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Biomedical subjects

R Webster

Publications and source records attributed to R Webster.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

Sublingual apomorphine in the treatment of Parkinson's disease complicated by motor fluctuations.

Subcutaneous apomorphine is a useful treatment for refractory motor fluctuations in Parkinson's disease. We have now clinically evaluated a formulation of sublingual apomorphine (57 mg) and performed preliminary pharmacokinetic studies. In acute studies, all 10 patients switched "on" after a mean latency of 25 min with a mean duration of motor benefit of 118 min. In three patients followed for a mean of 4.7 months, we have shown that chronic sublingual use can be effective, safe, and convenient in controlling motor fluctuations. The pattern of clinical response followed closely the plasma profile of apomorphine with a mean Cmax of 76 pmol/ml (50-106 pmol/ml) and a mean Tmax of 60 min (45-80 min), with moderate interpatient variability in bioavailability. Sublingual apomorphine is a practical alternative to subcutaneous use in selected patients with severe motor fluctuations.

Administration, Sublingual

Separation of the enantiomeric intermediates of some platelet-activating factor analogues on a naphthylalanine-type Pirkle column.

A chiral high-performance liquid-chromatographic separation method was developed for the analysis of some glycerol-based, ether-linked platelet-activating factor precursors. Using a D-naphthylalanine-type Pirkle-column and tetrahydrofuran-hexane eluents, the retention-structure relationships were determined for a large number of glycerol ether derivatives. The derivatives leading to the highest chiral selectivity factors in the analytical separations were surveyed for their applicability in large-scale isolation of chiral synthetic intermediates.

Alanine

Diurnal differences in response to oral levodopa.

Diurnal differences in duration and quality of motor response to levodopa are frequently described by patients. The quality and duration of motor responses were objectively assessed to morning and afternoon oral levodopa doses in five patients with Parkinsonian motor fluctuations who complained of diurnal variation in response to their normal levodopa medication. Results suggest that under controlled conditions which eliminated the effects of diet and overlapping levodopa effects the response to levodopa remained unchanged throughout the day, and that the duration of response could be predicted by plasma levodopa levels.

Administration, Oral

Spatial distribution on pasture of infective larvae of the gastro-intestinal nematode parasites of sheep.

The horizontal distributions of infective larvae on pasture grazed by sheep have been investigated. Using Taylor's Power Law it was found that larvae had a more aggregated distribution in September than August, the Law index of aggregation being 1.97 and 1.89 for the 2 months, respectively. However, at each time the degree of aggregation remained fairly constant for a range of spacings between points from 5 to 30 m. These results suggest that Taylor's Power Law could be used as a basis for devising an efficient pasture sampling strategy. More data are required, however, to determine the extent to which aggregation of the larvae varies with time of the year.

Analysis of Variance

Levodopa peripheral pharmacokinetics and duration of motor response in Parkinson's disease.

To assess the relative influence of central pharmacodynamic and peripheral pharmacokinetic factors on the duration of motor response to levodopa, the relationship between motor function and plasma levodopa levels was studied in 31 Parkinsonian patients. Duration of benefit from single levodopa doses while fasting depended on the degree to which the plasma levodopa level had declined over four hours; wearing off occurred when the plasma levodopa level had fallen to approximately 50% of peak concentration, irrespective of the duration of the motor response. Whilst the amplitude of motor response to levodopa is likely to be modified by alternations in dopamine receptor stimulation and sensitivity as the disease progresses, it is proposed that the duration of response is primarily determined by levodopa peripheral pharmacokinetics rather than by central pharmacodynamic factors associated with dopamine storage capacity.

Administration, Oral

The effects of oral protein on the absorption of intraduodenal levodopa and motor performance.

Four patients with levodopa induced fluctuations in motor performance were studied during the constant intraduodenal infusion of levodopa. The results confirm that steady plasma levodopa levels with stable motor control can be achieved. However, when patients were given oral protein loads, motor performance declined despite maintenance of plasma levodopa levels. These findings suggest that competition for levodopa carrier mediated transport by amino acids, is more important at the blood-brain barrier than across the gut mucosa; thereby possibly limiting the efficacy of long-term direct intraduodenal administration of levodopa.

Aged

Child-environment relationships: a cross-cultural study of educable mentally retarded children and their families.

A cross-cultural study was conducted to determine the generality of child-environment relationships in Japanese and American families with educable mentally retarded (EMR) children. A total of 90 families with EMR children in Japan and 93 families with EMR children in America participated. The Henderson Environment Learning and Process Scale, Family Environment Scale, and Home Quality Rating Scale were employed in home interviews and observations. The AAMD Adaptive Behavior Scale was used to measure social competency and psychosocial adjustment of the children. The results indicated that the relation between cognitive opportunities at home and the child's social competency appeared similar between the two cultures. However, the relation between the affective aspects of home environment and the child's psychosocial adjustment appeared to differ between the two cultures.

Activities of Daily Living