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Biomedical subjects

J Reeve

Publications and source records attributed to J Reeve.

At least 163 records · Page 9Linked to original sources

Brain life and brain death--the anencephalic as an explanatory example. A contribution to transplantation.

The current debate regarding the suitability of anencephalics as organ donors is due primarily to misunderstandings. The anatomical and neurophysiological literature shows that the anencephalic lacks a cerebrum because of the failure of neuralplate fusion. However, even the incomplete function of an atrophic brain stem is currently accepted at law in most if not all countries as sufficient for brain life: which is to say, cessation of breathing is currently required in order to make the diagnosis of brain death. Because of the extensive incompleteness of the anencephalic's brain, it is not possible to postpone death significantly by mechanical ventilation and intravenous feeding. It is acceptable to maintain life for a short period of time in order to allow organ transplantation subsequent to the declaration of death at the point of cessation of the capacity for spontaneous respiration. The most important issue is not transplantation, but the issue of brain life raised by the case of anencephalics. Since brain life in any significant sense begins only after the closure of the neural tube on the 30th day after conception, it is reasonable to take this as the point at which brain life begins. Laws should be amended in all countries to allow the abortion of anencephalics at any time, in that they do not at any time possess brain life.

Aborted Fetus↗

Results of a stimulatory therapy of low bone metabolism in osteoporosis with (1-38)hPTH and diphosphonate EHDP. Protocol of study I, osteoporosis trial Hannover.

In contrast to prevention, the therapy of manifest osteoporosis remains a clinically significant problem. So far all therapeutic attempts have yielded unsatisfying results. For this reason we have tried to achieve a positive bone balance by sequential stimulation and inhibition of the osseous metabolism. The therapy consisted of six 14-day courses with 400 units (1-38)hPTH per day and, in addition, starting with the 2nd week of PTH therapy, EHDP 5 mg per kg body weight per day for a total of 2 weeks. Already the initial therapeutic course resulted in a stimulation of decreased bone metabolism which could be documented by an increase in the calcium-47 accretion rate (six patients). An increase of the alkaline phosphatase could be noted (four patients); this, however, did not correlate with the calcium accretion. A positive calcium balance could, nonetheless, only be attained in four of eight patients within this period, while neither the alkaline phosphatase nor the kinetics would allow a prediction of this effect. Changes of the balance coincided with equal changes in the net calcium absorption. The urinary calcium excretion increased temporarily during the therapeutic phase. We were not able to detect an influence on the vitamin D metabolites. Histomorphometric studies did not demonstrate an increase in bone mass in the iliac creast after six therapeutic courses. Nevertheless, progressive deformations of vertebral bodies did not occur. We conclude that already after 2 weeks this therapeutic concept can lead to a stimulation of bone metabolism.

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↗

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↗

An evaluation of the contribution of membrane lipids to protection against ultraviolet radiation.

Using dioleoylphosphatidylcholine liposomes incorporating various fatty acids and neutral lipids, we have examined the ability of such lipids to provide protection of Escherichia coli and vesicular stomatitis virus (VSV) against the lethal effect of ultraviolet (254 nm) radiation. While the presence of varying amounts of saturated (palmitic) or polyunsaturated (arachidonic) fatty acids or the lipid antioxidant, alpha-tocopherol, had little effect on killing by ultraviolet radiation, considerable radioprotection was observed with beta-carotene, retinal and vitamin K-1 at final concentrations of 1 mg/ml. In another approach, vesicular stomatitis virus grown under conditions in which its envelope fatty acid composition was substantially modified, showed little change in its sensitivity to inactivation by ultraviolet radiation. The results provide strong evidence for a radioprotective role of certain, relatively rare natural lipid components with conjugated polyene systems, but not of the more ubiquitous and abundant membrane fatty acids.

Carotenoids↗

Bone turnover and trabecular plate survival after artificial menopause.

Considerable bone loss often occurs after menopause, particularly if menopause is induced by surgery. For perhaps two years bone formation fails to keep pace with the rapid acceleration of bone resorption that occurs after sex hormone withdrawal. The threat that this poses to the integrity of the skeleton is not clear. Because ethical constraints limit histological studies in normal women existing normal data and statistical modelling techniques were used to explore the dynamics of iliac trabecular bone after menopause. Trabeculae are breached during remodelling when the osteoclasts resorb to a depth equal to the trabecular thickness. Since holes in trabecular plates cannot normally be bridged such defects are probably permanent. Men lose 7% of their vertebral trabecular bone every 10 years; deeper than average resorption of trabeculae at the thin end of the normal range would account for it. The dramatic losses of trabecular bone that are seen in some postmenopausal women, however, require a period of imbalance between bone formation and bone resorption since this leads rapidly to generalised thinning. The statistical model suggested that an imbalance lasting only two years may account for eventual losses of up to half of the iliac trabecular bone. Further understanding is needed of what determines the amount of bone lost in the immediate postmenopause, which varies considerably among women. A simple mean is needed of identifying women who will lose bone most rapidly at the menopause. This must be suitable for use in general practice because these women should probably be offered long term hormone replacement treatment within a few months of the last menstruation.

Bone Resorption↗

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↗

The assessment of bone formation and bone resorption in osteoporosis: a comparison between tetracycline-based iliac histomorphometry and whole body 85Sr kinetics.

Bone formation and resorption have been measured in patients with idiopathic osteoporosis by histomorphometry of 7.5-mm trephine biopsies and in the whole body by 85Sr radiotracer methodology and calcium balances. The studies were synchronized and most were preceded by double in vivo tetracycline labeling. Correlations between histological and kinetic bone formation indices were better when better when based on the extent of double tetracycline labels than on measurements of osteoid by visible light microscopy. Correction of the kinetic data for long-term exchange, using 5 months' serial whole body counting of retained 85Sr, improved the fit of the kinetic to the histological data. A statistical analysis of the measurement uncertainties showed that the residual scatter in the best correlations (between exchange-corrected bone formation rates and double-labeled osteoid surface indices) could be attributed to measurement imprecision alone. The exchange-corrected resorption rate correlated fairly well with iliac trabecular resorption surfaces, and using a volume referent rather than a surface referent for the histological index improved the statistical fit when patients with therapeutically accelerated bone turnover were included. A much better correlation was obtained by including osteoid volume acting as an independent predictor of bone resorption in a bivariate regression with a resorption surface index. The residual errors could then be accounted for by known measurement uncertainties. Whereas osteoid taking a double label closely predicted the kinetic rate of bone formation, further analysis suggested that osteoid that took no label or a single label was more closely related to bone resorption, presumably as a secondary result of the coupling of bone formation to bone resorption. The idea that continued bone loss in some patients is associated with defective osteoblastic bone formation is supported by the low rates found in some patients by both techniques. Heuristically these studies validate both in vivo tetracycline labeling for dynamic histomorphometry and corrections for long-term exchange in kinetic studies of bone formation, providing a quantitative framework for the design and analysis of future studies of bone remodeling in the osteoporoses.

Adult↗

Vertebral collapse in juvenile chronic arthritis: its relationship with glucocorticoid therapy.

Forty-six patients with juvenile chronic arthritis maintained on glucocorticoid therapy have been reviewed retrospectively for evidence of vertebral collapse. The 23 patients who had sustained vertebral fractures had received a daily dose 2.3 times higher than those without. No patients sustained a vertebral collapse until they had received a prednisolone cumulative dose of at least 5 g. It would appear that the ideal dose, if collapse of vertebrae is to be avoided, should be not more than 5 mgs daily, probably best given as 10 mg on alternate days; unfortunately, some children with serious systemic disease cannot be controlled on these low doses. In such cases it seems justified to investigate the possible use of the oxazoline derivative of prednisolone (deflazacort) in view of its reported bone-sparing properties in adults.

Arthritis, Juvenile↗

Skeletal blood flow in metabolic disorders of the skeleton.

Results are presented of measurements of skeletal blood flow made in 80 patients with painful benign or malignant diseases of the skeleton, excluding patients with Paget's disease. In crush fracture osteoporosis, total bone blood flow was slightly lower than normal although skeletal perfusion was normal. High values of bone blood flow were seen in 14/20 patients with osteomalacia and 3/12 patients with primary hyperparathyroidism. Very high values, comparable to those seen in the most severely affected patients with Paget's disease, were seen in polyostotic fibrous dysplasia, 2 out of 4 cases of Engelmann's disease and 1 out of 3 cases of renal osteodystrophy. Results were less elevated in myositis ossificans, secondary skeletal involvement with breast and prostatic carcinomata, myelomatosis and sympathetic osteodystrophy.

Adolescent↗

Periodic courses of human 1-34 parathyroid peptide alternating with calcitriol paradoxically reduce bone remodelling in spinal osteoporosis.

In an attempt to achieve an anabolic response in both axial and peripheral bone, we treated twelve patients with osteoporosis using human 1-34 parathyroid peptide given discontinuously. The peptide was given as seven daily subcutaneous injections followed by 21 days' treatment with 0.25 mg calcitriol orally. This regime was repeated cyclically for at least sixteen cycles, of which the first four were at a lower dose of hPTH 1-34 than used subsequently. The results of treatment were monitored by kinetic, densitometric, histomorphometric and biochemical studies performed before and during treatment. Two patients developed hPTH 1-34 binding in their plasma during treatment: this was presumed to be due to the development of antibodies. The remainder, instead of increasing their indices of bone turnover as judged by iliac bone histomorphometry, were found to have consistent reductions in trabecular resorption surfaces. The other indices of bone formation and resorption measured showed no change or comparable reductions. The small increases seen in total body calcium were consistent with 'in-filling' of deleted basic multicellular units (BMUs). Because there is no evidence that calcitriol alone causes comparable reductions in activation of bone remodelling in osteoporosis, interruption of treatment with hPTH 1-34 after 7 days may have led to a failure of the activation mechanism to proceed to the resorption stage, with a consequent overall reduction in remodelling activity. This type of treatment regime, with its calcitonin-like effect, might be effective in reducing net bone loss due to imbalance between bone formation and resorption at the BMU level, particularly in patients with increased numbers of BMUs ('high turnover' osteoporosis).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Transient hypoparathyroidism induced by synthetic human parathyroid hormone-(1-34) treatment.

Daily injections of low doses of a synthetic fragment of human PTH [hPTH-(1-34) have increased iliac trabecular bone volume when used in the treatment of osteoporosis. In approximately 50 patients no major side-effects had occurred. However, during daily sc 100-micrograms injections of the peptide, one patient repeatedly developed parathyroid hypofunction which resolved each time treatment was stopped. Specific immunoglobulin G (IgG) antibodies binding [125I]hPTH-(1-34) were identified in the patient's serum, and positive immunohistochemical reactions were obtained when bovine parathyroid sections were exposed to the patient's IgG. After adsorption with PTH, the patient's IgG, free of anti-PTH antibodies, reacted with renal cell membranes, as demonstrated by indirect immunofluorescence and blocked renal PTH-dependent adenylate-cyclase activation in vitro. These results support the hypothesis that anti-PTH receptor as well as anti-PTH antibodies were generated during hPTH-(1-34) treatment, which led to the development of hypoparathyroidism when their titers were high.

Adenylyl Cyclases↗

Trabecular and cortical bone in the radii of women with parathyroid adenomata: a greater trabecular deficit, with a preliminary assessment of recovery after parathyroidectomy.

Radial bone mineral content (BMC) has been reported to be lower than normal in patients with hyperparathyroidism, but those measurements have been made with techniques which do not discriminate between trabecular and cortical bone. We have used a low radiation dose computed tomography technique to make differential measurements of trabecular and cortical bone in the radii of 18 out of 27 eligible female patients with surgically proven adenomata. Prior to parathyroidectomy there was a mean deficit of 40% (P less than 0.001) in trabecular bone density in the distal radius, and a deficit of 16% in cortical bone in the radius mid-shaft compared to normal values. Seventeen months after parathyroidectomy there was a small but significant increase in trabecular bone density in the distal radius in 13 of these patients, and no significant change in cortical bone. If these results represented the situation throughout the skeleton, it is possible that parathyroidectomy may provide some reduction in future risk of fracture in women with primary hyperparathyroidism.

Adult↗

Effect of instructional units on the analysis of related and unrelated skills.

84 majors in elementary education were divided into three groups, one control group and two experimental groups. The control group received no instruction in skill analysis while the experimental groups were instructed via videotape in either the instep kick in soccer or in throwing, catching, and striking skills. All three groups were given a skill-analysis test composed of throwing, catching, and striking skills. Statistical analysis yielded significant effect for those who viewed the throwing, catching, and striking videotape. No effect was found for the control group or the group who viewed the soccer-instep videotape. The results suggest specificity may be as important in skill analysis as in acquisition.

Adolescent↗