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Biomedical subjects

A J Watson

Publications and source records attributed to A J Watson.

At least 253 records · Page 14Linked to original sources
PubMed1982

A survey of nematode control measures used by sheep farmers and of anthelmintic resistance on their farms. Part 2: South Island excluding the Nelson region.

Forty-three randomly selected farms located throughout South Island, excluding the Nelson region, were surveyed for anthelmintic usage and for sheep nematodes resistant to anthelmintics. Most farmers had used both benzimidazole and non-benzimidazole broad-spectrum drenches on their properties in previous years. Sheep were being drenched, on average, 5.6 times within their first year of life but much less frequently thereafter. Commercial interests played the dominant role in helping farmers formulate their drenching policies. On each farm 24 numbered ewe replacement lambs, born during the spring of 1980, were sampled for faeces at the beginning of the trial to provide material for egg counts and larval cultures. The lambs were weighed and divided into three groups of eight. One group received thiabendazole (TBZ) at 66 mg/kg, the second levamisole (LEV) at 8 mg/kg while the third remained untreated as controls. All were resampled 4 to 10 days later. On 32 (88%) of the 40 farms where drenching trials were successfully carried out during autumn 1981, the faecal egg count depression (FECD) following treatment with either drench was 100%. On one farm TBZ was less than 100% effective as gauged by FECD. LEV proved to be less than 100% effective on 7 farms. On one farm the FECD was less than 80%, on 2 between 90% and 95% and on 4 between 95% and 99%.

Journal Article↗
PubMed1982

Human colorectal tumours in short-term organ culture. A stathmokinetic study.

Short-term organ culture, using a technique to preserve epithelial/stromal interaction and metabolism, is a useful technique for carrying out kinetic studies on human colorectal carcinoma and adjacent normal mucosa, providing initial perturbations of proliferative indices are allowed to settle. Tumours require 3.0 micrograms/ml vincristine for complete metaphase arrest compared with mucosa, which needs 0.5 microgram/ml, a 6-fold difference. Using a stathmokinetic technique, the birth rate of tumour cells is 10.21 cells/1000 cells per hr, compared with 7.73 cells/1000 cells per hr for mucosa, a statistically significant difference (P less than 0.01).

Adenocarcinoma↗
PubMed1982

Effect of 1-deamino-8-D-arginine vasopressin on the prolonged bleeding time in chronic renal failure.

The prolonged bleeding times of 12 patients with chronic renal failure were significantly shortened at 1 and 2 h after an infusion of 0.4 microgram/kg 1-deamino-8-D-arginine vasopressin (DDAVP). In 5 of these patients, the bleeding times 24 h after infusion had returned to approximate baseline values, suggesting that the effect of DDAVP is a temporary one. The levels of factor VIII coagulant activity, factor VIII related antigen activity, and factor VIII ristocetin cofactor activity were all normal or elevated prior to infusion, and a tendency to further elevation, although significant only for the factor VIII ristocetin cofactor activity, was observed after infusion of DDAVP. The latter observation suggests that the effect of DDAVP infusion on the bleeding time is unrelated to alteration of factor VIII activities.

Adult↗
PubMed1982

Adaptive cell-proliferative changes in the small-intestinal mucosa in coeliac disease.

Cell proliferation in the small-intestinal crypts of rodents has been intensively investigated and lends itself to the deployment of techniques which are inapplicable in man. In particular there are ethical and economic objections to methods involving the use of tritiated thymidine in vivo for specific labelling of DNA, while the validity of in vitro studies using organ culture is uncertain. It is possible, nevertheless to construct a profile of the size and cytokinetic status of the mucosal crypts by analysis of serial sections prepared from well orientated routine diagnostic biopsy specimens. Such studies can provide a measure of mean total crypt-cell population, and by studying the distribution of mitoses in the crypts relative measurements can be obtained of proliferation and maturation compartment sizes, and of crypt cell production rate (CCPR). These parameters have been compared in 62 patients with 'flat' avillous coeliac mucosae and in 85 patients with normal villous mucosae. A heterogeneous group of 47 patients with lesser degrees of abnormality (convoluted mucosae) were similarly studied. In addition, estimates of cell cycle times were obtained in a small group of patients with normal, convoluted and 'flat' mucosae by taking biopsies before and after the administration of the metaphase-arresting agent vincristine. 'Flat' coeliac mucosae show a threefold increase in the size of the proliferation compartment compared with normal and the cell cycle time is approximately halved leading to a net sixfold increase in CCPR. This is the basis of the change in mucosal morphology and presumably represents a compensatory reaction to the gluten-induced increase in loss of enterocytes from the mucosal surface. Convoluted mucosae occupy an intermediate position in terms of the parameters studied and should be regarded as stages in a continuum of adaptive change.

Adaptation, Physiological↗
PubMed1982

Crypt regeneration in adult human colonic mucosa during prolonged organ culture.

Using a system designed to preserve, in vitro, both the epithelial and the connective tissue elements, we have maintained adult colonic mucosa in organ culture for up to 336 hours and have investigated the sequential morphological changes which occur. During the first 48 hours, normal micro-architecture is preserved, but there is progressive loss of cytoplasmic mucin from crypt cells. Subsequently, accelerated degenerative changes develop; cells are lost from the crypts and, because cell proliferation in the crypt is reduced, these lost cells are not replaced. For a time, the crypts are represented by discrete acinar formations or clusters of cells in the lamina propria, apparently discontinuous with the intact surface epithelial layer. These remnants manifest intense proliferative activity during the period between 72 and 96 hours after explantation, leading to the restoration of well formed crypts lined by columnar epithelial cells between 120 and 144 hours; differentiation of goblet cells ensues and this state of virtually normal structure persists until the termination of culture between 186 and 336 hours. It is concluded that the determination of normal crypt structure and of crypt-cell differentiation is governed by intrinsic control mechanisms although these may be subject to extrinsic modulation. Whether or not the degeneration phase can be eliminated, it is clear that long term culture of adult human colonic mucosa is possible. Such a system may be useful in the study of mucosal function and of mucosal response to drugs, carcinogens and trophic factors.

Cell Differentiation↗
PubMed1981

Primary biliary cirrhosis--a revised clinical spectrum.

The presentation or method of detection of 93 patients with primary biliary cirrhosis (PBC) from Northern England is reported. Almost half (45/93) the patients had no symptoms of liver disease when PBC was diagnosed; in many of them serum antimitochondrial activity (AMA) was detected during immunological screening for other diseases. 13 patients with normal liver function tests had symptomless PBC. Liver histology in 6 of these was diagnostic for PBC, and 7 had histology suggestive of PBC; all had a positive AMA titre greater than or equal to 1/40. The mortality of the symptom-free AMA-positive patients over a mean follow-up of 4-5 years did not differ from that of the general population. Only 1 out of 45 initially symptom-free patients died in the follow-up period (8 months-12 years). 37 patients had disorders which may be associated with PBC--including 16 with thyroid disease, 9 with rheumatoid arthritis, and 5 with mixed connective tissue disease. It is suggest that, as with autoimmune thyroid disease, overt organ damage never develops in many patients with symptomless PBC.

Adult↗
PubMed1981

Acute changes occurring in the intestinal mucosae of rats given a single injection of 1,2 dimethylhydrazine.

In the long term, administration of dimethylhydrazine (DMH) to rats results in the development of tumours in both small intestine and colon. This study has been undertaken in order to document the sequence of changes occurring in the intestinal mucosa in the first 108 h following a single subcutaneous injection of DMH. After a lag of several hours there is evidence of damage to cells in the proliferation zone of the intestinal crypts, and a brief reduction in tritiated thymidine labelling index. A phase of compensatory regenerative activity emerges from the setting of continuing cell damage, resulting in restoration of the mucosa to normal. The severity of the toxic damage to the intestinal mucosa at various sites mirrors the vulnerability of the mucosa to the long term carcinogenic effects of DMH, suggesting that inherent properties of the mucosa may be of more importance than other cocarcinogenic influences in the ultimate development of tumours.

Animals↗
PubMed1981

Kinetics of the non-neoplastic mucosa of the large bowel of dimethylhydrazine-treated rats.

Administration of 1,2 dimethylhydrazine (DMH) to rats by weekly s.c. injections causes the development of multiple epithelial tumours of the large bowel. These appear to arise as localized dysplastic abnormalities in hitherto apparently morphologically normal crypts. This study was undertaken in order to examine cell proliferation in such apparently normal crypts of DMH-treated animals. A number of proliferative abnormalities are evident, including changes in the size of the crypts, changes in the disposition of proliferating cells within them and reduced cell-cycle times. The nature and the extent of the abnormalities vary from site to site along the length of the bowel, and reflect the vulnerability of the different segments of the bowel, not only to the carcinogenic effects of DMH, but also to short-term toxicity.

1,2-Dimethylhydrazine↗
PubMed1981

The effect of the topical steroid clobetasone butyrate on coeliac mucosa maintained in organ culture.

The effect of the topical corticosteroid clobetasone butyrate on enzyme activity and morphology of duodenal mucosa was studied in 9 patients with coeliac disease and 10 controls using organ culture techniques. There was significant increase in mucosal alkaline phosphatase, lactase and maltase activities, but inclusion of a soluble extract of gluten reduced this effect. When clobetasone butyrate was also included in the culture medium significant elevations in enzymes were again observed. Enterocyte height was not affected by incorporation of gluten into the medium. Intra-epithelial lymphocyte counts fell significantly during the culture period. This improvement was also inhibited by gluten and overcome by addition of steroid.

Adult↗
PubMed1981

Intrahepatocytic copper and copper-binding protein in primary biliary cirrhosis. Discrimination from chronic active hepatitis by means of orcein and rubeanic acid techniques.

Liver tissue samples from 111 patients with various hepatic disorders including 37 with primary biliary cirrhosis (PBC) and 22 with chronic active hepatitis (CAH) were studied. Of the PBC patients, 33 out of 37 (89%) showed orcein-positive and rubeanic acid-positive intrahepatocytic copper granules. In the 4 negative cases conventional staining methods revealed characteristic bile duct lesions and granuloma formations; all 4 were so-called presymptomatic patients. Amongst the liver biopsy samples from CAH patients, 12 out of 22 (55%) contained orcein-positive granules, but none showed stainable copper. We conclude that (1) combined orcein and rubeanic acid positivity in liver samples helps to distinguish between PBC and CAH; (2) in presymptomatic PBC the negativity of both methods is adequately compensated by a high frequency of characteristic bile duct lesions and granuloma formation: (3) the absence of orceinophilic intrahepatocytic granules, in our hands, does not accurately predict the response to steroid therapy.

Aged↗
PubMed1981

Clinical, biochemical and morphological responses of patients with villous atrophy to oral betamethasone valerate and clobetasone butyrate.

10 patients with sub-total villous atrophy were given the topical corticosteroids betamethasone valerate or clobetasone butyrate for a period of 4 months whilst continuing on a normal diet. 5 patients improved symptomatically while red cell folate, urinary xylose and faecal fat excretion also improved. Brush border enzymes increased in patients treated with higher dosages of each drug. Enterocyte height increased and intra-epithelial lymphocytes were significantly decreased although overall morphological appearances remained indistinguishable from untreated coeliac disease. Suppression of the pituitary adrenal axis occurred in 8 patients and there did not appear to be useful separation of topical from systemic activity. These compounds offer no advantage over prednisolone in non-responsive coeliac disease.

Administration, Oral↗