N-acetyl cysteine for prevention of oral mucositis in hematopoietic SCT: a double-blind, randomized, placebo-controlled trial.

Oral mucositis (OM) is a complication of high-dose chemotherapy (HDC) which is frequently observed in hematopoietic SCT settings. Antioxidant agents have been proposed to prevent OM and therefore N-acetyl cysteine (NAC) could have an important role. In the present study, we conducted a double-blind, randomized, placebo-controlled study to evaluate the NAC effect on OM incidence and severity, and also glutathione peroxidase-1 activity. Leukemia patients undergoing allogeneic hematopoietic SCT preceded by HDC were recruited into the study and received either NAC (100 mg/kg/day) (n=38) or placebo (n=42) from the starting day of HDC until day +15 after transplantation. OM was evaluated daily for 21 days after transplantation according to World Health Organization oral toxicity scale. The incidence of severe OM (grades 3-4) was significantly lower in the NAC group (23.7% vs 45.3%, P=0.04). Moreover, the mean duration of OM was significantly shorter in the intervention group (6.24(2.96) vs 8.12(3.97) days, P=0.02). The glutathione peroxidase-1 activity was also significantly higher in the NAC group seven days after transplantation (3.38(2.19) vs 2.41(1.70) ng/mL, P=0.003). It is concluded that parenteral NAC is effective in reducing the incidence of severe cases and the total duration of OM.

The efficacy of selenium in prevention of oral mucositis in patients undergoing hematopoietic SCT: a randomized clinical trial.

Oral mucositis (OM) is a complication of high-dose chemotherapy (HDC) followed by hematopoietic SCT (HSCT) with few effective treatments. Selenium has a cytoprotective role via the glutathione peroxidase (Glu.Px) enzyme and prevents chemotherapy-induced toxicities. We performed a double-blind, randomized, placebo-controlled study to evaluate the efficacy of selenium on the prevention of OM in 77 patients with leukemia, undergoing allogeneic HSCT. Thirty-seven patients received oral selenium tablets (200 mcg twice daily) from the starting day of HDC to 14 days after transplantation. OM was evaluated daily for 21 days after transplantation according to World Health Organization oral toxicity scale. The incidence of severe OM (grades 3-4) was significantly lower in the selenium group (10.8% vs 35.1%, P<0.05). We noted that the duration of objective OM (grades 2-4), excluding patient's self-declaration (grade 1), was significantly shorter in the selenium group (3.6±1.84 vs 5.3±2.2 days, P=0.014). Significant elevations in serum selenium level and plasma Glu.Px activity were observed 7 and 14 days after transplantation compared with baseline in the selenium group. We conclude that selenium can reduce the duration and severity of OM after HDC. Clinicaltrial.org ID: NCT01432873.

Progesterone downregulates oestrogen-induced expression of CFTR and SLC26A6 proteins and mRNA in rats' uteri.

UNLABELLED: Under progesterone (P) dominance, fluid loss assists uterine closure which is associated with pH reduction. We hypothesize that P inhibits uterine fluid secretion and HCO3⁻ transport. AIM: To investigate the expression of Cystic Fibrosis Transmembrane Regulator (CFTR) and Cl⁻/HCO3⁻ exchanger (SLC26A6) under P effect. METHOD: Uteri from ovariectomized steroid replaced and intact rats at different stages of oestrous cycle were analyzed for changes in protein and mRNA expressions. RESULTS: P inhibits CFTR and SLC26A6 proteins and mRNA expression while oestrogen (E) causes vice versa. E treatment followed by P causes a reduction in these transporters' mRNA and protein. Similar changes occur throughout the oestrous cycle; that is, CFTR mRNA expression was high at proestrus while SLC26A6 mRNA and protein expressions were increased at proestrus and estrus. At diestrus, however, the expression of these transporters' protein and mRNA was reduced. CONCLUSION: Inhibition of CFTR and SLC26A6 expressions may explain the reduced fluid volume and pH under P-mediated effect.

Comparison the inflammatory effects of early supplemental parenteral nutrition plus enteral nutrition versus enteral nutrition alone in critically ill patients.

BACKGROUND AND THE PURPOSE OF THE STUDY: It is believed that enteral nutrition (EN) support is the preferred route as compared to parenteral nutrition (PN). Critically ill patients on EN receive less than 60% of their metabolic requirements. To meet patients' calorie goal addition of PN to EN was proposed. This study was conducted to determine whether supplemental PN have any difference with EN alone in regard to inflammatory indices. METHODS: Twenty patients were randomized to either receive EN alone or EN+PN for 7 days. Pre albumin and inflammatory indices including interleukin IL-1, IL-6 and tumor necrosis factor-α (TNF-α) were measured on days of 0, 3,7. Also Sequential Organ Failure Assessment (SOFA) score and Therapeutic Intervention Scoring System-28 (TISS-28) score were calculated on days of 0, 3 and 7. RESULTS AND MAJOR CONCLUSION: IL-1, IL-6 and TNF-α did not show significant difference between two interventions. Pre-albumin was increased from baseline by 9% and 81% in EN and EN+PN groups respectively but it did not reach to statistical significance. SOFA score did not show significant difference. TISS score was higher in EN+PN group on days of 3 and 7. No difference was found between EN and EN+PN regimens in regard to inflammation, while severity of illness may not change with these regimens, nursing workload increases with implementation of supplemental PN.

Estimation of abbreviated mycophenolic acid area under the concentration-time curve during early posttransplant period by limited sampling strategy.

Area under the concentration curve (AUC) of mycophenolic acid (MPA) could help to optimize therapeutic drug monitoring during the early post-renal transplant period. The aim of this study was to develop a limited sampling strategy to estimate an abbreviated MPA AUC within the first month after renal transplantation. In this study we selected 19 patients in the early posttransplant period with normal renal graft function (glomerular filtration rate > 70 mL/min). Plasma MPA concentrations were measured using reverse-phase high-performance liquid chromatography. MPA AUC(0-12h) was calculated using the linear trapezoidal rule. Multiple stepwise regression analysis was used to determine the minimal and convenient time points of MPA levels that could be used to derive model equations best fitted to MPA AUC(0-12h). The regression equation for AUC estimation that gave the best performance was AUC = 14.46 C(10) + 15.547 (r(2) = .882). The validation of the method was performed using the jackknife method. Mean prediction error of this model was not different from zero (P > .05) and had a high root mean square prediction error (8.06). In conclusion, this limited sampling strategy provided an effective approach for therapeutic drug monitoring during the early posttransplant period.

Determination of phenytoin in human plasma by gas chromatography.

A gas chromatographic method for the determination of phenytoin in plasma is described. This assay allows the determination of phenytoin for therapeutic drug monitoring with a minimum detectable limit of 200 ngmL-1 for 500 mL plasma. Separation was performed on 2 m x 2 mm i.d. 1.5% OV17, 1.95 OV210 packed column using a flame-ionization detector. Barbital and tetramethyl ammonium hydroxide were used as internal standard and derivatizing agent, respectively. This method is simple, rapid and suitable for routine analysis of phenytoin in plasma.

Familiality of cancer in Utah.

The Utah Population Database allows examination of the genetic relationships among the 35.7% of all cancer cases in the state that have genealogical records. Familial clustering of cancer is measured by the Genealogical Index of Familiality and is examined by site, and within site by age of onset, histology, and gender. Most cancer sites examined show excess familiality for all cases considered together. Subsets of individuals with certain characteristics showed unusually high levels of familial clustering, specifically lymphocytic leukemias and especially chronic lymphocytic leukemia, lobular breast cancer, early lip cancer, early melanoma, and female lung cancers of alveolar/adenoma histology. These may represent characteristics of the most penetrant forms of inherited susceptibilities, those which are enhanced by environmental factors, chance aggregations, rare inherited syndromes, or a combination of these factors.