl oestradiol is shown to be dose dependent, near maximum response being achieved by a dose of 15 micrograms daily. Equivalent ethinyl oestradiol doses to a number of other gonadal hormone preparations have been assessed using the derived dose-response curve of the reduction in urinary calcium.

Calcium↗

Effects of dietary phosphorus and calcium on the intestinal absorption of Ca in sheep.

1. Wether sheep were used, some of which were prepared with a Thiry-Vella loop of jejunum. The long-term use of these loops was ensured by regular perfusion with fresh nutrient solution. 2. The net calcium absorption rate from a Thirty-Vella loop of jejunum increased with increasing intraluminal Ca concentration and was increased by the addition of 1 alpha-hydroxy-cholecalciferol (3 micrograms/l) to the loop fluid. 3. When the diet of sheep was changed from one which was normal in Ca to a diet low in Ca there was an increase in the efficiency of net Ca absorption from the jejunal loop. This dietary change was accompanied by an increase in the circulating concentration of 1,25-dihydroxy-cholecalciferol (1,25(OH)2D3). 4. An intravenous infusion of the Ca chelating agent EDTA increased the efficiency of net Ca absorption from the jejunal loop. The use of 47Ca demonstrated that this reflected an increase in the true absorption rate of Ca. 5. Dietary phosphorus deficiency reduced the efficiency of intestinal Ca absorption and was associated with a reduction in the plasma concentration of 1,25(OH)2D3.

Animals↗

Prevalence of urinary stone disease in vegetarians.

A study was carried out to determine the effect of a low animal protein diet, such as taken by vegetarians, on the risk of urinary stone disease. A nation-wide survey of vegetarians in the UK showed that the prevalence of urinary stone formation is 40-60% of that predicted for a group of individuals taken from the general population and matched for age, sex and social class with the vegetarians. The findings support the hypothesis that a diet low in animal protein reduces the risk of urinary stone formation.

Adult↗

A comparison of radioactive calcium absorption tests with net calcium absorption.

1. Four different methods of calculating calcium absorption by radioactive calcium procedures have been compared with each other and with net calcium absorption in calcium-balance studies in 100 consecutive studies on 71 patients. 2. All four isotope procedures yielded highly significant correlations with net calcium absorption derived from the balance studies, but there was little to choose between the validity of the double-isotope and single-isotope procedure judged by these criteria. 3. The rate of calcium absorption calculated from one or other isotope procedure correlated better with net calcium absorption than did the fraction of the radioactive calcium absorbed. 4. The measurement of plasma radioactivity 1 h after single-isotope administration, corrected for body weight, proved almost as useful as the more complex procedures but would be expected to underestimate calcium absorption in states of very high bone turnover.

Calcium↗