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Biomedical subjects

C Roux

Publications and source records attributed to C Roux.

At least 145 records · Page 8Linked to original sources

Design for an ipriflavone multicenter European fracture study.

In order to investigate the efficacy of ipriflavone (i.p.) on the prevention of vertebral fractures and the effect on bone mineral density (BMD) in women with postmenopausal osteoporosis, a large multicentric European study was designed and is presently ongoing. Included in the study were 460 Caucasian, nonobese postmenopausal women aged > 45 and < 75 years, menopaused for at least 12 months. Inclusion was on the basis of a lumbar bone mineral density (BMD) lower than 2 SD compared with healthy women aged 50 years, corresponding to values below 0.860 g/cm2 (antero-posterior measurement) by Hologic QDR 1000. Women with prevalent vertebral fractures were excluded as well as those presenting secondary osteoporosis or having been treated with medications that could affect bone metabolism. This study was designed as a 3-year, double-blind, placebo-controlled, parallel group study that randomized the women to the oral administration of either 3 x 200 mg/day of i.p. or placebo. All patients received a daily supplement of 500 mg calcium. The primary purpose of the study was to evaluate the efficacy of i.p. in preventing vertebral nontraumatic fractures. Fracture is defined here as a > or = 20% decrease in any anterior, central, or posterior T4-L4 vertebral height. Blinded vertebral X-ray readings and vertebral morphometry have been centralized in an independent Center, with standardized evaluation of two experts. Power calculations have been based on the hypothesis that 21% of placebo-treated patients would fracture within 3 years and that treatment with i.p. would lead to a 50% reduction in the incidence of fracture. Statistical tests have been designed to have a power of 80%, with a type I error equal to 5%. Secondary endpoints were changes in vertebral, radial, and femoral BMD. Centralized controls on 100% BMD scans would ensure the good quality of BMD readings. This study should verify the hypothesis that i.p. significantly decreases the risk of vertebral fracture in postmenopausal, osteoporotic women.

Absorptiometry, Photon↗

Estimation of aneuploidy levels for 8, 15, 18, X and Y chromosomes in 97 human sperm samples using fluorescence in situ hybridization.

OBJECTIVE: To estimate the mean frequency of aneuploidy levels of chromosomes 8, 15, 18, X, and Y in human sperm, while minimizing the effect of individual factors by analyzing sperm samples from a large set of patients. DESIGN: Prospective randomized analysis of sperm nuclei by fluorescence in situ hybridization. SETTING: University-based laboratory for reproductive biology. PATIENT(S): One hundred two patients with a large distribution of sperm parameters, randomly selected from volunteers who had presented seeking a semen analysis. INTERVENTION(S): The sperm samples were prepared for fluorescence in situ hybridization. MAIN OUTCOME MEASURE(S): The disomy frequencies for chromosomes 8, 15, 18, and sex chromosomes were determined using fluorescence in situ hybridization. RESULT(S): The mean frequencies of disomy for autosomes were 0.18% for chromosome 8, 0.06% for chromosome 15, 0.2% for chromosome 18, and 0.24% for gonosomes (XX, 0.04%; YY, 0.05%; XY, 0.15%). CONCLUSION(S): This study confirms other previous evaluations on restricted numbers of patients. Our results seem to confirm a relative equiprobability of disomy frequencies concerning the different chromosomal pairs during male meiosis.

Adult↗

DNA hypomethylation in breast cancer: an independent parameter of tumor progression?

The global DNA methylation status was investigated on a series of 59 breast cancers by Southern blotting, using methylation sensitive restriction enzymes. By comparison to control DNA, almost all tumor DNAs were found globally hypomethylated. However, the demethylation was variable from tumor to tumor. Compared to other biological parameters, the methylation did not correlate with chromosome alterations, steroid hormone receptor status, or histopathological grading. Tumors which appeared to be the most evolved for other parameters were only mildly hypomethylated, whereas tumors with strongly hypomethylated DNA corresponded to those with slight alterations of the other parameters. Thus, DNA hypomethylation is a consistent characteristic of breast cancer, but its variations may not correlate with tumor progression of most breast cancers.

Age Factors↗

Characterization of two cDNAs encoding auxin-binding proteins in Nicotiana tabacum.

The isolation and the characterization of two tobacco cDNAs, Nt-ERabp1 and Nt-ERabp2, homologous to Zm-ERabp1, encoding the major auxin-binding protein from maize coleoptiles, are described. Their predicted amino acid sequences correspond to proteins of ca. 21 kDa, in which the characteristic regions common to ABP1-related polypeptides are well-conserved. Southern analysis indicates that the genes corresponding to Nt-ERabp1 cDNA and Nt-ERabp2 cDNA derive respectively from Nicotiana tomentosiformis and Nicotiana sylvestris, the diploid progenitors of Nicotiana tabacum. Analysis of mRNA distribution in tobacco plants indicates that these two genes are preferentially expressed in flowers and growing seedlings. Whatever the tissue tested, Nt-ERabp1 mRNA is more abundant than Nt-ERabp2 mRNA. Furthermore, RT-PCR reveals developmental and organ-specific expression of these two genes in flower parts of tobacco plants. In particular, regulation of Nt-ERabp1 mRNA accumulation appears to be correlated with elongation growth of each floral organ. Recombinant Nt-ERabp1, produced in Escherichia coli, is recognized by antibodies raised against Zm-ERabp1.

Amino Acid Sequence↗

Biomedical information technology: medicine and health care in the digital future.

Advancements in medicine and health care are being significantly influenced by the exploding information technology developments. The IEEE Transactions on Information Technology in Biomedicine will address the applications and the infrastructure innovations that would harness biomedical and health care programs in the 21st century.

Biomedical Engineering↗

Normal and inhibited cholesterol synthesis in the cultured rat embryo.

The Smith-Lemli-Opitz syndrome-affected fetus presents a deficiency in delta7-dehydrocholesterol reductase, the last enzymatic step in the cholesterol biosynthesis pathway. Development of the abnormal human fetus takes place in a normal environment as the heterozygous mother's cholesterolemia remains normal. An animal model for this disease has been obtained from the offspring of pregnant rats treated with "distal" inhibitors of delta7-dehydrocholesterol reductase, AY-9944 or BM15766. In the animal model, embryonic development occurs in a disturbed environment characterized by hypocholesterolemia and accumulation of delta7-dehydrocholesterol and delta8-dehydrocholesterol in the maternal serum. The purpose of the present study was to assess, in cultured rat embryos at early developmental stages, the relative contributions of exogenous and de novo synthesized cholesterol in the total embryonic cholesterol, according to the conditions of normal and altered de novo biosynthesis. Cultured rat embryos are able to synthesize cholesterol as shown by 13C-incorporation into cholesterol from 13C-labeled precursors added to the culture medium. De novo cholesterol biosynthesis is altered by addition to the culture medium of AY-9944 which inhibits the delta7-dehydrocholesterol reductase and the delta8-delta7-sterol isomerase as suggested by the emergence of characteristic aberrant sterols in the embryonic tissues. Cholesterol-rich serum used for embryo culture alters the pattern in a way that confirms that the rat embryos are able to import exogenous cholesterol which down-regulates de novo cholesterol biosynthesis. Exogenous cholesterol substitutes for the deficit in a manner efficient enough to prevent the embryonic abnormalities induced by AY-9944.

Adaptation, Physiological↗

Hip axis length measurement using dual-energy X-ray absorptiometry.

Hip axis length (HAL) has been reported, in the United States, to influence the risk of hip fractures independently from age and proximal femoral bone mineral density. Last-generation dual-energy X-ray absorptiometry units can perform automatic hip axis length measurements. The present study was designed to evaluate the feasibility of this measurement in clinical practice and to establish the range of normal values obtained in French women using single- and fan-beam absorptiometry. Short-term reproducibility determined by performing two measurements with repositioning in 50 women was 1.67%. Long-term reproducibility calculated based on five measurements taken at six-month intervals in 60 women was 1.5%. No statistically significant differences were found between hip axis length on the right and left sides in 50 women. Mean values calculated based on measurements in 190 women aged 54 +/- 12 years (single-beam absorptiometry) and in 50 women aged 80 +/- 5 years (fan-beam absorptiometry) were 10.4 +/- 0.6 cm and 11.5 +/- 0.7 cm, respectively. Hip axis length was correlated with height but not with age or femoral neck bone mineral density. Our data are consistent with studies conducted in the United States. The interpretation of hip axis length measurements requires knowledge of the type of X-ray beam used (single or fan-shaped). Whether hip axis length predicts the hip fracture risk in Europeans remains to be demonstrated.

Absorptiometry, Photon↗

[Cholesterol and development].

The teratogenic action of distal inhibitors of cholesterol synthesis has been known for some time. The induced malformations are of a particular type: they include holoprosencephalies. Recently these observations have solicited increased interest due to: 1/ the discovery in 1993 of a similar form of inhibition of cholesterol synthesis which is responsible for a human malformation syndrome, Smith-Lemli-Opitz; 2/ the demonstration of the involvement of the Sonic Hedgehog gene in normal development of prosencephalon and the description of the mode of action of the protein Shh: autoprocessing followed by "cholesterolisation".

Animals↗

[Embryotoxic factors and recurrent spontaneous abortions].

About 30% of recurrent spontaneous abortions remain unexplained by traditional or biological anomalies. The purpose of this work was to investigate embryotoxic factors produced by trophoblast stimulated lymphocytes from women with unexplained recurrent spontaneous abortion. The samples from 36 women with recurrent abortion before and during the next pregnancy and from 7 women with normal pregnancies and no history of spontaneous abortion have been tested. The lymphocytes were stimulated with trophoblastic extracts. The supernatants of the stimulated lymphocytes were tested in a 4-cell mouse embryo culture. The secretion of embryotoxic factor was determined if the number of life blastocysts was less than 50% of control values after 4 days. The lymphocytes from 59% women with 3 or more recurrent abortion produced the embryotoxic factor, this factor may be useful in predicting pregnancy outcome in women with a history of unexplained recurrent miscarriage. The embryotoxic factor might be a new cause of recurrent abortion and a predictive factor.

Abortion, Habitual↗

Bone assessment in patients with ileal pouch-anal anastomosis for inflammatory bowel disease.

BACKGROUND: Patients with ulcerative colitis are at risk of low bone mineral density (BMD). Proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis diminishes the risk of bone disease. The aims of this study were to assess the mechanism of low BMD and to measure bone density changes after IPAA. METHODS: Twenty patients with IPAA for ulcerative colitis, of mean(s.d.) age 38(9) (range 21-58) years, had measurements of lumbar spine and femoral neck BMD by dual energy X-ray absorptiometry, a mean(s.d.) 28(23) (range 3-84) months after proctocolectomy. Serum levels of calcium, phosphate, parathyroid hormone, osteocalcin and 25-hydroxy vitamin D were determined. Fifteen patients were followed for 28(12) (range 8-50) months. RESULTS: At baseline, six patients had spine BMD more than two standard deviations below the normal value, and three had vertebral crush fractures. Mean vitamin D values were normal and no patient had osteomalacia. BMD increased with time elapsed since IPAA (spine: r = 0.71, P = 0.005). During follow-up, mean(s.d.) changes in bone density were +2.3(3.8) and +2.1(5.6) per cent per year at the spine and femoral neck respectively. CONCLUSION: These results suggest that in patients with IPAA for ulcerative colitis, low BMD is not associated with vitamin D malabsorption and may be reversible after surgery.

Adult↗

Estrogen therapy in postmenopausal osteoporosis. What we know and what we don't.

Replacement estrogen therapy is of proven efficacy for the prevention and treatment of postmenopausal bone loss. Oral and transdermal 17 beta estradiol have provided similar benefits in clinical studies. The lowest effective doses are 0.625 mg per day for conjugated estrogens, 2 mg per day for oral 17 beta estradiol, 1.5 micrograms per day for 17 beta estradiol gel, and 50-microgram 17 beta estradiol patch per day. Bone mineral density should be monitored if lower doses are used. Several epidemiologic studies found that a decrease in the incidence of osteoporotic fractures was achieved only when the duration of estrogen replacement therapy exceeded seven years. It follows that replacement therapy should be started at cessation of menses, if possible. However delayed replacement therapy (i.e., at 65 years of age) is unquestionably effective.

Aged↗

Inhibition of 7-dehydrocholesterol reductase by the teratogen AY9944: a rat model for Smith-Lemli-Opitz syndrome.

Our aim is to verify the validity of a rat model proposed for Smith-Lemli-Opitz (SLO) syndrome, a developmental disorder characterized by a defect in 7-dehydrocholesterol-delta 7 (7DHC)-reductase and by facial dysmorphism close to the holoprosencephaly caused by the teratogen AY9944. We investigated the sterol profile in rats treated with AY9944 blocking 7DHC-reductase. AY9944 was given orally to rats on gestation day 3 (D3). The sera were sampled for kinetic data on D3, D6, D9, D12, and D21. Cholesterol was measured in parallel by the routine enzymatic method and by the gas chromatography/mass spectrometry (GC-MS) procedure used in SLO diagnosis. In addition to sterols, we dosed steroid hormones punctually on D4 and on D10, and examined D21 fetuses in other animals. The enzymatic method was not specific for cholesterol, and measured 70% pure 7DHC added to a normal serum. On D21, 77% live fetuses showed pituitary agenesis. Cholesterol was rapidly reduced by more than 50% on D6 involving an accumulation of 7DHC, 8DHC, and trienols, as identified in SLO-affected children. The most abundant 7DHC reached a maximum from D9 to D12, equaling cholesterol on D9 (11 mg/dl). On D10, the magnitudes of hypocholesterolemic and of 7DHC accumulation were found to be dose-dependent. Progesterone was reduced as early as 24 hr after treatment and dropped to 40% of the levels in the controls on D10, correlating to the decrease in cholesterolemia. This rat model reproduces the same biochemical perturbations as seen in SLO, strongly suggesting that aberrant sterols (7DHC, 8DHC, or nortrienol) may contribute to the developmental defects.

Animals↗

Broadband ultrasound attenuation imaging: a new imaging method in osteoporosis.

The purpose of this study was to evaluate the usefulness in osteoporosis of a new ultrasound imaging device able to create a parametric image of broadband ultrasound attenuation (BUA) at the os calcis. Three regions of interest were located in the great tuberosity of the os calcis. Precision was evaluated in 37 patients. Calcaneal bone mineral density (BMD) and BUA were compared in 33 patients. In 236 patients (including 77 with osteoporotic fractures), BUA and lumbar and femoral BMD measurements were performed. The measurements were compared using correlation coefficients. Their clinical value was estimated by comparisons of the results between patients with fractures and age-matched controls, using comparisons of the means, areas under the ROC curves, and logistic regression. Precision was in a 1.4-3.3% range. Local BUA and BMD were highly correlated (r = 0.88). Significant correlations were found between BUA and lumbar (r = 0.56) and femur (r = 0.66) BMD. In multiple regression, years since menopause and weight were significant predictors of BUA. Patients with fractures had lower BUA and BMD than age-matched controls. BUA showed the largest difference between the two populations (13-16%). Areas under the ROC curves were similar for BUA and BMD. Logistic regression after adjustment for confounding factors showed that BUA discriminated between fracture and nonfracture subjects. Broadband ultrasound attenuation imaging improves the reproducibility of ultrasound measurements. It may be useful in osteoporosis, due to its good discriminating value.

Adult↗

Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz and the lethal acrodysgenital syndromes.

UNLABELLED: The Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder characterized by dysmorphic facial features with abnormal limbs and genitalia. Two forms have been recognized based on clinical course and severity: the classical SLO (type I) and the lethal acrodysgenital syndrome (type II). Type I SLO has been recently ascribed to a defect in cholesterol synthesis. Taking advantage of a series of seven patients including five type I and two type II SLO, we describe micrognathia, severe microcephaly, major ante and post natal growth retardation and feeding difficulties as consistent features in the disease. In addition, we give support to the presence of abnormal cholesterol levels in the lethal acrodysgenital syndrome but find no correlation between plasma sterol levels and the clinical severity of the disease. CONCLUSION: The identification of the same biochemical defect in both types of Smith-Lemli-Opitz Syndrome suggests that despite major discrepancies in clinical course and severity, type I and type II SLo are probably allelic disorders.

Child↗

Bone effects of dydrogesterone in ovariectomized rats: a biologic, histomorphometric, and densitometric study.

It has been suggested that progesterone might affect bone metabolism. Dydrogesterone (DD) has a chemical structure very close to that of natural progesterone, without androgenic effects. We compared the effect of a daily treatment with DD and estradiol (E2, 40 micrograms/kg) on 70 female rats (8 weeks old), divided in seven groups: controls; ovariectomized (OVX); OVX + E2, OVX + DD 2.5 mg/kg; OVX + DD 5 mg/kg; OVX + E2 + DD 2.5 mg/kg; and OVX + E2 + DD 5 mg/kg. Two months later we studied estradiol, osteocalcin, and acid phosphatases (TRAP) levels; histomorphometric parameters at the trabecular part of the femur; and bone mineral density of the tibiae (trabecular and cortical areas) and caudal vertebrae (cortical bone) by dual energy X-ray absorptiometry (Hologic QDR 2000). In the OVX group, we found a nonsignificant increase of osteocalcin and TRAP, a decrease in the trabecular bone volume, and an increase in the intertrabecular distance. These variations were not seen in the groups treated with E2 (with or without DD). DD had no effect on trabecular architecture parameters. It induced a dose-dependent increase in the osteoclast number (TRAP + cells), without increase in trabecular separation. There was no difference in bone density of caudal vertebrae between the different groups, nor of the tibial density between the OVX and OVX + DD groups. The bone densities were not different in the control and E2-treated groups, with or without DD. During dydrogesterone treatment, there is an increase in osteoclast number, without an apparent increase in osteoclast function. Dydrogesterone did not prevent bone loss due to ovariectomy in rats, and it did not affect the protective effect of estradiol.

Analysis of Variance↗

Analysis of the sex chromosomal equipment in spermatozoa of a 47,XYY male using two-colour fluorescence in-situ hybridization.

The sex chromosomes in spermatozoa of a 47,XYY fertile male were analysed simultaneously by dual fluorescence in-situ hybridization (FISH), with two probes (pHY2.1 and pXBR). Of the 100000 cells analysed, 95179 spermatozoa (95.18%) exhibited one or more hybridization signals. Of the hybridized nuclei, 85.37% showed a normal sex chromosome constitution (37.37% X-bearing cells and 48.00% Y-bearing cells), with an X:Y ratio of 0.78:1. A total of 14.63% of the hybridized nuclei exhibited sex chromosome aneuploidy with a majority of XY- and YY-bearing spermatozoa (9.37 and 4.65% respectively). Even if the majority of spermatozoa have chromosomal haploidy, a large proportion of them exhibits numerical errors for the sex chromosomes. These observations raise questions about the commonly-admitted notions concerning the absence of chromosomal risk for XYY male offspring.

Humans↗