Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Synthesis and solvolysis of tricyclo [ 3.2.1.0 2,4] oct-8-7l derivatives

Some of the evidence supporting the olefin-like character of cyclopropyl groups, the double-bond assisted solvolysis of 7-norbornenyl derivatives and the ability of the cyclopropyl group to anchimerically assist ionization is reviewed. With regard to the high rate of solvolysis of 7-norbornenyl esters, the similarity of olefins and cyclopropyl groups and the steric features of the tricyclo [3.2.1.0 ²'⁴] octane ring system, a solvolytic study of tricyclo [3.2.1.0²'⁴] oct-8-yl derivatives was undertaken to determine whether a suitably oriented cyclopropyl group can also provide a large anchimeric assistance to ionization. The synthesis of the four isomeric tricyclo [3.2.1.0²'⁴] octan- 8-ols (II-OH, VIII-OH, XVI-OH and XVII-OH) is described. The cuprous chloride-catalyzed addition of diazomethane to anti-7-norbornenol gave pure exo-anti-tricyclo [3.2.1.0²'⁴] octan-8-ol (II-OH). Addition of diazomethane to 7,7-dimethoxynorbornene gave exo-8,8-dimethoxytricyclo [3.2.1.0²'⁴] octane (Vl) which was hydrolyzed to the corresponding ketone (VII) with acid. Reduction of the exo ketone afforded pure exo-syn-tricyclo [3.2.1.0²'⁴] octan-8-ol (VIII-OH). Attempts to prepare endo methylene adducts from norbornenes failed, although they were obtained from norbornadienes. The endo-tricyclo [3.2.1.0²'⁴] octan-8-ols were therefore prepared by a different route. Reaction' of 5,5-dimethoxy-l,2,3,'f-tetrachlorocyclopentadiene with cyclo- propene gave the endo Diels-Alder adduct (Xii). Dechlorination of this compound with metallic sodium, followed by catalytic hydrogenation, gave endo-8,8-dimethoxytricyclo [3.2.1.0²'⁴] octane (XIV). This ketal, upon acid hydrolysis, afforded the endo ketone (XV) which was reduced by a variety of reagents to give mixtures of the two endo alcohols. Preparative gas-liquid phase chromatography (glpc) gave pure samples of endo-syn and endo-anti-tricyclo [3.2.1.0²'⁴] octan-8-ols (XVI-OH and XVII-OH). Acetolysis of the p-bromobenzenesulfonates (brosylates) of the endo-syn and exo-syn alcohols in acetic acid and hydrolysis of the p-nitro- benzoates of the endo-anti alcohol and of anti-T-norbornenol in 70% aqueous dioxane gave relative rates of ionization of 37, 10⁴, 10¹² and 10⁹, respectively, compared to the solvolytic rate of a 7-norbornyl derivative at 100°. The exo-anti derivative (II-OBs) had previously been shown to have a relative solvolytic rate of 1.65 under these conditions. Acetolysis of the exo-syn and endo-syn brosylates gave rise to mixtures of entirely rearranged products which were not identified. Hydrolysis of the endo-anti p-nitrobenzoate in 70% aqueous dioxane gave rise only to endo-tricyclo [5-1.0.0⁴'⁸] oct-3-yi (XVIIl) products. The kinetic and product study data are consistent with the proposal that the endo-anti derivatives ionize to the 2,4-ethanotrishomocyclopropenyl cation. The stereochemistry of the reactions by which the tricycle [3.2.1.0²'⁴] octane ring system is formed, the effect of the stereochemistry of this ring system on the spectral characteristics of its derivatives and the mechanistic implications of the kinetic and product study data are discussed. [Symbols and illustrations omitted].Science, Faculty ofChemistry, Department ofGraduat

Methylene addition to some 7-norbornadienyl derivatives

The synthesis of exo-antl-tricyclo [3,2,1,02,4] octan-8-ol (V) and exo-anti-8-methoxy-tricyclo [3,2,1,02,4] octane (VI) was carried out by the cuprous chloride catalysed reaction of diazoraethane with anti-7-norbornenol (IV). The methyl ether (VI) was previously thought to be the endo isomer of (V). Methylene addition to the syn double bond of 7-norbornadienyl acetate (III) was accomplished using the above method to give a 5 to 1 mixture of exo-syn-tricyclo [3,2,1,02,4] oct-6-ene-8- acetate (VII) and endo-syn-tricyclo [3,2,1,02,4] oct-6-ene-8- acetate (VIII). These two acetates were inseparable but the corresponding alcohols exo-syn-tricyclo [3,2,1,02,4] oct-6-ene-8-ol (X) and endo-syn-tricyclo [3,2,1,02,4] oct-6-ene-8-ol (XI), formed by reduction of the acetate mixture with lithium aluminum hydride, could be separated by gas-liquid partition chromatography. The stereochemistry of these two products was determined by the multiplicity and by the chemical shift of the olefinic proton signals in their proton nuclear magnetic resonance spectra. Catalytic reduction of these two alcohols gave exo-syn-tricyclo [3,2,1,02,4] octan-8-ol (XIII) and endo-syn-trlcyclo [3,2,1,02,4] octan-8-ol (XIV). From the diazomethane-7-norbornadienyl acetate reaction a diadduct acetate, tetracyclo [3,3,1,02,4,06,8]nonan-9-acetate (IX), was also obtained which reduced to the alcohol tetracyclo [3,3,1,02,4,06,8] nonan-9-ol (XII). The stereochemistry of these diadducts was not determined. Acetolysis studies on the p-bromobenzene- sulfonyl (brosylate) derivative of exo-anti-tricyclo [3,2,1,02,4]octan-8-ol (V) at 200° indicate that the reaction proceeds by formation of a carbonium ion at C8, which then rearranges, destroying the cyclopropyl group. Although unchanged (V) could be obtained by lithium aluminum hydride reduction of about 80% solvolysed brosylate at 200°, none of the products of complete solvolysis could be identified.Science, Faculty ofChemistry, Department ofGraduat

The Mosaic Genome of Anaeromyxobacter dehalogenans Strain 2CP-C Suggests an Aerobic Common Ancestor to the Delta-Proteobacteria

©2008 Thomas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.doi:10.1371/journal.pone.0002103Anaeromyxobacter dehalogenans strain 2CP-C is a versaphilic delta-Proteobacterium distributed throughout many diverse soil and sediment environments. 16S rRNA gene phylogenetic analysis groups A. dehalogenans together with the myxobacteria, which have distinguishing characteristics including strictly aerobic metabolism, sporulation, fruiting body formation, and surface motility. Analysis of the 5.01 Mb strain 2CP-C genome substantiated that this organism is a myxobacterium but shares genotypic traits with the anaerobic majority of the delta-Proteobacteria (i.e., the Desulfuromonadales). Reflective of its respiratory versatility, strain 2CP-C possesses 68 genes coding for putative c-type cytochromes, including one gene with 40 heme binding motifs. Consistent with its relatedness to the myxobacteria, surface motility was observed in strain 2CP-C and multiple types of motility genes are present, including 28 genes for gliding, adventurous (A-) motility and 17 genes for type IV pilus-based motility (i.e., social (S-) motility) that all have homologs in Myxococcus xanthus. Although A. dehalogenans shares many metabolic traits with the anaerobic majority of the delta- Proteobacteria, strain 2CP-C grows under microaerophilic conditions and possesses detoxification systems for reactive oxygen species. Accordingly, two gene clusters coding for NADH dehydrogenase subunits and two cytochrome oxidase gene clusters in strain 2CP-C are similar to those in M. xanthus. Remarkably, strain 2CP-C possesses a third NADH dehydrogenase gene cluster and a cytochrome cbb3 oxidase gene cluster, apparently acquired through ancient horizontal gene transfer from a strictly anaerobic green sulfur bacterium. The mosaic nature of the A. dehalogenans strain 2CP-C genome suggests that the metabolically versatile, anaerobic members of the delta-Proteobacteria may have descended from aerobic ancestors with complex lifestyles