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Biomedical subjects

K W Simpson

Publications and source records attributed to K W Simpson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Evaluation of the long-acting somatostatin analogue octreotide in the management of insulinoma in three dogs.

The response of dogs with insulinoma to surgical and medical management is variable, with the majority developing intractable hypoglycaemia. A long-acting somatostatin analogue, Octreotide (SMS 201-995; Sandostatin) has been useful in the management of hypoglycaemia in humans with insulinoma, and preliminary reports suggest a beneficial clinical response in dogs with insulinoma. The present study objectively evaluated Octreotide in the management of three dogs with immunohistochemically confirmed insulinoma. Octreotide had no benefit over placebo, and little effect on circulating glucose and insulin concentrations despite clearly detectable plasma concentrations of Octreotide. No clinical improvement was apparent in two dogs given Octreotide over a period of two and three weeks. These results contrast with the positive clinical responses noted previously and indicate that further placebo controlled, objective studies are necessary before clear statements on the treatment of insulinoma with Octreotide are made.

Animals↗
PubMed1994

Macrothrombocytosis in cavalier King Charles spaniels.

Low platelet counts (< 150 x 10(9)/litre) have been measured by autoanalyser in cavalier King Charles spaniels with a wide range of diseases. However, the direct examination of blood smears revealed adequate numbers of platelets but many abnormally large platelets and it was not clear whether the large platelets were the result of disease or a breed abnormality. The numbers and diameters of the platelets in a group of clinically normal King Charles spaniels and a group of other breeds were measured by autoanalyser and manually. The automated platelet counts were lower in the King Charles spaniels than in the other breeds (P < 0.01), but the manual counts were similar. The platelet diameter was greater in the cavalier King Charles spaniels (median values 2.5 to 3.75 microns, P < 0.001) than the other breeds (median values 1.25 to 2.5 microns) and had a bimodal distribution with peaks at 1.25 to 2.5 microns and 3.75 to 5 microns. No clinical evidence of platelet dysfunction was detected. These findings indicate that cavalier King Charles spaniels may have large platelets which could lead to the erroneous diagnosis of thrombocytopenia by automated haematological analysis.

Animals↗
PubMed1993

Systemic mycosis caused by Acremonium sp in a dog.

A 4-year-old female German Shepherd Dog was examined to determine the cause of ataxia, progressive head tilt, anorexia, lethargy, and weight loss of 3 weeks' duration. A vestibular syndrome, generalized lymphadenopathy, bilateral uveitis, and chorioretinitis with complete detachment of the left retina were detected. Abnormal clinicopathologic findings were isosthenuria and hyperglobulinemia. The non-functional left eye was enucleated and fungal organisms resembling Aspergillus spp were identified on histologic examination. Microbial culture of a urine sample yielded Acremonium sp, which was initially considered a contaminant. The dog was considered to have systemic aspergillosis and was treated with itraconazole for 7 months, until it was euthanatized because of persistent vomiting and anorexia. Postmortem examination revealed multisystemic pyogranulomatous and necrotizing inflammation of the myocardium, pericardium, liver, and kidneys; and granulomatous splenitis, lymphadenitis, retinitis, endometritis, and meningoencephalitis. Fungal culture of affected organs yielded Acremonium sp. These findings indicated that Acremonium spp can be pathogenic and should not be ignored when cultured.

Acremonium↗
PubMed1993

Hypercholesterolaemia in briards in the United Kingdom.

Elevated fasting plasma cholesterol concentrations were identified in clinically healthy briards. Biochemical investigations revealed no other major abnormalities. Plasma lipoprotein electrophoresis demonstrated a marked increase in the intensity of the alpha 2 band (compared with control dogs) which was reduced by dextran sulphate-magnesium chloride or sodium phosphotungstate-magnesium chloride precipitation of apo B and apo E containing lipoproteins in the plasma. The study has identified a hyperlipidaemia in briards characterised by increased cholesterol but normal triglyceride concentrations. The absence of obvious metabolic changes associated with secondary hypercholesterolaemia, suggests the breed may have a primary abnormality in cholesterol metabolism. The increased density of the precipitable lipoprotein which migrates to the alpha 2 band suggests that the hypercholesterolaemia may be due to an abnormal accumulation of high density lipoprotein (HDL) possibly HDLc. The possibility that abnormality in lipid metabolism might play a role in the development of retinal pigment epithelial dystrophy in briards is currently being investigated.

Animals↗
PubMed1993

Cellular localization and hormonal regulation of pancreatic intrinsic factor secretion in dogs.

Gastric mucosal cells are considered to be the principal site of intrinsic factor (IF) production in most mammals. Recent observations in dogs suggest that the pancreas is the major site of IF production in this species. The present study was undertaken to determine the cellular origins of canine pancreatic IF by combining in situ hybridization with immunocytochemistry and to examine the potential role of physiological pancreatic secretagogues, cholecystokinin octapeptide (CCK-8) and secretin, as mediators of canine pancreatic IF secretion. A human IF cDNA probe (J. Hewitt et al., Genomics 10: 432-440, 1991), validated for use in the dog, identified IF mRNA in parietal cells in the gastric fundus, gastric gland cells in the pyloric antrum, and in secretory duct cells of the pancreas. Immunocytochemistry using antibody against rat IF confirmed that these cells, as well as secretory ducts of salivary glands, synthesized an immunoreactive protein. In stimulated secretions of anesthetized dogs, mean 45-min outputs of IF, haptocorrin, and trypsinogen were 13-, 8-, and 16-fold greater during stimulation with CCK-8 than with secretin. No synergistic effects of combined stimulation were observed for IF or haptocorrin, although a synergistic effect was observed for trypsinogen. These findings demonstrate that IF is synthesized in the canine stomach, pancreas, and probably salivary glands and that CCK-8 mediates IF secretion from pancreatic duct cells.

Animals↗
PubMed1992

Pancreatic function following partial pancreatectomy and anastomosis of the pancreatic duct to the stomach or duodenum in dogs.

The effects of pancreatic duct anastomosis to stomach (stomach group) or duodenum (duodenal group) on pancreatic function were examined in dogs following two thirds pancreatectomy. Normal fasting blood glucose concentrations were maintained in both groups despite significant reductions in glucose tolerance in the stomach group, and reductions in fasting insulin and insulin peak response in both groups. Pancreatic exocrine function was significantly decreased in both groups, though plasma p-aminobenzoic acid (PABA) concentrations were generally higher in the duodenal group. A correlation was found between plasma trypsin-like immunoreactivity (TLI) and pancreatic weight. These results indicate that anastomosis of the pancreas to bowel can be undertaken with minimal postoperative complications and that the site of the anastomosis influences pancreatic function. They suggest that preservation of more than one third of the pancreas is required for optimal function. The complementary information provided by the PABA and TLI tests suggests their dual application will be clinically useful for the detection and characterisation of naturally occurring pancreatic diseases.

4-Aminobenzoic Acid↗
PubMed1992

Small intestinal bacterial overgrowth and enhanced intestinal permeability in healthy beagles.

The small intestine of healthy adult Beagles was examined to determine whether subclinical abnormalities might exist that would be relevant to the use of Beagles in pharmacologic studies. Duodenal juice was obtained for qualitative and quantitative bacteriologic examinations; jejunal mucosa was taken for morphologic and biochemical investigation, and intestinal permeability was assessed by quantification of 24-hour urinary excretion of 51Cr-labeled EDTA after its oral administration. Comparisons were made with findings in healthy adult dogs of other breeds that served as controls. Small intestinal bacterial overgrowth was found in 14 of the 21 Beagles examined, and represented a mixed flora that included obligate anaerobic bacteria in 8 dogs and exclusively aerobic bacteria in 6 dogs. Intestinal permeability (percentage urinary recovery of 51Cr-labeled EDTA; mean +/- SEM) was considerably higher (P < 0.01) in Beagles with anaerobic overgrowth (37.6 +/- 3.2%) or aerobic overgrowth (30.5 +/- 4.8%), compared with Beagles with no overgrowth (17.3 +/- 1.6%) and with controls (11.1 +/- 1.0%). In Beagles, significant (r = 0.54, P = 0.03) correlation was observed between 24-hour urinary recovery of 51Cr-labeled EDTA and bacterial numbers in duodenal juice. Morphologic changes in jejunal mucosa were minimal, and specific activities of brush border enzymes were not significantly decreased, apart from aminopeptidase N, but activities of lysosomal and endoplasmic reticular marker enzymes were higher in the 3 groups of Beagles with anaerobic, aerobic, or no overgrowth, compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of pancreatectomy on plasma activities of amylase, isoamylase, lipase and trypsin-like immunoreactivity in dogs.

The contribution of the pancreas to the plasma activities of amylase, isoamylase, lipase and the concentration of trypsin-like immunoreactivity (TLI) in the dog was examined by measuring the activities of these enzymes before and after total pancreatectomy. Pancreatectomy was followed by a decrease in the concentration of TLI (from 6.2 +/- 0.3 micrograms litre-1 to 1.2 +/- 0.3 micrograms litre-1; P less than 0.001) and activity of isoamylase peak 4 (from 1257 +/- 105 iu litre-1 to 894 +/- 171 iu litre-1; P less than 0.05). Though significantly reduced, the activities of peak 4 isoamylase were still within the normal range for control dogs. Pancreatectomy did not significantly alter the activities of amylase, lipase or isoamylase peaks 1, 2 and 3. These findings provide strong evidence that the pancreas is not the sole source of circulating amylase, isoamylase and lipase activities. In contrast the marked reductions in TLI to values close to the limits of assay sensitivity suggest that TLI is derived from the pancreas alone. The results indicate that assay of circulating TLI provides a more sensitive and specific indicator of pancreatic exocrine mass than plasma amylase, lipase or isoamylase activities.

Amylases↗
PubMed1990

Effects of exocrine pancreatic insufficiency and replacement therapy on the bacterial flora of the duodenum in dogs.

The influence of pancreatic secretions on the bacterial flora of the small intestine in 6 dogs was investigated by determining effects of exocrine pancreatic insufficiency on numbers and types of bacteria in duodenal juice, and by examining the subsequent response to dietary supplementation with bovine pancreatic extract. Exocrine pancreatic insufficiency was induced by ligation of pancreatic ducts and was confirmed by indirect assessment of exocrine pancreatic function. Duct ligation was followed by large increases (P less than 0.01) in total numbers of bacteria, reflecting increased numbers particularly of Lactobacillus spp and Streptococcus spp, in 3 dogs accompanied by obligate anaerobes. Total numbers of aerobes and anaerobes decreased markedly (P less than 0.05) after supplementation with bovine pancreatic extract to values that were not significantly different from those determined before duct ligation. Exocrine pancreatic insufficiency therefore resulted in small intestinal bacterial overgrowth that was reversed by pancreatic replacement therapy, indicating that pancreatic secretions can have an important influence on the small intestinal bacterial flora of dogs.

Animals↗
PubMed1989

Identification and characterization of a pancreatic intrinsic factor in the dog.

An intrinsic factor has been identified in the canine pancreas, and output and properties of this protein have been compared with those of gastric intrinsic factor in the dog. Mean concentrations of intrinsic factor and peak outputs per minute were approximately 5- to 10-fold higher in pure pancreatic juice after stimulation with secretin and cholecystokinin, respectively, than in pentagastrin-stimulated gastric juice. Purified gastric and pancreatic intrinsic factors had an identical molecular mass of 65 kDa, estimated by gel filtration on Sephacryl S-200, while sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated single bands corresponding to 53 kDa. Immunoblots showed that rabbit polyclonal antiserum to canine gastric intrinsic factor cross-reacted with canine pancreatic intrinsic factor. Gastric and pancreatic intrinsic factor-cyano[57Co]cobalamin complexes exhibited comparable association constants for ileal receptors in canine brush-border vesicles, while there was minimal binding to jejunal vesicles. These findings demonstrate that the canine pancreas is an important source of an intrinsic factor that closely resembles gastric intrinsic factor in the dog.

Animals↗
PubMed1989

Circulating concentrations of trypsin-like immunoreactivity and activities of lipase and amylase after pancreatic duct ligation in dogs.

The possibility that assay of circulating trypsin-like immunoreactivity (TLI) could assist in the diagnosis of acute pancreatitis in dogs has been examined by assaying plasma TLI concentrations after pancreatic duct ligation and comparing the results with plasma activities of lipase and amylase. Venous blood samples were obtained from 8 dogs before surgery, then daily for 5 days and at 14 days after ligation of pancreatic ducts. Plasma concentrations of TLI increased within 24 hours and tended to peak before and to decrease more rapidly than activities of lipase and amylase, remaining greater than the control range for 5 days in all but 2 dogs. Plasma lipase and amylase activities increased together and remained greater than the control range in all dogs for 5 days after surgery. Regression analysis of all postoperative data indicated significant correlations between concentration of TLI and lipase activity (r = 0.67, P less than 0.001), concentration of TLI and amylase activity (r = 0.53, P less than 0.001), and between lipase and amylase activities (r = 0.74, P less than 0.001). These findings suggested that assay of TLI may provide an early indication of acute pancreatitis in dogs. Because TLI is specifically pancreatic in origin, high plasma TLI concentration may prove a more reliable indicator of clinical pancreatitis than high activities of amylase or lipase, which may be derived from extrapancreatic tissues.

Amylases↗
PubMed1989

Biochemical changes in the jejunal mucosa of dogs with exocrine pancreatic insufficiency following pancreatic duct ligation.

The effects of exocrine pancreatic insufficiency on the small intestinal mucosa were examined in dogs following pancreatic duct ligation. There were no significant changes either in villus architecture or enterocyte height after duct ligation, but numbers of bacteria in duodenal juice increased then subsequently decreased following treatment with exogenous pancreatic enzymes. Pancreatic insufficiency resulted in a considerable increase in the proportion of microvillar membrane proteins of molecular mass over 200 kDa from 3.3 +/- 4 per cent (mean +/- SEM) to 13.6 +/- 7.2 per cent, and this decreased to 6.9 +/- 5.2 per cent following pancreatic enzyme supplementation. However, anticipated increases in activities of maltase and sucrase were not observed following duct ligation, and there was a reduction in lactase activity which was reversed by pancreatic supplementation. Activities of marker enzymes for the other subcellular organelles showed relatively minor or no changes throughout the study. These findings are consistent with a specific role for pancreatic enzymes in the post-translational processing of intestinal microvillar membrane proteins, and suggest that reduced degradation of brush border proteins in the absence of pancreatic secretions may be masked by quantitative and qualitative changes in the intestinal microflora.

Alkaline Phosphatase↗
PubMed1989

Effect of exocrine pancreatic insufficiency on cobalamin absorption in dogs.

The possibility that the canine pancreas might have an important role in the physiologic absorption of cobalamin (vitamin B12) has been explored by determining the effect of exocrine pancreatic insufficiency on cobalamin absorption and by examining the subsequent influence of bovine pancreatic enzymes and canine pancreatic juice. Exocrine pancreatic insufficiency was induced by ligation of pancreatic ducts and confirmed by indirect assessment of exocrine pancreatic function. Cobalamin absorption was determined by oral administration of cyano[58Co]cobalamin and quantitation of radioactivity in blood, urine, and feces during 48 hours. Pancreatic duct ligation resulted in a significant (P less than 0.001) decrease in cobalamin absorption, which was not restored by oral administration of bovine pancreatic enzymes, despite considerable improvements in steatorrhea and in vivo proteolytic activities. In marked contrast, malabsorption of cobalamin was significantly (P less than 0.05) reversed by oral administration of canine pancreatic juice. These results indicate that pancreatic secretions have an important role in the normal absorption of cobalamin in the dog, a role that does not appear to be attributable to pancreatic enzymes, but is consistent with the existence of a pancreatic intrinsic factor in this species.

Animals↗