A case of coccidioidomycosis with unique clinical features.

Primary coccidioidomycosis, occurring in a microbiologist whose initial symptoms were cough, fever, night sweats, and chest pain, was unique, because for six months following infection his sera remained nonreactive, and his chest roentgenograms showed no lesions. Throughout this period, his sputa continued to yield Coccidioides immitis. His skin test, which showed negative results 12 days after the onset of symptoms, became positive for coccidioidomycosis eight months later. Spherule formation by C immitis cultures was demonstrated in human pleural fluid medium at 40 degrees C within four to six days and in the internal organs of a mouse inoculated with an arthrospore suspension. After six months of rest and without specific antibiotic treatment, the patient's sputa became negative and his clinical recovery was complete. We emphasize culture isolation and accurate identification of C immitis in diagnosis, and serology in the assessment of therapy.

Digoxin pharmacokinetics: role of renal failure in dosage regimen design.

Radioimmunoassayed serum concentration and urinary excretion data for digoxin from azotemic patients were characterized using a 2-compartment open model. Urinary excretion rates of digoxin as well as serum concentration data are needed to accurately characterize the disposition of the drug. Seven patients with renal failure showed highly variable steady-state volumes of distribution (V-ss-D equals 195 to 489 liters/1.73 m-minus2) and t1/2beta values (1.5 to 5.2 days). This variability is a major limiting factor in the use of dosage regimen nomograms that assume a constant V-ss-D and a rigorous relationship between t1/2beta and creatinine clearance (Cl-CR). Body clearance (Cl-B) is a parameter that is affected by both elimination and distribution of drugs. A linear relationship between Cl-B and renal clearance of digoxin or Cl-CR was found and was used to develop a model-independent approach to calculation of maintenance doses of digoxin. Several methods for calculating steady-state serum concentrations of digoxin (C-ss-p) were compared with actual measurements obtained in 16 chronically medicated patients. Optimum computation of C-ss-p is obtained by use of digoxin renal and body clearances. Variability in the digoxin:creatinine renal clearance ratio is the major limiting factor in prediction of digoxin dosage regimens.

Membranoproliferative glomerulonephritis with polyarteritis: a case report.

A case of membranoproliferative glomerulonephritis with polyarteritis is described. The patient was a 68 year old male who had the disease for about four months. A kidney biopsy specimen taken just before the patient died was studied by light, immunofluorescence, and electron microscopy. Splitting of the basement membrane, IgG, IgA, BlC, Clq, fibrinogen, and electron dense deposits were found in the glomeruli. It is considered that perhaps some cases of membranoproliferative glomerulonephritis are produced by circulating immune complexes.

In situ hybridization as a technique for the immunological investigation of canine intestine: jejunal expression of IFNgamma and IL10 in Irish setters and beagles.

In situ hybridization (ISH) has found numerous applications in biology and medicine. However, its use to demonstrate expression of cytokines within the canine small intestine has not been described. Digoxigenin-labelled riboprobes complementary to mRNA encoding canine IFNgamma and IL10 were used to demonstrate expression of these cytokines within formalin-fixed, paraffin-embedded sections of jejunum obtained from healthy control Irish setter (IS) dogs (n = 4), gluten-sensitive IS in remission (n = 7), and beagles with high enteric bacterial populations (n = 5). Proportional areas of cells within the lamina propria showing one of three mutually exclusive staining intensities were measured, as well as the total stained area. Intensity categories were chosen arbitrarily to represent cells showing weak, moderate or dense staining (grades 1-3 respectively), reflecting increasing expression of mRNA. Control and gluten-sensitive IS showed similar total and grade-by-grade areas of expression of IFNgamma and IL10 in the lamina propria (p>0.05), in contrast to beagles, which showed greater total and grade 1 areas of expression of IFNgamma, and greater total, grade 1 and grade 2 areas of expression of IL10, than both groups of IS (p<0.05). Epithelial expression of both cytokines was demonstrated in beagles and IS, but differences between groups for each cytokine were not apparent (p>0.05). This study has validated the use of in situ hybridization for the detection of IFNgamma and IL10 mRNA within canine intestinal biopsies, andhas shown heightened jejunal expression of both cytokines in beagles with high enteric bacterial populations.

Quantitative and qualitative immunohistochemistry of T cell subsets and MHC class II expression in the canine small intestine.

In man and rodents, cells of the gastrointestinal immune system include B and T lymphocytes, granulocytes, macrophages and dendritic cells. Abnormalities in leucocyte numbers and function have been described in diseases of humans, such as coeliac disease and inflammatory bowel disease. The purpose of this study is to describe the normal distribution of T cells and MHC Class II expression in the small intestine of clinically normal dogs, to allow subsequent comparison with disease states. Full-thickness sections of duodenum, jejunum and ileum from seven young adult beagle dogs were immediately snap-frozen following euthanasia. Avidin-biotin-enhanced immunocytochemistry was used to detect expression of canine CD3, CD4, CD8 and MHC Class II antigens. Positively stained lamina propria cells were quantified using an eyepiece graticule, and positively stained intraepithelial cells by counts per 100 epithelial cells. In the lamina propria, the density of all leucocyte subsets was significantly increased towards the villus tip for all regions (p < 0.05). There was no apparent difference in the distribution of CD3+, CD4+ and CD8+ leucocytes between the three portions of the small intestine. The ratios of CD4+ cells to CD8+ cells in the lamina propria and epithelium were 59:41 and 15:85, respectively. Subtractive analysis suggested that 50-55% of CD3+ intraepithelial cells were CD4-CD8-. MHC Class II expression was apparent upon lamina propria cells with a dendritic morphology, as well as round cells. Epithelial MHC Class II expression was apparent in 7/7 ileal sections, compared with only 1/7 duodenal and 1/7 jejunal sections. This study shows that the small intestinal mucosa of the dog contains similar leucocyte populations to those found in other species, and suggests that these cells may play similar roles in gastrointestinal immunity.

Cholelithiasis and hyperthyroidism in a cat.

A 14-year-old domestic short-hair cat presented with a history of intermittent malaise and increased drinking. A diagnosis of hyperthyroidism and cholelithiasis was made by a combination of blood testing, radiography and ultrasonography. After medical management of hyperthyroidism, thyroidectomy and cholecystectomy were successfully performed. Removed choleliths were comprised of calcium carbonate and bilirubinate. Histopathological analysis of tissue suggested low grade pancreatic and hepatobiliary disease, as well as hyperthyroidism, might have contributed to stone formation.

Small intestinal bacterial overgrowth in dogs with chronic intestinal disease.

Small intestinal bacterial overgrowth (SIBO) was diagnosed by quantitative bacterial culture of duodenal juice samples obtained endoscopically in 41 of 80 dogs that were admitted with chronic diarrhea, vomiting, or weight loss. Thirteen dogs had aerobic bacterial overgrowth, most frequently comprising Escherichia coli, staphylococci, and enterococci, and 28 dogs had mixed anaerobic overgrowth, most frequently including Clostridium and Bacteroides spp. Affected dogs comprised 23 breeds, including 10 German Shepherd Dogs and median age at diagnosis was 2 years (range, 6 months to 11 years). High serum folate and low serum cobalamin concentrations had fair specificity (79 and 87%, respectively), but low sensitivity (51 and 24%, respectively) in detecting SIBO. Histologic examination of duodenal biopsy specimens did not reveal abnormalities (26/41 dogs), or revealed mild to moderate lymphocytic (12/41) or eosinophilic (2/41) infiltrates, or lymphosarcoma (1/41). Oral antibiotic treatment was effective in 77% (23/30 dogs), but prolonged treatment (> 4 weeks) was required to control signs and prevent recurrence in 50% (15/30). Corticosteroids were used alone in a dog with eosinophilic enteritis and in combination with antibiotics in 4 dogs with marked gastrointestinal lymphocytic/plasmacytic infiltrates. This study suggested that SIBO may be observed in dogs of many breeds, without an obvious primary cause, and that, although results of indirect tests may be suggestive of SIBO, bacterial culture of duodenal juice samples remains necessary for definitive diagnosis.

Gastrointestinal immunity in health and disease.

The gastrointestinal lymphoid tissue (GALT) is under constant antigenic challenge from bacteria and food and must be able to distinguish between benign and pathogenic organisms. Recent advances in understanding the organization and function of GALT reveal how it is able to direct appropriate immune responses according to the nature of the antigen and how inappropriate immune responses can lead to local and systemic immunopathology and/or infection. The interaction of the normal bowel flora and GALT is critical to normal local and systemic immune function and plays a major role in the pathogenesis of some immune-related diseases. This review draws upon information from veterinary, human, and laboratory animal studies to provide an update of mechanisms and consequences of function and dysfunction in the gastrointestinal immune system.

Macrothrombocytosis in cavalier King Charles spaniels.

Low platelet counts (< 150 x 10(9)/litre) have been measured by autoanalyser in cavalier King Charles spaniels with a wide range of diseases. However, the direct examination of blood smears revealed adequate numbers of platelets but many abnormally large platelets and it was not clear whether the large platelets were the result of disease or a breed abnormality. The numbers and diameters of the platelets in a group of clinically normal King Charles spaniels and a group of other breeds were measured by autoanalyser and manually. The automated platelet counts were lower in the King Charles spaniels than in the other breeds (P < 0.01), but the manual counts were similar. The platelet diameter was greater in the cavalier King Charles spaniels (median values 2.5 to 3.75 microns, P < 0.001) than the other breeds (median values 1.25 to 2.5 microns) and had a bimodal distribution with peaks at 1.25 to 2.5 microns and 3.75 to 5 microns. No clinical evidence of platelet dysfunction was detected. These findings indicate that cavalier King Charles spaniels may have large platelets which could lead to the erroneous diagnosis of thrombocytopenia by automated haematological analysis.

Insulin-like growth factor axis of gluten-sensitive dogs during a gluten challenge.

Eight gluten-sensitive Irish setters underwent a gluten challenge to investigate changes in the insulin-like growth factor (IGF) axis. In the first study, they were challenged with an acute intraduodenal administration of tryptic-peptic gluten digest and then maintained on dietary gluten for three months. In the second study, the challenge came solely from dietary gluten fed for three months. After the acute intraduodenal administration of gluten, serum IGF-I levels decreased significantly by 21.8 per cent, (P = 0.01) on day 3 after challenge and then returned to normal. There was also a decrease (52.5 per cent, P < 0.03) in the levels of serum IGF-binding protein-3 (IGFBP-3) until day 14 after challenge but they had returned to normal by day 28. In two dogs IGFBP-3 levels decreased through specific serum protease activity. There were no changes in serum IGF-I or IGFBP levels during the second study after the dietary gluten challenge alone, or in four non-gluten-sensitive beagles studied as controls during the acute intraduodenal/dietary gluten challenge.

Humoral and cell-mediated responses to Malassezia pachydermatis in healthy dogs and dogs with Malassezia dermatitis.

The in vitro proliferative responses of peripheral blood mononuclear cells from seven healthy basset hounds exposed to Malassezia pachydermatis antigen (500 micrograms/ml) exceeded (P < 0.05) those of seborrhoeic basset hounds with high populations of M pachydermatis and eight Irish setters with gluten-sensitive enteropathy. The stimulation indices in the latter two groups and in eight healthy beagles were comparable. The stimulation indices of the four groups after exposure to phytohaemaglutinin did not differ significantly. The serum titres of M pachydermatis-specific IgG and IgA measured by enzyme-linked immunosorbent assays (ELISA) in 21 seborrhoeic basset hounds and 11 affected dogs of various breeds exceeded those of 14 healthy basset hounds and eight healthy beagles (P < 0.01 for IgG, P < 0.05 for IgA). Total serum IgA concentrations measured by ELISA in the affected dogs were not lower than those of healthy dogs.

Risk factors for gastric dilatation in Irish setter dogs.

Questionnaires were used to obtain data about Irish setters with gastric dilatation (GD) and control Irish setters. The risk of GD increased with age (P < 0.01) but was not associated with gender. Age and gender-matched controls were compared with cases (n = 74). Predisposing risks were aerophagia (unadjusted odds ratio 12.44, P < 0.001), a single food type (adjusted odds ratio 3.15, P < 0.01) and feeding once daily (adjusted odds ratio 2.90, P < 0.02). Apparent risk from a dry food diet and a condition score of less than 2 was not confirmed by logistic regression. Precipitating risks were recent kennelling (unadjusted odds ratio 100, P < 0.005) or a car journey (unadjusted odds ratio 3.29, P < 0.025). No risk was attributed to intensity or duration of exercise, temperament, appetite, speed of eating, vomiting or diarrhoea.

Assessment of an ECG event recorder in healthy dogs in a hospital environment.

Ambulatory electrocardiography techniques are superior to standard electrocardiography in evaluating rhythm disturbances in dogs with episodic weakness or collapse. Disadvantages include cumbersome equipment, short recording periods and an inherent delay in trace analysis. A small programmable cardiac event recorder with combined automatic and owner-triggered recording capability was evaluated in 13 healthy dogs in a hospital environment. The unit was well tolerated and produced diagnostic recordings directly to a personal computer, with useful information about continuous heart rate. It detects premature complexes, pauses and bradycardias according to programmed detection thresholds. These events were counted frequently but trace review revealed concerns regarding specificity. Recordings were often triggered by sinus arrhythmia, sinus tachycardia and unclassifiable rate changes rather than by clinically significant arrhythmias. Correct detection of ventricular ectopic complexes, a single supraventricular premature complex, sinus arrest and second-degree atrioventricular block occurred in individual dogs. Visual review of all automatically recorded events was essential and significantly increased the time required for event recording analysis. Manual recordings might be more useful and the overall results suggest that further studies are warranted to evaluate the system in clinical cases in the home environment.

Traumatic partial hypopituitarism in a cat.

Traumatic hypopituitarism was diagnosed in an 11-month-old male neutered cat. The presenting complaints were polydipsia, polyuria and lethargy of three months' duration. Craniocerebral trauma, as a result of a road traffic accident, had preceded the onset of clinical signs by six weeks. Neurological examination revealed right-sided mydriasis, reduced visual and tactile left forelimb placing reflexes and decreased proprioception in both the left fore- and hindlimb. Initial laboratory findings included hypernatraemia, hyperchloraemia, mild azotaemia, eosinophilia and isosthenuria. Low basal cortisol, thyroxine, thyroid-stimulating hormone and insulin growth factor-1 were noted. Subsequent to treatment with prednisolone, a water deprivation test confirmed the presence of central diabetes insipidus and therapy with synthetic antidiuretic hormone successfully ameliorated the polydipsia.

A potential causal association between gastrointestinal disease and primary polydipsia in three dogs.

Polydipsia, defined as a water intake of over 100 ml/kg/day, is a common presenting medical complaint in dogs. Polydipsia can be secondary (eg, to central or nephrogenic diabetes insipidus) or primary in origin, where increased water intake cannot be explained as a response to obligatory water loss. Primary polydipsia is confirmed by ruling out other known causes of polydipsia and demonstrating that renal concentrating ability is intact. The causes and associations of primary polydipsia in dogs are poorly defined. This report describes three dogs presented with signs of gastrointestinal disease with concurrent polydipsia. Investigations (including water deprivation testing) showed normal renal urinary concentrating ability and indicated primary polydipsia. Treatment of the gastrointestinal signs resulted in resolution of the polydipsia in each case. This is the first description of a possible association between gastrointestinal disease and primary polydipsia in the dog, the pathophysiology of which remains obscure.

Trilostane treatment of a dog with functional adrenocortical neoplasia.

A 13-year-old, crossbreed dog presented with a history of recent onset polydipsia, progressive lethargy, weakness and reduced appetite. Blood tests showed raised concentrations of alkaline phosphatase and alanine aminotransferase with marginally low serum potassium. There was a leucocytosis with a mature neutrophilia and no eosinophils. Endocrine tests showed a normal aldosterone concentration and an exaggerated adrenocorticotropic hormone (ACTH) stimulation test, consistent with a diagnosis of hyperadrenocorticism (HAC). A diagnosis of adrenal-dependent HAC was made, based on the presence of a calcified mass involving the left adrenal gland, and hepatomegaly, on radiography and ultrasonography. The owners declined surgical adrenalectomy. Medical management with trilostane rapidly improved the clinical signs and normalised the serum chemistry. ACTH stimulation tests showed an improvement in post-ACTH cortisol concentrations and were used to make dose adjustments where necessary. At the time of writing, no adverse side effects had been seen and the dog remained well after 80 weeks of treatment.

Treatment of acquired myasthenia gravis associated with thymoma in two dogs.

Two cases of myasthenia gravis associated with thymoma are reported. Both were female German shepherd dogs and the thymoma was surgically resected. Aspiration pneumonia secondary to persistent megaoesophagus was a complication in both cases. The myasthenia gravis did not resolve, but there was a more satisfactory control of clinical signs with anticholinesterase treatment. Corticosteroid therapy was used in one case, but the resulting polydipsia increased the incidence of regurgitation, resulting in recurrent episodes of aspiration pneumonia.

Evaluation of the long-acting somatostatin analogue octreotide in the management of insulinoma in three dogs.

The response of dogs with insulinoma to surgical and medical management is variable, with the majority developing intractable hypoglycaemia. A long-acting somatostatin analogue, Octreotide (SMS 201-995; Sandostatin) has been useful in the management of hypoglycaemia in humans with insulinoma, and preliminary reports suggest a beneficial clinical response in dogs with insulinoma. The present study objectively evaluated Octreotide in the management of three dogs with immunohistochemically confirmed insulinoma. Octreotide had no benefit over placebo, and little effect on circulating glucose and insulin concentrations despite clearly detectable plasma concentrations of Octreotide. No clinical improvement was apparent in two dogs given Octreotide over a period of two and three weeks. These results contrast with the positive clinical responses noted previously and indicate that further placebo controlled, objective studies are necessary before clear statements on the treatment of insulinoma with Octreotide are made.

Intestinal permeability and function in dogs with small intestinal bacterial overgrowth.

Small intestinal bacterial overgrowth (SIBO) has been reported to occur commonly in dogs with signs of chronic intestinal disease. There are usually few intestinal histological changes, and it is uncertain to what extent bacteria cause mucosal damage. The aim of this study was to apply a differential sugar absorption test for intestinal permeability and function to the objective assessment of intestinal damage in dogs with SIBO. Studies were performed on 63 dogs with signs of chronic small and, or, large bowel disease, in which SIBO (greater than 10(5) total or greater than 10(4) anaerobic colony forming units/ml) was diagnosed by quantitative culture of duodenal juice obtained endoscopically. None of the dogs had evidence of intestinal pathogens, parasites, systemic disease or pancreatic insufficiency. differential sugar absorption was performed by determining the ratios of urinary recoveries of lactulose/rhamnose (L/R ratio, which reflects permeability) and D-xylose/3-O-methylglucose (X/G ratio, which reflects intestinal absorptive function) following oral administration. Dogs with SIBO comprised 28 different breeds, including 13 German shepherd dogs. SIBO was aerobic in 18/63 dogs (29 per cent), and anaerobic in 45/63 (71 per cent). Histological examination of duodenal biopsies showed no abnormalities in 75 per cent, and mild to moderate lymphocytic infiltrates in 25 per cent of the dogs. The L/R ratio was increased (greater than 0.12) in 52 per cent, and the X/G ratio reduced (less than 0.60) in 33 per cent of the dogs. Differential sugar absorption was repeated in 11 dogs after their four weeks of oral antibiotic therapy. The L/R ratio declined in all 11 dogs (mean +/- SD pre: 0.24 +/- 0.14; post: 0.16 +/- 0.11; P < 0.05), but changes in the X/G ratio were more variable. These findings show that SIBO is commonly associated with mucosal damage not detected on histological examination of intestinal biopsies, and that changes in intestinal permeability following oral antibiotics may be used to monitor response to treatment.

Whole blood manganese concentrations in dogs with primary hepatitis.

OBJECTIVES: Increased whole blood manganese concentrations have been reported in humans with primary liver disease. Due to the neurotoxic effects of manganese, altered manganese homeostasis has been linked to the development of hepatic encephalopathy. Whole blood manganese concentrations are increased in cases of canine congenital portosystemic shunts, but it remains unclear whether dogs with primary hepatopathies also have altered manganese homeostasis. METHODS: Whole blood manganese concentrations were measured by graphite furnace atomic absorption spectrometry in 21 dogs with primary hepatitis, 65 dogs with a congenital portosystemic shunt, 31 dogs with non-hepatic illnesses and 18 healthy dogs. RESULTS: The whole blood manganese concentrations were significantly different between dogs with primary hepatitis, dogs with non-hepatic illnesses and healthy dogs (P=0·002). Dogs with primary hepatitis had significantly increased whole blood manganese concentrations compared with healthy dogs (P<0·05) and dogs with non-hepatic illnesses (P<0·01). Dogs with primary hepatitis had significantly lower whole blood manganese concentration compared with dogs with congenital portosystemic shunts (P=0·0005). CLINICAL SIGNIFICANCE: Dogs with primary hepatopathies have increased concentrations of whole blood manganese although these concentrations are not as high as those in dogs with congenital portosystemic shunts. The role of altered manganese homeostasis in canine hepatic encephalopathy is worthy of further study.