Distribution of K and L cells in the feline intestinal tract.

Glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide (GLP)-1 and GLP-2 are hormones secreted from specialized K cells (GIP) and L cells (GLP-1, GLP-2) in the intestinal mucosa. These hormones play major roles in health and disease by modulating insulin secretion, satiety, and multiple intestinal functions. The aim of this study was to describe the distribution of K cells and L cells in the intestines of healthy cats. Samples of duodenum, mid-jejunum, ileum, cecum, and colon were collected from 5 cats that were euthanized for reasons unrelated to this study and had no gross or histologic evidence of gastrointestinal disease. Samples stained with rabbit-anti-porcine GIP, mouse-anti-(all mammals) GLP-1, or rabbit-anti-(all mammals) GLP-2 antibodies were used to determine the number of cells in 15 randomly selected 400× microscopic fields. In contrast to other mammals (eg, dogs) in which K cells are not present in the ileum and aborally, GIP-expressing cells are abundant throughout the intestines in cats (>6/high-power field in the ileum). Cells expressing GLP-1 or GLP-2 were most abundant in the ileum (>9/high-power field) as in other mammals, but, although GLP-1-expressing cells were abundant throughout the intestines, GLP-2-expressing cells were rarely found in the duodenum. In conclusion, the distribution of GIP-secreting K cells in cats is different from the distribution of K cells that is described in other mammals. The difference in distribution of GLP-2- and GLP-1-expressing cells suggests that more than 1 distinct population of L cells is present in cats.

Skeletal muscle tissue transcriptome differences in lean and obese female beagle dogs.

Skeletal muscle is a large and insulin-sensitive tissue that is an important contributor to metabolic homeostasis and energy expenditure. Many metabolic processes are altered with obesity, but the contribution of muscle tissue in this regard is unclear. A limited number of studies have compared skeletal muscle gene expression of lean and obese dogs. Using microarray technology, our objective was to identify genes and functional classes differentially expressed in skeletal muscle of obese (14.6 kg; 8.2 body condition score; 44.5% body fat) vs. lean (8.6 kg; 4.1 body condition score; 22.9% body fat) female beagle adult dogs. Alterations in 77 transcripts was observed in genes pertaining to the functional classes of signaling, transport, protein catabolism and proteolysis, protein modification, development, transcription and apoptosis, cell cycle and differentiation. Genes differentially expressed in obese vs. lean dog skeletal muscle indicate oxidative stress and altered skeletal muscle cell differentiation. Many genes traditionally associated with lipid, protein and carbohydrate metabolism were not altered in obese vs. lean dogs, but genes pertaining to endocannabinoid metabolism, insulin signaling, type II diabetes mellitus and carnitine transport were differentially expressed. The relatively small response of skeletal muscle could indicate that changes are occurring at a post-transcriptional level, that other tissues (e.g., adipose tissue) were buffering skeletal muscle from metabolic dysfunction or that obesity-induced changes in skeletal muscle require a longer period of time and that the length of our study was not sufficient to detect them. Although only a limited number of differentially expressed genes were detected, these results highlight genes and functional classes that may be important in determining the etiology of obesity-induced derangement of skeletal muscle function.

The GLP-1 mimetic exenatide potentiates insulin secretion in healthy cats.

The glucagon-like peptide-1 mimetic exenatide has a glucose-dependent insulinotropic effect, and it is effective in controlling blood glucose (BG) with minimal side effects in people with type 2 diabetes. Exenatide also delays gastric emptying, increases satiety, and improves ß-cell function. We studied the effect of exenatide on insulin secretion during euglycemia and hyperglycemia in cats. Nine young, healthy, neutered, purpose-bred cats were used in a randomized, cross-over design. BG concentrations during an oral glucose tolerance test were determined in these cats previously. Two isoglycemic glucose clamps (mimicking the BG concentration during the oral glucose tolerance test) were performed in each cat on separate days, one without prior treatment (IGC) and the second with exenatide (1 µg/kg) injected subcutaneously 2 h before (ExIGC). BG, insulin, and exenatide concentrations were measured, and glucose infusion rates were recorded and compared in paired tests between the two experiments. After exenatide injection, insulin serum concentrations increased significantly (2.4-fold; range 1.0- to 9.2-fold; P = 0.004) within 15 min. This was followed by a mild decrease in BG concentration and a return of insulin concentration to baseline despite a continuous increase in serum exenatide concentrations. Insulin area under the curve (AUC) during ExIGC was significantly higher than insulin AUC during IGC (AUC ratio, 2.0 ± 0.4; P = 0.03). Total glucose infused was not significantly different between IGC and ExIGC. Exenatide was detectable in plasma at 15 min after injection. The mean exenatide concentration peaked at 45 min and then returned to baseline by 75 min. Exenatide was still detectable in the serum of three of five cats 8 h after injection. No adverse reactions to exenatide were observed. In conclusion, exenatide affects insulin secretion in cats in a glucose-dependent manner, similar to its effect in other species. Although this effect was not accompanied by a greater ability to dispose of an intravenous glucose infusion, other potentially beneficial effects of exenatide on pancreatic ß cells, mainly increasing their proliferation and survival, should be investigated in cats.

The incretin effect in cats: comparison between oral glucose, lipids, and amino acids.

Incretin hormones are secreted from the intestines in response to specific nutrients. They potentiate insulin secretion and have other beneficial effects in glucose homeostasis. We aimed to study the incretin effect in cats and to compare the effect of oral glucose, lipids, or amino acids on serum concentrations of insulin, total glucose-dependent insulinotropic peptide (GIP) and total glucagon-like peptide 1 (GLP-1). Ten healthy cats were used in a repeated measures design. Glucose, lipid, or amino acids were administered through nasoesophageal tubes on separate days. Blood glucose (BG) concentrations were matched between experiments by measuring BG every 5 min and infusing glucose intravenously at a changing rate. Intravenous glucose infusion with no prior treatment served as control. The incretin effect was estimated as the difference in insulin area under the curve (AUC) after oral compared with intravenous glucose. Temporal changes and total amount of hormone secretions were compared between treatment groups with the use of mixed models. Total glucose infused (TGI) at a mean dose of 0.49 g/kg resulted in slightly higher BG compared with 1 g/kg oral glucose (P = 0.038), but insulin concentrations were not significantly different (P = 0.367). BG and the TGI were not significantly different after the 3 oral challenges. Total GIP AUC was larger after lipids compared with amino acids (P = 0.0012) but GIP concentrations did not increase after oral glucose. Insulin and GIP concentrations were positively correlated after lipid (P < 0.001) and amino acids (P < 0.001) stimulations, respectively, but not after oral glucose stimulation. Total GLP-1 AUC was similar after all three oral stimulations. Insulin and GLP-1 concentrations were positively correlated after glucose (P = 0.001), amino acids (P < 0.001), or lipids (P = 0.001) stimulations. Our data indirectly support an insulinotropic effect of GIP and GLP-1. Potentiation of insulin secretion after oral glucose is minimal in cats and is mediated by GLP-1 but not GIP.

Dietary macronutrients and feeding frequency affect fasting and postprandial concentrations of hormones involved in appetite regulation in adult dogs.

Identifying dietary effects on appetite-regulating hormones will enhance our understanding of appetite control. Before complex diets are tested, effects of specific macronutrients or feeding frequency should be identified. The objectives of this nutrition study were to identify differences in endocrine response with feeding frequency (Exp. 1) and after a single dose of a sole macronutrient (Exp. 2). A control diet supplying similar energy content from carbohydrate, protein, and fat was fed to maintain ideal BW. In Exp. 1, 8 healthy adult (1.9 ± 0.1 yr old) female hound cross dogs with an average BW of 22 kg (4.8 ± 0.8 BCS based on a 9-point scale) were randomly allotted to 1 of 2 treatments (fed once or twice daily) in a crossover design. After a 14-d adaptation period, a blood sample was taken (10 mL) before feeding, and samples were collected every 2 h postprandially for 24 h. In Exp. 2, dogs were randomly allotted to 1 of 4 treatments in a 4 × 4 Latin square design. After a 6-d adaptation period, the normal meal on d 7 was replaced with a bolus of maltodextrin (50 g in water; CARB), canned chicken (50 g; PROT), lard (25 g; fat), or water (200 mL). A blood sample (10 mL) was taken at 0, 30, 60, 90, 120, 150, 180, 240, 300, and 360 min postprandial. Total ghrelin, active glucagon-like peptide-1 (GLP-1), insulin, and glucose concentrations were measured. Data were analyzed to compare changes from baseline and area under the curve (AUC) among treatments. In Exp. 1, all hormones were quite variable throughout the day, with a few insulin and GLP-1 differences because of feeding frequency. In Exp. 2, CARB produced a marked peak in glucose and insulin concentrations compared with PROT, fat, or water, resulting in increased glucose (P < 0.001) and insulin (P = 0.07) incremental AUC values. On the other hand, the fat treatment led to increased GLP-1 concentrations over time. Ghrelin AUC was not different among treatments. The circulating hormone data were highly variable and indicate that diet plays a role in insulin and GLP-1 secretion, but more research is required to elucidate these effects.

Pharmacodynamics of insulin detemir and insulin glargine assessed by an isoglycemic clamp method in healthy cats.

BACKGROUND: Insulin detemir and insulin glargine are synthetic long-acting insulin analogs. In people, insulin glargine is longer acting and has a relatively flat time-action profile, while insulin detemir has significantly less within-subject variability. Insulin detemir is also associated with less undesired weight gain and decreased frequency of hypoglycemic events. OBJECTIVES: To compare the pharmacodynamics of insulin detemir and insulin glargine in healthy cats. ANIMALS: Ten young, healthy, neutered, purpose-bred cats. METHODS: Randomized, cross-over design. Pharmacodynamics of insulin detemir and insulin glargine were determined by the isoglycemic clamp method after a 0.5 U/kg SC injection. RESULTS: The only significant difference in the pharmacodynamics of insulin detemir and insulin glargine was onset of action (1.8+/-0.8 and 1.3+/-0.5 hours for insulin detemir and insulin glargine, respectively, P=.03). End of action of insulin detemir was reached at 13.5+/-3.5 hours and for insulin glargine at 11.3+/-4.5 hours (P=.18). Time-to-peak action of insulin detemir was reached at 6.9+/-3.1 hours and for insulin glargine at 5.3+/-3.8 hours (P=.7). The time-action curves of both insulin analogs varied between relatively flat curves in some cats and peaked curves in others. CONCLUSION AND CLINICAL IMPORTANCE: Insulin detemir and insulin glargine have shorter durations of action than in people when assessed by the clamp method, but in some cats these insulin analogs could be useful as once-a-day drugs. Peak effects of both insulin analogs are pronounced in some cats.

Cloning and sequencing of the calcium-sensing receptor from the feline parathyroid gland.

Messenger RNA of the calcium-sensing receptor from feline parathyroid gland (fCaSR) was reversed transcribed to cDNA, amplified by polymerase chain reaction (PCR) and cloned into E. coli. Sequences obtained from cloned E. coli were used for genetic characterization of the fCaSR mRNA and for exonic PCR primer design. Multiple fCaSR exons sequence alignments obtained from PCR amplification of genomic DNA of 5 healthy domestic shorthair cats indicated the presence of 3 synonymous missense single-nucleotide polymorphisms (SNP) and 1 nonsynonymous missense SNP, which changed an amino acid from arginine to proline. The fCaSR has 96%, 96%, and 94% homology to the canine, human, and bovine amino acid sequences, respectively.

Impact of ovariohysterectomy and food intake on body composition, physical activity, and adipose gene expression in cats.

The mechanisms contributing to BW gain following ovariohysterectomy in domestic cats are poorly understood. Moreover, the effects of food restriction to maintain BW following spaying have been poorly studied. Thus, our primary objective was to determine the effects of spaying and food restriction to maintain BW on adipose and skeletal muscle mRNA abundance and activity levels in cats. After a 4-wk baseline period (wk 0), 8 adult (approximately 1.5 yr old) domestic shorthair cats were spayed and fed to maintain BW for 12 wk. After 12 wk, cats were fed ad libitum for an additional 12 wk. Body composition was determined, activity levels were measured, and adipose and muscle biopsies were collected at wk 0, 12, and 24. Fasting blood samples were collected at wk 0, 6, 12, 18, and 24. To maintain BW post-spay, food intake was decreased (P < 0.05) by 30%. During this phase, mRNA abundance of adipose tissue lipoprotein lipase and leptin was decreased (P < 0.05), representing only 52 and 23% of baseline expression, respectively. Interleukin-6 mRNA, however, was increased (P < 0.05) 2-fold. Physical activity was decreased (P < 0.05) by wk 12, most dramatically during the dark period (approximately 20% of baseline activity). During ad libitum feeding (wk 12 to 24), food intake, BW, body fat percentage, and total fat mass were greatly increased (P < 0.05). Compared with wk 0, circulating leptin concentrations tended to increase (P < 0.10) by wk 18 and 24 (4.45 vs. 10.02 and 9.14 ng/mL, respectively), whereas glucose (91 vs. 162 mg/dL) and triacylglyceride (30 vs. 48 mg/dL) concentrations were increased (P < 0.05) by wk 24. Adipose tissue lipoprotein lipase, hormone sensitive lipase, and adiponectin mRNA were decreased (P < 0.05) at wk 24. Adipose interleukin-6 mRNA was increased (P < 0.05) at 24 wk. Physical activity was further decreased (P < 0.05) by wk 24, during the light (60% of baseline) and dark (33% of baseline) periods. In summary, spaying and food restriction affect physical activity levels and several genes associated with lipid metabolism (decreased lipoprotein lipase), food intake (decreased leptin expression), and insulin insensitivity (increased interleukin-6). By identifying these changes, targets for nutritional intervention or lifestyle management have been identified that may curb the risk of obesity and related disorders in spayed cats.

Ovariohysterectomy alters body composition and adipose and skeletal muscle gene expression in cats fed a high-protein or moderate-protein diet.

The objective of this study was to measure changes in body composition, physical activity and adipose and skeletal muscle gene expression of cats fed a high-protein (HP) diet or moderate-protein (MP) diet, following ovariohysterectomy. Eight cats were randomized onto HP or MP diets and were fed those diets for several months prior to baseline. All cats underwent an ovariohysterectomy at baseline (week 0) and were allowed ad libitum access to dietary treatments for 24 weeks. Food intake was measured daily, and BW and body condition score were measured weekly. Blood, adipose and skeletal muscle tissue samples were collected, physical activity was measured, and body composition was determined using DEXA (dual-energy X-ray absorptiometry) at weeks 0, 12 and 24. Caloric intake increased soon after ovariohysterectomy, resulting in increased (P < 0.05) BW at weeks 12 and 24 compared to week 0. Body condition score and body fat percentage increased (P < 0.05) over time. Blood glucose increased (P < 0.05) linearly over time. Non-esterified fatty acids were decreased (P < 0.05) at weeks 12 and 24 compared to week 0. Blood leptin increased (P < 0.05) over time. Total physical activity decreased (P < 0.05) from week 0 to weeks 12 and 24 in all cats. Adipose tissue mRNA abundance of adiponectin, hormone sensitive lipase, toll-like receptor-4, uncoupling protein-2 (UCP2) and vascular endothelial growth factor decreased (P < 0.05) linearly over time, regardless of diet. Skeletal muscle mRNA abundance for glucose transporter-1, hormone sensitive lipase and UCP2 were decreased (P < 0.05), regardless of dietary treatment. Our research noted metabolic changes following ovariohysterectomy that are in agreement with gene expression changes pertaining to lipid metabolism. Feeding cats ad libitum after ovariohysterectomy is inadvisable.

Misfolded growth hormone causes fragmentation of the Golgi apparatus and disrupts endoplasmic reticulum-to-Golgi traffic.

In some individuals with autosomal dominant isolated growth hormone deficiency, one copy of growth hormone lacks amino acids 32-71 and is severely misfolded. We transfected COS7 cells with either wild-type human growth hormone or Delta 32-71 growth hormone and investigated subcellular localization of growth hormone and other proteins. Delta 32-71 growth hormone was retained in the endoplasmic reticulum, whereas wild-type hormone accumulated in the Golgi apparatus. When cells transfected with wild-type or Delta 32-71 growth hormone were dually stained for growth hormone and the Golgi markers beta-COP, membrin or 58K, wild-type growth hormone was colocalized with the Golgi markers, but beta-COP, membrin and 58K immunoreactivity was highly dispersed or undetectable in cells expressing Delta 32-71 growth hormone. Examination of alpha-tubulin immunostaining showed that the cytoplasmic microtubular arrangement was normal in cells expressing wild-type growth hormone, but microtubule-organizing centers were absent in nearly all cells expressing Delta 32-71 growth hormone. To determine whether Delta 32-71 growth hormone would alter trafficking of a plasma membrane protein, we cotransfected the cells with the thyrotropin-releasing hormone (TRH) receptor and either wild-type or Delta 32-71 growth hormone. Cells expressing Delta 32-71 growth hormone, unlike those expressing wild-type growth hormone, failed to show normal TRH receptor localization or binding. Expression of Delta 32-71 growth hormone also disrupted the trafficking of two secretory proteins, prolactin and secreted alkaline phosphatase. Delta 32-71 growth hormone only weakly elicited the unfolded protein response as indicated by induction of BiP mRNA. Pharmacological induction of the unfolded protein response partially prevented deletion mutant-induced Golgi fragmentation and partially restored normal TRH receptor trafficking. The ability of some misfolded proteins to block endoplasmic reticulum-to-Golgi traffic may explain their toxic effects on host cells and suggests possible strategies for therapeutic interventions.

Calcium responses to thyrotropin-releasing hormone, gonadotropin-releasing hormone and somatostatin in phospholipase css3 knockout mice.

These studies examined the importance of phospholipase Cbeta (PLCbeta) in the calcium responses of pituitary cells using PLCbeta3 knockout mice. Pituitary tissue from wild-type mice contained PLCbeta1 and PLCbeta3 but not PLCbeta2 or PLCbeta4. Both Galphaq/11 and Gbetagamma can activate PLCbeta3, whereas only Galphaq/11 activates PLCss1 effectively. In knockout mice, PLCbeta3 was absent, PLCbeta1 was not up-regulated, and PLCbeta2 and PLCbeta4 were not expressed. Since somatostatin inhibited influx of extracellular calcium in pituitary cells from wild-type and PLCbeta3 knockout mice, the somatostatin signal pathway was intact. However, somatostatin failed to increase intracellular calcium in pituitary cells from either wild-type or knockout mice under a variety of conditions, indicating that it did not stimulate PLCbeta3. In contrast, somatostatin increased intracellular calcium in aortic smooth muscle cells from wild-type mice, although it evoked no calcium response in cells from PLCbeta3 knockout animals These results show that somatostatin, like other Gi/Go-linked hormones, can stimulate a calcium transient by activating PLCbeta3 through Gbetagamma, but this response does not normally occur in pituitary cells. The densities of Gi and Go, as well as the relative concentrations of PLCbeta1 and PLCbeta3, were similar in cells that responded to somatostatin with an increase in calcium and pituitary cells. Calcium responses to 1 nM and 1 microM TRH and GnRH were identical in pituitary cells from wild-type and PLCbeta3 knockout mice, as were responses to other Gq-linked agonists. These results show that in pituitary cells, PLCbeta1 is sufficient to transmit signals from Gq-coupled hormones, whereas PLCbeta3 is required for the calcium-mobilizing actions of somatostatin observed in smooth muscle cells.

Effects of methimazole on renal function in cats with hyperthyroidism.

The purpose of this study was to investigate the effects of methimazole on renal function in cats with hyperthyroidism. Twelve cats with naturally occurring hyperthyroidism and 10 clinically normal (i.e., control) cats were included in this study. All cats initially were evaluated with a history, physical examination, complete blood count, serum biochemistry profile, basal serum total thyroxine concentration, complete urinalysis, and urine bacterial culture. Glomerular filtration rate (GFR) was estimated by a plasma iohexol clearance (PIC) test. After initial evaluation, hyperthyroid cats were treated with methimazole until euthyroidism was achieved. Both groups of cats were then reevaluated by repeating the initial tests four to six weeks later. The mean (+/-standard deviation) pretreatment estimated GFR for the hyperthyroid cats was significantly higher (3.83+/-1.82 ml/kg per min) than that of the control cats (1.83+/-0.56 ml/kg per min). Control of the hyperthyroidism resulted in a significantly decreased mean GFR of 2.02+/-0.81 ml/kg per minute when compared to pretreatment values. In the hyperthyroid group, the mean increases in serum urea nitrogen (SUN) and creatinine concentrations and the mean decrease in the urine specific gravity after treatment were not statistically significant when compared to pretreatment values. Two of the 12 hyperthyroid cats developed abnormally high serum creatinine concentrations following treatment. These results provide evidence that cats with hyperthyroidism have increased GFR compared to normal cats, and that treatment of feline hyperthyroidism with methimazole results in decreased GFR.

The incubation period of hantavirus pulmonary syndrome.

In 1993 Sin Nombre virus was recognized as the cause of hantavirus pulmonary syndrome (HPS) and the deer mouse (Peromyscus maniculatus) was identified as the reservoir host. Surveillance by the Centers for Disease Control and Prevention and state health departments includes investigation to determine the likely site(s) and activities that led to infection, an environmental assessment of the home and workplace, and possibly rodent trappings at these sites. As of December 31, 1998, there were 200 confirmed cases from 30 states (43% case-fatality ratio). The national HPS case registry was examined to determine the incubation period of HPS. Review of 11 case-patients with well-defined and isolated exposure to rodents suggests that the incubation period of HPS is 9 to 33 days, with a median of 14-17 days. Case investigations allow a better understanding of the incubation time of HPS and may define high-risk behaviors that can be targeted for intervention.

Assessment of quality of life indicators among selected patients in a community cancer center.

Quality of life and outcome assessments are particularly critical for nurses in assessing clinical care for diseases such as cancer because of potential mortality and the exacting modalities of treatment. The 278 study participants were patients at the M.D. Anderson Cancer Center Orlando. The respondents were assessed with the Health Status Questionnaire (HSQ; D. M. Radosevich, H. Wetzler, & S. M. Wilson, 1995). Prostate cancer patients scored higher (had a higher quality of life) on average (6.08%) than breast cancer patients on all subscales except Physical Functioning. The diagnostic center patients scored higher (9.68%) than breast cancer patients and prostate cancer patients (3.47%). Breast cancer respondents scored 16.61% lower than the normative values for individuals less than 65 years of age, whereas prostate cancer respondents scored 10.91% higher than the normative values for those older than 65. The data analysis confirmed that breast cancer and prostate cancer patients have statistically different scores on the HSQ, implying different quality of life concerns for each group.

Surgical treatment of bile peritonitis in 24 dogs and 2 cats: a retrospective study (1987-1994).

OBJECTIVE: The purpose of this study was to determine the signalment, history, clinical signs, diagnosis, treatment, outcome, and factors affecting outcome of dogs and cats surgically treated for bile peritonitis. STUDY DESIGN: Retrospective study. ANIMALS OR SAMPLE POPULATION: Twenty-four dogs and two cats surgically treated for bile peritonitis. METHODS: The medical records of dogs and cats surgically treated for biliary effusions at the Ohio State University and Michigan State University between 1987 and 1994 were reviewed. Statistical analysis was performed to compare factors affecting outcome. RESULTS: The cause of the biliary effusion was determined in 24 animals, and resulted from disruption of the biliary tract secondary to trauma (n = 13) or necrotizing cholecystitis (n = 11). Determination of the bilirubin concentration of the abdominal effusion was the only diagnostic test that was 100% effective in diagnosing bile leakage before surgical intervention. The bilirubin concentration of the effusion was consistently at least two times higher than the serum bilirubin concentration. Bacteriologic culture and sensitivity revealed that a septic, biliary effusion was usually associated with multiple types of gram-negative bacteria. The overall survival rate was 50% (13 of 26). The peripheral white blood cell count was significantly lower in survivors (mean 20,608/uL) compared with nonsurvivors (mean 35,712/uL). The immature neutrophil count was also significantly lower in survivors (mean 686/uL) than in nonsurvivors (4,852/uL). Only 27% (3 of 11) of the animals with a septic biliary effusion survived. In contrast, 100% (6 of 6) of the animals in which no bacteria were isolated from the abdominal effusion survived. Open abdominal drainage was not a successful treatment for 7 of 9 animals with septic biliary effusions. Survival was not significantly affected by the distribution of the peritonitis, cause of biliary effusion, or duration of clinical signs before surgical intervention. CONCLUSIONS: Patients with sterile biliary effusions have a much lower mortality rate than those with septic biliary effusions. The successful treatment of sterile biliary effusions does not require open abdominal drainage, and is not affected by the duration of the effusion. CLINICAL RELEVANCE: This retrospective study provides information that may aid the surgeon in the diagnosis and treatment of bile peritonitis.

A potentially misleading presentation and course of acute myelomonocytic leukemia in a dog.

A nine-year-old, castrated male golden retriever had lethargy, fever, massive peripheral lymphadenomegaly, hepatosplenomegaly, and pale mucous membranes. There was a marked leukocytosis (456.3 x 10(3) cells/microliter) with 99% blasts; a moderate, nonregenerative anemia; and marked thrombocytopenia. A tentative diagnosis of acute lymphocytic leukemia was made pending results of cytochemical staining. Despite the severity of the laboratory and clinical findings, the dog exhibited a partial response to an induction chemotherapy protocol commonly used for lymphoma. Subsequent cytochemical staining of the original blood and bone-marrow samples resulted in a revised diagnosis of acute myelomonocytic leukemia (AML-M4). Clinicopathological findings, response to treatment, and clinical outcome in this case of canine AML-M4 are discussed.

Changes in renal function associated with treatment of hyperthyroidism in cats.

We measured glomerular filtration rate (GFR) estimated by plasma disappearance of 99mTc-labeled diethylenetriaminepentaacetic acid, serum concentrations of thyroxine (T4), creatinine, and urea nitrogen, and urine specific gravity in 13 cats with naturally acquired hyperthyroidism before and 30 days after treatment by bilateral thyroidectomy, and in a group of 11 control cats. Mean (+/- SD) serum T4 concentration decreased from a pretreatment value of 120.46 (+/- 39.21) nmol/L to a posttreatment value of 12.15 (+/- 6.26) nmol/L (P < 0.0001; reference range, 10 to 48 nmol/L). Treatment of hyperthyroidism resulted in a decrease in mean (+/- SD) glomerular filtration rate, from 2.51 (+/- 0.69) ml/kg of body weight/min to a posttreatment value of 1.40 (+/- 0.41) ml/kg/min (P < 0.0001). Mean serum creatinine concentration increased from 1.26 (+/- 0.34) mg/dl to 2.05 (+/- 0.60) mg/dl (P < 0.01). Mean serum urea nitrogen concentration increased from 26.62 (+/- 6.83) mg/dl to a mean postthyroidectomy concentration of 34.92 (+/- 8.95) mg/dl (P < 0.01). All changes were significant. Two cats developed overt renal azotemia after treatment of hyperthyroidism. Our results provide further evidence that treatment of hyperthyroidism can result in impaired renal function. In addition, our results suggest that, in some instances, thyrotoxicosis might mask underlying chronic renal insufficiency.

Basal and ACTH-stimulated plasma aldosterone concentrations are normal or increased in dogs with trichuriasis-associated pseudohypoadrenocorticism.

We measured plasma concentrations of cortisol and aldosterone before and after administration of adrenocorticotropin (ACTH) in dogs with trichuriasis. These dogs had physical examination, historical, and serum electrolyte findings suggestive of hypoadrenocorticism; trichuriasis-associated pseudohypoadrenocorticism has been reported previously. We found normal basal and ACTH-stimulated plasma cortisol concentrations. Basal and ACTH-stimulated plasma aldosterone concentrations were normal in 2 dogs and increased in 3 dogs, suggesting that the electrolyte abnormalities seen in this clinical syndrome are not due to aldosterone deficiency.

Diagnostic tests for feline hyperthyroidism.

Until recently, the diagnosis of hyperthyroidism in cats was thought to be simple; however, not all cases of the disease are straightforward. Although single resting serum thyroid-hormone determinations may well be adequate to confirm the diagnosis, in many cases, the diagnosis of feline hyperthyroidism requires more extensive investigation.

Prolonged gestation in a Holstein cow: adenohypophyseal aplasia and skeletal pathology in the offspring.

A Holstein fetus was delivered by Caesarean section at a gestational age of 441 days. The pituitary pars distalis was aplastic and the adrenal and thyroid glands were severely hypoplastic. Arrested or retarded cartilage cell maturation resulted in absence or minimal development of epiphyseal ossification centers, delayed ossification of carpal bones, and arrest of longitudinal growth of bones. The pathophysiology of prolonged gestation and of skeletal pathology is discussed.