Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis.

Multiple sclerosis (MS), a chronic disorder of the central nervous system and common cause of neurological disability in young adults, is characterized by moderate but complex risk heritability. Here we report the results of a genome-wide association study performed in a 1000 prospective case series of well-characterized individuals with MS and group-matched controls using the Sentrix HumanHap550 BeadChip platform from Illumina. After stringent quality control data filtering, we compared allele frequencies for 551 642 SNPs in 978 cases and 883 controls and assessed genotypic influences on susceptibility, age of onset, disease severity, as well as brain lesion load and normalized brain volume from magnetic resonance imaging exams. A multi-analytical strategy identified 242 susceptibility SNPs exceeding established thresholds of significance, including 65 within the MHC locus in chromosome 6p21.3. Independent replication confirms a role for GPC5, a heparan sulfate proteoglycan, in disease risk. Gene ontology-based analysis shows a functional dichotomy between genes involved in the susceptibility pathway and those affecting the clinical phenotype.

[Does a victim's fault exonerate medical responsibility?]. / La faute de la victime est-elle exonératoire de la responsabilité médicale?

Victim fault constitutes a paradox in which the person creates herself her damage and runs the risk to suffer of it. That situation can occur in several cases, exploration or therapeutics. French liability rules consist in application of Civil code articles n(o) 1382 and 1383, but mainly 1147 concerning contractual liability since 1936. Indubitably, victim fault exonerates practitioner from her liability, at least partly. After report of a few files, the author proposes safety rules which can help to avoid problems.

[Administrative procedures in cases of medical errors: the jurisdiction of the hospitalist]. / Procédure administrative en cas de faute médicale: la juridiction du médecin hospitalier.

The administrative jurisdiction is, with the exception of free practice within hospitals, that which judges whether actions of hospital doctors are at fault, and evaluates the harm done to the plaintiff. After a reminder of the fundamentals of medical liability as regards the administration, a short update on private practice in hospital, and the notion of fault being separate from the hospital function, the author analyses the important elements such as the concept of the preliminary decision and the status of the expert, and then a number of characteristic elements of this type of procedure, stressing in particular the absolute necessity of a perfectly kept hospital medical record.

Metabolic regulation of plasma apolipoprotein E by estrogen and progesterone in the baboon (Papio sp).

Apolipoprotein (apo) E plays an important role in the metabolism of lipoproteins. To determine the effects of estrogen and progesterone on plasma levels and metabolism of apo E, we used 12 ovariectomized baboons fed a cholesterol- and fat-enriched diet. These baboons were divided into four groups and treated with estrogen, progesterone, estrogen + progesterone, and a placebo control. After 10 months, although the lipid levels were not different among the treatment groups, low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratios in the estrogen + progesterone group were significantly lower than those in the control and progesterone groups. Estrogen alone or in combination with progesterone decreased plasma apo E levels significantly compared with those in the control group. Plasma apo E levels in the progesterone group were similar to those in the control group. In all groups, most (greater than 60%) of the apo E was present in HDL. HDL apo E concentrations in the estrogen and estrogen + progesterone groups were significantly lower than those in the control and progesterone groups. To determine the metabolic mechanisms of these changes in apo E levels, turnover studies were conducted by injection of iodinated apo E-labeled very-low-density lipoprotein (VLDL) and HDL. Residence times were calculated using multicompartment modeling. Progesterone alone and in combination with estrogen decreased residence times of apo E injected in both HDL and VLDL compared with estrogen alone and control groups. Progesterone alone also increased the apo E production rate compared with other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic regulation of apoproteins of high-density lipoproteins by estrogen and progesterone in the baboon (Papio sp).

To determine the metabolic regulation of the apoproteins of high-density lipoproteins (HDL) by estrogen and progesterone, 12 ovariectomized and hysterectomized baboons were fed a high cholesterol, high fat diet and were divided into four groups. One of these groups was the untreated control and the remaining three groups were treated with estrogen, progesterone, or a combination of both. After 10 months of treatment, there were significant differences in HDL apolipoprotein (apo) A-I and apo A-II levels in these groups. The apo A-I level was highest in baboons treated with the combination therapy, followed by those treated with estrogen. Baboons treated with progesterone and those in the control group had similar levels of apo A-I. Baboons treated with both estrogen and progesterone and estrogen alone had significantly higher levels of apo A-I than those in the control or progesterone group. Baboons treated with hormones had higher apo A-II levels than controls, and those treated with the combination therapy had the highest level. Metabolic studies suggested that both estrogen and progesterone increased apo A-I and apo A-II production. Progesterone also increased the fractional catabolic rate of apo A-I, but not of apo A-II. On the other hand, estrogen did not affect the fractional catabolic rate of either apo A-I or apo A-II. Thus, increased apo A-I content of HDL in baboons treated with both estrogen and progesterone or estrogen alone appears to be due to increased apo A-I synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between metabolic and reproductive hormones in salmonid fish.

Circulating concentrations of estradiol (E2), vitellogenin (VTG), thyroxine (T4), triiodothyronine (T3) and insulin were measured in reproductively maturing four and five year-old Atlantic salmon. Blood samples were collected from the fish in seawater for one year prior to their spawning in November in fresh water. In females, E2 and VTG were low but detectable from December to July, and then increased to peak levels in September and October. Plasma levels of T4 and T3 were relatively constant in winter and spring, and decreased in July. Plasma concentration of T4 increased in November when the fish returned to fresh water. Plasma T3 levels remained low during the autumn. Both T4 and T3 levels tended to be higher in males than in females during September through November. Plasma insulin concentrations increased during the spring to peak values in May, and then decreased in June and July in fish of both sexes. There was a significant elevation of plasma insulin in males during October, and the levels in males tended to be higher than those found in females during final maturation.