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Biomedical subjects

P Charles

Publications and source records attributed to P Charles.

At least 73 records · Page 4Linked to original sources
PubMed1993

Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha.

OBJECTIVE: To evaluate the safety and efficacy of a chimeric monoclonal antibody to tumor necrosis factor alpha (TNF alpha) in the treatment of patients with rheumatoid arthritis (RA). METHODS: Twenty patients with active RA were treated with 20 mg/kg of anti-TNF alpha in an open phase I/II trial lasting 8 weeks. RESULTS: The treatment was well tolerated, with no serious adverse events. Significant improvements were seen in the Ritchie Articular Index, which fell from a median of 28 at study entry to a median of 6 by week 6 (P < 0.001), the swollen joint count, which fell from 18 to 5 (P < 0.001) over the same period, and in the other major clinical assessments. Serum C-reactive protein levels fell from a median of 39.5 mg/liter at study entry to 8 mg/liter at week 6 (P < 0.001), and significant decreases were also seen in serum amyloid A and interleukin-6 levels. CONCLUSION: Treatment with anti-TNF alpha was safe and well tolerated and resulted in significant clinical and laboratory improvements. These preliminary results support the hypothesis that TNF alpha is an important regulator in RA, and suggest that it may be a useful new therapeutic target in this disease.

Adult↗
PubMed1993

Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry.

Type I collagen makes up more than 90% of bone matrix. Therefore, analysis of antigens related to collagen formation and degradation in bone should provide good and specific estimates of both bone resorption and bone formation rates. In this study we measured serum levels of the pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) as a marker of bone resorption and serum carboxy-terminal propeptide of type I procollagen (PICP) as a marker of bone formation. Serum levels of the two antigens were correlated to histomorphometric indices of bone resorption and bone formation calculated from iliac crest bone biopsies in a group of 18 individuals with high- and low-turnover bone disease (myxedema, primary hyperparathyroidism, and thyrotoxicosis). After logarithmic transformation the regression of S-ICTP on volume-referent resorption rate (BRs/R/BV) was significant (r = 0.61, p < 0.01, SEM/Y = 56%). S-ICTP also showed a significant regression on the volume-referent cancellous bone balance (r = -0.45, p < 0.05, SEM/Y = 412%). S-PICP was significantly correlated to the mineral appositional rate (r = 0.53, p < 0.05) and volume-referent bone formation rate (r = 0.61, p < 0.01, SEM/Y = 48%). The correlation to bone turnover as expressed in the activation frequency was also highly significant (r = 0.61, p < 0.01, SEM/Y = 51%). No significant correlation with wall thickness or bone balance was demonstrable per remodeling cycle. Thus, assays employing antigens that reflect collagen formation and degradation are useful instruments for the evaluation of rates of bone remodeling in metabolic bone disease.

Adult↗
PubMed1993

Unchanged noradrenaline reactivity and blood pressure after corrective surgery in primary hyperparathyroidism.

In order to evaluate the role of the hyperparathyroid state for blood pressure and volume homeostasis, eight patients with primary hyperparathyroidism were studied before and after corrective surgery. Neither noradrenaline induced blood pressure changes nor basal blood pressure were affected by the operation, and the values were the same as in an age- and sex-matched control group. Noradrenaline infusion induced an increase in PTH(1-84) values before (72-86 ng l-1, medians, p < 0.02), in contrast to a decrease after (28 to 19 ng l-1, p < 0.05) operation for primary hyperparathyroidism. Basal plasma atrial natriuretic peptide was lower before than after removal of adenomata (3.2 vs. 4.8 pmol l-1, medians, p < 0.02). Cyclic 3'-5'-guanosine monophosphate was not significantly changed (4.7 vs. 5.5 nmol l-1). Aldosterone was higher before than after surgery (139 vs. 71 pmol l-1, p < 0.02), whereas angiotensin II was unaltered (20 vs. 9 pmol l-1). Arginine vasopressin was higher before than after the operation (0.9 vs. 0.7 pmol l-1, p < 0.05), but urinary excretion of prostaglandin E2 was unchanged. In conclusion primary hyperparathyroidism was not associated with changes in noradrenaline reactivity or basal blood pressure despite derangements of hormones adjusting sodium and water homeostasis. It is suggested that the hormonal changes may be secondary to a relative volume depletion.

Adult↗
PubMed1993

Thyroid disease and other autoimmune phenomena in a family study of primary Sjögren's syndrome.

Autoimmune diseases and autoantibodies have been documented in 42 index cases with definite primary Sjögren's syndrome (1 degree SS), 207 relatives and 39 spouses. The results were compared with control data from a local population survey. Thyroid disease, 1 degree SS and their associated autoantibodies were the commonest autoimmune abnormalities observed and found predominantly in older female relatives. The HLA-DR3 phenotype associated with 1 degree SS, antinuclear factor, hypothyroidism, and thyroid microsomal antibody. Rheumatoid arthritis and systemic lupus erythematosus were not found in excess in the families. Primary Sjögren's syndrome is frequently associated with thyroid disease and we suggest that there is a common genetic predisposition between these diseases which differs from 2 degrees SS associated with rheumatoid arthritis and systemic lupus erythematosus. This includes MHC and non-MHC genes.

Adolescent↗
PubMed1993

Autoantibodies in malaria, tuberculosis and hepatitis B in a west African population.

Following reports of associations between autoantibodies and living in the tropics, we have studied the seroprevalence and nature of anti-nuclear antibodies, anti-cardiolipin antibodies, antibodies to extractable nuclear antigens and anti-neutrophilic cytoplasmic antibodies in 351 West Africans with malaria, tuberculosis or hepatitis B, or in good health. Amongst healthy West Africans we found a seroprevalence of 7% for anti-nuclear antibodies with several staining patterns, and of 30.3% for anti-cardiolipin antibodies. Among patients with tuberculosis and malaria there was twice that frequency of anti-nuclear antibodies (predominantly speckled in pattern), and anti-neutrophil cytoplasmic antibodies (predominantly IgM) were demonstrated in a few cases. A possible association between IgG anti-cardiolipin antibodies and tuberculosis was observed (P < 0.05), but antibodies to double-stranded DNA were not elevated and no antibodies to extractable nuclear antigens were found in any of the patients or healthy individuals studied. Our findings suggest the need for caution in the interpretation of autoantibody tests in subjects from or living in the tropics, as well as in patients with tropical infections.

Acute Disease↗
PubMed1993

The effect of single doses of inhaled beclomethasone dipropionate on the circadian rhythm in serum osteocalcin in normals.

A single dose of 2.5 mg prednisone leads to a significant transient decrease in serum osteocalcin, which is only demonstrated by frequent serum sampling. The aim of the present study was to evaluate whether a single dose of inhaled beclomethasone dipropionate causes transient changes in serum osteocalcin, indicating a systemic effect on bone cells. In a double-blind, placebo controlled, cross-over design we evaluated the effects of single doses of 250 micrograms and 1000 micrograms beclomethasone on the circadian rhythm in serum osteocalcin. Fifteen normal subjects aged 23-38 years were studied twice with an interval of one week with hourly blood sampling from 16.30 until 17.00 the following day; 1000 micrograms beclomethasone, but not 250 micrograms, suppressed serum cortisol by 14.4 +/- 6.7% (p = 0.03). Neither of the beclomethasone doses significantly altered the time pattern of serum osteocalcin. We conclude that a single inhaled dose of beclomethasone in the therapeutical range does not acutely influence osteoblastic activity as judged from serial measurements of serum osteocalcin.

Administration, Inhalation↗
PubMed1993

Treatment of psoriasis vulgaris with topical calcipotriol has no short-term effect on calcium or bone metabolism. A randomized, double-blind, placebo-controlled study.

The purpose of this double-blind, placebo-controlled study was to examine whether the vitamin D analogue calcipotriol, topically applied to psoriatic skin lesions, had any effect on calcium or bone metabolism. Thirty-four outpatients with psoriasis vulgaris were randomized to treatment with either calcipotriol ointment (50 micrograms/g) or vehicle ointment twice daily for 3 weeks. The patients were put on a calcium energy fixed diet and examined once weekly. The mean amount of calcipotriol ointment used was 40.3 g/week (range 8.2-95.4 g/week). The results of biochemical markers on calcium and bone metabolism showed no significant differences between the two groups. No correlation was found between the amount of ointment used and changes in parameters on calcium and bone metabolism during the 3-week treatment. It is concluded that calcipotriol ointment (50 micrograms/g), applied in doses of 8.2-95.4 g/week for 3 weeks to psoriatic skin lesions, has no effect on calcium or bone metabolism.

Administration, Cutaneous↗
PubMed1992

Assessment of bone formation by biochemical markers in metabolic bone disease: separation between osteoblastic activity at the cell and tissue level.

In this study , serum levels of classical serum markers of bone formation [carboxyterminal propeptide of procollagen type I (S-PICP), bone Gla protein (S-BGP)], and total alkaline phosphatase (S-AP)) were related to the calcium kinetic index of whole skeletal mineralization rate (m) by regression analysis in a variety of metabolic bone diseases. For each disease, the regression coefficient (r) as well as the fraction: standard error of estimate/mean dependent variable (SEE/Y) were determined. In a group of 19 normals, only the regression of S-PICP on m reached significance (r = 0.53, P < 0.02, SEE/Y = 0.44), whereas regressions of S-AP and S-BGP on m were nonsignificant. In a pooled material of high- and low-turnover bone diseases without mineralization defects or spinal fracture [myxedema, thyrotoxicosis, and primary hyperparathyroidism (n = 48)], a highly significant positive regression of S-PICP on m was demonstrable (r = 0.50, SEE/Y = 0.63, P < 0.001). The regression coefficients obtained for S-BGP and S-AP were 0.74 (P < 0.001, SEE/Y = 0.41) and 0.42 (P < 0.01, SEE/Y = 0.55), respectively. When analyzing individual diseases in this group, significant differences among the three markers were detectable. In a group of 52 osteoporotics, S-PICP correlated significantly to m (r = 0.49, P < 0.001, SEE/Y = 0.50). Corresponding r-values for S-BGP and S-AP were 0.21 (NS) and 0.48 (P < 0.001, SEE/Y = 0.61), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of a short course of oral phosphate treatment on serum parathyroid hormone(1-84) and biochemical markers of bone turnover: a dose-response study.

To investigate the possible use of oral phosphate as an activator of bone remodeling in coherence treatment of osteoporosis, 82 postmenopausal females, aged 50-75 years, were randomized to treatment with oral phosphate (750, 1500, or 2550 mg/day) or placebo for 7 days and followed for 4 months thereafter. All patients had sustained at least one previous fracture of the distal forearm and had a bone mineral content of the contralateral forearm or bone mineral density of the lumbar spine lower than normal mean for age. Urinary phosphate/creatinine ratio increased in a dose-dependent fashion during treatment (P less than 0.001), whereas no significant changes were seen in serum phosphate or serum calcium. Serum parathyroid hormone (PTH) rose significantly (P less than 0.05) during treatment to a maximum of 36 and 33% in the groups receiving 1500 and 2250 mg/day, respectively, whereas serum 1,25-dihydroxycholecalciferol remained unchanged. In the group receiving 1500 mg/day, mean serum osteocalcin was increased in the period from day 1 to day 28 (P less than 0.05), but no significant changes were observed in urinary hydroxyproline/creatinine ratio, or serum bone alkaline phosphatase. We conclude that a short course of oral phosphate treatment increases serum PTH considerably. Furthermore, 1500 mg/day but not 2250 mg/day increases serum osteocalcin. No clear biochemical evidence, however, of increased activation of bone remodeling could be demonstrated in either group.

Administration, Oral↗
PubMed1992

Treatment of hypothyroidism reduces low-density lipoproteins but not lipoprotein(a).

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apo B) is attached to a large plasminogen-like protein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated. LDL and apo B levels are often elevated in untreated hypothyroidism and lowered by thyroxine (T4) treatment, probably due to an increase in LDL receptors. We measured plasma concentrations of LDL, apo B, and Lp(a) in 13 patients with symptomatic primary hypothyroidism before and during T4 therapy. The mean concentration of LDL decreased significantly (P = .006) from 6.05 mmol/L to 4.07 mmol/L, and the mean concentration of apo B decreased significantly (P = .005) from 1.42 g/L to 1.12 g/L. Median Lp(a) concentrations remained unchanged (P = .77); they were 17.05 mg/dL before and 16.59 mg/dL during T4 treatment. In both the untreated condition and during substitution therapy, Lp(a) levels were higher in patients than in healthy controls, probably due to a relatively high frequency of the small Lp(a) phenotypes in our patients. Since Lp(a) contains apo B, which is a ligand for the LDL receptor, it is surprising that Lp(a) is not reduced along with LDL and apo B. These findings suggest that the catabolism of LDL and Lp(a) differ in some respect, and that thyroid hormones have little, if any, effect on Lp(a).

Female↗
PubMed1992

Calcium metabolism in postmenopausal osteoporotic women is determined by dietary calcium and coffee intake.

Eighty-five patients, age 48 to 77 y with postmenopausal crush fracture osteoporosis, were investigated using a 7-d combined calcium balance and 47Ca tracer-kinetic turnover method taking the dermal calcium loss into account. Individual dietary records were obtained based on a 4-d registration at home before hospital admission and on questioning by a dietitian. The following dietary constituents were estimated: energy content, protein, methionine, cysteine, calcium, phosphate, magnesium, coffee, fiber and vitamin C. All patients were served individual diets based on the dietary records during study. Dietary calcium was measured in duplicates of all the meals served. All urine and feces were collected and analyzed for calcium content. The 47Ca kinetic data were analyzed according to a modification of the expanding calcium pool model. The overall calcium balance correlated significantly to energy content (r = 0.31, P less than 0.005), protein (r = 0.22, P less than 0.05), calcium (r = 0.28, P less than 0.01), phosphate (r = 0.27, P less than 0.02) and coffee (r = -0.21, P less than 0.05). However, a multiple backward linear regression analysis disclosed that only calcium (rp = 0.38, P less than 0.0005) and coffee intake (rp = -0.25, P less than 0.05) significantly influenced calcium balance. The equation was: calcium balance (mmol/d) = 0.14 x (dietary calcium, mmol/d) - 0.0016 x (coffee intake, mL/d) - 3.62. A coffee intake in excess of 1000 mL could induce an extra calcium loss of 1.6 mmol calcium/d, whereas intakes of 1-2 cups of coffee per day would have little impact on calcium balance.

Aged↗
PubMed1992

Association of DR3 with susceptibility to and severity of primary Sjögren's syndrome in a family study.

A study of HLA and primary Sjögren's syndrome (1 degree SS) was performed in 40 index cases and 180 relatives all of whom were Caucasian. The association of DR3 and 1 degree SS was confirmed. In probands, DR3 associated with extraglandular manifestations of 1 degree SS and homozygosity for DR3 associated with younger onset of disease. Familial clustering of 1 degree SS was evident. Definite or probable 1 degree SS (Fox criteria) occurred with a prevalence of 4.4% in the relatives, exclusively in older female first degree relatives and was associated with DR3. The relative risk was greatest in those who expressed anti-nuclear factor, rheumatoid factor or Ro and DR3. We identified a group of young females expressing some criteria for 1 degree SS and the same immunogenetic markers. They may be at risk of full expression of 1 degree SS as they become older. Milder forms of 1 degree SS were common in older relatives but not DR3 associated. 1 degree SS in males was rare and mild irrespective of immunogenetic status. Symptoms of 1 degree SS in relatives were mild or absent. Such individuals will only be identified through a family study or a community survey.

Adolescent↗
PubMed1992

Calcium absorption and calcium bioavailability.

Calcium is important for bone health. It has been customary to focus on dietary calcium intake, but of central importance for the body needs in the individual patient is the actual calcium absorption. This absorption consists of an active vitamin D-mediated component and a passive diffusional component. A number of different methods are available for the evaluation of calcium absorption. At present the calcium absorption tests using calcium isotopes (radioactive or stable) appear to be the most reproducible way of determining calcium absorption. The major nutrient sources for calcium are milk and milk products, whereas some of the green vegetables have a low bioavailability of calcium. When deciding whether an increased calcium intake is advisable, the following questions must be answered. What is the calcium absorptive status of the patient? How should the calcium supplement be dispensed? What calcium salt should be used? When should calcium supplements be taken? What is the compliance of the patient? When should the treatment be evaluated? The calcium supplement might be taken as milk (or milk products) or, in patients with lactose intolerance, as calcium supplements. Quite a number of calcium supplements are available on the market, and many of them are marketed without proper knowledge of the bioavailability of the actual preparation. For the benefit of our patients it is now reasonable to demand such investigations before marketing calcium supplements.

Biological Availability↗
PubMed1992

Inhibition of the morning cortisol peak abolishes the expected morning decrease in serum osteocalcin in normal males: evidence of a controlling effect of serum cortisol on the circadian rhythm in serum osteocalcin.

Osteocalcin (OC) in serum varies in a remarkably constant circadian rhythm with zenith at night and nadir in the morning. The factors controlling this rhythm are unknown, but several studies indicate that serum cortisol could be of major importance. We tested this hypothesis in a double-blind, placebo-controlled, cross-over study comprising 10 normal male volunteers (aged 23-31 yr) by measuring the response in serum OC and cortisol rhythms to a single dose of metyrapone (30 mg/kg body weight) administered at midnight. During placebo, serum cortisol consistently peaked early in the morning before 0730 h. Ingestion of metyrapone at 2400 h significantly postponed and flattened this peak (P less than 0.01). On both occasions, serum OC increased towards peak levels around 0300 h (P less than 0.01) with no overall differences in the OC profiles. However, when the serum OC time series were synchronized according to the individual cortisol nadirs, we found a significant (P less than 0.01) decrease in serum OC on the placebo day approximately 4 h after the cortisol nadir, whereas no significant changes (P greater than 0.50) were seen on the metyrapone day. Moreover, the mean serum OC level tended to be higher (P less than 0.10 in the interval 0-12 h, and P = 0.06 in the interval 4-8 h) on the metyrapone day compared with the placebo day. On the placebo day, the mean level of serum cortisol during the interval 0-4 h correlated inversely with the mean level of serum OC in the interval 4-8 h (r = 0.77, P less than 0.05). This relation was not found on the metyrapone day. In conclusion, administration of metyrapone, which reduced and postponed the early morning cortisol peak, abolished the normal morning decrease in serum OC. This strongly supports that changes in endogenous serum cortisol are of major importance for the circadian rhythm in serum OC.

Adult↗
PubMed1992

Factors affecting blood stem cell collections following high-dose cyclophosphamide mobilization in lymphoma, myeloma and solid tumors.

Sixty patients with malignancy were enrolled in a study of high-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT). Stem cells were harvested prior to PBSCT using high-dose cyclophosphamide (CY) mobilization (4 or 7 g/m2) with collection of a median of 4.6 x 10(8)/kg mononuclear cells (range 0.2-9.5) and 21.6 x 10(4)/kg colony forming unit-granulocyte/macrophage (CFU-GM) (range 0.1-220). Forty-seven patients were mobilized once, 11 required two cycles and two required three cycles. Eight patients (13%) failed to reach the optimum CFU-GM target (greater than 15 x 10(4)/kg) following CY mobilization. A number of factors identified those patients who were likely to achieve optimum CFU-GM collections with CY mobilization. These included the use of the higher CY mobilization dose, a longer interval from last chemotherapy cycle to mobilization, and a higher premobilization bone marrow CFU-GM level. Patient's age, the degree of bone marrow infiltration, the nature of disease or the number of pre-mobilization chemotherapeutic cycles did not affect the ability to collect optimum CFU-GM numbers. Whilst the mobilization procedure was associated with moderate non-hematologic toxicity, significant hematological morbidity was observed primarily in patients mobilized using the 7 g/m2 dose. Refinements to the protocol, in particular the use of hematopoietic growth factors, are currently under investigation.

Adolescent↗