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Biomedical subjects

J Reeve

Publications and source records attributed to J Reeve.

At least 181 records · Page 10Linked to original sources
PubMed1986

A stochastic analysis of iliac trabecular bone dynamics.

Published normal histomorphometric data were used to derive distributions of thicknesses of trabecular plates and completed bone remodelling units (the basic multicellular unit carrying out bone remodelling, the BMU, when completed is termed a structural unit BSU). A stochastic model was set up to investigate the predictions of current BMU theory. Each of 100 trabecular "thicknesses" was drawn from the appropriate normal distribution using a pseudorandom number generator. Each day, each of its two surfaces when quiescent was assumed to have a 1:900 chance of initiating a remodelling cycle. Resorption (active, 12 days; reversal phase, 27 days) was followed by formation (94 +/- 35 days) and resulted in BMU balance when resorption depth was 36.8 +/- 9.2 micron. Fenestration (thickness less than 0) was assumed to lead to permanent loss of the trabecula. The original model unrealistically increased its mean trabecular thickness as thin trabeculae were lost. This was corrected by assuming that thin trabeculae had greater osteoblastic stimulation and a consequent tendency to thicken, perhaps due to higher mechanical loading. Over 20 years, 14% of trabeculae were lost when the BMU balance was exact and the distribution of trabecular thicknesses was unchanged. About one-half of fenestrations were due to deeper-than-average resorption cavities developing in thin trabeculae, and the remainder to coincident remodelling on both surfaces. A 10% fall in osteoblast lifespan resulted in an additional 36.7% loss of trabecular bone volume and mean trabecular thickness fell to 83.1 micron, compatible with Courpron's data. Simulating more rapid mechanisms of bone loss, approximately 50% of trabeculae could be lost after ten years by the arrest of bone formation; the doubling of resorption depth with unchanged bone formation; and a doubling in the rate of initiation of new BMUs with unchanged bone formation rate, all three followed by complete recovery of BMU balance after only two years. In each case, mean trabecular thickness fell only transiently but trabeculae continued to be lost after recovery. Prolonged osteoblast life span was the most likely explanation for the increased mean trabecular thicknesses and trabecular bone volumes seen in patients with osteoporosis, when treated with sodium fluoride plus calcium supplements or daily injections of parathyroid peptide hPTH 1-34.

Biomechanical Phenomena↗
PubMed1985

Gamma-glutamylcysteine: a substrate for glutathione S-transferases.

A new high performance liquid chromatography (HPLC) method for the separation of gamma-glutamylcysteine (GC) from glutathione (GSH) following derivatization with 1-chloro-2,4-dinitrobenzene (CDNB) was developed using a Vydac C18 column and an acetonitrile-trifluoroacetic acid gradient. When the derivatization of GC, GSH, cysteine, and cysteinylglycine was performed with GSH S-transferase, peak heights for the GC and GSH derivatives were accentuated markedly, suggesting that GC, like GSH, is an enzyme substrate. Subsequently, GC was found to be a substrate for five purified forms of rat hepatic GSH S-transferase. However, the Km for GC was about 6-20 times higher than that for GSH. GSH was a competitive inhibitor of GC-CDNB conjugation, indicating that GC and GSH share the same binding site on the transferase. However, endogenous hepatic GC content in fed rats was only 5.8 +/- 0.1 nmoles/g, three orders of magnitude lower than GSH. Thus, under normal circumstances, GC would not be expected to contribute to detoxification reactions catalyzed by the GSH S-transferases. Its weak interaction with the GSH site of the GSH S-transferases supports the role of the glycine moiety of GSH in enhancing this interaction.

Animals↗
PubMed1985

Reduction of skeletal blood flow in Paget's disease with disodium etidronate therapy.

Fourteen patients with Paget's disease of bone were treated with disodium etidronate in doses of 5 to 7 mg/kg per day. Skeletal blood flow (SBF), was measured by the modified 18F clearance technique of Wootton et al. (1976) before treatment and again during treatment. In 10 patients restudied 3-4 months after the start of therapy, SBF had fallen by a mean of 21% of the initial value, and the individual differences correlated well with the individual reductions in serum alkaline phosphatase (r = 0.77, P less than 0.01). The results were similar to those seen in an earlier study in patients treated with calcitonin. However, no early reduction in SBF was seen in six repeat studies performed at the end of the second week of treatment, in contrast with our previous findings with calcitonin.

Alkaline Phosphatase↗
PubMed1985

Pharmacokinetics of synthetic human parathyroid hormone 1-34 in man measured by cytochemical bioassay and radioimmunoassay.

Synthetic human parathyroid hormone (hPTH) 1-34 was given by intravenous injection to two healthy men. The time course of its appearance in and disappearance from the plasma was monitored both by cytochemical bioassay and by a specific radioimmunoassay (RIA) system. Immunoreactive N-region parathyroid hormone (iPTH) reached peak concentrations in plasma at 2 min after injection, whereas peak concentrations of biologically active parathyroid hormone (bioPTH) were delayed until 4-6 min. Bioassayable PTH-like activity then disappeared from the plasma (mean transit times 5.8 and 8.6 min), approximately twice as fast as immuno-reactivity. After separate subcutaneous administrations, a calculated 22-37% of administered hPTH 1-34 was subsequently detected in the plasma, by both assay systems. It was not possible to explain fully the non-parallel appearances of bio- and immuno-reactivities in the plasma after intravenous injection nor the non-parallel disappearances after both intravenous and subcutaneous injections on the basis of the present data. It seems likely, however, that in the process of biological degradation the immuno-reactive locus is inactivated by a different reaction from that which destroys bioactivity. To investigate these activity dissociations further will require the application of micro-fractionation procedures in conjunction with both types of assay system.

Adult↗
PubMed1985

Bone turnover in early rheumatoid arthritis. 1. Biochemical and kinetic indexes.

Biochemical, hormonal, and kinetic indexes of bone turnover were measured in 17 ambulant female patients with rheumatoid arthritis (RA) of recent onset (mean disease duration 14.2 months) and 19 controls. Mean serum osteocalcin concentration and 85Sr accretion rates were reduced and mean urinary hydroxyproline-creatinine ratios were increased in RA, but these differences were not significant compared with control values. Mean total body potassium (TBK), an index of skeletal muscle mass, was significantly reduced in RA, and the ratio of observed to predicted TBK correlated with indexes of bone formation. No abnormality of skeletal metabolism could be shown in early RA, but reduced rates of bone formation associated with diminished muscle mass may influence the development of osteopenia later in the disease.

Adult↗
PubMed1985

Bone turnover in early rheumatoid arthritis. 2. Longitudinal bone density studies.

Serial measurements of bone mineral in 17 ambulant female patients with rheumatoid arthritis (RA) of recent onset and 19 age matched female controls were made in the radius by computed tomography and in the vertebrae by dual photon absorptiometry. Loss of trabecular bone from the distal radius was more rapid in RA (p = 0.0014), but there was no difference in the rate of loss of bone mineral from the radial midshaft or lumbar spine compared with the controls. This study is consistent with the hypothesis that the predominant form of bone loss early in the disease is the vicinity of affected joints.

Arthritis, Rheumatoid↗
PubMed1985

Calcium absorption in rheumatoid arthritis.

Calcium absorption, assessed by a double isotope method, was found to be impaired in postmenopausal women with rheumatoid arthritis of recent onset (mean 14.2 months) compared with controls. Circulating levels of 1,25-dihydroxyvitamin D (calcitriol) were higher than in controls, suggesting a primary malabsorption of calcium in these patients. The reduction in calcium absorption correlated with several measures of disease activity, suggesting that the disease process was responsible for the intestinal defect, but an effect from non-steroidal anti-inflammatory agents cannot be excluded. A primary reduction in calcium absorption may increase the risk of osteoporosis in women with rheumatoid arthritis.

Adult↗
PubMed1985

Electrochemical detection of depressed circulating levels of vitamin K1 in osteoporosis.

If gamma-carboxylation, by the vitamin K1 - cycle, of glutamate residues of bone-matrix peptides is essential for the formation of bone, the circulating levels of this vitamin might indicate the potential efficiency of this process. Methods involving HPLC with electrochemical detection have very recently been developed for assaying the low levels of vitamin K1 that occur in normal plasma. Using such methods, we found that the circulating levels of vitamin K1 in osteoporotic patients (who had sustained either spinal crush-fractures or fractures of the neck of the femur) were significantly lower than those of age-matched control subjects.

Aged↗
PubMed1985

Measurement of lumbar spine bone mineral: a comparison of dual photon absorptiometry and computed tomography.

A comparison of computed tomography (CT) and dual photon absorptiometry (DPA) in the measurement of spinal bone mineral was made in 44 subjects of whom 26 had vertebral crush fractures. Although CT measures only trabecular bone within the vertebral body whilst DPA measures the whole vertebral segment, a good correlation was observed (r = 0.80) when these quantities were expressed in dimensionally similar units. Trabecular bone in the distal radius measured by CT correlated less well with vertebral CT (r = 0.65). Cortical bone in the radius correlated poorly with the spinal DPA measurement (r = 0.38).

Adult↗
PubMed1984

Impaired osteoblast function in osteoporosis: comparison between calcium balance and dynamic histomorphometry.

Osteoblast function was investigated in 27 patients with idiopathic osteoporosis. Transiliac bone biopsy specimens were taken after double labelling with tetracycline, and metabolic calcium balance was studied almost simultaneously. Many of the patients showed poor double labelling of their otherwise unremarkable trabecular osteoid, suggesting impaired formation of bone at many of these surfaces. This phenomenon was not accompanied by increased width of osteoid seams (as seen in osteomalacia), indicating that formation of the matrix and its mineralisation were in equilibrium. For the first time, highly significant positive correlations (p less than 0.01) were found between indices of bone formation, determined by labelling with tetracycline, and calcium balance. Thus some patients with osteoporosis who are rapidly losing bone have low rates of formation of trabecular bone both by individual osteoblasts and in relation to available bone surfaces. As histological indices of bone resorption also independently correlated strongly and inversely (p less than 0.01) with calcium balance the rate of initiation of new basic multicellular units by osteoclastic resorption of trabecular surfaces (or the depth of resorption at these surfaces) also appears to be an important determinant of mineral balance. The mechanisms that regulate the effective life span of mature osteoblasts require further investigation, particularly as some promising treatments that can increase trabecular bone volume in osteoporosis, such as parathyroid peptide hPTH (1-34) and sodium fluoride, must work through a reversal of osteoblastic depression.

Aged↗
PubMed1984

Trends in trabecular and cortical bone in the radius compared with whole body calcium balance in osteoporosis.

Mean linear attenuation coefficients for trabecular bone (T) in the distal radius and total absorption coefficients (TA) in the radial mid-shafts of 22 patients with crush fracture osteoporosis were measured serially for a year by using computed tomography. After approximately 6 months, each patient was admitted to a metabolic ward for an 18-day calcium balance study. The rate of change (trend) in trabecular bone (T) in the distal radius was a better predictor of calcium balance than the trend in mid-shaft cortical bone (TA). The scatter in the regressions of the trends of T and TA on calcium balance could be accounted for by known methodological uncertainties.

Absorptiometry, Photon↗
PubMed1984

Intestinal absorption of calcium in greyhounds: the response to intermittent and continuous administration of human synthetic parathyroid hormone fragment 1-34 (hPTH 1-34).

Long-term studies of gastrointestinal radio-calcium absorption were undertaken in adult greyhounds before and during two treatment regimes with human parathyroid hormone fragment 1-34 (hPTH 1-34). The results were correlated with plasma vitamin D metabolite levels and kinetic indices related to the balance of fluxes of calcium between plasma and the rapidly exchangeable calcium pools of bone. Compared with adult man, results obtained before treatment started showed lower indices of gastrointestinal calcium absorption and considerably higher concentrations of 24-hydroxycalcidiol in the dogs. Daily injections of hPTH 1-34 at 1.7 microgram day-1 kg-1 significantly increased indices of radiocalcium absorption and plasma calcitriol concentrations, while only causing transient calcaemic responses. The individual magnitudes of the calcaemic response correlated positively with indices of radiocalcium retention in the exchangeable pools of bone which in turn correlated positively with 'late-phase' absorption of radiocalcium from the gut. Subcutaneous infusions of hPTH 1-34 at 0.5 microgram day-1 kg-1 to the same dogs were just insufficient to cause hypercalcaemia, but increased plasma calcitriol concentrations. Indices of radiocalcium absorption were not increased. Continuous parathyroid hormone (PTH) infusion is now known to substantially down-regulate renal PTH receptor density, whereas recovery after a brief exposure to PTH occurs within 24 h. It is possible that the differences in response of the gut to the two regimes may in part be related to their differing effects on some PTH receptors.

Animals↗
PubMed1983

Skeletal blood flow measured with 18F in patients with osteomalacia and hyperparathyroidism.

Blood flow to bone was measured using the 18F clearance method described by Wootton et al. (1976) in osteomalacia (nine cases) and primary hyperparathyroidism (eight cases). Bone blood flow was elevated above normal in the osteomalacia group and was normal in the hyperparathyroid group (range 3.6%-6.8% blood volume/min). It is suggested that bone blood flow is linked with the osteoblastic response of bone, and remains normal in cases of hyperparathyroidism when no clinical signs of bone involvement are present.

Adult↗
PubMed1983

Peripheral and axial measurements of trabecular bone density in patients suspected of idiopathic vertebral osteoporosis.

In 18 patients with idiopathic crush fracture syndrome, iliac trabecular bone volume measured in 8 mm trephine biopsies correlated well with trabecular bone density as estimated in low thoracic or high lumbar vertebrae by computed tomography (CT). The CT of trabecular bone in the radius correlated poorly with the other two measurements, but it discriminated fairly well between patients and age-matched controls. These results suggest that abnormally low trabecular bone density values in the radius may be useful in predicting some patients at risk for crush fractures, but ranking patients in order of severity of axial bone loss after they have acquired a fracture requires measurements on the spine or iliac crest.

Aged↗