Rituximab for follicular lymphoma

Treatment with the chimeric anti-CD20 antibody rituximab has been rapidly accepted into the clinical treatment of patients with CD20 positive lymphoma. The low toxicity profile, relative ease of administration, and encouraging response rates observed as a single agent allow it to be used alone or in combination with or following standard chemotherapies. Patients with follicular non-Hodgkin's lymphoma (NHL) have a high response rate to treatment with this new modality, with overall response rates of 50% to 60% in the relapsed setting and 70% in the initial setting. The addition of scheduled retreatment or maintenance therapy leads to improved clinical responses and delays time to progression. Combination trials with chemotherapy demonstrate feasibility and promising response rates including clearing of minimal residual disease detected using molecular techniques. To date, there are limited randomized clinical trial data available to guide the use of this new modality in this patient population and few long-term results. It remains difficult to determine when and how to use this new modality best in the overall treatment course of these patients. This paper discusses the rationale for the use of rituximab in patients with follicular NHL and discusses the available data involving dosing, schedule, timing, and combinations with chemotherapy.     

New Directions in Intracardiac Echocardiography

Introduction: Pulmonary vein (PV) isolation (PVI) has been recently proposed as an effective technique to cure atrial fibrillation (AF).Aims of the Study: The aim of this study was to investigate the efficacy of a novel technique utilizing a computerized three-dimensional mapping system (QMS2^TM) with a multielectrode basket catheter (MBC) for PVI and to reveal the relation between the style of breakthrough and the network of the PV musculature.Methods: Sixty-five consecutive patients with frequent AF attacks underwent PV mapping with a 31-mm MBC, and a three-dimensional color animation of the potential map was constructed by the QMS2^TM. The animation color schema was arranged to minimize the low-amplitude left atrial (LA) potentials and emphasize the high-amplitude PV potentials (PVPs). The longitudinal PVP map enabled us to recognize the true breakthroughs and reveal the network of the PV musculature.Results: A total of 205 PVs (65 left superior PVs, 65 right superior PVs, 57 left inferior PVs and 18 right inferior PVs) were mapped and successful PVI was achieved in all PVs, except one that had no PVPs, with a mean radiofrequency duration of 7 ± 5 minutes per PV. In about 90% of the PVs, a final radiofrequency application eliminated all the distal PVPs simultaneously because the PVI was performed at the appropriate LA-PV junction. A single segmental breakthrough was detected in 17 PVs, single broad breakthrough in 83 PVs, multiple separate breakthroughs with a distal connection between the PV musculatures extending from each separate breakthrough in 88 PVs and multiple separate breakthroughs without that connection in 16 PVs. During the follow-up period, fifty-one (78%) patients were free of symptomatic AF without any antiarrhythmic drugs after multiple procedures (thirty-three (51%) of those patients after the first procedure) and no PV stenosis was found.Conclusions: Computerized three-dimensional potential mapping can be useful for PVI because it can not only identify the true breakthrough, but can also confirm the elimination of the breakthroughs by the change in the activation sequence through the network of the PV musculature.There was no financial support for this study.     

Indirect recognition of allopeptides promotes the development of cardiac allograft vasculopathy

Graft loss from chronic rejection has become the major obstacle to the long-term success of whole organ transplantation. In cardiac allografts, chronic rejection is manifested as a diffuse and accelerated form of arteriosclerosis, termed cardiac allograft vasculopathy. It has been suggested that T-cell recognition of processed alloantigens (allopeptides) presented by recipient antigen-presenting cells through the indirect pathway of allorecognition plays a critical role in the development and progression of chronic rejection. However, definitive preclinical evidence to support this hypothesis is lacking. To examine the role of indirect allorecognition in a clinically relevant large animal model of cardiac allograft vasculopathy, we immunized MHC inbred miniature swine with synthetic polymorphic peptides spanning the alpha(1) domain of an allogeneic donor-derived swine leukocyte antigen class I gene. Pigs immunized with swine leukocyte antigen class I allopeptides showed in vitro proliferative responses and in vivo delayed-type hypersensitivity responses to the allogeneic peptides. Donor MHC class I disparate hearts transplanted into peptide-immunized cyclosporine-treated pigs not only rejected faster than unimmunized cyclosporine-treated controls (mean survival time = 5.5 +/-1.7 vs. 54.7 +/-3.8 days, P < 0.001), but they also developed obstructive fibroproliferative coronary artery lesions much earlier than unimmunized controls (<9 vs. >30 days). These results definitively link indirect allorecognition and cardiac allograft vasculopathy.     

Alcohol Drinking Among the Students of the University of Maribor,Slovenia

Background

Hazardous and harmful alcohol drinking is an important health, social and economic issue in Slovenia amongst all age groups. While drinking in Slovenia has been well researched amongst elementary and high school students, there is a lack of research on drinking amongst university students.

Methods

We conducted a cross-sectional study among first- and fourth-year students of the University of Maribor, Slovenia, attending the mandatory preventive health check between October 2009 and May 2010. During this health check, they filled in a non-anonymous lifestyle questionnaire. AUDIT–C questionnaire on alcohol use and questions on smoking and illicit drug use were also included.

Results

3.130 students were included in the analysis, 1219 (38.9%) were males. There were 871 (27.8%) students that were screened as risky drinkers. The highest percentage of risky drinkers attended the Faculty for Wood Technology and the lowest the Faculty for Health Sciences. Students, recognized as healthier by the physicians, reported risky drinking significantly less often (p=0.015). Students with higher BMI reported risky drinking significantly more often (p=0.012). Variables, proved to be independently associated with the risky drinking in the multivariate analysis, were: bad health status (p=0.044), male sex (p<0.001), daily consumption of fried food (p=0.017), smoking (p<0.001), illicit drugs (p<0.001), attending the Faculty for Civil Engineering (p=0.006), not attending the Faculty for Health Sciences (p=0.002)

Conclusions

While the prevalence of risky drinking among students in this study is high, a structured preventive programme should be implemented for students, which will include also illicit drug use and smoking.     

Significance of cannabis use to dental practice

The illicit use of the three main forms of cannabis--marijuana, hash, hash oil--pose certain obstacles and challenges to the dental professional. There are a number of systemic, as well as oral/head and neck manifestations, associated with cannabis use. Dentists need to be aware of these manifestations in order to take whatever precautions and/or modifications to the proposed treatment that might be necessary.     

Prevention of ulceration, amputation, and reduction of hospitalization: outcomes of a prospective multicenter trial of tibial neurolysis in patients with diabetic neuropathy

This is the first multicenter prospective study of outcomes of tibial neurolysis in diabetics with neuropathy and chronic compression of the tibial nerve in the tarsal tunnels. A total of 38 surgeons enrolled 628 patients using the same technique for diagnosis of compression, neurolysis of four medial ankle tunnels, and objective outcomes: ulceration, amputation, and hospitalization for foot infection. Contralateral limb tibial neurolysis occurred in 211 patients for a total of 839 operated limbs. Kaplan-Meier proportional hazards were used for analysis. New ulcerations occurred in 2 (0.2%) of 782 patients with no previous ulceration history, recurrent ulcerations in 2 (3.8%) of 57 patients with a previous ulcer history, and amputations in 1 (0.2%) of 839 at risk limbs. Admission to the hospital for foot infections was 0.6%. In patients with diabetic neuropathy and chronic tibial nerve compression, neurolysis can result in prevention of ulceration and amputation, and decrease in hospitalization for foot infection.     

High cell density attenuates reactive oxygen species: implications for in vitro assays

In vitro cell-based assays are an essential and universally used step in elucidation of biological processes as well as in drug development. However, results obtained depend on the validity of protocols used. This statement certainly pertains to in vitro assays of oxidative stress. The holy grail of in vitro models is reliability and predictability of outcomes that relate to a single variable like addition of hydrogen peroxide or xanthine oxidase. Without such validated outcomes, comparison of results among different laboratories is not possible. Achieving this goal requires a thorough understanding of the complex interplay between the cells, their environment, and the experimental assays. Furthermore, as this knowledge is attained, it must be disseminated and used to update and standardize existing protocols. Here, we confirm and extend the effect of pyruvate and cell density on in vitro oxidative stress assays. Cell viability was assessed using a colorimetric assay measuring the reduction of a tetrazolium salt (XTT) into a colored formazan dye. Extracellular hydrogen peroxide concentrations were measured using the foxp3 assay. We confirmed a previously reported finding that pyruvate, a common ingredient in cell culture media, acts as an extracellular scavenger of reactive oxygen species. We also demonstrated that cell density directly correlates with resistance to oxidative stress in tissue culture. It is theorized that the protective effect due to cell density predominantly relates to intracellular factors such as reduced glutathione and extracellular factors such as catalase.