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Biomedical subjects

Jean Gaudart

Publications and source records attributed to Jean Gaudart.

14 recordsLinked to original sources
PubMed2006

Hemodynamics in experimental gastric juice induced aspiration pneumonitis.

OBJECTIVE: To characterize hemodynamic changes during experimental aspiration pneumonitis, paying special attention to echocardiographic assessment. DESIGN AND SETTING: Animal study in a university-based research laboratory. SUBJECTS: Fourteen mechanically ventilated New Zealand white rabbits INTERVENTIONS: We instilled 1 ml/kg human gastric juice (mean pH: 4.1+0.2) intratracheally. Hemodynamic and respiratory parameters were measured every hour for 4 h, associated with a transthoracic echocardiography. MEASUREMENTS AND RESULTS: Lung injury occurred within 1 hour with a marked decrease in PaO(2)/FIO(2) and an increase in plateau pressure; after this initial drop the ratio remained stable throughout the experiment. Seven rabbits experienced only a mild to moderate alteration in lung oxygenation function as defined by a PaO(2)/FIO(2) ratio above 200 (group A), while the other seven developed a severe alteration with a ratio below 200 (group B). At the end of the experiment pH and cardiac output were lower in group B than in group A. Using a PaO(2)/FIO(2) threshold value of 150, pH, mean arterial pressure, and cardiac output were lower in the animals with the more severe hypoxemia. Neither left nor right ventricular dysfunction occurred during the experiment, and no animal experienced circulatory failure CONCLUSION: Experimental aspiration pneumonitis after intratracheal infusion of human gastric juice is characterized by a stable fall in PaO(2)/FIO(2). Animals with the most severe lung injury experienced a lower systemic arterial pressure, cardiac output, and metabolic acidosis without circulatory failure or cardiac dysfunction.

Animals↗
PubMed2006

Space-time clustering of childhood malaria at the household level: a dynamic cohort in a Mali village.

BACKGROUND: Spatial and temporal heterogeneities in the risk of malaria have led the WHO to recommend fine-scale stratification of the epidemiological situation, making it possible to set up actions and clinical or basic researches targeting high-risk zones. Before initiating such studies it is necessary to define local patterns of malaria transmission and infection (in time and in space) in order to facilitate selection of the appropriate study population and the intervention allocation. The aim of this study was to identify, spatially and temporally, high-risk zones of malaria, at the household level (resolution of 1 to 3 m). METHODS: This study took place in a Malian village with hyperendemic seasonal transmission as part of Mali-Tulane Tropical Medicine Research Center (NIAID/NIH). The study design was a dynamic cohort (22 surveys, from June 1996 to June 2001) on about 1300 children (<12 years) distributed between 173 households localized by GPS. We used the computed parasitological data to analyzed levels of Plasmodium falciparum, P. malariae and P. ovale infection and P. falciparum gametocyte carriage by means of time series and Kulldorff's scan statistic for space-time cluster detection. RESULTS: The time series analysis determined that malaria parasitemia (primarily P. falciparum) was persistently present throughout the population with the expected seasonal variability pattern and a downward temporal trend. We identified six high-risk clusters of P. falciparum infection, some of which persisted despite an overall tendency towards a decrease in risk. The first high-risk cluster of P. falciparum infection (rate ratio = 14.161) was detected from September 1996 to October 1996, in the north of the village. CONCLUSION: This study showed that, although infection proportions tended to decrease, high-risk zones persisted in the village particularly near temporal backwaters. Analysis of this heterogeneity at the household scale by GIS methods lead to target preventive actions more accurately on the high-risk zones identified. This mapping of malaria risk makes it possible to orient control programs, treating the high-risk zones identified as a matter of priority, and to improve the planning of intervention trials or research studies on malaria.

Animals↗
PubMed2006

Characteristics of arterial stiffness in very low birth weight premature infants.

Premature birth is a factor of increased blood pressure in adulthood. Little is known about the physiologic characteristics of the arterial bed in neonates. The aim of this study was to characterize in vivo the arterial compliance in neonates and its maturation profile in very low birth weight (VLBW) premature infants. A group of stable, VLBW premature infants was compared with a control group of near term neonates. The abdominal aortic wall distensibility coefficient (DC) and whole-body arterial compliance (WBAC) were determined using specifically designed noninvasive methods, based on ultrasonic measurements in combination with synchronous, beat-to-beat recording of aortic pulse pressure (PP). On the fifth day of life, WBAC and the CD were lower in VLBW premature infants than in controls. Furthermore, WBAC and the DC remained unchanged in VLBW premature infants 7 wk after birth. In conclusion, VLBW premature infants are characterized as early as the fifth day of life by high arterial stiffness, which persists when they reach their theoretical term. It can be speculated that early alteration of arterial elastic properties may pave the way for long-term elevation of arterial pressure in VLBW premature infants.

Adult↗
PubMed2006

IL13RA2 gene polymorphisms are associated with systemic sclerosis.

OBJECTIVE: To investigate the influence of genetic variability on the phenotypic expression of systemic sclerosis (SSc), by testing possible associations between single nucleotide polymorphisms (SNP) in IL13RA1 and IL13RA2 genes and SSc in a Caucasian population. METHODS: As IL13RA1 and IL13RA2 are located on the X chromosome and SSc occurs far more frequently in women than in men, only women were genotyped. The study group comprised 97 women with SSc, 36 with diffuse (dcSSc) and 61 with limited (lcSSc) cutaneous forms of disease, and 109 healthy controls. Patients and controls were Caucasian. We investigated 4 SNP in IL13RA1 and 3 in IL13RA2 by polymerase chain reaction amplifications and enzymatic digestion or primer extension reactions and denaturing high-performance liquid chromatography. RESULTS: We detected an association between IL13RA2 rs638376 and patients with SSc [p = 0.004, odds ratio (OR) = 1.85, confidence interval (CI) 1.22-2.74, p corr = 0.02], as well as with dcSSc in that subgroup of patients (p = 0.01, OR 2.22, 95% CI 1.27-3.89, p corr = 0.05). The IL13RA2 rs638376G allele frequency was higher in patients with SSc (51.6%) than in controls (36.4%, p = 0.003, OR 1.86, 95% CI 1.24-2.79, p corr = 0.015) and in the subgroup with dcSSc (57.6%) than in controls (36.4%, p = 0.003, OR 2.37, 95% CI 1.35-4.15, p corr = 0.015). One other IL13RA2 SNP was only associated with the dcSSc subgroup: the IL13RA2 rs5946040G allele was more common in patients with dcSSc (33.8%) than in controls (17%, p = 0.004, OR 2.5, 95% CI 1.36-4.60, p corr = 0.02). CONCLUSION: Our data suggest that IL13RA2 gene polymorphisms may be involved in susceptibility to SSc. Further studies are under way to show that they contribute to disease.

Adult↗
PubMed2006

Evaluation of interleukin 13 polymorphisms in systemic sclerosis.

Systemic sclerosis (SSc) is a multisystem disease of unknown etiology. It is characterized by excessive cutaneous and visceral fibrosis, damage to small blood vessels, and production of autoantibodies. Interleukin-13 (IL-13) has been shown to be involved in abnormal fibrosis in other diseases. Therefore, we have evaluated its possible involvement in SSc. We analyzed four IL13 gene polymorphisms, rs1800925 (IL13-1055), rs20541 (Arg130Gln), rs847, and rs2243204 in 107 unrelated SSc patients (40 patients having diffuse cutaneous form and 67 patients having limited cutaneous form) and in 170 controls. All subjects were Caucasians. In the total patient population and in the diffuse cutaneous subset, we observed an association between two IL13 polymorphisms, IL13 rs1800925 (IL13-1055), and IL13 rs2243204, and disease (p=0.03-0.04). The IL13 rs2243204T allele was more common in SSc patients (p=0.01, OR=2.3 CI 1.21-4.38) and in the diffuse cutaneous form (p=0.01, OR=2.95, CI 1.35-6.49) than in control subjects. Our result supports the suggestion that polymorphisms in IL13 are associated to SSc and skin fibrosis process. However, further studies on larger and independent population and functional analyses are needed to confirm these findings.

Aged↗
PubMed2005

Evaluation of a chromatometer: a new method for blue-yellow or green-red visual comparisons, and anomaly screening techniques.

BACKGROUND: Malbrel's chromatometer is a new apparatus which allows color vision to be monitored. The aim of this study was to assess the accuracy of this new examination method. MATERIAL/METHODS: The color vision of a patient was analyzed using a chromatometer for direct heterochromatic visual comparisons. The patient's task was to adjust, using one eye only, the brightness of a yellow (or red) window to the one of a fixed blue (or green) window. Overall, 158 patients, aged 20 to 28, took part in the experiment. First, parametric means were used to study the response distributions and the luminous effects on the responses. Second, using non-parametric means, we considered that a patient had an anomalous color vision according to the chromatometer if the response was higher than the 95th percentile or lower than 5th percentile. Third, anomalous responses were compared with the Ishihara plates and Farnsworth 28-hue responses. RESULTS: The effect of a luminous stimulus on the response was significant (adjusted to the patient effect). Thus, the chromatometer appears to be a good method to analyze color vision. This apparatus was easy to use and constituted a sensitive and specific test with high negative predictive value. CONCLUSIONS: The chromatometer can be used as a first-line screening test to detect color vision anomalies during ophthalmology consultations. The chromatometer can be useful in identifying early ocular disease, monitoring disease development, or checking possible iatrogenic effects of a specific treatment.

Adult↗
PubMed2005

Oblique decision trees for spatial pattern detection: optimal algorithm and application to malaria risk.

BACKGROUND: In order to detect potential disease clusters where a putative source cannot be specified, classical procedures scan the geographical area with circular windows through a specified grid imposed to the map. However, the choice of the windows' shapes, sizes and centers is critical and different choices may not provide exactly the same results. The aim of our work was to use an Oblique Decision Tree model (ODT) which provides potential clusters without pre-specifying shapes, sizes or centers. For this purpose, we have developed an ODT-algorithm to find an oblique partition of the space defined by the geographic coordinates. METHODS: ODT is based on the classification and regression tree (CART). As CART finds out rectangular partitions of the covariate space, ODT provides oblique partitions maximizing the interclass variance of the independent variable. Since it is a NP-Hard problem in RN, classical ODT-algorithms use evolutionary procedures or heuristics. We have developed an optimal ODT-algorithm in R2, based on the directions defined by each couple of point locations. This partition provided potential clusters which can be tested with Monte-Carlo inference. We applied the ODT-model to a dataset in order to identify potential high risk clusters of malaria in a village in Western Africa during the dry season. The ODT results were compared with those of the Kulldorff' s SaTScan. RESULTS: The ODT procedure provided four classes of risk of infection. In the first high risk class 60%, 95% confidence interval (CI95%) [52.22-67.55], of the children was infected. Monte-Carlo inference showed that the spatial pattern issued from the ODT-model was significant (p < 0.0001). Satscan results yielded one significant cluster where the risk of disease was high with an infectious rate of 54.21%, CI95% [47.51-60.75]. Obviously, his center was located within the first high risk ODT class. Both procedures provided similar results identifying a high risk cluster in the western part of the village where a mosquito breeding point was located. CONCLUSION: ODT-models improve the classical scanning procedures by detecting potential disease clusters independently of any specification of the shapes, sizes or centers of the clusters.

Africa, Western↗
PubMed2004

Doppler echocardiographic predictors of outcome in newborns with persistent pulmonary hypertension.

PATIENTS: We studied retrospectively the echocardiographic features of newborns with persistent pulmonary hypertension who had been randomised to receive inhaled nitric oxide or conventional therapy. We sought to identify the predictors of extracorporeal membrane oxygenation therapy, death, and response to inhaled nitric oxide. RESULTS: Among 85 neonates studied, an extrapulmonary right-to-left shunt through either an oval foramen and/or an arterial duct was present in 80 (94%) cases. In the 64 patients (75%) with adequate images for measurements, left ventricular ejection fraction was normal or mildly depressed in 87%, but there was a decreased index of left ventricular output, inferior to 2 l/min/m2, in 61% of the cases. Using multivariate analysis, an exclusive right-to-left ductal shunt was found to be an independent predictor of death, with odds ratio of 7.8, and 95% confidence intervals from 1.2 to 52.8, with a p value of 0.04. There was also a non-significant trend toward greater use of extracorporeal membrane oxygenation in patients with a predominant left-to-right ductal shunt, the odds ratio being 0.13, with 95% confidence intervals from 0.01 to 1.22, and a p value of 0.07. In the 40 patients randomised to receive inhaled nitric oxide, 28 had a positive response as defined by a 20% reduction in the index of oxygenation as measured from the post-ductal arterial blood gas sample. A left-to-right atrial shunt increased the risk of failing to respond to inhaled nitric oxide, with an odds ratio of 7.46, 95% confidence intervals from 1.23 to 45.1, and a p value of 0.028. CONCLUSION: Detailed Doppler echocardiographic screening of patients with suspected persistent pulmonary hypertension of the newborn may refine the selection of groups for specific treatment, and identify risk factors.

Administration, Inhalation↗
PubMed2004

Thyroid follicular adenomas may display features of follicular carcinoma and follicular variant of papillary carcinoma.

Thyroid follicular adenomas (FA) are encapsulated tumors lacking vascular, capsular or lymphatic invasion and the typical nuclear features of papillary carcinoma (PC). However, some FA demonstrate nuclear atypia reminiscent of either follicular carcinomas (FC) or follicular variant of papillary carcinomas (FVPC), suggesting they may represent precursors of malignant transformation. We hypothesized that an objective evaluation of nuclear chromatin patterns could be used to define atypical follicular tumors (AFT) that are likely to be premalignant. To test this hypothesis, we used a computer-aided image analysis system to define the chromatin pattern of nuclei from thyroid tumors. To validate the system, we analyzed 3000 nuclei from 10 FA, 10 FC, and 10 FVPC samples and accurately distinguished between these classes of tumors. Then, we analyzed nine AFT and, in parallel, we analyzed the tumors for activating mutations of N2-RAS and over-expression of RET. The predominant chromatin pattern of AFT was of FA type in two cases, FC type in two cases, and PC type in three cases. One case contained similar numbers of FC and PC nuclei and one was comprised of a mixture of the three nuclear types. Neither RAS mutation nor RET overexpression were detected in FA. N2-RAS mutations were found in 33% of AFT, 20% of FC and 20% of FVPC without correlation with chromatin pattern. Over-expression of RET was detected in 45% of AFT, 20% of FC and 50% of FVPC and was correlated with PC nuclei. These results show that AFT are a heterogeneous group of tumors, containing genuine benign tumors and tumors that share morphological and molecular features with follicular and papillary carcinomas that might be precursors of both types of thyroid carcinomas.

Adenoma↗
PubMed2003

IFN-gamma polymorphisms (IFN-gamma +2109 and IFN-gamma +3810) are associated with severe hepatic fibrosis in human hepatic schistosomiasis (Schistosoma mansoni).

Schistosome infection is a major public health concern affecting millions of people living in tropical regions of Africa, Asia, and South America. Schistosomes cause mild clinical symptoms in most subjects, whereas a small proportion of individuals presents severe clinical disease (as periportal fibrosis (PPF)) that may lead to death. Severe PPF results from an abnormal deposition of extracellular matrix proteins in the periportal spaces due to a chronic inflammation triggered by eggs and schistosome Ags. Extracellular matrix protein production is regulated by a number of cytokines, including IFN-gamma. We have now screened putative polymorphic sites within this gene in a population living in an endemic area for Schistosoma mansoni. Two polymorphisms located in the third intron of the IFN-gamma gene are associated with PPF. The IFN-gamma +2109 A/G polymorphism is associated with a higher risk for developing PPF, whereas the IFN-gamma +3810 G/A polymorphism is associated with less PPF. The polymorphisms result in changes in nuclear protein interactions with the intronic regions of the gene, suggesting that they may modify IFN-gamma mRNA expression. These results are consistent with the results of previous studies. Indeed, PPF is controlled by a major locus located on chromosome 6q22-q23, closely linked to the gene encoding the alpha-chain of the IFN-gamma receptor, and low IFN-gamma producers have been shown to have an increased risk of severe PPF. Together, these observations support the view that IFN-gamma expression and subsequent signal transduction play a critical role in the control of PPF in human hepatic schistosome infection (S. mansoni).

Adenine↗
PubMed2003

No evidence for a major effect of tumor necrosis factor alpha gene polymorphisms in periportal fibrosis caused by Schistosoma mansoni infection.

Hepatic periportal fibrosis (PPF), associated with portal hypertension, is a major pathological consequence of infections with Schistosoma mansoni and Schistosoma japonicum. Indeed, affected subjects may die from portal hypertension. Previous studies have indicated that tumor necrosis factor alpha (TNF-alpha) may aggravate fibrosis. We therefore investigated whether PPF was associated with certain polymorphisms of the TNF-alpha gene. Four polymorphisms (TNF-alpha -376 G/A, -308 G/A, -238 G/A, and +488 G/A) were investigated in two Sudanese populations living in an area in which S. mansoni is endemic. These polymorphisms were analyzed for 105 Sudanese subjects with various grades of PPF, from mild to advanced; all subjects were from two neighboring villages (Taweela and Umzukra). They were then analyzed for 70 subjects with advanced liver disease and for 345 matched controls from the Gezira region. We found no evidence of associations between these four polymorphisms and PPF in both of these studies. Thus, these four polymorphisms, two of which (TNF-alpha -376 and -308) were found to increase TNF-alpha gene transcription, are unlikely to have a major effect on PPF progression in these populations. However, this result does not exclude the possibility that these polymorphisms have a minor effect on PPF development.

Base Sequence↗
PubMed2002

Cytokine regulation of periportal fibrosis in humans infected with Schistosoma mansoni: IFN-gamma is associated with protection against fibrosis and TNF-alpha with aggravation of disease.

Hepatic periportal fibrosis, which affects 5-10% of subjects infected by Schistosoma mansoni, is caused by the T cell-dependent granuloma that develop around schistosome eggs. Experimental models of infection have shown that granuloma and fibrosis are tightly regulated by cytokines. However, it is unknown why advanced periportal fibrosis occurs only in certain subjects. The goal of the present study was to evaluate the cytokine response of S. mansoni-infected subjects with advanced liver disease in an attempt to relate susceptibility to periportal fibrosis with an abnormal production of cytokines that regulate granuloma and fibrosis. Fibrosis was evaluated by ultrasound on 795 inhabitants of a Sudanese village in which S. mansoni is endemic: advanced periportal fibrosis was observed in 12% of the population; 35% of the affected subjects exhibited signs of portal hypertension. Age (odds ratio (OR), 11.5), gender (OR, 4.2), and infection levels (OR, 2.2) were significantly (p < or = 0.01) associated with hepatic fibrosis. Cytokines produced by egg-stimulated blood mononuclear cells from 99 subjects were measured (75 with no or mild fibrosis; 24 subjects with advanced fibrosis). Multivariate analysis of cytokine levels showed that high IFN-gamma levels were associated with a marked reduction of the risk of fibrosis (p = 0.01; OR, 0.1); in contrast, high TNF-alpha levels were associated with an increased risk (p = 0.05; OR, 4.6) of periportal fibrosis. Moreover, infection levels were negatively associated with IFN-gamma production. These results with observations in experimental models strongly suggest that IFN-gamma plays a key role in the protection of S. mansoni-infected patients against periportal fibrosis, whereas TNF-alpha may aggravate the disease.

Adult↗
PubMed2002

Management and outcome of patients with abnormal ventriculo-arterial connections and mitral valve cleft.

BACKGROUND: In patients with abnormal ventriculo-arterial connections, a mitral valve cleft different from an atrioventricular canal is occasionally associated. It may cause outflow obstruction, mitral regurgitation, and complicate biventricular repair. METHODS: A retrospective review identified 21 patients operated upon with mitral valve cleft, abnormal ventriculo-arterial connections, and two well-developed ventricles. Eight patients had a ventricular outflow obstruction due to the mitral valve, whereas 2 had more than mild mitral regurgitation. One patient required initial mitral valve surgery. Eleven patients underwent biventricular repair, associated with mitral valve repair in 2 cases: arterial switch operation (n = 4), Senning operation (n = 3) associated with an arterial switch operation in one case, intraventricular repair (n = 3), and Rastelli-type extracardiac conduit repair (n = 1). Single-ventricle palliation was preferred in 10 patients with major mitral valve straddling (n = 5), outflow tract obstruction (n = 2), and noncommitted or multiple VSDs (n = 3). RESULTS: There were three hospital deaths, two of which occurred after biventricular repair and one after an early reoperation after a bidirectional cavopulmonary anastomosis. Postoperatively after biventricular repair, 1 patient required permanent pacemaker implantation and 3 patients were reoperated on for subaortic stenosis (n = 1) and mitral regurgitation (n = 2), with one late death. By multivariate analysis, patients with a double-outlet right ventricle were at greater risk of death (p = 0.04). After a mean follow-up period of 60.7 months (+/- 68.6 months), 16 patients are in New York Heart Association (NYHA) class I. One patient with a moderate mitral regurgitation on Doppler study is in NYHA class II. CONCLUSIONS: The surgical management remains controversial in patients with abnormal ventriculo-arterial connections and mitral valve cleft. Biventricular repair may not always be feasible, especially in cases of complex intracardiac anatomy associated with mitral valve straddling. Single-ventricle palliation can be achieved in these patients, although it is unknown whether the long-term results are as good as those obtained with biventricular repair.

Adolescent↗