Long-term efficacy of (90)Y ibritumomab tiuxetan therapy in follicular non-Hodgkin lymphoma and health-related quality of life.

The aim of this study was to analyze the outcomes of 37 follicular lymphoma (FL) patients treated with (90)ytrium ibritumomab tiuxetan (90Y-IT), outside of clinical trial, according to protocol ISCRTN36210045, after ≥5 years follow-up to February 2014. Health-related quality of life (HRQoL) was evaluated with the SF-36, Spanish version, and compared with the general population of Spain. Patients had a mean age of 61.9 (range, 30-85) years and included 18 males. FLIPI, low: 25 (67.6 %), intermedium 9 (24.3 %), and low 3 (8.1 %). Previous therapy schedules >2: 48.6 % The median follow-up was 66 months, mean Time to Relapse (TTR) 71.3 months (58.8-83.8) median not reached. Thirty-four patients achieved complete response (91.8 %), and three no response. Mean overall survival: 82.3 months (71.6-92.9). Four patients presented with concomitant tumors (colon, breast, prostate, lung) after radioimmunotherapy, and three developed second primary neoplasms (esophagus, renal, and myelodysplastic syndrome in a relapsed patient who received fludarabine). Four of 10 deaths were related to lymphoma progression. Hematological toxicities were mild and easily managed. No patients required hospitalization. Negative scores were obtained in the physical and emotional roles items; however, the perception of general health and vitality were better than in the general population, with the best outcomes in non-relapsed patients. Radioimmunotherapy with 90Y-IT was safe and effective as long-term therapy in patients with FL. Early use of radioimmunotherapy could offer good, sustained responses with low toxicity over the long term and acceptable HRQoL.

RIT with Y90-Ibritumomab Tiuxetan in Follicular Non-Hodgkin Lymphoma: Evaluation of Recent Outcomes in a Single Institution.

Background. Based on historical data we reviewed our hospital clinical database to analyse our updated information and therapy outcomes of follicular non-Hodgkin lymphoma (F-NHL) patients treated with (90)Y-Ibritumomab tiuxetan. Patients and Methods. Between 2005 and 2011, 56 F-NHL patients were included in a clinical protocol conducted by a multidisciplinary team and treated in the same centre. All patients received 0.3 or 0.4 mCi/kg IV (88%) of (90)Y-IT; response evaluation was performed 12 weeks after. Results. M/F 44.6%/55.4%, mean age 61.45 years (30-85); ECOG 0-1 96.9%. According to FLIPI score, distribution were good: 58.5%, intermediate: 29.2%, and poor: 12.3%. Previous therapies: >2: 40% (26). ORR was 94.6% (53/56). CR: 85.7%; CR according to previous disease: relapsed disease: 90% (27/30), refractory disease: 42.85% (3/7), consolidation with CR: 92.85% (13/14), and consolidation with PR: 100% (5/5). Global PR and NR were 8.9% (5) and 5.3% (3), respectively. Mean OS 63.86 months with a mean follow-up time of 57 months (2-73). Mean TTP: 52.65 months (95% CI: 43.83-61.48). Median OS and TTP were not achieved. No hospital submissions or deaths were registered. Conclusions. This study confirms the safety and high efficacy of (90)Y-IT in F-NHL patients, RIT in early stage of disease could improve outcomes.

Effect of age on cytokine response in an experimental model of osteomyelitis.

To study the effect of age on cytokine response in an experimental model of osteomyelitis. Forty adult male Wistar rats received a stainless steel needle, intramedullarly in the left tibia. Young rats (3 months old) and old rats (22 months old) were allotted in: Group A: Sterile implant. Group B: Sterile implant + slime producing S. aureus. Rats were sacrificed 9 weeks after surgery. Determinations: Cytokines (ELISA) in blood and in tibia extract and the number of bacteria in tibia and implant. The Wilcoxon, Mann-Whitney U tests were used (P < or = 0.01 significant). Infection was detected in every old rat receiving S. aureus, and in 7 of 10 young rats. In blood: prior to surgery, old rats presented higher IL-2 and lower IL-4 levels. Surgery alone did not induce significant changes in old rats; surgery + S. aureus induced significant increases of IL-2 and IL-10 in young rats, and of IL-6 in old rats. Tibia analysis S. aureus group showed increased levels of: IL-10 in young rats, and IL-1beta in old rats. In experimentally induced osteomyelitis, significant differences were observed in cytokine response with regard to age.

Influence of platelet time activation on articular cartilage growth in the rabbit knee: preliminary study.

PURPOSE: The aim of the present article was to study the influence of platelets and different time activation on cartilage growth in articular defects in the rabbit knee. METHODS: Twelve male New Zealand rabbits (12 weeks) were divided in two groups. Under general anaesthesia, a 4 mm diameter and 2 mm deep defect was performed in medial condyles in both knees. The right knee defect was filled with platelet concentrate 5 min after being activated with ClCa in group A, and 2 min afterwards in group B. Platelets were obtained by centrifuging 10 ml arterial blood from the rabbit prior to the surgical procedure. The left knee defect was not filled. Rabbits were sacrificed 6 weeks after surgery. Macroscopic and microscopic studies were performed. RESULTS: In group A, hyaline cartilage was observed in the right knee defect at the end of the experiment in five rabbits. None of the defects of the left knees showed hyaline cartilage growth. In group B, hyaline cartilage was observed in the right knee defect in only one rabbit. Nevertheless, in group B, all rabbits presented better chondral cellularity and regeneration and lower fibrosis in defects treated with platelets than in non-treated ones. CONCLUSIONS: This technique for articular defect reconstruction with platelets is simple and easy, and has shown satisfactory results in our study. Platelets may be useful as an autologous source of multiple growth factors for articular defect reconstruction. Nevertheless, this is a preliminary study and further research is required.

Interleukin-1, interleukin-6, and interleukin-10 responses after antibiotic treatment in experimental chronic Staphylococcus aureus osteomyelitis.

BACKGROUND: Staphylococcal implant infections' response to treatment may be correlated with cytokine production. We investigated the effect of certain antibiotics on the cytokine response in experimental osteomyelitis. METHODS: A stainless steel needle with an adherent slime-producing Staphylococcus aureus was implanted intramedullarly in the left tibia of 40 adult male Wistar rats. At 42 days after implantation, cefuroxime, vancomycin, tobramycin, and ciprofloxacin were administered intramuscularly every 12 h for 21 days. The control group was given no antibiotic. At the end of the treatment, implants and tibias were retrieved, and the bacterial numbers were estimated. Cytokines [interleukin-1alpha (IL-1alpha), IL-6, and IL-10] were determined (ELISA) in the tibial extract. RESULTS: Vancomycin and cefuroxime inhibited bone colonization in all tibias, and tobramycin and ciprofloxacin inhibited it only partially. Cefuroxime reduced the number of bacteria that adhered to the implants more than the other antibiotics. IL-1alpha and IL-6 showed higher levels in the ciprofloxacin-treated group than in the cefuroxime-treated and control groups. IL-6 levels in rats treated with cefuroxime were lower than in rats treated with tobramycin or vancomycin and the control group. Cefuroxime decreased IL-10 levels more than ciprofloxacin or vancomycin or those seen in the control group. CONCLUSIONS: The cefuroxime group showed the greatest decrease of pro-inflammatory cytokines. Different antibiotics produce different cytokine reactions that should be studied to choose the best treatment.

[Polymorphisms in cystathionine beta-synthase and methylenetetrahydrofolate reductase genes as risk factors for cerebral vascular disease]. / Polimorfismos en los genes cistationina beta-sintasa y metilentetrahidrofolato reductasa como factores de riesgo de enfermedad vascular cerebral.

BACKGROUND AND OBJECTIVE: High plasma total homocysteine (tHcy), low dietary intake of folate and other B vitamins, and genetic polymorphisms related to the metabolism of homocysteine may interactively contribute to the risk of cerebral vascular disease (CVD). We explored interrelations between total homocysteine levels and mutations in genes for the two key enzymes in methionine-homocysteine metabolism. PATIENTS AND METHOD: We analyzed two polymorphisms, C677T in the MTHFR gene and 844ins68 in the CBS gene. We assessed their association with fasting homocysteine in 64 patients with CVD, and in 159 controls. RESULTS: No differences in CBS and MTHFR genotype frequencies between cases and controls were found (C677T p = 0.87 and 844ins68 p = 0.63), nor was a particular CBS and MTHFR genotype associated with an elevated risk of CVD. None of the genotypes defined by the CBS and MTHFR variants studied showed an association with elevated fasting homocysteine concentrations (C677T p = 0.07 and 844ins68 p = 0.47). CONCLUSIONS: We did not find any indication that genetic variation in the CBS and MTHFR genes are associated with homocysteine-related risk of CVD, hence needing further investigation. The contributions to total plasma homocysteine levels of the common mutations of genes coding for the enzymes controlling homocysteine metabolism are modest.

Polimorfismos en los genes cistationina â -sintasa y metilentetrahidrofolato reductasa como factores de riesgo de enfermedad vascular cerebral / Polymorphisms in cystathionine â -synthase and methylenetetrahydrofolate reductase genes as risk factors for cerebral vascular disease

FUNDAMENTO Y OBJETIVO: La interacción entre altas concentraciones de homocisteína plasmática, baja ingesta de folato y otras vitaminas B, y la presencia de polimorfismos en genes relacionados con el metabolismo de la homocisteína, puede aumentar el riesgo de padecer una enfermedad cerebrovascular (ECV). Se ha estudiado la interrelación entre la concentración de homocisteína y la presencia de mutaciones en dos genes relacionados con el metabolismo metionina homocisteína. PACIENTES Y MÉTODO: Se han analizado dos polimorfismos, C677T en el gen MTHFR y 844ins68 en el gen CBS, en 64 pacientes con ECV y 159 controles sanos, estableciendo su posible asociación con la homocisteína total. RESULTADOS: No se han encontrado diferencias en las frecuencias enotipificadas de los genes CBS y MTHFR entre casos y controles (C677T, p = 0,87, y 844ins68, p = 0,63). Ningún genotipo estuvo asociado con un mayor riesgo de ECV. Tampoco se pudo establecer su asociación con un aumento de la concentración de homocisteína total (C677T, p = 0,07, y 844ins68, p = 0,47). CONCLUSIONES: No se ha observado ningún indicio de asociación entre las variables genotipificadas en los genes CBS y MTHFR y la concentración de homocisteína que supongan un aumento del riesgo de ECV. La contribución de estas mutaciones al incremento de la concentración de homocisteína es modesto

BACKGROUND AND OBJECTIVE: High plasma total homocysteine (tHcy), low dietary intake of folate and other B vitamins, and genetic polymorphisms related to the metabolism of homocysteine may interactively contribute to the risk of cerebral vascular disease (CVD). We explored interrelations between total homocysteine levels and mutations in genes for the two key enzymes in methionine-homocysteine metabolism. PATIENTS AND METHOD: We analyzed two polymorphisms, C677T in the MTHFR gene and 844ins68 in the CBS gene. We assessed their association with fasting homocysteine in 64 patients with CVD, and in 159 controls. RESULTS: No differences in CBS and MTHFR genotype frequencies between cases and controls were found (C677T p = 0.87 and 844ins68 p = 0.63), nor was a particular CBS and MTHFR genotype associated with an elevated risk of CVD. None of the genotypes defined by the CBS and MTHFR variants studied showed an association with elevated fasting homocysteine concentrations (C677T p = 0.07 and 844ins68 p = 0.47).CONCLUSIONS: We did not find any indication that genetic variation in the CBS and MTHFR genes are associated with homocysteine related risk of CVD, hence needing further investigation. The contributions to total plasma homocysteine levels of the common mutations of genes coding for the enzymes controlling homocysteine metabolism are modest