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Biomedical subjects

L McLean

Publications and source records attributed to L McLean.

At least 73 records · Page 4Linked to original sources

Bacterial overgrowth in the duodenum of dogs with exocrine pancreatic insufficiency.

Bacterial overgrowth (greater than 10(5) colony-forming units/ml duodenal juice) in the duodenum was demonstrated in 8 of 11 dogs with exocrine pancreatic insufficiency (EPI). In 4 of these 8 dogs, the overgrowth included large numbers (greater than 10(4) colony-forming units/ml) of obligate anaerobic bacteria and was associated with decreased activities of several brush border marker enzymes and, in 2 dogs, with partial villous atrophy in the jejunum. Changes in the jejunal mucosa of the remaining dogs (with either no overgrowth or overgrowth of aerobic bacteria alone) were characterized by increased activities of some brush border disaccharides and of lysosomal hydrolases. One dog was euthanatized without treatment, at the owner's request. The response of 4 of the remaining 10 dogs treated with enzyme replacement alone was poor or suboptimal, and all of these 4 dogs had bacterial overgrowth. One of these dogs had an excellent clinical response when also given oxytetracycline orally for 14 days, but the other 3 dogs did not improve further in response to the same treatment. It was concluded that bacterial overgrowth in the duodenum is common in dogs with EPI and that, when such overgrowth includes large numbers of obligate anaerobes, there may be associated biochemical and morphologic abnormalities in jejunal mucosa. Functional disturbances related to abnormal intestinal microflora may be responsible for the failure of some dogs with EPI to respond fully to oral pancreatic enzyme supplementation without antibiotic therapy.

Animals↗

Sequential morphologic and biochemical studies of naturally occurring wheat-sensitive enteropathy in Irish setter dogs.

This study has investigated the potential role of wheat in the pathogenesis of a naturally occurring enteropathy in Irish setter dogs. At eight months on a cereal-containing diet, jejunal biopsies from affected animals exhibited partial villus atrophy, increased intraepithelial lymphocytes, and distinct biochemical abnormalities in the brush border. Activities of alkaline phosphatase and leucyl-2-naphthylamidase were almost undetectable while disaccharidases were unaltered. Activity of 5'-nucleotidase (basolateral membrane) was low, and reduced malate dehydrogenase reflected a loss of mitochondrial activity, but other organelles were unaffected. Recovery was achieved on a wheat-free diet. Relapse on subsequent wheat challenge was characterized by partial villus atrophy and a selective effect on the brush border: modal density was decreased and there was a severe loss of brush-border alkaline phosphatase activity. These findings document a wheat-sensitive enteropathy in Irish setter dogs and suggest that brush-border alkaline phosphatase is specifically susceptible to damage by wheat.

5'-Nucleotidase↗

Comparison of the biochemical changes in the jejunal mucosa of dogs with aerobic and anaerobic bacterial overgrowth.

Subcellular biochemical changes in the jejunal mucosa have been compared in dogs with either aerobic or anaerobic bacterial overgrowth to explore relationships between composition of the flora and mucosal damage. Affected animals comprised 17 German shepherd dogs with chronic diarrhea or weight loss, or both. Analysis of duodenal juice demonstrated aerobic overgrowth in 10 cases, most frequently comprising enterococci and Escherichia coli, and obligate anaerobic overgrowth in 7 cases, most frequently including Clostridia spp. Histologic changes were minimal; however, examination of peroral jejunal biopsy specimens by sucrose density gradient centrifugation revealed specific biochemical abnormalities. In the dogs with aerobic overgrowth, there was a selective loss of brush border alkaline phosphatase activity, and gamma-glutamyl transferase activity was increased, whereas activities of disaccharidases and aminopeptidase N were unaltered. In contrast, anaerobic overgrowth was associated with a reduction in brush border density, indicative of a considerable fall in the glycoprotein-to-lipid ratio of the brush border membrane, whereas brush border enzyme activities were unaltered. There was a loss of peroxisomal catalase activity in dogs with aerobic overgrowth, and an indication of mitochondrial disruption in dogs with anaerobic overgrowth, but little evidence for damage to other subcellular organelles. These findings demonstrate that aerobic and anaerobic overgrowth may be associated with distinct but different mucosal abnormalities particularly affecting the brush border membrane.

Alkaline Phosphatase↗

The place of percutaneous transluminal angioplasty in the treatment of patients having angiography for ischaemic disease of the lower limb.

A prospective survey was made during 1 year of all 226 patients having angiography for lower limb ischaemia, to assess the accuracy of selection for angiography and the current treatment of the disease. Sixty-two percent of the patients presented with intermittent claudication and were found to have a fall in ankle systolic blood pressure on exercise. Thirty-one percent had rest pain or ischaemic skin changes. All patients had abnormal angiograms, with aorto-iliac disease present in 42%, combined with distal disease in 22%. There was a normal aorto-iliac segment in 58% of patients who had more distal disease. Calf-vessels only were affected in 15%. Treatment was by surgery only in 49%, and balloon dilatation only in 19%. A further 2% had dilatation as a complement to surgery, and 6% had surgery when dilatation failed or had complications. Dilatation was attempted unsuccessfully in 6%. No treatment was offered to 20% of patients. It is concluded that selection of patients for angiography using clinical and vascular laboratory assessment avoids unnecessary examinations and that approximately one-third of these selected patients are candidates for angioplasty, which is the preferred first option for treatment in all suitable patients.

Adult↗

Organ culture of rabbit ileum as a model for the investigation of the mechanism of intestinal damage by enteropathogenic Escherichia coli.

Organ culture of rabbit ileum has been established as a model for the investigation of the mechanism of intestinal damage by enteropathogenic Escherichia coli (EPEC). Loops of rabbit ileum were filled in vivo with saline, non-enteropathogenic P-fimbriate E coli (PFEC), or EPEC. After 45 minutes the loops were washed, then mucosal biopsies were taken and cultured for up to 48 hours. The earliest changes discernable by electron microscopy were observed at 18 hours postinfection, at which time EPEC were closely adherent to the surface of enterocytes at the base of microvilli, some of which were elongated. By 24 hours postinfection there were large areas of brush border effacement with pedestal formation around the EPEC. No such damage was seen in biopsies from the control loops (saline, PFEC), and intracellular ultrastructure was extremely well preserved in all preparations for up to 48 hours. While there were no differences at eight hours, biochemical analyses at 24 hours postinfection showed a marked increase in the release of brush border enzymes into the culture medium from EPEC-infected explants compared to explants from the control loops. These findings provide morphological and biochemical evidence for damage to the microvillus membrane by EPEC, and validate organ culture of rabbit ileum as a model for the investigation of EPEC-pathogenicity.

Alkaline Phosphatase↗

Ruptured abdominal aortic aneurysm in Marfan's syndrome.

A rare case of ruptured abdominal aortic aneurysm in Marfan's syndrome is described. The patient was treated successfully with a straight aortic tube graft. Histology of the aneurysm wall showed changes typical of cystic medial necrosis.

Adult↗

Ultrastructural and biochemical changes in human jejunal mucosa associated with enteropathogenic Escherichia coli (0111) infection.

A case of prolonged diarrhoea following Escherichia coli 0111 gastroenteritis is reported. Electron microscopy of the jejunal biopsy revealed effacement of the brush border and attachment of bacteria by pedestal formation. Specific activities of brush border enzymes showed marked depression of disaccharidases, zinc-resistant alpha-glucosidase, and alkaline phosphatase. In contrast, marker enzymes for basolateral membranes and endoplasmic reticulum were unaffected. The biochemical changes support the pathogenic mechanism suggested by ultrastructural studies previously reported.

Biopsy↗

Wheat-sensitive enteropathy in Irish setter dogs: possible age-related brush border abnormalities.

The pathogenesis of a wheat-sensitive enteropathy was explored in a litter bred from two Irish setters with a naturally occurring enteropathy. Jejunal biopsies from all eight progeny exhibited morphological changes comparable to those in the parents, while biochemical abnormalities appeared to be related to age. In biopsies obtained from the first group of four dogs at eight months, the activities of alkaline phosphatase and of leucyl-2-naphthylamidase were almost undetectable while disaccharidases were unaltered. In contrast, analytical subcellular fractionation of biopsies obtained from the second group of four dogs at nine months showed that specific activities now reflected a major deficiency of brush border alkaline phosphatase, and normal brush border leucyl-2-naphthylamidase accompanied by elevated soluble activity. Further studies are indicated to determine whether these findings represent an age-related abnormality affecting specific microvillus membrane proteins.

Age Factors↗

Morphological and biochemical studies of a naturally occurring enteropathy in the Irish setter dog: a comparison with coeliac disease in man.

A naturally occurring enteropathy was identified in Irish setter dogs and wheat-sensitivity was demonstrated in a litter bred from two of the affected animals. The morphological and biochemical features of this enteropathy are described and compared to coeliac disease in man. Affected animals comprised 10 dogs that presented with poor weight gain or weight loss, with or without diarrhoea. Exocrine pancreatic function was normal and culture of duodenal juice demonstrated no marked bacterial overgrowth. Serum vitamin B12 concentrations were unaltered, but in some cases low serum and erythrocyte folate concentrations and reduced xylose absorption provided indirect evidence for proximal small intestinal disease. Examination of peroral jejunal biopsies revealed patchy morphological changes within individual animals, comprising predominantly partial, but in one case subtotal, villous atrophy. Brush border enzymes were selectively altered: the specific activities of alkaline phosphatase, leucyl-2-naphthylamidase and of zinc-resistant alpha-glucosidase were reduced by approximately 40 per cent, while activities of maltase, sucrase, lactase and gamma-glutamyl transferase were unaltered. Activity of a lysosomal enzyme was increased and there was evidence for enhanced lysosomal fragility. The activity of malate dehydrogenase, with a dual mitochondrial and cytoplasmic localisation, was decreased but there were no changes in the activities of marker enzymes for basal-lateral membranes, endoplasmic reticulum or peroxisomes. These findings, particularly the specific biochemical abnormalities, were comparable to those in partially treated coeliac disease in man; however, a specific role for wheat in the pathogenesis of the disease has yet to be defined.

Animals↗

Anatomico-radiological study of the borderline sella.

Multidirectional thin section tomography was performed on 62 excised sphenoidal bones. The pituitary gland was then sectioned and examined microscopically for evidence of microadenoma, cellular hyperplasia or cysts. There is absolutely no meaningful correlation between the radiological and the histological findings. Minor sellar changes in the form of slight irregularity of the lamina dura, asymmetry of the sellar floor or thinning of the dorsum sellae may be found in the absence of any histopathological abnormality.

Adolescent↗

Central effects of arginine vasopressin on blood pressure in rats.

In anesthetized male Sprague-Dawley rats, intraventricular injection of 25-5000 pmol AVP caused short-latency, dose-related increases in blood pressure. Blood pressure increases occurred before any changes in urine flow were observed, suggesting that the AVP was acting centrally. Similar increases in blood pressure were observed after central AVP injection into homozygous Brattleboro rats which lack AVP, indicating these effects were not due to release of pituitary AVP stores. These results raise the possibility that endogenous AVP plays a role in the central control of blood pressure.

Animals↗

Bronchial reactions to western red cedar (Thuja plicata).

The clinical features and the results of investigations (including immunological tests) of three patients with asthma due to western red cedar are described. Bronchial provocation tests with extract of this wood produced immediate asthmatic reaction in one patient, late asthmatic and peripheral reactions in another and late asthmatic reaction alone in the third. While mild immediate skin reactions were detected in two patients, no late skin reactions were observed. Serum precipitins to this extract were not detected. An attempt was made to identify the responsible allergen in the red cedar extract.

Adult↗