An outbreak of imipenem-resistant Pseudomonas aeruginosa in an intensive care unit.
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Anti-Bacterial Agents↗
Biomedical subjects
J Eddleston
Publications and source records attributed to J Eddleston.
Effect of dopexamine on outcome after major abdominal surgery: a prospective, randomized, controlled multicenter study. European Multicenter Study Group on Dopexamine in Major Abdominal Surgery.
OBJECTIVE: To test the hypothesis that dopexamine reduces postoperative mortality and morbidity in high-risk, major abdominal surgery patients, when given to fluid-resuscitated patients starting before the operation and continued for 24 hrs after surgery. DESIGN: Prospective, randomized, controlled, double-blind multicenter trial. SETTING: Intensive care units in 13 hospitals from six European countries. PATIENTS: A total of 412 patients with predefined high-risk criteria, undergoing major abdominal surgery with an expected duration of at least 1.5 hrs. INTERVENTIONS: The patients received placebo (n = 140), dopexamine at 0.5 microg/kg/min (n = 135), or dopexamine at 2.0 microg/kg/ min (n = 137) starting after preoperative hemodynamic stabilization and continued for 24 hrs after surgery. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was mortality at 28 days. Analysis was by intention to treat. Dopexamine had no effect on mortality (at 28 days, 13%, 7%, and 15%, for the groups receiving placebo, dopexamine at 0.5 microg/kg/ min, and dopexamine at 2.0 microg/kg/min, respectively), despite the expected dose-dependent hemodynamic responses. No effect was observed on the occurrence of organ dysfunction, duration of intensive care unit stay, or length of hospital stay. CONCLUSION: We conclude that dopexamine in doses that result in increased cardiac output and oxygen delivery after preoperative stabilization with fluids does not improve outcome after major abdominal surgery compared with fluids alone. Based on post hoc subgroup analysis and stratification according to the number of risk factors, we suggest that the concept should be further tested in patients at higher risk of complications or undergoing emergency surgery.
Adrenergic beta-Agonists↗
Physical and transcriptional map of a 3-Mb region of mouse chromosome 1 containing the gene for the neural tube defect mutant loop-tail (Lp).
The Lp mouse mutant provides a model for the severe human neural tube defect (NTD), cranio-rachischisis. To identify the Lp gene, a positional cloning approach has been adopted. Previously, linkage analysis in a large intraspecific backcross was used to map the Lp locus to distal mouse chromosome 1. Here we report a detailed physical map of this region. The interval surrounding Lp has been cloned in a yeast artificial chromosome (YAC) contig consisting of 63 clones spanning approximately 3.2 Mb. Fifty sequence tagged sites (STSs) have been used to construct the contig and establish marker order across the interval. Based on the high level of conserved synteny between distal mouse chromosome 1 and human 1q21-q24, many of these STSs were designed from expressed sequences identified by cross-screening human and mouse databases of expressed sequence tags. Added to other known genes in the region, a total of 29 genes were located and ordered within the contig. Seven novel polymorphisms were identified within the region, allowing refinement of the genetic map and a reduction in the size of the physical interval containing the Lp gene. The Lp interval, between D1Mit113 and Tagln2, can be spanned by two nonchimeric overlapping YACs that define a physical distance of approximately 1 Mb. Within this region, 10 potential candidate genes have been mapped. The materials and genes described here will provide a resource for the identification and further study of the mutated Lp gene that causes this severe neural tube defect and will provide candidates for other defects known to map to the homologous region on human chromosome 1q.
Animals↗
Sequence and expression analysis of Nhlh1: a basic helix-loop-helix gene implicated in neurogenesis.
Nhlh1 is a basic helix-loop-helix (bHLH) gene that has been implicated in mouse neurogenesis. Previous studies have shown it to be expressed in regions in which there are differentiating neurons during late embryonic and fetal development, but detailed studies of the role of Nhlh1 earlier in embryonic development have not been performed. In this paper, we examine the expression of Nhlh1 transcripts at early embryonic stages (E8.5-E10.5), at the onset of neurogenesis, and compare the pattern of expression with that of Islet-1, a marker of postmitotic neurons. We show that Nhlh1 is expressed in early postmitotic neurons but is down-regulated as these cells migrate from the ventricular zone. We have also determined the genomic structure of mouse Nhlh1 and have characterised the promoter sequence, as a first step towards identifying factors that may control Nhlh1 expression. Nhlh1 has been implicated previously as a candidate for the neural tube defect mutant loop-tail (Lp); here, we present sequence and expression data indicating that Nhlh1 is unlikely to be responsible for the Lp mutation.
Amino Acid Sequence↗
Vascular surgical society of great britain and ireland: randomized double-blind study of dopexamine versus placebo in aortic surgery
BACKGROUND: Mechanisms involved in the development of colon- ic ischaemia are not fully understood and there are conflicting reports regarding predisposing factors. The aim of this study was to evaluate the effect of dopexamine hydrochloride on the incidence of colonic ischaemia following aortic surgery and to correlate immunohistochemical markers of inflammatory activation in its pathogenesis. METHODS: Thirty patients, of mean age 65 (range 46-84) years, undergoing elective infrarenal aortic surgery were randomized to receive a perioperative infusion of either dopexamine 2 &mgr;g kg-1 min-1 (n = 12) or 0.9 per cent saline placebo (n = 18). All patients underwent colonoscopy and biopsy following induction of anaesthesia and at 1 week after operation. Sections were stained with haematoxylin and eosin, and for mast cell tryptase (MCT), myeloperoxidase (MPO) and both the inducible (iNOS) and endothelial (eNOS) isoforms of nitric oxide synthase. Sections were analysed blindly and independently by two histopathologists. Patient and operative data were collected and stored separately. RESULTS: Colonic ischaemia was noted in nine patients based on microscopic findings. Endoscopy alone had a sensitivity of 56 per cent. There was a significantly lower incidence of colonic ischaemia in patients receiving dopexamine compared with placebo (P < 0.05). One death resulted from colonic infarction in the placebo group 11 days after operation. There was increased MPO and MCT expression in patients with histological evidence of ischaemia (P < 0.05); iNOS staining within the vascular (P = 0.001) and lamina propria (P < 0.05) components of the mucosa was also significantly greater. No association was found with eNOS. CONCLUSION: Perioperative dopexamine infusion confers a degree of protection to colonic mucosa following aortic surgery, possibly through an anti-inflammatory effect.
Journal Article↗
Paralogous sm22alpha (Tagln) genes map to mouse chromosomes 1 and 9: further evidence for a paralogous relationship.
SM22alpha (TAGLN) is one of the earliest markers of differentiated smooth muscle, being expressed exclusively in the smooth muscle cells of adult tissues and transiently in embryonic skeletal and cardiac tissues. We have identified and mapped the mouse Tagln gene and a closely related gene, Sm22alpha homolog (Tagln2). The chromosomal localization for Tagln was identified by linkage analysis to distal mouse chromosome 9 between D9Mit154 and D9Mit330, closely linked to the anchor locus D9Nds10. The localization of Tagln2 was also determined and was found to map between Fcgr2 and D1Mit149 on distal mouse chromosome 1. This localization is homologous to a region of human 1q21-q25 to which an EST representing human TAGLN2 was previously mapped. The two regions, distal mouse chromosome 1 and proximal mouse chromosome 9, and the human regions with conserved synteny (1q21-q25 and 11q22-qter) are believed to be paralogous, reflecting either conserved remnants of duplicated chromosomes or segments of chromosomes during vertebrate evolution.
Amino Acid Sequence↗
An evaluation of intercostal nerve blockade for analgesia following renal transplantation.
In a double-blinded study we examined the effect of supplementing patient-controlled morphine analgesia with intercostal nerve blockade to identify if this improved analgesia and reduced morphine requirements following renal transplantation. Fifty patients were randomized to receive unilateral intercostal nerve block with either 0.5% bupivacaine or saline to the lower five intercostal nerves. Each block was performed on the side of surgical incision following the completion of surgery. Patients receiving bupivacaine blockade reported reduced pain scores and used less morphine in the initial 4 h following renal transplantation, but did not demonstrate a significant reduction in overall pain scores, total 24 h morphine requirements, or sedation scores. Two patients developed a pneumothorax, neither of which were clinically apparent at the time of diagnosis, and only detected by chest radiography. A chest radiograph should therefore be considered mandatory after intercostal nerve blockade.
Adult↗
Linkage mapping of Lims1l, the murine homolog of the human LIM domain gene PINCH, to mouse chromosome 10.
The human LIM domain gene LIMS1 was used to identify a mouse homolog. The resulting mouse sequence was used to identify a polymorphism by SSCP analysis. Linkage studies performed in the EUCIB backcross placed Lims1l on the proximal portion of mouse Chromosome 10. This localisation makes it an interesting candidate for the deafness mutant, waltzer (v).
Adaptor Proteins, Signal Transducing↗
Localization of the mouse gene encoding tyrosine kinase receptor type 10 on distal chromosome 1.
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Alleles↗
Genetic basis of neural tube defects: the mouse gene loop-tail maps to a region of chromosome 1 syntenic with human 1q21-q23.
A genetic basis for neural tube defects (NTD) is rarely doubted, but the genes involved have not yet been identified. This is partly due to a lack of suitable families on which to perform linkage analysis. An alternative approach is to use the many mouse genes that cause NTD as a means of isolating their human homologues. Loop-tail (Lp) is a semidominant mouse gene that, in homozygous mutants, causes the severe NTD phenotype cranio-rachischisis. As a first step toward cloning Lp, we have performed linkage analysis on an intraspecific backcross, using microsatellite and RFLP DNA markers. This study has localized Lp to a region of approximately 1.46 cM on mouse chromosome 1, flanked by the gene for the alpha chain of high-affinity Fc receptor for IgE (Fcer1 alpha) and a microsatellite repeat D1Mit113. Physical mapping data in the region suggest that the interval is likely to be no more than 1.8 Mb in size. The localization is several centimorgans distal to that previously assigned by linkage studies with biochemical and visible markers and suggests that the human homologue of Lp is likely to reside in a region of conserved homology on 1q21-q23.
Animals↗