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Biomedical subjects

P Charles

Publications and source records attributed to P Charles.

At least 55 records · Page 3Linked to original sources
PubMed1996

Bone histomorphometry in hypoparathyroid patients treated with vitamin D.

Parathyroid hormone (PTH) and vitamin D are both active regulators of bone remodeling. Several studies, mostly in animals and in vitro, have suggested that the two hormones act synergistically or interdependently. The aim of the present study was therefore to describe the actions of vitamin D alone on bone remodeling in the absence of circulating PTH. Bone biopsies were obtained from 12 patients with vitamin D-treated hypoparathyroidism and from 13 age- and gender-matched normal controls. Mean total resorption rate was reduced (0.9 vs. 3.8 mu m/day,p < 0.001), the resorption period was prolonged (80.8 vs. 25.7 days, p < 0.001), and the resorption depth was reduced (41.7 vs. 55.3 mu m, p < 0.001). The fractional active and the total eroded surface were not significantly reduced. The fractional formation surface was reduced (5.2 vs. 12.5 mu m, p < 0.001). Trends toward prolongation of the formation period and reduction of the final wall thickness were found. The balance between resorption depth and final wall thickness was not significantly different from normal (0.96 vs. -4.4 mu m). The quiescent period was prolonged (7.6 vs. 1.7 years, p < 0.001) and the activation frequency was reduced (0.13 vs. 0.6 year(-1), p < 0.001). The structural parameters, trabecular bone volume, trabecular thickness, marrow space star volume, and trabecular star volume, remained unchanged. In the absence of PTH, Vitamin D alone is not able to normalize bone resorption and bone turnover in hypoparathyroid patients.

Adult↗
PubMed1996

Skeletal responsiveness to thyroid hormone is not altered at menopause.

Hyperthyroidism is characterized by increased bone turnover and resorptive activity. Similar changes in remodeling are seen after menopause. To study the role of thyroid hormone in the menopause-related changes in bone metabolism, we investigated thyroid status and the sensitivity of bone to thyroid hormone in 14 premenopausal and 15 early postmenopausal women. Triiodothyronine (T3) was administered to the two groups as 20 micrograms doses three times daily for 7 days. The skeletal response was assessed by monitoring bone alkaline phosphatase (BAP), osteocalcin (BGP), pyridinium crosslinked telopeptide domain of type I collagen (ICTP) in serum and urinary excretion of hydroxyproline (OHP), pyridinoline (PYR), and deoxypyridinoline (DPR) at days 0, 8, 15, and 57. The early postmenopausal women had increased bone turnover as reflected in sBAP (p < 0.05), sBGP (p < 0.05), and uOHP (p < 0.01) when compared with premenopausal controls. T3 stimulation of early postmenopausal and premenopausal women significantly increased the markers of bone resorption: sICTP (56% vs. 44%), uOHP (45% in both groups), and UPYR (83% vs. 17%) without any significant differences between groups. Of the formative markers, only sBGP increased significantly after stimulation (34% vs. 41%), but both sBGP and sBAP displayed significant increases from days 15 to 57. Thus, stimulation with thyroid hormone results in an immediate stimulation of ongoing bone formation and bone resorption, but also initiation of new remodeling which, after 8 weeks, reached the formative phase. PTH decreased (p < 0.01) in both groups but serum calcium and serum phosphate were unaltered. In conclusion, menopause is not characterized by altered levels of thyroid hormones or altered skeletal responsiveness to thyroid hormones.

Alkaline Phosphatase↗
PubMed1996

Bone mass, bone turnover, body composition, and calcium homeostasis in former hyperthyroid patients treated by combined medical therapy.

It is still uncertain whether bone mass and bone turnover are completely normalized after treatment of hyperthyroidism. The aim of the present investigation was to determine bone mass, bone turnover, body composition, and calcium homeostasis in former hyperthyroid patients who had been euthyroid for at least 4 years following combined medical therapy. Thirty-nine former hyperthyroid patients and 67 normal sex- and age-matched controls participated. Height, body weight, and body composition were similar in the two groups. All patients were euthyroid. However, serum FT3I (free T3-index) was reduced by 9% (p < 0.01) in the patients compared to controls, serum FT4I was normal, while serum TSH was nonsignificantly reduced by 39%. No significant differences were observed between patients and controls with respect to total or regional bone mineral content (BMC) or density (BMD). The former hyperthyroid patients had slightly higher serum calcium (2.35 +/- 0.06 vs. 2.32 +/- 0.07 mmol/L, p < 0.05) and lower serum phosphate (1.15 +/- 0.15 vs. 1.24 +/- 0.15 mmol/L, p < 0.01) than their controls. Renal excretion of calcium and serum levels of magnesium, 1,25-vitamin D and intact PTH were unchanged. Renal excretion of pyridinoline was increased by 30% (p < 0.05) in the patients, whereas the remaining resorptive markers, renal excretion of hydroxyproline and deoxypyridinoline and serum cross-linked carboxy-terminal teleopeptide of type I collagen (ICTP) were unaltered. Among the formative bone markers the average serum carboxy-terminal propeptide of human type I procollagen (PICP) level was 12% lower (p < 0.05) than in the control group, whereas serum levels of osteocalcin and total and bone alkaline phosphatase were normal. In conclusion, former hyperthyroid patients treated by combined medical therapy have normal bone mineral content and density in spite of minor variations in thyroid hormones and skeletal homeostasis.

Biomarkers↗
PubMed1996

Bone mass, bone turnover, calcium homeostasis, and body composition in surgically and radioiodine-treated former hyperthyroid patients.

Untreated hyperthyroidism is characterized by increased bone turnover with loss of bone and bone mineral. The aim of the present investigation was to evaluate the reversibility of these changes by measuring bone mass, bone turnover, and calcium homeostasis in surgically treated former hyperthyroid patients who had been euthyroid for at least 6 years. Sixty euthyroid former hyperthyroid patients and 94 normal sex- and age-matched controls participated. Heights and body weights and composition were similar in the two groups. In the thyroxine substituted patients (n = 27) both serum T4 and serum free T4-index (S-FT4I) were increased (p < 0.001) compared to the normal controls as well as the nonsubstituted patients. In the nonsubstituted patients. In the nonsubstituted patients (n = 33), serum TSH was increased (p < 0.001) compared to the normal controls. No significant differences were observed between substituted and nonsubstituted patients and normal controls with respect to serum T3, serum free T3-index (S-FT3I), or regional or total bone mineral content (BMC) and density (BMD) values. Serum levels of calcium, phosphate, magnesium, intact PTH, and renal excretion of calcium were unchanged. However, serum levels of 1,25-dihydroxy- and 25-hydroxyvitamin D were reduced. Urinary excretion of hydroxyproline was increased by 16% (p < 0.05), but serum cross-linked carboxy-terminal teleopeptide of type I collagen (ICTP) was decreased by 11% (p < 0.01). Urinary excretion of collagen cross-links was normal. Serum levels of osteocalcin, carboxy-terminal propeptide of human type I procollagen (PICP), and total and bone alkaline phosphatase were all normal. In conclusion, surgically treated former hyperthyroid patients have normal bone mass, bone turnover, and calcium homeostasis in spite of minor variations in thyroid hormones and vitamin D metabolites.

Adult↗
PubMed1996

Bioavailability of calcium supplements and the effect of Vitamin D: comparisons between milk, calcium carbonate, and calcium carbonate plus vitamin D.

Our aim was to examine a regimen for calcium supplementation because various factors seem to be important for its bioavailability, and to examine the effect of adding vitamin D to the supplement. The participants were 20 healthy women aged 28-59 y (chi: 38 y). During the 3-d periods and 1 d before, the participants were consuming a calcium and energy-balanced diet as similar to their usual daily diet as possible. The study was designed as a randomized, placebo-controlled, partly blinded crossover study divided into four periods of 3 d each: 1) three tablets containing 1000 mg CaCO3/d, 2) three tablets containing 1000 mg CaCO3 plus 5 micrograms (200 IU) vitamin D/d, 3)1 L more milk than in the usual daily diet, and 4) three placebo tablets daily. Bioavailability of the different calcium-supplement regimens were evaluated by changes in 24-h urinary excretion of calcium, phosphate, and magnesium. A significant increase in urinary calcium excretion was found during all periods of supplementation compared with the placebo period (P<0.01). Excretion of calcium in the calcium carbonate period was not significantly higher that that in the milk period, but calcium carbonate plus vitamin D resulted in significantly higher calcium excretion compared with that in the milk period. We conclude that the examined calcium carbonate regimen is at least as good a calcium supplement as milk, and that addition of 600 IU vitamin D/d promptly resulted in an increase in urinary calcium excretion after an increase in calcium absorption, even in healthy women.

Adult↗
PubMed1996

Chimaeric monoclonal antibodies encoded by the human VH26 gene from naïve transgenic mice display a wide range of antigen-binding specificities.

To elucidate the molecular basis for the ability of antibodies encoded by the human VH26 heavy-chain variable region gene to react with diverse antigens, we have generated 34 hybridomas secreting chimaeric monoclonal antibodies (human mu heavy chain/mouse light chains) from transgenic mice. The transgenic mice carry an immunoglobulin minilocus containing the human VH26 gene, human DH and JH gene segments, and genes encoding the human C mu region. The minilocus in these animals undergoes functional rearrangement resulting in the production of chimaeric antibodies in which human mu heavy chains utilizing the VH26 gene are paired with mouse kappa or lambda light chains. The hybridomas described in this study were generated from naïve animals and were selected solely on the basis of human mu-chain expression. The antibodies described have covalently attached mouse light chains and are multimeric in structure. The binding properties of the antibodies were examined using a panel of both self- and foreign antigens using enzyme-linked immunosorbent assays, agglutination or radio-immunoprecipitation assays and immunofluorescence. Chimaeric immunoglobulins from 21 of the 34 hybridoma clones (61.7%) reacted with one or more antigens, of which 13 (38.2%) reacted with more than two antigens. These studies demonstrate that the VH26 gene, in combination with human DH and JH gene segments, and mouse light-chain genes, is able to encode antibodies with a wide range of ligand-binding specificities. These findings have important implications in the context of the possible origins of autoantibodies encoded by VH26 which may play a role in the pathogenesis of a number of autoimmune conditions.

Animals↗
PubMed1996

Assessment of bone involvement in patients with multiple myeloma using bone densitometry.

To evaluate the use of dual energy X-ray absorptiometry (DXA) in multiple myeloma (MM) we performed a prospective study of 34 patients with newly diagnosed MM. Most patients had advanced disease and all but two patients had osteolytic bone destructions and/or pathological fractures. Bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine (L1-L4) and hip were measured using a Hologic QDR-1000 scanner. Collapsed vertebrae were not excluded from analysis. Data from 289 healthy Danish volunteers aged 21-79 yr were used for calculation of Z-scores. Lumbar spine BMC (Z-score -0.46 +/- 0.23, p = 0.05) and lumbar spine BMD (Z-score -0.56 +/- 0.23, p = 0.02) were significantly reduced in MM patients, whereas no reduction was seen in hip BMC or BMD. Collapsed vertebrae had marked reduced BMD (Z-score -1.34 +/- 0.22, p < 0.001), as had non-fractured vertebrae in the same individuals (Z-score -1.42 +/- 0.25, p < 0.001). Lumbar spine BMD correlated with radiologically assessed bone morbidity (r -0.37, p = 0.03) and stronger with the incidence of vertebral fractures (r -0.64, p < 0.001). Thus, osteopenia of the back is common in multiple myeloma and correlates with an increased incidence of fractures. DXA may identify subjects with increased risk of vertebral fractures for more intensive chemotherapeutic or anti-resorptive treatment.

Absorptiometry, Photon↗
PubMed1996

Bone mass, bone turnover and body composition in former hypothyroid patients receiving replacement therapy.

The aim of the present cross-sectional study was to disclose whether long-term thyroxine replacement therapy (TRT) in primary hypothyroidism causes osteopenia. We compared 36 adult biochemically and clinically euthyroid patients who had received TRT for more than 5 years (mean 13 years) for primary hypothyroidism with 80 sex- and age-matched normal controls. Height, body weight and lean body mass were similar, but the patients had 21% higher fat body mass (p = < 0.01) than their controls. Furthermore, compared to controls the patients had 29% higher serum thyroxine (T4) and 31% higher serum free T4 index (FT4I) levels (p < 0.001), whereas serum triiodothyronine (T3) and FT3I levels were both reduced by 7% (p < 0.05). In the patients, serum TSH was reduced significantly (p < 0.001). No significant differences were observed between patients and normals in regional or total bone mineral content or bone mineral density levels, apart from 20% higher lumbar bone mineral content among the premenopausal patients (p < 0.05). Surprisingly, the mean serum calcium level was slightly elevated (2.38 +/- 0.08 vs 2.33 +/- 0.07 mmol/l, p < 0.001), serum phosphate decreased (1.13 +/- 0.19 vs 1.23 +/- 0.16 mmol/l, p < 0.01) and 24-h renal calcium excretion was reduced by 19% (p < 0.05). No changes were observed in serum magnesium, intact parathyroid hormone or calcitriol. The biochemical markers of bone resorption (serum carboxyterminal telopeptide of type I collagen, renal excretion of hydroxyproline, pyridinoline and deoxypyridinoline) and formation (serum levels of carboxyterminal propeptide of type I procollagen, osteocalcin and total and bone alkaline phosphatase) were similar in the two groups. We conclude that long-term thyroxine replacement therapy in primary hypothyroidism does not exert a negative effect on bone mass or alter bone turnover.

Adult↗
PubMed1995

[Vitamin D and osteoporosis].

Vitamin D constitutes a complex endocrine-regulated system, and is both a prohormone for the endogenous synthesis of the active hormone, calcitriol, and a vitamin which may be administered to supply the organism's requirements. No single test or investigation is available for the demonstration of vitamin D deficiency. Both vitamin D intake and ability to synthesise vitamin D decrease with increasing age, and particularly the elderly in institutionalised care are at risk of developing vitamin D deficiency. Iceland excepted, mean daily vitamin D consumption in the Nordic countries is less then 5 micrograms; and in approximately 10-25 per cent of the population, daily intake is less than 2.5 micrograms which is insufficient to maintain an adequate serum calcidiol concentration in individuals unexposed to sunlight. The recommended daily intake of 5 micrograms, currently adopted in the Nordic countries, may be too low-an intake of 10 micrograms is probably necessary to satisfy requirements in the elderly.

Adrenal Cortex Hormones↗
PubMed1994

Repeated therapy with monoclonal antibody to tumour necrosis factor alpha (cA2) in patients with rheumatoid arthritis.

Our in-vitro, animal, and early clinical data suggest that tumour necrosis factor alpha (TNF alpha) is an important target for specific biological therapy in rheumatoid arthritis. We report the results of repeated treatment with a chimeric monoclonal antibody to TNF alpha (cA2) in patients having disease flares. 7 patients originally enrolled in an open-label trial completed two to four cycles, each of which was followed by a good clinical response, with median improvements in the swollen-joint count and C-reactive protein exceeding 80%. cA2 may be useful therapy in the control of acute disease flares in rheumatoid arthritis and treatment programmes including cA2 may be effective in the long-term management of this disease.

Antibodies, Monoclonal↗
PubMed1994

Cloning and analysis of cDNA encoding a major airway glycoprotein, human tracheobronchial mucin (MUC5).

Two unique nucleotide probes for human tracheobronchial mucin glycoprotein (TBM) were generated via polymerase chain reaction with degenerate primers deduced from the TBM:TR-3A tryptic peptide sequence and were used to isolate a 3.6 kilobase cDNA, clone NP3a, from a human nasal polyp cDNA library. Clone NP3a was localized to chromosome 11 and contained a 3168 nucleotide open reading frame which encoded three TBM peptide fragments, thus confirming that clone NP3a partially encodes TBM. TBM also contains five tandem repeats of TTVGP/S and an octapeptide GQCGTCTN, which is conserved in human intestinal mucin MUC2 and rat intestinal mucin-like protein (MLP) suggesting that this sequence has a functional significance for secreted mucins. TBM has amino acid similarity to the cysteine-rich domains at the carboxyl termini of MUC2, rat MLP, bovine and porcine submaxillary mucins, and human von Willebrand factor. Strikingly, a large percentage of the cysteine residues in the overlaps are highly conserved: 90% in MUC2 and von Willebrand factor, 80% of bovine submaxillary mucin, 70% in porcine submaxillary mucin, and 64% in rat MLP, suggesting that conserved cysteines may be important for the tertiary structure of secreted glycoproteins. These studies demonstrate that clone NP3a is a candidate for MUC5, making it the only human mucin gene reported to date whose gene product has been isolated from airway secretions.

Amino Acid Sequence↗
PubMed1994

Anticoagulant therapy in deep venous thrombosis. A randomized controlled study.

Ninety patients with venographically proven deep venous thrombosis(DVT) but without clinical signs of pulmonary embolism(PE) were randomized into two different treatment regimens to compare the safety and efficacy of continuous intravenous heparin and oral anticoagulant(AC) treatment versus non-AC treatment. All patients in the two treatment groups were actively mobilized from the day of admission and wore graduated compressing stockings. In the non-AC-group the patients were treated with phenylbutazone for ten days. Treatment with heparin was maintained for 6 days and oral AC treatment was given from the third day and continued for 3 months. Venography was repeated after 30 days. A perfusion-ventilation lung scan was performed on day 1-2, 10 and 60. In fifty-nine patients a revenography was performed, twenty nine in the AC-group and thirty in the non-AC group. For distal veins regression was found in nine and eight respectively (4.4% in favour of AC, 95% confidence limit 27.5% to -18.7%) and in proximal veins regression was found in five and eight, respectively (10.9% in favour of AC, 95% confidence limit 32.0% to -10.1%). No difference in lung scans was found after 10 days (0.8% in favour of AC, 95% confidence limit 21.5% to -19.9%) or after 60 days (3.3% in favour of non-AC treatment, 95% confidence limit 21.8% to -28.5%). In the AC group the incidence of bleeding complications was 8.3%. No side-effects of phenylbutazone was found. The present controlled clinical study demonstrated no effect of AC-treatment on DVT progression in actively mobilized patients wearing graduated compressing stockings when compared to a non-AC treated group receiving analgetic therapy with phenylbutazone. However, the patient population of the study is relatively small with wide confidence intervals for differences between groups. Before more general recommendations can be made, a large scale placebo-controlled study is needed to evaluate the possible effect of AC-treatment in DVT patients, who can be mobilized from the first day.

Administration, Oral↗
PubMed1994

Observer variation in the interpretation of ventilation-perfusion lung scintigraphy.

The diagnosis of pulmonary embolism (PE) remains one of the most difficult in clinical medicine, and the diagnostic value of lung scintigraphy has been questioned. To evaluate the observer variation in the interpretation of ventilation-perfusion lung scanning in the diagnosis of PE, 87 lung scintigrams from consecutive patients with phlebography-proven deep venous thrombosis and without clinical signs of PE were randomly mixed with 50 reference lung scintigrams from patients with PE symptoms. The scintigrams were reevaluated blind by two experienced clinical physiologists. Each observer evaluated each lung scintigram twice and recorded whether the lung scan was normal or abnormal. If it was abnormal, the location and number of segment defects were registered. The intraobserver agreement, including number and location of segments, ranged from 0.77 to 0.85 and for the diagnosis of PE from 0.88 to 0.92 with a kappa of 0.80-0.84. The values for the interobserver agreement for the diagnosis of PE were 0.73-0.80 with a kappa of 0.56-0.67. It is concluded that in the interpretation of ventilation-perfusion lung scintigraphy the use of a simple scheme-deciding whether there is segmental ventilation-perfusion mismatch or not-has a good reproducibility with a high kappa for inter- and intraobserver variation and can serve as a simple routine method for diagnosing PE.

Double-Blind Method↗
PubMed1994

A comparison of the effects of oestrogen/progestogen, high-dose oral calcium, intermittent cyclic etidronate and an ADFR regime on calcium kinetics and bone mass in postmenopausal women with spinal osteoporosis.

The effects of four different treatments for osteoporosis were compared in a prospective, randomized, 3-year study in 74 postmenopausal women with spinal crush fracture osteoporosis. Patients were randomly assigned to cyclic oestrogen/progestogen therapy (group 1, n = 20), a daily oral calcium dose of 2 g (group 2, n = 17), intermittent cyclic etidronate therapy (group 3, n = 19), or an ADFR treatment with triiodothyronine as activator and etidronate as depressor (group 4, n = 18). Spine and forearm bone mineral content was measured before entry and every 30 weeks. Combined calcium balance and 47Ca kinetic studies were performed before and after 1 and 3 years of treatment. Bone turnover, estimated by serum alkaline phosphatase and renal hydroxyproline excretion, decreased in all four groups during the first half of the treatment period but remained reduced during the second half in groups 1 and 3 only. Group 1 had a significantly positive calcium balance after 60 weeks of treatment. After 150 weeks, the positive effect on calcium balance was significant and greater in groups 1 and 3 than in the other groups. This was achieved by a greater reduction in resorption rate in group 1 at week 60 and in groups 1 and 3 at week 150 as compared with the other groups. Only group 1 had a significant increase in spinal bone mass while a decrease in bone mass at the distal forearm was observed in the etidronate-treated group. We conclude that treatment of postmenopausal osteoporosis with oestrogen/progestogen for 3 years results in net spinal bone gain and a positive effect on calcium balance slightly better than that of intermittent etidronate. These effects were inferior in the groups receiving a large calcium supplementation or the ADFR group where no change in calcium balance or bone mass was found.

Administration, Oral↗
PubMed1994

Assessment of bone remodeling using biochemical indicators of type I collagen synthesis and degradation: relation to calcium kinetics.

In this study, we investigated the relation between calcium kinetic indices of bone remodeling (resorption rate, r; and formation rate, m, respectively) and two serum markers of type I collagen turnover: the pyridinoline cross-linked carboxyterminal telopeptide domains of type I collagen (S-ICTP a marker of bone matrix degradation) and the carboxyterminal propeptide of human type I procollagen (S-PICP, a marker of bone matrix formation). We studied three groups: (i) healthy controls (n = 19), (ii) a mixed group of high and low-turnover bone diseases without mineralization defects (myxedema, thyrotoxicosis and primary hyperparathyroidism n = 38), and (iii) osteoporosis (n = 52). In healthy controls, a significant regression of S-PICP on m was obtained (R = 0.53, SEE/Y = 0.44, P < 0.02). Significant regressions were also demonstrable in high- and low-turnover bone disease (R = 0.50, P < 0.001), SEE/Y = 61%) and osteoporosis (R = 0.49, P < 0.001, SEE/Y = 50%). In controls the regression coefficient for the regression of S-ICTP on r was 0.19 (NS), in high and low turnover bone disease 0.66, (SEE/Y = 59%, P < 0.001) and in the osteoporotic group 0.40 (SEE/Y = 61%, P < 0.01). We conclude that S-PICP and S-ICTP reflect whole skeletal bone formation and resorption rates in a variety of metabolic bone diseases including osteoporosis.

Adolescent↗
PubMed1994

Silent pulmonary embolism in patients with deep venous thrombosis. Incidence and fate in a randomized, controlled trial of anticoagulation versus no anticoagulation.

OBJECTIVES: A high frequency of asymptomatic pulmonary embolism (PE) in patients with deep venous thrombosis (DVT) has been reported, but information about the outcome of the patients with PE remains sparse. The aims of the present study were to assess the prevalence of silent PE in patients with symptomatic, venographically proven DVT, and to evaluate the natural history of silent PE. DESIGN: Consecutive patients from one centre of primary care were included in a randomized, open study with blinded control. All patients gave written, informed consent. SUBJECTS: Eighty-seven consecutive patients with venographically proven DVT and with a perfusion-ventilation lung scintigraphy performed within 48 h of the DVT diagnosis were included. On the 10th and 60th days the lung scintigraphy was repeated in 80 and 60 patients, respectively. All the patients were followed for 3 months in the out-patient clinic. INTERVENTIONS: All patients were ambulated from the first day and were allocated randomly to no anticoagulant (non-AC) therapy or to AC therapy with intravenous heparin infusion for at least 6 days and oral AC therapy for 3 months. RESULTS: Forty-three of these patients had a high probability lung scintigraphy for PE. Distal vein and femoral vein thrombosis embolized in 33 and 53% of patients, respectively. The progression rate after 60 days was 3% in both the AC and the non-AC group and after 10 days the rates were 13 and 8%, respectively. CONCLUSIONS: A high frequency of silent PE in patients with DVT both above and below the knee is demonstrated. AC treatment did not influence the resolution rate of PE or the rate of clinical PE in a 3-month follow-up period.

Adolescent↗