Our study aimed to determine the efficacy and safety of colistin in the treatment of ventilator-associated pneumonia (VAP) caused by pan-drug-resistant Pseudomonas aeruginosa or Acinetobacter ...baumanii.
Pairwise, retrospective exposed-unexposed study.
Combined medical and surgical intensive care unit of Habib Bourguiba University Hospital (Sfax, Tunisia).
Sixty patients with VAP caused by pan-drug-resistant A. baumanii or P. aeruginosa matched to 60 controls with VAP caused by A. baumanii or P. aeruginosa susceptible to imipenem. All patients had normal renal function at the onset of antibiotic therapy.
Case patients were treated by colistin intravenously and control patients were treated by imipenem intravenously.
Baseline characteristics were similar between the colistin and imipenem groups. The mean duration of antibiotic therapy for VAP was 9.5+/-3.8 days (range 5-22 days) with colistin and 8.9+/-2.8 days (range 5-20 days) with imipenem (p=0.32). A favorable clinical response to antibiotic therapy for VAP occurred in 45 patients (75%) in the colistin group and in 43 patients (71.7%) in the imipenem group (p=0.68). The time to resolution of infectious parameters after the initiation of antibiotic therapy was not statistically different between the two groups. During the antibiotic course, none of the patients in either group developed renal failure.
We conclude that colistin can be a safe and effective option in the treatments of VAP caused by pan-drug-resistant P. aeruginosa or A. baumanii.
Our study aimed to determine the efficacy and safety of colistin in the treatment of ventilator-associated pneumonia (VAP) caused by pan-drug-resistant Pseudomonas aeruginosa or Acinetobacter ...baumanii. Pairwise, retrospective exposed-unexposed study. Combined medical and surgical intensive care unit of Habib Bourguiba University Hospital (Sfax, Tunisia). Sixty patients with VAP caused by pan-drug-resistant A. baumanii or P. aeruginosa matched to 60 controls with VAP caused by A. baumanii or P. aeruginosa susceptible to imipenem. All patients had normal renal function at the onset of antibiotic therapy. Case patients were treated by colistin intravenously and control patients were treated by imipenem intravenously. Baseline characteristics were similar between the colistin and imipenem groups. The mean duration of antibiotic therapy for VAP was 9.5+/-3.8 days (range 5-22 days) with colistin and 8.9+/-2.8 days (range 5-20 days) with imipenem (p=0.32). A favorable clinical response to antibiotic therapy for VAP occurred in 45 patients (75%) in the colistin group and in 43 patients (71.7%) in the imipenem group (p=0.68). The time to resolution of infectious parameters after the initiation of antibiotic therapy was not statistically different between the two groups. During the antibiotic course, none of the patients in either group developed renal failure. We conclude that colistin can be a safe and effective option in the treatments of VAP caused by pan-drug-resistant P. aeruginosa or A. baumanii.
In this study, we have evaluated the ability of human satellite cells isolated from subjects aged from 5 days to 86 years to proliferate in culture. Cells were cultivated until they became senescent. ...The number of cell divisions was calculated by counting the number of cells plated in culture compared to the number of cells removed following proliferation. Telomere length, which is known to decrease during each round of cell division, has been used to analyze the in vitro replicative capacity and in vivo replicative history of human satellite cells at isolation. The rate of telomere shortening in myonuclei of these muscle biopsies was also examined. Our results show that both proliferative capacity and telomere length of satellite cells decreases with age during the first two decades but that the myonuclei of human skeletal muscle are remarkably stable because telomere length in these myonuclei remains constant from birth to 86 years. The lack of shortening of mean terminal restriction fragments (TRF) in vivo confirms that skeletal muscle is a stable tissue with little nuclear turnover and therefore an ideal target for cell-mediated gene therapy. Moreover, our results show that it is important to consider donor age as a limiting factor to obtain an optimal number of cells.
Introduction Le syndrome métabolique est actuellement considéré comme une pathologie fréquente. Il s’agit d’une constellation de facteurs de risque cardio-vasculaire. Chez le patient diabétique, ce ...syndrome semble associé à une fréquence plus élevée de complications dégénératives. Objectif Analyser au long cours l’évolution des profils clinique et métabolique d’un groupe de patients diabétique de type2 présentant un syndrome métabolique. Patients et méthodes Étude prospective ayant intéressé 46 diabétiques de type 2. Ces patients sont répartis en 2 groupes : – Un premier groupe de 32 patients qui présentent un syndrome métabolique (selon les critères de L’IDF 2005). – Un deuxième groupe témoin de 14 patients, ne présentant pas de syndrome métabolique. – Tous les patients ont bénéficié d’un contrôle clinique et métabolique trimestriel au cours de la période 2003-2007. Résultats L’âge moyen ainsi qu l’ancienneté du diabète sont comparables dans les deux groupes étudiés. Dans le groupe avec syndrome métabolique, on note un augmentation significative de la glycémie à jeun après 5 ans de suivi : 8,8 ± 2,1 mmol/l à T0 versus 10,5 ± 3,3 mmol/l à T5 (p = 0,01).Par ailleurs, on note une augmentation significative du poids aussi bien dans le groupe avec syndrome métabolique (p = 0,026) que dans le groupe sans syndrome métabolique (p = 0,022). La comparaison des profils clinique et métaboliques entre les deux groupes ne montre aucune différence significative aussi bien à T0 qu’à T5 hormis un tour de taille plus élevé dans le groupe avec syndrome métabolique uniquement à T0 (p = 0,04). Conclusion Le syndrome métabolique constitue un cercle vicieux difficile à gérer du fait de l’interférence de ses différentes composantes imposant une prise en charge précoce et rigoureuse incluant tous les facteurs de risque cardio-vasculaire.
Schwartz-Jampel syndrome (SJS1) is a rare autosomal recessive disorder characterized by permanent myotonia (prolonged failure of muscle relaxation) and skeletal dysplasia, resulting in reduced ...stature, kyphoscoliosis, bowing of the diaphyses and irregular epiphyses. Electromyographic investigations reveal repetitive muscle discharges, which may originate from both neurogenic and myogenic alterations. We previously localized the SJS1 locus to chromosome 1p34-p36.1 and found no evidence of genetic heterogeneity. Here we describe mutations, including missense and splicing mutations, of the gene encoding perlecan (HSPG2) in three SJS1 families. In so doing, we have identified the first human mutations in HSPG2, which underscore the importance of perlecan not only in maintaining cartilage integrity but also in regulating muscle excitability.
To report the clinical findings and the genetic linkage mapping of an autosomal recessive cerebellar ataxia associated to peripheral neuropathy, showing an early onset cerebellar ataxia with retained ...tendon reflexes (EOCA) phenotype.
EOCA is a clinical syndrome delimited by Harding distinguished from Friedreich's ataxia (FA) mainly by the preservation of tendon reflexes. Molecular genetic study of patients with EOCA has demonstrated genetic heterogeneity. A form of autosomal recessive spastic ataxia has been described in Charlevoix Saguenay area in Quebec (ARSACS); the gene responsible has been mapped to chromosome 13q.
Genetic linkage analysis was performed on 18 members of a large family including 8 of 9 members with EOCA. After exclusion of FA and ataxia with vitamin E deficiency loci as well as loci of autosomal dominant cerebellar ataxias, we performed a linkage analysis to markers of 13q11-12 region.
The 9 affected members of this family showed stereotyped clinical features with cerebellar ataxia, pyramidal syndrome, and a variable degree of axonal peripheral neuropathy. Linkage was detected between the disease locus and the microsatellite marker D13S232. Surrounding markers to D13S232 confirmed the linkage and showed the homozygosity of the affected members.
The family reported here showed the same locus as autosomal recessive spastic ataxia Charlevoix Saguenay disease.
Disorganization of the neurofilament network is a prominent feature of
several neurodegenerative disorders including amyotrophic lateral sclerosis
(ALS), infantile spinal muscular atrophy and axonal ...Charcot-Marie-Tooth disease. Giant axonal neuropathy (GAN, MIM 256850), a severe, autosomal
recessive sensorimotor neuropathy affecting both the peripheral nerves and
the central nervous system, is characterized by neurofilament accumulation,
leading to segmental distension of the axons. GAN corresponds
to a generalized disorganization of the cytoskeletal intermediate filaments
(IFs), to which neurofilaments belong, as abnormal aggregation of multiple
tissue-specific IFs has been reported: vimentin in endothelial cells, Schwann
cells and cultured skin fibroblasts, and glial fibrillary acidic protein (GFAP)
in astrocytes. Keratin IFs also seem to be alterated,
as most patients present characteristic curly or kinky hairs.
We report here identification of the gene GAN, which encodes a novel,
ubiquitously expressed protein we have named gigaxonin. We found one frameshift,
four nonsense and nine missense mutations in GAN of GAN patients. Gigaxonin
is composed of an amino-terminal BTB (for Broad-Complex, Tramtrack and Bric
a brac) domain followed by a six kelch repeats, which are predicted to adopt
a β-propeller shape. Distantly related proteins sharing
a similar domain organization have various functions associated with the cytoskeleton,
predicting that gigaxonin is a novel and distinct cytoskeletal protein that
may represent a general pathological target for other neurodegenerative disorders
with alterations in the neurofilament network.
Autosomal recessive Charcot-Marie-Tooth (CMT) disease (CMT4) is a complex group of severe childhood motor and sensory neuropathies, characterized by an early age of onset with rapidly progressive ...distal limb weakness and atrophy. One subgroup designated CMT4 type A (CMT4A) was selected from a series of Tunisian CMT4 families according to the following electrophysiological and pathological criteria: slow motor nerve conduction velocity (MCV), severe hypomyelination upon nerve biopsy with basal lamina onion bulbs and no myelin outfolding. In an attempt to localize the CMT4A locus, we studied four inbred families with 13 affected patients. Significant evidence for linkage was found for several markers from chromosome 8q13-21.1 (D8S279, D8S164, D8S286, D8S84, D8S275 and D8S167). An overall two point peak lod score of z(theta) = 9.19 at theta = 0.00 (95% confidence limit 0.00-0.08) was obtained for D8S164. No evidence of genetic heterogeneity was found. The chromosomal localization of one form of CMT4 will have important implications in clarifying the nosology of this complex group of disorders.
Friedreich ataxia and ataxia with selective vitamin E deficiency (AVED) share very similar clinical phenotypes. We have mapped the AVED locus to proximal 8q with only three large consanguinous ...Tunisian families, representing to our knowledge the first use of homozygosity mapping for primary linkage analysis. Subsequently, three additional families showed linkage with the same markers. A maximum lod score of 17.9 was obtained at theta = 0 for the haplotype D8S260-D8S510, consisting of the two closest markers. With only 6 families, the AVED locus is therefore mapped precisely as illustrated by the lod-1 confidence interval of 2.4 cM on either side of D8S260-D8S510. Isolation of a yeast artificial chromosome contig > 800 kilobases (kb) showed that D8S260 and D8S510 are less than 400 kb apart.
Muscular dystrophies are characterised by continuous cycles of degeneration and regeneration resulting in an eventual diminution of the muscle mass and extensive fibrosis. In somatic cells ...chromosomal telomeres shorten with each round of cell division and telomere length is considered to be a biomarker of the replicative history of the cell. We have previously shown that human myoblasts have a limited proliferative capacity, and that normal skeletal muscle has a very low level of nuclear turnover. However, in patients suffering from muscular dystrophy the satellite cells will be forced to make repeated rounds of cell division, driving the cells towards senescence. In this study we have used the telomere length to quantify the intensity of the muscle cell turnover in biopsies from dystrophic patients of different ages. Our results show that as soon as the first clinical symptoms become apparent the muscle has already undergone extensive regeneration and the rate of telomere loss is 14 times greater than that observed in controls. This confirms that the decline in regenerative capacity is due to the premature senescence of the satellite cells induced by their excessive proliferation during muscle repair.
