Search PubMed⌕ Search

Biomedical subjects

G F Grauer

Publications and source records attributed to G F Grauer.

35 records · Page 2Linked to original sources

Comparison of the effects of ethanol and 4-methylpyrazole on the pharmacokinetics and toxicity of ethylene glycol in the dog.

The purpose of this investigation was to compare the effects of ethanol and 4-methylpyrazole (4MP) on the toxicity and pharmacokinetics of ethylene glycol (EG) in the dog. All dogs received 173 mmol/kg EG, p.o. Dogs were randomly assigned to 3 groups: EG-treated only, EG + ethanol (19.3 mmol/kg, i.v. 3, 7, 14 and 24 h after EG) and EG + 4MP (0.24 mmol/kg, i.v. 3 h after EG, 0.18 mmol/kg at 24 h and 0.06 mmol/kg at 36 h). EG produced a rapid onset of metabolic acidosis (within 3 h) and acute oliguric renal failure (after 48 h), whereas administration of ethanol or 4MP greatly attenuated acidosis and prevented renal toxicity. The administration of ethanol, however, severely increased the central nervous system (CNS) depression that existed after ingestion of EG. The half-life of FG in serum was 10.8 +/- 0.7 h in the EG-only treatment group, 6.8 +/- 0.7 (P less than 0.05) in the EG + ethanol group and 9.8 +/- 0.9 h in the EG + 4MP group. Approx. 10% and 48% of the dose of EG was excreted unchanged in the urine at the 0-3 and 3-72 h periods, respectively. Treatment with 4MP increased the amount of EG excreted in the urine (71% from 3-72 h), whereas ethanol did not (51%). However, both ethanol and 4MP increased the rate constant of EG excretion into urine approx. 70%. These data demonstrate the utility of 4MP over ethanol for the treatment of EG-induced toxicity in dogs and indicate that ethanol and 4MP cause an increase in the rate constant of EG excretion in the urine and not a prolongation in EG half-life.

Animals↗

Clinicopathologic and histologic evaluation of Dirofilaria immitis-induced nephropathy in dogs.

Twelve beagles were infected with 200 Dirofilaria immitis infective larvae to study glomerular lesions associated with filariasis. All developed high serum levels of antibodies to dirofilarial antigens and became persistently microfilaremic. The dogs were killed at various times between 398 and 562 days post-infection and renal lesions were examined by light, electron, and immunofluorescent microscopy and antibody elution techniques. A membranoproliferative glomerulonephritis was observed in all dogs. Immunofluorescence was positive in all; predominantly in a fine granular pattern along the glomerular capillary wall. Ultrastructural examination showed intramembranous globular electron-dense deposits and a linear band of fine electron-dense particles in all dogs. Antibody elution studies demonstrated antibody reactive to dirofilarial antigens. In a subsequent experiment, an aqueous-soluble antigen prepared from adult female D. immitis was infused into the renal arteries of 5 heartworm-naive dogs. Immunofluorescent examination of the infused kidneys showed dirofilarial antigen present on the glomerular capillary wall in a fine granular pattern indicating there was adherence of the antigen to the capillary wall. These observations support the hypothesis of in situ immune complex formation as part of the pathogenesis of glomerulonephritis associated with dirofilariasis.

Animals↗

Ascites, renal abnormalities, and electrolyte and acid-base disorders associated with liver disease.

Ascites and renal dysfunction are often associated with decreased liver function and reflect the complex abnormalities of water, protein, electrolyte, and acid-base metabolism that may complicate severe liver disease. This article discusses the pathophysiology and management of ascites, polydipsia and polyuria, decreased renal function, and acid-base and electrolyte alterations that can complicate liver disease.

Acid-Base Imbalance↗

Estimation of quantitative proteinuria in the dog, using the urine protein-to-creatinine ratio from a random, voided sample.

The correlation between 24-hour urine protein excretion and the protein-to-creatinine ratio (U-P/C) from random, voided urine specimens was assessed in 16 healthy Beagles (9 to 11 months old) and in 14 dogs with suspected renal proteinuria. Initially, a voided urine specimen was obtained from each dog, and the U-P/C was determined. An attempt was not made to standardize the time of collection of the voided urine. Subsequently, each dog was placed in a metabolism cage, and 24-hour urine specimens were collected for quantitative protein analysis. The Coomassie blue technique was used to measure urine protein. The correlation between the U-P/C and the 24-hour urine protein excretion (mg/kg/24 hr), evaluated by linear-regression analysis, was found to be significant (r = 0.975, P less than 0.01). These results substantiate previous findings and indicate that random, voided urine specimens may be used to compute the ratio and to accurately reflect 24-hour urinary protein loss in the dog.

Animals↗

Clinicopathologic findings in dogs and cats with ethylene glycol intoxication.

Clinicopathologic findings were retrospectively evaluated in 26 cats and 24 dogs with ethylene glycol intoxication. Common clinical signs were ataxia, depression, vomiting, and hypothermia. Characteristic alterations in the hemogram and serum chemical profile included neutrophilia, lymphopenia, azotemia, hyperphosphatemia, hypocalcemia, hyperglycemia, and decreased whole blood bicarbonate. Common urinalysis findings included isosthenuria, proteinuria, glucosuria, hematuria, calcium oxalate and hippurate crystalluria, and the presence of renal epithelial cells, white blood cells, and granular and cellular casts in the urine sediment. The high death rate (78%) was attributed to delays in presentation, diagnosis, and therapy.

Acidosis↗

Early clinicopathologic findings in dogs ingesting ethylene glycol.

Fifteen dogs were given 9.5 ml of ethylene glycol/kg of body weight, orally. Physical examination and clinical laboratory findings were evaluated at 1 and 3 hours after ingestion. Three of these dogs were also evaluated at 6, 9, 12, 24, 48, and 72 hours after ingestion. At 1 and 3 hours, the dogs were depressed, ataxic, and polydipsic with increased urine output and serum osmolality. Plasma bicarbonate and urine osmolality were decreased. The osmolal and anion gaps were increased at 1 and 3 hours, respectively. Calcium oxalate crystalluria was first observed at 6 hours. Diminished renal excretory function was not evident until 48 hours. Depression, ataxia, metabolic acidosis, polydipsia, and polyuria in the presence of serum hyperosmolality were early (1 and 3 hour) findings that indicated ethylene glycol intoxication in dogs.

Animals↗

Evaluation of laparoscopy for obtaining renal biopsy specimens from dogs and cats.

Laparoscopic direction of renal biopsy was evaluated in 37 dogs and 1 cat suspected of having renal disease. Specimens adequate for morphologic diagnosis were obtained in 37 cases (97%). Eleven of the 38 animals were necropsied and the biopsy diagnosis was confirmed in 10 of the cases (91%). Excessive pericapsular hemorrhage and severe hematuria developed in 1 dog. Three dogs (8%) had macroscopic hematuria for 24 hours after biopsy.

Animals↗

Fluid therapy for gastrointestinal, pancreatic, and hepatic disorders.

Patients with gastrointestinal, hepatic, or pancreatic disease frequently require parenteral fluid therapy. The selection of the type and amount of fluid for administration should be based on a knowledge of physiologic derangements and the controlling mechanisms. Table 4 provides suggested replacement fluids and supplements for each disease. It must be remembered, however, that individual "tailoring" is required for each case. In addition to an expert knowledge of pathophysiology, monitoring of the patient's weight, fluid losses, serum electrolyte, and acid-base status is necessary for successful fluid therapy. In veterinary medicine the most common cause of inadequate fluid therapy is a deviation in the amount of fluid that the patient receives from the intended amount that may have been ever so carefully calculated.

Animals↗

Effects of a specific thromboxane synthetase inhibitor on development of experimental Dirofilaria immitis immune complex glomerulonephritis in the dog.

Twelve Beagle dogs were immunized with aqueous-soluble Dirofilaria immitis antigens, and subsequent to at least fivefold increases in serum antibody titer, 6 mg of homologous antigen was infused into the left renal artery. Six dogs were treated once daily starting the day of infusion with 0.75 mg/kg of 1-benzylimidazole (1-BIM) in saline. Six control dogs were given saline only. Light, immunofluorescent, and transmission electron microscopic examinations of renal tissue from control dogs, 10 days after antigen infusion, showed a mesangioproliferative glomerulonephritis in the left kidney with polymorphonuclear leukocyte (PMNL) infiltration and fibrin deposition. Immunoglobulin (Ig) G, M, C3, and Dirofilaria antigen deposits were observed in a segmental granular pattern. Mesangial, subendothelial, and intramembranous electron dense deposits were observed, and anti-Dirofilaria antibodies were demonstrated in kidney eluates from each dog. Administration of 1-BIM had no significant effect on IgG, IgM, C3, or antigen deposits, electron dense deposits, or concentration of antibody in kidney eluates. However, 1-BIM-treated dogs had less glomerular cell proliferation, periodic acid-Schiff (PAS) positive glomerular staining, PMNL infiltration, and fibrin deposition. These data suggest that thromboxane is an important mediator in the development of immune complex glomerulonephritis, and that in certain circumstances, inhibition of thromboxane synthesis may be an effective therapy for immune complex glomerulonephritis in the dog.

Animals↗

Plasma histamine and gastrin concentrations in 17 dogs with mast cell tumors.

Dogs with mast cell tumors (MCT) are often affected with paraneoplastic syndromes such as gastrointestinal ulceration. The mechanism of ulceration is believed to be related to hyperhistaminemia. To test this hypothesis, plasma histamine and gastrin concentrations were measured in 17 dogs with MCT. Plasma histamine concentrations in dogs with MCT were significantly higher than those in normal dogs. Conversely, plasma gastrin concentrations in dogs with MCT were significantly lower than gastrin concentrations in normal dogs. Additionally, plasma gastrin concentrations were inversely related to plasma histamine concentrations, which provided indirect evidence for the presence of hyperacidity secondary to hyperhistaminemia (r2 = 57.7). Plasma histamine and plasma gastrin concentrations were not related to clinical stage of disease, tumor histologic grade, or tumor size. Median survival time was 245 days, with a range of 90 to 1315 days. Because the degree of hyperhistaminemia could not be predicted in this study from the clinical stage, histologic grade, or tumor size, these data suggest that hyperhistaminemia may occur in any dog with MCT.

Animals↗

Treatment of membranoproliferative glomerulonephritis and nephrotic syndrome in a dog with a thromboxane synthetase inhibitor.

A 2-year-old spayed female Whippet with membranoproliferative glomerulonephritis and nephrotic syndrome was treated with a specific thromboxane synthetase inhibitor (3-methyl-2[3-pyridyl]-1-indoleoctanoic acid), resulting in decreased proteinuria and resolution of ascites and edema. Glomerular histology, however, appeared unaffected by treatment. Discontinuation of treatment for 10 weeks resulted in increased proteinuria and decreased serum albumin concentrations that were again attenuated when treatment was reinitiated. Thromboxane synthetase inhibitors have been used successfully to treat experimentally induced glomerulonephritis in several species and this treatment appears to hold promise for naturally occurring glomerulonephritis in dogs.

Animals↗

Estimation of quantitative enzymuria in dogs with gentamicin-induced nephrotoxicosis using urine enzyme/creatinine ratios from spot urine samples.

The correlation between 24-hour urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transferase (GGT) with urine NAG and GGT/creatinine ratios was assessed in dogs with gentamicin-induced nephrotoxicosis. Eighteen 6-month-old male Beagles with normal renal function were randomly divided into 3 groups of 6. Each group was fed a different concentration of protein (high protein, 27.3%; medium protein, 13.7%; and low protein, 9.4%) for 21 days. After dietary conditioning, gentamicin was administered at a dose of 10 mg/kg IM tid for 8 days and each group was continued on its respective diet. Endogenous creatinine clearance and 24-hour urinary excretion of NAG and GGT were determined after dietary conditioning (day 0) and on days 2, 4, 6, and 8 of gentamicin administration. In addition, urine NAG and GGT/creatinine ratios (IU/L divided by mg/dL) were determined from catheterized spot urine samples obtained between 7 and 10 AM on the same days. The correlation between 24-hour urinary enzyme excretion and urine enzyme/creatinine ratio in the spot urine samples was evaluated by simple linear regression analysis. Spot sample urine enzyme/creatinine ratios were significantly correlated with 24-hour urinary enzyme excretion through day 4 for dogs on low dietary protein, through day 6 for those on medium protein, and through day 8 for those on high dietary protein. Mean +/- SD baseline values for urine NAG/creatinine ratio and 24-hour urinary NAG excretion were 0.06 +/- 0.04 and 0.19 +/- 0.14 IU/kg/24 hr, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

Functional urethral obstruction in 3 dogs: clinical and urethral pressure profile findings.

Three dogs with dysuria and urine retention caused by excessive functional urethral resistance are described. All dogs had clinical histories and urologic signs that previously would have been classified as detrusor-urethral dyssynergia. Diagnosis of functional urinary obstruction was established by exclusion of anatomic urinary obstruction and confirmed by urethral pressure profilometry. In 2 cases, multiple pressure deflections recorded in the urethral pressure profile suggested spasm of urethral musculature, whereas in a 3rd dog, abnormally high pressures were recorded along a portion of the proximal urethra. Functional urinary obstruction was associated with prostatitis in 1 dog and with a history of urethral calculi in 1 dog, and no underlying disorder could be identified in the remaining dog. All 3 dogs improved with medical treatments that included alpha adrenergic antagonists. The etiology, diagnosis, and pharmacologic management of functional urinary obstruction are discussed.

Animals↗

Effects of enalapril versus placebo as a treatment for canine idiopathic glomerulonephritis.

A blinded, multicenter, prospective clinical trial assessed the effects of enalapril (EN) versus standard care in dogs with naturally occurring, idiopathic glomerulonephritis (GN). Twenty-nine adult dogs with membranous (n = 16) and membranoproliferative (n = 13) GN were studied. Dogs were randomly assigned to receive either EN (0.5 mg/kg PO q12-24h; n = 16) or placebo (n = 14) for 6 months (1 dog was treated first with the placebo and then with EN). All dogs were treated with low-dose aspirin (0.5-5 mg/kg PO q12-24h) and fed a commercial diet. At baseline, serum creatinine (SrCr), systolic blood pressure (SBP), and glomerular histologic grade were not different between groups, but the urine protein/creatinine ratio (UP/C) was greater in the EN group compared with the placebo group (8.7 +/- 4.4 versus 4.7 +/- 2.3). After 6 months of treatment, the change in UP/C from baseline was significantly different between groups (EN = -4.2 +/- 1.4 versus 1.9 +/- 0.9 in the placebo group). When data were adjusted for changes in SrCr (SrCr X UP/C) a similar significant reduction was noted ( 2.2 +/- 15.2 versus 8.4 +/- 10.1). The change in SBP after 6 months of treatment also was significantly different between groups (EN = -12.8 +/- 27.3 versus 5.9 +/- 21.5 mm Hg in the placebo group). Response to treatment was categorized as improvement (assigned a value of 2), no progression (assigned a value of 1), and progression (assigned a value of 0). Response was significantly better in the EN group (1.4 +/- 0.8) compared with the placebo group (0.3 +/- 0.5). These results suggest that EN treatment is beneficial in dogs with naturally occurring idiopathic GN.

Angiotensin-Converting Enzyme Inhibitors↗

Comparison of the effects of diltiazem and aspirin on platelet aggregation in cats.

Platelet aggregation in response to collagen (1 or 3 micrograms/ml), arachidonic acid (10(-2) M), and adenosine diphosphate (ADP, 2 microM) was compared in healthy cats treated with diltiazem (approximately 2 mg/kg body weight, q 8 hrs for 10 doses), aspirin (approximately 21 mg/kg body weight [1 baby aspirin], q 72 hrs for three doses), or a combination of diltiazem and aspirin. Baseline values obtained prior to treatment served as controls. Addition of arachidonic acid to blood resulted in an impedance change (i.e., aggregation) with time in samples from the nontreated cats and the cats treated with diltiazem, but the addition had no effect in blood from cats treated with aspirin alone or with a combination of diltiazem and aspirin. Platelet aggregation in response to either concentration of collagen or to ADP was not altered by any treatment. Secretion of adenosine triphosphate (ATP) from the platelets was measured when the aggregating agent was 3 micrograms/ml collagen; secretion was not affected by any treatment.

Adenosine Diphosphate↗