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Biomedical subjects

R Webster

Publications and source records attributed to R Webster.

At least 37 records · Page 2Linked to original sources
PubMed2000

A prototype haptic lumbar puncture simulator.

Lumbar punctures (LP) are complex, precise procedures done to obtain cerebro-spinal fluid from a patient for diagnostic purposes. Incorrect techniques resulting from inadequate training or supervision can result in sub-optimal outcomes. As tactile feedback is crucial for a successful lumbar puncture, this procedure serves as an ideal candidate for the development of a haptic training simulator. The intent of this project is to engineer a force feedback LP simulator that provides a safe method of training students (medical students, residents, or trained physicians) for an actual LP procedure on a patient.

Computer Graphics↗
PubMed1999

Temporal patterns in bovine tuberculosis in a brushtail possum population contiguous with infected cattle in the Ahaura Valley, Westland.

AIMS: To determine temporal and spatial patterns of bovine tuberculosis (Tb) in a population of brushtail possums (Trichosurus vulpecula) free from commercial and recreational hunting and living contiguously with livestock, and to relate these patterns to measures of possum health and density. METHODS: Possums were trapped on 11 lines located on a forest-rough grazing margin in the Ahaura Valley in Westland in 1979-80 and each August from 1992 to 1996, and were examined post mortem for gross lesions indicative of Tb. Infection levels in possums were compared with Th test data from cattle grazing in the same area. RESULTS: Tuberculosis was identified from the trapped sample of possums in 1980. Trapping of further possums on the same trap lines confirmed the presence of the disease each year from 1992 to 1996, and suggested a clustering of infection in time and space. The prevalence of Tb in possums declined with increasing possum population size and well being, and decreasing age. The prevalence of Tb in possums was highest in 1980 and 1992, and appeared to roughly coincide with similar upsurges in Tb in nearby cattle. CONCLUSIONS: Our results suggest that the exceptional levels of Tb recorded in possums in 1992 had a direct effect on possum numbers, and gave rise to very low trap catches in 1993-94. They also suggest that Tb can persist for several years in possum populations existing well below the 5% trap catch targeted by regional councils for Tb possum control.

Journal Article↗
PubMed1999

Role of sialylation in determining the pharmacokinetics of neutrophil inhibitory factor (NIF) in the Fischer 344 rat.

1. Recombinant neutrophil inhibitory factor (NIF) is a glycoprotein. Its amino acid sequence remains constant and has a molecular weight of 28.9 kD. However, approximately 40% of the total molecular weight consists of glycans with variable structure. 2. The pharmacokinetics of 11 different NIF batches with varying extents and patterns of sialylation have been investigated in the Fischer 344 rat following intravenous administration. These data indicate that reducing the extent of NIF sialylation reduces the half-life of the molecule due to an increase in the systemic clearance. Also, an increase in the number of unsialylated or neutral glycans may increase the volume of distribution of NIF, although this effect is marginal. 3. Isolated perfused rat liver (IPRL) investigations have shown that sialylated NIF has a low hepatic extraction (< 1%), while asialo NIF has an extraction that is > 20-fold higher. Co-administration of asialo NIF with asialo fetuin (a protein cleared by hepatic asialoglycoprotein receptor (possibly galactose)-mediated uptake reduced the hepatic extraction of asialo NIF. 4. These data suggest that NIF molecules that have free sugar moieties (possibly galactose) interact with an asialoglycoprotein receptor (possibly galactose-mediated) in the liver (parenchymal cells/hepatocytes). Interaction with this receptor leads to cellular internalization and degradation.

Animals↗
PubMed1999

The surface glycoproteins of H5 influenza viruses isolated from humans, chickens, and wild aquatic birds have distinguishable properties.

In 1997, 18 confirmed cases of human influenza arising from multiple independent transmissions of H5N1 viruses from infected chickens were reported from Hong Kong. To identify possible phenotypic changes in the hemagglutinin (HA) and neuraminidase (NA) of the H5 viruses during interspecies transfer, we compared the receptor-binding properties and NA activities of the human and chicken H5N1 isolates from Hong Kong and of H5N3 and H5N1 viruses from wild aquatic birds. All H5N1 viruses, including the human isolate bound to Sia2-3Gal-containing receptors but not to Sia2-6Gal-containing receptors. This finding formally demonstrates for the first time that receptor specificity of avian influenza viruses may not restrict initial avian-to-human transmission. The H5N1 chicken viruses differed from H5 viruses of wild aquatic birds by a 19-amino-acid deletion in the stalk of the NA and the presence of a carbohydrate at the globular head of the HA. We found that a deletion in the NA decreased its ability to release the virus from cells, whereas carbohydrate at the HA head decreased the affinity of the virus for cell receptors. Comparison of amino acid sequences from GenBank of the HAs and NAs from different avian species revealed that additional glycosylation of the HA and a shortened NA stalk are characteristic features of the H5 and H7 chicken viruses. This finding indicates that changes in both HA and NA may be required for the adaptation of influenza viruses from wild aquatic birds to domestic chickens and raises the possibility that chickens may be a possible intermediate host in zoonotic transmission.

Alpha-Globulins↗
PubMed1998

Microbial oxidative metabolism of diclofenac: production of 4'-hydroxydiclofenac using Epiccocum nigrum IMI354292.

The 4'-hydroxylated metabolite of diclofenac was produced by biocatalysis for probing specific human drug-metabolising enzymes (CYP2C9). An initial screen of 11 microorganisms was carried out (50 ml scale) to identify the organism best suited to the regioselective conversion of diclofenac to its 4'-hydroxylated metabolite. From this screen, the fungus Epicoccum nigrum IMI354292 was selected as the most suitable microorganism. Scale-up was carried out in a 30-l fermenter to which 2 g diclofenac was added. After 48 h, 50% of the diclofenac had been converted to it 4'-hydroxylated metabolite. The broth was then extracted with ethyl acetate and purified by chromatography and crystallisation. This yielded 0.3 g 4'-hydroxydiclofenac with a purity of at least 99%. The 4'-hydroxydiclofenac produced by E. nigrum was characterised by HPLC, mass spectrometry and NMR.

Biotransformation↗
PubMed1998

Multicenter study of oxygen-insensitive handheld glucose point-of-care testing in critical care/hospital/ambulatory patients in the United States and Canada.

OBJECTIVES: Existing handheld glucose meters are glucose oxidase (GO)-based. Oxygen side reactions can introduce oxygen dependency, increase potential error, and limit clinical use. Our primary objectives were to: a) introduce a new glucose dehydrogenase (GD)-based electrochemical biosensor for point-of-care testing; b) determine the oxygen-sensitivity of GO- and GD-based electrochemical biosensor test strips; and c) evaluate the clinical performance of the new GD-based glucose meter system in critical care/hospital/ambulatory patients. DESIGN: Multicenter study sites compared glucose levels determined with GD-based biosensors to glucose levels determined in whole blood with a perchloric acid deproteinization hexokinase reference method. One site also studied GO-based biosensors and venous plasma glucose measured with a chemistry analyzer. Biosensor test strips were used with a handheld glucose monitoring system. Bench and clinical oxygen sensitivity, hematocrit effect, and precision were evaluated. SETTING: The study was performed at eight U.S. medical centers and one Canadian medical center. PATIENTS: There were 1,248 patients. RESULTS: The GO-based biosensor was oxygen-sensitive. The new GD-based biosensor was oxygen-insensitive. GD-based biosensor performance was acceptable: 2,104 (96.1%) of 2,189 glucose meter measurements were within +/-15 mg/dL (+/-0.83 mmol/L) for glucose levels of < or = 100 mg/dL (< or = 5.55 mmol/L) or within +/-15% for glucose levels of > 100 mg/dL, compared with the whole-blood reference method results. With the GD-based biosensor, the percentages of glucose measurements that were not within the error tolerance were comparable for different specimen types and clinical groups. Bracket predictive values were acceptable for glucose levels used in therapeutic management. CONCLUSIONS: The performance of GD-based, oxygen-insensitive, handheld glucose testing was technically suitable for arterial specimens in critical care patients, cord blood and heelstick specimens in neonates, and capillary and venous specimens in other patients. Multicenter findings benchmark the performance of bedside glucose testing devices. With the new +/-15 mg/dL --> 100 mg/dL --> +/-15% accuracy criterion, point-of-care systems for handheld glucose testing should score 95% (or better), as compared with the recommended reference method. Physiologic changes, preanalytical factors, confounding variables, and treatment goals must be taken into consideration when interpreting glucose results, especially in critically ill patients, for whom arterial blood glucose measurements will reflect systemic glucose levels.

Adult↗
PubMed1998

Use of beta-hydroxybutyric acid levels in the emergency department.

UNLABELLED: The impact of a new test on the market, the beta-hydroxybutyric acid (BOH) assay, on clinical decision-making in the emergency department (ED) has not been well studied. In this retrospective analysis, we studied the potential benefit of this new test in the ED decision-making process in diabetic patients. BOH levels were measured on all patients who had glucose and acetone levels ordered by the emergency physician during a 3-month period in the ED of a university tertiary referral center. Two groups were analyzed: group 1 was acetone-positive and BOH-positive (n = 13); group 2 was acetone-negative BOH-positive (n = 31). There was no difference between the two groups in terms of gender (p = 0.55) or age (p = 0. 47). The length of stay (p = 0.97) and number of complications (p = 0.89) were also similar between the two groups. CONCLUSION: This study suggests that in those diabetic patients with a negative acetone test and a positive BOH test, the addition of the positive result on the BOH test may provide additional prognostic information for predicting hospital length of stay and number of in-hospital complications.

3-Hydroxybutyric Acid↗
PubMed1998

Binomial cokriging for estimating and mapping the risk of childhood cancer.

The incidences of human diseases vary from place to place, and this is also likely to be so for the risk of people developing many of them. We have analysed the spatial distribution of childhood cancer in the West Midland Health Authority Region of England from 1980 to 1984. This is a rare disease which is considered to be noncontagious. The observed frequencies of the disease in the electoral wards have been converted to proportions that estimate the risk of a child's developing it. The spatial autocorrelation of the risk, expressed in the variogram, was determined in a novel way from the proportions within electoral wards by treating them as binomial variables dependent on the risk and the numbers of children in the wards. The observed variogram was modelled by Whittle's elementary two-dimensional correlation. Covariances of the proportion and cross covariances between the proportion and the risk were derived, and from the latter and the proportions the risk was estimated in two ways by a form of cokriging: ordinary and conditional unbiased cokriging. The variogram of the risk shows strong autocorrelation, and the kriged estimates, when mapped, have a distribution that is far from even. There are patches where the estimated risk is large, especially in the rural south west and the suburban north east; and there are other patches, notably the more densely populated areas, where it is small.

Adolescent↗
PubMed1996

Development of immunity to lungworm in vaccinated calves treated with an ivermectin sustained release bolus or an oxfendazole pulse release bolus at turnout.

The ivermectin sustained release bolus (IVSRB), when used at turnout as recommended, will provide season-long control of parasitic bronchitis, thus obviating the need for use of a lungworm vaccine. However, some concerns have been expressed that calves treated with an IVSRB will receive so little exposure to Dictyocaulus viviparus that it will compromise their immunity in subsequent grazing seasons, which would be of particular importance in dairy herds. Although there is evidence that IVSRB-treated calves can develop immunity to D. viviparus when exposed to pasture infection, it was considered worthwhile to evaluate the compatibility of the IVSRB and lungworm vaccination to allow veterinary surgeons the option of using these products concurrently when they have particular concerns about the long term immune status of replacement dairy heifers. Thirty-two dairy replacement heifers were vaccinated with two doses of lungworm vaccine and, at turnout, half the calves received an IVSRB and the remainder an oxfendazole pulse release bolus (OPRB). At the end of the grazing season four replicate bolus treated pairs and four parasite-naive calves were challenged with 1000 D. viviparus infective larvae. At slaughter there was a 95% and 93% reduction in D. viviparus burdens in the IVSRB and OPRB treated calves respectively, compared with the unvaccinated, untreated controls. These results indicate that where it is considered necessary to use lungworm vaccination in addition to an IVSRB or an OPRB, the compatibility of these products with lungworm vaccine will allow development of a protective level of immunity to D. viviparus.

Animals↗
PubMed1996

Mapping heavy metals in polluted soil by disjunctive kriging.

The soil of some 50 km(2) around the town of Weinfelden in north-east Switzerland has been sampled and analysed to estimate and map the concentrations of heavy metals before an incinerator for the canton's waste is built. Given that the estimates are subject to error, the probabilities that true values exceed the maximum tolerable concentrations of the Swiss federal guide have also been estimated by disjunctive kriging. These may now be used by the local planners for making decisions. Of the metals examined, lead exceeded the guide value at several sampling points, and a moderate probability of excess of lead is fairly widespread. Copper exceeded the guide value in vineyards and orchards, but also in a few places elsewhere, and the estimated probabilities of excess were not negligible. The other two metals of concern, cadmium (with one exception) and zinc, had concentrations much less than the guide values. The patterns of distribution of the four metals were similar, the product-moment correlations among them are substantial, except in the vineyards and orchards, and it seems likely that they had common sources.

Journal Article↗
PubMed1994

Geostatistical analysis of soil contamination in the Swiss Jura.

The topsoil of a 14.5 km(2) region of the Swiss Jura has been surveyed to identify the distributions of trace metals in it. The soil was sampled at 366 sites selected by combining a square grid and nesting. Concentrations of seven potentially toxic metals, namely Cd, Co, Cr, Cu, Ni, Pb and Zn, were measured. Land use and geology (stratigraphy) were also recorded. Variograms were bounded in the range from 110 m to 1500 m with contributions to the variance at all distances exceeding 6 m. The variograms of Cd, Cr, Cu and Pb are dominated by short range correlation, those of Co and Ni by correlation of long range, and Zn is intermediate. The concentrations were estimated at the nodes of a fine grid by ordinary block kriging and then contoured to produce maps. The maps of Co and Ni have a coarse patchy pattern similar to that of the geology, suggesting that these metals derive from the bedrock. This is supported by analysing the variance by geology. Copper and Pb have finer patterns of distribution, and are more likely to have been added with fertilizer or manure or domestic waste. Cadmium could originate from human activities, such as smelters or fertilizer spreading, or from specific geological deposits, such as moraine.

Journal Article↗
PubMed1994

Association of a novel high oxygen affinity haemoglobin variant with delta beta thalassaemia.

We report an uncommon association of delta beta thalassaemia and a haemoglobin (Hb) variant with high oxygen affinity in an Asian Indian family. Minimal polycythaemia was seen in a heterozygote for this novel Hb variant, Hb Headington (beta 72 (E16) Ser-->Arg), while compound heterozygosity for Hb Headington and the Indian G gamma (A gamma delta beta)(0) thalassaemia produces a marked increase in erythrocytosis with a concomitant increase in the level of the variant Hb. The HbF in such compound heterozygotes remains at a level consistent with that usually observed in individuals heterozygous for the G gamma (A gamma delta beta)(0) thalassaemia alone. The purified Hb variant showed an increased oxygen affinity, moderately decreased co-operativity and a normal Bohr effect. Results of functional studies suggest that the high oxygen affinity of Hb Headington is due to the Ser-->Arg substitution which disrupts the normal and tight interaction between A, B and E helices leading to a destabilization of the T deoxy-structure of the abnormal haemoglobin.

Adult↗
PubMed1994

Effect of entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, on the motor response to acute treatment with levodopa in patients with Parkinson's disease.

Catechol-O-methyltransferase (COMT) inhibitors may be useful in the treatment of Parkinson's disease by improving the bioavailability of levodopa and by prolonging its effects. Entacapone (OR-611), a novel COMT inhibitor, which does not cross the blood brain barrier, was assessed in 12 patients with Parkinson's disease and motor fluctuations in a randomised, double-blind, cross-over, single dose study. The magnitude and duration of the therapeutic response to a single dose of 200 mg levodopa/50 mg carbidopa was evaluated after concomitant placebo, or 200 or 800 mg entacapone. A significant increase in the duration of the motor response to levodopa was seen when 200 mg entacapone was given with levodopa/carbidopa. Plasma levodopa concentrations were increased with both doses of the COMT inhibitor. The latency to onset of motor response did not differ significantly between active drug and placebo. Entacapone may prove useful in prolonging the duration of the benefit obtained from individual doses of levodopa.

Aged↗
PubMed1993

Crystallization and preliminary X-ray studies of influenza A virus neuraminidase of subtypes N5, N6, N8 and N9.

Neuraminidase heads from the following subtypes of influenza A virus have been crystallized: N5, N6, N8 and whale virus N9. The last three yielded crystals of X-ray diffraction quality; the N5 crystals obtained so far are not suitable for high resolution studies. The cell dimensions and space groups of crystals grown from the four subtypes have been determined.

Crystallography↗
PubMed1993

ZB51: a monoclonal antibody reactive with human plasma cells.

Several monoclonal antibodies have been raised in the past which react with human plasma cells but they have all shown additional reactions with other cell types. In this paper we describe a new monoclonal antibody, ZB51, which recognizes an intracellular antigen in normal plasma cells in cryostat tissue sections and cell smears, and which also reacts with neoplastic cells in most cases of myeloma and with plasma cell lines. The antibody shows minimal reactivity with a few eosinophils and myelocytes in bone marrow and stains a myeloid cell line. Whilst normal epithelium is not labelled, antibody ZB51 stains two carcinoma cell lines. Although it was not possible to characterize the target antigen in terms of molecular weight, the reactivity of antibody ZB51 with normal and neoplastic plasma cells makes it a useful new immunocytochemical reagent.

Antibodies, Monoclonal↗
PubMed1992

A geostatistical approach to the analysis of pattern in rare disease.

The incidences of human disease vary from place to place, and some show distinct patterns. Patterns in rare diseases, such as childhood cancer, are not readily discernible, however, and this makes it difficult to relate their distribution to factors in the environment in seeking possible causes of the disease. Provided cases are geographically indexed, data on a disease can be analysed geostatistically. Variograms can be computed to determine the strength and spatial scale of any pattern, and to summarize the variation, and then the risk of developing the disease can be estimated by kriging. This has been done for the incidence rates of childhood cancer from 1980 to 1984 in the West Midlands Health Authority Region of England. A novel modification was made to compute the variogram of the risk from that of the frequencies, taking into account the binomial nature of the data. The incidence of the disease appears patchy. The results show that this patchiness is spatially correlated and not purely random. The risk appears greatest in the rural south west of the Region and in some of the suburbs around the conurbation. This approach using geostatistics seems very promising and will be developed further as more data for this and other diseases become available.

Child↗