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Biomedical subjects

D B Church

Publications and source records attributed to D B Church.

At least 19 recordsLinked to original sources

Luteinizing hormone and follicle-stimulating hormone receptors and their transcribed genes (mRNA) are present in the lower urinary tract of intact male and female dogs.

In dogs, one of the side effects of neutering is the development of urinary incontinence. The relationship between neutering and urinary incontinence caused by acquired urethral sphincter mechanism incompetence (USMI) has been reported. Recently, GnRH analogue treatment that suppresses elevated plasma gonadotrophin concentrations post-spaying has been successfully used in incontinent bitches. These data and the fact that non-gonadal tissues may contain receptors for LH (LHR) and FSH (FSHR) suggest that there might be a functional relationship between gonadotrophins and the lower urinary tract in dogs. This study aimed to investigate the presence of LHR and FSHR in the lower urinary tract of intact male and female dogs. Four regions of the lower urinary tract, i.e. (i) body of the bladder, (ii) neck of the bladder, (iii) proximal urethra and (iv) distal urethra were collected from 10 healthy dogs (5 males and 5 anoestrous females). In situ hybridization and immunohistochemistry were performed to characterise the presence of receptor mRNA and receptor protein. Staining was rated semi-quantitatively, incorporating both the distribution and intensity of specific staining. The distribution of receptor expression in different tissue layers (epithelium, subepithelial stroma and muscle) in each region was statistically analyzed. Luteinizing hormone receptor and FSHR mRNA and protein were present in all four regions and in three tissue layers of males and females. Irrespective of region and layer, female dogs expressed significantly higher expression for LHR mRNA (P<0.001), LHR protein (P<0.05) and FSHR protein (P<0.001). The expression of LHR and FSHR mRNA and protein was not uniform and depended on region, tissue layer and gender. The expression of LHR mRNA was higher in the bladder, compared to the urethra (P<0.05). The FSHR mRNA significantly increased from the bladder to the urethra. Protein expression for LHR and FSHR was highest in the proximal urethra (P<0.05). The overall expression for LHR and FSHR at both mRNA and protein levels was highest in the epithelium, intermediate to low in the subepithelial stroma and muscle. A significant interaction between region and tissue layer showed that mRNA and protein expression for LHR and FSHR decreased from the bladder to the urethra in the epithelium and subepithelial stroma. In contrast, it gradually increased from the bladder to the urethra in the muscle. In conclusion, the present study showed that both mRNA and protein for LHR and FSHR were expressed in the canine lower urinary tract, and the expression levels varied between genders and among regions and tissue layers. The presence of these receptors suggests that gonadotrophins have a role in the physiology and/or pathology of the lower urinary tract function in the dog.

Animals↗

Investigation of serum IGF-I levels amongst diabetic and non-diabetic cats.

Since insulin-like growth factor-I (IGF-I) was first discovered as a mediator of glucose homeostasis, it has been extensively investigated in diabetes research in humans, rodents and primates. To date, however, relatively little work has been carried out on this hormone in the cat, despite the pathophysiological similarities between human and feline diabetes mellitus, as well as the relatively common nature of the disease in cats. This study reports on the IGF-I concentrations of 42 insulin treated diabetic cats and 25 normal cats. Diabetic subjects were grouped according to length of insulin treatment as either short, medium or long term. Analysis of variance (ANOVA) and Fischer's pair-wise comparisons revealed that mean IGF-I levels in short-term diabetic cats were significantly lower than those in normal cats whilst mean levels in long-term diabetics were significantly higher. The direction and extent of these alterations may have implications for our understanding of the pathophysiology of feline diabetes mellitus and for the use of this hormone in the diagnosis of acromegaly in diabetic cats.

Animals↗

Trilostane treatment of bilateral adrenal enlargement and excessive sex steroid hormone production in a cat.

A 14-year-old neutered female cat was presented for the investigation of aggression and male-type behaviour. Bilateral adrenal enlargement together with elevated plasma concentrations of oestradiol and testosterone were identified, with no evidence of hypercortisolaemia. These findings are similar to the syndrome of hyperadrenocorticism recognised most commonly in ferrets. The cat was treated for six months with the enzyme inhibitor drug, trilostane, and showed a moderate improvement in clinical signs.

3-Hydroxysteroid Dehydrogenases↗

Inefficacy of selegiline in treatment of canine pituitary-dependent hyperadrenocorticism.

OBJECTIVE: To evaluate selegiline, a monoamine oxidase-B inhibitor, for treating dogs with pituitary-dependent hyperadrenocorticism. DESIGN: Prospective clinical trial using client-owned dogs with pituitary-dependent hyperadrenocorticism treated at The University Veterinary Centre, Sydney, from September 1999 to July 2001. PROCEDURE: Eleven dogs with pituitary-dependent hyperadrenocorticism treated with selegiline were monitored at days 10, 30 and 90 by clinical examination, tetracosactrin stimulation testing, urinary corticoid:creatinine ratio measurement and client questionnaire. Endogenous adrenocorticotropic hormone measurements were also performed on most dogs on days 0 and 90. No dog treated with selegiline had satisfactory control of disease. CONCLUSION: Selegiline administration was safe and free of side-effects at the doses used, but did not satisfactorily control disease in pituitary-dependent hyperadrenocorticism affected dogs.

Administration, Oral↗

The urinary corticoid:creatinine ratio (UCCR) in healthy cats undergoing hospitalisation.

Thirty-one healthy pet cats had voided urine samples collected prior to, during and after a brief period of hospitalisation. Urinary corticoids were measured, both prior to and following an extraction technique, and the urinary corticoid:creatinine ratio (UCCR) was calculated. Associations between the UCCR and age, sex, breed and time of urine collection were investigated. There was no significant relationship established between age, sex and breed and the UCCR. A significant increase in the UCCR, however, did occur between the first home collected and first hospitalised urine sample, but only when comparing extracted corticoid results. A normal range for feline UCCR is established for the chemiluminescent immunoassay used in this study.

Animals↗

Evaluation of a continuous glucose monitoring system in diabetic dogs.

The generation of a blood glucose curve is important for assessing the response to insulin therapy in diabetic dogs. Disadvantages of this technique include patient discomfort and the potential for missing transient hypo- or hyperglycaemic episodes. The aim of the current study was to evaluate a continuous glucose monitoring system (CGMS) for use in diabetic dogs. Interstitial fluid glucose concentrations were recorded in 10 diabetic dogs, every five minutes for up to 48 hours, using a subcutaneous sensor attached to the CGMS device. Blood glucose concentrations were measured simultaneously using a glucometer. The correlation between interstitial fluid and blood glucose values was 0.81 (P < 0.01). The largest discrepancies between the two sets of data were seen during the one- to three-hour period following feeding, suggesting that postprandial hyperglycaemia might not be reflected in the interstitial fluid. The authors conclude that the CGMS is a potentially valuable tool in the management of canine diabetic patients.

Animals↗

Trilostane treatment in dogs with pituitary-dependent hyperadrenocorticism.

OBJECTIVE: To evaluate the efficacy of trilostane in treating dogs with pituitary-dependent hyperadrenocorticism. DESIGN: Prospective clinical trial using client-owned dogs with pituitary-dependent hyperadrenocorticism treated at University Veterinary Centre, Sydney from September 1999 to July 2001. PROCEDURE: Thirty dogs with pituitary-dependent hyperadrenocorticism treated with trilostane, a competitive inhibitor of 3beta-HSD, were monitored at days 10, 30 and 90 then 3-monthly by clinical examination, tetracosactrin stimulation testing, urinary corticoid:creatinine ratio measurement and by client questionnaire. RESULTS: Twenty-nine of 30 dogs were successfully treated with trilostane (median dose 16.7 mg/kg; range 5.3 to 50 mg/kg, administered once daily); one responded favourably but died of unrelated disease before full control was achieved. CONCLUSION: Trilostane administration controlled pituitary-dependent hyperadrenocorticism in these dogs. It was safe, effective and free of side-effects at the doses used. Most dogs were initially quite sensitive to the drug for 10 to 30 days, then required higher doses until a prolonged phase of stable dose requirements occurred. Urinary corticoid:creatinine ratio was useful in assessing duration of drug effect. Some dogs treated for more than 2 years required reduction or temporary cessation of drug because of iatrogenic hypoadrenocorticism.

3-Hydroxysteroid Dehydrogenases↗

Effect of phenobarbitone on the low-dose dexamethasone suppression test and the urinary corticoid: creatinine ratio in dogs.

OBJECTIVES: To investigate potential effects of phenobarbitone on the low-dose dexamethasone suppression (LDDS) test and urinary corticoid to creatinine ratio in dogs in a controlled prospective study and in a clinical setting. ANIMALS: Ten crossbreed experimental dogs and 10 client-owned dogs of mixed breeds treated chronically with phenobarbitone to control seizures. PROCEDURES: Experimental dogs were allocated to treatment (6 mg/kg oral phenobarbitone, n = 6) and control (n = 4) groups. LDDS tests (dexamethasone 0.01 mg/kg intravenously, cortisol concentration determined at 0, 2, 4, 6 and 8 h) were conducted repeatedly over a 3-month period. Urinary corticoid to creatinine ratios were measured before LDDS tests. A single LDDS test was performed on 10 epileptic dogs. RESULTS: LDDS and urinary corticoid to creatinine ratios in dogs were not affected by treatment with phenobarbitone. CONCLUSIONS: Phenobarbitone does not interfere with LDDS testing regardless of dosage or treatment time. Urinary corticoid to creatinine ratios are also unaffected.

Adrenal Cortex Function Tests↗

Effects of phenobarbitone on serum biochemical tests in dogs.

OBJECTIVES: To investigate effects of phenobarbitone on serum activities of alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transferase and concentrations of bilirubin, albumin, cholesterol and total protein in dogs. ANIMALS: Ten crossbreed experimental dogs and 10 client-owned dogs of mixed breeds treated chronically with phenobarbitone to control seizures. PROCEDURES: Experimental dogs were allocated to treatment (6 mg/kg oral phenobarbitone, n = 6) and control (no treatment, n = 4) groups in which serum biochemical tests were performed at intervals during a 3-month period. Biochemical tests were performed once on the 10 epileptic dogs. RESULTS: Phenobarbitone caused increased serum alkaline phosphatase activity but did not affect gamma-glutamyl transferase activity or bilirubin, cholesterol, albumin and total protein concentrations. Phenobarbitone had minimal effect on alanine aminotransferase activity. CONCLUSIONS: Individual dogs treated with phenobarbitone may have small increases in serum alanine aminotransferase activity and variable increases in alkaline phosphatase activity but are unlikely to have alterations in gamma-glutamyl transferase activity or bilirubin, cholesterol, albumin or total protein concentrations.

Alanine Transaminase↗

Echocardiographic measurements in greyhounds, whippets and Italian greyhounds--dogs with a similar conformation but different size.

OBJECTIVE: To determine the effect of body size on various echocardiographic measurements in dogs of widely differing size, but identical body conformation. DESIGN: A randomised echocardiographic study of healthy sighthounds. ANIMALS: 60 dogs comprising an equal number (20) of racing Greyhounds, Whippets and Italian Greyhounds. PROCEDURE: Following sedation with acepromazine and morphine, and acclimatization, a thorough echocardiographic examination was performed on each dog using standard methods. RESULTS: Dimensions measured echocardiographically were highly correlated with body size. These data were subsequently examined using analyses of variance and regression. Body surface area was the best overall predictor of dimensional measurements. In comparison to previous studies using dogs of differing size and conformation, the spread of values for measurements plotted against body surface area showed substantially narrower ranges. Thus, the relationship between echocardiographic measurements and body surface area was much closer for dogs with an identical somatotype than for dogs of differing size and conformation. Commonly used ejection phase indices (fractional shortening, ejection fraction and velocity of circumferential fibre shortening) were negatively correlated with body size. In contrast, the thickening fraction of the left ventricular posterior wall, another ejection phase index, was independent of body weight and body surface area for all three breeds and when the data were pooled. CONCLUSION: Taken in consideration with previous work, this study demonstrates that body conformation and body size both influence canine echocardiographic measurements. Commonly used ejection phase indices are significantly affected by body size, with larger sighthounds having lower values. A more appropriate method of quantitating left ventricular function may be the determination of the thickening fraction of the left ventricular posterior wall.

Animals↗

Regulation of insulin-like growth factor-binding protein-3 ternary complex in feline diabetes mellitus.

The 140 kDa ternary complex of insulin-like growth factor-binding protein-3 (IGFBP-3), IGFs and an acid-labile subunit (ALS) has previously been shown to be decreased in diabetes mellitus in humans and rats. We have studied IGF-I levels and ternary complex formation in normal and diabetic cats. Total IGF-I concentrations, measured by RIA using des(1-3)-IGF-I as tracer were (+/-s.e.m.) 54+/-13 nmol/l in eight normal and 227+/-57 nmol/l in eight diabetic cats (P<0.01). The size-distribution of IGFBPs in the cat circulation was determined by incubation with (125)I-IGF-II and Superose 12 chromatography. In normal animals 26+/-2% of the (125)I-IGF-II were in a 140 kDa form compared with 48+/-5% in diabetic cats (P<0.01). When samples from normal and diabetic animals were co-incubated 52+/-3% were at 140 kDa. A similar shift was seen when normal cat and normal human serum were co-incubated. A 2-fold increase in the 140 kDa form in diabetic cats was confirmed first by size-fractionating samples and then performing a ligand-binding assay with (125)I-IGF-I or -II and charcoal separation. SDS-PAGE and Western ligand blotting demonstrated a 45 kDa doublet (presumably IGFBP-3) and 30-35 kDa forms. There were no apparent differences between normal and diabetic profiles on SDS-PAGE, suggesting that a proportion of IGFBP-3 which circulates 'free' in normal cats forms a ternary complex in the diabetic circulation. We conclude that (i) in contrast to humans and rats, ALS is the limiting factor for ternary complex formation in normal cats, (ii) ALS concentrations increase in feline diabetes mellitus and, by promoting ternary complex formation, this leads to an increase in total IGF-I concentrations, and (iii) total IGF-I concentrations may not be reliable in the diagnosis of acromegaly in diabetic cats.

Acromegaly↗

Vegetative endocarditis in six cats.

Between 1990 and 1997 vegetative endocarditis was diagnosed in six neutered cats (three males, three females) aged between 3 and 9 years. Two cats were purebred (one Persian and one Tonkinese), the remaining four being domestic short haired cats. The diagnosis was made using echocardiography (five cases) or at necropsy (one case). Concurrent involvement of the aortic and mitral valve was noted in four cats, the aortic valve alone was affected in one case, and the tricuspid valve in another. A likely microbiological diagnosis was obtained in three cats: a Bartonella species in two cats based on positive blood culture and a Streptococcus species in one cat based on Gram stain of valve lesions at necropsy. In another cat, Gram-positive cocci were demonstrated histologically in tricuspid vegetations. Invariably, cats had signs of congestive heart failure (left-sided in five cats, right-sided in one), and this was the major factor contributing to mortality in four cases. Signs referable to sepsis were prominent in only two patients. Appropriate medical therapy, consisting of antimicrobials and drugs to treat congestive heart failure, resulted in survival for 5 and 11 months, respectively, in two cases. The other cats died within 2 weeks of diagnosis, including two which received aggressive treatment in hospital.

Animals↗

Morphometric study of the beta-cell volume of the canine pancreas with consideration of the axis of tissue transection.

The pancreatic beta-cell volume was assessed in 12 clinically normal crossbred dogs using immunohistochemical labelling for insulin and computer-assisted morphometric analysis. The beta-cell volume was less in the right lobe compared with the body and left lobe, but the beta-cell volume did not differ between the body and the left lobe as reported previously. The use of immunohistochemistry, computer-assisted morphometry, the inclusion here of extra-islet beta-cells and the exclusion of non-beta-endocrine cells in the investigation of the beta-cell volume may have contributed to this discrepancy. As most beta-cells form irregularly shaped three-dimensional bodies (islets of Langerhans), the effect of the plane of tissue transection (sagittal, transverse, oblique) on the calculation of the beta-cell volume was also examined. The beta-cell volume in the sagittal plane of the right lobe was lower than the volume in the oblique plane of the same lobe but was not different from the volume in the transverse plane. However, there were no differences in beta-cell volume in different planes in the body or left lobe. When quantifying beta-cell volume in health or disease, variation in the volume of beta-cells in different locations of the pancreas is an important consideration and the plane of transection may also influence results.

Animals↗

Effect of acute haemorrhage on QRS amplitude of the lead II canine electrocardiogram.

OBJECTIVE: To examine the effect of acute haemorrhage on the QRS amplitude of the canine lead II surface electrocardiograph (ECG). DESIGN: Ten adult racing Greyhounds were tranquilised, anaesthetised, positioned in right lateral recumbency and connected to recording electrodes of an ECG unit. Baseline six-lead ECG traces were recorded, and further traces were obtained after one unit (460 mL) of blood, and then a second unit, were collected from the femoral artery. RESULTS: There was a consistent and progressive reduction in amplitude of the QRS complex in all leads during acute haemorrhage. QRS amplitude in lead II after removal of two units of blood averaged 74% of the baseline voltage, with individual values of 61 to 91% (P < 0.0001). There were even greater reductions in QRS amplitudes in lead aVL during haemorrhage. In three additional dogs, reductions in QRS voltages were shown to be accompanied by reductions in end-diastolic left ventricular internal dimensions measured echocardiographically. Furthermore, the effects of haemorrhage on the QRS amplitude and echocardiographic measurements were reversed when circulating blood volume was restored by re-infusion of blood removed previously. CONCLUSION: Acute haemorrhage corresponding to an approximately one-third reduction in blood volume caused a substantial reduction in QRS voltage of the surface ECG. It is postulated that this resulted from diminished ventricular distension as a consequence of reduced venous return. A similar mechanism may account for the small-amplitude ECG complexes associated with pericardial effusion, severe dehydration and hypovolaemia.

Acute Disease↗

Plasma cortisol concentrations in normal dogs given hydrocortisone sodium succinate.

OBJECTIVE: To evaluate the effects on plasma cortisol concentration of a continuous infusion of a readily available steroid with equipotent glucocorticoid and mineralocorticoid effects. PROCEDURE: Plasma cortisol concentrations were measured before and regularly after hydrocortisone sodium succinate was administered as a continuous intravenous infusion over 6 h at 0.32 and 0.65 mg kg-1 h-1 to 12 healthy dogs weighing 12 to 22 kg. RESULTS: The infusion at both does rates produced significant and stable increases in plasma cortisol concentrations. The plateau concentrations produced by the large and small doeses were respectively above and below plasma cortisol concentrations likely to provide adequate glucocorticoid and mineralocorticoid activity in stressed dogs with significantly decreased adrenal function. CONCLUSION: This paper presents information regarding the changes in plasma cortisol concentrations in 12 normal dogs given an hydrocortisone sodium succinate infusion at two dose rates. The marked and continuous increase in plasma cortisol concentrations suggests a continuous HSS infusion may be a possible alternative to desoxycorticosterone acetate and dexamethasone in the treatment of acute adrenal dysfunction.

Animals↗

Benign masses in the pericardium of two dogs.

Two miniature Schnauzer dogs were treated for pericardial masses. In one dog the mass consisted of necrotic fat that was attached to the apex of the pericardium by a pedicle. No obvious communication with the abdomen was present. The second dog had a peritoneopericardial hernia associated with a chronic cystic haematoma. In each case the mass was presumed to have arisen following congenital displacement of the omentum into the pericardium. The pericardial mass was removed and subtotal pericardectomy performed in both dogs. Recovery was complete in each case.

Animals↗

Primary hypoparathyroidism in two horses.

Two Thoroughbred horses were presented with various clinical signs which included sweating, agitation, muscle twitching and synchronous diaphragmatic flutter. These signs were associated with profound hypocalcaemia. A diagnosis of primary hypoparathyroidism was made on the basis of low serum ionised calcium concentration, hyperphosphataemia and markedly reduced serum immunoreactive parathyroid hormone concentrations in the presence of normal renal function. Treatment with a combination of intravenous calcium and subsequently oral calcium, magnesium and a vitamin D analogue (dihydrotachysterol) for up to 65 days resulted in complete remission of clinical signs. Horse 1 was euthanased 12 months after the initial recognition of signs. Results of necropsy were unremarkable apart from an absence of detectable parathyroid tissue. Horse 2 returned to athletic activities while receiving only maintenance doses of oral calcium carbonate.

Animals↗

Plasma cortisol concentrations following cortisone infusion in dogs before and after treatment with cortisone acetate.

OBJECTIVE: To evaluate effects of iatrogenic hyperadrenocorticism on plasma cortisol concentrations produced by an infusion of hydrocortisone in dogs. PROCEDURE: Plasma cortisol concentrations were measured regularly during a 6 h infusion of hydrocortisone sodium succinate at two dose rates. The infusions were performed before and after treatment for 30 d with oral cortisone acetate at 10 mg/kg/24 h, divided thrice daily. Adrenal activity during the experimental period was assessed by weekly ACTH stimulation tests. RESULTS: Both infusion rates produced lower plasma cortisol concentrations after treatment for 30 d with cortisone. CONCLUSION: Prior exposure to high concentrations of glucocorticoids may result in accelerated metabolism of glucocorticoids administered subsequently. This may necessitate increased dosages when using glucocorticoids to support inadequate adrenal function.

Administration, Oral↗