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Biomedical subjects

B Grant

Publications and source records attributed to B Grant.

At least 19 recordsLinked to original sources

Noninvasive ventilation for prevention of post-extubation respiratory failure in obese patients.

Current recommendations for management of obese patients post-extubation are based on clinical experience and expert opinions. It was hypothesised that the application of noninvasive ventilation (NIV) during the first 48 h after extubation in severely obese patients would reduce post-extubation failure and avert the need for reintubation. Following protocol-driven weaning trials, 62 consecutive severely obese patients (body mass index > or =35 kg x m(-2)) were assigned to NIV via nasal mask immediately post-extubation and compared with 62 historically matched controls who were treated with conventional therapy. The primary end-point was the incidence of respiratory failure in the first 48 h post-extubation. Compared with conventional therapy, the institution of NIV resulted in 16% (95% confidence interval 2.9-29.3%) absolute risk reduction in the rate of respiratory failure. There was a significant difference in the intensive care unit and lengths of hospital stay between the two groups. Subgroup analysis of hypercapnic patients showed reduced hospital mortality in the NIV group compared with the control group. In conclusion, noninvasive ventilation may be effective in averting respiratory failure in severely obese patients when applied during the first 48 h post-extubation. In selected patients with chronic hypercarbia, early application of noninvasive ventilation may confer a survival benefit.

Adult↗

A randomised trial to evaluate the self-administered standardised chronic respiratory questionnaire.

The original chronic respiratory questionnaire (CRQ), one of the most widely used measures of health-related quality of life (HRQL) in chronic respiratory disease (CRD), is traditionally interviewer administered (IA) and includes an individualised dyspnoea domain. The present authors studied the impact of self-administered (SA) and standardised dyspnoea questions on CRQ measurement properties. In a factorial design multicentre trial, 177 patients with CRD (mean age 67.7 yrs; mean forced expiratory volume in one second per cent predicted 44.6%) were randomised to CRQ-IA (n = 86) or CRQ-SA (n = 91), and to initially complete the standardised or individualised items before and after respiratory rehabilitation. While maintaining validity, the CRQ-SA proved more responsive to changes in HRQL than the CRQ-IA in all domains. Compared with the standardised dyspnoea domain, the individualised dyspnoea domain indicated greater responsiveness. The correlations of baseline scores and change scores with other HRQL instruments indicated good validity of the CRQ-SA. In conclusion, self-administration and standardisation of the chronic respiratory questionnaire maintains validity and responsiveness relative to the interviewer-administered chronic respiratory questionnaire. These results challenge the assumption that interviewer-administered questionnaires are superior to self-administered questionnaires in older patients with chronic respiratory disease.

Adaptation, Physiological↗

Supporting families of critically ill children at home using videoconferencing.

Home videoconferencing links for families of children recently discharged with complex congenital heart disease may be useful in monitoring potentially unstable patients. A randomized controlled trial was carried out comparing home videoconferencing with telephone contact. Patients were randomized to an interventional videoconferencing group (n = 14), or to one of two control groups: the first (n = 9) received the same ad hoc telephone support that was available to all patients; the second group (n = 13) received regular telephone calls with the same protocol as those in the videoconferencing group. The results from the trial are still being analysed. Our experience with commercial cable modem transmission quickly showed that this is an unsuitable modality. Preliminary results with ISDN videoconferencing are encouraging. Initial results and feedback from families strongly suggest that videoconferencing provides significant benefits over telephone follow-up.

Child↗

Telemedicine applications for the regional paediatric cardiology service in Northern Ireland.

The regional paediatric cardiology centre in Northern Ireland has a telemedicine network linking the neonatal units of three district general hospitals using ISDN and IP-compliant equipment. We have previously reported the use of ISDN transmission at 128 kbit/s for remote echocardiography. In a series of 61 patients, a total of 59 transmitted scans were of sufficient diagnostic quality to confirm or exclude the presence of major congenital heart disease (CHD). There were three diagnostic errors (7%). Subsequently, we have examined the use of ISDN transmission at 384 kbit/s. Echocardiographic studies were carried out on 21 patients and all were followed up. Fourteen patients (67%) had CHD confirmed. There were two diagnostic errors (10%). Our experience of transmitting live echocardiographic images suggests that ISDN at 384 kbit/s provides the optimum balance between the clarity of the transmitted images and costs. We expect that IP videoconferencing will offer similar quality but at a lower running cost, and are currently assessing it in a pilot study. All sites within our network will remain capable of ISDN transmission until the efficacy and reliability of IP transmission has been demonstrated in a controlled trial. The clinical telemedicine service has led to the earlier diagnosis of and instigation of appropriate treatment for CHD.

Computer Communication Networks↗

Candida osteomyelitis and diskitis after spinal surgery: an outbreak that implicates artificial nail use.

Postoperative wound infection after laminectomy is uncommon. In February 1997, 3 patients were confirmed to have postlaminectomy deep wound infections due to Candida albicans. No similar case had been seen during the previous 10 years. The infections were indolent, with a mean time from initial operation to diagnosis of 54 days (range, 26-83 days). All patients were successfully treated. Pulsed-field gel electrophoresis revealed the Candida isolates to be identical. A case-controlled study and medical record review revealed that a single operating room technician scrubbed on all 3 infected case patients but on only 32% of the uninfected controls. The technician had worn artificial nails for a 3-month period that included the dates of laminectomy site infections, and C. albicans was isolated from her throat. She was treated with fluconazole and removed from duty. No subsequent cases have occurred during the ensuing 3 years. Artificial nails are known to promote subungual growth of gram-negative bacilli and yeast. This may be clinically relevant, and hospitals should enforce policies to prevent operating room personnel from wearing artificial nails.

Adult↗

Diurnal fluxes and the isotopomer ratios of N(2)O in a temperate grassland following urine amendment.

There is an urgent need to provide an accurate, up-to-date estimate of N(2)O fluxes in order that national policies can be developed to reduce emissions of N(2)O from soils. There are only limited data on temporal and diurnal patterns of N(2)O fluxes to the atmosphere, mainly due to constraints in the measurement techniques. In this paper we present the first terrestrial source values of N(2)O isotopomers and have measured and quantified the temporal and diurnal variability in N(2)O fluxes following urine addition to a grassland system in the UK. The experiment was carried out over a 2-week period on an artificially drained grassland system at the Institute of Grassland and Environmental Research (IGER), North Wyke, UK. Duplicate samples of urine, each of 2 L, were collected from dairy cows and applied to chambers (of area 0.16 m(2)). The N(2)O diurnal fluxes from urine and control (no urine) plots were measured by an automatic closed chamber technique. The isotopomers of N(2)O were obtained by analysing the gas samples collected during a peak emission phase. Soil and meteorological data were also collected. The results showed strong diurnal variations in N(2)O fluxes with minimum fluxes generally occurring between 7:00 and 14:00 hrs. The total cumulative flux of N(2)O for the whole experimental period was higher by a factor of >2 compared with estimates based on the daytime (between 10.00-16.00 hrs) measurements only. Therefore, measurements of N(2)O fluxes based on daily single exposure and expressed on a 24-h basis could impose a considerable bias and inaccuracy to the emission estimates, depending on when it was taken. The measured site preference values (difference between the centre (delta(15)Nalpha) and the end (delta(15)Nbeta) N atom of the N(2)O molecule) for soil-emitted N(2)O measured during our study were always lower than the tropospheric value. This work confirms that the enhanced tropospheric N(2)O site preference value could be the result of the back injection from the stratosphere. The intramolecular isotope ratios of nitrogen (delta(15)N) and oxygen (delta(18)O) and the site preference of the emitted N(2)O indicated that there was a shift of processes during the measurement period.

Algorithms↗

Caenorhabditis elegans auxilin: a J-domain protein essential for clathrin-mediated endocytosis in vivo.

The budding of clathrin-coated vesicles is essential for protein transport. After budding, clathrin must be uncoated before the vesicles can fuse with other membranous structures. In vitro, the molecular chaperone Hsc70 uncoats clathrin-coated vesicles in an ATP-dependent process that requires a specific J-domain protein such as auxilin. However, there is little evidence that either Hsc70 or auxilin is essential in vivo. Here we show that C. elegans has a single auxilin homologue that is identical to mammalian auxilin in its in vitro activity. When RNA-mediated interference (RNAi) is used to inhibit auxilin expression in C. elegans, oocytes show markedly reduced receptor-mediated endocytosis of yolk protein tagged with green fluorescent protein (GFP). In addition, most of these worms arrest during larval development, exhibit defective distribution of GFP-clathrin in many cell types, and show a marked change in clathrin dynamics, as determined by fluorescence recovery after photobleaching (FRAP). We conclude that auxilin is required for in vivo clathrin-mediated endocytosis and development in C. elegans.

Adaptor Proteins, Vesicular Transport↗

Rme-1 regulates the distribution and function of the endocytic recycling compartment in mammalian cells.

RME-1 is an Eps15-homology (EH)-domain protein that was identified in a genetic screen for endocytosis genes in Caenorhabditis elegans. When expressed in a CHO cell line, the worm RME-1 protein and a mouse homologue are both associated with the endocytic recycling compartment. Here we show that expression of a dominant-negative construct with a point mutation near the EH domain results in redistribution of the endocytic recycling compartment and slowing down of transferrin receptor recycling. The delivery of a TGN38 chimaeric protein to the trans-Golgi network is also slowed down. The function of Rme-1 in endocytic recycling is evolutionarily conserved in metazoans as shown by the protein's properties in C. elegans.

Adaptor Proteins, Signal Transducing↗

Evidence that RME-1, a conserved C. elegans EH-domain protein, functions in endocytic recycling.

In genetic screens for new endocytosis genes in Caenorhabditis elegans we identified RME-1, a member of a conserved class of Eps15-homology (EH)-domain proteins. Here we show that RME-1 is associated with the periphery of endocytic organelles, which is consistent with a direct role in endocytic transport. Endocytic defects in rme-1 mutants indicate that the protein is likely to have a function in endocytic recycling. Evidence from studies of mammalian RME-1 also points to a function for RME-1 in recycling, specifically in the exit of membrane proteins from recycling endosomes. These studies show a conserved function in endocytic recycling for the RME-1 family of EH proteins.

Animals↗

Distribution and transport of cholesterol in Caenorhabditis elegans.

Cholesterol transport is an essential process in all multicellular organisms. In this study we applied two recently developed approaches to investigate the distribution and molecular mechanisms of cholesterol transport in Caenorhabditis elegans. The distribution of cholesterol in living worms was studied by imaging its fluorescent analog, dehydroergosterol, which we applied to the animals by feeding. Dehydroergosterol accumulates primarily in the pharynx, nerve ring, excretory gland cell, and gut of L1-L3 larvae. Later, the bulk of dehydroergosterol accumulates in oocytes and spermatozoa. Males display exceptionally strong labeling of spermatids, which suggests a possible role for cholesterol in sperm development. In a complementary approach, we used a photoactivatable cholesterol analog to identify cholesterol-binding proteins in C. elegans. Three major and several minor proteins were found specifically cross-linked to photocholesterol after UV irradiation. The major proteins were identified as vitellogenins. rme-2 mutants, which lack the vitellogenin receptor, fail to accumulate dehydroergosterol in oocytes and embryos and instead accumulate dehydroergosterol in the body cavity along with vitellogenin. Thus, uptake of cholesterol by C. elegans oocytes occurs via an endocytotic pathway involving yolk proteins. The pathway is a likely evolutionary ancestor of mammalian cholesterol transport.

Animals↗

RME-8, a conserved J-domain protein, is required for endocytosis in Caenorhabditis elegans.

By genetic analysis of Caenorhabditis elegans mutants defective in yolk uptake, we have identified new molecules functioning in the endocytosis pathway. Here we describe a novel J-domain-containing protein, RME-8, identified by such genetic analysis. RME-8 is required for receptor-mediated endocytosis and fluid-phase endocytosis in various cell types and is essential for C. elegans development and viability. In the macrophage-like coelomocytes, RME-8 localizes to the limiting membrane of large endosomes. Endocytosis markers taken up by the coelomocytes rapidly accumulate in these large RME-8-positive endosomes, concentrate in internal subendosomal structures, and later appear in RME-8-negative lysosomes. rme-8 mutant coelomocytes fail to accumulate visible quantities of endocytosis markers. These observations show that RME-8 functions in endosomal trafficking before the lysosome. RME-8 homologues are found in multicellular organisms from plants to humans but not in the yeast Saccharomyces cerevisiae. These sequence homologies suggest that RME-8 fulfills a conserved function in multicellular organisms.

Amino Acid Sequence↗

Incidence of blindness due to diabetic eye disease in Fife 1990-9.

AIMS: In the light of goals for reducing blindness due to diabetes, published in the St Vincent Declaration, 1989, the aim of this study was to find the incidence and prevalence of blindness in the diabetic population of Fife. METHODS: All blind registrations for the period 1990-9 were studied. Those with diabetes as the first or main diagnosis were included as new diabetic blind. The prevalence of diabetes was studied in a large sample population and extrapolated to the estimated population of Fife. RESULTS: The incidence of blindness due to diabetes was 64 (SD 24, 95% CI 49-79) per 100 000 diabetic population/year. The point prevalence of blindness due to diabetes on 31 December 1999 was 210 per 100 000 diabetic population. CONCLUSION: The incidence of blindness due to diabetes, in a diabetic population, is now known. Without this benchmark it is impossible to assess the implementation of the St Vincent Declaration.

Blindness↗

Immuno-EM localization of GFP-tagged yolk proteins in C. elegans using microwave fixation.

Because of the presence of a low-permeability cuticle covering the animal, fixation of C. elegans tissue for immunoelectron microscopy has proved very difficult. Here we applied a microwave fixation protocol to improve penetration of fixatives before postembedding immunogold labeling. Using this technique, we were able to successfully localize several components of yolk (YP170) trafficking in both wild-type and transgenic strains expressing a vitellogenin::green fluorescent protein fusion (YP170::GFP). Green fluorescent protein (GFP) and its variants are commonly used as markers to localize proteins in transgenic C. elegans using fluorescence microscopy. We have developed a robust method to localize GFP at the EM level. This procedure is applicable to the characterization of transgenic strains in which GFP is used to mark particular proteins or cell types and will undoubtedly be very useful for high-resolution analysis of marked structures.

Animals↗

Effects of dung and urine amendments on the isotopic content of N(2)O released from grasslands.

The temporal and diurnal changes in nitrous oxide (N(2)O) fluxes were measured between 29(th) September and 2(nd) November 1999 from urine and dung patches from cattle deposited on grazed grassland. The delta(15)N and delta(18)O values of the N(2)O emitted from soil from both treatments were examined on four occasions during this period. The diurnal fluxes of N(2)O were measured by a chamber technique that provides hourly measurement of N(2)O fluxes. The (15)N and (18)O analysis of N(2)O were determined by isotope ratio mass spectrometry. N(2)O fluxes from the excreta patches were large, with peak emissions up to 1893 ng N m(-2) s(-1) occurring after heavy precipitation, measured one month after the treatment applications. Emissions from the urine patches were significantly greater than from the dung. The results showed that excretal patches are an important source of atmospheric N(2)O. The flux pattern showed a strong diurnal variation with maximum fluxes generally occurring in late afternoon or early morning, and generally not in phase with the soil temperature changes. The isotopic content of (15)N and (18)O in the N(2)O showed a similar trend to that of the N(2)O flux. The (15)N and (18)O values of the N(2)O emitted from the soil indicated that denitrification was the major process involved. After heavy precipitation on the 6(th) October, the larger delta(15)N and delta(18)O values suggested a consumption of the N(2)O by total denitrification.

Algorithms↗

Withdrawal and tolerance: prognostic significance in DSM-IV alcohol dependence.

OBJECTIVE: The clinical and research importance of tolerance and/or withdrawal in the diagnosis of substance dependence has been identified as a key area needing clarification. Earlier longitudinal studies did not identify whether diagnoses of alcohol dependence were current or lifetime. In this study, the prognostic significance of the DSM-IV physiological specifier was investigated among cases of alcohol dependence current at the baseline interview. The role of tremors, required in DSM-III and DSM-III-R, was investigated as well. METHOD: Household residents (N = 130; 57% men) meeting full criteria for current DSM-IV alcohol dependence in a baseline interview were re-interviewed a year later and DSM-IV alcohol dependence was again evaluated. Reliable structured interviews were used to make the diagnoses. The DSM-IV physiologic specifier and its components were tested as predictors of outcome of DSM-IV alcohol dependence, and included an additional definition of alcohol withdrawal that required tremors. Chi-square tests and adjusted odds ratios indicated statistical significance of group differences on outcome. RESULTS: The DSM-IV physiological specifier (tolerance or withdrawal) did not predict 1-year chronicity of DSM-IV alcohol dependence, nor did tolerance when considered separately. However, withdrawal predicted poor outcome (e.g., 1-year chronicity of DSM-IV alcohol dependence). The effect of withdrawal was strengthened when tremors were required as part of the withdrawal syndrome. CONCLUSIONS: In contrast to earlier longitudinal research, this study supports the prognostic relevance of one component of the present DSM-IV physiological specifier--withdrawal. Withdrawal appears to have stronger prognostic meaning when the DSM-III-R version, in which tremors were required, is used. Further studies of the physiological subtype may benefit from studying subjects who have been clearly identified at the baseline evaluation as having a current diagnosis of dependence.

Adolescent↗

Platelet adenylyl cyclase activity as a trait marker of alcohol dependence. WHO/ISBRA Collaborative Study Investigators. International Society for Biomedical Research on Alcoholism.

BACKGROUND: There is compelling evidence that genetic factors play a major role in the development of alcohol dependence. Platelet adenylyl cyclase (AC) activity has been proposed as a biochemical marker for differentiating alcohol-dependent and nondependent subjects, but the sensitivity and specificity of this marker have not been ascertained. The objective of this study was to determine the sensitivity and specificity of platelet AC activity in identifying alcohol-dependent subjects and to ascertain the effect of medical/ psychiatric variables, drinking and smoking history, and age and body weight on AC activity. METHODS: The cross-sectional study was conducted from 1995 to 1998. Participants were 210 Australian White men who were community volunteers and alcohol treatment inpatients in Sydney, Australia. There were 41 nondrinkers, 140 drinkers, and 29 men who were entering alcohol treatment. The main outcome measure was platelet AC activity. Classification variables were plasma ethanol, gamma-glutamyltransferase, aspartate aminotransferase, serum carbohydrate-deficient transferrin (CDT), and urinary 5-hydroxytryptophol/5-hydroxyindoleacetic acid (5-HTOL/5-HIAA) levels, and World Health Organization/International Society for Biomedical Research on Alcoholism Interview Schedule variables, which included alcohol use and dependence criteria. RESULTS: Among subjects who reported abstinence for at least 4 days, both cesium fluoride (CsF)- and forskolin-stimulated platelet AC activities were significantly lower in those with a lifetime history of alcohol dependence compared with those with no such history (p < 0.005 and p < 0.05, respectively). The sensitivity and specificity of CsF-stimulated AC activity to discriminate individuals with a lifetime history of alcohol dependence were 75% and 79%, respectively. Similar values for sensitivity and specificity for CsF-stimulated AC activity were calculated when discriminating current alcohol dependence in the subjects in our sample. Irrespective of the history of alcohol dependence, persons who had consumed alcohol recently (within the last 3-4 days) showed significantly higher mean basal, CsF-stimulated, and forskolin-stimulated AC activity (p < 0.001), as did those who had elevated 5-HTOL/5-HIAA ratios or CDT levels, indicative of recent (heavy) drinking. The "normalization" of platelet AC activity to baseline levels after an individual stops drinking may be related to the generation of new platelets during the abstinence period. Conduct disorder and antisocial personality disorder were not associated with low AC activity, but low forskolin-stimulated AC activity was associated with major depression. CONCLUSIONS: We found that CsF- and forskolin-stimulated platelet AC activity discriminates between subjects with and without alcohol dependence in a population of subjects who had not consumed significant quantities of ethanol recently. Recent alcohol consumption is a confounding variable that can alter the measured levels of AC activity. Forskolin-stimulated platelet AC activity also may be influenced by a history of major depression.

Adenylyl Cyclases↗

Domiciliary post-operative assessment following cataract surgery carried out by specialist nurses.

PURPOSE: To establish whether first day postoperative review by ophthalmic trained nurses following day case cataract surgery is a safe and effective practice. METHODS: A prospective study was undertaken of all patients undergoing day case cataract surgery followed by a domiciliary visit in 1996. Principal outcome measures were: (1) incidence of problems diagnosed by the nurses at the first visit, (2) the rate of referral to the hospital for medical review, (3) incidence of problems identified at the first clinic review (10-14 days later), with particular attention paid to any that might be attributed to an event 'missed' by the nurse at the first day, and (4) visual acuity at 3 months, to allow comparison with previously published national outcome measures. RESULTS: From 281 cases, although nurses identified a problem in 11%, only 4.2% required referral back to medical staff from the domiciliary visit; 2.1% required re-admission over the first 2 weeks. Only one case (0.35%) was found to have a missed pathology; this patient had no long-term adverse outcome. Visual acuity outcomes at 3 months compared favourably with results from the National Cataract Surgery Survey. CONCLUSIONS: Domiciliary visits by ophthalmic trained nurses are a safe alternative to routine hospital review by medical staff.

Ambulatory Surgical Procedures↗