Abstract: Determination of age at the time of death based on the observation of cranial sutures has led to numerous studies with sometimes contradictory results. The initial hypothesis being that suture closure is part of an age-related physiological process, the conflicting results have been interpreted by various authors as secondary to the choice of sutures, under the co-existing influence of pathological factors or genetic factors, or even independent of age. Despite these differences, macroscopic methods remain much used in anthropology and in forensic medicine. In our work, we evaluated the value of the degree of closure of the frontosphenoidal suture in estimating age at death of mature subjects, with the secondary objective of establishing a linear regression which could be used in routine practice. The study concerned bone specimens from individuals whose age, sex and medical history were known. Macroscopic observation was carried out on the ectocranial and endocranial sides according to four stages of closure previously defined. 290 sutures were taken from a population of whom two-thirds were men. The method can be repeated and reproduced and the regression established shows the confidence range for average error to be +/-1.5 years. While this result is of interest in terms of precision in prediction for a group of people, the prediction range is too great (+/-23 years) to be applicable to a single individual as part of a forensic procedure.
Abstract: INTRODUCTION: Residual masses are an important problem in oncology. The determination of their nature (fibrosis or active tumor) is crucial. The place of 18F-fluorodeoxyglucose -positron emitting tomography (PET) as a new imaging device remains to be determined in this context. OBJECTIVES: To evaluate the place of 18F-fluorodeoxyglucose -PET in the prediction of the nature of residual masses in children with solid tumors. PATIENTS AND METHODS: Between January 2004 and January 2006, 238 PETs were performed in children followed up in the pediatric oncology and hematology departments. This was a monocentric retrospective review of the medical files of 18 children, in whom the main objective of the PET was to evaluate a residual mass. The sex ratio was 1/5; the median age 100 months (range, 34 to 180 mo). The underlying diseases were Hodgkin disease (n=5), lymphomas (n=5), osteosarcomas (n=3), rhabdomyosarcomas (n=2), and others (n=3). The final diagnostic (remission or persistent disease) was given by follow-up (median, 18 mo; range, 18 to 40), together with clinical, radiologic, and biopsy (in 6 cases) data. RESULTS: PET was negative in 13 cases and positive in 5, among them 4 patients relapsed. Among the 13 negative PETs, there was 1 relapse and 12 remissions. The respective value of PET sensibility and specificity were0.8 and 0.92, respectively. Positive and negative predictive values were 0.8 and 0.92, respectively. CONCLUSION: On the basis of these preliminary results, PET seems to be an interesting tool to assess the nature of posttherapeutic residual masses in children, regardless of the underlying malignancy. Its role needs to be confirmed and further explored by multicentric studies tailored according to the underlying disease.
Abstract: OBJECTIVES: To assess the prognosis of surgically corrected complete atrio-ventricular canal and determine risk factors for death and redo surgery. PATIENTS: and method: From January 1984 to March 2006, 126 patients were distributed in 3 groups according to their date of intervention: group I (1984-1991), group II (1992-1999) and group III (2000-2006). They were operated at mean age of 8.35 + 13.3 months. Down syndrome was present in 99 patients (79%). A partial or total closure of the left atrio-ventricular valvular cleft was performed in 47 patients (37%). RESULTS: The in-hospital mortality was at 14.28% (18 patients), including 23.7% in group I, 16.2% in group II and 4.4% in group III (p=0.06). The predictive factors of survival were the Down syndrome (p<0.05) and surgery of the left atrio-ventricular valvular cleft (p=0.05). An early reoperation was required in 6 cases, for a severe leak of this valve (n=4) or an important residual shunt (n=2). After a mean follow-up of 9.5+6.9 years, the survival rate was at 83.6% and 10 patients (9.9%) had a redo surgery for a leak of the left atrio-ventricular valve (n=6) or sub-aortic stenosis (n=4). The rate of no-redo surgery for valve insufficiency was at 94.2% at 5 years, 91.1% at 10 years and 87.6% at 15 years. CONCLUSION: The surgical treatment of complete atrio-ventricular canal became more and more efficient with poor rates of mortality and redo surgery during these last years. The closure of the left atrio-ventricular valve cleft, mostly partial, is frequently performed. Patients with the Down syndrome have a better vital prognosis and lower rates of long-term redo surgery.
Abstract: BACKGROUND: Various statistical methods have been developed to describe spatial heterogeneity, in terms of high risk zones. If no source can be determined, this heterogeneity can be globally or locally described. Global methods test a statistic estimated over the whole studied geographical area, whereas local methods estimate a statistic on each spatial unit (or regrouping unit). This paper aimed to present, and to compare results of an epidemiological application, of five methods of spatial cluster detection. METHODS: The two global detection methods were: 1) Moran's coefficient, a classically used autocorrelation coefficient; 2) Tango's statistic, a spatial generalization of the Chi(2) statistic. The three local methods were: 1) the local application of Moran's coefficient, proposed by Anselin; 2) the scan statistic, which searches for grouping of spatial units; 3) the oblique regression tree, which splits the studied zone into sub-zones of different risks. These five methods were applied to the description of the spatial heterogeneity of the malaria risk over a hyperendemic village, in Mali. RESULTS: All the methods highlighted a significant spatial heterogeneity. Both global methods (Moran's coefficient and Tango's statistic) showed weak spatial correlations. Local Moran's coefficient (with Bonferronis' adjustment) highlighted five spatial units. The scan statistic identified a single high risk cluster. The regression oblique tree split the study area into six sub-zones; the sub-zone with the higher risk was consistent with the cluster identified by the scan statistic. CONCLUSION: These presented methods do not require any previous knowledge of a source. They allow evaluating spatial risk heterogeneity over the entire geographical area under study. It is noteworthy that shape, size, and spatial heterogeneity characteristics (either global or local) of the study area, as well as the definition of the proximity, significantly influence the spatial risk analysis' outcome. Although their results should be cautiously interpreted, these methods are useful for preliminary field studies or epidemiological surveys.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: 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.
Abstract: OBJECTIVE: To describe how pediatric residents involve children during medical decision-making and evaluate the relationship between practice patterns and residents characteristics. POPULATION AND METHODS: We conducted a prospective multicenter anonymous written survey. Self-reported involvement of children by 45 French pediatric residents in practice pattern was collected and analysed. RESULTS: Most residents reported they informed patients in more than 50% of the cases (82%). Only a minority of the residents asked for consent, respected children refusal or presented other choices to the treatment. The main reasons that explain the lack of partnership are children incompetence and the medical situation. No statistically significant relationship between practice patterns and residents characteristics was found. CONCLUSIONS: Partnership with children varies across residents and according to the level of involvement considered. No statistical differences were obtained to explain variations between residents' attitude toward involvement of children. Nevertheless medical education in ethics or decision-making could increase partnership with children.
Abstract: 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.
Abstract: INTRODUCTION: echocardiographic evaluation in neonates with persistent pulmonary artery hypertension is often limited to pressure measurements and analysis of pulmonary artery blood flow. The prognostic significance of a more detailed analysis, in particular of the extra-pulmonary shunt, is not known. PATIENTS AND METHOD: we analysed retrospectively the echocardiographs of neonates with persistent pulmonary artery hypertension who were also entered in a randomised therapeutic trial of treatment with inhaled nitric oxide. Our aim was to identify the predictive echographic factors for extra-corporeal circulatory assistance, death and a good response to nitric oxide. RESULTS: out of the 85 neonates studied, an extra-pulmonary right-left shunt across the foramen ovale or the ductus arteriosus was present in 80 patients (94%). Biventricular function was normal in the majority of patients while the cardiac index was reduced (< 2L/min/m2) in 61% of cases. With multivariate analysis, an exclusively right-left ductal shunt was a predictive factor for death (odds ratio 7.8; 95% confidence interval 1.2 to 52.8; p=0.04) while an exclusively left-right ductal shunt was at the limit of significance for circulatory assistance (odds ratio 0.13; 95% confidence interval 0.01 to 1.22; p=0.07). In the 40 patients randomised to receive nitric oxide, 28 responded positively with a reduction of at least 20% in the oxygenation index measured by post-ductal arterial gasometry. The existence of a left-right atrial shunt increased the risk of a poor response to nitric oxide (odds ratio 7.46; 95% confidence interval 1.23 to 45.1; p=0.028). CONCLUSION: precise echocardiographic evaluation of these patients allows identification of prognostic factors and adjustment of vasodilator treatment.
Abstract: 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.
