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991.
Screening for hereditary hemochromatosis, although largely discussed, is not yet implemented in clinical practice. We evaluated the cost-effectiveness of 165 hemochromatosis population-screening algorithms involving two or three of several screening tests by developing a computer program that simulates all possible screening scenarios. Input data comprised government estimates of health services data and costs and a virtual population with user-defined demographic characteristics (including variable HFE mutation frequencies and penetrance values). We show that when C282Y homozygote prevalence is set at 3:1000, population screening appears cost-effective when penetrance of the biochemical phenotype is >0.70. When only hepatocellular carcinoma and cirrhosis are considered as the cost-driving complications, population-based screening is not significantly more cost-efficient than no screening, but life expectancy of individuals identified with hereditary hemochromatosis and treated is still improved by 7 years. Among the 165 screening algorithms tested in 91 different virtual populations of one million individuals, biochemical tests usually perform better as the initial test than genetic testing. Indeed, the genetic testing is most cost-effective as the final confirmatory test. Finally, for most combinations of prevalence and penetrance of HFE, one screening algorithm--unbound iron-binding capacity + transferrin saturation--appeared robust enough to be always within the top 5 most cost-effective strategies. 相似文献
992.
The effect of molecules in mother-of-pearl on the decrease in bone resorption through the inhibition of osteoclast cathepsin K 总被引:2,自引:0,他引:2
Duplat D Gallet M Berland S Marie A Dubost L Rousseau M Kamel S Milet C Brazier M Lopez E Bédouet L 《Biomaterials》2007,28(32):4769-4778
This study evaluates the effect of the mother-of-pearl (nacre) organic matrix on mammalian osteoclast activity and on cathepsin K protease. Rabbit osteoclasts were cultured on bovine cortical bone slices in the presence of water-soluble molecules extracted from nacre of the pearl oyster Pinctada margaritifera. Osteoclast resorption activity was determined by quantification of the resorption surface area on bovine bone slices. Papain and cathepsin K, B and L inhibition tests were performed in the presence of the nacre water-soluble extracts. The active crude extract was fractionated by dialysis and reversed-phase high-performance liquid chromatography before electrospray mass spectrometry analysis of inhibitory fractions. The water-soluble molecules extracted from nacre decreased bone resorption without jeopardizing osteoclast survival. The hydrolytic activity of cysteine proteinases was reduced when the enzymes were incubated with the nacre water-soluble molecules. Trending towards characterization of the molecules involved, it appears that cathepsin K inhibitors remain in different nacre water-soluble organic matrix subfractions, composed of low molecular weight molecules. Mollusk shell nacre contains molecules capable of reducing osteoclast bone resorption activity by inhibiting cathepsin K, giving a new facet of the bioactivity of nacre as bone biomaterial. 相似文献
993.
Bak Z Sjöberg F Rousseau A Steinvall I Janerot-Sjoberg B 《Acta physiologica (Oxford, England)》2007,191(1):15-24
Aim: The aim of the study was to examine the central and peripheral cardiovascular adaptation and its coupling during increasing levels of hyperoxaemia. We hypothesized a dose‐related effect of hyperoxaemia on left ventricular performance and the vascular properties of the arterial tree. Methods: Oscillometrically calibrated arterial subclavian pulse trace data were combined with echocardiographic recordings to obtain non‐invasive estimates of left ventricular volumes, aortic root pressure and flow data. For complementary vascular parameters and control purposes whole‐body impedance cardiography was applied. In nine (seven males) supine, resting healthy volunteers, aged 23–48 years, data was collected after 15 min of air breathing and at increasing transcutaneous oxygen tensions (20, 40 and 60 kPa), accomplished by a two group, random order and blinded hyperoxemic protocol. Results: Left ventricular stroke volume [86 ± 13 to 75 ± 9 mL (mean ± SD)] and end‐diastolic area (19.3 ± 4.4 to 16.8 ± 4.3 cm2) declined (P < 0.05), and showed a linear, negative dose–response relationship to increasing arterial oxygen levels in a regression model. Peripheral resistance and characteristic impedance increased in a similar manner. Heart rate, left ventricular fractional area change, end‐systolic area, mean arterial pressure, arterial compliance or carbon dioxide levels did not change. Conclusion: There is a linear dose–response relationship between arterial oxygen and cardiovascular parameters when the systemic oxygen tension increases above normal. A direct effect of supplemental oxygen on the vessels may therefore not be excluded. Proximal aortic and peripheral resistance increases from hyperoxaemia, but a decrease of venous return implies extra cardiac blood‐pooling and compensatory relaxation of the capacitance vessels. 相似文献
994.
Thauvin-Robinet C Laurent N Rousseau T Couvreur S Cusin V Callier P Mugneret F Durand C Huet F Sagot P Faivre L 《European journal of medical genetics》2007,50(1):85-91
Casamassima-Morton-Nance syndrome belongs to the heterogeneous group of spondylocostal dysostoses (SCD) represented by a large heterogeneous group in which diverse diagnoses, associations and modes of inheritance are found. Common features include segmentation abnormalities of the vertebrae and ribs. Here, we report on a fetal case with spondylocostal dysostosis, anal and genitourinary malformations and discuss Casamassima-Morton-Nance syndrome. 相似文献
995.
Duchenne muscular dystrophy (DMD) is the most severe muscular dystrophy. It is caused by the absence of dystrophin in muscle fibers. The autologous transplantation of genetically corrected muscle precursor cells (MPCs) is a possible cure for DMD. A non-viral method of genetic modification was tested in this study. The co-transfection (nucleofection) of a phiC31 integrase and a transgene expressing plasmid in MPCs led to an increased stable expression in vitro. The stable expression of a small transgene (eGFP) in muscle fibers was initially demonstrated following the transplantation of the genetically modified cells. The stable expression of a truncated version of dystrophin as well as the full-length dystrophin fused with eGFP was then demonstrated in MPCs obtained from an mdx mice. The transplantation of these cells led not only to the expression of these fusion proteins in muscle fibers but also to the reconstitution of the dystrophin complex. Human MPCs were also genetically modified with a plasmid coding for the full-length human dystrophin gene fused with eGFP and transplanted in severe combined immuno deficient mice leading to the expression of eGFP dystrophin in muscle fibers. This work indicates that cell transplantation after correction of MPCs with phiC31 integrase is a possible approach to treat DMD. 相似文献
996.
Russell HV Strother D Mei Z Rill D Popek E Biagi E Yvon E Brenner M Rousseau R 《Journal of immunotherapy (Hagerstown, Md. : 1997)》2007,30(2):227-233
In murine models, transgenic chemokine-cytokine tumor vaccines overcome many of the limitations of single-agent immunotherapy by producing the sequence of T-cell attraction followed by proliferation of tumor antigen-activated clones. The safety and immunologic effects of this approach in humans were tested in 7 patients with relapsed or refractory neuroblastoma. They each received up to 8 subcutaneous injections of a vaccine combining lymphotactin--and interleukin-2 (IL-2)--secreting autologous neuroblastoma cells in a dose-escalating scheme. Adverse events were limited to grade 1 or 2 localized reactions in all patients, pain in 3 patients, and fever in 3 patients. Injection site biopsies revealed increased cellularity caused by infiltration of CD4 and CD8 lymphocytes, eosinophils, and dendritic cells with a decrease in dendritic cells from the first to the second vaccination. Systemically, vaccine was associated with increased tumor recognition as measured by enzyme-linked immunosorbent spot assays. Two patients had interferon-gamma predominant responses and 3 had IL-5 predominant responses. Only 1 patient received all 8 injections, 1 patient stopped the study early, and all other patients progressed before completion of the study. Hence, autologous tumor cell vaccines combining transgenic lymphotactin with IL-2 seem to have little toxicity in humans and can induce an antitumor immune response. In this setting, the immune response was insufficient to overcome active recurrent neuroblastoma. 相似文献
997.
Rubin MR Silverberg SJ D'Amour P Brossard JH Rousseau L Sliney J Cantor T Bilezikian JP 《Clinical chemistry》2007,53(8):1470-1476
BACKGROUND: A new parathyroid hormone (PTH) species, the N-terminal PTH form (N-PTH), is distinct from intact human PTH of 84 amino acid residues [hPTH(1-84)] and is recognized in a 3rd-generation assay of "whole" PTH (wPTH; the 1-2 epitope) but not in a 2nd-generation assay of "total" PTH (tPTH; the 12-18 epitope). N-PTH usually represents <15% of wPTH but can be overproduced in severe primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism. We investigated whether N-PTH is also overproduced in parathyroid cancer and whether N-PTH concentration is influenced by calcimimetic therapy. METHODS: We studied 8 patients with parathyroid carcinoma before and at week 16 of cinacalcet therapy, 6 patients with PHPT, and 6 control individuals. We fractionated sera with HPLC and analyzed fractions with the 2 assays to quantify hPTH(1-84), N-PTH, and non-(1-84) PTH fragments. RESULTS: Half of parathyroid carcinoma patients had an increased wPTH:tPTH ratio [mean (SD), 1.35 (0.29)]; the others had a typical ratio [0.72 (0.12)]. HPLC fractionation of sera from 2 high-ratio patients confirmed N-PTH overproduction [65% (12%) of wPTH]. The N-PTH fraction was <15% of wPTH in PHPT and healthy individuals. Calcimimetic therapy appreciably reduced calcium concentrations in parathyroid carcinoma patients but had little influence on PTH concentration, the wPTH:tPTH ratio, or the PTH HPLC profile. CONCLUSION: N-PTH is overproduced in some parathyroid cancer patients, but calcimimetic therapy does not influence its production. The clinical implications of this finding in parathyroid carcinoma await additional studies with an emphasis on N-PTH's biological activity and with larger numbers of patients. 相似文献
998.
Supplementation and inhibition of nitric oxide synthesis influences bacterial transit time during bacterial translocation in rats 总被引:2,自引:0,他引:2
Samel S Keese M Lanig S Kleczka M Gretz N Hafner M Sturm J Post S 《Shock (Augusta, Ga.)》2003,19(4):378-382
In the obstructed gut, nitric oxide (NO) may influence intestinal barrier function and translocation of bacteria. By using a novel experimental approach, we investigated the effect of supplementation and inhibition of NO synthesis on the time interval necessary for translocation of green fluorescent protein-transfected Escherichia coli (GFP-uv E. coli) in a rat model of small bowel obstruction. In anesthetized Wistar rats, 4 x 10(8) GFP-uv E. coli were administered into a reservoir of terminal ileum formed by ligature. Animals were randomized to receive either i.v. arginine (10 mg/kg), aminoguanidine (300 mg/kg), L-NAME (25 mg/kg), or saline (control). Translocation of GFP-uv E. coli was assessed using intravital video microscopy. Minimal transit time of translocation was measured as time from injection of GFP-uv E. coli into the gut lumen until bacteria were observed in the lamina submucosa and as time from injection of bacteria into the gut lumen until bacteria were observed in the lamina muscularis propria. Minimal transit times were expressed as mean +/- SD. Bacterial translocation into the submucosa and muscularis propria took 36 +/- 7 min and 81 +/- 9 min, respectively in control animals receiving saline. Aminoguanidine and L-NAME caused a marked delay of minimal transit time into the submucosa (63 +/- 5 min and 61 +/- 7 min, respectively; P < 0.05). Arginine significantly accelerated bacterial translocation into the muscularis propria (61 +/- 9 min, P < 0.05). GFP-uv E. coli were detected on frozen sections of small bowel, mesentery, liver, and spleen 2 h after GFP-uv E. coli administration in all animals. A marked upregulation of inducible NO synthase (NOS) in the obstructed bowel segment was demonstrated on immunohistochemistry. The assessment of a newly defined parameter, minimal bacterial transit time, may serve as an additional functional aspect of intestinal barrier function for pathophysiological and pharmacological studies. Aminoguanidine, L-NAME, and arginine were effective in influencing minimal transit time of E. coli during small bowel obstruction. 相似文献
999.
Santiago?Salazar Botero Yuka?Igeta Sybille?Facca Chiara?Pizza Juan?José?Hidalgo Diaz Philippe?A.?LiverneauxEmail author 《European journal of orthopaedic surgery & traumatology : orthopedie traumatologie》2018,28(8):1525-1530
This study describes a new total wrist implant (Prosthelast®) designed to reduce the risk of distal migration of the carpal component. The Prosthelast® implant consists in a one-block radial implant replacing the metaphysis and the articular surface fixed to a radial elastic centromedullar wire and a carpal component in titanium with an articular condylar surface in polyethylene. We operated on five patients (three male patients and two female patients) and followed them up for 12 months on average. Two of the patients presented with rheumatoid arthritis of the wrist, and an ulnar osteotomy (Darrach procedure) was carried out at the same time of the arthroplasty. All clinical variables improved postoperatively (Quick DASH score, pain score, range of motion) except from wrist flexion which was reduced. No patients underwent revision surgery. Two patients presented with a periprosthetic radiolucent loosening around the radial component, but no implant migration was observed. Overall, the preliminary results of our case series show that the new Prosthelast® implant presents comparable short-term results to those described in the literature. We will follow up the patients to verify that long-term results are as satisfactory as the short-term results. 相似文献
1000.
Rouffet Alban Florczak Anne Sophie Vimont Thibault Deranque Clément Boucher Sophie Rousseau Pascal 《Journal of plastic, reconstructive & aesthetic surgery》2018,71(9):1352-1361