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Biomedical subjects

E M Welsh

Publications and source records attributed to E M Welsh.

15 recordsLinked to original sources

Decrease in beta-cell mass leads to impaired pulsatile insulin secretion, reduced postprandial hepatic insulin clearance, and relative hyperglucagonemia in the minipig.

Most insulin is secreted in discrete pulses at an interval of approximately 6 min. Increased insulin secretion after meal ingestion is achieved through the mechanism of amplification of the burst mass. Conversely, in type 2 diabetes, insulin secretion is impaired as a consequence of decreased insulin pulse mass. beta-cell mass is reported to be deficient in type 2 diabetes. We tested the hypothesis that decreased beta-cell mass leads to decreased insulin pulse mass. Insulin secretion was examined before and after an approximately 60% decrease in beta-cell mass achieved by a single injection of alloxan in a porcine model. Alloxan injection resulted in stable diabetes (fasting plasma glucose 7.4 +/- 1.1 vs. 4.4 +/- 0.1 mmol/l; P < 0.01) with impaired insulin secretion in the fasting and fed states and during a hyperglycemic clamp (decreased by 54, 80, and 90%, respectively). Deconvolution analysis revealed a selective decrease in insulin pulse mass (by 54, 60, and 90%) with no change in pulse frequency. Rhythm analysis revealed no change in the periodicity of regular oscillations after alloxan administration in the fasting state but was unable to detect stable rhythms reliably after enteric or intravenous glucose stimulation. After alloxan administration, insulin secretion and insulin pulse mass (but not insulin pulse interval) decreased in relation to beta-cell mass. However, the decreased pulse mass (and pulse amplitude delivered to the liver) was associated with a decrease in hepatic insulin clearance, which partially offset the decreased insulin secretion. Despite hyperglycemia, postprandial glucagon concentrations were increased after alloxan administration (103.4 +/- 6.3 vs. 92.2 +/- 2.5 pg/ml; P < 0.01). We conclude that an alloxan-induced selective decrease in beta-cell mass leads to deficient insulin secretion by attenuating insulin pulse mass, and that the latter is associated with decreased hepatic insulin clearance and relative hyperglucagonemia, thereby emulating the pattern of islet dysfunction observed in type 2 diabetes.

Animals↗

Dermoid sinus at the lumbosacral junction in an English springer spaniel.

A dermoid sinus was identified in a springer spaniel that presented with hindlimb neurological deficits. The sinus was continuous with the dura mater at the level of the lumbosacral junction. The presence of hair and debris adjacent to neural tissue had elicited a myelitis. A dorsal laminectomy was required to allow complete surgical resection of the sinus. The dog's neurological status improved after treatment and this improvement was maintained over a five-month follow-up period.

Animals↗

Spontaneous laryngeal paralysis in four white-coated German shepherd dogs.

Four cases of spontaneous laryngeal paralysis in juvenile white-coated German shepherd dogs are described. The presenting signs were typical for laryngeal paralysis, with stridor present in all four cases. Laryngoscopy revealed bilateral laryngeal paralysis in three cases, and unilateral paralysis in one. Concurrent megaoesophagus was also identified in one dog. All dogs underwent surgical treatment for laryngeal paralysis. Euthanasia was performed in one case due to intractable regurgitation and aspiration pneumonia. A possible association with white coat colour is discussed.

Animals↗

Preliminary clinical observations on the use of piroxicam in the management of rectal tubulopapillary polyps.

Rectal tubulopapillary polyps were diagnosed in eight dogs following proctoscopy and mucosal pinch biopsy. Histological examination of the pinch biopsies revealed evidence of malignant transformation in three of the cases. The remaining cases were diagnosed as benign polyps. Inflammatory changes were observed in four cases. Seven dogs were treated with piroxicam suppositories and one with oral piroxicam. All dogs were re-examined after four to six weeks of piroxicam therapy and the extent of haematochezia, tenesmus and faecal mucus production was reduced in all cases. The owners of seven of the dogs considered the improvement in clinical signs to be good or excellent. Cases with and without evidence of inflammation responded equally well. This finding supports the hypothesis that piroxicam has an antineoplastic effect due to apoptosis and alteration in the cell cycle. Medical management with piroxicam may provide a non-invasive treatment option for dogs with rectal polyp formation in which surgical treatment is likely to be associated with complications such as incontinence, infection and wound breakdown, or where the owner declines such treatment.

Animals↗

Rectal prolapse of an ileocaecal neoplasm associated with intussusception in a cat.

Intussusception associated with lymphoma of the ileocaecocolic junction was diagnosed in a 12-year-old female domestic short-haired cat that presented with a 3-week history of diarrhoea and a protruding anal mass. Surgical exploration revealed an ileocolonic intussusception proximal to the mass at the ileocaecal junction which was excised. A diagnosis of ileocaecocolic lymphosarcoma was made and euthanasia was later performed. This is an unusual case of an ileocaecal junction tumour that manifested as a rectal prolapse associated with intussusception in a cat.

Animals↗

Plexiform vascularisation of a retropharyngeal lymph node in a cat.

Plexiform vascularisation of a retropharyngeal lymph node is described in an adult cat. The cat presented with a chronic history of inspiratory stridor and a slowly growing mass in the cranial cervical area. Clinical signs resolved after excision of the affected node. This appears to be the first clinical report of plexiform vascularisation of a retropharyngeal lymph node and its treatment in a cat.

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Effect of flunixin meglumine on the thresholds to mechanical stimulation in healthy and lame sheep.

The antinociceptive effect of flunixin meglumine was assessed in healthy and lame sheep by using a noxious mechanical stimulus. Sheep suffering from the chronically painful condition, footrot, have previously been shown to have lower thresholds to noxious mechanical stimuli than healthy animals. In the present study, 22 sheep suffering from footrot did not have a lower mean mechanical threshold than 25 matched healthy animals, but it was significantly greater than that recorded from eight experimental sheep (5.0 [2.5], 4.9 [2.1] and 3.0 [1.0] Newtons, respectively). Doses of 1.0 or 2.0 mg kg-1 of flunixin meglumine had no effect on the thresholds to noxious mechanical stimulation in either experimental sheep tested over six hours, or in lame sheep tested over a period of 30 minutes. The repeated administration of flunixin to sheep suffering from footrot over a period of three days reduced their thresholds to noxious mechanical stimulation.

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Effects of non-steroidal anti-inflammatory drugs on the hyperalgesia to noxious mechanical stimulation induced by the application of a tourniquet to a forelimb of sheep.

A tourniquet was used in conjunction with a mechanical threshold testing device to investigate the suitability of the technique for the investigation of analgesic drugs in sheep. The changes to the mechanical thresholds to noxious stimulation during and after the inflation of a pneumatic tourniquet on a limb were recorded, and the influence of pre-treatment with two non-steroidal anti-inflammatory drugs was studied. Fentanyl, an opioid agonist with known analgesic properties in sheep, was used as a positive control. The tourniquet significantly reduced the mechanical thresholds on the ipsi- but not the contralateral limb. Pretreatment with either flunixin meglumine or carprofen attenuated the development of mechanical hyperalgesia, and fentanyl initially caused a significant anti-nociceptive effect. The time to aversion was not significantly different between the treatments. These results suggest that hyperalgesia induced by a tourniquet may be a useful technique for the investigation of the anti-nociceptive effects of analgesic drugs in sheep.

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The pharmacokinetics of flunixin meglumine in the sheep.

Flunixin meglumine was administered intravenously and intramuscularly in sheep and the pharmacokinetics of the drug studied. Plasma concentrations of flunixin were measured by high performance liquid chromatography. The decline in plasma flunixin concentration with time was best fitted by a triexponential equation. The pharmacokinetics following intravenous administration of 1.0 mg/kg indicate that flunixin has a rapid distribution half-life (t1/2 pi = 2.3 min), a slow body clearance rate (Clb = 0.6 ml/kg/min) and an elimination half-life of 229 min. Similarly, at 2.0 mg/kg, flunixin is rapidly distributed from the plasma, t1/2 pi = 2.7 min, has a slow body clearance rate (Clb = 0.7 ml/kg/min) and an elimination half-life of 205 min. Following intramuscular injection flunixin is rapidly and well absorbed from the injection site. It had a mean maximum concentration (Cmax) of > or = 5.9 micrograms/ml when administered at a dose rate of 1.1 mg/kg, and a relative bioavailability of 70%. Plasma concentrations increase proportionally to dose over the range 1.1 mg/kg-2.2 mg/kg when administered by the intramuscular route.

Absorption↗

Comparison of a visual analogue scale and a numerical rating scale for assessment of lameness, using sheep as a model.

A study was designed to compare use of an numerical rating scale (NRS) and a visual analogue scale (VAS) for subjective assessment of lameness, using sheep as a model. The NRS consisted of 5 divisions, 0, 1, 2, 3, and 4; 4 of these divisions (1-4) described lameness. The VAS used a 100-mm horizontal line with vertical bars at either end; one end was labeled 'sound' and the other was labeled 'could not be more lame.' Two independent observers graded lameness in 62 sheep, and between- and within-observer differences were assessed for each scoring system to compare the NRS with the VAS. Results indicated no significant differences between the 2 observers scoring lameness, using either the VAS or the NRS. The scores obtained, using the VAS, were not normally distributed, although differences between scores for the 2 observers were. The NRS scores followed a normal distribution pattern. Investigation of repeated measurement for the same sheep, using both scales, revealed no significant difference between either. A comparison of the NRS and VAS scores made by each observer indicated that although correlation was good (observer 1; r = 0.94; observer 2; r = 0.95), there was not perfect agreement. The maximal NRS score of 4 was associated with VAS values > 68 mm, indicating that the NRS divisions did not reflect equal increases in lameness. The VAS and NRS scores for each observer were highly reproducible, although they were more variable for sheep that were regarded as moderately lame.(ABSTRACT TRUNCATED AT 250 WORDS)

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Pharmacokinetics of carprofen administered intravenously to sheep.

Carprofen was administered intravenously to sheep at two dose rates (0.7 and 4.0 mg kg-1), and the pharmacokinetics of the drug studied. Plasma concentrations of the drug were measured by high performance liquid chromatography. Carprofen had a small volume of distribution (Vd[area], 95.5 and 118.4 ml kg-1), a prolonged elimination half-life (t1/2 beta, 26.1 and 33.7 hours) and a slow body clearance rate (Clb, 2.5 ml kg-1 h-1) in sheep.

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