Environmental researchers wait anxiously for salvation.
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Biomedical subjects
Publications and source records attributed to J Rose.
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BACKGROUND: We report on a prospective observational multicenter study of more than 1,000 consecutive patients undergoing laparoscopic colorectal procedures. The aim of the current study was to investigate the safety of laparoscopic colorectal surgery as reflected by the anastomotic insufficiency rates in the various sections of the bowel, and to compare these rates with those of open colorectal surgery. METHODS: The study was begun on August 1, 1995. Twenty-four centers in Germany, Austria, and Switzerland participated in this prospective multicenter study. All patients undergoing laparoscopic colorectal surgery were included in the study. No selection criteria were applied, which means that every operation begun as a laparoscopic procedure was included. Data on patient demographics, surgical indications, surgical course, and patient outcome were recorded prospectively in a computer database. All data were rendered anonymous. RESULTS: Between August 1995 and February 1998, the 24 participating centers treated 1,143 patients (male/female ratio, 1:1.36; mean age, 60.7 years). In all, 626 operations were performed for benign indications and 517 for cancer. Most procedures involved the sigmoid colon and rectum (80.9%). An anastomosis was performed in 83% of the operations. Most of the anastomoses were laparoscopically assisted using the stapling technique. We observed an overall leakage rate of 4.25% (colon 2.9%; rectum 12.7%), and surgical reintervention was required in 1% of the cases. The rate of conversion to open surgery was 5.6%. Intraoperative complications occurred in 5.9%, and reoperation was necessary in 4.1% of the cases. The overall morbidity rate was 22.3%, and the 30-day mortality rate was 1.57%. CONCLUSIONS: The feasibility and safety of the laparoscopic colorectal approach is demonstrated clearly. The current study shows that the laparoscopic or laparoscopically assisted approach to colorectal surgery is not associated with a higher risk of anastomotic leaks. Morbidity and mortality rates with this method approximate those seen with conventional colorectal surgery.
The present study describes the development of a questionnaire, and the subsequent collection of data, to gather information on the demands and supports which influence stress (as measured by anxiety and depression scales) in direct care staff who work with people with intellectual disability. The results from the questionnaire were also used to explore the relationships between the factors derived from the questionnaire and to consider how these may be influential in building organizational models. The questionnaire was specifically constructed to measure the demands and supports experienced by direct care staff. The participants included 216 staff working in community residential services for people with intellectual disability. These individuals included staff working for two British health trusts and similar staff working for one local authority. The questionnaire consisted of 33 demands items and 23 supports items. Separate factor analyses were conducted on the demands and supports scales. Analyses of the reliability and validity of the resulting factors were conducted. Stepwise multiple regressions were conducted to further explore the relationship of factors with the measures of anxiety and depression. Four factors were extracted from the demands scale and three factors from the support scale. There was some concern over levels of reliability and validity for individual factors; however, the reliability of the main scales appeared to be satisfactory. All but one support factor correlated significantly with levels of anxiety and depression. The factors explained a modest amount of the variance in the regressions. While there are some concerns about the psychometric properties of the questionnaire, it is argued that the scales and factors can be used to confirm and further understanding of the relationship between groups of demands, supports and stress in staff. The usefulness of the questionnaire as a means of diagnosing specific sources of demand and support is considered. It is suggested that the questionnaire could form the basis for assessment and subsequent intervention in houses where staff are reporting relatively high levels of anxiety and depression.
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Crystals of recombinant obelin, the Ca(2+)-regulated photoprotein from the marine hydroid Obelia longissima, have been grown from sodium citrate solutions. Crystals grow as hexagonal light-yellow rods (0.1 x 0.1 x 1.0 mm) which diffract to beyond 1.8 A with synchrotron radiation of 1.0 A wavelength. The crystals have a primitive hexagonal lattice with unit-cell parameters a = 81.55, c = 86.95 A. The asymmetric unit contains two molecules. This represents the successful preparation of single crystals of a photoprotein obelin which have promising diffraction properties.
The promoter region of the mouse adenine phosphoribosyltransferase (aprt) gene contains one non-consensus Sp1 binding site at its 5' end followed by three consensus Sp1 binding sites. The two 3'-most binding sites are sufficient for maximal expression of aprt , suggesting that the non-consensus and consensus binding sites at the 5' end are redundant. However, the two 3' sites are not sufficient to block epigenetic inactivation, which led to the hypothesis that the redundant consensus and/or non-consensus 5' Sp1 binding sites are required to block inactivation events. To test this hypothesis, promoter region constructs were made in which the two 5' Sp1 binding sites were mutated alone or in tandem, and then each construct was tested for its ability to withstand epigenetic inactivation. A cis -acting methylation center that is normally located 1.2 kb upstream of the promoter was used to induce inactivation. The results demonstrate that the presence of the redundant consensus Sp1 binding site is required to block methylation-associated gene inactivation. Therefore, the Sp1 binding sites comprising the mouse aprt promoter have evolved two distinct functions, one to promote transcription and the other to block epigenetic inactivation.
OBJECTIVE: To examine the relationship between HIV protease genotype and altered protease inhibitor sensitivity of isolates from patients after therapy with saquinavir (SQV) in its hard gelatin formulation. DESIGN: Forty-one post-therapy isolates and corresponding baseline samples were obtained from 37 patients in four different clinical trials after therapy with SQV for 16-147 weeks. Post-therapy isolates were selected on the basis of preliminary sequence or drug sensitivity data. RESULTS: Fifteen out of 17 isolates without detectable Val-48 or Met-90 mutations retained sensitivity to SQV. (The remaining isolates showed only a marginal increase in median inhibitory concentration.) In addition, three out of 15 isolates with Met-90 retained sensitivity to all other protease inhibitors tested (indinavir, ritonavir, amprenavir, nelfinavir). Of the isolates showing reduced sensitivity to SQV, six out of 22 retained sensitivity to all other protease inhibitors, whereas only four out of 22 showed broad cross-resistance to all protease inhibitors tested. The reduction in sensitivity correlated closely with the presence of Val-48 or Met-90. Subsequent accessory substitutions were also linked to reduced sensitivity. However, significant linkage was observed only between mutations at residues 48 and 82 and between those at residues 82 and 74. CONCLUSIONS: Recruitment of Val-48/Met-90 mutations was not found to be synonymous with cross-resistance. Indeed, the majority of isolates with these mutations retained sensitivity to at least one protease inhibitor (Val-48, 86%; Met-90, 77%). The recruitment of accessory mutations may occur only after the selection of key resistance mutations. Furthermore, Met-90 was found to be a poor marker of cross-resistance in SQV-treated patients.
To determine the role that cellular immune responses play in the protection conferred by vaccination with attenuated SIVmac32H (pC8), we have attempted to deplete macaques of their CD8+ cells prior to challenge with wild-type SIVmac32H (pJ5). In two of four pC8-infected macaques, N109 and N112, a transient partial depletion of CD8+ cells by antibody treatment was achieved. On the day of challenge peripheral CD2+CD4-CD8+ cell counts were reduced by 92 and 95%, respectively, in animals N109 and N112 and their lymph nodes revealed a 46 and 58% reduction, respectively, in CD2+CD4-CD8+ cells. Two other pC8-immunized macaques, N110 and N111, treated in the same way, did not show significant depletion of CD8+ cells. None of these four pC8-immunized animals became infected when challenged with 50 MID50 of pJ5. Treatment of a further four pC8-infected and protected macaques and two naive control animals with Campath-1H antibody successfully depleted peripheral CD3+ cell counts by >99% in all treated animals. Campath-1H depletion resulted in enhanced, longer lasting lymphoid depletion. Yet subsequent challenge with 20 MID50 of pJ5 still failed to infect the pC8-immunized animals. All eight of the naive controls, including two Campath-1H-treated animals, became infected following challenge. In summary, partial depletion of circulating CD8+ cells or total lymphocytes prior to challenge failed to abrogate the protection conferred by vaccination with pC8.
The crystal structure of the glutamine-binding protein (GlnBP) complexed with its ligand (Gln) was determined and refined to 1.94 A resolution. This ellipsoidal protein has two globular domains and is approximately 52 Ax40 Ax35 A in size. The glutamine ligand is located in the cleft between the two domains and stablized by hydrogen bondings and ionic interactions with Asp10, Gly68, Thr70, Ala67, Asp157, Arg75, Lys115, Gly119 and His156. The aliphatic portion of the glutamine ligand is sandwiched in a hydrophobic pocket formed between Phe13 and Phe50 and has 21 van der Waals contacts with GlnBP. Lys115 and His156, that are unique to GlnBP among amino acid binding proteins, apparently contribute to the ligand binding specificity of GlnBP. Asp10 is within 3 A of Lys115. These two residues are over 10 A apart in the ligand-free form of the GlnBP. In addition, GlnBP-Gln exhibits a large-scale movement of the two hinges connecting the two globular domains upon ligand binding. The most significant changes are 41.1 degrees in the phi angle of Gly89 and 34.3 degrees in the psi angle of Glu181 from the first and the second hinge of the protein, respectively. Besides the original six hydrogen bonds, three extra hydrogen bonds can be observed between the two hinge strands upon ligand binding. A hydrogen bond network connects the large domain to the second hinge and a second hydrogen bond network coalesces the small domain to the same strand, both via interaction with the glutamine ligand. Although the two strands of the hinge connecting the domains do not directly participate in the ligand binding, Gln183 and Tyr185 from the second hinge may be involved in the cascade of the conformational change that is induced by ligand binding.
Measurements of standing balance were determined for 92 children and adolescents, 5-18 years old, while they stood on a force plate with eyes open or eyes closed. The measurements included center-of-pressure calculations for path length per second, average radial displacement, anterior-posterior and mediolateral amplitudes, area per second, mean frequency of sway, Brownian random motion measure of short-term diffusion coefficient, and long-term scaling exponent. All balance parameters improved from youngest to oldest subjects, and the parameters improved when measured with the subjects' eyes open compared with closed. The mean values for data from three trials varied by only 5% when compared with the mean values from 10 trials. Data from this study suggest that force-plate center-of-pressure data can be used to determine differences in standing balance between children and adolescents of different ages and those with movement and balance abnormalities.
In rabbits, inhibition of either protein kinase C or protein tyrosine kinase abolishes the infarct size reduction achieved by ischemic preconditioning. In pigs, however, inhibition of protein kinase C does not attenuate ischemic preconditioning. The present study tested whether inhibition of protein tyrosine kinase alone or in combination with inhibition of protein kinase C interferes with ischemic preconditioning in pigs. In 29 enflurane-anesthetized pigs, the LAD was cannulated and perfused from an extracorporeal circuit. Protein tyrosine kinase and protein kinase C were inhibited by continuous intracoronary infusion of genistein (5x10(-6) mol/l) and staurosporine (10(-7) mol/l), respectively. Subendocardial blood flow (ENDO) was measured with microspheres. Infarct size was analysed by TTC staining (% of LV area at risk) following 90 min low-flow ischemia and 120 min reperfusion. In the presence of genistein, 90 min ischemia at an ENDO of 0.06+/-0.01 (+/-s.e.m.) ml/min/g resulted in an infarct size of 16.7+/-4.2% (n=8). With genistein, ischemic preconditioning by 10 min ischemia and 15 min reperfusion still reduced infarct size to 6.5+/-2.7% (ENDO: 0.05+/-0. 01 ml/min/g, n=7, P<0.05). In the presence of both genistein and staurosporine, infarct size following 90 min ischemia was 14.1+/-3. 6% (ENDO: 0.06+/-0.01 ml/min/g, n=7). With genistein and staurosporine, ischemic preconditioning no longer reduced infarct size significantly (11.5+/-3.1%, ENDO: 0.06+/-0.01 ml/min/g, n=7). The effective attenuation of ischemic preconditioning only by simultaneous inhibition of both, protein kinase C and protein tyrosine kinase, suggests a complex signal cascade involving both protein kinases.
OBJECTIVE: Short-term myocardial hibernation is characterized by an adaptation of contractile function to the reduced blood flow, the recovery of creatine phosphate content and lactate balance back towards normal, whereas ATP content remains reduced at a constant level. We examined the hypothesis that, despite the absence of ATP recovery, the short-term hibernating myocardium regains an energetic balance. METHODS: An enzymatic method was modified for the measurement of inorganic phosphate (Pi) in transmural myocardial drill biopsies (about 5 mg). In 12 anaesthetized swine, moderate ischemia was induced by reduction of coronary inflow into the cannulated left anterior descending coronary artery to decrease regional myocardial function (sonomicrometry) by 50%. RESULTS: The development of short-term hibernation was verified by the recovery of creatine phosphate content, the persistence of inotropic reserve in response to dobutamine and the absence of necrosis (triphenyl tetrazolium chloride). At 5-min ischemia, Pi was increased from 3.6 +/- 0.3 (SD) to 8.1 +/- 1.1 mumol/gwet wt (p < 0.05). The free energy of ATP hydrolysis (delta GATP) was decreased from -57.8 +/- 0.8 to -52.2 +/- 1.4 kJ/mol (p < 0.05). The relationships between function and Pi (r = -0.81) and delta GATP (r = -0.83), respectively, during control and at 5-min ischemia became invalid at 90-min ischemia, as myocardial blood flow and function remained reduced at a constant level, but Pi decreased back to 4.9 +/- 0.9 mumol/g (p < 0.05 vs. control and 5-min ischemia), and delta GATP fully recovered back to -57.2 +/- 1.3 kJ/mol (p < 0.05 vs. 5-min ischemia). CONCLUSIONS: In short-term hibernating myocardium, myocardial inorganic phosphate content recovers partially and the free energy change of ATP hydrolysis returns to control values. Contractile function remains reduced by mechanisms other than an energetic deficit.
We investigated the relationship between serum concentrations of prolactin (PRL) and dehydroepiandrosterone (DHEA) during initiation and development of summer and winter hair growth (anagen) cycles in mink. In the spring, haloperidol (HAL) increased PRL concentrations and induced summer anagen earlier than controls, whereas melatonin (MEL) inhibited PRL secretion and completely blocked summer anagen. In the fall, HAL increased PRL concentrations, inducing anagen at an earlier time than controls, although the resulting fur was abnormal being almost devoid of underhair fibers. Exogenous MEL during the fall reduced PRL concentrations, initiating winter anagen 4 weeks earlier than controls. Adrenalectomy (ADX) induced earlier onset of summer and winter anagen and neutralized the inhibitory effects of HAL in the fall and MEL in the spring. No change in serum DHEA concentrations was observed during the onset of summer or winter anagen in any group although MEL increased DHEA levels from 27 March through 5 June relative to HAL-treated mink. We conclude that changes in serum levels of DHEA and PRL are not requisite to onset of summer or winter anagen in mink. It is possible that metabolites of DHEA and/or PRL may still affect other aspects of the hair growth cycle.
Direct care staff working in six residential group homes for people with intellectual disability were asked to complete a questionnaire which asked for information on levels of stress (anxiety and depression), the types of demand experienced by the staff, the support they received and the constraints they faced at work. Staff were also observed at work using a schedule which detailed who they interacted with, the content and type of interaction, and what activities staff were involved in. Measurement of workers' anxiety and depression levels confirmed management assessments of staff stress levels in the homes: two residential group homes were classified as 'low stress' and four as 'high stress'. A number of differences emerged between the two groups. Staff in the high stress homes reported greater demands and less support than those in the low stress homes. Higher levels of interaction were found between staff and residents in low stress houses, where more of the interaction was given as assistance and positive interactions. However, activities in higher-stress group homes appeared to be more community oriented, with staff spending a much greater amount of time out of the house. The importance of these results for both staff and residents is discussed, and suggestions for further work are made.
The Checklist of Challenging Behaviour (CCB) was developed to survey the prevalence of challenging behaviour among people with intellectual disability. It describes 32 behaviours, and data are collected on the frequency, management difficulty and severity of these states. The present paper reports on the relationship between challenging behaviour (as measured by the CCB) and mental health (as measured by the Psychopathology Inventory for Mentally Retarded Adults). In addition, it discusses the differences between the two groups of clients used in the study, i.e. hospital and community subject groups, in terms of challenging behaviour and mental health.
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