World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs.

Evaluation of canine renal biopsy tissue has generally relied on light microscopic (LM) evaluation of hematoxylin and eosin-stained sections ranging in thickness from 3 to 5 µm. Advanced modalities, such as transmission electron microscopy (TEM) and immunofluorescence (IF), have been used sporadically or retrospectively. Diagnostic algorithms of glomerular diseases have been extrapolated from the World Health Organization classification scheme for human glomerular disease. With the recent establishment of 2 veterinary nephropathology services that evaluate 3-µm sections with a panel of histochemical stains and routinely perform TEM and IF, a standardized objective species-specific approach for the diagnosis of canine glomerular disease was needed. Eight veterinary pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89 dogs. Hierarchical cluster analysis of the data revealed 2 large categories of glomerular disease based on the presence or absence of immune complex deposition: The immune complex-mediated glomerulonephritis (ICGN) category included cases with histologic lesions of membranoproliferative or membranous patterns. The second category included control dogs and dogs with non-ICGN (glomerular amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on only the LM parameters led to misdiagnosis of 22 of the 89 cases-that is, ICGN cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby emphasizing the importance of advanced diagnostic modalities in the evaluation of canine glomerular disease. Salient LM, TEM, and IF features for each pattern of disease were identified, and a preliminary investigation of related clinicopathologic data was performed.

Prevalence of urinary tract infection in dogs after surgery for thoracolumbar intervertebral disc extrusion.

BACKGROUND: Urinary tract infection (UTI) is a common complication in people with spinal cord injury (SCI). Dogs with acute intervertebral disc extrusion (IVDE) have similar risk factors for UTI when compared with human SCI patients and have a high perioperative prevalence of UTI. OBJECTIVES: Determine the prevalence of UTI in dogs for 3 months after surgery for thoracolumbar IVDE and identify risk factors for development of UTI. ANIMALS: Twenty-five dogs treated surgically for 26 acute disc extrusions. METHODS: Prospective study. Urinalysis and urine culture were performed perioperatively. At home, owners monitored urine with dipsticks every 48 hours for 1 month then once a week until 3 months. Dogs returned for assessment of motor function, urinalysis, and urine culture at 1 and 3 months after surgery. Presence of UTI over the 3-month period was correlated to potential risk factors. RESULTS: Ten dogs (38%) developed 12 UTIs over the 3-month period, with the majority occurring between weeks 1 and 6; 60% of the UTIs were occult. Hematuria in the absence of pyuria or UTI was a common finding in the perioperative period. Sex, breed, and ambulatory status influenced the risk of developing a UTI. CONCLUSIONS AND CLINICAL IMPORTANCE: There is a high prevalence of UTIs, many of which are occult, in the 3 months after surgery for thoracolumbar IVDE. These dogs should be routinely monitored for UTI with urine culture regardless of urinalysis results.

Urine sodium concentrations are predictive of hypoadrenocorticism in hyponatraemic dogs: a retrospective pilot study.

OBJECTIVES: To determine if a urine sodium concentration could be used to rule out hypoadrenocorticism in hyponatraemic dogs. MATERIALS AND METHODS: Medical records were reviewed for hyponatraemic dogs (serum sodium<135 mmol/L) that had recorded urine sodium concentrations. Twenty hyponatraemic dogs were included: 11 diagnosed with classical hypoadrenocorticism and nine with non-adrenal causes of hyponatraemia. A Wilcoxon rank-sum test was used to compare results between groups. RESULTS: No dog with hypoadrenocorticism had a urine sodium concentration less than 30 mmol/L. Urine sodium concentration in dogs with hypoadrenocorticism was significantly higher (median 103 mmol/L, range: 41 to 225) than in dogs with non-adrenal illness (median 10 mmol/L, range: 2 to 86) (P<0·0005). Serum sodium concentrations were not significantly different between dogs with hypoadrenocorticism and dogs with non-adrenal illness. CLINICAL SIGNIFICANCE: These results suggest that urine sodium concentrations can be used to prioritise a differential diagnosis of hypoadrenocorticism in hyponatraemic dogs. A urine sodium concentration less than 30 mmol/L in a hyponatraemic dog makes classical hypoadrenocorticism an unlikely cause of the hyponatraemia. Nevertheless, because of the small sample size our results should be interpreted with caution and a larger follow-up study would be valuable.

Effect of Cranberry Extract on the Frequency of Bacteriuria in Dogs with Acute Thoracolumbar Disk Herniation: A Randomized Controlled Clinical Trial.

BACKGROUND: Dogs with spinal cord injury are at increased risk of developing bacteriuria due to increased residual urine volume. Cranberry extract inhibits binding of E. coli to uroepithelial cells, potentially reducing risk of bacteriuria. HYPOTHESIS: Cranberry extract reduces risk of bacteriuria in dogs after acute TL-IVDH. ANIMALS: Client-owned dogs with acute onset TL-IVDH causing nonambulatory status. METHODS: Randomized, placebo-controlled, blinded, prospective clinical trial. Dogs with acute TL-IVDH were recruited 48 hours postoperatively and randomized to receive cranberry extract or placebo in a masked fashion. Urine cultures and neurological examinations were performed 2, 4, and 6 weeks postoperatively. The number of dogs with bacteriuria (all bacterial species) and bacteriuria (E. coli) were primary and secondary outcome measures and were evaluated using chi-squared test. Urine antiadhesion activity (AAA) was measured in a subset (N = 47) and examined in a secondary analysis evaluating additional risk factors for bacteriuria. RESULTS: Bacteriuria was detected 17 times in 94 dogs (6 placebo, 11 cranberry, P = .12). There were 7 E. coli. positive cultures (1 placebo, 6 cranberry, P = .09). Dogs in both groups had positive urine AAA (14/21: placebo, 16/26: cranberry), and dogs with urine AAA had significantly fewer E. coli positive cultures (n = 1) than dogs without it (n = 4) (P = .047). CONCLUSIONS AND CLINICAL IMPORTANCE: This clinical trial did not show a benefit of oral cranberry extract but had low power. Cranberry extract supplementation did not impact urine AAA, but a possible association between urine AAA and lower risk of E. coli bacteriuria was identified. Other doses could be investigated.

Evaluation of colonoscopic allergen provocation as a diagnostic tool in dogs with proven food hypersensitivity reactions.

OBJECTIVE: To evaluate the colonoscopic allergen provocation (COLAP) test as a new tool for the diagnosis of IgE-mediated food allergy. METHODS: Oral food challenges as well as COLAP testing were performed in a colony of nine research dogs with proven immediate-type food allergic reactions. In addition, COLAP was performed in five healthy dogs. RESULTS: When compared with the oral challenge test, COLAP accurately determined 18 of 23 (73 per cent) positive oral challenge reactions (73 per cent) in dogs with food allergies and was negative in the healthy dogs. CLINICAL SIGNIFICANCE: The accuracy of this new test may be higher than that for gastric sensitivity testing. Therefore, COLAP holds promise as a new test to confirm the diagnosis of suspect IgE-mediated food allergy in dogs.

Development and characterization of an isolated and perfused tumor and skin preparation for evaluation of drug disposition.

The purpose of this study was to develop a model in which the regional pharmacokinetics of a drug in tumor and nontumorous tissue could be evaluated under a variety of physiological conditions. To this effect, the growth of a human choriocarcinoma cell line (JAR) was evaluated in pigs immunosuppressed with 25 mg cyclosporine/kg every 24 h. During an initial study, we demonstrated that suspensions containing approximately 3 million JAR cells with and without 1 million normal human fibroblasts injected s.c. into the inguinal region of pigs resulted in the growth of tumors consisting primarily of polygonal neoplastic cells. Multinucleate tumor cells, inflammatory cells, necrotic debris, and vascular endothelial cells were also present. Maximal tumor size was noted on day 12, after which time tumor regression occurred. The coinoculation of fibroblasts resulted in significantly larger tumors. Two single pedicle, axial pattern tubed flaps were created in the inguinal area of 4 pigs. JAR cells and fibroblasts were transplanted to one flap to allow for tumor formation. The other flap served as a nontumorous control. Both flaps were removed for perfusion with a physiological solution 11 days later. Glucose utilization, lactate concentrations, lactate dehydrogenase activities, and microscopic evaluation of skin samples were used to assess flap viability. All flaps remained viable for 8 h of perfusion. The only differences detected between nontumorous and tumor flaps was the initial perfusion pressure which was significantly lower in tumor flaps (P < 0.05). The isolated perfused tumor and skin flap is unique in that it consists of a tumor surrounded by normal tissue with an intact microvascular system and can be utilized to design regional pharmacokinetic studies describing drug distribution in tumor tissue.

Cardiovascular-renal axis disorders in the domestic dog and cat: a veterinary consensus statement.

OBJECTIVES: There is a growing understanding of the complexity of interplay between renal and cardiovascular systems in both health and disease. The medical profession has adopted the term "cardiorenal syndrome" (CRS) to describe the pathophysiological relationship between the kidney and heart in disease. CRS has yet to be formally defined and described by the veterinary profession and its existence and importance in dogs and cats warrant investigation. The CRS Consensus Group, comprising nine veterinary cardiologists and seven nephrologists from Europe and North America, sought to achieve consensus around the definition, pathophysiology, diagnosis and management of dogs and cats with "cardiovascular-renal disorders" (CvRD). To this end, the Delphi formal methodology for defining/building consensus and defining guidelines was utilised. METHODS: Following a literature review, 13 candidate statements regarding CvRD in dogs and cats were tested for consensus, using a modified Delphi method. As a new area of interest, well-designed studies, specific to CRS/CvRD, are lacking, particularly in dogs and cats. Hence, while scientific justification of all the recommendations was sought and used when available, recommendations were largely reliant on theory, expert opinion, small clinical studies and extrapolation from data derived from other species. RESULTS: Of the 13 statements, 11 achieved consensus and 2 did not. The modified Delphi approach worked well to achieve consensus in an objective manner and to develop initial guidelines for CvRD. DISCUSSION: The resultant manuscript describes consensus statements for the definition, classification, diagnosis and management strategies for veterinary patients with CvRD, with an emphasis on the pathological interplay between the two organ systems. By formulating consensus statements regarding CvRD in veterinary medicine, the authors hope to stimulate interest in and advancement of the understanding and management of CvRD in dogs and cats. The use of a formalised method for consensus and guideline development should be considered for other topics in veterinary medicine.

Effect of tumor presence on cisplatin and carboplatin: disposition in the isolated, perfused tumor and skin flap.

The purpose of this study was to evaluate the disposition of elemental platinum (Pt) derived from cisplatin (CDDP) or carboplatin (CBDCA) in the isolated, perfused tumor and skin flap (IPTSF). Flaps were perfused with either 3.0 micrograms CDDP/ml perfusion medium (n = 4 tumor, n = 4 control) or 15 micrograms CBDCA/ml (n = 4 tumor, n = 3 control) at a rate of 1 ml/min for 3 h. A 2-h (CDDP experiments) or 3-h (CBDCA experiments) washout phase using undosed medium was then performed. The disposition kinetics of free (ultrafilterable) Pt were characterized using a four-compartment physiologically relevant pharmacokinetic model. A tumor effect on the disposition of Pt was noted in that the Pt mass from CDDP in the central and mobile tissue compartments was greater in tumor flaps than in control flaps (P < 0.05). Similar trends were noted in CBDCA-treated flaps, but these were not significant. The Pt mass in the fixed tumor and non-tumor tissue compartments was significantly greater when Pt was derived from CDDP than when it was derived from CBDCA (P < 0.05). A linear relationship existed between the estimated micrograms of Pt in the flaps from both CDDP and CBDCA and the cross-sectional vascular resistance of the flaps at 30 (CDDP, r = 0.78; CBDCA, r = 0.89) and 60 min (CDDP, r = 0.65; CBDCA, r = 0.85) of perfusion. We conclude that the IPTSF is a useful model for evaluating the disposition of Pt drugs in tumor and non-tumor tissue and that tumor presence alters the disposition of CDDP.

Inotropic, chronotropic and coronary vasodilator potency of forskolin.

The cardiodynamic profile of forskolin, a direct activator of adenylate cyclase, was examined in an isovolumic left ventricular (LV) preparation of coronary-perfused guinea-pig hearts. Forskolin consistently induced concentration-dependent increases in LV systolic pressure development, increases in spontaneous beating frequency and decreases in coronary vascular resistance. However, the forskolin concentration required for one-half of the maximal effect (EC50) for coronary vasodilation (3.8 +/- 0.6 X 10(-8) M, n = 6) was 7- to 10-fold less than the EC50 for positive chronotropy (29.3 +/- 4.6 X 10(-8) M, P less than 0.01) and 17- to 20-fold less than the EC50 for positive inotropy (66.3 +/- 7.4 X 10(-8) M, P less than 0.001). The inotropic response to forskolin was not secondary to the concomitant increase in bearing frequency. Also, the coronary vasodilator response persisted in K+-depolarized non-beating hearts, and therefore did not depend on endogeneous coronary vascular autoregulation secondary to increased myocardial oxygen demand. We conclude that forskolin induces direct pharmacologic effects in ventricular muscle, pacemaker cells and the coronary vasculature, but add that the coronary vasculature is over one order of magnitude more sensitive to forskolin than is ventricular muscle. Perhaps adenylate cyclase systems in the heart exist as different subtypes with different affinity characteristics for forskolin-like drugs.

An in vitro-in vivo validation of the isolated perfused tumor and skin flap preparation as a model of cisplatin delivery to tumors.

The isolated perfused tumor and skin flap (IPTSF) is a unique model system in which drug disposition is evaluated in tumor tissue and surrounding normal tissue, both of which are supplied by the same vascular system. We compared tissue Pt concentrations obtained following systemic administration of cisplatin (CDDP) to whole pigs bearing tumored skin flaps with data obtained from IPTSF treated similarly. During the in vivo study, CDDP was administered intravenously to six pigs that had tumor and skin flaps. IPTSF were created in four pigs and isolated in a perfusion chamber and perfused with medium containing CDDP for 180 min. Venous plasma or perfusate samples were serially collected throughout perfusion. Tissue samples were collected after perfusion was complete. All samples were assayed for Pt by atomic absorption spectroscopy. Area under the curve of Pt profiles from IPTSF and in vivo perfused flaps were not significantly different. Pt concentrations were significantly higher in tumor samples from in vivo perfused flaps than in samples from IPTSF. Pt concentrations in skin and subcutaneous tissue were not significantly different. When consideration is given to all of the potential variables that were operative in these experiments, the results of this study demonstrate that Pt distribution within the IPTSF was comparable to that obtained in vivo.

Auto IgG anti-IgE and IgG x IgE immune complex presence and effects on ELISA-based quantitation of IgE in canine atopic dermatitis, demodectic acariasis and helminthiasis.

Atopic dermatitis is a common allergic disease manifestation in dogs; however, there is no correlation between clinical disease and detectable total serum IgE. Auto antibodies of the IgG subclass against IgE may affect the detection of serum IgE by immunoassay and may be important in the regulation of IgE production by B cells. ELISA were developed to detect serum antibodies specific for IgE using a newly available canine monoclonal IgE of known antigen specificity, generated from a canine x murine heterohybridoma. To test for correlation of auto IgG anti-IgE levels with manifestation of atopic dermatitis, the sera from 101 atopic dogs were compared with sera from non-atopic dogs of various breeds, foxhounds manifesting clinical signs of demodectic acariasis and helminth parasitized random bred dogs for quantities of IgG anti-IgE measured in units/ml compared to a high titer standard serum. To test for serum effects on quantitation of IgE, known amounts of canine monoclonal IgE were added to various sera and measured by capture ELISA with detecting monoclonal antibodies specific for heat labile or heat stabile epitopes. Unheated sera from dogs manifesting clinical atopic dermatitis and helminth parasitized dogs had levels of IgG anti-IgE that were significantly lower than various breeds of dogs not manifesting dermatologic lesions and foxhounds manifesting demodectic acariasis. Heating sera at 56 degrees C for 3 h to denature the high affinity binding site on the IgE heavy chain caused a marked increase over non-heated sera in detectable IgG anti-IgE in almost all dogs. This increase was most profound in helminth-infected dogs and foxhounds manifesting demodectic mange with 7 fold increases each, respectively, and in atopic dogs with a 5 fold increase compared to 3 fold increases for clinically-normal springer spaniels and all soft coated wheaten terriers. The terriers demonstrated an association of lower heated serum values of IgG anti-IgE with manifestation of a familial syndrome of protein-losing enteropathy and protein-losing nephropathy. The ability of mouse anti-canine IgE monoclonal antibodies specific for either heat labile or heat stabile epitopes to detect canine monoclonal IgE added to sera in known amounts varied from serum to serum and at different concentrations of the same serum, but did not correlate with IgG anti-IgE values for these sera. The range of absolute levels of serum IgE in dogs showing little or no inhibition of detection of added IgE was < 0.5 ng/micromilligram to 2 micrograms/micromilligram. It was concluded that the increase in detectable IgG anti-IgE after heating sera indicates that IgG x IgE immune complexes are normally present in most dogs; however, the increase over uncomplexed IgG anti-IgE was most pronounced in dogs manifesting atopic dermatitis and demodectic acariasis. A quantitative comparison of IgG anti-IgE or IgG x IgE to total serum IgE was not made because the ability of monoclonal antibodies specific for either heat labile or heat stable epitopes on the IgE heavy chain to detect IgE added to serum, as well as innate serum IgE, was highly variable in different dilutions of serum from individual to individual.

A retrospective case-control of acute renal failure in 99 dogs.

The objective of this study was to evaluate retrospectively demographic and clinicopathologic factors that may be associated with the diagnosis and outcome of acute renal failure (ARF) in dogs presented to a large referral hospital. Medical records of dogs presented to the hospital were searched for a diagnosis of ARF. The diagnosis of ARF was based on clinical signs, renal imaging findings, and clinicopathologic data and, in most cases, was confirmed by histopathology, prior serum creatinine concentrations, response to therapy, and known recent nephrotoxin exposure or ischemic event. Demographics, selected clinicopathologic findings, and concurrent disorders that may have been associated with development of ARF were extracted from these records. A reference population was derived from 481 dogs presenting to the same hospital. Demographic data also were collected from these medical records. The demographic factors associated with a diagnosis of ARF and the factors associated with outcome of ARF were assessed by reviewing a series of multiple logistic regression models. Conclusions from this study were as follows: (1) Intact male dogs and nonsporting dogs were more likely to develop ARF and be admitted to the teaching hospital. (2) Dogs with severe azotemia (serum creatinine concentration > 10 mg/dL), hypocalcemia (< 8.6 mg/ dL), and proteinuria were less likely to survive ARF and be discharged from the hospital. (3) Dogs that survived in the hospital for more than 5 days were more likely to recover and be discharged from the hospital.

Hypercalcemia in cats: a retrospective study of 71 cases (1991-1997).

A retrospective study was conducted to characterize the diseases, clinical findings, and clinicopathologic and ultrasonographic findings associated with hypercalcemia (serum calcium concentration >11 mg/dL) in 71 cats presented to North Carolina State University Veterinary Teaching Hospital. The 3 most common diagnoses were neoplasia (n = 21), renal failure (n = 18), and urolithiasis (n = 11). Primary hyperparathyroidism was diagnosed in 4 cats. Lymphoma and squamous cell carcinoma were the most frequently diagnosed tumors. Calcium oxalate uroliths were diagnosed in 8 of 11 cats with urolithiasis. Cats with neoplasia had a higher serum calcium concentration (13.5 +/- 2.5 mg/dL) than cats with renal failure or urolithiasis and renal failure (11.5 +/- 0.4 mg/dL; P < .03). Serum phosphorus concentration was higher in cats with renal failure than in cats with neoplasia (P < .004). Despite the fact that the majority of cats with uroliths were azotemic, their serum urea nitrogen and creatinine concentrations and urine specific gravity differed from that of cats with renal failure. Additional studies are warranted to determine the underlying disease mechanism in the cats we identified with hypercalcemia and urolithiasis. We also identified a small number of cats with diseases that are not commonly reported with hypercalcemia. Further studies are needed to determine whether an association exists between these diseases and hypercalcemia, as well as to characterize the underlying pathophysiologic mechanism for each disease process.

Familial protein-losing enteropathy and protein-losing nephropathy in Soft Coated Wheaten Terriers: 222 cases (1983-1997).

Records and pedigrees of Soft Coated Wheaten Terriers (SCWT) with protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN) were studied retrospectively. Criteria for inclusion were defined based on analysis of blood (panhypoproteinemia for PLE, hypoalbuminemia for PLN) and urine (proteinuria for PLN) and histopathologic examination of tissue. Two hundred twenty-two affected dogs (female:male ratio = 1.6, P < .001) were clinically identified. Dogs were diagnosed with PLE earlier (P < .005; mean +/- SD age: 4.7+/-2.6 years, n = 76) than with PLN (6.3+/-2.0 years, n = 84) or with both diseases (5.9+/-2.2 years, n = 62). Clinical signs included vomiting, diarrhea, weight loss, pleural and peritoneal effusions, and less commonly thromboembolic disease. Dogs with PLE generally had panhypoproteinemia and hypocholesterolemia; intestinal lesions included inflammatory bowel disease, dilated lymphatics, and lipogranulomatous lymphangitis. Dogs with PLN generally had hypoalbuminemia, proteinuria, hypercholesterolemia, and azotemia; renal lesions typically showed chronic glomerulonephritis/glomerulosclerosis, and less commonly endstage renal disease. Dogs with combined PLE/PLN had intermediate mean values (P < .001) for serum total protein, albumin, globulin, and cholesterol but had a higher mean urine protein:creatinine ratio than did PLN dogs (P < .05); intestinal and renal lesions in these dogs were similar to those in the other groups. Two dogs had incidental mild renal dysplasia. Pedigree analysis from 188 dogs demonstrated a common male ancestor, although the mode of inheritance is unknown. Both PLE and PLN are common diseases in this small breed population. The prognosis is poor. Compared with previously reported intestinal and renal diseases in dogs, a new, distinctive familial predisposition for both PLE and PLN has been recognized in the SCWT breed.

Splenic infarction in 16 dogs: a retrospective study.

Sixteen dogs with splenic infarction due to causes other than splenic torsion were identified. Dogs with splenic infarction often had multiple concurrent diseases, and surgical management of splenic infarction was associated with high mortality. Splenic infarction occurred in dogs with hypercoagulable conditions associated with liver disease, renal disease, and hyperadrenocorticism, or as a consequence of uniform splenomegaly, neoplasia, or thrombosis associated with cardiovascular disease. Clinical signs and common laboratory findings generally reflected the underlying disease process. A variety of splenic abnormalities were detected by abdominal ultrasound in 15 dogs, with the ventral extremity of the spleen being most often abnormal. Four dogs were euthanized or died because of the presence of severe systemic disease, whereas 12 dogs underwent laparotomy. Complete splenectomy was performed in 9 dogs and partial splenectomy was performed in 2 dogs. Seven dogs died in the immediate postoperative period, 3 required chronic veterinary care, and 2 had uncomplicated long-term recoveries. Splenic infaraction should be regarded as a sign of altered blood flow and coagulation, rather than as a primary disease, and surgical management should be reserved for patients with life-threatening complications such as hemoabdomen or sepsis.

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.

Food hypersensitivity reactions in Soft Coated Wheaten Terriers with protein-losing enteropathy or protein-losing nephropathy or both: gastroscopic food sensitivity testing, dietary provocation, and fecal immunoglobulin E.

The purpose of this study was to evaluate Soft Coated Wheaten Terriers (SCWTs) affected with protein-losing enteropathy (PLE) or protein-losing nephropathy (PLN) or both for allergy to food. We performed gastroscopic food-sensitivity testing, a provocative dietary trial, and measurement of fecal immunoglobulin E (IgE) in 6 SCWTs affected with PLE or PLN or both. Positive gastroscopic food-sensitivity test reactions were noted in 5 of 6 dogs. Positive reactions were found to milk in 4 dogs, to lamb in 2 dogs, and to wheat and chicken each in 1 dog. Adverse reactions to food (diarrhea, vomiting, or pruritus) were detected in all 6 dogs during the provocative dietary trial. Adverse reactions were found to corn in 5 dogs, to tofu in 3 dogs, to cottage cheese in 2 dogs, to milk in 2 dogs, to farina cream of wheat in 2 dogs, and to lamb in 2 dogs. Serum albumin concentrations significantly decreased and fecal alpha1-protease inhibitor concentration significantly increased 4 days after the provocative trial when compared with baseline values. Antigen-specific fecal IgE varied throughout the provocative trial, with peak levels following ingestion of test meals. We conclude that food hypersensitivities are present in SCWTs affected with the syndrome of PLE/PLN. Mild inflammatory bowel disease was already established in the 6 SCWTs of this report at the time of study, making it impossible to determine if food allergies were the cause or result of the enteric disease.

The effects of cyclosporine versus standard care in dogs with naturally occurring glomerulonephritis.

Glomerulonephritis (GN) is a leading cause of chronic renal failure in dogs. However, little is known about the efficacy of available treatment options for GN in this species. The purpose of this study was to determine the effects of cyclosporine (Cy) administration on the outcome of naturally occurring GN in dogs. Thirteen dogs from 4 institutions were included in the study. Randomization of dogs into placebo-versus Cy-treated groups was stratified according to initial morphological diagnosis and contributing institution. Seven and 6 dogs were assigned to be given placebo or Cy, respectively. The initial Cy dose of 10 mg/kg every 24 hours was adjusted to maintain 24-hour trough, whole blood Cy concentrations between 250 and 400 ng/mL. There were no statistically significant differences between placebo- and Cy-treated groups with respect to serum total protein, albumin, urea nitrogen and creatinine, and plasma protein concentrations; platelet count; urine protein-creatinine ratio; endogenous creatinine clearance; 24-hour urine protein concentrations; or 24-hour urine protein-endogenous creatinine clearance ratio. However, PCV was significantly lower in the Cy-treated group. Decreased appetite, diarrhea, vomiting, weight loss, involuntary shaking, and thrombocytopenia were noted in both treatment groups; however, clinical signs in Cy-treated dogs subjectively were more severe. One Cy-treated dog developed gingival hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics, inhibition of lymphoblast transformation, and toxicity of cyclosporine in clinically normal pigs.

Pharmacokinetic variables were calculated from time-concentration data obtained after IV (10 mg/kg of body weight; n =9) and oral (12.5 mg/kg to group A [n = 3]; 25 mg/kg to group B [n = 3]; and 50 mg/kg to group C [n = 3] pigs) cyclosporine (formerly, cyclosporine A) administration. Resulting mean (+/- SD) pharmacokinetic variables were as follows: half life of distribution, 0.96 (+/- 0.7) hours; half life of elimination, 7.71 (+/- 2.6) hours; volume of distribution at steady state, 4.47 (+/- 2.22) L/kg; volume of the central compartment, 1.71 (+/- 0.78) L/kg; and systemic clearance, 8.95 (+/- 2.7) ml/kg/min. Oral bioavailability was: overall 57 (+/- 19) %; group A, 44 (+/- 11) %; group B, 78 (+/- 15) %; group C, 48 (+/- 6) %. Time to peak concentration was 3.55 (+/- 0.88) hours. During the 22 days of daily oral cyclosporine administration, blood 24-hour trough concentrations were: group A, 224.3 (+/- 78.4) ng/ml; group B, 640.7 (+/- 174.6) ng/ml; and group C, 2,344 (+/- 1,095) ng/ml. Lymphoblast transformation stimulation index was suppressed in all pigs except 1, which had a corresponding cyclosporine concentration of 92.4 ng/ml. Minimal, although statistically significant, decreases in serum albumin and magnesium concentrations and increases in serum creatinine and urea nitrogen concentrations were evident in pigs of some treatment groups. Histologic examination of necropsy specimens revealed mild hepatic necrosis (n = 1 pig), renal tubular dilatation (n = 5), and pulmonary inflammation (n = 2). Pigs given 25 and 50 mg of cyclosporine/kg failed to gain weight.