The association of abdominal muscle with outcomes after scheduled abdominal aortic aneurysm repair.

Sarcopenia is the degenerative loss of core muscle mass. It is an aspect of frailty, which is associated with increased rates of peri-operative harm. We assessed the association of the cross-sectional areas of abdominal muscles, including psoas, with survival during a median (IQR [range]) follow-up of 3.8 (3.2-4.4 [0.0-5.1]) years after scheduled endovascular (132) or open (5) abdominal aortic aneurysm repair in 137 patients. In multivariate analysis, mortality hazard (95%CI) was independently associated with: age, 1.06 (1.01-1.13) per year, p = 0.03; and the adjusted area of the left psoas muscle, 0.94 (0.81-1.01) per mm2 .kg-0.83 , p = 0.08. Shortened hospital stay was independently associated with haemoglobin concentration and adjusted left psoas muscle area, hazard ratio (95%) 1.01 (1.00-1.02) per g.l-1 and 1.05 (1.02-1.07) per mm2 .kg-0.83 , p = 0.04 and 0.001, respectively.

An in vitro study comparing two dose regimes of fresh frozen plasma on conventional and thromboelastographic tests of coagulation after major hepatic resection.

BACKGROUND: After hepatic resection, post-operative increases in international normalised ratio (INR) are frequent, but rarely associated with bleeding complication. Coagulation as assessed by thrombin generation may be normal, despite the increased INR. This study tests the hypothesis that viscoelastic tests (VET) of coagulation remain normal, despite mild elevations in INR, examines the efficacy of fresh frozen plasma (FFP) in reversing prolongation of INR in such patients and determines the effect of FFP on VET. METHODS: A prospective cohort study of 47 patients undergoing major hepatectomy. In vitro spiking with FFP (7·5 and 15 mL kg(-1)) was carried out if post-operative day 2 (POD2) INR levels were ≥1·5. Thromboelastography (TEG®) and INR were measured before and after FFP spiking. RESULTS: Blood from patients with an INR ≥ 1·5 on POD2 was spiked with FFP. There was a significant reduction in the INR from 1·94 [standard deviation (SD): 0·59] to 1·46 (SD: 0·27, P = 0·005) and 1·36 (SD: 0·18, P = 0·0007) with FFP 7·5 or 15 mL kg(-1), respectively. At baseline, the TEG R-time [6·17 min (NR, 9-27 min)] and maximum amplitude (MA) [66·9 mm (NR, 44-64 mm)] were hypercoagulable, and remained so on POD2 for the R-time (6·7 min), but fell to within the normal range for the MA (54·0 mm). FFP spiking had no significant effect on TEG variables. CONCLUSIONS: Despite the rise in INR after hepatectomy, VET do not show evidence of hypocoagulability. In vitro addition of FFP had no significant effect on TEG parameters. Clinical use of FFP in this situation is questionable.

Absolute density-profile tomography of molecular beams using multiphoton ionization.

We describe an approach for the absolute density measurement of rotationally symmetric molecular beams via multiphoton ionization. This simple single-projection tomographic technique requires only knowledge of the spatial intensity profile and ionization characteristics of the focused laser beam that probes the pulsed molecular jet. Multiphoton ionization (MPI) of a xenon beam allowed tomographic reconstruction of a two-dimensional density profile with a peak density of (4.2+/-0.4)x10(18) m(-3), which was compared with the theoretical predictions of the sudden freeze model. An analytic solution to the Abel transform is derived for Gaussian projected density profiles which greatly simplifies the reconstruction of the absolute radial density. MPI is sufficiently general that this technique can be readily applied to atomic beams with a broad range of chemistries.

Evaluation of the topical hemostatic efficacy and safety of TISSEEL VH S/D fibrin sealant compared with currently licensed TISSEEL VH in patients undergoing cardiac surgery: a phase 3, randomized, double-blind clinical study.

AIM: TISSEEL VH is the only commercially available fibrin sealant indicated as an adjunct to conventional methods of hemostasis during cardiac surgery. A next generation fibrin sealant (TISSEEL VH S/D) has been developed in frozen, ready-to-use form with an added virus inactivation step (solvent/detergent [S/D] treatment) to provide added safety and convenience to the currently licensed product. This study was performed to compare efficacy and safety of the two products. METHODS: Phase 3, prospective, randomized, double-blind, multicenter study to compare TISSEEL VH S/D to TISSEEL VH during cardiac surgery. The primary efficacy endpoint was the proportion of patients who achieved hemostasis at the primary treatment site within 5 min, and maintained hemostasis until surgical closure. RESULTS: The proportion of patients who achieved hemostasis at the primary treatment site within 5 min, and maintained hemostasis until surgical closure was 88.2% for TISSEEL VH S/D and 89.6% for TISSEEL VH in the intent-to-treat population. The difference in proportions, TISSEEL VH S/D minus TISSEEL VH, was 1.4% with a standard error of 3.70%. The lower 97.5% confidence bound of this difference was 8.6%, which is above the predefined noninferiority margin of 15%. Therefore, TISSEEL VH S/D is at least as efficacious as TISSEEL VH. The safety profile of TISSEEL VH S/D was very similar to that of currently licensed TISSEEL VH as assessed by the safety endpoints. CONCLUSION: TISSEEL VH S/D is safe and effective for use as an adjunct to hemostasis in patients undergoing cardiac surgery.

Issues in environmental water allocation--an Australian perspective.

Environmental water allocation is a critical issue in Australia and internationally. It has been prominent in Australia for a little over ten years during which time major policy and scientific advances have been made, but little implementation. This paper examines current understanding of environmental water allocation across a broad range of disciplines including the biophysical sciences, social sciences, economics, law, and policy. Development of practical methods for assessing environmental water requirements and experience with implementation in Australia are discussed. The paper concludes with thoughts on future needs.

Immunoreactive galanin expression in ovine gonadotropin-releasing hormone neurones: no effects of gender or reproductive status.

The neuropeptide, galanin, has been implicated to play a significant role in numerous physiological functions, including reproduction. Studies on several species have shown that galanin enhances gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone secretion. In rodents, a subset of GnRH neurones expresses galanin in a sexually dimorphic manner and it has been suggested that this may underpin the differences in GnRH secretion observed between the sexes. However, there are few data available for other species. Previous studies in sheep have shown that the distribution of GnRH neurones overlaps with galanin cells. The primary objectives of our study were to determine whether GnRH and galanin coexist in the sheep brain and, importantly, if a sex difference is apparent in the colocalization of these two peptides. Using immunocytochemistry coupled to high temperature antigen retrieval, we found that all GnRH neurones in the ovine brain colocalize with galanin. There is also a distinct population of galanin neurones that do not secrete GnRH. In addition, the distribution of galanin-immunoreactive cells was similar to that previously reported for colchicine treated ewes and, in agreement with earlier studies, the number of GnRH neurones did not differ between rams and ewes or between ewes killed at different stages of the oestrous cycle. These results suggest that, in sheep, GnRH and galanin may be cosecreted but the functional significance of this coexpression and possible cosecretion remains to be elucidated.

Randomized controlled trial of motivational interviewing, cognitive behavior therapy, and family intervention for patients with comorbid schizophrenia and substance use disorders.

OBJECTIVE: Comorbidity of substance abuse disorders with schizophrenia is associated with a greater risk for serious illness complications and poorer outcome. Methodologically sound studies investigating treatment approaches for patients with these disorders are rare, although recommendations for integrated and comprehensive treatment programs abound. This study investigates the relative benefit of adding an integrated psychological and psychosocial treatment program to routine psychiatric care for patients with schizophrenia and substance use disorders. METHOD: The authors conducted a randomized, single-blind controlled comparison of routine care with a program of routine care integrated with motivational interviewing, cognitive behavior therapy, and family or caregiver intervention. RESULTS: The integrated treatment program resulted in significantly greater improvement in patients' general functioning than routine care alone at the end of treatment and 12 months after the beginning of the study. Other benefits of the program included a reduction in positive symptoms and in symptom exacerbations and an increase in the percent of days of abstinence from drugs or alcohol over the 12-month period from baseline to follow-up. CONCLUSIONS: These findings demonstrate the effectiveness of a program of routine care integrated with motivational interviewing, cognitive behavior therapy, and family intervention over routine psychiatric care alone for patients with comorbid schizophrenia and alcohol or drug abuse or dependence.

Use of differential fluorescence induction and optical trapping to isolate environmentally induced genes.

The techniques of differential fluorescence induction (DFI) and optical trapping (OT) have been combined to allow the identification of environmentally induced genes in single bacterial cells. Designated DFI-OT, this technique allows the in situ isolation of genes driving the expression of green fluorescent protein (Gfp) using temporal and spatial criteria. A series of plasmid-based promoter probe vectors (pOT) was developed for the construction of random genomic libraries that are linked to gfpUV or egfp. Bacteria that do not express Gfp on laboratory medium (i.e. non-fluorescent) were inoculated into the environment, and induced genes were detected with a combined fluorescence/optical trapping microscope. Using this selection strategy, rhizosphere-induced genes with homology to thiamine pyrophosphorylase (thiE) and cyclic glucan synthase (ndvB) were isolated. Other genes were expressed late in the stationary phase or as a consequence of surface-dependent growth, including fixND and metX, and a putative ABC transporter of putrescine. This strategy provides a unique ability to combine spatial, temporal and physical information to identify environmental regulation of bacterial gene expression.

Informing river management policies and programs with science.

Conventional wisdom has it that we already have enough science to address the problems causing degradation of our environment, including rivers. This is not true. However it is the case that we could be using existing knowledge better, and that we could be doing more to learn the lessons from the huge sums being spent on river restoration and management. Informing good policy and practical on-ground management with R&D outputs has proven to be is difficult, but essential. This paper reviews some of the history of water and river management in Australia and how perceptions of rivers have evolved. It discusses the challenge of enhancing the linkages between science, policy and practice in river management. It outlines the knowledge exchange, R&D and capacity building strategies of the National Rivers Consortium--a new initiative whose founding partners are LWRRDC, the MDBC, CSIRO Land and Water and the Western Australian Waters and Rivers Commission. This strategic collaboration between policy makers, river managers and scientists brings together organisations with responsibility and expertise to improve the health and management of Australian rivers. The National Rivers Consortium is making a major investment in knowledge exchange and capacity building, based on direct personal contact and learning by doing. The Consortium is establishing a program of training activities targeting river managers and policy makers, based on the best available science and high quality information products. It will support river managers as they plan and implement river restoration and protection projects. The paper concludes with a discussion of the key knowledge gaps that remain impediments to the better management of Australia's unique and diverse river landscapes.

Schizophrenia and substance misuse problems: a comparison between patients with and without significant carer contact.

AIM: Many researchers and clinicians in the mental health field have given much attention over the last few years to patients with co-morbid problems of schizophrenia and substance use. This population is becoming a focus of attention for all service providers owing to the suggested increase in numbers of patients with these dual diagnoses and the observed negative effects on patients and costs to services. The advantages for providing family interventions in schizophrenia are now well established and increasingly these interventions are being evaluated for families of dual diagnosis patients. Many dually diagnosed patients do not, however, have a great deal of contact with a carer/relative. This paper looks at whether differences exist between patients with a dual diagnosis that have carer contact and those who do not have carer contact in terms of their illness history and type of substance use. For the purpose of this article 'carer' refers to an individual who is an informal carer or relative with whom the client has weekly contact of 10 h. Many of these carers provide the client with emotional, physical and material support. METHOD: The identification process for both'carer contact' and 'no carer contact' patients was conducted through the screening of the hospital's care programme approach (CPA) lists and through contact with care coordinators and consultants. Case notes of all patients identified were screened and information on demographic data, duration of illness, admissions and substance use was collected. RESULTS: Results indicated that the 'no carer contact' group was older and had significantly more days in hospital at last admission. CONCLUSIONS: It is possible that as patients get older their contact with significant others decreases, i. e. loss of contact with key relatives is due to age rather than severity of substance use. Furthermore, patients' reduced contact results in them having longer stays in hospital possibly because they will not receive additional support when discharged.

Identification of amino acid residues critical for aggregation of human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES. Characterization of active disaggregated chemokine variants.

Human CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation normal T cell expressed) self-associate to form high-molecular mass aggregates. To explore the biological significance of chemokine aggregation, nonaggregating variants were sought. The phenotypes of 105 hMIP-1alpha variants generated by systematic mutagenesis and expression in yeast were determined. hMIP-1alpha residues Asp26 and Glu66 were critical to the self-association process. Substitution at either residue resulted in the formation of essentially homogenous tetramers at 0.5 mg/ml. Substitution of identical or analogous residues in homologous positions in both hMIP-1beta and RANTES demonstrated that they were also critical to aggregation. Our analysis suggests that a single charged residue at either position 26 or 66 is insufficient to support extensive aggregation and that two charged residues must be present. Solution of the three-dimensional NMR structure of hMIP-1alpha has enabled comparison of these residues in hMIP-1beta and RANTES. Aggregated and disaggregated forms of hMIP-1alpha, hMIP-1beta, and RANTES generally have equivalent G-protein-coupled receptor-mediated biological potencies. We have therefore generated novel reagents to evaluate the role of hMIP-1alpha, hMIP-1beta, and RANTES aggregation in vitro and in vivo. The disaggregated chemokines retained their human immunodeficiency virus (HIV) inhibitory activities. Surprisingly, high concentrations of RANTES, but not disaggregated RANTES variants, enhanced infection of cells by both M- and T-tropic HIV isolates/strains. This observation has important implications for potential therapeutic uses of chemokines implying that disaggregated forms may be necessary for safe clinical investigation.

Regulation of the extracellular ligand binding activity of integrins.

Integrins are a large heterodimeric family of cell surface adhesion receptors that bind extracellular matrix and cell surface ligands. The extracellular ligand binding activity of integrins is a dynamic and highly regulated event involving the induction of conformational changes within the integrin structure. The adhesive properties of integrins can be controlled by altering the activation state of the integrin, either through conformational change or receptor clustering, using mechanisms that are regulated by intracellular proteins. In this review, we will discuss what is currently known about integrin structure and the ligand binding sites present within the receptor. In addition, the mechanisms by which the ligand binding event is regulated through conformational change will be addressed, and the potential role of intracellular cytoplasmic proteins will be discussed.

Alpha4 integrin binding interfaces on VCAM-1 and MAdCAM-1. Integrin binding footprints identify accessory binding sites that play a role in integrin specificity.

Integrins are a family of heterodimeric adhesion receptors that mediate cellular interactions with a range of matrix components and cell surface proteins. Vascular cell adhesion molecule-1 (VCAM-1) is an endothelial cell ligand for two leukocyte integrins (alpha4beta1 and alpha4beta7). A related CAM, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is recognized by alpha4beta7 but is a poor ligand for alpha4beta1. Previous studies have revealed that all alpha4 integrin-ligand interactions are dependent on a key acidic ligand motif centered on the CAM domain 1 C-D loop region. By generating VCAM-1/MAdCAM-1 chimeras and testing recombinant proteins in cell adhesion assays we have found that alpha4beta1 binds to the MAdCAM-1 adhesion motif when present in VCAM-1, but not when the VCAM-1 motif was present in MAdCAM-1, suggesting that this region does not contain all of the information necessary to determine integrin binding specificity. To characterize integrin-CAM specificity further we measured alpha4beta1 and alpha4beta7 binding to a comprehensive set of mutant VCAM-1 constructs containing amino acid substitutions within the predicted integrin adhesion face. These data revealed the presence of key "regulatory residues" adjacent to integrin contact sites and an important difference in the "footprint" of alpha4beta1 and alpha4beta7 that was associated with an accessory binding site located in VCAM-1 Ig domain 2. The analogous region in MAdCAM-1 is markedly different in size and sequence and when mutated abolishes integrin binding activity.

Identification of chromosomal genes located downstream of dctD that affect the requirement for calcium and the lipopolysaccharide layer of Rhizobium leguminosarum.

In Rhizobium leguminosarum both the C4-dicarboxylate transport system and wild-type lipopolysaccharide layer (LPS) are essential for nitrogen fixation. A Tn5 mutant (RU301) of R. leguminosarum bv. viciae 3841, was isolated that is only able to synthesize LPS II, which lacks the O-antigen. Strain RU301 exhibits a rough colony morphology, flocculates in culture and is unable to swarm in TY agar. It also fails to grow on organic acids, sugars or TY unless the concentration of calcium or magnesium is elevated above that normally required for growth. The defects in the LPS and growth in strain RU301 were complemented by a series of cosmids from a strain 3841 cosmid library (pRU3020-pRU3022) and a cosmid from R. leguminosarum bv. phaseoli 8002 (pIJ1848). The transposon insertion in strain RU301 was shown to be located in a 3 kb EcoRI fragment by Southern blotting and cloning from the chromosome. Sub-cloning of pIJ1848 demonstrated that the gene disrupted by the transposon in strain RU301 is located on a 2.4 kb EcoRI-PstI fragment (pRU74). R. leguminosarum bv. viciae VF39-C86, which is one of four LPS mutants previously isolated by U. B. Priefer (1989, J Bacteriol 171, 6161-6168), was also complemented by sub-clones of pIJ1848 but not by pRU74, suggesting the mutation is in a gene adjacent to that disrupted in strain RU301. Complementation and Southern analysis indicate that the region contained in pIJ1848 does not correspond to any other cloned Ips genes. Two dctA mutants, RU436 and RU437, were also complemented by pIJ1848 and pRU3020. Mapping of pIJ1848 and Southern blotting of plasmid-deleted strains of R. leguminosarum revealed that dctD and the region mutated in strain RU301 are located approximately 10 kb apart on the chromosome. Analysis of homogenotes demonstrated that there is not a large region important in calcium utilization, organic acid metabolism or LPS biosynthesis located between the gene disrupted in strain RU301 and dctD. Strain VF39C-86 also required an elevated concentration of calcium for growth on succinate, while strains mutated in the alpha-chromosomal or beta-plasmid group of Ips genes grew at the same calcium concentrations as the wild type, demonstrating that the additional calcium requirement is not a property of all LPS rough mutants. Strain RU301 nodulates peas, but does not reduce acetylene, demonstrating that the gene mutated in this strain is essential for nitrogen fixation.

Interrelations among children, parents, premedication, and anaesthetists in paediatric day stay surgery.

OBJECTIVE: To investigate the incidence of difficulties associated with parental presence during the induction of anaesthesia in children and the influence of premedication with special reference to vomiting after papaveretum. DESIGN: Mixed factual and multiple choice questionnaire completed by medical and nursing staff and parents during and after admission. SETTING: Teaching hospital with regional paediatric general surgical unit where parental presence during induction of anaesthesia is long established. PATIENTS: 151 Children aged 1-14 years who had not previously undergone surgery attending with parents for day stay general surgical procedures. INTERVENTION: Children were randomly allocated to receive no premedication (group 1), oral diazepam elixir (0.3 mg/kg) (group 2), or intramuscular papaveretum with hyoscine (0.3 mg/kg with 0.006 mg/kg) (group 3). No other modification to established day stay routine was made. RESULTS: No major problems were associated with the presence of parents during the induction of anaesthesia. Only 10 of the 141 parents who accompanied their child caused some difficulty, and five became distressed. Premedication with both diazepam and papaveretum resulted in sedation but did not ease induction of anaesthesia. Papaveretum greatly reduced pain and distress immediately after the operation, pain and discomfort being observed in only 15% of children (7/48) compared with 66% (27/41) in group 1 and 49% (22/45) in group 2. Papaveretum, however, must be given intramuscularly, and nurses observed that the children preferred being given premedication orally to intramuscularly. In addition, the incidences of nausea and vomiting were significantly higher in the postoperative ward and at home with papaveretum, although no patient who had been given the drug was nauseous or vomited in the recovery area. The incidences of nausea in group 3 were 62% (31/50) and 57% (27/47) in the postoperative ward and at home, respectively, v 21% (7/33) and 14% (4/29) in group 1 and 13% (5/38) and 14% (5/37) in group 2; the incidences of vomiting in group 3 were 60% and 43% in the postoperative ward and at home, respectively, v 18% and 7% in group 1 and 11% and 11% in group 2. Finally, neither the administration or otherwise of premedication nor the drug given affected the children's or parents' perception of day care surgery. CONCLUSIONS: Difficulties with parents in anaesthetic rooms were not common or severe. Premedication provides preoperative sedation and papaveretum improves the immediate postoperative course but the incidences of nausea and vomiting after operation are higher with its use than without.

Costs of replacement of anaesthetic equipment. Projected expenditure for clinical anaesthetic equipment in a teaching health district.

A study was made of all the anaesthetic equipment in clinical use to substantiate estimates of the cost of its replacement on four hospital sites. The years during which replacement was likely to become necessary were estimated from the list compiled and an existing full inventory, together with costs at 1986 prices. The predicted costs for each year until 2000 AD were derived. To these were added sums required to make good existing shortfalls and to introduce a moderate amount of equipment incorporating newer technology. The totals showed that the capital currently available in the health district is sufficient only for anaesthetic equipment and requires a substantial increase to replace medical apparatus belonging to all specialties already in routine clinical use. Health authorities must be given detailed projections of these costs.

Does halothane anaesthesia decrease the metabolic and endocrine stress responses of newborn infants undergoing operation?

Concern about the side effects of various anaesthetic agents in newborn infants has led to the widespread use of anaesthesia with unsupplemented nitrous oxide and oxygen with muscle relaxants in such patients. To investigate the efficacy of such a regimen 36 neonates undergoing operations were randomised to two groups: one group received anaesthesia with nitrous oxide and curare alone and the other was additionally given halothane. Concentrations of metabolites and hormones were measured before and at the end of operation and at six, 12, and 24 hours after operation and the values compared between the two groups. Neonates given halothane anaesthesia showed decreased hormonal responses to operation, with significant differences between the two groups in the changes in adrenaline, noradrenaline, and cortisol concentrations and the ratio of insulin to glucagon concentration. Changes in blood concentrations of glucose and total ketone bodies and plasma concentrations of non-esterified fatty acids were also decreased in neonates receiving halothane anaesthesia. Neonates given anaesthesia with unsupplemented nitrous oxide showed significantly greater increases in the urinary ratio of 3-methylhistidine to creatinine concentration and their clinical condition was also more unstable during and after operation. Unless specifically contraindicated potent anaesthesia with halothane or other anaesthetic agents should be given to all neonates undergoing surgical operations as it decreases their stress responses and improves their clinical stability during and after operation.