Search PubMed⌕ Search

Biomedical subjects

P Charles

Publications and source records attributed to P Charles.

At least 91 records · Page 5Linked to original sources
PubMed1991

The consensus workshops for the detection of autoantibodies to intracellular antigens in rheumatic diseases.

In 1988 and in 1989 consensus workshops were organized in order to define the interlaboratory concordance in detecting autoantibody specificities in selected sera from patients with rheumatoid disorders and to determine the possible causes of discrepancies. In total 20 sera were tested for the presence of antibodies against nRNP, Sm, Ro (SS-A), La (SS-B), Scl-70, centromeric antigens, ribosomal RNP and Jo-1. The methods used for detection by the 28 European laboratories who participated included immunofluorescence, counter-immunoelectrophoresis, immunodiffusion, immunoblotting and ELISA. The results showed that only a combination of two or more techniques was able to detect all specificities with an adequate efficiency. Recommendations to improve the efficiency of autoantibody detection and to standardize laboratory protocols are given.

Antibody Specificity↗
PubMed1991

Effects of a combined estrogen-gestagen regimen on serum levels of the carboxy-terminal propeptide of human type I procollagen in osteoporosis.

Estrogen stimulates osteoblastic collagen production in vitro, but whether the same stimulation takes place in vivo is still unknown. To test the stimulatory effects of a combined estrogen-gestagen regimen in vivo we monitored serum levels of the carboxy-terminal propeptide of human type I procollagen (S-PICP) in a group of 12 osteoporotic women over a 150 week treatment period. Spinal bone mineral content (BMC) increased to a maximum of 5% over pretreatment values around week 90. Serum alkaline phosphatase (S-AP) and serum bone gla protein (S-BGP) both fell from initial values of 220 U/liter and 39 ng/ml, respectively, to 146 U/liter (p less than 0.01) and 27.2 ng/ml (NS) around week 60 and remained reduced over the remaining treatment period. S-PICP also fell from 117 to 68 micrograms/liter at week 60 and 70 micrograms/ml at week 150 (P less than 0.01). This is equal to a reduction to 32 +/- 10% pretreatment levels. The reduction in S-PICP was not significantly different from that of the other two markers of bone formation (S-AP and S-BGP). Thus, provided the metabolic clearance of PICP remains unaltered after hormone replacement therapy, no major stimulation of osteoblastic collagen type I synthesis was demonstrable during estrogen-gestagen treatment in this population of osteoporotic women. The changes in bone markers seen in this study are therefore consistent with an estrogen-mediated reduction in the frequency of remodeling activation. Because of the reduction in bone turnover and methodologic limitations of bone marker assays, however, smaller increases in the amount of bone formed per activation could remain undetectable.

Aged↗
PubMed1991

Skeletal size and bone mineral content in Turner's syndrome: relation to karyotype, estrogen treatment, physical fitness, and bone turnover.

Bone mineral content (BMC), bone mineral density, and metacarpal dimensions were studied in 50 women with Turner's syndrome aged 21-45 years in relation to karyotype, estrogen treatment, physical fitness, and biochemical markers of bone turnover. No differences were found between the 25 women with karyotype 45.X and women with other karyotypes. Forty-six women had received estrogen. Significant partial correlations were found between bone mineral density of the forearm and duration of estrogen treatment and physical fitness. BMC of the lumbar spine corrected for vertebral height (BMC(C)spine) was directly correlated with duration of estrogen treatment and height, marginally correlated with physical fitness, and inversely correlated with age. Outer metacarpal width was positively correlated with duration of estrogen treatment, age at initiation of therapy, and body weight. The diameter of medullary space showed negative correlation with physical fitness and height, and positive correlation with age at initiation of estrogen treatment. Cortical thickness was positively correlated with duration of estrogen treatment, physical fitness, and height. No convincing effects of estrogen could be demonstrated in women below the age of 30. Above the age of 30, all bone mineral measurements were markedly elevated in women treated for longer than the average of this age group. BMC(C)spine was inversely correlated with biochemical markers of bone formation. Our results demonstrate that estrogen treatment and physical fitness are important determinants of bone mineral status in Turner's syndrome and add to the evidence that estrogen treatment increases BMC in Turner's syndrome.

Adult↗
PubMed1991

Hypercalcemia of malignancy: pathophysiology, diagnosis and treatment.

Malignancy is the most frequent cause of hypercalcemia in hospitalized patients. The pathophysiology of hypercalcemia of malignancy (HM) is complex. Increased bone resorption is involved in most cases caused either by extensive local bone destruction or by humoral factors. Tumor extracts from patients with humoral hypercalcemia of malignancy (HHM) often contain PTH-like bioactivity. Recently, cDNAs coding for a PTH-related protein (PTH-rP) has been cloned. The N-terminal amino acid sequence of this protein shows a considerable homology with human PTH. However, other bone resorbing factors including prostaglandins, transforming growth factors, colony stimulating factors, leucocyte cytokines and 1,25-dihydroxyvitamin D may be involved in different types of malignancy. HM is usually progressive with troublesome symptoms and a high mortality. Several treatment alternatives are available including rehydration, bisphosphonates, calcitonin, plicamycin, phosphate, and glucocorticoids. Others are under investigation. Treatment should be individualized taking into account the pathophysiological mechanisms involved, the extent of hypercalcemia and renal failure, and the prognosis related to the malignant disease.

Amino Acid Sequence↗
PubMed1991

The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: a randomized study comparing intermittent treatment and an ADFR regime.

Thirty-seven patients were randomized to receive intermittent cyclic etidronate (400 mg/day oral for 2 weeks, followed by 13 weeks off treatment) or an ADFR treatment (100 micrograms/day oral triiodothyronine for 7 days, followed by 400 mg/day etidronate for 2 weeks and 12 weeks off treatment). Supplemental calcium (120 mg/day) and vitamin D3 (400 IU/day) were given throughout the study period to all patients. Biochemical analyses, iliac-crest bone biopsies, and lumbar bone mineral content (BMC) measurements were performed before and during 60 weeks of treatment. Sixteen patients in the intermittent cyclic etidronate group and 15 in the ADFR group completed 60 weeks of treatment. Serum alkaline phosphatase decreased from 185 (43) (mean, (SD] to 144 (35) (p less than 0.001) and from 221 (69) to 156 (43) (p less than 0.002) during intermittent cyclic etidronate treatment and ADFR treatment, respectively, without any significant changes in renal hydroxyproline excretion. Final resorption depth, trabecular bone activation frequency, and bone formation rate decreased significantly from 51.5 (48.4/60.0) microns (median (25%/75% quartiles] to 44.0 (39.6/46.2) microns (p less than 0.04), from 0.30 (0.17/0.62) year-1 to 0.10 (0.02/0.19) year-1 (p less than 0.03) and from 0.035 (0.020/0.081) microns3/microns2/day to 0.015 (0.002/0.025) microns3/microns2/day, p less than 0.03 respectively, during intermittent cyclic etidronate treatment, but were unchanged during ADFR treatment. No significant changes in trabecular bone volume, bone balance per remodeling cycle, or BMC were noted in either treatment group; no evidence of osteomalacia was found. Intermittent cyclic etidronate treatment may be effective in preventing bone loss and in decreasing the risk of trabecular plate perforation, and thereby maintaining the integrity of bone architecture, in postmenopausal osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Dermal, intestinal, and renal obligatory losses of calcium: relation to skeletal calcium loss.

Calcium balance is the difference between dietary calcium intake on the one hand and dermal, fecal, and urinary losses on the other. Bone is lost throughout adult life by at least three different mechanisms. Whether all these processes are affected by dietary calcium is at present unknown. In case they are not, dietary calcium intake should balance an adjusted value estimated as obligatory skeletal calcium loss minus obligatory external (dermal + intestinal + urinary) calcium loss. Such a correction would reduce estimated calcium allowances. To solve this question it is important, however, to ascertain whether obligatory bone loss is affected by dietary intake of calcium, ie, Can a high dietary calcium or calcium supplementation influence bone metabolism and reduce bone loss at all ages?

Bone Development↗
PubMed1991

Primary Sjögren's syndrome in north east England--a longitudinal study.

We have documented the initial clinical features of 100 patients with primary Sjögren's syndrome (SS) together with the results of their baseline investigations. The evolution of the disease in these patients has been followed for a median of 34 months (range 3-84 months). The majority of patients were females aged 40-60 years, and common clinical features included eye symptoms (100%), xerostomia (100%), polyarthralgia (94%), Raynaud's phenomenon (81%) and salivary gland swelling (47%). Thyroid disease was relatively common (14%) while other endocrine disease was rare. Four patients died during follow-up, and three cases of lymphoma were detected. Other serious complications included pericarditis (10%), pleuroparenchymal lung disease (9%), renal tubular acidosis (3%) and cerebrovascular accidents (2%). The presence of anti-Ro antibodies identifies patients with more severe systemic disease. Spontaneous improvement occurred in 12 patients, while steroids were required for specific complications in 18. Overall, although lymphoma was found to excess in our group, the high mortality reported with primary SS elsewhere was not seen.

Adolescent↗
PubMed1991

Mobilization of haemopoietic stem cells by cyclophosphamide into the peripheral blood of patients with haematological malignancies.

Thirty one peripheral blood stem cell mobilizations using cyclophosphamide, followed by leucapheresis, were performed in 25 patients with a variety of haematological malignancies. Cyclophosphamide at doses ranging from 0.25 g/M2/day x 4 days to 4 g/M2 on one day were given. Total doses of cyclophosphamide less than 4 g/M2 failed to induce a significant mobilization of stem cells into the peripheral blood. This compares to cyclophosphamide doses of 4 g/M2 given over one or two days where 70%-75% of patients yielded adequate stem cells for transplantation (greater than 20 x 10(4) CFU-GM/kg). Both the presence of tumour cells in the bone marrow and previous chemotherapy within 12 months of cyclophosphamide infusion significantly diminished the patients stem cell mobilizations. The rate of recovery of the patient's leucocyte count following cyclophosphamide was highly correlated to the peak level of PB CFU-GM and is a good indicator of the total stem cell yield. Fever in 50% of patients during the period of cytopaenia was the only complication seen in our patients and thus high dose cyclophosphamide is a suitable and safe agent for mobilizing haemopoietic stem cells.

Adult↗
PubMed1991

[Asthma due to isocyanates in a theoretically non-exposed worker].

We report a case of isocyanate induced asthma in a patient who had been previously exposed to isocyanate and had become a porter in a factory producing polyurethene foam. The test for exposure to TDI was positive. The recognition of occupational asthma was nevertheless challenged and the patient was not considered to be carrying out work involving exposure to the inhalation of isocyanates. The effect of a change of job in the development of occupational asthma, and the risk of asthma induced by isocyanates despite inhaled concentrations inferior to the VME, the difficulty of obtaining a recognition of occupational asthma when the working conditions fulfilled do not exactly correspond to those labelled in the schedule for occupational diseases, are discussed in this paper.

Adult↗
PubMed1991

24-h profile of serum osteocalcin in growth hormone (GH) deficient patients with and without GH treatment.

Serum osteocalcin (OC), which is a specific, sensitive, and rapidly responding biochemical bone marker of osteoblastic activity, varies in a circadian rhythm in both normal adults and children with the highest levels during nighttime. In the present study, we characterized the 24-h rhythm of serum OC in 8 growth hormone (GH)-deficient children without treatment, and during two regimens of recombinant human GH (r-hGH), i.e. 2 IU/day s.c. at 08:00 h or at 20:00 h, in comparison with 5 normal, untreated children. Without treatment and when r-hGH was administered at 08:00 h, the 24-h profile of serum OC was correlated with that of the healthy controls in only 1 of 8 patients (r = 0.26 +/- 0.09 (mean +/- SE) and r = 0.10 +/- 0.08) whereas the correlation was significant in 6 of 8 patients (r = 0.44 +/- 0.05) during evening r-hGH administration. Within GH-deficient patients, mean OC level was lower during no r-hGH or evening administration compared with morning administration. In conclusion, untreated GH-deficient children have an abnormal 24-h serum OC profile. Evening administration of 2 IU of r-hGH/day s.c. tends to normalise the 24-h profile but not the average daily level, whereas morning administration of GH increases average daily OC level but does not normalize the circadian rhythm.

Adolescent↗
PubMed1990

Calcium metabolism in postmenopausal osteoporosis: the influence of dietary calcium and net absorbed calcium.

A group of 85 females aged 48-77 years with postmenopausal crush fracture osteoporosis were investigated using a 7 day combined calcium balance and calcium tracer kinetic turnover study to assess the influence of dietary calcium and net absorbed calcium on bone metabolism. During the study, patients were on their habitual diet, as determined by a prestudy registration. Dietary calcium was measured after double serving of all the meals. All urine and feces were collected and analyzed for calcium content. Bone mineralization rate and bone resorption rate were determined by applying the continuously expanding calcium pool model to the tracer kinetic data. Urine calcium excretion and net absorbed calcium were correlated (r = 0.64, p less than 0.0001) with the following equation: urinary excreted calcium (mmol/day) = 2.4 + 0.4 X net absorbed calcium (mmol/day). Dermal calcium loss was not correlated with net absorbed calcium or urinary calcium. The net amount of absorbed calcium necessary to balance urinary and dermal losses was calculated to be 4.2 mmol calcium per day. The daily calcium intake necessary for obtaining a net absorbed calcium in excess of the urinary and dermal calcium losses and thereby ensure skeletal integrity was estimated to be 34.2 mmol calcium per day compared to an average intake of 27.9 +/- 7.6 (mean +/- SD) mmol/day. Net absorbed calcium correlated negatively to bone resorption rate (r = -0.31, p less than 0.005) and positively to bone mineralization rate (r = 0.29, p less than 0.01) and to calcium balance (r = 0.66, p less than 0.0001). Dietary calcium intake and calcium balance correlated positively (r = 0.38, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Alcohol decreases serum osteocalcin in a dose-dependent way in normal subjects.

The acute effect of 25 and 50 g of alcohol on the variation in serum osteocalcin, a specific and sensitive marker of bone formation, and on serum cortisol and serum parathyroid hormone (PTH)(1-84) was calculated in 6 normal young adults. They were studied during three periods, each lasting from 4 p.m.-7:30 a.m. Alcohol was ingested between 4:15 and 5 p.m. during period two and three. Blood was taken at 4 p.m. and every 15 minutes from 4:30 til 6 p.m., followed by hourly sampling until 12 p.m. The last blood sample was taken after an overnight fast at 7:30 a.m. Initial and end values before and after alcohol ingestion did not differ significantly from control values. Repeated measures analysis of variance showed that 50 g of ethanol decreased serum osteocalcin significantly (P less than 0.02) and increased serum cortisol (P less than 0.05) during the 4-12 p.m. interval. The interaction of 50 g of ethanol on the variation in serum osteocalcin was already significant during the first 2 hours (P less than 0.02), where no significant effect on serum cortisol could be detected. Although insignificant, the same pattern was observed after 25 g of alcohol. There was no significant change in the variation of serum iPTH(1-84) during the 4-6 p.m. after alcohol intake. We conclude that 3-4 drinks of alcohol taken over 45 minutes decreases serum osteocalcin in a dose-dependent way. The time lag between changes in serum osteocalcin and cortisol indicates that the decrease in serum osteocalcin is not related to the increase in serum cortisol.

Adult↗
PubMed1990

Single high doses of cyclophosphamide enable the collection of high numbers of hemopoietic stem cells from the peripheral blood.

We used single high doses of cyclophosphamide (4 g/m2) to produce rebound increases in peripheral blood (PB) stem cells (PBSC) during recovery from myelosuppression, enabling their collection by apheresis for later autotransplantation. Thirty-three courses of cyclophosphamide were given to 30 patients with malignant lymphoma, multiple myeloma, or solid tumors. The neutrophil count was less than 0.5 x 10(9)/liter for a mean of 6.9 days (median 7 days), and fever occurred in 17 of 33 courses. Positive blood cultures occurred in two patients, one of whom died. The mean peak level of PB granulocyte-macrophage colony-forming units (CFU-GM) was 1517 x 10(3)/liter (median 2447 x 10(3)/liter), a 14-fold increase above the mean in normal subjects. The peak occurred at a mean of 16.6 days (median 16 days) after cyclophosphamide, generally coinciding with the time to reach 1.0 x 10(9) neutrophils per liter. Normal or minimally involved bone marrow and a rapid rise in leukocyte count during recovery were independent variables correlated to the peak of the rebound increase in PB CFU-GM levels. Previous chemotherapy and the duration of neutropenia were additional independent variables in the group with peak PB CFU-GM levels of greater than 1000 x 10(3)/liter. The mean total CFU-GM collected after a mean of five aphereses was 43.8 x 10(4)/kg body weight (BW) (median 35.5 x 10(4)/kg BW), significantly correlated with the mononuclear cell yield. We conclude that single 4 g/m2 doses of cyclophosphamide effectively produce high levels of PBSC, particularly but not exclusively in patients with normal or minimally involved bone marrow and who have not had intensive recent chemotherapy.

Adult↗
PubMed1990

Effect of near normoglycemia for 5 years on progression of early diabetic retinopathy and renal involvement.

The effect of strict metabolic control for 5 years on renal function and retinal morphology was estimated in 24 insulin-dependent diabetic individuals (age 29 +/- 8 years, diabetes duration 10 +/- 6 years) with albustix negative urine and minimal or no background retinopathy before the study. They were randomized to conventional insulin treatment (CIT) or continuous subcutaneous insulin infusion (CSII) with a portable pump. During CSII treatment the metabolic status was significantly improved. HbA1c fell from 8.9 +/- 2.0 to 7.4 +/- 1.3% (p less than 0.01) whereas HbA1c was unchanged during CIT treatment. The mean value of urinary albumin excretion (UAE) was not statistically significantly changed (from 12 +/- 10 mg/24 h to 13 +/- 5 mg/24 h in CSII patients and from 14 +/- 12 to 11 +/- 6 mg/24 h in CIT patients (p greater than 0.1). On the other hand, the elevated GFR values were significantly reduced in both CSII and CIT patients, 129 +/- 17 to 120 +/- 9 and 129 +/- 18 to 119 +/- 12 ml/min.1,73m2, respectively (p less than 0.05). Both the number of microaneurysms, haemorrhages and exudates tended to increase mor in CIT patients than in CSII patients during the 5 year study period, but the differences did not reach statistically significance (p greater than 0.1). Pump treatment did not induce proliferations or "cotton wool" exudates. We conclude that no statistically significantly differences between GFR values, UAE rates, and progression of background retinopathy was observed between normoalbuminuric IDDM patients treated for 5 years with CIT and CSII, respectively. However, due to the size of the material a type II error must be taken into consideration.

Adult↗
PubMed1990

Effects of thyroid hormones on bone and mineral metabolism.

Because of pronounced symptoms and early detection, severe hyperthyroidism is usually treated before skeletal symptoms are evident. However, previous hyperthyroidism may involve a risk of later postmenopausal or senile osteoporosis, since some of the bone loss apparently is irreversible. Borderline hyperthyroidism in clinically euthyroid patients may induce accelerated bone loss and thereby increase the risk of low-energy fractures. Moreover, it is unknown whether interindividual differences exist in skeletal sensitivity to circulating thyroid hormones and thereby in the rate of bone loss. From these considerations it appears that disturbed thyroid function may be involved in the pathogenesis of osteoporosis, one of the major health problems in the western hemisphere.

Bone and Bones↗