Dietary restriction increases variability in longevity.

Nutritional environments, particularly those experienced during early life, are hypothesized to affect longevity. A recent cross-taxa meta-analysis found that, depending upon circumstance, average longevity may be increased or decreased by early-life dietary restriction. Unstudied are the effects of diet during development on among-individual variance in longevity. Here, we address this issue using emerging methods for meta-analysis of variance. We found that, in general, standard deviation (s.d.) in longevity is around 8% higher under early-life dietary restriction than a standard diet. The effects became especially profound when dietary insults were experienced prenatally (s.d. increased by 29%) and/or extended into adulthood (s.d. increased by 36.6%). Early-life dietary restriction may generate variance in longevity as a result of increased variance in resource acquisition or allocation, but the mechanisms underlying these largely overlooked patterns clearly warrant elucidation.

Sex in unisexual salamanders: discovery of a new sperm donor with ancient affinities.

Although bisexual reproduction has considerable evolutionary benefits, several all-female vertebrates exist. Unisexual salamanders in the genus Ambystoma are common around the Great Lakes region in eastern North America. They originated from a hybridization event that involved a female that shared a common ancestor with Ambystoma barbouri 2.4 to 3.9 million years ago but, unexpectedly, A. barbouri nuclear genomes were unknown in unisexuals. Unisexual salamanders steal sperm from donors of normally bisexual species, so their reproductive mode is described as kleptogenesis. Most known unisexuals are polyploid and they all possess at least one A. laterale genome. One or more other genomes are taken from sperm donors that may include A. jeffersonianum, A. laterale, A. texanum and A. tigrinum. We examined unisexual adults and larvae in a southern Ohio pond where unisexual individuals coexist with male A. barbouri. This population provided an opportunity to test hypotheses pertaining to the role of A. barbouri in the evolution of the disparate cytoplasmic and nuclear genomes in unisexual salamanders. Microsatellite DNA loci, mitochondrial DNA sequences and genomic in situ hybridization were used to identify the genomic constitution of individuals. A. barbouri was found to be an acceptable sperm donor for unisexuals but only contributed genomes in ploidy-elevated individuals. In the absence of A. jeffersonianum, this Ohio population is likely experiencing a recent switch in sperm donors from A. jeffersonianum to A. barbouri and demonstrates the evolutionary flexibility and dynamics of kleptogenesis.

An observational study of changes to long-term medication after admission to an intensive care unit.

Many patients admitted to intensive care units consume long-term medication. New drugs may be commenced during intensive care intended for the short term or longer. Patients are often cared for by several teams during hospital admission and long-term medication may inadvertently be permanently discontinued. Following admission, new therapies relevant only in the short term could be continued beyond intensive care and hospital discharge. We conducted a retrospective analysis of drug prescription by examining patients' notes and charts before, during and after intensive care admission. Of 197 drugs prescribed up to intensive care admission to 59 patients, 112 (57%) were stopped. Ninety-nine of these were not reintroduced by intensive care discharge and 34 were not reintroduced by hospital discharge. Of 154 drugs commenced during intensive care, 96 (62%) had no listed reason for their introduction. Twenty-eight were continued beyond hospital discharge, some without apparent ongoing indication. Reliable mechanisms to prevent prescription errors are required.

Selenium supplementation for critically ill adults.

BACKGROUND: Selenium is a trace mineral essential to human health, which has an important role in the immune response, defence against tissue damage and thyroid function. Improving selenium status could help protect against overwhelming tissue damage and infection in critically ill adults. OBJECTIVES: This review assessed the effects of selenium supplementation including the selenium-containing compound, ebselen, on adults recovering from critical illness. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library, Issue 2, 2003), MEDLINE, (1966 to July 2003), EMBASE (1980 to Week 30 2003),CAB NAR (1973 to March 2003), BIOSIS (1985 to July 2003), CINAHL (1982 to July 2003), HEALTHSTAR (1975 to September 2002), Current Controlled Trials, and reference lists. We contacted investigators, and handsearched four journals. Date of the most recent search: December 2003. SELECTION CRITERIA: Randomized trials of selenium or ebselen supplementation by any route, in adults with critical illness (including burns, head injury, brain haemorrhage, cerebrovascular accident and surgery). DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. We sought additional information as required from trialists. We also undertook pooling of data for outcomes and selected exploratory analyses were undertaken. MAIN RESULTS: Seven randomized trials involving813participants were included. The quality of trials, as reported, was poor, particularly for allocation concealment. The availability of outcome data was limited and trials involving selenium supplementation, were small. Thus the results must be interpreted with caution. Because of heterogeneity, results are presented for the random effects models. Four selenium trials showed no statistically significant difference in mortality (relative risk (RR) 0.52, 95% confidence interval (CI) 0.20 to 1.34). Three trials of ebselen also showed no statistically significant difference in mortality (RR 0.83, 95% CI 0.51 to 1.35). One trial of selenium found no statistically significant difference between groups for participants developing infection (RR 1.33, 95% CI 0.55 to 3.24). Three trials of ebselen provided data for participants developing infections (pyrexia, respiratory infections or meningitis), which was not statistically significant (RR 0.60, 95% CI 0.36 to 1.02). No clear evidence emerged for the benefits of selenium or ebselen supplementation for the outcomes of days on a ventilator, length of intensive care unit stay, length of hospital stay or quality of life. REVIEWERS' CONCLUSIONS: There is insufficient evidence to recommend supplementation of critically ill patients with selenium or ebselen. Trials are required which overcome the defects of the reviewed studies, particularly inadequate size and methodology. This review will be updated when four ongoing trials are completed.

Hypoxia and surgical patients--prevention and treatment of an unnecessary cause of morbidity and mortality.

Hypoxia is a common phenomenon peri-operatively. Although mild hypoxaemia of short duration is likely to have little effect more severe and prolonged hypoxaemia can seriously affect surgical outcome. Rational use of oxygen therapy may limit these adverse effects.

Effects of ketorolac and dextran-70 alone and in combination on haemostasis.

BACKGROUND: Dextran may be used in surgical patients for thromboprophylaxis or volume expansion along with ketorolac, a nonsteroidal anti-inflammatory drug, for analgesia. As these two agents can influence the haemostatic system at different sites, it is important to demonstrate that there is no adverse haemostatic interaction between them. METHODS: The haemostatic interaction between intravenous dextran-70 and intramuscular ketorolac was assessed in a double-blind, randomised, crossover study of healthy male volunteers each given all four combinations of ketorolac/placebo intramuscularly and dextran/placebo intravenously. The effect of ketorolac and dextran on haemostasis was assessed by the following techniques: skin bleeding time, in vitro platelet aggregation function, whole blood thromboxane generation, von Willebrand factor antigen, factor VIII coagulant activity and tissue plasminogen activator. The results were analysed for the effects of ketorolac and dextran and for any evidence of an interaction. RESULTS: Ketorolac inhibited platelet function and thromboxane generation. Dextran reduced factor VIII coagulant activity. Neither agent had a significant effect on bleeding time, von Willebrand factor or tissue plasminogen activator. There was only evidence of a small but statistically significant interaction between ketorolac and dextran on thromboxane generation. There was no evidence of any other interaction of ketorolac with dextran. CONCLUSION: This interaction on thromboxane generation is unlikely to be of clinical significance as substantial inhibition of thromboxane generation occurs with ketorolac alone.

Effects of adrenaline and hyaluronidase on plasma concentrations of lignocaine and bupivacaine after peribulbar anaesthesia.

We have measured peak plasma concentrations of lignocaine and bupivacaine after dual injection peribulbar block and investigated the influence of adrenaline and hyaluronidase. Twenty-four patients were allocated randomly to one of four groups: (I) local anaesthetic alone (lignocaine 10 mg ml-1-bupivacaine 3.75 mg ml-1); (II) local anaesthetic with adrenaline (5 micrograms ml-1); (III) local anaesthetic with hyaluronidase (75 iu ml-1); or (IV) local anaesthetic with adrenaline and hyaluronidase. Venous plasma concentrations of lignocaine and bupivacaine were measured in 24 patients using gas liquid chromatography before and at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180, 300 and 540 min after completion of the peribulbar injections. Main outcome measures were analysed using two-way analysis of variance. All patients, with one exception, received 10 ml of the local anaesthetic mixture. Overall peak plasma concentrations varied from 230 to 1910 micrograms ml-1 for lignocaine and from 160 to 1090 micrograms ml-1 for bupivacaine. Adrenaline significantly reduced peak plasma concentrations of lignocaine to 57% (P = 0.001) and bupivacaine to 61% (P = 0.004) compared with the nonadrenaline groups. Hyaluronidase had no significant effect on peak plasma concentrations of lignocaine and bupivacaine, which were 90% (P = 0.34) and 100% (P = 0.84) of the non-hyaluronidase groups. The area under the plasma concentration-time curves to 300 min (AUC300) behaved similarly. There was a reduction in AUC300 for lignocaine (P = 0.005) and bupivacaine (P = 0.011) in the adrenaline groups compared with the non-adrenaline groups, in contrast with no significant effects of hyaluronidase on AUC300 for lignocaine (P = 0.14) or bupivacaine (P = 0.53) compared with the non-hyaluronidase groups.

The effect of oral omeprazole on the disposition of lignocaine.

The effects of the gastric antisecretory drug, omeprazole, on the disposition of lignocaine were studied in 10 healthy male volunteers in a double-blind, randomised, placebo-controlled, two-period crossover trial. Omeprazole 40 mg or placebo was taken daily for one week before administration of lignocaine 1 mg.kg-1 (3.7 mumol.kg-1) given intravenously over 10 min. Venous concentrations of lignocaine and its metabolite monoethylglycinexylidine were measured in plasma with reversed phase liquid chromatography. The mean (95% CI) areas under the curve at infinity for lignocaine after pretreatment with omeprazole or placebo were 6.67 (4.90-8.45) mumol.h.l-1 and 6.14 (5.05-7.23) mumol.h.l-1, respectively (p = 0.44). The respective areas for monoethylglycinexylidine were 1.85 (1.25-2.45) mumol.h.l-1 and 1.79 (1.44-2.14) mumol.h.l-1 (p = 0.78). Similarly, omeprazole had no significant effect on the half-lives of lignocaine or methylglycinexylidine.