The treatment of hepatitis C: history, presence and future

The treatment of chronic hepatitis C has made remarkable progress over the past two decades. For interferon-alpha monotherapy, sustained virological response rates were between 2 and 9% in genotype 1 and between 16 and 23% in genotypes 2 and 3. By adjusting treatment duration up to 48 weeks for genotype 1 and combining regular interferon-alpha with ribavirin, sustained response rates could be improved to 28 to 31% in genotype 1 and around 65% in genotypes 2 and 3. Attempts to further increase efficacy included the addition of amantadine without conclusive evidence up till now. With the recent introduction of long-acting pegylated interferon-alpha in combination with ribavirin, sustained virological response rates of 8o% can be obtained in genotypes 2 and 3. However, sustained virological response rates for patients with either genotype 1, nonresponse to prior treatment, cirrhosis or a combination of these characteristics are still less than 50%. In view of results with daily high-dose interferon-alpha induction in combination with prolongation of treatment duration up to 18 months, such patients might benefit from induction and prolonged PEG-IFN-alpha treatment and should be treated in an experimental setting

Прибыльность предприятия и стратегия ее обеспечения

Целью статьи является системное развитие теоретических, научно-методических и практических положений обеспечения прибыльности предприятия с помощью специально разработанных стратегий, которые направлены на повышение конкурентоспособности и эффективности развития предприятия, обоснование путей улучшения управления прибыльностью предприятий на основе различных исследований

Intrinsic factors associated with medial tibial stress syndrome in athletes: A large case-control study

Background. Medial tibial stress syndrome (MTSS) is the most common lower-leg injury in athletes, and is thought to be caused by bony overload. To prevent MTSS, both pathophysiological and aetiological factors specific to MTSS need to be identified. The intrinsic risk factors that contribute to the development of MTSS are still uncertain.Objective. To determine the intrinsic risk factors of MTSS by sampling a large population of athletic MTSS patients and controls.Methods. Athletes with MTSS and control subjects were medically examined in terms of range of motion of the leg joints (hip abduction, adduction, internal and external range of motion; ankle plantar and dorsal flexion; hallux extension and flexion; subtalar inversion and eversion), measures of over-pronation and maximal calf girth.Results. Ninety-seven subjects agreed to participate in the study: 48 MTSS patients and 49 active controls. The following variables were considered: gender, age, body mass index (BMI), hip abduction, hip adduction, internal and external hip range of rotation, ankle plantar and dorsal flexion, hallux flexion and extension, subtalar inversion and eversion, maximal calf girth, standing foot angle and navicular drop test. In multivariate logistic regression analysis, hip abduction (odds ratio (OR) 0.82; 95% confidence interval (CI) 0.72 - 0.94), ankle plantar flexion (OR 0.73; 95% CI 0.61 - 0.87) and subtalar inversion (OR 1.24; 95% CI 1.10 - 1.41) were significantly associated with MTSS. The Nagelkerke R2 for this model was 0.76, indicating that 76% of the variance in the presence of MTSS could be explained by these variables.Conclusion. Decreased hip abduction, decreased ankle plantar flexion and an increased subtalar inversion could be considered risk factors for MTSS

Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer

Sunitinib has been registered for the treatment of advanced renal cell cancer (RCC). As patient inclusion was highly selective in previous studies, experience with sunitinib in general oncological practice remains to be reported. We determined the efficacy and safety of sunitinib in patients with advanced RCC included in an expanded access programme. ECOG performance status >1, histology other than clear cell and presence of brain metastases were no exclusion criteria. Eighty-two patients were treated: 23% reached a partial response, 50% had stable disease, 20% progressed and six patients were not evaluable. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 15 months. Importantly, 47 patients (57%) needed a dose reduction, 35 (43%) because of treatment-related adverse events, 10 (12%) because of continuous dosing, and two because of both. Stomatitis, fatigue, hand–foot syndrome and a combination of grade 1–2 adverse events were the most frequent reasons for dose reduction. In 40 patients (49%), there was severe toxicity, defined as dose reduction or permanent discontinuation, which was highly correlated with low body surface area, high age and female gender. On the basis of age and gender, a model was developed that could predict the probability of severe toxicity

Symmetry breaking in crossed magnetic and electric fields

We present the first observations of cylindrical symmetry breaking in highly excited diamagnetic hydrogen with a small crossed electric field, and we give a semiclassical interpretation of this effect. As the small perpendicular electric field is added, the recurrence strengths of closed orbits decrease smoothly to a minimum, and revive again. This phenomenon, caused by interference among the electron waves that return to the nucleus, can be computed from the azimuthal dependence of the classical closed orbits.Comment: 4 page REVTeX file including 5 postscript files (using psfig) Accepted for publication in Physical Review Letters. Difference from earlier preprint: we have discovered the cause of the earlier apparent discrepancy between experiment and theory and now achieve excellent agreemen

Recipient IL28B polymorphism is an important independent predictor of posttransplant diabetes mellitus in liver transplant patients with chronic hepatitis C

IL28B polymorphisms are strongly associated with response to treatment for HCV infection. IL28B acts on interferon-stimulated genes via the JAK-STAT pathway, which has been implicated in development of insulin resistance. We investigated whether IL28B polymorphisms are associated with posttransplant diabetes mellitus (DM). Consecutive HCV patients who underwent liver transplantation between 1-1995 and 1-2011 were studied. Genotyping of the polymorphism rs12979860 was performed on DNA collected from donors and recipients. Posttransplant DM was screened for by fasting blood glucoses every 1-3 months. Of 221 included patients, 69 developed posttransplant DM (31%). Twenty-two patients with recipient IL28B genotype TT (48%), 25 with IL28B genotype CT (25%) and 22 with IL28B genotype CC (29%) developed posttransplant DM. TT genotype was statistically significantly associated with posttransplant DM over time (log rank p = 0.012 for TT vs. CT and p = 0.045 for TT vs. CC). Multivariate Cox regression analysis correcting for donor age, body mass index, baseline serum glucose, baseline serum cholesterol, recipient age and treated rejection, showed that recipient IL28B genotype TT was independently associated with posttransplant DM (hazard ratio 2.51; 95% confidence interval 1.17-5.40; p = 0.011). We conclude that the risk of developing posttransplant DM is significantly increased in recipients carrying the TT polymorphism of the IL28B gene. An analysis of liver transplant recipients with hepatitis C virus infection finds that the risk of developing posttransplant diabetes mellitus is significantly increased in recipients carrying the TT polymorphism of the IL28B gene

Bichromatic electromagnetically induced transparency in cold rubidium atoms

In a three-level atomic system coupled by two equal-amplitude laser fields with a frequency separation 2$\delta$, a weak probe field exhibits a multiple-peaked absorption spectrum with a constant peak separation $\delta$. The corresponding probe dispersion exhibits steep normal dispersion near the minimum absorption between the multiple absorption peaks, which leads to simultaneous slow group velocities for probe photons at multiple frequencies separated by $\delta$. We report an experimental study in such a bichromatically coupled three-level $\Lambda$ system in cold $^{87}$Rb atoms. The multiple-peaked probe absorption spectra under various experimental conditions have been observed and compared with the theoretical calculations.Comment: RevTex, 4 pages, 6 figures, Email address: [email protected]