Recognition of a novel naturally processed, A2 restricted, HCV-NS4 epitope triggers IFN-gamma release in absence of detectable cytopathicity

Using short term CTL lines derived from HLA A2/K^b transgenic mice and IFN-gamma release assays we demonstrate that the NS4.1769 epitope, is generated from natural processing of the NS4 antigen, and presented in the context of the A2/K^b molecules. Interestingly, T cell recognition of the naturally processed form of the NS4.1769 epitope was associated with significant IFN-gamma release, but no direct cytolytic activity. Epitopes of this phenotype might be of interest, in terms of therapy of chronic HCV infection by associating the benefit of localized lymphokine release with low or absent direct cytopathicity.     

A hypothetical model of the biomechanical interaction of the teeth and the abutment tissues of the jaws during masticatory loading of different values]

Biomechanical model "tooth-jaw" in considered. This biomechanical model takes into account local nonhomogeneous mechanical constructions tooth-jaw, its special geometry, physical properties of firm tissues of tooth, periodontium and jaw. Using mathematical methods, determination of supporting jaw tissues depending by computer tomograms was grounded. The system SPLEN-K has calculated tension-deformed condition of dental tissues in area of a group of chew teeth.     

Possibilities of computerized tomography in the diagnosis of gastric tumors

On basis of experience in computed tomography (CT) of the stomach in 76 individuals, in 44 of whom gastric tumors were diagnosed, the possibilities of this method in the recognition of this pathological condition are discussed. The authors discuss in detail their own method of CT of the stomach, which combines elements of the classical gastroroentgenology and the specific features of CT characteristic of it as an independent method. The method is based on fractional contrasting of the gastric lumen by introducing air through a nasogastric catheter. It practically excludes the possibility of diagnostic errors associated with visualization of "pseudothickenings" of the gastric wall, and thus removes the main limiting factor of using CT in the diagnosis of gastric tumors. Appraising quite highly the CT potential in neoplastic diseases of the stomach, the authors emphasize that the method must be used in complex with the existing traditional means of examination of the stomach.     

Substitute Consent for Research Involving the Elderly: A Comparison Between Quebec and France

The authors first describe the rules enacted in Quebec and France to protect adults with decisional impairment who may be approached by investigators to participate in research protocols. They then present two consecutive postal surveys conducted among Quebec and French researchers in aging and designed to (1) assess their knowledge of the legal provisions implemented to protect decisionally incapable adults, (2) elicit their opinions regarding the person best suited to provide substitute consent for research participation, and (3) document their conduct related to obtaining consent for prospective subjects with impaired decisional capacity. Knowledge of the legislation governing substitute consent was poor, even more so among French than Quebec researchers (p < 0.001). In both samples, the majority of respondents felt that the substitute decision-maker does not have to be legally appointed when the study poses little risk to the participant. Practice data revealed a certain discrepancy between the conduct of researchers in aging and the legal provisions regarding consent for research purposes that prevail in their jurisdictions. These findings underscore the need to better educate clinical investigators about existing measures to protect prospective subjects who lack decisional capacity. They also provide some support for allowing close relatives to consent to research participation on behalf of older adults who are unable to consent by themselves and have not been appointed a legal representative.     

Inhibitory effects of Serenoa repens on the kinetic of pig prostatic microsomal 5α-reductase activity

The pathogenesis of benign prostatic hyperplasia is linked to the accumulation of dihydrotestosterone (DHT), the active form of testosterone (T), in prostatic tissue. We have defined characteristics of 5α-reductase enzyme which catalyzes the conversion of T into DHT in prostatic microsomes of growing pigs. Peaks for the 5α-reductase activity were found at pH 5.5 and 8.0, which indicates the presence of both type 1 and type 2 isozymes. Kinetic parameters of porcine 5α-reductase in the presence of Serenoa repens extracts revealed uncompetitive, noncompetitive, and mixed types of inhibitions. Our results show the inhibitory action of S. repens on prostate porcine microsomal 5α-reductase activity.     

A pilot study of 220 mg/m2 melphalan followed by autologous stem cell transplantation in patients with advanced haematological malignancies: pharmacokinetics and toxicity

We studied the pharmacokinetics and toxicity of 220 mg/m² melphalan (HDM 220) followed by autologous stem cell transplantation in 16 patients with advanced haematological malignancies. Pharmacokinetic parameters (mean values of steady-state volume of distribution 14.6 l/m², total body clearance 313 ml/min/m², elimination half-life 46 min) were the same as those of 140 or 200 mg/m² melphalan in previous reports. HDM 220 was feasible. Extramedullary toxicity was mainly W.H.O. grade 4 mucositis (13/16 patients). The median duration of 41 d (10, not reached) of thrombocytopenia <25 × 10⁹/l was long. In multiple myeloma the response rate was 89% in heavily pretreated patients, suggesting that HDM 220 could be considered earlier in the course of the disease as an alternative consolidation therapy.     

Measuring pressure-derived fractional flow reserve through four French diagnostic catheters

Measurement of fractional flow reserve (FFR) with a pressure wire is used to discriminate between patients with and without functionally significant lesions. FFR can be assessed through a conventional 4Fr diagnostic catheter, which is a more convenient method of assessment. The aim of this study was to assess the feasibility, safety, repeatability, and reliability of routine FFR measurements through 4Fr diagnostic catheters. From a single-center prospective registry, results of FFR assessment through a 4Fr catheter were used to determine: (1) feasibility and safety, by the procedural success rate and immediate and 30-day clinical outcome; (2) repeatability, by the intraclass correlation coefficient and comparison of the difference (means +/- 2 SDs); and (3) reliability, by comparison of results obtained using 4Fr versus 7Fr guiding catheters. During the study period, FFR was measured in 190 patients, in 122 using a diagnostic 4Fr catheter (study population) and in 68 using a 7Fr guiding catheter. Measurement of FFR wa successful in 115 of 122 patients (94%). No complications related to the use of the 4Fr catheter occurred. Repeatability was determined from 108 repeated measurements: the intraclass correlation coefficient was 0.942 and the mean difference between repeated FFR measurements was -0.001 +/- 0.038. Reliability was determined from 15 unselected patients; there was no systematic error and only 1 value was out of the range of 2 SDs of the mean difference. Using a threshold value of 0.75, the Kappa coefficient for the qualitative agreement was 0.84. Thus, pressure-derived FFR assessment can safely be performed through 4Fr diagnostic catheters, with similar repeatability and reliability as 7Fr guiding catheters, resulting in a simplification of the measurement procedure.