Risk of Clostridium difficile-associated disease among patients receiving proton-pump inhibitors in a Quebec medical intensive care unit.

Our study was conducted to determine whether use of gastric acid-suppressive agents increased the risk of Clostridium difficile-associated disease (CDAD) in a medical intensive care unit of one of the first hospitals to be threatened by the current CDAD epidemic in Quebec, Canada. Our findings suggest that efforts to determine risk factors for CDAD should focus on other areas, such as older age and antibiotic use.     

Platelet receptor expression on three human megakaryoblast-like cell lines.

Platelets, the progeny of bone marrow megakaryocytes, are nonnucleated cells; many platelet proteins, including platelet membrane receptors, are believed to be derived from megakaryocytes. Several hematopoietic cell lines that exhibit megakaryocytic characteristics have been established as models for the study of megakaryocyte biology. We report here the screening of platelet receptor expression, in terms of functional coupling with the formation of two second messengers, calcium and cAMP, in three cell lines exhibiting megakaryoblastic properties: HEL, MEG-01, and DAMI. We show that all these cell lines respond to thrombin, ADP, epinephrine, and prostaglandin E1 (PGE1). However, transmembrane signaling pathways appear partly different from those present in mature platelets, because the action of thrombin was found to be positively coupled with the cAMP pathway, in addition to that of calcium, and because PGE1, which interacts with the cAMP pathway, also raises intracellular calcium levels in the three cell lines studied. Furthermore, an endothelin-1-induced increase in intracellular calcium level was observed in MEG-01 cells, strongly suggesting the expression of endothelin receptors on platelet precursors cells, whereas the presence of such receptors is controversial on platelets. These cell lines should prove useful in further studies of the expression and molecular pharmacology of platelet receptors on platelet precursor cells, as well as for the investigation of functional roles for platelet receptors on megakaryoblastic cells.     

Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder.

BACKGROUND: Executive dysfunctions have been studied as a potential endophenotype associated with the genetic basis of autism. Given that recent findings from clinical and molecular genetic studies suggest that autism and obsessive-compulsive disorder (OCD) could share a common pattern of heritability, we assessed executive functions as a possible common cognitive endophenotype in unaffected family members of individuals with either autism or OCD. METHODS: Five tests assessing executive functions (Tower of London, verbal fluency, design fluency, trail making and association fluency) were proposed to 58 unaffected first-degree relatives (parents and siblings) of probands with autism and 64 unaffected first-degree relatives of OCD patients. Results were compared with those of 47 healthy controls matched for age, sex, and level of education. RESULTS: In the Tower of London test, both groups of unaffected relatives showed significantly lower scores and longer response times compared with controls. No differences were observed between autism and OCD relatives and healthy controls in the four other tasks (verbal fluency, design fluency, trail making test and association fluency). CONCLUSIONS: Our findings show the existence of executive dysfunction in the unaffected first-degree relatives of probands with OCD, similar to those observed in the relatives of patients with autism. These results support and extend previous cognitive studies on probands indicating executive dysfunctions in autism and OCD. Planning and working memory processes could thus represent a common cognitive endophenotype in autism and OCD that could help in the identification of genes conferring vulnerability to these disorders.     

Evaluation of the end-expiratory lung volume as an indirect index of bronchial constriction in asthma

The purpose of this study was to evaluate the merits of the end expiratory lung volume as an indirect ventilatory index of bronchial obstruction and to show an application of continuous monitoring of lung volume in asthmatic patients. The accuracy of the external measurements (IS) of functional residual capacity (FRC) was controlled by comparing them with the helium measurements (DS) obtained during nine methacholine tests (IS = 0.06 + 1.065 DS in litres: R2 = 0.99). Seven asthmatics (18-48 yr) were monitored by measuring rib cage and abdominal perimeter variations. This was done in basal condition, after methacholine-induced bronchoconstriction and after bronchodilation by either salbutamol or oxytropium bromide inhalation. All the subjects were investigated on two separate days and were their own control. Bronchoconstriction produced a significant increase (p less than 0.01) of tidal volume (VT: + 67%), external minute ventilation (VE: + 58%), mean inspiratory flow (VT/TI: + 78%) and FRC (+ 26.5%) while frequency (f) and fractional inspiratory time (TI/TT) fluctuated non significantly. In the group of seven tested subjects, there was a significant correlation (p less than 0.01) between forced expiratory volume in one second (FEV1) and VE, FEV1 and VT/TI, FEV1 and FRC. However, the individual regression line showed a significant relationship only between FEV1 and FRC (R2 = 0.80 +/- 0.04). We therefore conclude that the variation of the end expiratory level can be chosen as an indirect index of bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Methylation of a euchromatin-heterochromatin transition region in Arabidopsis thaliana chromosome 5 left arm

Cytosine methylation was studied at the level of the euchromatin/heterochromatin transition genomic region of the Arabidopsis chromosome 5 left arm. It has been shown using a monoclonal antibody against 5-methylcytosines that the density of DNA methylation increases from the euchromatin towards the heterochromatin. YACs mapped along this region were characterized for their repeated sequences content. Some of them, corresponding to euchromatin, euchromatin/heterochromatin border and heterochromatin regions, were used as probes for a Southern blot analysis of methylation. This revealed that the degree of mCmCGG and GATmC methylation increases significantly from the euchromatin towards the heterochromatin. Moreover, an analysis of cytosine methylation levels (% of 5-methylcytosine) of different DNA fragments, inside the same genomic region, was performed using PCR and/or Southern blot approaches. There is a gradual increase of methylation along the genomic region analyzed: CpG methylation in the euchromatic fraction, CpG and CpNpG methylation at the euchromatin/heterochromatin transition and an additional asymmetrical methylation in the repeated-heterochromatic fraction. The most methylated repeated family at CpG, CpNpG and asymmetrical sites is the 5S ribosomal DNA, highly methylated even though it is transcribed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Fertility in myotonic dystrophy in Saguenay-Lac-St-Jean: a historical perspective

Myotonic dystrophy (MD) is an autosomal dominant disorder that has a high prevalence in Saguenay-Lac-St-Jean. A case-control study, based on a population register, of 373 MD patients who married in this region between 1855 and 1971 was conducted to determine whether their fertility was affected by the disorder. Six demographic parameters, that is the number of children, the age at marriage, the ages at the time of birth of the first and the last child, the interval between the marriage and the birth of the first child, and the interval between consecutive births, were analyzed. The mean number of children born to MD and control individuals was not different (P > 0.05). However, MD males had more children than MD females although they have started delaying their marriage since 1921. Fertility fell significantly in both the MD and control groups during the period of observation. This change reflects the decline in fertility of French Canadians in general during this period, but mainly after 1940.     

Recurrence of pulmonary embolism during anticoagulant treatment: a prospective study.

The risk of early recurrence of pulmonary embolism in patients with venous thromboembolic disease treated by anticoagulants is not well established. To determine the risk linked to contemporary proximal deep venous thrombosis, a prospective study was organised to give clinical and scintigraphic surveillance to 50 patients with angiographically proved pulmonary embolism plus phlebographically proved proximal deep vein thrombosis during the first 15 days of anticoagulant treatment. Perfusion lung scans were performed initially and on days 3, 7, and 15. Only two patients had a recurrence of pulmonary embolism during this period; both episodes were revealed by new symptoms, and one recurrence was fatal. The systematic performance of angiography in four patients found to have new scintigraphic defects led to the diagnosis of "spurious scintigraphic recurrence" in three of them. It is concluded that (a) adjusted anticoagulant treatment showed an effectiveness of 96% for preventing early recurrence of pulmonary embolism in this group of supposed high risk patients, and (b) in patients with recent pulmonary embolism new defects on systematic perfusion lung scans are not specific indicators of recurrent pulmonary embolism.     

Prenatal diagnosis of genetic diseases in France]

Prenatal diagnosis has been introduced in medicine in the seventies with aminocenteses and amniotic cells cultures. It was applied to the diagnosis, during the second trimester of pregnancy for chromosomal abnormalities (mainly Down syndrome in women 38 years of age) and inborn errors of metabolism with very severe handicaps). Since 1970, obstetrical techniques have improved giving access to several fetal biological samples, knowledge in genetics has identified more diseases and biological analyses have become more accurate. During the same time legislation has been instituted: in France the law of 1994 July 29th established rules for prenatal diagnosis. Among theses rules are defined the objective of prenatal diagnosis, the requirement for medical genetic counselling and official authorizations for cytogenetic, infectious diagnosis, biological diagnosis of genetic diseases (biochemical, molecular genetic, hematology, immunology) and maternal plasma markers of chromosomal abnormalities (Down syndrome). Recently (1997 may 28th) have been established "pluridisciplinary prenatal diagnosis centers", including complementary, clinical and biological services to insure the safety of Prenatal Diagnosis. Preimplantation Diagnosis (PID) inherited diseases has become recently possible with the techniques of in vitro fertilization, blastomere biopsy of the early embryo and DNA analysis of the single blastomere. Only a very few centres worldwide offer PID. In France PID is not yet allowed but the National Ethical Committee examined the question and legislation is about to be published.