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Biomedical subjects

F Marchand

Publications and source records attributed to F Marchand.

At least 19 recordsLinked to original sources

Increased bone resorption in moderate smokers with low body weight: the Minos study.

Tobacco was found to be a risk factor for osteoporosis, mainly in postmenopausal women. We studied the effect of smoking on bone mineral density (BMD) and bone turnover in a cohort of 719 men, aged 51-85 yr, composed of 83 current smokers, 405 former smokers, and 231 men who never smoked. Most current and former smokers were moderate smokers (median, 10 cigarettes/d). Current smokers were younger, thinner, and drank more coffee and more alcoholic beverages. After adjustment for age, body weight, alcohol intake, and caffeine intake, current and former smokers had similar BMD, except at the forearm. Former smokers had lower BMD compared with never-smokers at most skeletal sites. Men who had smoked more than 7120 packs (third quartile) had lower BMD of total hip (P < 0.01) and distal forearm (P = 0.03) compared with men in the 2 lower tertiles. In the 3 groups, levels of bone formation markers did not differ. After adjustment for confounding variables, levels of urinary markers of bone resorption (beta-isomerized C-terminal telopeptide, free and total deoxypyridinoline) were higher in the current smokers than in former smokers and never-smokers. Concentrations of T, total 17beta-E2, and androstenedione were higher, whereas that of 25-hydroxyvitamin D was lower, in current smokers. When men were divided according to tertiles of body weight, increased bone resorption, decreased BMD and biochemical indexes of secondary hyperparathyroidism were observed in current smokers in the lowest tertile of body weight (<75 kg) compared with the never-smokers, but not in men in the two highest tertiles of body weight. Current smokers had a higher prevalence of vertebral deformities after adjustment for age and body weight (13% vs. 5%; P < 0.005). In summary, in moderate smokers with low body weight (<75 kg), increased bone resorption, not matched by increased bone formation, results in decreased BMD and an increased prevalence of vertebral deformities. In this group, low serum 25-hydroxyvitamin D and secondary hyperparathyroidism may explain, at least partly, the effect of tobacco on bone turnover. In former smokers, bone resorption is not increased, but BMD remains lower compared with that in never-smokers.

Aged↗

Semiquantitative evaluation of prevalent vertebral deformities in men and their relationship with osteoporosis: the MINOS study.

Epidemiologic studies have shown a high prevalence of vertebral deformities in men without a steep increase with aging, suggesting that a substantial number of these deformities are not related to osteoporosis. To determine which vertebral deformities are likely to be osteoporotic fractures, we compared vertebral deformities and bone mineral density (BMD) in a cohort of 786 men aged 51-85 years (the MINOS study). Normal vertebral height ratios were defined in a group of 120 healthy men aged 21-50 years. We classified vertebral deformities by using the semiquantitative method described by Genant et al., which was slightly modified at the level of thoracic kyphosis (T6-T9). At that level, grade 1 wedge deformities were defined as a 25-30% decrease in anterior vertebral height and grade 2 by a 30-40% decrease. The same cutoff of 40% was used for grade 3 for all vertebrae from T4 to L4. BMD was measured with a Hologic 1500 device at the lumbar spine, hip and whole body and with an Osteometer DTX 100 device at the forearm. Z-scores were calculated in 10-year age groups. The prevalence of vertebral deformities increased significantly with age. After adjustment for age and body weight, BMD did not differ between those with and without vertebral deformities. In patients having grade 2 and 3 deformities, BMD was lower than in men having no deformities or only grade 1 deformities when adjusted for age and body weight. Using the age- and body-weight-adjusted test of linear trend for sextiles of BMD, prevalence of grade 2 and 3 vertebral deformities increased with a decrease in BMD at all the sites of measurement. Grade 1 deformities were not correlated with BMD at any site. Among 126 patients who had only grade 1 vertebral deformities, 32 deformities in 30 men were confirmed as vertebral fractures according to their morphology but their BMD did not differ from the nonfractured men. These findings were confirmed when vertebral deformities were measured by the conventional morphometric method in a subgroup of 131 men. Our data suggest that a cutoff of 30% for wedge deformities from T6 to T9 and of 25% for other deformities has a high specificity and a moderate sensitivity for identifying vertebral deformities related to low BMD in men. Grade 1 deformities are often either false positive or deformities related to nonosteoporotic disease of the spine.

Age Distribution↗

Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study.

The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1-9.4) and a weak predictor of 'other' limb fractures (RR = 1.6; 95% CI 1.1-2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6-1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0-17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and 'other' limb fractures; however, they do not predict distal forearm fractures.

Aged↗

Bioavailable estradiol may be an important determinant of osteoporosis in men: the MINOS study.

During recent years, experimental data, case reports, and epidemiological studies have suggested an important role for estradiol in bone metabolism in men. In a cohort of 596 men, aged 51-85 yr, we measured bone mineral density (BMD) of the lumbar spine, hip, total body, and forearm; serum levels of sex steroid hormones [total and free testosterone, total estradiol (17betaE(2)), bioavailable estradiol (bio-17betaE(2)), androstenedione, and sex hormone-binding globulin]; and markers of bone turnover [serum osteocalcin, bone alkaline phosphatase, N-terminal extension propeptide of type I collagen, and beta-isomerized C-terminal telopeptide of collagen type I (betaCTX)], as well as urinary excretion of betaCTX and deoxypyridinoline (DPyr). An age-related decrease was found for bio-17betaE(2) (r = -0.16; P < 0.001), free testosterone (r = -0.25; P < 0.001), free testosterone index (r = -0.32; P < 0.001), and androstenedione (r = -0.22; P < 0.001), but not for total 17betaE(2) or total testosterone. 17betaE(2) and bio-17betaE(2), but not other hormones, were correlated with BMD after adjustment for age and body weight. In men with a bio-17betaE(2) level in the lowest quartile, the average BMD was lower than in men having a bio-17betaE(2) level in the highest quartile by 6.6-8.7% according to the site of measurement, which corresponded to 0.45-0.65 SD. In age- and body weight-adjusted models, bio-17betaE(2), but not other hormones, was negatively correlated with bone markers (e.g., osteocalcin: r = -0.14; P < 0.001; urinary betaCTX: r = -0.20; P = 0.0001; DPyr: r = -0.14; P < 0.001). In men with the lowest concentration of bio-17betaE(2) (first quartile), the concentrations of markers of bone turnover were higher by 11-35% (or 0.4-0.7 SD) than in men having the highest bio-17betaE(2) level (upper quartile). In men in the lowest quartile for bio-17betaE(2) and in the highest quartile for urinary DPyr or betaCTX, the BMD of total hip and that of distal forearm were 8% and 10% lower than in men in the highest quartile for bio-17betaE(2) and in the lowest quartile for DPyr or ssCTX. In the age- and body weight-adjusted multiple regression models, bio-17betaE(2) contributed significantly to the explanation for the variability in all markers. In summary, we found in a cross-sectional analysis of a cohort of men that low levels of bio-17betaE(2) are associated with high bone turnover and low BMD. These data suggest that the age-related decrease in bio-17betaE(2) contributes to bone loss in elderly men by increasing bone turnover. Low 17betaE(2) levels may be an important risk factor for osteoporosis in men.

Aging↗

Cross-sectional evaluation of bone metabolism in men.

There are relatively few data concerning age-related changes of bone turnover in men. The aim of the study was to evaluate age-related changes of the levels of serum and urinary biochemical markers of bone metabolism in a large cohort of 934 men aged 19-85 years and to investigate their association with bone mineral density (BMD). Bone formation was evaluated using serum levels of osteocalcin (OC), bone alkaline phosphatase (BAP), and N-terminal extension propeptide of type I collagen (PINP). Bone resorption was evaluated by measurement of urinary excretion of beta-isomerized C-terminal telopeptide of collagen type I beta-CTX) of free deoxypyridinoline (fDpyr) and total Dpyr (tDPyr) and of the serum level of beta-CTX. Levels of biochemical bone markers were very high in young men and decreased rapidly until the age of 40 years and then more slowly until 60 years of age. After the age of 60 years, markers of bone formation remained stable while resorption markers showed a moderate and variable increase with aging. Serum and urinary beta-CTX levels were elevated only in about 5% of elderly men. The age-related increase of urinary excretion of tDpyr and of its free and peptide-bound fractions was related to the presence of elevated levels in a subgroup of about 15% of elderly men. Before 60 years of age, levels of biochemical bone markers were not correlated with BMD, whereas after 60 years of age, they were correlated negatively with BMD. After adjustment for age and body weight, BMD in men with the highest levels of biochemical bone markers (i.e., in the upper quartile) was 1.8-12.5% (i.e., 0.25-0.89 SD) lower than in men with levels of biochemical bone markers in the lowest quartile. In conclusion, bone turnover in men is high in young adults and decreases to reach a nadir at 55-60 years of age. After the age of 60 years, bone resorption markers--but not bone formation markers--increase in some men and are associated with lower BMD, suggesting that this imbalance is responsible for increasing bone loss in elderly men.

Adult↗

Cross-sectional assessment of age-related bone loss in men: the MINOS study.

There are few data on osteoporosis in men, but cross-sectional studies have shown that age-related bone loss in men is of lower magnitude than in women. To elucidate some controversies related partially to methodological aspects, we measured bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) at various skeletal sites (spine, hip, and whole body using a Hologic QDR-1500 device; forearm using an Osteometer DTX 100 device) in a large cohort of 1040 men, aged 19-85 years. The final investigation was performed on 934 men, aged 19-85 years, after exclusion of 106 men with disease or treatment known to affect bone metabolism. Peak BMD was achieved at 25 and 29 years at the lumbar spine and hip, respectively, but only at 40 and 37 years at the distal forearm and whole body, respectively. The magnitude of bone loss between peak bone mass and 80 years of age was linear at most sites and averaged 13%-18%; that is, SD of 1.1-1.8 from peak BMD, except for Ward's triangle, which showed a marked bone loss of 43% (i.e., 2.5 SD), and for the lumbar spine. In the entire cohort, increase of the average lumbar spine BMD after the age of 55 years was related to the development of osteoarthritis, because, in men without severe arthritis, lumbar spine BMD continued to decrease. Height-adjusted partial correlations indicate that both the mineral content and the area of long bones of the limbs increased with age up to 50 years, followed by a significant decrease of BMD without change of bone surface. SD of mean BMD increased significantly with age at most skeletal sites. In summary, age-related change of BMD varied according to skeletal site in men with peak bone mass achieved earlier at sites rich in trabecular bone than at those rich in cortical bone. Bone loss varied according to skeletal site from 14% to 43%. The variability of BMD increased with age, which may reflect interindividual variability of age-related bone loss.

Absorptiometry, Photon↗

Fc epsilonRI-mediated induction of TNF-alpha gene expression in the RBL-2H3 mast cell line: regulation by a novel NF-kappaB-like nuclear binding complex.

Using rat basophilic leukemia (RBL-2H3) cells as a model, we investigated how aggregation of the high affinity receptor for IgE (Fc epsilonRI) regulates TNF-alpha gene expression. Antigenic stimulation of RBL-2H3 cells led to an increase in newly synthesized TNF-alpha mRNA that was dependent on continuous receptor aggregation and did not require de novo protein synthesis. Kinetic analysis showed that maximal levels were achieved at 60 min and waned by 180 min of stimulation. Concomitant with the transcriptional activation of the TNF-alpha gene, the rapid appearance and disappearance of a previously uncharacterized nuclear NF-kappaB DNA binding activity, comprised of two distinct protein complexes, were observed. These protein complexes bound to NF-kappaB sites within the TNF-alpha gene and contained novel proteins (three species of Mr between 90,000-110,000) distinct from the classical proteins in NF-kappaB complexes. The induced NF-kappaB binding activity required continuous receptor stimulation and induced NF-kappaB-dependent reporter gene expression. Consistent with a role for the novel NF-kappaB nuclear binding activity in TNF-alpha gene expression, deletion of several 5' kappaB elements in the TNF-alpha promoter abolished all measurable Fc epsilonRI-dependent induction of a reporter construct. Pharmacologic agents that inhibited the NF-kappaB binding activity also inhibited TNF-alpha mRNA expression. Our results demonstrate that a novel NF-kappaB-like nuclear binding activity plays an important role in regulation of the rapid and transient transcriptional activation of the TNF-alpha gene via Fc epsilonRI.

Animals↗

Specific signaling pathways in the regulation of TNF-alpha mRNA synthesis and TNF-alpha secretion in RBL-2H3 mast cells stimulated through the high affinity IgE receptor.

OBJECTIVE: In the present study, we investigated signal transduction pathways involved in TNF-alpha gene expression and TNF-alpha secretion by mast cells stimulated through the high affinity IgE receptor (FcepsilonRI). MATERIALS AND METHODS: TNF-alpha mRNA steady state levels and TNF-alpha secretion in the presence of specific pharmacological agents were monitored using rat basophilic leukemia cells (RBL-2H3) stimulated through FcepsilonRI. Relative amounts of TNF-alpha mRNA versus beta-actin levels were quantified by RNase protection and RT-PCR assays. TNF-alpha secretion was measured by a current ELISA test. RESULTS: We show that EGTA (5 mM) prevented TNF-alpha mRNA expression and TNF-alpha secretion in antigen-stimulated cells. The protein kinase C (PKC) inhibitor bisindolylmaleimide I substantially blocked TNF-alpha secretion at 2 microM but had only a marginal effect on TNF-alpha mRNA expression. The results were similar when PKC isoforms were depleted by long-term exposure to 100 nM phorbol ester (PMA). The PI 3-kinase inhibitor wortmannin blocked TNF-alpha secretion at low doses (EC50= 13 nM), but only partially affected mRNA expression. CONCLUSIONS: Our results show that in FcepsilonRI-stimulated RBL-2H3 cells calcium mobilization, activation of PKC and PI 3-kinase are necessary for TNF-alpha secretion while for the increased TNF-alpha mRNA expression PKC activity is dispensable and PI 3-kinase activity only partially required.

Androstadienes↗

Mortality associated with vertebral deformity in men and women: results from the European Prospective Osteoporosis Study (EPOS).

Clinically apparent vertebral deformities are associated with reduced survival. The majority of subjects with radiographic vertebral deformity do not, however, come to medical attention. The aim of this study was to determine the association between radiographic vertebral deformity and subsequent mortality. The subjects who took part in the analysis were recruited for participation in a multicentre population-based survey of vertebral osteoporosis in Europe. Men and women aged 50 years and over were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Radiographs were evaluated morphometrically and vertebral deformity defined according to established criteria. The participants have been followed by annual postal questionnaire--the European Prospective Osteoporosis Study (EPOS). Information concerning the vital status of participants was available from 6480 subjects, aged 50-79 years, from 14 of the participating centres. One hundred and eighty-nine deaths (56 women and 133 men) occurred during a total of 14,380 person-years of follow-up (median 2.3 years). In women, after age adjustment, there was a modest excess mortality in those with, compared with those without, vertebral deformity: rate ratio (RR) = 1.9 (95% confidence interval (CI) 1.0,3.4). In men, the excess risk was smaller and non-significant RR = 1.3 (95% CI 0.9,2.0). After further adjusting for smoking, alcohol consumption, previous hip fracture, general health, body mass index and steroid use, the excess risk was reduced and non-significant in both sexes: women, RR = 1.6 (95% CI 0.9,3.0); men RR = 1.2 (95% CI 0.7,1.8). Radiographic vertebral deformity is associated with a modest excess mortality, particularly in women. Part of this excess can be explained by an association with other adverse health and lifestyle factors linked to mortality.

Aged↗

Prevalence of vertebral deformities according to the diagnostic method.

Vertebral deformities are a major complication of osteoporosis. Although their prevalence is known to increase with age, the absence of reference criteria complicates their radiologic diagnosis. We evaluated variations in the prevalence of vertebral deformities according to the diagnostic method used in 291 men and 262 women older than 50 years included in the European Vertebral Osteoporosis Study. Lateral radiographs of the thoracic and lumbar spine were obtained in all subjects using standardized parameters. Six morphometric and quantitative methods were used to detect vertebral deformities. The prevalence of vertebral deformities, the number of vertebral deformities per 100 subjects and the prevalence of deformities for each vertebra varied according to the method used. With most methods, the percentage of subjects with vertebral deformities and the number of vertebral deformities were similar among the men and among the women. In the women, the prevalence and the number of vertebral deformities increased with age; beyond 70 years of age, however, the prevalence remained stable with advancing age, although the number of deformities per patient increased. In men, the prevalence of vertebral deformities remained stable with advancing age, suggesting that osteoporosis was not the only cause of vertebral deformity in this group. In conclusion, the prevalence of vertebral deformities varies according to the diagnostic method used. In men, none of the six methods evaluated in this study adequately differentiates osteoporotic deformities from deformities due to other causes.

Age Factors↗

[Intra-parotid neurogenic tumors of the facial nerve. Value of MRI].

Facial nerve intraparotid neuromas are rare. We report two cases with no facial paralysis. In the first case, the clinical protocol for the evaluation of a parotid mass did not suggest the intramastoid tumor extension. This extension was shown by CT and MRI and confirmed by gross and microscopic appearance. In the second case, no intrapretrous extension was observed with MRI. The diagnosis of neuroma was made during surgery. With a literature review, we discuss the diagnostic difficulties encountered in the investigation of parotid facial nerve tumors, emphasizing on the usefulness of CT and MRI in its diagnosis.

Adult↗

[Narcolepsy disclosing neurosarcoidosis].

A 37-year-old man developed excessive daytime sleepiness, sleep attacks and cataplexy revealing an hypothalamic tumour. Multiple Sleep Latency Tests (MSLT) were characteristics of narcolepsy. Tissue typing was positive for HLA DR2 and DQ1. Most cases of narcolepsy are idiopathic without any evidence of brain pathology. Although symptomatic narcolepsy may occur occasionally with diencephalic lesions. The relationship between narcolepsy with diencephalic lesions is unsettled and will be discussed.

Adult↗

[Tubular sterilization in the immediate postpartum period using local anesthesia and laparoscopy].

Puerperal laparoscopic sterilization was performed in 732 women under anaesthesia at the Maternity of Noumea (New-Caledonia). There were no complications. Among the per-operative and postoperative incidents which occurred, there were 0.8% pregnancies, 3.6% bleeding of the broad ligament which was controlled during laparoscopy and 3% events (adhesion, pain) which required general anaesthesia. It was concluded that the described technique of puerperal laparoscopic sterilization is a safe, simple, rapid, inexpensive and reliable surgical technique in expert hands.

Adult↗

In vitro inhibition, by loratadine and descarboxyethoxyloratadine, of histamine release from human basophils, and of histamine release and intracellular calcium fluxes in rat basophilic leukemia cells (RBL-2H3).

The effect of the H1-antihistamine drug loratadine and its active metabolite descarboxyethoxyloratadine upon histamine release was examined on anti-immunoglobulin E (IgE) triggered human basophils and 2,4-dinitrophenyl (DNP) triggered rat basophilic leukemia (RBL-2H3) cells. In both experimental systems, dose-dependent inhibition of histamine release was observed at descarboxyethoxyloratadine and loratadine doses above 2 and 7 microM, respectively. In the RBL-2H3 experimental system, inhibition by loratadine increased when the concentration of extracellular Ca2+ was reduced from 1.8 to 0.45 mM. We further investigated the effect of loratadine and descarboxyethoxyloratadine on the increase in cytosolic calcium concentration (Ca2+)i, an early step in biochemical events leading to exocytosis. The effect of these two drugs upon (Ca2+)i changes was measured using the fluorescent probe fura-2 loaded into RBL-2H3 cells passively sensitized with DNP-specific IgE. Both drugs inhibited, in a dose-dependent manner (2.5-25 microM), the (Ca2+)i rise induced by DNP-BSA challenge in sensitized RBL cells, a process observed in both the presence and absence of extracellular Ca2+. Loratadine also inhibited the Mn2+ influx into these cells, thus reflecting the Ca2+ influx. These results suggest that loratadine and descarboxyethoxyloratadine impair the increase in (Ca2+)i following cell activation by decreasing both the influx of extracellular Ca2+ and the release of Ca2+ from intracellular stores.

Animals↗

Non-pharmacological approaches to the treatment of narcolepsy.

A way of evaluating the part played by non-drug treatments is to study cases of patients who discontinued stimulant medications but still came back for follow-up visits. Out of 40 patients with narcolepsy-cataplexy, three refused medication because their work was compatible with a regimen of naps (follow-up 1 year), and 10 stopped taking drugs when they could adapt nap therapy to a new life-style (follow-up 6.9 +/- 5 years). Three interrelated levels of non-pharmacological treatments of narcolepsy were examined: 1) Behavioral management, which includes: (A) structured sleep schedules: literature shows that a single long afternoon nap proffered greatest performance benefits in reaction time, significantly increased over a no-nap control condition, with no evidence of sleep inertia. The placement of this nap might yield better results if scheduled 1 hour before that of a normal subject. (B) Dietary factors: little is known about the effects of diet in narcoleptics; however, avoiding simple sugars will improve alertness in some patients. 2) Medical and psychiatric aspects of care. 3) Social factors as an interface between the patients and their environment.

Adolescent↗