PTX3 genetic variations affect the risk of Pseudomonas aeruginosa airway colonization in cystic fibrosis patients

Cystic fibrosis (CF) is a common life-threatening autosomal recessive disorder in the Caucasian population, and the gene responsible is the CF transmembrane conductance regulator (CFTR). Patients with CF have repeated bacterial infection of the airways caused by Pseudomonas aeruginosa (PA), which is one of the predominant pathogen, and endobronchial chronic infection represents a major cause of morbidity and mortality. Pentraxin 3 (PTX3) is a gene that encodes the antimicrobial protein, PTX3, which is believed to have an important role in innate immunity of lung. To address the role of PTX3 in the risk of PA lung colonization, we investigated five single nucleotide polymorphisms of PTX3 gene in 172 Caucasian CF patients who were homozygous for the F508del mutation. We observed that PTX3 haplotype frequencies were significantly different between patients with PA colonization, as compared with noncolonized patients. Moreover, a protective effect was found in association with a specific haplotype (odds ratio 0.524). Our data suggest that variations within PTX3 affect lung colonization of Pseudomonas in patients with CF.     

Excessive checking for non-anxiogenic stimuli in obsessive-compulsive disorder

BackgroundRepetitive checking in obsessive-compulsive disorder (OCD) would serve to relieve obsession-related anxiety and/or to compensate memory deficit, but experimental literature on this subject is inconsistent. The main objective is to test the influence of obsession-related anxiety and memory on repetitive checking in OCD.MethodsTwenty-three OCD checkers, 17 OCD non-checkers and 41 controls performed a delayed-matching-to-sample task with an unrestricted checking option. Some stimuli were obsession-related in order to measure the influence of anxiety on checking. A version of the task without checking possibility was used to assess memory abilities.ResultsOCD checkers had similar memory performances but checked more than the other groups when presented with non-anxiogenic stimuli. Level of anxiety associated to the stimulus did not influence the number of checks.ConclusionsIncreased checking in OCD checkers, being independent of memory abilities and primary obsession-related anxiety, would, therefore, be closer to an automated behaviour than a coping strategy.     

Outcomes of open versus closed treatment of mandibular subcondylar fractures.

OBJECTIVES: The purpose of this study was to compare the long-term treatment results of open reduction and rigid internal fixation (ORIF) with closed reduction and maxillomandibular fixation (CRMMF) for subcondylar fractures when guided by specific indications and contraindications. PATIENTS AND METHODS: A protocol for the treatment of condylar process fractures was developed that included absolute and relative indications and contraindications as well as a technique regimen. To evaluate the results of this protocol, 10 patients treated with CRMMF and 10 treated by ORIF were recalled after a minimum of 6 months and examined for gender, race, diagnosis, age at injury, time since operation, and cause of the fracture. Each group was assessed by 2 blinded investigators for maximum interincisal opening, right lateral excursion, left lateral excursion, protrusive movement, deviation on opening, scar perception, motor function, sensory perception, contour perception, occlusion, and perception of pain. Nonparametric data were compared for statistical significance with a chi-square analysis and parametric data with an independent samples t-test (P < .05). RESULTS: No statistically significant differences existed between the ORIF and CRMMF groups for gender, race, diagnosis, or cause. Moreover, no differences existed for age at injury, maximum interincisal opening, right lateral excursion, left lateral excursion, protrusive movement, deviation on opening, or occlusion. Differences were noted between groups for time since operation, scar perception, and perception of pain. Using the protocol outlined, there were no differences between the ORIF and CRMMF groups for ranges of motion, occlusion, contour, and motor or sensory function. The ORIF group was associated with perceptible scars. The CRMMF group was associated with chronic pain. CONCLUSIONS: Using a treatment protocol, there were few differences in outcomes between patients treated with CRMMF and ORIF for subcondylar fractures.     

Renal effects of cyclosporin A in children treated for idiopathic nephrotic syndrome

Little data have been published on tubular renal function during cyclosporin A treatment in children without transplants. We studied 12 young subjects (mean age 10 years) with steroid-responsive idiopathic nephrotic syndrome and with signs of steroid toxicity. After achieving remission with prednisone 60 mg/m², 8 children started cyclosporin A therapy (6 mg/kg/day) (group A) and 4 children were given cyclophosphamide 2.5 mg/kg/day (group B). The latter were considered as controls together with 10 other children with idiopathic nephrotic syndrome in complete remission and off therapy (group C). We monitored creatinine clearance and tubular handling of β₂-microglobulin, sodium, phosphorus and uric acid for one year. Cyclosporin A induced a decrease in creatinine clearance with a decrease in fractional excretion of β₂-microglobulin; sodium excretion was similar in the two treated groups and a transient decrease in fractional excretion of uric acid was seen only in patients receiving cyclosporin A. Both groups showed an increased renal threshold phosphate concentration. Our results suggest that in children, cyclosporin A therapy induces a decrease in glomerular filtration rate associated with increased reabsorption activity of proximal tubular cells.     

Epidemiology and survival analysis of cystic fibrosis in an area of intense neonatal screening over 30 years

This population-based study was conducted in Veneto and Trentino (northwestern Italy, population 5 million). In this area, neonatal screening for cystic fibrosis started in 1973 and has been virtually universal since the early 1980s. During this study, the estimated incidence of cystic fibrosis in this region was 1/2,650 livebirths per year. The authors analyzed data on 593 patients born in 1938-2000 and living in the region who were followed by a single referral center. Median time from birth to confirmation of diagnosis after screening was 32 days (range, 0-1,531). For patients whose disease was recognized after symptoms occurred, median age at diagnosis was always less than 1 year. Median survival age was 37.7 years. Long-term survival (to age 20-30 years) was not significantly influenced by mode of diagnosis (screened or unscreened), sex, or age at diagnosis for unscreened patients (<1, 1-5, >5 years). Current survival analysis of three consecutive decades showed that improving survival tended to vanish in the last years of the study. The authors concluded that a regional neonatal screening program allows very early recognition of cystic fibrosis. They could not conclude that neonatal screening improves long-term survival if compared with diagnosis by symptoms in early infancy.     

Kinetics and efficacy of theophylline in the treatment of apnea in the premature newborn

Summary Aminophylline (theophylline-ethylenediamine) was administered to 27 premature newborns to prevent apneic spells. Of the 22 patients monitored for theophylline concentration, a therapeutic blood level was reached in 19 in 1–2 days, and 3 stayed below it. Toxic blood levels (20 µg/ml) were reached in 3 cases, one of whom showed signs of toxicity. Theophylline treatment was not efficient in the prevention of apnea when a serious underlying disease was present. Theophylline blood half-life (mean : 27.0 h) and clearance (mean 12.9 ml/h/kg) confirmed the slow elimination pattern of the drug in the premature infant.     

Mast cell activation and degranulation occur early during induction of periosteal bone resorption

We have previously postulated that mast cells participate in the cellular network involved in osteoclastic resorption, probably through histamine release. In this study, we examined mast cell activation and histamine release during origination of resorption. Groups of 10 rats were killed 0, 0.5, 1, 1.5, 3, 6, 9, 12 and 18 h after induction of resorption in a synchronized model of cortical resorption along the mandible. The total number of mast cells was transiently decreased by about one-third at 1 and 9 h. Mast cell activation was monitored by Alcian blue-safranin staining. Early after induction, mast cells started to release their mediator stores; complete release led to the apparent disappearance of the cells with the staining technique used. Histamine immunostaining confirmed the release of histamine and its diffusion in the extracellular environment. Massive degranulation was observed at 1.5 and 9 h with toluidine blue staining. Cell recovery, assessed in terms of histidine decarboxylase expression, occurred gradually. The number of ED1+ osteoclast precursors strongly increased from 12 h up to 18 h. Most parameters had returned to baseline at 18 h, except the ED1+ cells. H2 receptor inhibition with famotidine strongly decreased ED1+ osteoclast precursors at 12 h and subsequently osteoclasts at the peak of resorption. These data support a role of mast cells in resorption origination. They show an early and transient intervention of mast cells in the events regulating the recruitment of circulating osteoclast precursors and ultimately of resorption. Mast cell activation and degranulation induce the release of mediators, particularly histamine acting through its H2 receptors, which are likely involved in these reactions.