A randomized placebo controlled trial of preoperative carbohydrate drinks and early postoperative nutritional supplement drinks in colorectal surgery.

AIM: There is evidence that preoperative carbohydrate drinks and postoperative nutritional supplements improve the outcome of colorectal surgery. There is little information on their individual contribution. METHOD: A prospective four-arm double-blind controlled trial was carried out in which patients were randomized to carbohydrate or placebo drinks preoperatively and a polymeric supplement or placebo drink postoperatively. The primary outcome was insulin resistance (using the short insulin tolerance test and HOMA-IR). Secondary outcomes included handgrip strength, pulmonary function, intestinal permeability and postoperative complications. RESULTS: A total of 120 patients were randomized to four demographically well matched groups. Patients who received preoperative and postoperative supplements had better glucose homeostasis (P = 0.004), peak expiratory flow rate (P = 0.035), handgrip strength (P = 0.002) and less insulin resistance (P = 0.001) compared with those who only received placebo drinks. CONCLUSION: Oral nutritional supplements given preoperatively and postoperatively improve postoperative handgrip strength, pulmonary function and insulin resistance. A weaker effect was seen in patients who received supplements either preoperatively or postoperatively. Oral nutritional supplements should be given both preoperatively and postoperatively.

Pre-operative oral iron supplementation reduces blood transfusion in colorectal surgery - a prospective, randomised, controlled trial.

INTRODUCTION: Allogeneic blood transfusion confers a risk to the recipient. Recent trials in colorectal surgery have shown that the most significant factors predicting blood transfusion are pre-operative haemoglobin, operative blood loss and presence of a transfusion protocol. We report a randomised, controlled trial of oral ferrous sulphate 200 mg TDS for 2 weeks' pre-operatively versus no iron therapy. PATIENTS AND METHODS: Patients diagnosed with colorectal cancer were recruited from out-patient clinic and haematological parameters assessed. Randomisation was co-ordinated via a telephone randomisation centre. RESULTS: Of the 49 patients recruited, 45 underwent colorectal resection. There were no differences between those patients not receiving iron (n = 23) and the iron-supplemented group (n = 22) for haemoglobin at recruitment, operative blood loss, operation duration or length of hospital stay. At admission to hospital, the iron-supplemented group had a higher haemoglobin than the non-iron treated group (mean haemoglobin concentration 13.1 g/dl [range, 9.6-17 g/dl] versus 11.8 g/dl [range, 7.8-14.7 g/dl]; P = 0.040; 95% CI 0.26-0.97) and were less likely to require operative blood transfusion (mean 0 U [range, 0-4 U] versus 2 U [range, 0-11 U] transfused; P = 0.031; 95% CI 0.13-2.59). This represented a cost reduction of 66% (47 U of blood = pound4700 versus oral FeSO(4) at pound30 + 15 U blood at pound1500). At admission, ferritin in the iron-treated group had risen significantly from 40 microg/l (range, 15-222 microg/l) to 73 microg/l (range, 27-386 microg/l; P = 0.0036; 95% CI 46.53-10.57). CONCLUSIONS: Oral ferrous sulphate given pre-operatively in patients undergoing colorectal surgery offers a simple, inexpensive method of reducing blood transfusions.

Genetics of the DST-mediated mRNA decay pathway using a transgene-based selection.

mRNA sequences that control abundance, localization and translation initiation have been identified, yet the factors that recognize these sequences are largely unknown. In this report, a transgene-based strategy designed to isolate mutants of Arabidopsis thaliana that fail to recognize these sequences is described. In this strategy, a selectable gene and a screenable marker gene are put under the control of the sequence element being analysed and mutants are selected with altered abundance of the corresponding marker RNAs. The selection of mutants deficient in recognition of the DST (downstream) mRNA degradation signal is used as a test-case to illustrate some of the technical aspects that have facilitated success. Using this strategy, we report the isolation of a new mutant, dst3, deficient in the DST-mediated mRNA decay pathway. The targeted genetic strategy described circumvents certain technical limitations of biochemical approaches. Hence, it provides a means to investigate a variety of other mechanisms responsible for post-transcriptional regulation.

New molecular phenotypes in the dst mutants of Arabidopsis revealed by DNA microarray analysis.

In this study, DNA microarray analysis was used to expand our understanding of the dst1 mutant of Arabidopsis. The dst (downstream) mutants were isolated originally as specifically increasing the steady state level and the half-life of DST-containing transcripts. As such, txhey offer a unique opportunity to study rapid sequence-specific mRNA decay pathways in eukaryotes. These mutants show a threefold to fourfold increase in mRNA abundance for two transgenes and an endogenous gene, all containing DST elements, when examined by RNA gel blot analysis; however, they show no visible aberrant phenotype. Here, we use DNA microarrays to identify genes with altered expression levels in dst1 compared with the parental plants. In addition to verifying the increase in the transgene mRNA levels, which were used to isolate these mutants, we were able to identify new genes with altered mRNA abundance in dst1. RNA gel blot analysis confirmed the microarray data for all genes tested and also was used to catalog the first molecular differences in gene expression between the dst1 and dst2 mutants. These differences revealed previously unknown molecular phenotypes for the dst mutants that will be helpful in future analyses. Cluster analysis of genes altered in dst1 revealed new coexpression patterns that prompt new hypotheses regarding the nature of the dst1 mutation and a possible role of the DST-mediated mRNA decay pathway in plants.

Mutants of Arabidopsis defective in a sequence-specific mRNA degradation pathway.

One of the ways a cell can rapidly and tightly regulate gene expression is to target specific mRNAs for rapid decay. A number of mRNA instability sequences that mediate rapid mRNA decay have been identified, particularly from multicellular eukaryotes, but pinpointing the cellular components that play critical roles in sequence-specific decay in vivo has been more difficult. In contrast, general pathways of mRNA degradation in yeast have been well established through the analysis of mutants affecting the general mRNA decay machinery. Strategies to isolate mutants in sequence-specific mRNA decay pathways, although extremely limited so far, have the potential to be just as powerful. In the study reported here, a selection in transgenic plants allowed the isolation of rare mutants of Arabidopsis thaliana that elevate the abundance of mRNAs that contain the plant mRNA instability sequence called DST (downstream element). This instability sequence is highly conserved in unstable small auxin up RNA (SAUR) transcripts. Genetic analysis of two dst mutants isolated via this selection showed that they are incompletely dominant and represent two independent loci. In addition to affecting DST-containing transgene mRNAs, mutations at both loci increased the abundance of the endogenous DST-containing SAUR-AC1 mRNA, but not controls lacking DST sequences. That these phenotypes are caused by deficiencies in DST-mediated mRNA decay was supported by mRNA stability measurements in transgenic plants. Isolation of the dst mutants provides a means to study sequence-specific mRNA degradation in vivo and establishes a method to isolate similar mutants from other organisms.

Glucose and memory: fractionation of enhancement effects?

Recent research findings indicate that glucose administration enhances some aspects of cognitive functioning. To date, those studies which have investigated the effects of glucose on memory in human participants have concentrated on its apparent ability to attenuate memory impairment. Relatively little research has been done in humans investigating the effects of glucose on memory performance in young healthy participants in whom no memory deficits exist. Moreover, the work which has been conducted in this population has produced somewhat equivocal findings. In this study, after overnight fasting the influence of a 25 g oral dosage of glucose on a range of measures of memory performance was investigated in healthy young female participants. Two control treatments (saccharin and water) were also administered. There was a significant glucose facilitation effect upon performance of long-term verbal free and cued recall tasks which did not vary with test delay. Performance on these free and cued verbal recall measures correlated significantly with blood glucose levels across all participants. No glucose-related facilitation was observed on either a test of short-term verbal memory (forwards/backwards digit recall) or a test of long-term non-verbal memory (complex figure reproduction). However, the significant glucose-related effects observed with long-term free and cued recall remained after controlling for participants' differential baseline blood glucose levels and individual levels of immediate memory performance. Therefore, memory improvement after glucose ingestion was not merely a consequence of lower baseline blood glucose or lower immediate memory performance in the glucose treatment group. These findings indicate that there may be some fractionation in the memory facilitation effects of glucose: the memory enhancing effect of glucose administration in healthy young adults may be greatest on tests of long-term verbal recall. The results suggest that glucose may enhance retention in and/or retrieval from long-term verbal memory.