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Biomedical subjects

M Peacock

Publications and source records attributed to M Peacock.

At least 91 records · Page 5Linked to original sources

Contrasting microanatomy of idiopathic and corticosteroid-induced osteoporosis.

Previous studies of microanatomic changes in normal bone with age have suggested that underlying differences in bone remodeling between male subjects and female subjects give rise to different patterns of bone loss. The relationship between microanatomic and histologic levels of organization are herein examined in two groups of osteoporotic subjects, one with idiopathic and the other with corticosteroid-induced osteoporosis. Using tissue from the iliac crest, total trabecular surface and trabecular width and number were measured, together with bone volume and static and dynamic indices of formation (osteoid surface, seam width, mean wall thickness, lamellar thickness, calcification fronts, and mineralization rate) and resorption (total resorption cavities and osteoclast incidence). The results suggest that while a similar loss of trabecular bone volume is common to both groups, there is a marked distinction in the distribution of the remaining bony tissue and indices of remodeling. A decline in trabecular number accompanied by a relative increase in resorption characterized both sexes with primary osteoporosis, whereas a decline in trabecular width associated with depressed formation was the predominant feature in the secondary disease. Thus trabecular attenuation is principally the manifestation of depressed formation, while trabecular discontinuity is primarily the manifestation of bone resorption.

Adrenal Cortex Hormones↗

Distributions of neuropeptides in the human esophagus.

The distributions of nerve cells and fibers with immunoreactivity for the peptides substance P, somatostatin, enkephalin, vasoactive intestinal peptide, gastrin-releasing peptide, and neuropeptide Y and the enzyme tyrosine hydroxylase were examined in 25 samples of human esophagus. These were compared with samples of stomach and intestine. In the smooth muscle of the muscularis externa, the muscularis mucosae, and beneath the epithelium, the most abundant nerve fibers contained vasoactive intestinal peptide and neuropeptide Y, in contrast to the scarcity of substance P, enkephalin, somatostatin, and gastrin-releasing peptide. Gastric and intestinal samples contained dense populations of fibers containing vasoactive intestinal peptide, neuropeptide Y, substance P, and enkephalin in the equivalent layers, but somatostatin- and gastrin-releasing peptide-immunoreactive fibers were scarce. Complete coexistence of vasoactive intestinal peptide and neuropeptide Y in nerve fibers within the muscle layers was demonstrated in the esophagus, but not in gastric and intestinal samples. The myenteric plexus along the length of the esophagus contained cell bodies and fibers reactive for vasoactive intestinal peptide, neuropeptide Y, enkephalin, and substance P. Somatostatin-immunoreactive cell bodies were very rare in the myenteric plexus, no gastrin-releasing peptide-immunoreactive cell bodies were seen, and both somatostatin and gastrin-releasing peptide-immunoreactive fibers were rare. In the upper esophagus, striated muscle bundles did not contain nerve fibers reactive for these peptides but immunoreactive fibers were seen in the muscularis mucosae and subepithelium. It is concluded that the esophagus has a different pattern of innervation by peptide-containing neurons than the stomach and intestines. Esophageal neurons can be classified into separate classes on the basis of their peptide content.

Adult↗

Local action of oral 1,25-dihydroxycholecalciferol on calcium absorption in osteoporosis.

To investigate whether low calcium absorption in osteoporosis improves by increasing 1,25-dihydroxyvitamin D both systemically in plasma and locally in gut, the effects of oral 25-hydroxycholecalciferol and oral 1,25-dihydroxycholecalciferol on plasma 1,25-dihydroxy-vitamin D (1,25-(OH)2D) and calcium absorption were studied in 20 postmenopausal patients with vertebral osteoporosis. In 10 patients taking oral 0.25 micrograms 1,25-dihydroxycholecalciferol twice daily for 7 d, calcium absorption increased more than in 10 patients taking oral 40 micrograms 25-hydroxycholecalciferol once daily for 7 d (p less than 0.02) despite both groups having a similar increase in plasma 1,25-(OH)2D. These results support the view that the major effects of oral 1,25-dihydroxycholecalciferol on absorption is due to a local action on the gut and that it is possible to increase calcium absorption in osteoporosis with oral 1,25-dihydroxycholecalciferol without increasing its undesirable action on bone resorption.

Administration, Oral↗

Effect of chronic administration of ammonium sulfate on phosphatic stone recurrence.

Urine alkalinization favours the formation of calcium phosphate (CaP) and struvite stones. In this retrospective study we analyze the effect of chronic urinary acidification on phosphatic stone recurrence. Twenty-four patients with CaP-struvite recurrent stones and persistently high urinary pH were divided in two groups: group A, 11 patients who failed to lower the urinary pH below 5.5 during a standard acid load test: group B, 13 patients with preserved acidification power. Ammonium sulfate 2-3 g/day was given for 4.7 and 6.5 years to groups A and B, respectively. A persistent reduction in urinary pH, relative saturation for CaP and stone formation rate was observed in both groups. The treatment did not cause systemic acidosis as long as renal function remained normal. Urinary daily excretion of Ca and P as well as their renal tubular handling did not change with time. Results suggest acidifying agents might be useful in preventing recurrence of CaP-struvite stones even in the presence of a mild acidification defect and encourage undertaking properly controlled prospective trials.

Adult↗

Vitamin D metabolism in women with femoral neck fracture.

Abnormalities in plasma vitamin D metabolites and an increased prevalence of osteomalacia have been described in elderly patients sustaining a fracture of the femoral neck. In order to investigate whether the plasma concentrations of the vitamin D metabolites are normal, and whether vitamin D deficient osteomalacia in patients with femoral fracture can be diagnosed using biochemical criteria alone, we have studied before and after 7 days of 40 micrograms oral 25-hydroxyvitamin D3 elderly patients admitted to hospital with a femoral fracture, elderly patients undergoing elective replacement of the femoral head and elderly control patients in hospital with no clinical evidence of bone disease. Plasma 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D increased after 7 days of oral 25-hydroxyvitamin D3 to the same levels in the three groups, but in contrast to the controls there was no significant increase in plasma 1,25-dihydroxyvitamin D or radiocalcium absorption in femoral fracture and hip replacement patients. However, when femoral fracture patients were restudied 6-12 months after fracture, plasma 1,25-dihydroxyvitamin D increased after oral 25-hydroxyvitamin D3 to the same extent as it had in the control patients. We conclude that reduced calcium absorption due to low plasma 25(OH)D levels, i.e., vitamin D insufficiency is common in all elderly patients. Furthermore biochemical criteria for diagnosis of vitamin D-deficient osteomalacia are of very limited use at the time of fracture in elderly patients since there is a failure of production of 1,25 dihydroxyvitamin D which resolves within 6-12 months of the fracture. This failure makes the 1,25-dihydroxyvitamin D response to oral 25(OH)D an unreliable guide to the presence of vitamin D-deficient osteomalacia at the time of fracture. The abnormality in 1,25-dihydroxyvitamin D is also present in patients undergoing hip replacement surgery, and is therefore unlikely to be involved in the aetiology of femoral neck fracture. It may, however, contribute to the morbidity after fracture.

24,25-Dihydroxyvitamin D 3↗

Dose dependent response of symptoms, pituitary, and bone to transdermal oestrogen in postmenopausal women.

The effect of the plasma oestradiol concentration on climacteric symptoms, gonadotrophin release, and bone resorption was studied in three groups of postmenopausal women given 0.025 mg, 0.05 mg, or 0.1 mg transdermal oestradiol daily. There was a dose related reduction in symptoms, plasma follicle stimulating hormone concentration, and urinary calcium and hydroxyproline excretion. The relation of the response to plasma oestradiol values was similar for each variable with an initial large reduction and little change in response to increases in the plasma oestradiol concentration above 150 pmol/l (41 pg/ml). Hormone replacement therapy producing an effect equivalent to higher oestradiol concentrations is likely to increase the risk of side effects without conferring any additional benefit.

Administration, Cutaneous↗

Characteristics of antisera to antigenic forms of 1,25-dihydroxycholecalciferol.

Antisera to 1,25-dihydroxycholecalciferol were raised to 1,25-dihydroxycholecalciferol 25-hemisuccinate-bovine serum albumin, 1,25-dihydroxycholecalciferol 3-hemisuccinate-bovine serum albumin, 1,25-dihydroxycholecalciferol 3-hemisuccinate-porcine thyroglobulin and (5Z,7E)-(1S,3R)-1,3 dihydroxy-9,10-seco-24,25, 26,27-tetrakisnor-5,7,10(19)-cholestatrien-23-oic acid porcine thyroglobulin in rabbits. The antisera cross-reacted with a wide spectrum of vitamin D metabolites but their affinity was highest for 1,25-dihydroxycholecalciferol and some differentiated between ergo- and cholecalciferol metabolites. The presence of vitamin D binding protein and the pH of incubation markedly affected the sensitivity and specificity of antisera. A number of antisera were capable of measuring the normal plasma concentrations of vitamin D metabolites and their different affinities could be used for the measurement of 1,25-dihydroxyergocalciferol and 1,25-dihydroxycholecalciferol in plasma. None however were specific enough for the direct measurement of the metabolites in plasma. Immunisation increased the plasma concentration of endogenous 1,25-dihydroxyergo- and cholecalciferol in the animals.

Antigen-Antibody Complex↗

Ethinyl estradiol and norethindrone in the treatment of primary hyperparathyroidism in postmenopausal women.

Treatment with ethinyl estradiol or norethindrone reduces the bone-turnover rate and plasma calcium levels in normal postmenopausal women, without affecting the secretion of calcium-regulating hormones. To assess the effect of these sex steroids in patients with primary hyperparathyroidism, we treated postmenopausal women who had hyperparathyroidism with either ethinyl estradiol (n = 6) or norethindrone (n = 11). After three weeks of treatment, the bone-turnover rate declined and plasma calcium fell from a mean (+/- 1 SE) of 2.77 +/- 0.07 mmol per liter (11.1 +/- 0.3 mg per deciliter) to 2.58 +/- 0.05 mmol per liter (10.3 +/- 0.2 mg per deciliter; P less than 0.01) in the group treated with ethinyl estradiol, and from 2.93 +/- 0.08 mmol per liter (11.7 +/- 0.3 mg per deciliter) to 2.84 +/- 0.08 mmol per liter (11.4 +/- 0.3 per deciliter; P less than 0.05) in the patients who received norethindrone. No significant changes in the plasma levels of parathyroid hormone, calcitonin, or calcitriol were observed after the estrogen-induced increases in vitamin D-binding protein had been taken into account. Since the decline in plasma calcium levels did not stimulate secretion of parathyroid hormone, we conclude that treatment with either sex steroid resets the threshold for secretion of parathyroid hormone. Thus, although the reductions in plasma calcium levels were moderate, sex-hormone therapy may be useful in the treatment of mild hyperparathyroidism in postmenopausal women.

Bone Resorption↗

Osteomalacia in Paget's disease treated with short term, high dose sodium etidronate.

Eleven patients with Paget's disease treated with sodium etidronate 20 mg/kg/day for two and four weeks showed significant reductions in plasma alkaline phosphatase activity and urinary hydroxyproline excretion, both of which are biochemical markers of bone turnover. After four weeks of treatment, however, histological examination of iliac crest biopsy samples showed that despite a rapid reduction in bone resorption there was an appreciable mineralisation defect; even after only two weeks' treatment the abnormalities in bone formation persisted for up to 10 weeks. The adverse effects of sodium etidronate on mineralisation cannot be dissociated from its beneficial effect on resorption even when it is given for short periods.

Aged↗

Purification of vitamin D binding protein from human plasma using high performance liquid chromatography.

Vitamin D binding protein/group-specific component was purified from human plasma by chromatographic techniques utilising high performance liquid chromatography and by traditional low pressure chromatographic techniques alone. Use of high performance liquid chromatography considerably reduced the time taken to prepare pure vitamin D binding protein and increased the yield to 16% compared with 2.8% using the traditional methods. The vitamin D binding protein prepared by high performance liquid chromatography was shown to be highly pure by amino acid sequence, SDS gel electrophoresis and by antibody production. The amino acid sequence was confirmed and extended. The affinity constants of the high pressure liquid chromatography purified vitamin D binding protein for 25 hydroxycholecalciferol (25 OHD3) and 1,25 dihydroxycholecalciferol 1,25(OH)2D3 were 1.9 X 10(7) mol/l and 2.6 X 10(6) mol/l, respectively.

Amino Acid Sequence↗

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↗

Serological diagnosis of Q fever endocarditis.

The diagnosis of Q fever endocarditis cannot be made by bacterial cultures and necessitates serological identification of specific antibodies to Coxiella burnetii which stimulates mainly the production of anti-phase II antibodies during the acute disease, but primarily anti-phase I antibodies in endocarditis. Indirect microimmunofluorescence allows rapid detection of specific IgA, IgG and IgM. The results of serological analyses of 191 acute cases of Q fever were compared with those of 8 cases of Coxiella burnetii endocarditis. All sera were evaluated by complement fixation and microimmunofluorescence tests. The highest titre differences between primary Q fever and Q fever endocarditis were observed with anti-phase I IgA and IgG antibodies measured by microimmunofluorescence followed by anti-phase I antibodies measured by complement fixation tests. Antiphase I IgG and IgM titres were consistently higher than anti-phase II titres in endocarditis. The reverse is true in acute Q fever. In addition, anti-phase I IgA appeared to be diagnostic for Coxiella burnetii endocarditis. Accordingly we recommend the testing of these specific IgA, IgG, and IgM by microimmunofluorescence in cases of culture-negative endocarditis. These tests could also prove useful for following the development of Coxiella burnetii endocarditis in patients under treatment.

Antibodies, Bacterial↗