The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up.

A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at alpha = 0.05 level (P-value \u3c0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for \u3c5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality

Effect of thymol on microbial diversity in the porcine jejunum

Thirty two weaned pigs (24 d-old) were fed a diet without or with 1 % (w/w) thymol. Pigs from each dietary treatment remained unchallenged or were challenged with Salmonella enterica serovar typhimurium. Jejunal content was collected and molecular microbial diversity was investigated using 16S rRNA gene polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Shannon index analysis showed no differences in diversity but Pearson coefficient analysis showed clear clustering of profiles, which delineated thymol fed and control groups irrespective of Salmonella challenge. Moreover, absence of bands corresponding to Actinobacillus minor (98-99 % identity) was observed in thymol groups. A band corresponding to Citrobacter freundii (98 % identity) was observed in almost all pigs from thymol groups, and only in 4 samples from pigs fed no thymol in the diet. Supplementation of pig diet with thymol caused clear changes in small intestine microbacterial community. Surprisingly, Salmonella infection caused no major perturbations to the community structure

Investigations on the Effects of Dietary Essential Oils and Different Husbandry Conditions on the Gut Ecology in Piglets after Weaning

Essential oils (EO) are being considered as possible alternatives to in-feed antibiotic growth promoters in pig nutrition. The effects of an EO mixture consisting of limonene, eugenol and pinene (10.0, 2.0, and 4.8 mg/kg diet, resp.) on gut physiology and ecology were studied in piglets. The experiment was conducted at low (commercial farm) and high hygienic conditions (experimental farm), to elucidate interactions between EO supplementation and husbandry methods. Piglets were weaned at 28 days of age, when they were offered either a control diet (C) or C with EO. Four piglets were sacrificed in each group on day 29, 30, 33 and 39. Digesta from the third distal part of the small intestine and from the colon were sampled and analysed for pH, dry matter, lactic acid, short chain fatty acids and ammonia concentrations. Enterobacteria, enterococci, lactobacilli and yeast counts were obtained by plating. Genomic DNA was extracted from digesta and polymerase chain reaction—denaturing gradient gel electrophoresis was performed. Individual microbial communities were identified at each farm. Age affected the intestinal parameters. No effects of the EO with exception for a significant reduction in colon bacterial diversity at 39 days of age could be recorded at experimental farm

Effect Of Barley Fibres And Barley Intake On The Ileal Endogenous Nitrogen Losses In Piglets

Ileal endogenous N losses (ENL) were measured, using the 15N isotope dilution technique, in piglets (17 kg) fed different barley genotypes (naked, spring, winter with low/high beta-glucan content) or diets containing 330, 530, 730 or 930 g of a blend of barleys/kg diet. The apparent protein and amino acid digestibilities of the naked variety and the winter variety with a high beta-glucan content were, on average, significantly higher than those for the other two varieties. The ENL were inversely correlated (p0·05). The ENL increased linearly with the inclusion level of barley in a N-free basal diet (2 mg endogenous N/g barley). Isolated hulls added to a N-free diet at the rate of 100 or 200 g/ kg diet exerted no significant effect on the ENL (1·80 g endogenous N/kg diet in both cases vs. 1·76 g for the basal level). On the contrary, the effect of isolated bran, measured under similar conditions, was significantly higher and dependent on fibre intake (2·59 and 3·31 g N/kg diet, respectively). It is concluded that the ENL are affected by the insoluble bran fibre but not by the hulls, nor by the level of beta-glucan