Alcohol consumption and insulin resistance syndrome parameters: associations and evolutions in a longitudinal analysis of the French DESIR cohort

PURPOSE: To determine the effects of average alcohol consumption and changes in alcohol intake on the insulin resistance syndrome parameters in a 3-year follow-up study. METHODS: Longitudinal study of 1856 and 1529 alcohol drinking men and women in the French DESIR study (Data from an Epidemiological Study on the Insulin Resistance syndrome), aged 30 to 64 years. RESULTS: In men, fasting glucose, body mass index, waist circumference, systolic blood pressure, and HDL-cholesterol were positively associated with average alcohol consumption while there was no association with insulin or triglycerides concentrations. A change in alcohol intake was positively associated with HDL-cholesterol concentration and systolic blood pressure at follow-up. These effects of alcohol could not be attributed specifically to the intake of wine. In women, while the alcohol HDL-cholesterol relation was similar to that found in the men, the only significant effect of average alcohol intake was an increase in systolic blood pressure, with a spurious decrease in blood pressure related to a 3-year increase in alcohol intake. CONCLUSIONS: Alcohol only provided a beneficial effect on HDL-cholesterol. The beneficial effect seen by other authors of moderate alcohol drinking on diabetes and cardiovascular risk may be due to effects on parameters other than those included in the current definitions of the insulin resistance syndrome.     

Molecular screening of the 11beta-HSD1 gene in men characterized by the metabolic syndrome

Adipose tissue type 1 11beta-hydroxysteroid dehydrogenase (11beta-HSD1), which generates hormonally active cortisol from inactive cortisone, has been shown to play a central role in adipocyte differentiation and abdominal obesity-related metabolic complications. The objective was to investigate whether genetic variations in the human 11beta-HSD1 gene are associated with the metabolic syndrome among French-Canadian men. We sequenced all exons, the exon-intron splicing boundaries, and 5' and 3' regions of the human 11beta-HSD1 gene in 36 men with the metabolic syndrome, as defined by the National Cholesterol Education Program-Adult Treatment Panel III, and two controls. Three intronic sequence variants were identified: two single-nucleotide polymorphisms in intron 3 (g.4478T>G) and intron 4 (g.10733G>C) and one insertion in intron 3 (g.4437-4438insA). The relative allele frequency was 19.6%, 22.1%, and 19.6% for the g.4478G, g.10733C, and g.4438insA alleles, respectively. One single-nucleotide polymorphism was identified in exon 6 (c.744G>C or G248G). The frequency of the c.744C allele was only 0.46% in a sample of 217 men. Variants were not associated with components of the metabolic syndrome except for plasma apolipoprotein B levels. In conclusion, molecular screening of the 11beta-HSD1 gene did not reveal any sequence variations that can significantly contribute to the etiology of the metabolic syndrome among French-Canadians.     

Prevention of neuropathology in the mouse model of Hurler syndrome

A defect of the lysosomal enzyme alpha-L-iduronidase (IDUA) interrupts heparan and dermatan sulfate degradation and causes neuropathology in children with severe forms of mucopolysaccharidosis type I (MPSI, Hurler syndrome). Enzyme substitution therapy is beneficial but ineffective on the central nervous system. We could deliver the missing enzyme to virtually the entire brain of MPSI mice through a single injection of gene transfer vectors derived from adenoassociated virus serotype 2 (AAV2) or 5 (AAV5) coding for human IDUA. This result was reproducibly achieved with both vector types in 46 mice and persisted for at least 26 weeks. Success was more frequent, enzyme activity was higher, and corrected areas were broader with AAV5 than with AAV2 vectors. Treatment presumably reversed and certainly prevented the accumulation of GM2 and GM3 gangliosides, which presumably participates to neuropathology. Lysosomal distension, which already was present at the time of treatment, had disappeared from both brain hemispheres and was minimal in the cerebellum in mice analyzed 26 weeks after injection. This study shows that pathology associated with MPSI can be prevented in the entire mouse brain by a single AAV vector injection, providing a preliminary evaluation of the feasibility of gene therapy to stop neuropathology in Hurler syndrome.     

Life events and trauma in chronic negligent mothers

The present study examines more closely the chronic behaviors of maltreating mothers. Events that these mothers have experienced during childhood are examined, experiences including abuse, placement, separation, bereavement, rejection, neglect, lack of love and role reversal. Signs of unresolved trauma found in the discourse of mothers, such as dissociation, are also studied. It is proposed that negligent mothers from the chronic group will evoke more negative experiences and/or more intense negative experiences which occurred during childhood than the mothers from the transitory group. The chronic group will also show more signs of dissociation. From a six years follow-up study, a sample of 20 mothers was recruited from the Child Protection Services, including the cases of 10 chronic maltreating mothers and 10 transitory maltreating mothers. Two main measures were used: the Child Abuse Potential Inventory (CAPI) and the Adult Attachment Interview (AAI) (Main et Goldwyn, 1998). The experiences from childhood and complete discourse in AAI were analysed with the method used by Main et Goldwyn (1998). Non parametric analysis indicate that mothers from the chronic group evoke more negative and very negative childhood experiences than the mothers from the transitory group. Content analysis show that chronic maltreating mothers relate having gone through more potentially traumatic events such as foster care placements, separations and abuse. The analysis of the Adult Attachment Interview according to Main and Goldwyn's system demonstrate that the majority of the chronic maltreating mothers have two times more unresolved traumas.     

Pharmacokinetics of omeprazole in healthy adults and in children with gastroesophageal reflux disease

Studies of the pharmacokinetics of omeprazole in children with gastroesophageal reflux disease (GERD) remain scarce despite the vast number of reports on its efficacy. The objectives of this study were to assess the pharmacokinetics of omeprazole in healthy adults and in children with GERD. Omeprazole (Losec, delayed-release capsules) was administered orally to 18 healthy adults (mean age 36.8 years) and 12 children with GERD (mean age 6.1 years). Blood samples were collected over 5 hours, and plasma concentrations were assessed using liquid chromatography. Population pharmacokinetic parameters were calculated using NONMEM. A 1-compartment model with zero-order absorption and a lag time was used. The population approach was well suited to the limited number of samples available, and residual variability was low. Oral clearance (CL/F) and apparent volume of distribution (V(ss)/F) in healthy adults (Mean +/- SD: 0.62 +/- 0.27 L/h/kg and 0.76 +/- 0.26 L/kg, respectively) were not significantly different than those in children with GERD (0.51 +/- 0.34 L/h/kg and 0.66 +/- 0.25 L/kg, respectively). Healthy adults displayed a statistically significantly longer delay in drug absorption (Lag time: 0.62 +/- 0.15 hours) as compared with that observed in children with GERD (0.12 +/- 0.03 hours, P < 0.05). On the basis of these findings, omeprazole dosings on a milligram-per-kilogram basis are recommended with no further adjustments for the treatment of GERD in children.     

The MicAB two-component signaling system is involved in virulence of Streptococcus pneumoniae

In Streptococcus pneumoniae, the two-component signaling system MicAB was previously shown to contribute to repression of competence when oxygen is limited. In virulent strains expressing the serotype 2 and 6 capsule, mutation of the MicB kinase reduced the lag period of growth when cultures were switched from an aerobic to anaerobic atmosphere. After intranasal challenge of mice, the micB::km mutation decreased virulence, as shown by the absence of symptoms and by a lower level of recovery of CFU from lungs and blood. It is proposed that MicAB is involved in the adaptive response of the bacteria to changes in oxygen level during the course of infection.     

Perception of the social support for adolescents who undergo corrective back surgery for scoliosis

The objective of this study is to compare the perception of social support upon admission and 6 weeks postoperation of adolescents aged 13 to 19 years (M = 14.7 years), who underwent corrective back surgery for scoliosis. Twenty-two French-speaking participants were found from three different hospital centers located in two large cities in the Quebec province. Data were collected using the French version of Interpersonal Relationships Inventory (IPRI). No significant difference was observed between the results obtained on admission and those obtained 6 weeks later for the global measures of social support available. Nevertheless, analysis of data at the two time points showed a significant difference with regard to intimacy of adolescents. Adolescents reported feeling more invaded in the postoperative period (6 weeks after the surgery) than on admission at the hospital. These results serve to point out the nursing care involvement as well as the surgical techniques and ambulatory care that reduce hospitalization time. The results raise questions about the nurse's role in the adequate support for adolescents as well as the impact of reduced length of hospitalization.     

North Star Project: reality orientation in an acute care setting for patients with traumatic brain injuries

OBJECTIVE: The North Star Project is an acute care rehabilitation approach for patients with moderate and severe traumatic brain injuries. This patient-centered project uses the concepts of Reality Orientation Therapy to develop a unique approach that focuses "environment," "consistency" and "standardization" to promote a total team effort. Patients, treatment staff and members of the patient's family collaborate in a unified bedside protocol that stimulates orientation, encourages patients' appropriate interactions and aims to decrease the length of post-traumatic amnesia. Development of materials, protocols, training and outcome measurement initiatives are described.