Co-impairment of autonomic and glucagon responses to insulin-induced hypoglycemia in dogs with naturally occurring insulin-dependent diabetes mellitus.

This study aimed to investigate the contributions of two factors potentially impairing glucagon response to insulin-induced hypoglycemia (IIH) in insulin-deficient diabetes: 1) loss of paracrine disinhibition by intra-islet insulin and 2) defects in the activation of the autonomic inputs to the islet. Plasma glucagon responses during hyperinsulinemic-hypoglycemic clamps ([Formula: see text]40 mg/dL) were assessed in dogs with spontaneous diabetes (n = 13) and in healthy nondiabetic dogs (n = 6). Plasma C-peptide responses to intravenous glucagon were measured to assess endogenous insulin secretion. Plasma pancreatic polypeptide, epinephrine, and norepinephrine were measured as indices of parasympathetic and sympathoadrenal autonomic responses to IIH. In 8 of the 13 diabetic dogs, glucagon did not increase during IIH (diabetic nonresponder [DMN]; ∆ = -6 ± 12 pg/mL). In five other diabetic dogs (diabetic responder [DMR]), glucagon responses (∆ = +26 ± 12) were within the range of nondiabetic control dogs (∆ = +27 ± 16 pg/mL). C-peptide responses to intravenous glucagon were absent in diabetic dogs. Activation of all three autonomic responses were impaired in DMN dogs but remained intact in DMR dogs. Each of the three autonomic responses to IIH was positively correlated with glucagon responses across the three groups. The study conclusions are as follows: 1) Impairment of glucagon responses in DMN dogs is not due to generalized impairment of α-cell function. 2) Loss of tonic inhibition of glucagon secretion by insulin is not sufficient to produce loss of the glucagon response; impairment of autonomic activation is also required. 3) In dogs with major ß-cell function loss, activation of the autonomic inputs is sufficient to mediate an intact glucagon response to IIH.NEW & NOTEWORTHY In dogs with naturally occurring, insulin-dependent (C-peptide negative) diabetes mellitus, impairment of glucagon responses is not due to generalized impairment of α-cell function. Loss of tonic inhibition of glucagon secretion by insulin is not sufficient, by itself, to produce loss of the glucagon response. Rather, impaired activation of the parasympathetic and sympathoadrenal autonomic inputs to the pancreas is also required. Activation of the autonomic inputs to the pancreas is sufficient to mediate an intact glucagon response to insulin-induced hypoglycemia in dogs with naturally occurring diabetes mellitus. These results have important implications that include leading to a greater understanding and insight into the pathophysiology, prevention, and treatment of hypoglycemia during insulin treatment of diabetes in companion dogs and in human patients.

Curricular Revision and Reform: The Process, What Was Important, and Lessons Learned.

Beginning in 2005, the Doctor of Veterinary Medicine program at the University of California underwent major curricular review and reform. To provide information for others that follow, we have documented our process and commented on factors that were critical to success, as well as factors we found surprising, difficult, or problematic. The review and reform were initiated by the Executive Committee, who led the process and commissioned the committees. The planning stage took 6 years and involved four faculty committees, while the implementation stage took 5 years and was led by the Curriculum Committee. We are now in year 2 of the institutionalizing stage and no longer refer to our reform as the "new curriculum." The change was driven by a desire to improve the curriculum and the learning environment of the students by aligning the delivery of information with current teaching methodologies and implementing adult learning strategies. We moved from a department- and discipline-based curriculum to a school-wide integrated block curriculum that emphasized student-centered, inquiry-based learning. A limit was placed on in-class time to allow students to apply classroom knowledge by solving problems and cases. We found the journey long and arduous, requiring tremendous commitment and effort. In the change process, we learned the importance of adequate planning, leadership, communication, and a reward structure for those doing the "heavy lifting." Specific to our curricular design, we learned the importance of the block leader role, of setting clear expectations for students, and of partnering with students on the journey.

Laparoscopic Adrenalectomy for Removal of Unilateral Noninvasive Pheochromocytomas in 10 Dogs.

OBJECTIVE: To report the surgical technique and outcome of dogs undergoing laparoscopic adrenalectomy for removal of unilateral noninvasive pheochromocytoma. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs with unilateral noninvasive adrenal tumors (n=10). METHODS: Medical records of dogs that underwent laparoscopic adrenalectomy for histologically confirmed pheochromocytoma were reviewed. Dogs were positioned in lateral recumbency with the table tilted up to create a semi-sternal position. Three or 4 ports were used and dissection of the mass proceeded using a combination of laparoscopic instrumentation, bipolar vessel-sealing devices, and in some cases monopolar electrosurgical probes. Conversion rate, complications, surgical time, hospitalization time, and long-term follow-up were recorded. RESULTS: The procedure was completed without the need for conversion in 9 of 10 dogs. In 1 dog, hemorrhage obscured the visual field and conversion to an open approach was elected. In 5 cases, a 3-port approach was used, and in 5 cases, a 4th port was placed. Median surgical time was 105 minutes (range, 65-250). Intraoperative complications included 1 splenic laceration. Postoperatively, 1 dog developed gastric dilatation-volvulus. All dogs were discharged from the hospital. Median follow-up time was 16.0 months (range, 6.9-38.0). CONCLUSION: With careful case selection, laparoscopic adrenalectomy for resection of pheochromocytoma was feasible and could be performed efficiently by experienced laparoscopic surgeons.

Evaluation of total dietary fiber concentration and composition of commercial diets used for management of diabetes mellitus, obesity, and dietary fat-responsive disease in dogs.

OBJECTIVE: To determine total dietary fiber (TDF) concentration and composition of commercial diets used for management of obesity, diabetes mellitus, and dietary fat-responsive disease in dogs. DESIGN: Cross-sectional study. SAMPLE: Dry (n = 11) and canned (8) canine therapeutic diets. PROCEDURES: Insoluble and soluble dietary fiber (IDF and SDF), high-molecular-weight SDF (HMWSDF), and low-molecular-weight SDF (LMWSDF) concentrations were determined. Variables were compared among diets categorized by product guide indication, formulation (dry vs canned), and regulatory criteria for light and low-fat diets. RESULTS: SDF (HMWSDF and LMWSDF) comprised a median of 30.4% (range, 9.4% to 53.7%) of TDF; LMWSDF contributed a median of 11.5% (range, 2.7% to 33.8%) of TDF. Diets for diabetes management had higher concentrations of IDF and TDF with lower proportions of SDF and LMWSDF contributing to TDF, compared with diets for treatment of fat-responsive disease. Fiber concentrations varied within diet categories and between canned and dry versions of the same diet (same name and manufacturer) for all pairs evaluated. Diets classified as light contained higher TDF and IDF concentrations than did non-light diets. All canned diets were classified as low fat, despite providing up to 38% of calories as fat. CONCLUSIONS AND CLINICAL RELEVANCE: Diets provided a range of TDF concentrations and compositions; veterinarians should request TDF data from manufacturers, if not otherwise available. Consistent responses to dry and canned versions of the same diet cannot necessarily be expected, and diets with the same indications may not perform similarly. Many diets may not provide adequate fat restriction for treatment of dietary fat-responsive disease.

Comparison of perioperative morbidity and mortality rates in dogs with noninvasive adrenocortical masses undergoing laparoscopic versus open adrenalectomy.

OBJECTIVE: To describe the clinicopathologic features of a cohort of dogs with adrenocortical masses that underwent laparoscopic adrenalectomy and to compare perioperative morbidity and mortality rates in these dogs with rates for dogs that underwent open adrenalectomy for resection of similarly sized (maximal diameter, ≤ 5 cm) adrenocortical masses. DESIGN: Retrospective case series. ANIMALS: 48 client-owned dogs that underwent laparoscopic (n = 23) or open (25) adrenalectomy for noninvasive tumors (ie, tumors that did not invade the vena cava or other surrounding organs). Procedures-Medical records were reviewed. History, clinical signs, physical examination findings, clinicopathologic findings, imaging results, and surgical variables were recorded. A 3- or 4-port approach was used for laparoscopic adrenalectomy. Surgical time, perioperative complications, postoperative and overall hospitalization times, and perioperative deaths were recorded and compared between groups. RESULTS: The surgical method for 1 dog was converted from a laparoscopic to an open approach. Perioperative death occurred in no dogs in the laparoscopic group and 2 dogs in the open adrenalectomy group. Surgical time was shorter for laparoscopic (median, 90 minutes; range, 40 to 150 minutes) than for open (median, 120 minutes; range, 75 to 195 minutes) adrenalectomy. Laparoscopic adrenalectomy was associated with shorter hospitalization time and more rapid discharge from the hospital after surgery, compared with the open procedure. CONCLUSIONS AND CLINICAL RELEVANCE: With careful patient selection, laparoscopic adrenalectomy was associated with a low complication rate and low conversion rate for resection of adrenocortical masses as well as shorter surgical and hospitalization times, compared with open adrenalectomy.

Animal models of disease: classification and etiology of diabetes in dogs and cats.

Diabetes mellitus is a common disease in dogs and cats. The most common form of diabetes in dogs resembles type 1 diabetes in humans. Studies suggest that genetics, an immune-mediated component, and environmental factors are involved in the development of diabetes in dogs. A variant of gestational diabetes also occurs in dogs. The most common form of diabetes in cats resembles type 2 diabetes in humans. A major risk factor in cats is obesity. Obese cats have altered expression of several insulin signaling genes and glucose transporters and are leptin resistant. Cats also form amyloid deposits within the islets of the pancreas and develop glucotoxicity when exposed to prolonged hyperglycemia. This review will briefly summarize our current knowledge about the etiology of diabetes in dogs and cats and illustrate the similarities among dogs, cats, and humans.

Total dietary fiber composition of diets used for management of obesity and diabetes mellitus in cats.

OBJECTIVE: To determine total dietary fiber (TDF) composition of feline diets used for management of obesity and diabetes mellitus. DESIGN: Cross-sectional survey. SAMPLE: Dry veterinary (n = 10), canned veterinary (12), and canned over-the-counter (3) feline diets. PROCEDURES: Percentage of TDF as insoluble dietary fiber (IDF), high-molecular-weight soluble dietary fiber (HMWSDF), and low-molecular-weight soluble dietary fiber (LMWSDF) was determined. RESULTS: Median measured TDF concentration was greater than reported maximum crude fiber content in dry and canned diets. Median TDF (dry-matter) concentration in dry and canned diets was 12.2% (range, 8.11% to 27.16%) and 13.8% (range, 4.7% to 27.9%), respectively. Dry and canned diets, and diets with and without a source of oligosaccharides in the ingredient list, were not different in energy density or concentrations of TDF, IDF, HMWSDF, or LMWSDF. Similarly, loaf-type (n = 11) and gravy-type (4) canned diets differed only in LMWSDF concentration. Disparities in TDF concentrations among products existed despite a lack of differences among groups. Limited differences in TDF concentration and dietary fiber composition were detected when diets were compared on the basis of carbohydrate concentration. Diets labeled for management of obesity were higher in TDF concentration and lower in energy density than diets for management of diabetes mellitus. CONCLUSIONS AND CLINICAL RELEVANCE: Diets provided a range of TDF concentrations with variable concentrations of IDF, HMWSDF, and LMWSDF. Crude fiber concentration was not a reliable indicator of TDF concentration or dietary fiber composition. Because carbohydrate content is calculated as a difference, results suggested that use of crude fiber content would cause overestimation of both carbohydrate and energy content of diets.

Serum 17alpha-hydroxyprogesterone concentrations during the reproductive cycle in healthy dogs and dogs with hyperadrenocorticism.

OBJECTIVE: To determine concentrations of 17alpha-hydroxyprogesterone (17OHP) in serum of healthy bitches during various stages of the reproductive cycle and in bitches with hyperadrenocorticism and to compare the dynamics of 17OHP with those of progesterone. DESIGN: Prospective evaluation study. ANIMALS: 15 healthy sexually intact bitches and 28 spayed bitches with hyperadrenocorticism. PROCEDURES: 11 healthy bitches were evaluated during estrus, nonpregnant diestrus, and anestrus (group 1); 4 other healthy bitches were evaluated during pregnancy and after ovariohysterectomy (group 2). Cycle stages were determined via physical examination, vaginal cytologic evaluation, and serum progesterone concentration. Bitches with hyperadrenocorticism were evaluated once at the time of diagnosis (group 3). Serum hormone concentrations were determined with immunoassays. RESULTS: In group 1, the serum 17OHP concentration was significantly higher in diestrus (median, 1.8 ng/mL) than in estrus (median, 1.1 ng/mL) and anestrus (median, 0.2 ng/mL) and higher in estrus than in anestrus. Changes in serum progesterone concentrations accounted for 22% (estrus) or 23% (diestrus) of the variation in serum 17OHP concentrations. In group 2, 17OHP and progesterone concentrations were significantly higher during pregnancy than after ovariohysterectomy. The serum 17OHP concentration in group 3 was significantly lower (median, 0.2 ng/mL) than in group 1 in estrus and diestrus and in group 2 during pregnancy (median, 0.7 ng/mL) but was not different from 17OHP concentrations in anestrus or after ovariohysterectomy (median, 0.2 ng/mL). CONCLUSIONS AND CLINICAL RELEVANCE: Serum 17OHP concentrations in healthy bitches increased during estrus, diestrus, and pregnancy and at those times were higher than in spayed bitches with hyperadrenocorticism.

Evaluation of six portable blood glucose meters for measuring blood glucose concentration in dogs.

OBJECTIVE: To evaluate accuracy of 6 portable blood glucose meters (PBGMs) by comparing results of these meters with results obtained with a reference chemistry analyzer. DESIGN: Evaluation study. ANIMALS: 49 dogs (158 blood samples). Procedures-Venous blood samples were tested with the 6 PBGMs, and results were compared with results of a commercially available analyzer that used a reference method based on the hexokinase reaction. RESULTS: Plasma glucose concentrations obtained with the reference analyzer ranged from 41 to 639 mg/dL. There were significant correlations between blood glucose concentrations obtained with the 6 PBGMs and plasma glucose concentrations obtained with the reference analyzer (r > or = 0.96). However, for all 6 PBGMs, results differed from results for the reference analyzer, with the difference increasing as plasma glucose concentration increased. Significant differences in bias were found among meters. For 142 samples classified as hypoglycemic, euglycemic, or hyperglycemic on the basis of results of the reference analyzer, the percentage of samples that were misclassified on the basis of results of the PBGMs ranged from 2.1% to 38.7%. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the present study suggested that there were substantial differences in the accuracy of currently available PBGMs when used to determine blood glucose concentration in dogs.

Evaluation of urine specific gravity and urine sediment as risk factors for urinary tract infections in cats.

BACKGROUND: It has been suggested that diseases that promote isosthenuria predispose to urinary tract infections because of a lack of the common bacteriostatic properties present in concentrated urine. OBJECTIVES: The purpose of this study was to assess the clinicopathologic risk factors for positive urine culture outcome in cats with chronic kidney disease (CKD), diabetes mellitus (DM), uncontrolled hyperthyroidism (HT), or lower urinary tract disease (LUTD). METHODS: For this retrospective study, medical records of all cats in which a urinalysis and aerobic bacterial urine culture were performed between January 1995 and December 2002 were reviewed. Signalment, body weight, and clinicopathologic data were recorded. Based on the medical records, cats were diagnosed with CKD, DM, HT, or LUTD. Prevalence odds ratios and 95% confidence intervals were calculated using logistic regression. Multivariate models were created for each variable of interest while controlling for the confounding effect of disease group. RESULTS: Six hundred fourteen cats met the criteria for inclusion in the study. Overall, positive urine cultures were identified in 16.9% of cats with CKD, 13.2% of cats with DM, 21.7% of cats with HT, and 4.9% of cats with clinical signs of LUTD. Decreasing urine specific gravity was not associated with positive urine culture when controlled for disease but pyuria, bacteriuria, and hematuria were all associated with positive urine culture outcome. Persians, females, increasing age, and decreasing body weight were all associated with positive urine culture outcome. CONCLUSIONS: Performing a urine culture sample based solely on the presence of isosthenuria does not seem warranted. Further studies are warranted to help identify host predisposing factors for urinary bacterial colonization in cats with these diseases.

Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism.

OBJECTIVE: To evaluate the effects of twice-daily oral administration of a low-dose of trilostane treatment and assess the duration of effects after once-daily trilostane administration in dogs with naturally occurring hyperadrenocorticism (NOH). DESIGN: Prospective study. ANIMALS: 28 dogs with NOH. PROCEDURES: 22 dogs received 0.5 to 2.5 mg of trilostane/kg (0.23 to 1.14 mg/lb) orally every 12 hours initially. At intervals, dogs were reevaluated; owner assessment of treatment response was recorded. To assess drug effect duration, 16 of the 22 dogs and 6 additional dogs underwent 2 ACTH stimulation tests 3 to 4 hours and 8 to 9 hours after once-daily trilostane administration. RESULTS: After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [3]). At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.

Serum insulin-like growth factor-I concentration in cats with diabetes mellitus and acromegaly.

BACKGROUND: Serum insulin-like growth factor-I (IGF-I) has been used in place of serum growth hormone quantification for identifying acromegaly in diabetic cats. The utility of IGF-I as a screening test for acromegaly has not been critically evaluated. This retrospective study was performed to evaluate the usefulness of serum IGF-I concentration for identifying acromegaly. HYPOTHESIS: Serum IGF-I is a useful screening test for acromegaly in diabetic cats. ANIMALS: A review was made of the medical records of 74 diabetic cats that had serum IGF-I quantified. The diabetes was classified as well controlled (15 cats), poorly controlled because of problems with the insulin treatment regimen, concurrent disease, or both (40), or poorly controlled with clinical findings consistent with acromegaly (19). METHODS: A review of medical records was made. RESULTS: Serum IGF-I concentration was significantly (P < .0001) increased in acromegalic diabetic cats, compared with well-controlled and poorly controlled diabetic cats. Sensitivity and specificity for serum IGF-I concentration were 84% (95%/ confidence interval [CI] = 60.4-96.6%) and 92% (95% CI = 81.3-97.2%), respectively. There was no significant correlation between serum IGF-I concentration and duration of insulin treatment (r = 0.23, P = .089), insulin dosage (r = 0.14, P = .30), age (r = 0.16, P = .12), and pituitary volume (r = 0.40, P = .11), but a modest correlation was found between serum IGF-I concentration and body weight (r = 0.48, P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Results support the use of serum IGF-I concentration as a screening test for acromegaly in diabetic cats that have clinical findings supportive of the disease.

Clinical features and heritability of hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers: 25 cases (1994-2006).

OBJECTIVE: To evaluate the clinical features and heritability of naturally occurring hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers (NSDTRs). DESIGN: Retrospective case series. ANIMALS: 25 NSDTRs with hypoadrenocorticism. PROCEDURES: Questionnaires completed by owners of NSDTRs with hypoadrenocorticism and medical records from veterinarians were reviewed for information regarding diagnosis, age at diagnosis, concurrent diseases, age at death, and cause of death. Pedigrees were analyzed for heritability and mode of inheritance of hypoadrenocorticism (including complex segregation analysis of pedigrees of 1,515 dogs). RESULTS: On the basis of results of ACTH stimulation testing, hypoadrenocorticism was diagnosed in 16 female and 9 male NSDTRs (including 6 full siblings). Median age at diagnosis was 2.6 years; the diagnosis was made prior to 2 years of age in 11 dogs. Seventeen dogs had hyponatremia, hyperkalemia, or both, and serum electrolyte concentrations were within reference ranges for 8 dogs at the time of diagnosis. Median survival time after diagnosis for 4 dogs that died or were euthanized as a result of medical causes was 1.6 years. Heritability was calculated at 0.98 with no sex effect, and complex segregation analysis fit a major gene model with an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL RELEVANCE: In NSDTRs, hypoadrenocorticism was diagnosed at an earlier age, compared with published reports of age at diagnosis among the general dog population. Among the study dogs, 32% had no serum electrolyte abnormalities at the time of diagnosis, and the disease appeared to have an autosomal recessive mode of inheritance in the breed.

Adrenalectomy and caval thrombectomy in a cat with primary hyperaldosteronism.

A 13-year-old, castrated male, domestic longhaired cat was diagnosed with primary hyperaldosteronism from an adrenal gland tumor and a thrombus in the caudal vena cava. Clinical signs included cervical ventriflexion, lethargy, weakness, inappetence, and diarrhea. Laboratory tests revealed hypokalemia, normonatremia, hyperglycemia, hypophosphatemia, and elevated creatine kinase activity. Hypokalemia worsened despite oral potassium supplementation. An adrenalectomy and caval thrombectomy were successfully performed utilizing deliberate hypothermia followed by progressive rewarming.

Comparison of serologic evaluation via agar gel immunodiffusion and fungal culture of tissue for diagnosis of nasal aspergillosis in dogs.

OBJECTIVE: To compare the sensitivity and specificity of serologic evaluation and fungal culture of tissue for diagnosis of nasal aspergillosis in dogs. DESIGN: Prospective study. ANIMALS: 58 dogs with nasal discharge and 26 healthy dogs. PROCEDURES: Dogs with nasal discharge were anesthetized and underwent computed tomography and rhinoscopy; nasal tissues were collected for histologic examination and fungal culture. Sera were assessed for antibodies against Aspergillus spp (healthy dog sera were used as negative control specimens). Nasal aspergillosis was diagnosed in dogs that had at least 2 of the following findings: computed tomographic characteristics consistent with aspergillosis, fungal plaques detected during rhinoscopy, and histologically detectable fungal hyphae in nasal tissue. Histologic characteristics of malignancy were diagnostic for neoplasia. Without evidence of neoplasia or fungal disease, nonfungal rhinitis was diagnosed. RESULTS: Among the 58 dogs, 21 had nasal aspergillosis, 25 had nonfungal rhinitis, and 12 had nasal neoplasia. Fourteen aspergillosis-affected dogs and 1 dog with nonfungal rhinitis had serum antibodies against Aspergillus spp. Fungal culture results were positive for Aspergillus spp only for 17 dogs with aspergillosis. With regard to aspergillosis diagnosis, sensitivity, specificity, and positive and negative predictive values were 67%, 98%, 93%, and 84%, respectively, for serum anti-Aspergillus antibody determination and 81%, 100%, 100%, and 90%, respectively, for fungal culture. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that seropositivity for Aspergillus spp and identification of Aspergillus spp in cultures of nasal tissue are highly suggestive of nasal aspergillosis in dogs; however, negative test results do not rule out nasal aspergillosis.

Relative adrenal insufficiency in dogs with sepsis.

BACKGROUND: A syndrome of relative adrenal insufficiency has been identified in septic humans, and is associated with hypotension and death. Relative adrenal insufficiency is generally associated with basal serum cortisol concentration within or above the reference range and a blunted cortisol response to adrenocorticotropic hormone administration. It is unknown whether relative adrenal insufficiency occurs in septic dogs. HYPOTHESIS: That relative adrenal insufficiency occurs in septic dogs, and that relative adrenal insufficiency is associated with hypotension and mortality. ANIMALS: Thirty-three septic dogs admitted to a small animal intensive care unit. METHODS: Dogs were included in the study if they had a known or suspected infectious disease and had systemic inflammatory response syndrome. Dogs were excluded if they had disease or medication history expected to affect the hypothalamic-pituitary-adrenal axis. Serum cortisol and endogenous plasma adrenocorticotropic hormone concentrations were measured before, and serum cortisol concentration measured 1 hour after, intramuscular administration of 250 microg of cosyntropin/dog. The change in cortisol concentration (delta-cortisol) before and after cosyntropin administration was determined in each dog. RESULTS: Hypotension was associated with lower delta-cortisol values (OR 1.3; CI 1.0-1.9; P = .029). delta-Cortisol cutoff of 3.0 microg/dL was most accurate for predicting hypotension, survival to discharge, and 28-day survival. The rate of death in dogs with delta-cortisol < or = 3 microg/dL was 4.1 times that of dogs with delta-cortisol > 3 microg/dL (RR 4.1; CI 1.5-12.3; P = .01). CONCLUSIONS AND CLINICAL RELEVANCE: Delta-cortisol < or = 3 microg/dL after adrenocorticotropic hormone administration is associated with systemic hypotension and decreased survival in septic dogs.

Incidence of and risk factors for diabetes mellitus in cats that have undergone renal transplantation: 187 cases (1986-2005).

OBJECTIVE: To compare incidence of diabetes mellitus in cats that had undergone renal transplantation with incidence in cats with chronic renal failure, compare mortality rates in cats that underwent renal transplantation and did or did not develop diabetes mellitus, and identify potential risk factors for development of posttransplantation diabetes mellitus (PTDM) in cats. DESIGN: Retrospective case series. ANIMALS: 187 cats that underwent renal transplantation. PROCEDURES: Medical records were reviewed. RESULTS: 26 of the 187 (13.9%) cats developed PTDM, with the incidence of PTDM being 66 cases/1,000 cat years at risk. By contrast, the incidence of diabetes mellitus among a comparison population of 178 cats with chronic renal failure that did not undergo renal transplantation was 17.9 cases/1,000 cat years at risk, and cats that underwent renal trans-plantation were 5.45 times as likely to develop diabetes mellitus as were control cats with chronic renal failure. The mortality rate among cats with PTDM was 2.38 times the rate among cats that underwent renal transplantation but did not develop PTDM. Age, sex, body weight, and percentage change in body weight were not found to be significantly associated with development of PTDM. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cats that undergo renal transplantation have an increased risk of developing diabetes mellitus, compared with cats with chronic renal failure, and that mortality rate is higher for cats that develop PTDM than for cats that do not.

Comparable myelinated nerve pathology in feline and human diabetes mellitus.

The occurrence of diabetic neuropathy in cats provides an opportunity to study the development and treatment of neurological complications not present in diabetic rodent models, where few pathological alterations are evident. The present study further defines pathological alterations in nerve biopsies from 12 cats with spontaneously occurring diabetes mellitus. Peroneal nerve biopsies displayed concurrent injury to both Schwann cells and axons of myelinated fibers that was remarkably similar to that present in human diabetic neuropathy. In addition to demyelination, remyelination (constituting 20-84% of the total myelinated fiber population) was indicated by fibers with inappropriately thin myelin sheaths. Unlike our previous investigations, striking axonal injury was apparent, and consisted of dystrophic accumulations of membranous debris or neurofilaments, as well as degenerative fiber loss resulting in a 50% decrease in myelinated fiber density. In spite of extensive fiber loss, regenerative clusters were apparent, suggesting that axonal regeneration was not completely frustrated. These data highlight the potential utility of feline diabetic neuropathy as a model that faithfully replicates the nerve injury in human diabetes mellitus.

Inhaled flunisolide suppresses the hypothalamic-pituitary-adrenocortical axis, but has minimal systemic immune effects in healthy cats.

Feline bronchial disease is commonly treated with oral glucocorticoids (OGC), which might be contraindicated in cats with certain infectious, endocrine, renal, or cardiac diseases. Inhalant GC (IGC) maximize local efficacy and minimize systemic bioavailability. We evaluated systemic endocrine and immune effects of IGC (flunisolide, 250 microg/puff q12h) versus OGC (prednisone, 10 mg/d PO) and placebo. Six healthy cats received each drug for 2 weeks followed by a 1-month washout. Testing included determination of single early morning cortisol concentration, results of ACTH stimulation, the urine cortisol-to-creatinine ratio (UC: Cr), lymphocyte phenotype, lymphocyte blastogenesis, serum total IgA and IgM concentrations, and cytokine profiles. Significant differences between treatments were not apparent for serum immunoglobulin concentrations, or expression (mRNA) for the cytokines, interleukin (IL-) 2, IL-4, and IL-10, or gamma interferon. Single early morning cortisol concentration was lower for IGC (0.68 - 0.74 microg/dL), compared with that associated with placebo (2.82 +/- 1.94 microg/dL; P = .033). The ACTH-stimulated peak cortisol concentrations were lower after treatment in cats receiving IGC (before, 8.5 +/- 50.2 microg/dL; after, 2.9 +/- 3.3 microg/dL, P = .0004), but not OGC (before, 8.0 +/- 6.1 microg/dL; after, 6.0 +/- 4.5 microg/dL, P = .07). Similarly, UC: Cr (0.8 +/- 0.8) before IGC was lower than the value (5.02 +/- 3.62; P = .019) after IGC. Compared with placebo, cats given OGC, but not IGC, had significantly lower total percentages of T and B cells. Lymphocyte proliferation was decreased in cats receiving OGC, but not IGC, in comparison with placebo (6.9 +/- 3.3; 24.0 +/- 6.5; 18.8 +/- 14.0, respectively). Significantly more IL-10 mRNA transcription was detected in cats administered OGC or IGC, compared with placebo. Although IGC suppress the hypothalamic-pituitary-adrenocortical axis, IGC had minimal effects on the systemic adaptive immune system.

Comparison of ultrasonographic characteristics of the thyroid gland in healthy small-, medium-, and large-breed dogs.

OBJECTIVE: To determine ultrasonographic characteristics of the thyroid gland in healthy small-, medium-, and large-breed dogs and evaluate the relationships of thyroid gland size and volume with body weight and body surface area (BSA). ANIMALS: 72 dogs of small (6 Toy and 6 Miniature Poodles), medium (12 Beagles), and large breeds (12 Akitas and 36 Golden Retrievers). PROCEDURE: Each dog's thyroid gland was examined ultrasonographically with a 10- to 5-MHz multifrequency linear-array transducer. Size, shape, echogenicity, and homogeneity of thyroid lobes were evaluated on longitudinal and transverse images. Thyroid lobe volume was estimated by use of the equation for an ellipsoid (pi/6 [length x height x width]). RESULTS: Thyroid lobes appeared fusiform or elliptical on longitudinal images and triangular or round to oval on transverse images. In most dogs, thyroid lobes were hyperechoic or isoechoic, compared with surrounding musculature, and had a homogeneous echogenic pattern. Mean length, width, height, and volume of thyroid lobes were significantly greater in Akitas and Golden Retrievers, compared with findings in Beagles or Poodles; mean length, width, and height were significantly greater in Beagles, compared with findings in Poodles. Total thyroid gland volume correlated with body weight (r = 0.73) and BSA (r = 0.74). CONCLUSIONS AND CLINICAL RELEVANCE: Among the dog breeds examined ultrasonographically, thyroid lobe size and volume were more variable than shape, echogenicity, and homogeneity. The correlation of thyroid gland volume with BSA suggests that size of the dog, rather than breed, should be considered when assessing thyroid glands ultrasonographically.