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Biomedical subjects

Stéphane Moutereau

Publications and source records attributed to Stéphane Moutereau.

11 recordsLinked to original sources

A single procalcitonin level does not predict adverse outcomes of women with pyelonephritis.

OBJECTIVES: Predicting medical outcomes for pyelonephritis in women is difficult, leading to unnecessary hospitalization. Unlike other serious infectious diseases, high procalcitonin (PCT) level has never been associated with 28-d adverse medical outcomes in women with pyelonephritis. Therefore, we sought to determine the accuracy of PCT in discriminating between pyelonephritis with adverse medical outcome (PAMO) and pyelonephritis without adverse medical outcome (PWAMO). PATIENTS AND METHODS: Adult women with pyelonephritis presenting to the emergency department of a French tertiary care hospital were consecutively included. Those patients who developed adverse medical outcomes during a 28-d follow-up period were identified as having PAMO. Baseline characteristics and PCT level were compared between patients with PAMO and PWAMO. RESULTS: Eleven women (19.0%) had PAMO and 47 (81%) had PWAMO. The median PCT level was higher in PAMO compared with PWAMO 0.51 ng/ml (IQR: 0.04-3.8) and 0.08 ng/ml (IQR: 0.01-1.0), but this difference was not statistically significant (p=0.07). We failed to find a threshold value for PCT that discriminated between PAMO and PWAMO (ROC, AUC=0.67 [95%CI, 0.51-0.86]). All but one subject with PAMO had either a PCT level >0.1 ng/ml or an underlying genitourinary abnormality by radiographic testing. CONCLUSIONS: A single PCT level was a poor predictor of 28-d adverse medical outcomes in women with pyelonephritis treated in the emergency department. Prediction based on underlying genitourinary abnormality by radiographic testing in addition to the PCT level should be investigated in future studies.

Acute Disease↗

Living high-training low: effect on erythropoiesis and maximal aerobic performance in elite Nordic skiers.

The "living high-training low" model (Hi-Lo) may improve aerobic performance in athletes, and the main mechanism of this improvement is thought to be augmented erythropoiesis. A positive effect of Hi-Lo has been demonstrated previously by using altitudes of 2,000-3,000 m. Since the rate of erythropoiesis is altitude-dependent, we tested whether a higher altitude (3,500 m) during Hi-Lo increases erythropoiesis and maximal aerobic performance. Nordic skiers trained for 18 days at 1,200 m, while sleeping at 1,200 m in ambient air (control group, n = 5) or in hypoxic rooms (Hi-Lo, n = 6; 3 x 6 days at simulated altitudes of 2,500, 3,000 and finally 3,500 m, 11 h day(-1)). Measurements were done before, during (blood samples only) and 2 weeks after the intervention (POST). Maximal aerobic performance was examined from VO(2max) and time to exhaustion (T(exh)) at vVO(2max) (minimum speed associated with VO(2max)), respectively. Erythropoietin and soluble transferrin receptor responses were higher during Hi-Lo, whereas reticulocytes did not change. In POST (vs. before): hematological parameters were similar to basal levels, as well as red blood cell volume, being 2.68 +/- 0.83 l (vs. 2.64+/-0.54 l) in Hi-Lo and 2.62+/-0.57 l (vs. 2.87 +/- 0.59 l) in controls. At that time, neither VO(2max) nor T(exh) were improved by Hi-Lo, VO(2max) being non-significantly decreased by 2.0% (controls) and 3.7% (Hi-Lo). The present results suggest that increasing the altitude up to 3,500 m during Hi-Lo stimulates erythropoiesis but does not confer any advantage for maximal O2 transport.

Adult↗

Sonic Hedgehog-dependent proliferation in a series of patients with colorectal cancer.

BACKGROUND: The Hedgehog (Hh) gene family is known to regulate development of stem cells. In addition, activation is responsible for the induction of GLI1 proto-oncogene and subsequent cellular proliferation. Sonic Hedgehog (SHh), one of the Hh family members promotes carcinogenesis in airway and pancreatic epithelia, is expressed in colonic stem cells. As differentiated colonic cells arise from constant renewal of Hedgehog-expressing colonic stem cells, SHh could be involved in human colonic carcinogenesis. METHODS: Tissue samples of colorectal adenocarcinoma (T) and adjacent normal colon tissue (NT) were sampled from each of 44 consecutive patients with colorectal cancer. Specific transcription of SHh, GLI1, and the GLI1 downstream target FOXM1 were evaluated using semiquantitative reverse transcriptase polymerase chain reaction. Similar in vitro measurements of mRNA of GLI1 and FOXM1 transcription levels after specific induction by SHh-Np were performed in the HT-29 colorectal tumor cell line to confirm the in vivo results. RESULTS: SHh mRNA was overexpressed in colorectal adenocarcinomas in 38 of 44 (86%) patients. Expression of transcription levels of GLI1 and FOXM1 correlated with SHh expression (SHh vs GLI1, r = 0.77, P < .0001; GLI1 vs FOXM1, r = 0.68, P < .0001; SHh vs FOXM1, r = 0.79, P < .0001). SHh overexpression did not appear to correlate with the patient characteristics evaluated. Similarly, when studied in the HT-29 colorectal cell line, exogenous SHh promoted cell proliferation, while inhibition of SHh expression decreased proliferation. Expression of GLI1 and FOXM1 mRNA increased with exogenous exposure to SHh. CONCLUSIONS: We demonstrated increased expression of SHh mRNA in human colonic adenocarcinomas and in a colorectal cell line with downstream increased expression of GLI1 and FOXM1 mRNA known to promote cell proliferation. This upregulation within human colorectal adenocarcinoma tissue confirms the potential role of the Hh pathway in colorectal carcinogenesis and suggests a potential therapeutic target of Hh blockade in colorectal cancer.

Adenocarcinoma↗

Urinary cystatin C as a specific marker of tubular dysfunction.

BACKGROUND: Cystatin C (CST3), a strong inhibitor of cysteine proteinases, is freely filtered by the kidney glomerulus and is reabsorbed by the tubules, where it is almost totally catabolized, with the remainder then eliminated in urine. In tubular diseases, it seems sensible to postulate that CST3 degradation would be reduced and consequently an increase in its urinary elimination would be observed. METHODS: We report here the development of an automatic quantitative assay to measure CST3 concentrations in urine using a Behring N-Latex Cystatin C kit on a BNII laser nephelometer. We tested its clinical relevance on several kidney disease patients. RESULTS: This assay is sensitive (limit of detection 0.008 mg/L) and precise (within- and between-day CVs < 4%). Reference values for freshly collected urine samples range from 0.03 to 0.18 mg/L. Mean urine CST3 concentrations obtained from 52 patients with kidney tubular disease (4.31 +/- 3.85 mg/L) were significantly higher than those for 60 controls (0.096 +/- 0.044 mg/L; p < 0.0001) and 47 glomerular disease patients (0.106 +/- 0.133 mg/L; p < 0.0001). CONCLUSION: Increased urinary CST3 concentrations allow the accurate detection of tubular dysfunction among pure and mixed nephropathies. Because of its ability to be processed on automated clinical chemistry analyzers, this assay could easily be used as an adjunct to the standard panel used to screen kidney pathologies, even in emergency situations.

Aged↗

Living high-training low: effect on erythropoiesis and aerobic performance in highly-trained swimmers.

The "living high-training low" model (LHTL), i.e., training in normoxia but sleeping/living in hypoxia, is designed to improve the athletes performance. However, LHTL efficacy still remains controversial and also little is known about the duration of its potential benefit. This study tested whether LHTL enhances aerobic performance in athletes, and if any positive effect may last for up to 2 weeks after LHTL intervention. Eighteen swimmers trained for 13 days at 1,200 m while sleeping/living at 1,200 m in ambient air (control, n=9) or in hypoxic rooms (LHTL, n=9, 5 days at simulated altitude of 2,500 m followed by 8 days at simulated altitude of 3,000 m, 16 h day(-1)). Measures were done before 1-2 days (POST-1) and 2 weeks after intervention (POST-15). Aerobic performance was assessed from two swimming trials, exploring .VO(2max) and endurance performance (2,000-m time trial), respectively. Reticulocyte, serum EPO and soluble transferrin receptor responses were not altered by LHTL, whereas reticulocytes decreased in controls. In POST-1 (vs. before): red blood cell volume increased in LHTL only (+8.5%, P=0.03), .VO(2max) tended to increase more in LHTL (+8.1%, P=0.09) than in controls (+2.5%, P=0.21) without any difference between groups (P=0.42) and 2,000-m performance was unchanged with LHTL. In POST-15, both performance and hematological parameters were similar to initial levels. Our results indicate that LHTL may stimulate red cell production, without any concurrent amelioration of aerobic performance. The absence of any prolonged benefit after LHTL suggests that this LHTL model cannot be recommended for long-term purposes.

Altitude↗

Eighteen days of "living high, training low" stimulate erythropoiesis and enhance aerobic performance in elite middle-distance runners.

The efficiency of "living high, training low" (LHTL) remains controversial, despite its wide utilization. This study aimed to verify whether maximal and/or submaximal aerobic performance were modified by LHTL and whether these effects persist for 15 days after returning to normoxia. Last, we tried to elucidate whether the mechanisms involved were only related to changes in oxygen-carrying capacity. Eleven elite middle-distance runners were tested before (Pre), at the end (Post1), and 15 days after the end (Post2) of an 18-day LHTL session. Hypoxic group (LHTL, n = 5) spent 14 h/day in hypoxia (6 nights at 2,500 m and 12 nights at 3,000 m), whereas the control group (CON, n = 6) slept in normoxia (1,200 m). Both LHTL and CON trained at 1,200 m. Maximal oxygen uptake and maximal aerobic power were improved at Post1 and Post2 for LHTL only (+7.1 and +3.4% for maximal oxygen uptake, +8.4 and +4.7% for maximal aerobic power, respectively). Similarly oxygen uptake and ventilation at ventilatory threshold increased in LHTL only (+18.1 and +12.2% at Post1, +15.9 and +15.4% at Post2, respectively). Heart rate during a 10-min run at 19.5 km/h decreased for LHTL at Post2 (-4.4%). Despite the stimulation of erythropoiesis in LHTL shown by the 27.4% increase in serum transferrin receptor and the 10.1% increase in total hemoglobin mass, red cell volume was not significantly increased at Post1 (+9.2%, not significant). Therefore, both maximal and submaximal aerobic performance in elite runners were increased by LHTL mainly linked to an improvement in oxygen transport in early return to normoxia and probably to other process at Post2.

Adaptation, Physiological↗

Acetazolamide: a treatment for chronic mountain sickness.

RATIONALE: Chronic mountain sickness or Monge's disease is characterized by an excessive polycythemia in high-altitude dwellers, with a prevalence of 5 to 18% above 3,200 m. To date, no pharmacologic treatment is available. OBJECTIVES: We evaluated the efficacy of acetazolamide in the treatment of chronic mountain sickness and the importance of nocturnal hypoxemia in its pathophysiology. METHODS: A double-blind placebo-controlled study was performed in three groups of patients from Cerro de Pasco, Peru (4,300 m), treated orally for 3 weeks with placebo (n = 10), 250 mg of acetazolamide (n = 10), or 500 mg of acetazolamide (n = 10), daily. RESULTS: Acetazolamide decreased hematocrit by 7.1% (p < 0.001) and 6.7% (p < 0.001), serum erythropoietin by 67% (p < 0.01) and 50% (p < 0.001), and serum soluble transferrin receptors by 11.1% (p < 0.05) and 3.4% (p < 0.001), and increased serum ferritin by 540% (p < 0.001) and 134% (p < 0.001), for groups treated with 250 and 500 mg of acetazolamide, respectively. Acetazolamide (250 mg) increased nocturnal arterial O(2) saturation by 5% (p < 0.01) and decreased mean nocturnal heart rate by 11% (p < 0.05) and the number of apnea-hypopnea episodes during sleep by 74% (p < 0.05). The decrease in erythropoietin was attributed mainly to the acetazolamide-induced increase in ventilation and arterial O(2) saturation. CONCLUSIONS: Acetazolamide, the first efficient pharmacologic treatment of chronic mountain sickness without adverse effects, reduces hypoventilation, which may be accentuated during sleep, and blunts erythropoiesis. Its low cost may allow wide development with a considerable positive impact on public health in high-altitude regions.

Acetazolamide↗

Immunobead multiplex RT-PCR detection of carcinoembryonic genes expressing cells in the blood of colorectal cancer patients.

Circulating cell detection using reverse transcriptase-polymerase chain reaction (RT-PCR) techniques has been studied as a new prognostic factor in colorectal cancer patients. With the view of enhancing detection sensitivity, we developed a new multiplex RT-PCR assay for circulating cell detection based on the expression of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5; formerly CEA) and CEACAM7 (formerly CGM2). Between November 2002 and December 2003, 45 stage III-IV, 39 stage I-II colorectal cancer patients, 32 non-colorectal cancer patients and 41 healthy individuals were included. Positive selection using HEA-125 immunobeads was applied to blood samples before mRNA extraction, cDNA synthesis and a multiplex CEACAM5/CEACAM7 RT-PCR assay. For both CEACAM5 and CEACAM7, the limit of detection was found to be as low as 1 expressing cell in 10(6) nucleated blood cells. The multiplex RT-PCR assay was negative for the 41 healthy individuals and the 32 non-colorectal cancer patients. The test was positive in 53/84 (63%) of the colorectal cancer patients for CEACAM5 and/or CEACAM7, whereas 32/84 (38%) were positive for both markers. Colorectal cancer patients were positive for one of the two markers in 80% of cases (36/45) for stage III-IV patients (CEACAM5 73%, CEACAM7 51%) and in 44% of cases (17/39) for stage I-II patients. This multiplex RT-PCR assay with two markers proved to be more sensitive than use of a single marker in detecting circulating tumour cells. The discrepant expression of CEACAM5 and CEACAM7 may label circulating tumour cells that have different levels of differentiation and subsequent aggressive behaviour.

Aged↗

An improved electronic microarray-based diagnostic assay for identification of MEFV mutations.

Recent technological advances, such as DNA chip devices that allow automated, high-throughput genotyping, promise to considerably improve the detection capability of single-nucleotide polymorphisms (SNPs) in clinically relevant genes. We used the NanoChip(R) Molecular Biology Workstation (Nanogen, www.nanogen.com) and recently introduced microelectronic array technology to develop a detection method for the more frequent mutations involved in familial Mediterranean fever (FMF), an autosomal recessive disease that affects several ethnic groups in the Mediterranean population, whose early diagnosis is crucial if severe complications are to be prevented. We adapted the previously described Nanogen procedures to FMF mutation analysis, introducing modifications that notably improve the technique. First, as the original procedure makes use of costly dye-tagged reporter sequences, we devised a universal reporter strategy, which was first evaluated and validated on the robust, previously established factor V Leiden and factor II (prothrombin) NanoChip diagnostic assays. FMF (MEFV), factor V (F5), and factor II (F2) genotypes identified using this improved system were totally concordant with results of other genotyping methods (denaturing gradient gel electrophoresis [DGGE], SSCP, and RFLP analysis). Second, we showed that the target sequences loaded on the NanoChip cartridges can be rehybridized several times in a highly reproducible manner, allowing sequential analysis of mutations. Thus, we devised a strategy that allows us to monitor the possible interference of additional mutations or SNPs at probe or stabilizer sequences. Finally, a comparative cost per sample analysis demonstrates that the accurate and reproducible FMF mutation detection assay we developed can be readily implemented in the clinical laboratory setting at reasonable expense.

Base Sequence↗