Juvenile nephropathy in 37 boxer dogs.

OBJECTIVES: The purpose of this study was to review and characterise the clinical presentation of young boxer dogs with chronic kidney disease referred to the authors' institutions. METHODS: Records were collected retrospectively from 37 boxer dogs, less than five years of age, which had presented with azotaemia, inappropriately low urine concentrating ability, and ultrasound or radiographic evidence of abnormal kidneys. RESULTS: Clinicopathological findings included azotaemia, hyperphosphataemia, anaemia, isosthenuria and proteinuria. Ultrasonographic findings included hyperechoic renal cortices, loss of corticomedullary junction definition, dilated pelves and irregularly shaped small kidneys. Renal histopathological findings included pericapsular and interstitial fibrosis, inflammatory cell infiltration, dilated tubules, sclerotic glomeruli and dystrophic calcification. Survival time of the dogs varied from zero to over five years after diagnosis. CLINICAL SIGNIFICANCE: This paper documents features of the presentation and progression of juvenile nephropathy in boxer dogs. While juvenile nephropathy has been reported in individual cases of boxer dogs previously, this is the first reported case series.

Prospective evaluation of a peripherally administered three-in-one parenteral nutrition product in dogs.

OBJECTIVES: Peripheral parenteral nutrition is an option for short-term nutritional support in dogs which cannot be supported with enteral nutrition. The objective of this study was to examine the use of a three-in-one, 840 mOsmol/l peripheral parenteral nutrition product containing amino acids, lipids and glucose in separate compartments in dogs. METHODS: Nine dogs were administered the three-in-one product, and two dogs were administered the amino acid part of the product, via a peripheral vein. Dogs were monitored for mechanical and metabolic complications. RESULTS: Mechanical complications (apparent thrombus or thrombophlebitis) caused failure of infusion at a median of 36 hours. None of the dogs appeared to develop catheter-related sepsis. Using a 10-hour infusion period appeared to decrease the incidence of line failure. Mild and clinically non-significant hyperglycaemia was the only metabolic complication. In four of the dogs, serum folate, cobalamin and homocysteine concentrations were determined before and after peripheral parenteral nutrition administration. Oral and parenteral administration of methionine has been previously associated with lowered serum folate concentrations. Low serum folates and the subsequent hyperhomocysteinaemia have been associated with venous endothelial damage and venous thrombus in other species. Serum cobalamin also affects homocysteine metabolism. Median serum folate, cobalamin and homocysteine concentrations were not affected by the short-term administration of this three-in-one product. CLINICAL SIGNIFICANCE: Using the product for 24 hours/day may require catheter replacement due to line failure. Other than line failure, which may be improved by 10- to 12-hour infusion times, this product was found to be safe and practical for short-term peripheral parenteral nutrition in dogs.

Insulin degradation. XV. Use of different assay methods for the study of mechanism of action of glutathione-insulin transhydrogenase.

Insulin degradation by glutathione-insulin transhydrogenase has been studied using three different assay procedures: the measurement of the change in insulin immunoreactivity; the formation of 5% trichloroacetic acid-soluble radioactivity from 125 I-labeled insulin and the formation of GSSG via coupling to the oxidation of NADPH with the use of glutathione reductase. The extent of reaction as measured by each assay was different, and the ratios between the assays were not constant with time. Kinetic experiments with the NADPH-coupled assay and the trichloroacetic acid assay yielded similar results: Line-weaver-Burke plots with insulin as variable and GSH as fixed substrate gave a set of straight, intersecting lines, and such plots with GSH as variable and insulin as fixed substrate were parabolic. Apparent Km values for insulin at 1 mM GSH were found to be quite similar by three assay techniques; however, the V values per unit of enzyme protein varied considerably with different procedures. The results are interpreted as indicating that immunoreactivity is lost after reduction of only one of the disulfide bonds of insulin whereas the two interchain disulfide linkages must be broken to produce the trichloroacetic acid-soluble A chain. The results of the NADPH-coupled assay suggest that all three disulfide bonds of insulin are possible substrates for the enzyme. The trichloroacetic acid precipitation assay seems to be the most practicable technique for general use because of the greater ease in performing large number of samples, precision and sensitivity.

Neuroprotective effects of eliprodil in retinal excitotoxicity and ischemia.

PURPOSE: To evaluate whether eliprodil (SL82.0715), a NR2B-selective N-methyl-D-aspartate (NMDA) antagonist, is protective of retina subjected to an excitotoxic or ischemic insult. METHODS: To evaluate protection against retinal excitotoxicity, eliprodil was administered intraperitoneally before and after the injection of NMDA (5 microl, 20 nmol) into the vitreous of rats. Integrity of the retina was assessed by counting cells in the retinal ganglion cell layer (GCL) and measuring choline acetyltransferase (ChAT) activity. In a subsequent experiment, total retinal ischemia, as measured by a cessation of electroretinographic (ERG) activity, was induced in anesthetized rabbits by elevating intraocular pressure above systolic blood pressure for 65 minutes. After ischemia, recovery of ERG activity was assessed at 24 and 48 hours in animals treated with vehicle or eliprodil (1.0-10.0 mg/kg). RESULTS: Intravitreal NMDA injection resulted in a dose-related decrease in cells of the GCL and in ChAT activity. Eliprodil administered intraperitoneally at 10 mg/kg completely prevented the loss of ChAT and the loss of cells in the GCL. Twenty-four hours after retinal ischemia, A and B waves of vehicle-treated animals were suppressed by 60% to 70%. Eliprodil administered intraperitoneally at 10 mg/kg ameliorated the A- and B-wave depression throughout the 48-hour experiment. CONCLUSIONS: Eliprodil is neuroprotective of retinae subjected to either an excitotoxic or ischemic challenge and may be useful for treating a variety of retinal and optic nerve head disorders.

Efficacy of treatment after measurable diabeticlike retinopathy in galactose-fed rats.

PURPOSE: To determine whether the diabeticlike retinal microangiopathies of the galactose-fed rat model could be ameliorated if intervention by withdrawal of the galactose diet or treatment with the aldose reductase inhibitor AL-3152 was initiated after quantifiable microangiopathies had occurred. METHODS: Weanling male Sprague-Dawley rats were randomized into five groups and fed for up to 24 months Purina laboratory chow (#5001) plus 50% starch (control [CON]), 50% D-galactose (galactose [GAL]), 50% D-galactose with AL-3152 (approximately 14 mg/kg per day) (prevention [PRV]), 50% D-galactose for 6 months followed by intervention with the inhibitor (intervention [INT]), or 50% D-galactose for 6 months followed by replacement with the 50% starch diet (withdrawal [GWD]). In rats on experimental diets and killed after 6, 18, and 24 months, one retina was prepared for transmission electron microscopy; the other was used for vessel wholemounts using elastase digestion. Capillary images were analyzed by computer morphometry. RESULTS: At 6 months, the GAL rats exhibited statistically significant (P < 0.05) increases over CON rats in mean capillary basement membrane thickness, capillary density, and dilated channels. These parameters tended to increase with time in most groups, and the differences between GAL and age-matched CON rats were maintained at the 18- and 24-month endpoints. Although the microangiopathies were ameliorated by AL-3152 treatment from the onset (PRV), intervention after 6 months of galactosemia with either galactose withdrawal (GWD) or addition of inhibitor (INT) showed amelioration in only some parameters at 18 months and no statistically significant benefit at the 24-month endpoint. CONCLUSIONS: Amelioration of galactose-induced retinal microangiopathies with AL-3152 in the prevention group suggests an efficacious application of aldose reductase inhibitors in treating diabetic retinopathy, provided treatment can begin soon after the onset of diabetes. Intervention after some of the earliest microscopic lesions neither halted progression of the angiopathy nor provided appreciable benefit at the 24-month follow-up.

Effects of two new aldose reductase inhibitors, AL-1567 and AL-1576, in diabetic rats.

Two new potent aldose reductase inhibitors, AL-1567 (DL-spiro(2-fluoro-9H-fluoren-9,4'-imidazolidine)-2',5'-dione) and AL-1576 (spiro-(2,7-difluoro-9H-fluoren-9,4'-imidazolidine)2',5'-dione), have been characterized with respect to in vitro activity toward rat lens and human placental aldose reductase and in vivo activity in uncontrolled, severely diabetic rats dosed acutely with the compounds. The IC50 values for inhibition of rat lens aldose reductase are 2.7 X 10(-8) mol/L for AL-1567 and 8.5 X 10(-9) mol/L for AL-1576; very similar IC50 values were measured for each compound with the human placental enzyme. When the compounds were administered orally once per day to 3-week diabetic rats for a period of eight days, the ED50 values for normalization of lens sorbitol levels were 0.60 mg/kg for AL-1567 and 0.05 mg/kg for AL-1576, and for normalization of sciatic nerve sorbitol levels; 0.22 mg/kg for AL-1567 and 0.04 mg/kg for AL-1576. Compared with published data on other aldose reductase inhibitors evaluated in very similar diabetic rat models, both compounds have unusually high activity in lens, and AL-1576 appears to be the most active such compound in both lens and sciatic nerve reported thus far. The evidence linking increased sorbitol pathway activity to diabetic complications, such as cataract and neuropathy in animal models, suggests that aldose reductase inhibitors will be useful therapeutic agents in human diabetics.

Increased optic nerve head blood flow after 1 week of twice daily topical brinzolamide treatment in Dutch-belted rabbits.

OBJECTIVES: Using a three-way crossover study design, we compared the effects of brinzolamide 2%, dorzolamide 2%, and placebo (vehicle) on microvascular optic nerve head (ONH) blood flow, intraocular pressure (IOP), blood pressure, heart rate, and acid-base balance in nine acepromazine-tranquilized Dutch-belted rabbits. METHODS: Baseline measurements were taken before treatment and after drug-free washout periods of 7-14 days. Microvascular ONH blood flow was measured with a fundus camera-based laser Doppler flowmeter (LDF). Intraocular pressure was measured with a Tono-Pen XL. One drop of brinzolamide, dorzolamide, or vehicle was administered twice daily (9 A.M. and 5 P.M.) in right eyes only for 7 days. Experimental measurements were made 90 minutes after the 9 A.M. topical dose was administered on day 8. RESULTS: ONH blood flow was significantly increased (P< or =0.05) in carbonic anhydrase inhibitor (CAI)-treated rabbits, as compared with vehicle-treated controls. The percent increase from baseline was 11.2+/-1.8% in brinzolamide-treated animals and 8.4+/-4.3% in dorzolamide-treated animals. Compared with controls, IOP in the brinzolamide- and dorzolamide-treated groups was significantly decreased (P< or =0.05). The changes in ONH blood flow and IOP were not significantly different between the CAI treatment groups. Small but significant changes in systemic blood gas tensions and pH were present in both CAI treatment groups, as compared with the vehicle group. Systemic blood pressure and heart rate were not significantly changed. CONCLUSIONS: Topical ocular CAI treatment for 1 week with either brinzolamide or dorzolamide significantly reduced IOP and significantly increased ONH blood flow in tranquilized Dutch-belted rabbits, while eliciting minimal systemic acid-base balance disturbances.

Occurrence and activity of myofibroblasts in human capsular tissue surrounding mammary implants.

Capsular tissue obtained from a series of 16 patients with silicone mammary implants was exposed in vitro to smooth-muscle stimulants and relaxants. Capsule relaxation was produced in 75 percent of the patients. The most active antagonists were papaverine and veratrine. Capsule contracture was produced in 69 percent of the patients. The most active agonists were histamine and epinephrine. Myofibroblasts were identified in several capsules. These data support the hypothesis that the myofibroblasts is a probable cause of capsular contracture.

A pilot study of protein sparing in healthy dogs using peripheral parenteral nutrition.

Total parenteral nutrition is the standard nutritional support of dogs when the enteral route is contraindicated, but it can be difficult because of cost, technical difficulties, and potential complications. Peripheral parenteral nutrition (PPN) may be a feasible option for short-term support in some cases. The objectives of this study were to determine the effect of PPN on nitrogen balance (as an indicator of the effect on protein sparing), serum folate concentrations and serum insulin-like growth factor-I (IGF - I) concentrations in fasting dogs. The effect of PPN on these parameters has not previously been reported in dogs. Using a cross-over design, three healthy adult fasting dogs were randomly assigned to three treatments: 5 per cent amino acid solution, 5 per cent glucose solution, and a control electrolyte solution. The solutions were administered into a peripheral vein at 60 ml kg(-1)per day for 4 days. The amino acid infusion resulted in a positive nitrogen balance and the glucose infusion produced less nitrogen loss than the control. Amino acid, but not glucose or electrolyte infusions, decreased serum folate concentrations. Amino acid and glucose infusions resulted in higher serum IGF -I concentrations than electrolyte infusions, although the differences were small and IGF -I decreased in all cases. In conclusion, these findings suggest that PPN increases nitrogen balance in healthy dogs undergoing short-term fasting.

Radiopaque markers to evaluate gastric emptying and small intestinal transit time in healthy cats.

Determinations of gastric emptying time (GET) and small intestinal transit time (SITT) are useful in detecting gastrointestinal motility disorders and partial obstructions of the pylorus or small intestine. Barium-impregnated, polyethylene radiopaque spheres with diameters of 1.5 mm and 5.0 mm have been developed for quantitative assessment of gastrointestinal transit. The purpose of this study was to evaluate GET and SITT using these radiopaque spheres in 10 healthy cats. The cats were randomly assigned to 1 of 3 treatment groups: fasted, fed, and fed plus sedation (acetylpromazine maleate 0.10 mg/kg subcutaneously). A repeated measures study design was used. The mean GETs of 50%, 75%, and 90% of the 1.5-mm and the 5-mm spheres in the unfed cats were 0.36, 0.58, and 0.74 hours, and 0.41, 0.68, and 1.02 hours, respectively. These values were significantly (P < or = .05) more rapid than the GETs of 50%, 75%, and 90% of the 1.5-mm and 5-mm spheres of either the sedated fed cats (4.39, 5.68, 6.65 and 5.15, 5.99, 6.91 hours) or the unsedated fed cats (6.43, 8.12, 9.06 and 7.49, 8.49, 9.22 hours). The mean GETs of 50% and 75% of the 1.5-mm and 5-mm and of 90% of the 1.5-mm spheres were significantly (P < or = .05) more rapid in sedated than in unsedated fed cats. The GET of 50% of the 1.5-mm spheres was significantly more rapid (P < or = .05) than that of the 5-mm spheres in the fed cats. The mean SITTs, which ranged from 2.25 to 3.05 hours, were not significantly different (P > .05) among the treatment groups or between the 1.5-mm and 5-mm spheres. The GET of spheres given to fasted cats is significantly more rapid than that of fed cats. Subcutaneous injection of acetylpromazine speeds GET in fed cats. The SITT of small and large spheres was not influenced by feeding or by acetylpromazine injection.

Comparison of continuous versus intermittent enteral feeding in dogs.

In humans, continuous intragastric feeding has been suggested to cause fewer gastrointestinal (GI) adverse effects, better weight gain and nitrogen balance, and less glucose intolerance than bolus feeding. The aim of this study was to compare the GI adverse effects and the metabolic and nutritional consequences of intragastric feeding of an enteral formula (Jevity; Ross Laboratories, Columbus, OH) intermittently or continuously to dogs. Using a cross-over study design, 10 healthy dogs were randomly assigned to be fed Jevity via gastrostomy tube either continuously (CF) or in 3 bolus meals/day (IF) for 10 days. The dogs were weighed daily. Serum chemistry and glucose tolerance tests (GTT) were performed before and after each 10-day trial period. Fecal dry matter (FDM), serum osmolality (sOsm), and serum electrolytes (sElec) were determined 5 times during each 10 day trial period. Urine specific gravity was checked intermittently. Hydrogen breath tests were performed on days 0, 3, and 10. During the last 6 days of each trial period, nitrogen balance and digestibility of the Jevity were determined. There were no GI adverse effects noted on either protocol, and no significant (P > .05) differences in body weights, serum chemistry results, sElec, sOsm, GTT, hydrogen breath tests, digestibility trials, or nitrogen balance. There was a significant (P < .05) decrease in FDM over time for both protocols, and a significant (P < .05) increase in urine volume for IF compared with CF. In summary, there were no significant differences between treatments in weight maintenance, GI adverse effects, GTT, nitrogen balance, or feed digestibility. Changes in FDM suggest that the dogs received excess water. In conclusion, this study of healthy dogs provides no support for the preferential use of continuous intragastric feeding over bolus feeding.

Use of adult dog serum as a substitute for colostrum in the neonatal dog.

Failure to obtain passive transfer of immunity via colostrum can be detrimental to the health and survival of a young pup. It has been stated that pups that do not receive colostrum in the first 2 days after birth, be given adult dog serum as a source of protective immunoglobulins. Twenty-five Beagle pups were obtained by cesarean section from 6 Beagle bitches. The pups were allotted to 3 groups at birth. Group 1 was a control group and was allowed to suckle colostrum. Group-2 pups received 22 ml of pooled adult dog serum/kg of body weight (10 ml/lb) SC at birth. Group-3 pups were given 22 ml of pooled adult dog serum/kg by stomach tube at birth. Pups from groups 2 and 3 were separated from the bitch for 48 hours to prevent colostral antibody absorption and were fed a commercially available milk replacer by stomach tube. After 48 hours, all pups were returned to the bitch until they were weaned at 6 weeks of age. Blood samples were collected from all of the pups at birth and on days 1, 2, 7, 14, 21, 28, and 35. The concentration of IgA, IgG, and IgM in serum was determined by radial immunodiffusion and compared by use of a one-way analysis of variance. The control pups had significantly higher serum concentrations of IgA and IgG, than the pups in groups 2 and 3 on days 1 and 2 and 2 and 7, respectively. Group-2 pups had significantly higher serum IgM concentrations on day 1 than either group 1- or group-3 pups.

Clinical evaluation of the new compound diphenylsilanediol for ani-epileptic efficacy and toxicity.

A controlled clinical trial of the anti-epileptic efficacy and toxic side effects of diphenylsilanediol was conducted on 24 client-owned epileptic dogs. Data obtained from an abbreviated procedural treatment program indicated that diphenylsilanediol compared favorably with primidone as an anti-epileptic compound, but had limiting toxic side effects to the liver, pancreas, and possibly to other tissues. There was a mean reduction of 60.7% in seizure frequency in 15 epileptic dogs treated with diphenylsilanediol when compared with their pretreatment frequency. There was a mean reduction of 55.6% in seizure frequency in 9 spileptic control dogs treated with primidone. Samples of blood obtained from the dogs in the program on the 4th, 8th, 12th, 24th, and 36th weeks of treatment were examined for complete blood cell count, blood urea nitrogen, liver function, and pancreatic function. Toxic side effects were not seen among the primidone-treated control dogs, with the exception of occasional dose-related drowsiness. Among the diphenylsilanediol-treated dogs, 3 developed liver disease, 2 developed definite pancreatic changes, and 2 showed evidence of bone marrow suppression. Four dogs died during treatment with diphenylsilanediol, whereas no deaths occurred during the same interval of primidone therapy.

Transient renal tubulopathy in a Labrador retriever.

A four-month-old male Labrador retriever was presented for polyuria, polydipsia and persistent euglycaemic glucosuria. On referral, diagnostic tests demonstrated abnormal fractional excretions of electrolytes, increased urinary excretion of selected amino acids, mild renal tubular acidosis and mild proteinuria, indicating renal tubular dysfunction. Pyelonephritis was suspected and potentiated amoxycillin was administered. On re-evaluation at six months of age, the dog was no longer polyuric or polydipsic and the metabolic abnormalities associated with the tubulopathy had resolved. Transient Fanconi's syndrome has not previously been reported in small animals. This report demonstrates the potential for recovery of function in cases presenting with renal tubulopathies.

Neutrophilic leucocytosis in a dog with a rectal tumour.

A nine-year-old cocker spaniel was presented with a three-year history of intermittent haematochezia and a palpable rectal mass. Routine haematological examination revealed a marked mature neutrophilia (86.04 x 10(9) neutrophils/litre). A friable mass in the middle portion of the rectum was detected on colonoscopy. Histopathological examination of mucosal pinch biopsies collected from the mass confirmed a diagnosis of adenomatous tubulopapillary polyp. Some evidence of malignant transformation was observed. Palliative treatment with piroxicam suppositories at a dose of 1.4 mg/kg administered rectally every third day was instituted. On re-evaluation, 47 days after starting medical therapy, the owner reported a significant reduction in haematochezia and tenesmus; however, frequency of defecation had remained unaltered. Routine haematology revealed a reduction in the mature neutrophil count (33.67 x 10(9) neutrophils/litre). This report describes a case of a rectal tumour associated with a neutrophilic leucocytosis, which responded to palliative therapy with piroxicam suppositories.

Canine inflammatory bowel disease: retrospective analysis of diagnosis and outcome in 80 cases (1995-2002).

The case records of 80 dogs in which idiopathic inflammatory bowel disease (IBD) had been diagnosed were reviewed, and owners were contacted for follow-up information using a telephone questionnaire. The types of IBD encountered were lymphocytic (n=6), lymphocytic-plasmacytic (n=38), eosinophilic (n=6) and mixed inflammation (n=30). Prednisolone, sulphasalazine, metronidazole and tylosin were the most frequently prescribed medications. At follow-up, 21 dogs (26 per cent) were classified as being in remission (for a median of 14 months), 40 dogs (50 per cent) had intermittent clinical signs (for a median of 17 months) and three dogs (4 per cent) had uncontrolled disease (for a median of 19 months). Ten dogs (13 per cent) had been euthanased due to refractory IBD and four of these had entered remission for a median of 21 months prior to developing severe relapse and refractoriness to further treatment. Six dogs (8 per cent) had been euthanased or had died for reasons unrelated to IBD. Hypoalbuminaemia at the time of diagnosis was significantly associated with a negative outcome (P=0.0007). No association was found between the site (P=0.75), type (P=0.44) and severity (P=0.75) of disease. Dietary change to single protein and carbohydrate commercial diets had no association with outcome (P=0.12). Owner assessment of quality of life at follow-up was significantly associated with outcome (P=0.006).

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.

Psychotherapy for adult attention deficit/hyperactivity disorder: a comparison with cognitive behaviour therapy.

Attention deficit/hyperactivity disorder (ADHD), a disorder generally associated with children, has become a valid disorder for adults in the last decade. The first line treatment of adult ADHD is medications, but historically there have been limitations to medication as the only treatment. Psychotherapy has become a feasible modality in the treatment of ADHD for those who have residual symptoms. The aim of this review of literature is to compare cognitive behaviour therapy with other psychotherapeutic treatment for effectiveness in improving symptoms of ADHD in adults and adolescences. The evidence-based practice approach by Stillwell et al. is adopted to guide the systematic review. The use of this small evidence utilization project that led to a synthesis of available research will provide direction for future research and expand knowledge in treatment for adult ADHD.

Chronic gastric instability and presumed incomplete volvulus in dogs.

Chronic gastric volvulus in dogs results in long-standing gastrointestinal signs unlike those of acute gastric dilatation and volvulus. This report describes chronic gastric volvulus in seven dogs. The majority of dogs presented with weight loss, chronic vomiting, lethargy and abdominal pain. A combination of radiographic, ultrasonographic and endoscopic imaging indicated altered positioning of gastric landmarks. Dynamic changes were identified in some cases. Exploratory coeliotomy and surgical gastropexy were performed in all dogs. Clinical signs improved or resolved in six of seven dogs postoperatively. Chronic gastric volvulus is an uncommon condition in dogs, but should be considered as a differential in cases presenting with the above clinical signs.