Erythropoietin abuse in athletes.
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Adult↗
Biomedical subjects
M Audran
Publications and source records attributed to M Audran.
Pharmacokinetics and haematological parameters of recombinant human erythropoietin after subcutaneous administrations in horses.
The pharmacokinetics of recombinant human Epo (rHuEpo) were investigated after subcutaneous administration to horses. Four horses received a single 30IU kg-1 dose of rHuEpo. One horse received three repeated doses of 120 IU kg-1 at 48 h intervals. Plasma erythropoietin (Epo) was measured by radioimmunoassay. In both cases pharmacokinetic parameters were evaluated using a one-compartment open model and first-order input and output rates. The mean values (+/-SD) for elimination half-life, CL/F, and Vd/F after a single dose were 12.9 +/- 3.34 h, 11.8 +/- 4.96 L h-1, and 233 +/- 126 L, respectively. After repeated doses, elimination half-life, CL/F, and Vdss/F were 11.3 h, 8.94 L h-1, and 145.6 L, respectively. No significant differences were observed between the haematological parameters after a single 30 IU kg-1 administration compared to baseline values. Multiple and high doses of rHuEpo modified red blood cells, haemoglobin, and hematocrit. According to our results, plasma Epo assay can help, during an antidoping control procedure, to support a positive result only up to 72 h after the last rHuEpo.
Animals↗
Altered trabecular architecture induced by corticosteroids: a bone histomorphometric study.
Prolonged corticosteroid (CS) therapy induces osteoporosis and fractures. Osteoporosis is characterized at the histomorphometric level by reduced bone volume (BV/TV) and disruption of the three-dimensional (3D) trabecular architecture. Several stereological methods have been proposed to characterize these alterations: measurements of trabecular thickness and trabecular number, star volumes, interconnectivity index (ICI) of the bone marrow spaces, and trabecular bone pattern factor (TBP(f)). These methods were computerized with a single program running on an image analyzer to evaluate the bone changes in a series of iliac biopsies performed on 31 male patients. All of them were asthmatic and had received CS for a long period of time. BV/TV was reduced when compared with age-matched controls. In the CS-treated population, exponential relationships were obtained between bone volume and the different connectivity parameters. The various methods used to measure connectivity were well correlated. When the population was divided into two groups (BV/TV greater or less than an 11% threshold), the architectural disturbances were found to imply two mechanisms. A progressive decline in trabecular thickness was noted in both groups versus controls. Trabecular perforations were not established in the group with BV/TV> 11% with the star volume or ICI, although some alterations were detected by trabecular bone pattern factor measurement. However, perforations were revealed in the group with BV/TV < 11% by all the different methods. Perforations seemed to occur when the trabecular thickness was below 70 mu m. This strongly suggests that bone histomorphometry should take into consideration bone volume in combination with detailed 3D descriptors of the trabecular architecture. Several histological methods need to be used in combination to appreciate the 3D architecture of trabecular bone.
Adrenal Cortex Hormones↗
Spontaneous multiple vertebral fractures revealed primary haemochromatosis.
The association of haemochromatosis and bone disease is well established, but osteoporotic fracture is an unusual presentation of the disease. We describe a male patient with osteoporotic fractures as a presenting feature of haemochromatosis. The bone histomorphometry showed a dramatic decrease in trabecular bone volume associated with a decrease in cortical bone thickness. Osteoblastic and osteoclastic activities were reduced without any sign of osteomalacia. Staining for iron with Perl's stain showed focal localization at the interface between mineralized trabecular bone and bone marrow. This observation leads us to review the possible mechanisms of osteoporosis.
Hemochromatosis↗
Recommendations for the registration of agents used in the prevention and treatment of glucocorticoid-induced osteoporosis.
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Animals↗
Osteoclast cytomorphometry in patients with femoral neck fracture.
In patients with femoral neck fracture, nutritional deficiencies have been shown to be common. A low calcium diet and/or a reduced vitamin D intake have been suspected to cause secondary hyperparathyroidism responsible for increased bone turn over and bone loss. Parathyroid hormone (PTH) levels are increased in these patients, data which are in accordance with the pronounced changes observed on bone biopsies reflecting a true hyperparathyroidism. We have used a cytomorphometrical approach to characterize PTH-induced changes on the osteoclastic population. Osteoclasts were detected histochemically (by tartrate resistant acid phosphatase staining) on bone biopsies from 10 control subjects, 8 patients with primary hyperparathyroidism and 10 patients with a femoral neck fracture of osteoporotic origin. The maximum Feret's diameter of each osteoclast (Oc.Le) was determined with a semiautomatic image analyzer. In all groups, the frequency distribution of Oc.Le appeared positively skewed. In both hip fractured patients and primary hyperparathyroid patients, the mode of the distribution was higher (25-30 microns) than in controls (20-25 microns). When graphically converted on a probability graph, the osteoclastic populations appeared homogeneous and well described by a lognormal distribution in the three groups. However, osteoclasts appeared similarly enlarged in the groups of patients with primary hyperparathyroidism and with femoral neck fracture. PTH has been shown to increase both the recruitment of mononucleated precursors and their fusion into larger osteoclasts than controls. In the present study, a cytomorphometric method appeared able to identify the border line hyperparathyroidism in the hip fractured patients.
Adult↗
Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in athletes. Blood sampling and doping control.
1. The pharmacokinetics of recombinant human erythropoietin (rHuEpo) were initially determined in two healthy volunteers after a single subcutaneous dose (50 u kg-1). Twenty subjects then received repeated subcutaneous administrations of high dose (200 u kg-1) rHuEpo and 10 subjects received placebo. An immunoradiometric assay was used to measure the concentrations of erythropoietin (Epo) in serum and urine. 2. Serum Epo concentration-time profiles were best described by a one-compartment open model with zero-order input. The mean elimination half-life (+/- s.d.) was 42.0 +/- 34.2 h. Clearance, uncorrected for bioavailability, was 0.05 +/- 0.011 h-1 kg-1. Erythropoietin concentrations returned to normal values in serum and urine, 7 and 4 days after the last administration, respectively. 3. The recombinant hormone was well tolerated. Significant changes in reticulocytes and red blood cells, haemoglobin concentrations and haematocrit were observed after administration of rHuEpo. In the control group, these parameters remained unchanged. 4. The change in reticulocytes was used as an index of the therapeutic effect of rHuEpo. The concentration-effect relationship was best described by an exponential model. 5. These data show the limitations of the measurement of Epo concentrations in blood and urine samples, collected in athletes during competition, for antidoping control. Epo doping can be detected only during or within 4 to 7 days of ending a course of rHuEpo.
Adult↗
Bacterial endocarditis revealed by infectious discitis.
A study of 30 patients admitted for infectious discitis identified four cases with concomitant bacterial endocarditis. All four patients were male and had concomitant streptococcal septicemia. Two patients had known aortic valve disease. The vertebral infection was located to the thoracic or lumbar spine. Ultrasonography disclosed aortic lesions in all four patients and mitral lesions in two. Management consisted of intravenous antimicrobial therapy for four weeks followed by a three-month course of oral antimicrobial therapy. The outcome of the discitis was favorable within the usual period of time. However, the endocardial lesions continued to progress, and three patients rapidly required valve replacement. Analysis of available data in the 30 patients with discitis showed that half the patients with streptococcal discitis also had bacterial endocarditis and that the latter condition developed in all the patients with streptococcal discitis and a history of valve disease. A number of risk factors were identified. An echocardiogram should be done routinely in patients with infectious discitis and risk factors for bacterial endocarditis.
Adult↗
Comparative study of 6 types of criteria in adult Still's disease.
OBJECTIVE: To compare the sensitivity of 6 sets of criteria proposed for adult Still's disease in published papers in a well defined patient population. METHODS: For inclusion we required a diagnosis of adult Still's disease established by a senior internist or senior rheumatologist. Sensitivity was evaluated in 65 new cases of adult Still's disease from a multicenter study based on signs and symptoms (1) in the first 6 months of illness, (2) in the same period in patients followed more than one year (52 patients), and (3) at any time in patients followed more than one year. RESULTS: The Yamaguchi criteria are most sensitive (93.5%), followed by those of Calabro and Londino. Medsger et al (80.6%), Kahn (69.3%), Reginato (55.2%), and Goldman (43.7%). Sensitivity was high even from the first 6 months, except for the 2 less sensitive criteria. CONCLUSION: Awareness of these discrepancies in adult Still's disease criteria are crucial to ensure comparability of different series of this condition.
Adult↗
An etiologic study of Paget's disease.
The objective of this case-control questionnaire study was to determine whether a history of measles or of dog ownership occurred with different frequencies in Paget's disease patients and in age- and sex-matched controls. Clustering of Paget's disease cases in geographic foci was also looked for, as well as a difference in the prevalence of Paget's disease according to whether the subsoil was composed of rocks from the primary or the tertiary-quaternary geologic periods. Completed questionnaires were obtained from 247 Paget's disease patients and 281 controls. Paget's disease was significantly associated with a history of measles (odds ratio, 2.46) but not with a history of mumps (odds ratio, 0.79) or with dog ownership (odds ratio, 0.97). The 174 cases of Paget's disease in subjects from the study district were distributed throughout the district, with no geographic clustering. This result was confirmed by the analysis of the ratios of Paget's disease cases over the total population in each county in the study district. The incidence of Paget's disease was slightly higher in areas with a primary subsoil, but the difference was not statistically significant (chi-square, 0.79; P = 0.37).
Aged↗
Minocycline related lupus.
The determination of a factor triggering lupus-like symptoms could yield new insights into the management of rheumatic disease. We describe a case of minocycline related lupus in a young patient positive for HLA-DR2 who was prescribed minocycline 4 times for mild acne and developed rheumatic symptoms each time. We review 8 other cases.
Acne Vulgaris↗
The initial site of bone lesions in Paget's disease. A review of two hundred cases.
We retrospectively evaluated the initial site of bone lesions in 200 patients with Paget's disease. There were 117 males and 83 females. Mean follow-up was 13 years in 98 patients. The initial site can be determined accurately only if less than one third of the bone is involved. Paget's disease usually begins in the cancellous bone of an epiphysis or metaphysis. A diaphysis is the first site involved in some instances, and the anterior subperiosteal area of the proximal half of the tibia in a very small number of cases. The distribution of initial pagetic lesions in our series is reported for each of the main bones. Lesions usually arose in the proximal ends of long bones, which are richly vascularized but contain no hematopoietic marrow in adults. This suggests that the distribution of pagetic lesions may be more closely dependent on local circulatory conditions than on the presence of hematopoietic marrow, which is, however, the only source of osteoclasts.
Adult↗
Felty's syndrome, pseudo-felty's syndrome, monoclonal or polyclonal CD3 lymphocytosis of undetermined significance.
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Arthritis, Rheumatoid↗
[Systemic scleroderma and sarcoidosis: 3 new cases].
We observed 3 patients with successive scleroderma (SS) and (what is considered to be) sarcoidosis (SA). The diagnosis SS included in the 3 patients: Raynaud's syndrome with pulpal necrosis and capillaritis, sclerodactylia and acro-osteolysis, multiple joint pain and FAN+. Also observed were: esophagus involvement (n = 3), pulmonary artery hypertension (n = 1), telangiectasia (n = 2) and anti-Scl 70 (n = 2). Initially, all patients had restrictive pulmonary disease. SS was diagnosed 5 to 9 years prior to SA in 2 patients. Diagnosis of SA was based on the following arguments: Loëfgren's syndrome with erythema nodosa (n = 1), parotiditis (n = 2), sicca syndrome (n = 2), myalgia (n = 2), joint involvement (n = 2), non-infectious pluropericarditis (n = 2), epitheloid and giant cell granulomas without caseous necrosis (lung = 3, liver = 1, lymph nodes = 1, salivary glands = 1, synovia = 1), negative search for bacilli, elevated conversion enzyme (n = 1) and, in each case, by the lack of any other cause. One patient died from lung cancer and another from respiratory failure. Nome of the patients had primary biliary cirhosis. This rare association between SS and SA demonstrates the confluent limits of certain systemic diseases and raises a difficult problem to differentiate pulmonary involvement in these diseases. The gravity of this localization and the poor sensitivy to corticosteroids.
Adult↗
Effects of tiludronate on bone loss in paraplegic patients.
Immobilization secondary to spinal cord injury is associated with a marked and rapid atrophy of trabecular bone (disuse osteoporosis). This is due to an early increase of osteoclastic bone resorption associated with a pronounced decreased osteoblastic bone formation. Bisphosphonates are antiosteoclastic compounds and they have been effective in preventing disuse osteoporosis. However, some of them also depress osteoblastic activity and may impair the mineralization process. Tiludronate was shown effective in reducing bone resorption in several metabolic bone diseases without inducing mineralization defects. Twenty paraplegic patients (6 females and 14 males) were randomly assigned to three groups: 6 patients entered the placebo group; 7 patients received tiludronate 200 mg/day; and 7 received 400 mg/day. Histomorphometric analysis was performed on transiliac bone biopsies before and after 3 months treatment. An insignificant decrease of bone volume was observed in the placebo group and the 200 mg group. In patients receiving 400 mg/day, a slight increase was noted. Osteoid parameters changed nonsignificantly in three groups although the 400 mg group exhibited a slight tendency to decrease osteoid volume and thickness. Eroded surfaces increased in all groups. The number of osteoclasts (identified histochemically by TRAP staining) increased in the placebo group but decreased in groups receiving tiludronate. Tiludronate appears effective in reducing bone resorption without impairing bone formation in a manner that preserved bone mass and bone cell coupling.
Adolescent↗
Recommendations for the registration of new chemical entities used in the prevention and treatment of osteoporosis.
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Animals↗
Calciotropic hormones in elderly people with and without hip fracture.
The effects of age on calciotropic hormones are not completely understood. The presence of secondary hyperparathyroidism has previously been demonstrated, particularly in patients with hip fracture. The role of a disturbance of vitamin D metabolism, especially a defect in 1 alpha-hydroxylation, is debated. The aim of this study was to compare serum parathyroid hormone (PTH), osteocalcin and vitamin D metabolites (25(OH)D and 1,25(OH)2D) in osteoporotic elderly patients with hip fracture (HF) and in elderly controls. We studied 57 HF patients aged 83.9 +/- 5.9 years (mean +/- SD) and 68 controls aged 82.5 +/- 5 years recruited during two periods: 1 January and 30 April 1988 and 1989. Patients with chronic renal failure (serum creatinine above 150 mumol/l), cancer, or other metabolic bone disease were excluded. Thirty healthy young adults were studied in 1989 only for measurement of 1,25(OH)2D. (1,25(OH)2D was measured by different laboratories in 1988 and 1989 for technical reasons.) We also measured serum PTH, osteocalcin, total calcium and ionized calcium. 1,25(OH)2D levels were not statistically different between HF patients and controls for the two years, nor between HF patients and young healthy adults in 1989. 25(OH)D was decreased in HF patients (p < 0.003), as was ionized calcium. Serum PTH levels were higher in HF patients than in controls (p < 0.01). A positive correlation has been found between PTH and age in HF patients (r = 0.29; p < 0.03) and in the whole group of HF patients and controls. There was a significant decrease in osteocalcin in HF patients versus elderly controls (p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Direct effect of calcitriol on the regulation of parathyroid hormone secretion in a case of pseudo-hypoparathyroidism (a 24-month follow-up study).
The diagnosis of pseudohypoparathyroidism with osteitis fibrosa was made in a 51-year-old woman on the basis of hypocalcaemia, elevated plasma PTH (1-84) and blunted cAMP response to hPTH infusion. Radiologically, widespread signs of hyperparathyroidism were observed and quantitative histomorphometry confirmed the increased bone cellular turnover. Treatment with calcitriol (1,25 dihydroxyvitamin D3) induced a dramatic improvement of bone lesions. During treatment PTH (1-84) normalized with high dosage of calcitriol in spite of low or subnormal levels of serum calcium, and subsequently increased for each reduction of calcitriol dosage despite normal calcium levels. Our observations support a major and direct effect of 1,25 dihydroxyvitamin D3 on the regulation of parathyroid secretion of parathyroids glands.
Biopsy↗