A genome-wide scan for childhood obesity-associated traits in French families shows significant linkage on chromosome 6q22.31-q23.2

We conducted a genome-wide search for childhood obesity-associated traits, including BMI >/==" BORDER="0">95th percentile (PCT95), 97th percentile (PCT97), and 99th percentile (PCT99) as well as age of adiposity rebound (AAR), which corresponds to the beginning of the second rise in childhood adiposity. A set of 431 microsatellite markers was genotyped in 506 subjects from 115 multiplex French Caucasian families, with at least one child with a BMI >/==" BORDER="0">95th percentile. Among these 115 pedigrees, 97 had at least two sibs with a BMI >/==" BORDER="0">95th percentile. Fine-mapping was performed in the seven most positive loci. Nonparametric multipoint analyses revealed six regions of significant or suggestive linkage on chromosomes 2q33.2-q36.3, 6q22.31-q23.2, and 17p13 for PCT95, PCT97, or PCT99 and 15q12-q15.1, 16q22.1-q24.1, and 19p13.3-p13.11 for AAR. The strongest evidence of linkage was detected on chromosome 6q22.31 for PCT97 (maximum likelihood score: 4.06) at the marker D6S287. This logarithm of odds score meets genome-wide significance tested through simulation (empirical genome-wide P = 0.01 [0.0027-0.0254]). Six independent ge-nome scans in adults have reported quantitative trait loci on 6q linked to energy or glucose homeostasis-associated phenotypes. Possible candidate genes in this region include SIM1, MCHR2, and PC-1.     

Cochlear implants in elderly people: preliminary results

The objective of this study was to evaluate the benefit of cochlear implantation in adults aged 60 years and over. Twenty-eight patients, older than 60 years and with profound bilateral sensorineural hearing loss, received a cochlear implant between 1991 and 2001. The mean age was 66 years and the median follow-up was 22.5 months. Speech perception scores before and after implantation were analyzed retrospectively in order to evaluate the benefit of cochlear implantation. There was a significant improvement of the disyllabic words and sentences scores after implantation. The patients who were over 70 years performed as well as those who were younger. The surgical procedure was well tolerated in all patients. One patient developed a postoperative vertigo due to a perilymphatic fistula. In conclusion, cochlear implantation offers improvement in speech perception to the elderly population, as in the younger population. A careful assessment of the physical status of these patients remains essential in order to evaluate the risk-benefit of this procedure.     

Airway colonisation in long-term mechanically ventilated patients

Objective To evaluate the impact of continuous subglottic suctioning and semi-recumbent body position on bacterial colonisation of the lower respiratory tract.Design A randomised controlled trial.Setting The ten-bed medical ICU of a French university hospital.Patients Critically ill patients expected to require mechanical ventilation for more than 5 days.Interventions Patients were randomly assigned to receive either continuous suctioning of subglottic secretions and semi-recumbent body position or to receive standard care and supine position.Measurements and results Oropharyngeal and tracheal secretions were sampled daily and quantitatively cultured. All included patients were followed up from day 1 (intubation) to day 10, extubation or death. Ninety-seven samples of oropharynx and trachea were analysed (40 for the suctioning group and 57 for the control group). The median bacterial counts in trachea were 6.6 Log₁₀ CFU/ml (interquartile range, IQR, 4.4–8.3) in patients who received continuous suctioning and 5.1 Log₁₀ CFU/ml (IQR 3.6–5.5) in control patients. Most of the patients were colonised in the trachea after 1 day of mechanical ventilation (75% in the suctioning group, 80% in the control group). No significant difference was found in the daily bacterial counts in the oropharynx and in the trachea between the two groups of patients.Conclusion Tracheal colonisation in long-term mechanically ventilated ICU patients was not modified by the use of continuous subglottic suctioning and semi-recumbent body position.     

Gene expression profiling for molecular characterization of inflammatory breast cancer and prediction of response to chemotherapy

Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer with a 5-year survival limited to approximately 40%. Diagnosis, based on clinical and/or pathological criteria, may be difficult. Optimal systemic neoadjuvant therapy and accurate predictors of pathological response have yet to be defined for increasing response rate and survival. Using DNA microarrrays containing approximately 8,000 genes, we profiled breast cancer samples from 81 patients, including 37 with IBC and 44 with noninflammatory breast cancer (NIBC). Global unsupervised hierarchical clustering was able to some extent to distinguish IBC and NIBC cases and revealed subclasses of IBC. Supervised analysis identified a 109-gene set the expression of which discriminated IBC from NIBC samples. This molecular signature was validated in an independent series of 26 samples, with an overall performance accuracy of 85%. Discriminator genes were associated with various cellular processes possibly related to the aggressiveness of IBC, including signal transduction, cell motility, adhesion, and angiogenesis. A similar approach, with leave-one-out cross-validation, identified an 85-gene set that divided IBC patients with significantly different pathological complete response rate (70% in one group and 0% in the other group). These results show the potential of gene expression profiling to contribute to a better understanding of IBC, and to provide new diagnostic and predictive factors for IBC, as well as for potential therapeutic targets.     

Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter

Our objectives were to determine the reproducibility of diffusion tensor imaging (DTI) in volunteers and to evaluate the ability of the method to monitor longitudinal changes occurring in the normal-appearing white matter (NAWM) of patients with multiple sclerosis (MS). DTI was performed three-monthly for one year in seven MS patients: three relapsing-remitting (RRMS), three secondary progressive (SPMS) and one relapsing SP. They were selected with a limited cerebral lesion load. Seven age- and sex-matched controls also underwent monthly examinations for three months. Diffusivity and anisotropy were quantified over the segmented whole supratentorial white matter, with the indices of trace (Tr) and fractional anisotropy (FA). Results obtained in volunteers show the reproducibility of the method. Patients had higher trace and lower anisotropy than matched controls (P < 0.0001). Over the follow-up, both Tr and FA indicated a recovery after the acute phase in RRMS and a progressive shift towards abnormal values in SPMS. Although this result is not statistically significant, it suggests that DTI is sensitive to microscopic changes occurring in tissue of normal appearance in conventional images and could be useful for monitoring the course of the disease, even though it was unable to clearly distinguish between the various physiopathological processes involved.     

Prophylaxis of iodinated contrast media-induced nephropathy: a pharmacological point of view

Iodinated contrast media are a frequent cause of acute renal failure, especially in patients whose renal function is already impaired. In addition to hydration, which remains the most commonly acknowledged means of protection, numerous pharmacological approaches for the prophylaxis of contrast nephropathy have been tested so far. They include diuretics, calcium channel blockers, adenosine receptor antagonists, N-acetylcysteine, low-dose dopamine and the dopamine D1 receptor agonist fenoldopam, endothelin receptor antagonists, and even captopril. The present review of the literature critically discusses the drugs used to prevent contrast nephropathy from a pharmacological point of view.     

In vivo magnetic resonance imaging of large spontaneous aortic aneurysms in old apolipoprotein E-deficient mice

Old ApoE-deficient mice were studied in vivo by magnetic resonance imaging (MRI) to prospectively evaluate vascular remodeling associated with atherosclerotic lesions. MATERIAL AND METHODS: Old female ApoE-/- mice on a normal diet were followed by MRI at 2 Tesla for a 3-month period and killed for histopathology. Aortic dimensions were measured and compared. RESULTS: High-quality in vivo MR images were obtained at 2 Tesla with in plane spatial resolution of 86 X 86 microm2. On MRI, aortic lumen enlargement (>1.5-fold dilation) was seen in 10 of 13 mice, located predominantly in the suprarenal portion of the aorta. The mean maximal diameter of the aneurysms and of the aorta above and below the aneurysm were, respectively, 1.12 +/- 0.32 mm and 0.53 +/- 0.08 mm by MRI and 1.3+/- 0.41 mm and 0.55 +/- 0.15 mm by histology. Matched histologic cross-sections of the aortic wall showed medial degradation with rupture of the internal elastic lamina at multiple sites, associated with fibrolipidic plaque containing cholesterol crystals. CONCLUSIONS: Aortic lumen enlargement was diagnosed in old ApoE-/- mice at sites with advanced atherosclerotic plaques. MRI has potential both as an in vivo imaging technique for screening mouse models for vascular wall pathology and to follow arterial remodeling associated with the disease progression.     

Infection of human astrocytes and glioblastoma cells with<Emphasis Type="Italic"> Toxoplasma gondii</Emphasis>: monocyte chemotactic protein-1 secretion and chemokine expression in vitro

In immunocompromised hosts, disruption of toxoplasmic cysts and conversion from bradyzoites to tachyzoites occur in brain. In these areas, infiltrates of mononuclear cells are observed. In the murine toxoplasmosis model, recent data suggest that chemokines may play a role in leukocyte recruitment in the central nervous system (CNS). This study analyzed the monocyte chemotactic protein-1 (MCP-1) secretion and chemokine expression after Toxoplasma gondii infection of human astrocytes, glioblastoma cells (U373) and fibroblasts (MRC5) in vitro. T. gondii infection of these CNS cells, astrocytes and glioblastoma cells significantly increased MCP-1 secretion, particularly for astrocytes. In our cellular models, the pattern of chemokine gene expression is dominated by MCP-1 expression. MCP-1 mRNAs were also quantified by real-time-PCR (LightCycler). The behavior of cells studied after T. gondii infection was different (invasion and growth) and the cell mechanisms of chemokine regulation could be dependent on the type of cells infected, while MCP-1 may contribute to the cell recruitment during human cerebral reactivation of T. gondii.