The cystic fibrosis tansmembrane regulator gene, one of the most commonly mutated in the European population, was cloned in 1989 and since then has been extensively analysed in patients of various ethnic backgrounds. We have screened the entire coding sequences of the cystic fibrosis transmembrane regulator gene and identified many mutations and polymorphisms. In this paper we propose a general strategy to improve prenatal diagnosis and genetic counselling of cystic fibrosis (CF). As this approach based on denaturing gradient gel electrophoresis is adaptable to different populations, it greatly increases the sensibility and specificity of CF prenatal diagnosis.
The combination of high PEEP and low tidal volume (VT) decreases some risks of mechanical ventilation, including pulmonary overdistention, damage due to cyclic opening and closing of the alveoli, and inflammatory responses that can lead to multiple-organ dysfunction. We hypothesized that high VT and high PEEP induce mesenteric microcirculatory disturbances and that those disturbances would be attenuated by pentoxifylline, which is anti-inflammatory.
METHODS:
We anesthetized (isoflurane 1.5%), tracheostomized, and mechanically ventilated 57 male Wistar rats with PEEP of 10 cm H2O and FIO2 of 0.21 for 2 hours. One group received low VT (7 mL/kg), another group received high VT (10 mL/kg), and a third group received high VT plus pentoxifylline (25 mg/kg). We measured mean arterial pressure, respiratory mechanics, mesenteric blood flow, and leukocyte-endothelial interactions.
RESULTS:
The mean arterial pressure was similar among the groups at baseline (108 mm Hg [IQR 94–118 mm Hg]) and after 2 hours of mechanical ventilation (104 mm Hg [IQR 90–114 mm Hg]). Mesenteric blood flow was also similar between the groups: low VT 15.1 mL/min (IQR 12.4–17.7 mL/min), high VT 11.3 mL/min (IQR 8.6–13.8 mL/min), high-VT/pentoxifylline 12.4 mL/min (10.8–13.7 mL/min). Peak airway pressure after 2 hours was lower (P = .03) in the low-VT group (10.4 cm H2O [IQR 10.2–10.4 cm H2O]) than in the high-VT group (12.6 cm H2O [10.2–14.9 cm H2O]) or the high-VT/pentoxifylline group (12.8 cm H2O [10.7–16.0 cm H2O]). There were fewer adherent leukocytes (P = .005) and fewer migrated leukocytes (P = .002) in the low-VT group (5 cells/100 μm length [IQR 4–7 cells/100 μm length] and 1 cell/5,000 μm2 [IQR 1–2 cells/5,000 μm2], respectively) and the high-VT/pentoxifylline group (5 cells/100 μm length [IQR 3–10 cells/100 μm length] and 1 cell/5,000 μm2 [IQR 1–3 cells/5,000 μm2], respectively) than in the high-VT group (14 cells/100 μm length [IQR 11–16 cells/100 μm length] and 9 cells/5,000 μm2 [IQR 8–12 cells/5,000 μm2], respectively).
CONCLUSIONS:
Low VT with high PEEP was lung-protective, and early pentoxifylline reduced the inflammatory response to high VT with high PEEP (and presumed lung overdistention) during mechanical ventilation.
L'absence bilaterale congenitale des canaux deferents (CBAVD) est une cause importante de sterilite masculine. L'etude des mecanismes moleculaires en cause dans cette affection a montre qu'environ la moitie des malades ont une mutation du gene CFTR, responsable de la mucoviscidose. Aujourd'hui, les resultats de l'analyse detaillee du gene CFTR chez un tres grand nombre de patients montre que la base genetique de la CBAVD est complexe. La presence d'un variant polypyrimidique (5T) dans le site accepteur d'epissage de l'intron 8 du gene, responsable d'une diminution tres importante de la synthese du CFTR, est fortement associee a la CBAVD. Il faut noter, cependant, que dans 22 % des cas, on ne retrouve aucune anomalie du gene CFTR. L'affection est donc probablement genetiquement heterogene et d'autres facteurs ou genes sont en cause.
We have previously reported a significant increase of HLA-DR4 antigen frequency in giant cell arteritis (GCA). This finding suggested an important role of immunogenetic factors in this syndrome. Recent data suggest that inherited susceptibility to several autoimmune diseases was associated with specific DR4 associated DQ beta alleles. DNAs from 27 DR4 positive patients with GCA were digested with Taq I and Bam HI, analysed on 0.7% agarose gel and hybridized with DR beta, DQ alpha and DQ beta probes. DR beta hybridization produced no variant detectable within DR4. DQ beta probe confirmed two clusters among DR4 associated DQW3 alleles: DQW 3.1 (Bam HI 360 Kb) and DQw 3.2 (Taq I 1.9 Kb and Bam HI 11 Kb). Among our 27 DR4 positive patients, 34% were DQW 3.1 and 66% were DQW 3.2. These frequencies are the same as those observed in healthy controls.
