We have analyzed the molecular dynamics of emergence of drug-resistant strains in patients receiving lamivudine therapy for chronic hepatitis B. Twenty consecutive patients with lamivudine resistance were studied ( Major advances in the antiviral treatment of chronic hepatitis B have been made with the development of new antiviral compounds that inhibit the reverse transcriptase activity of hepatitis B virus (HBV). Recently, lamivudine has been approved for the therapy of chronic hepatitis B. Results of clinical trials in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B showed that lamivudine administration was associated with an increased rate of HBV-DNA clearance and antibody to hepatitis B e antigen (anti-HBe) seroconversion together with a significant improvement in liver histology, by comparison with patients who received placebo. [1][2][3][4] In patients infected with a precore mutant associated with an HBeAg-negative chronic hepatitis B, lamivudine therapy for 12 months was also associated with HBV-DNA suppression, normalization of alanine transaminase (ALT) levels, and improvement in liver histology in approximately 60% of patients. 5 In liver transplant recipients with HBV recurrence on the liver graft, lamivudine therapy for 52 weeks allowed suppression of viral replication in 60% of patients. 6 However, in immune competent patients, selection of lamivudine-resistant strains, which may lead to failure of antiviral therapy of chronic hepatitis B, occurs in approximately 16% to 43% of the patients treated for 1 year. 2-5 Selection of drugresistant mutants has also been observed in human immunodeficiency virus (HIV)-HBV coinfected patients treated with lamivudine for their HIV infection 7 and in liver transplant recipients treated with lamivudine for HBV recurrence on the liver graft. 6 Drug resistance is associated with a rise in serum HBV-DNA titers above the detection limit of the assay, which is commonly referred to as phenotypic resistance. In these trials, appearance of viral resistance starts after 6 months of treatment and increases with the duration of treatment. Despite phenotypic resistance, HBV-DNA levels and ALT levels remained lower by comparison with baseline values. In the majority of these patients, lamivudine resistance was not associated with significant clinical or histologic worsening. [2][3][4]6 However, some patients showed clinical deterioration with liver failure, especially in the liver transplantation setting. 6,8 Viral resistance is associated with the selection of major mutations in the YMDD motif within the C domain of the viral reverse transcriptase, and in the conserved B domain. These mutants have been classified in group I with B and C domain Abbreviations: HBV, hepatitis B virus; HBeAg, hepatitis B e antigen; anti-HBe, antibody to hepatitis B e antigen; ALT, alanine transaminase; HIV, human immunodeficiency virus; ULN, upper limit of normal; bDNA, branched DNA; PCR, polymerase chain reaction; HBsAg, hepatitis B surface antigen.From 1 INSERM Unit 2...

Eight different asymptotic models, of which some are entirely new while others are revised versions, are compared with respect to their goodness of fit for the description of the longitudinal growth of stature in 27 healthy children from the French Auxological Survey. Some growth models are based on total age, defined as measured from the time of fertilization, and may be particularly suitable if prenatal data are to be included in the analysis or if prenatal extrapolations are desired. Other models are based on postnatal age (age after birth), and some of these are the most accurate, but they would not be suitable for prenatal data or extrapolations. More general models, such as the polynomial logistic or the triple logistic, can be used but are not the most accurate among those included in the present study. Two new models are proposed which possess an improved goodness of fit. © 1992 Wiley-Liss, Inc.

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 have measured anterior and posterior displacement in 563 normal knees and 487 knees with chronic deficiency of the anterior cruciate ligament (ACL). We performed stress radiography using a simple apparatus which maintained the knee at 20 degrees of flexion while a 9 kg load was applied. There was no significant difference in posterior translation dependent on the condition of the ACL. Measurement of anterior translation in the medial compartment proved to be more reliable than in the lateral compartment for the diagnosis of rupture of the ACL, with better specificity, sensitivity and predictive values. We have classified anterior laxity based on the differential anterior translation of the medial compartment and identified four grades in each of which we can further distinguish four subgrades for laxity of the lateral compartment. Within each of these subgroups, either internal or external rotation may dominate and sometimes there is a major translation of both compartments. Radiological evaluation of displacement of the knee in 20 degrees of flexion provides conclusive evidence of rupture of the ACL. A detailed study of pathological displacement is the basis for a classification of laxity. It is then possible to decide for each type of laxity, the surgical treatment which is specifically adapted to the lesion, and to define a reference value for judging outcome.

W e have measured anterior and posterior displacement in 563 normal knees and 487 knees with chronic deficiency of the anterior cruciate ligament (ACL). We performed stress radiography using a simple apparatus which maintained the knee at 20° of flexion while a 9 kg load was applied. There was no significant difference in posterior translation dependent on the condition of the ACL. Measurement of anterior translation in the medial compartment proved to be more reliable than in the lateral compartment for the diagnosis of rupture of the ACL, with better specificity, sensitivity and predictive values. We have classified anterior laxity based on the differential anterior translation of the medial compartment and identified four grades in each of which we can further distinguish four subgrades for laxity of the lateral compartment. Within each of these subgroups, either internal or external rotation may dominate and sometimes there is a major translation of both compartments. Radiological evaluation of displacement of the knee in 20° of flexion provides conclusive evidence of rupture of the ACL. A detailed study of pathological displacement is the basis for a classification of laxity. It is then possible to decide for each type of laxity, the surgical treatment which is specifically adapted to the lesion, and to define a reference value for judging outcome.

No abstract

Without electronic detection, a large majority of barrier breakdowns would remain undetected by the surgical team and lead to prolonged contact with potentially contaminating body fluids. The use of double gloving provides real protection against such contamination risks.

This longitudinal study analyses the development and predictability of static strength and their interactions with maturation in youth. Of 515 children followed annually from age 6 to 18 years, 59 males and 60 females were measured again at age 35. Early, average, and late maturity groups were established. Body height and mass were assessed. Static strength was measured using handgrip dynamometry. Pearson correlations were used as tracking coefficients. From 6 to 12 years of age, no static strength differences were found to exist between the maturity groups of both sexes. Static strength is significantly higher in early than in average and late maturing boys (age 13-16). In girls, a dose-response effect exists (age 11-14). Adult static strength predictability is low in early maturing boys and late maturing girls. It is moderate to high (50-76%) in the other maturity groups up to age 14. Predictors for adult static strength are childhood and adolescent handgrip dynamometry (in females only), medicine ball throw, sit-up, hockey ball throw, and 25-m sprint. Handgrip is a fair predictor of adult static strength at most ages in early and average maturing females; in average maturing males, it is a predictor at age 11. Other indicators of strength (e.g. hockey ball throw) are predictors in males.