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Biomedical subjects

P Charles

Publications and source records attributed to P Charles.

At least 109 records · Page 6Linked to original sources
PubMed1989

Efficacy of wheat germ lectin-precipitated alkaline phosphatase in serum as an estimator of bone mineralization rate: comparison to serum total alkaline phosphatase and serum bone Gla-protein.

Serum levels of total alkaline phosphatase activity (S-T-AP), wheat germ lectin-precipitated alkaline phosphatase activity (S-L-AP), and bone Gla-protein immunoreactivity (S-BGP) were measured in 26 patients (23 females and 3 males) aged 35-73 years (mean 59 years) with primary hyperparathyroidism (n = 7), hyperthyroidism (n = 9), and hypothyroidism (n = 10) in whom the bone mineralization rate (m) was determined by 47Ca-kinetics (continuously expanding calcium pool model). A weak positive correlation (r = 0.42, P less than 0.05) was found between S-T-AP and m, which in the range from 0-18 mmol Ca/day could be estimated with a standard error of 4.6 mmol/day. A closer correlation (r = 0.65, P less than 0.001) was found between S-L-AP and m which was estimated with an error of 3.9 mmol Ca/day. The AP activity in the supernatant showed no significant correlation to m (r = 0.11, P greater than 0.50). The highest correlation coefficient (r = 0.81, P less than 0.001) was found between S-BGP and m which could be predicted with an error of 3.4 mmol Ca/day. S-BGP showed a closer correlation to S-L-AP (r = 0.71, P less than 0.001) than to S-T-AP (r = 0.58, P less than 0.01). We concluded that S-L-AP predicts bone mineralization at organ level better than S-T-AP in selected metabolic bone disorders and that the supernatant activity shows no relation to bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Determinants for serum 1,25-dihydroxycholecalciferol in primary hyperparathyroidism.

Serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 25-hydroxyvitamin D3 (25(OH)D3), C-terminal immunoreactive PTH (iPTH), calcium and phosphate, and endogenous creatinine clearance (Clcr) were measured in 34 patients with primary hyperparathyroidism. Clcr ranged from 13 to 161 ml/min (mean 72). S-iPTH was elevated in 82% of the patients and correlated positively to serum calcium (r = 0.74, P less than 0.001) and inversely to Clcr (r = -0.50, P less than 0.02). S-25(OH)D3 was reduced in 28% of the patients and depended on regular multivitamin supplementation (P less than 0.005). S-1,25(OH)2D3 was increased in 26% of the patients and decreased in 9%. It was positively correlated to S-25(OH)D3 (r = 0.39, P less than 0.05) and Clcr (r = 0.42, P less than 0.02) and inversely to serum levels of calcium (r = -0.39, P less than 0.05), phosphate (r = -0.42, P less than 0.02) and iPTH (r = -0.40, P less than 0.05). Multiple regression analysis revealed a positive correlation to 25(OH)D3 when Clcr was taken into account and to Clcr when S-25(OH)D3 was taken into account. When both variables were considered no significant partial correlations were found between S-1,25(OH)2D3 and serum calcium, phosphate and PTH, respectively. It is concluded that serum levels of 25(OH)D3 and renal function are the main determinants for S-1,25(OH)2D3 in primary hyperparathyroidism.

Adult↗
PubMed1989

A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone remodeling in postmenopausal osteoporosis.

Thirty-seven patients with postmenopausal crush fracture osteoporosis were randomized to oral cyclic estrogen/gestagen (n = 20) or oral calcium (2000 mg elemental calcium per day) (n = 17). Fourteen in each group completed 1 year of treatment. Iliac crest bone biopsies were obtained after intravital double labeling with tetracycline before and after treatment in 10 patients on estrogen/gestagen and 11 patients on calcium. In the estrogen/gestagen group the activation frequency in trabecular bone decreased from 0.52 + 0.11 (SEM) year-1 to 0.27 + 0.08 year-1 (p less than 0.01). No significant changes were found in resorption or formation periods. The osteoid surfaces and the mineralizing surfaces decreased (p less than 0.05), whereas the decrease in eroded surfaces was insignificant. Furthermore, no significant changes were observed in final resorption depth, wall thickness or bone balance per remodeling cycle. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.002), whereas the lumbar bone mineral content (BMC) increased (p less than 0.01). In the calcium group the extent and thickness of osteoid surfaces decreased (p less than 0.05) without significant changes in activation frequency. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.02). No significant changes were observed in lumbar BMC or the other histomorphometric parameters. The study supports that the positive effect of estrogen/gestagen on BMC can be explained by a reduction in the activation frequency of new remodeling cycles leading to a decreased remodeling space and an increase in mean bone age. There is no evidence of a positive balance per remodeling cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Seasonal variation of serum bone GLA protein.

The seasonal variation of serum Bone Gla Protein (BGP) was investigated in 15 normal young individuals (seven women and eight men, aged 27-39 years). Serum BGP exhibited a significant seasonal variation of 23% around the yearly mean (p less than 0.001) with zenith in February and nadir in July. Significant seasonal variations were noted also for serum alkaline phosphatase (p less than 0.01) and serum phosphate (p less than 0.01). Serum calcium, bone mineral content (BMC) and creatinine clearance revealed no significant seasonal variation. The seasonal variation of BGP did not follow the variation in serum total alkaline phosphatase. The seasonal variation of BGP has to be taken into account when using the protein as a marker of bone remodelling activity. The variation was probably caused by changes in the production rate of the protein, since the renal excretion of the protein, as reflected in creatinine clearance, remained unchanged throughout the year.

Adult↗
PubMed1989

Elevated angiotensin II and vasopressin in primary hyperparathyroidism. Angiotensin II infusion studies before and after removal of the parathyroid adenoma.

In order to evaluate the role of calcium metabolism in blood pressure regulation, 15 patients with primary hyperparathyroidism and 9 healthy control subjects were studied before and during angiotensin II infusion. The patients were re-investigated 2-5 months after removal of the parathyroid adenoma. Blood pressure, plasma levels of angiotensin II, aldosterone, arginine vasopressin, and atrial natriuretic peptide, and creatinine clearance were determined. Blood pressure and the blood pressure response to angiotensin II infusion were both the same before and after the operation. Angiotensin II and arginine vasopressin during basal conditions were significantly higher before than after the operation (angiotensin II: 17 (median) to 10 pmol/l, P less than 0.02; arginine vasopressin: 2.9 to 1.9 pmol/l, P less than 0.01), whereas aldosterone, atrial natriuretic peptide, and creatinine clearance were unchanged. During angiotensin II infusion, aldosterone, arginine vasopressin, and atrial natriuretic peptide increased to approximately the same levels before and after the operation. Blood pressure was not correlated to any of the hormones measured. Thus, patients with primary hyperparathyroidism have elevated plasma levels of angiotensin II and arginine vasopressin which may be compensatory phenomena counteracting volume depletion owing to a decreased renal concentrating ability induced by hypercalcemia, and owing to PTH-induced inhibition of renal sodium reabsorption.

Adenoma↗
PubMed1988

Specificity of anti-Sm antibodies by ELISA for systemic lupus erythematosus: increased sensitivity of detection using purified peptide antigens.

Sm antigen was purified by immunoaffinity chromatography using a murine monoclonal anti-Sm antibody and was confirmed to be free from contaminating polypeptides. This was then used to detect anti-Sm antibodies in patients' sera by enzyme linked immunosorbent assay (ELISA). Antibodies against Sm were detected in only 9/52 (17%) patients with systemic lupus erythematosus (SLE) by immunodiffusion, but 15/52 (29%) were positive for IgG anti-Sm antibodies by ELISA. The presence of anti-Sm antibodies remained disease specific despite the increase in sensitivity of this assay and validates its potential use for clinical application. There was no correlation between the presence of anti-Sm antibodies and any clinical features of SLE. In 23 renal biopsies a membranous component to the glomerulonephritis correlated with anti-Sm antibodies (p less than 0.05). Patients from West Africa, the Carribean Islands, and Asia had a higher prevalence of anti-Sm antibodies than the local Caucasian population.

Antibody Specificity↗
PubMed1988

The effect of single oral doses of prednisone on the circadian rhythm of serum osteocalcin in normal subjects.

Serum osteocalcin (OC), which is a sensitive marker of bone formation, is reduced during chronic glucocorticoid treatment in accordance with the finding of reduced bone formation, and even short term glucocorticoid treatment reduces serum OC. In a double blind placebo-controlled study, we measured the effects of 2.5 and 10 mg prednisone, orally, on the circadian variation of serum OC in 15 normal subjects (8 women and 7 men), aged 22-46 yr. All subjects were studied twice at an interval of 1 week. Blood samples were collected every 60 min from 1630 until 1700 h the following day. Prednisone or placebo was given at 2000 h. Serum OC was measured by an in-house RIA. After placebo administration serum OC increased from 2230 h to a peak value around 0230 h, followed by a gradual decline to a nadir around 1500 h. Both doses of prednisone inhibited and even reversed the nocturnal rise in serum OC levels; the inhibition occurred within 3-4 h. There was no significant difference in the time from prednisone ingestion to maximal decrease (7.2 h vs. 9.8 h) or in the maximal decrease (52% vs. 54%). However, the duration of the inhibition was significantly shorter after 2.5 mg than after 10 mg prednisone (approximately 6 h vs. 12 h; (p less than 0.01). We conclude that serum OC is sensitive to small doses of prednisone, and that serial serum OC measurements may be a sensitive marker of the effect of exogenous glucocorticoids on osteoblastic activity in vivo.

Administration, Oral↗
PubMed1988

The effects of high-dose glucocorticoid administration on serum bone gamma carboxyglutamic acid-containing protein, serum alkaline phosphatase and vitamin D metabolites in normal subjects.

The effects of 40 mg of prednisone given daily for 5 days to normal individuals on serum levels of bone Gla-protein (BGP), alkaline phosphatase, calcium phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone (S-iPTH) and on renal excretions of calcium, phosphate and hydroxyproline were evaluated in a double-blind, placebo controlled study. In the prednisone group a 75% decrease (P less than 0.001) was found in serum BGP compared to a 6% decrease (P less than 0.05) in serum alkaline phosphatase. The renal hydroxyproline excretion remained unchanged. Serum calcium was unchanged while the fasting urinary calcium excretion showed a 2-fold increase (P less than 0.001). Serum 1,25-dihydroxyvitamin D increased (P less than 0.01) in spite of unchanged serum 25-hydroxyvitamin D, serum phosphate and parathyroid function (as judged by S-iPTH and the maximal tubular reabsorption capacity for phosphate (TmP/GFR]. The data suggest a direct inhibition of osteoblast number and/or function by short-term glucocorticoid administration with unchanged bone resorption leading to a negative bone mineral balance. The increase in serum 1,25-dihydroxyvitamin D is probably due to a direct stimulation by glucocorticoids of the renal 1 alpha-hydroxylase. The effects of the vitamin D metabolite, however seem to be blunted.

Adult↗
PubMed1987

Nature of the interactions involved in the lipid-protein complexes of the Escherichia coli N-acetylmuramoyl-L-alanine amidase.

Depending on its concentration, phosphatidylglycerol, one of the three main Escherichia coli phospholipid species, is able to activate or inactivate the E. coli murein amidase (N-acetylmuramoyl-L-alanine amidase, EC 3.5.1.28) (Vanderwinkel, E. and De Vlieghere, M. (1985) Biochim. Biophys. Acta 838, 54-59). The mechanisms underlying the modulation of this enzyme activity were studied by analyzing the effects of cations, polycationic molecules, various surfactants and amphiphilic water-soluble compounds. K+, Mg2+ and polyamines were all able to prevent completely the enzyme inactivation produced by millimolar order concentration of phosphatidylglycerol. The efficiencies of the ionic species tested were in the order K+ less than Mg2+ = putrescine less than spermidine less than spermine. The kinetics of the counteraction processes were all sigmoidal. By contrast, the activation of the murein amidase produced by phosphatidylglycerol in micromolar concentration appeared to be insensitive to the ionic strength of the medium. Surfactants and amphiphilic molecules differing in their polar head and hydrophobic tail were found to activate the enzyme at various degrees for concentrations below their critical micellar concentration. The non-ionic surfactants were the most potent activators and remarkably mimicked the phosphatidylglycerol activation. The enzyme activation process appeared to require only a hydrophobic solvation shell around the protein. All kinetic data supported our previous interpretation of the phosphatidylglycerol-enzyme interactions in terms of multisite non-allosteric theory.

Amidohydrolases↗
PubMed1987

Etidronate disodium in the management of malignancy-related hypercalcemia.

To evaluate the efficacy of intravenous etidronate disodium (etidronate) in controlling hypercalcemia of malignancy, 20 patients with known malignant disease and hypercalcemia were randomly assigned on a two-to-one basis to receive etidronate, 7.5 mg/kg of body weight, or placebo for three to five days. All patients received 3,000 ml of saline and 40 mg of furosemide per day. Eighteen patients completed the study. Eleven of 12 patients (92 percent) in the etidronate group attained normocalcemia, compared with two of six (33 percent) in the placebo group (p = 0.05). The etidronate group showed a greater decrease in the serum calcium level than did the placebo group (p less than 0.02). Renal calcium excretion decreased significantly in the etidronate group but not in the placebo group. Intravenous etidronate in combination with rehydration and furosemide constitutes a safe and effective alternative in the treatment of hypercalcemia of malignancy.

Adult↗
PubMed1987

Bone turnover and balance evaluated by a combined calcium balance and 47calcium kinetic study and dynamic histomorphometry.

Bone resorption and formation rates were evaluated at the organ level using calcium kinetic methods and at the trabecular bone tissue level using dynamic histomorphometry in 20 patients with various metabolic bone diseases (primary hyperparathyroidism (N = 9), hyperthyroidism (N = 6), and hypothyroidism (N = 5). Highly significant correlations were demonstrated between resorption and formation rates at organ level (r = .90, P less than .001) and at tissue level (volume referent) (r = .93, P less than .001), indicating a high degree of coupling between resorption and formation within the three disease states. Tissue level resorption rates (surface referent, as well as volume referent) both correlated significantly (P less than .01) to organ level resorption rate (r = .60 and r = .63, respectively). Fractional active resorption surface and cellular level resorption rate did not reveal significant correlations to calcium kinetic estimates. No correlation could be demonstrated between organ level mineralization rate and formative or labeled trabecular surfaces. However, all tetracycline based tissue level formation rates revealed highly significant correlations (P less than .01) to organ level mineralization rate (calcification rate, r = .71; surface referent bone formation rate, r = .59; volume referent bone formation rate, r = .68). Based on histomorphometric parameters for resorption and formation, actual and predicted tissue level trabecular bone balances were calculated. Both the actual and predicted bone balance correlated significantly to the organ level calcium balance (P less than .05). Correction for skeletal size based on BMC measurements did not improve any of the correlations significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Exogenous triiodothyronine activates bone remodeling.

The effect of exogenous triiodothyronine (T3) as an activator of bone remodeling was investigated by measuring biochemical marker levels. Fourteen people received 100-160 micrograms of T3 for 1 week and were followed for a total of 10 weeks. Serum T3 increased markedly during the first week, whereas serum TSH and serum thyroxine (T4) decreased. Bone resorption was stimulated during the first week as evaluated from serum calcium and renal excretion of calcium, phosphate, and hydroxyproline. Serum osteocalcin showed an increase in the first week, probably caused by stimulation of existing osteoblasts. Serum alkaline phosphatase increased from week 6 to week 8, and serum osteocalcin increased at week 8 to a level higher than the initial level. The results indicate that T3 acts as an activator of bone remodeling and initiates bone resorption followed by bone formation. The observed timetable for the remodeling sequence is in accordance with that obtained by bone histomorphometry. Osteopenic states may be treated by synchronizing the skeletal remodeling processes and then selectively depressing bone resorption with calcitonin or diphosphonates (ADFR treatment). Synchronization may be achieved by short-term treatment with a drug that stimulates the formation rate of new remodeling cycles (an activator). The results from this study indicate that exogenous T3 may be used as an activator.

Adult↗
PubMed1987

Chronic schizophrenic disorder. I. Psychophysiological responses, laterality and social stress.

Bilateral palmar skin conductance and heart rate were measured throughout a series of psychological tests and during both sitting and ambulant social interactions in 14 right-handed men with chronic schizophrenic disorder and 12 healthy volunteers matched for age and handedness. Miniature radio telemetry equipment was used to collect the physiological data. The schizophrenic group was effectively unresponsive to 70-dB auditory stimuli, while all but one of the control group responded and habituated to a nil response by the tenth tone in sequence. The schizophrenic group showed some evidence of increased skin conductance activity at rest, and in socially demanding conditions skin conductance level and variability were increased in the right hand. The present group of electrodermal 'non-responders' was not in general autonomically under-active. Asymmetry of skin conductance activity during social interaction may be a characteristic of chronic schizophrenic disorder.

Adult↗