Ad CFTR, a replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator (CFTR), was administered by aerosolization in a single escalating dose to three pairs (cohorts) of cystic fibrosis (CF) patients. Buffer only was administered to the nose and lungs 9-14 days before nasal instillation of virus followed the day after by aerosolization of Ad CFTR to the lung. Nasal doses (defined in terms of viral plaque forming units, pfu) were 10(5), 10(7), and 4 x 10(8), whereas aerosolized doses were 10(7), 10(8), 5.4 x 10(8) for each cohort, respectively. No acute toxic effects were observed in the first 4 weeks after virus treatment. Shedding of infectious Ad CFTR was never detected, whereas detection of vector DNA sequences and CFTR expression demonstrated DNA transfer to the nose and airways of patients. No significant deviations in immunological and inflammatory parameters were observed in serum and in bronchoalveolar lavage (BAL). Importantly, for all patients, the serum anti-adenovirus antibody levels did not change significantly from baseline and no antibodies against adenovirus were found in BAL.

Objective: To determine the effect of a new venoactive ftav?no~d fraction (S 5682) in the treatment of symptomatic disturbances of the venolymphatic system.Design: Double-blind, randomized, placebo-controlled, parallel group trial conducted in two centres. P~nt~: One hundred and sixty patients with sympto-!1latlc disturbances of the venolymphatic system, includ-109 chronic venous insufficiency, were included in the stUdy.Interventions: Treatment lasted 8 weeks and consisted of the daily administration of two tablets of either S 5682 (n=8O) or placebo (n=80). Main o.utcome "!easures:The primary end-point was the evolution of eight symptoms of disturbance of the Venolymphatic system over the 2-month observatioñ riod. The secondary end-point was the change of Clr~umference of each affected leg over the same observation period. es~/ts: When compared with placebo, S 5682 led to a Sl~mficant improvement in four symptoms (functional discomfort, sensation of heaviness, nocturnal cramps, sensation of swelling) at week 4 and in two additional symptoms (pain and sensation of heat or burning) at Correspondence and offprint requests to: Dr G. Pillion, IRIS, 6 place des Pleiades, 92415 Courbevoie Cedex, France.week 8. Similarly, S 5682 was associated with a significant decrease in calf muscle and supra malleolar circumferences at week 4 (p

Lipid peroxidation biomarkers and antioxidant status were measured in 76 cystic fibrosis (CF) patients and compared to 40 control subjects. Univariate and multivariate statistics were performed in this study. Results showed that indicators of lipid peroxidation were higher in CF patients than in controls; thiobarbituric acid reactants and autoantibodies against oxidized low-density lipoproteins were significantly increased in CF patients. Red blood cells and whole blood glutathione peroxidase activities were lower in CF patients than in controls. No difference in red blood cell superoxide dismutase activity was observed. Measured concentration of glutathione peroxidase in plasma showed a higher mean value of this protein in CF patients than in controls. Retinol, alpha-tocopherol and beta-carotene concentrations were all reduced in CF patients as compared to controls; this was particularly pronounced for beta-carotene. The decreased alpha-tocopherol concentration was associated with higher percent hemolysis in CF patients. The results of this study indicate that both lipid peroxidation biomarkers and antioxidant status were disturbed in CF patients, despite medical assistance. Measures of oxidative stress parameters, such as thiobarbituric acid reactants, glutathione peroxidase, and beta-carotene concentrations can be considered as significant indicators to discriminate CF patients and control subjects.

We examined the protein and fat nutritional status of 65 cystic fibrosis patients aged 4-26 y (x +/- SD: 11.2 +/- 5.6 y). Patients were treated with pancreatic enzyme extracts to improve nutrient absorption; in addition, most patients were supplemented with vitamins A and E. Results were compared with those in a control group of 39 subjects aged 5-29 y (x: 14.3 +/- 5.6 y) with no digestive diseases or nutritional deficiencies. Protein determination showed low albumin concentrations in 42% of the cystic fibrosis patients and decreased blood concentrations of retinol binding protein in 12% of the patients. Lipoprotein components were characterized by decreased cholesterol concentrations in 25% of the cystic fibrosis group. Also, mean concentrations of apolipoprotein A-I were significantly lower in the cystic fibrosis group than in control subjects. The results of fatty acid status, expressed in relative (%) and absolute (mg/L) values, showed concentrations of essential fatty acids, represented by linoleic and arachidonic acids, to be significantly decreased in cystic fibrosis patients; this decrease was markedly significant for fatty acid status expressed in absolute values, especially in the cholesteryl ester subfraction. Serum retinol and alpha-tocopherol concentrations were lowered by 8% and 46% in cystic fibrosis patients and control subjects, respectively: retinol, 1.80 +/- 0.50 and 2.37 +/- 0.60 micromol/L, P < 0.001, and alpha-tocopherol, 18.1 +/- 8.7 and 25.7 +/- 5.0 micromol/L, P < 0.001. In conclusion, despite regular treatment with pancreatic enzyme replacements, neither protein nor fat malnutrition in cystic fibrosis patients was completely corrected.

To determine whether significant historical differences distinguish the near-miss for Sudden Infant Death from the infants who died of SIDS, we analysed the histories and clinical data from two groups of infants seen in our University Hospital and from collaborative research group. The data were obtained with the use of a standardised questionnaire and consultation of all available medical data. Sixty-five infants were identified as near-miss for SIDS after they had suffered a severe cardiorespiratory incident during sleep for which no cause could be found despite a complete medical examination. After an autopsy had failed to reveal a cause for the unexpected death 95 cases of SIDS were retained in the study. A series of 353 variables were collected from the parents, the gynaecologists, neonatologists and attending physicians. After statistical analysis, only 15 of the 353 items studied significantly differentiated between the two groups. A step-wise discriminant analysis performed on these items led to the identification of six independent variables: the time of the incident; the circumstances leading to the observation of the child; the child's sleep position; previous minor intestinal problems; the size of the family and the mother's coffee consumption. Most variables indicate that the near-miss infants were discovered and rescued earlier than the infants who died. No other historical information appeared significantly to differentiate between the two groups of infants. These data need confirmation from a prospective epidemiological survey.