The effect of obesity and subsequent weight reduction on cardiac structure and function in dogs.

BACKGROUND: In people, the cardiovascular effects of obesity include systemic hypertension, cardiac remodelling and both systolic and diastolic dysfunction, whilst weight reduction can reverse myocardial remodelling and reduce risk of subsequent cardiovascular disease. To date, variable results are reported in studies of the effect of obesity and controlled weight reduction on cardiovascular morphology and function in dogs. This prospective study aimed to assess cardiac function, heart rate variability, cardiac biomarkers and body composition before and after weight reduction in pet dogs with obesity. Twenty-four client-owned dogs referred for weight management due to obesity were recruited. To assess the cardiac effects of obesity, body composition analysis (by dual energy X-ray absorptiometry, DEXA) and cardiovascular assessment (echocardiography, Doppler blood pressure, electrocardiography, cardiac biomarkers) were performed prior to weight management. Twelve dogs completed the study and reached target weight, receiving a further cardiovascular assessment and DEXA. A Wilcoxon-signed rank test was used to compare each variable pre- and post- weight reduction. RESULTS: Median (interquartile range) duration of weight loss was 224 days (124-245 days), percentage weight loss was 23% (18-31%) of starting weight. Median change in body fat mass was -50% (-44% to -55%; P = 0.004), whilst median change in lean mass was -7% (+ 1% to -18%, P = 0.083). Before weight reduction, diastolic dysfunction (evidence of impaired relaxation in all dogs), increased left ventricular wall thickness and mildly elevated systolic blood pressure (14/24 ≥ 160 mmHg, median 165 mmHg (140-183)) were common features in dogs with obesity. However, systolic left ventricular wall dimensions were the only variables that changed after weight reduction, with a decrease in both the systolic interventricular septum (P = 0.029) and systolic left ventricular free wall (P = 0.017). There was no evidence of decreased heart rate variability in dogs with obesity (P = 0.367), and no change in cardiac biomarker concentrations with weight reduction (N-terminal proBNP, P = 0.262; cardiac troponin I P = 0.657). CONCLUSIONS: Canine obesity results in diastolic dysfunction and left ventricular hypertrophy, the latter of which improves with significant weight and fat mass reduction. Further studies are required to clarify the clinical consequences of these findings.

Cor triatriatum dexter of unusual morphology in a miniature schnauzer.

A five-year-nine-month-old, male entire, miniature schnauzer presented for further investigation of pleural effusion. Echocardiography revealed a perforated membrane dividing the right atrium into two chambers: the true right atrium (a small, lower-pressure, cranioventral chamber communicating with the tricuspid valve and right ventricle) and the accessory right atrium (a larger, higher-pressure, caudodorsal chamber), consistent with a cor triatriatum dexter. This was confirmed using computed tomography angiography. Imaging studies revealed that both the cranial and caudal vena cava entered the higher-pressure accessory right atrium and the coronary sinus entered both the accessory and true right atrial chambers. This differed from the more usual canine cor triatriatum dexter presentation with the cranial vena cava entering the lower-pressure cranial chamber and the caudal vena cava entering the higher-pressure caudal chamber. Balloon membranostomy was successful in reducing the pressure gradient between the two right atrial chambers with subsequent resolution of the clinical signs. The patient continues to do well after three-years of follow-up.

Familial cerebellar ataxia with hydrocephalus in bull mastiffs.

Familial cerebellar ataxia with concurrent hydrocephalus has previously been described in a family of bull mastiff pups, and recently has been identified in a litter from Louisiana. The 4 affected pups had ataxia, hypermetria, conscious proprioceptive deficits, behavioral abnormalities, and a visual deficit. In magnetic resonance imaging of the brain of two of the pups, there were symmetric hydrocephalus and two focal areas of increased signal intensity within the central nuclei of the cerebellum. Histopathologically there was vacuolization and mild astrogliosis within the deep cerebellar nuclei (dentate, interpositus, fastigial), caudal colliculi, and lateral vestibular nuclei. Although the postmortem results were not exactly the same as in the previously published report, the clinical features and histopathologic findings strongly support the diagnosis. This disorder is most likely inherited in an autosomal recessive manner.

Evaluation of the safety of fenbendazole in cats.

OBJECTIVE: To evaluate the safety of fenbendazole in domestic cats. ANIMALS: 28 six- to seven-month old domestic short-hair cats. PROCEDURE: Cats were randomly assigned to 1 of 3 treatment groups or a control group (n = 7/group). Cats in the treatment groups were given fenbendazole at a dosage of 50, 150, or 250 mg/kg, PO, every 24 hours for 9 days; control cats were given a placebo. A fecal examination, coagulation tests, serum biochemical analyses, CBC, and urinalyses were performed before and 5, 9, and 21 days after initiation of treatment; cats were closely monitored for adverse reactions. After the last dose of fenbendazole was given, 4 control cats and 4 cats given fenbendazole at the highest dosage were euthanatized, and necropsies were performed. RESULTS: None of the cats developed any adverse reactions. For cats in the control and all treated groups, laboratory test results were within reference limits, and there were no significant differences in results of laboratory tests among groups. No gross or histologic lesions were identified in the control or treated cats that were euthanatized. CONCLUSIONS AND CLINICAL RELEVANCE: Fenbendazole administered to healthy cats at a dosage 5 times the dosage and 3 times the duration approved for use in dogs and wild felids did not cause any acute or subacute adverse reactions or pathologic changes. Results suggest that cats may be safely treated with fenbendazole.

Lateral spine densitometry in obese women.

The lateral (LAT) spine scan has been suggested as a more sensitive measure than posterior-anterior (PA) scanning for assessing age-related bone loss in normal-weight postmenopausal women. The measurement error of PA and LAT bone mineral density (BMD) using dual energy X-ray absorptiometry (DXA) has also been shown to rise with incremental increases in fat and from large variance in fat thickness, respectively. The purpose of this cross-sectional study was to determine specific affects of obesity on paired PA and LAT lumbar (L2-L4) BMD and Z score (BMD of patient versus age-matched reference data-base) correlation in 30 obese postmenopausal women (mean BMI +/- SD = 33.3 +/- 4.06). The mean PA and LAT BMD +/- SD were 0.946 +/- 0.123 and 0.749 +/- 0.134, respectively. The mean PA and LAT Z scores were -0.17 +/- 1.15 and 0.80 +/- 1.7. The correlation between PA and LAT BMD was significantly lower (r = 0.55; P < 0.05) than previously reported, and PA and LAT Z score correlation was (r = 0.57; P = 0.0016). After adjusting for body mass index (BMI), percent body fat, fat mass, and truncal fat by DXA, waist:hip ratio (WHR) and visceral and subcutaneous abdominal fat by computerized axial tomography (CT), PA and LAT Z score correlation increased to r = 0.62; P = 0.0065. In our subjects, the mean LAT Z score was 4.6 times higher than the mean AP Z, contrary to previous observations in normal-weight postmenopausal women. Our findings may be due to increased soft tissue composition and fat inhomogeneity in the LAT scanning field resulting in increased X-ray attenuation in obesity.

A case of partial mole associated with trisomy 13.

The majority of second-trimester partial moles are found in association with triploidy. Rarely are they associated with tetraploidy or other aneuploidies and, to our knowledge, this is the first reported case of the prenatal diagnosis of partial mole in a pregnancy presenting with trisomy. The patient was referred at 21 weeks of gestation after a routine ultrasound examination had shown fetal and placental features suggesting a partial mole triploidy. Owing to the severe structural malformations and poor prognosis, the parents requested termination. Prenatal and postnatal cytogenetic investigations demonstrated an additional chromosome 13. Histopathological examination of the placenta showed focal areas of villous edema but no evidence of trophoblastic dysplasia. The maternal serum human chorionic gonadotropin level was within the normal range at all times. This case shows that trisomy can resemble a triploid partial mole in utero without the potential long-term risk to the mother of persisting trophoblastic disease, as villous molar changes can obviously develop without trophoblastic dysplasia.

Exogenous androgens influence body composition and regional body fat distribution in obese postmenopausal women--a clinical research center study.

Abdominal fat distribution is influenced by androgen levels in both men and women. The purpose of this study was to assess the effects on fat distribution of administering nandrolone decanoate (ND; an anabolic steroid with weak androgenic activity) or spironolactone (SP; an antiandrogen) in obese postmenopausal women. The design was a randomized, placebo-controlled, 9-month trial with simultaneous calorie restriction for weight loss. Women in all three groups lost comparable amounts of weight, but the ND-treated women gained lean mass relative to the other two groups (P < 0.0005) and lost more body fat than women in the SP group (P < 0.01). The resting metabolic rate also increased slightly in the ND group. ND treatment produced a gain in visceral fat, as determined by computed tomography scan, and a relatively greater loss of sc abdominal fat. SP-treated women lost significantly less sc fat than the other two groups. Serum cholesterol decreased in the placebo group, but increased slightly in the other two groups (significant for SP vs. placebo, P < 0.05). High density lipoprotein cholesterol decreased significantly in the ND-treated women. There were no significant changes in fasting glucose or insulin sensitivity. We conclude that administration of exogenous androgens modulates body composition in obese postmenopausal women and independently affects visceral and sc abdominal fat.

Autonomic activity assessed by heart rate spectral analysis varies with fat distribution in obese women.

Obesity in humans has been associated with altered autonomic nervous system activity. The objective of this study was to examine the relationship between autonomic function and body fat distribution in 16 obese, postmenopausal women using power spectrum analysis of heart rate variability. Using this technique, a low frequency peak (0.04-0.12 Hz) reflecting mixed sympathetic and parasympathetic activity, and a high frequency peak (0.22-0.28 Hz) reflecting parasympathetic activity, were identified from 5-minute consecutive heart rate data (both supine and standing). Autonomic activity in upper body (UBO) vs. lower body obesity (LBO)(by waist-to-hip ratio) and subcutaneous vs. visceral obesity (by CT scan) was evaluated. Power spectrum data were log transformed to normalize the data. The results showed that standing, low-frequency power (reflecting sympathetic activity) and supine, high-frequency power (reflecting parasympathetic activity) were significantly greater in UBO than in LBO, and in visceral compared to subcutaneous obesity. Women with combined UBO and visceral obesity had significantly higher cardiac sympathetic and parasympathetic activity than any other subgroup. We conclude that cardiac autonomic function as assessed by heart rate spectral analysis varies in women depending on their regional body fat distribution.

Oral anabolic steroid treatment, but not parenteral androgen treatment, decreases abdominal fat in obese, older men.

OBJECTIVE: To compare the effects of testosterone enanthate (TE), anabolic steroid (AS) or placebo (PL) on regional fat distribution and health risk factors in obese middle-aged men undergoing weight loss by dietary means. DESIGN: Randomized, double-blind, placebo-controlled clinical trial, carried out for 9 months with primary assessments at 3 month intervals. Due to adverse blood lipid changes, the AS group was switched from oral oxandrolone (ASOX) to parenteral nandrolone decaoate (ASND) after the 3 month assessment point. SUBJECTS: Thirty healthy, obese men, aged 40-60 years, with serum testosterone (T) levels in the low-normal range (2-5 ng/mL). MAIN OUTCOME MEASURES: Abdominal fat distribution and thigh muscle volume by CT scan, body composition by dual energy X-ray absorptiometry (DEXA), insulin sensitivity by the Minimal Model method, blood lipids, blood chemistry, blood pressure, thyroid hormones and urological parameters. RESULTS: After 3 months, there was a significantly greater decrease in subcutaneous (SQ) abdominal fat in the ASOX group compared to the TE and PL groups although body weight changes did not differ by treatment group. There was also a tendency for the ASOX group to exhibit greater losses in visceral fat, and the absolute level of visceral fat in this group was significantly lower at 3 months than in the TE and PL groups. There were significant main effects of treatment at 3 months on serum T and free T (increased in the TE group and decreased in the ASOX group) and on thyroid hormone parameters (T4 and T3 resin uptake significantly decreased in the ASOX group compared with the other two groups). There was a significant decrease in HDL-C, and increase in LDL-C in the ASOX group, which led to their being switched to the parenteral nandrolone decanoate (ASND) after 3 months. ASND had opposite effects on visceral fat from ASOX, producing a significant increase from 3 to 9 months while continuing to decrease SQ abdominal fat. ASND treatment also decreased thigh muscle area, while ASOX treatment increased high muscle. ASND reversed the effects of ASOX on lipoproteins and thyroid hormones. The previously reported effect of T to decrease visceral fat was not observed, in fact, visceral fat in the TE group increased slightly from 3 to 9 months, although SQ fat continued to decrease. Neither TE nor AS treatment resulted in any change in urologic parameters. CONCLUSIONS: Oral oxandrolone decreased SQ abdominal fat more than TE or weight loss alone and also tended to produce favorable changes in visceral fat. TE and ASND injections given every 2 weeks had similar effects to weight loss alone on regional body fat. Most of the beneficial effects observed on metabolic and cardiovascular risk factors were due to weight loss per se. These results suggest that SQ and visceral abdominal fat can be independently modulated by androgens and that at least some anabolic steroids are capable of influencing abdominal fat.

Magnetic resonance angiography in vertebrobasilar ischemia. Preliminary experience.

Forty-five patients were evaluated for vertebrobasilar ischemic disease by magnetic resonance imaging and magnetic resonance angiography (MRA). Ten also underwent intraarterial digital subtraction angiography. All were sorted into three groups based on results of the MRA and their clinical presentation. In the first group, vertebrobasilar ischemic disease could be reasonably excluded. In the second, such disease was nearly certain. In the third group, the vertebrobasilar system could not readily be assessed by the MRA alone and often required further studies. In 8 of 10 patients a strong correlation was found between MRA and intraarterial digital subtraction angiography. MRA provided valuable information for assessing vertebrobasilar disease and, in many instances, eliminated the need for invasive angiography.

Transvenous coil embolization for treatment of patent ductus venosus in a dog.

A congenital intrahepatic portosystemic shunt was successfully closed in a 3-month-old Golden Retriever by use of a transvenous coil embolization procedure. The pup's patent ductus venosus was occluded by placing 8 Dacron fiber-covered, stainless steel, spring embolization coils into the shunt vessel through a catheter placed through the jugular vein. Four separate embolization procedures were performed to gradually close the portosystemic shunt and to allow intrahepatic portal perfusion to reform. Transvenous embolization may prove to be a better therapeutic alternative than surgery for correction of intrahepatic shunts because of its decreased invasiveness, lower mortality, and ability to gradually narrow the shunt lumen.

Flow dynamics of lateral carotid artery aneurysms and their effects on coils and balloons: an experimental study in dogs.

PURPOSE: To investigate the hemodynamic characteristics of lateral carotid artery aneurysms in a canine model and to determine their influence on coils and balloons. MATERIALS AND METHODS: Forty aneurysms were created in fourteen dogs and their hemodynamic characteristics and influence on coils and balloons were evaluated with angiography and color Doppler pre- and postplacement. Twenty aneurysms were treated with coils, eight with balloons, and 12 aneurysms served as controls. RESULTS: The aneurysms demonstrated three distinct zones of flow: 1) an inflow zone entering at the distal aspect of the aneurysm ostium, 2) an outflow zone exiting at the proximal ostium, and 3) a central slow flow vortex. The inflow zone is a determining factor in the placement and stability of coils and balloons placed within the aneurysm and in the thrombosis of an aneurysm. The force of the inflow is considerable and can alter the shape of coils and displace both coils and balloons positioned within the aneurysm. CONCLUSIONS: Coils and balloons need to be of shapes and sizes that do not conform to the inflow and outflow zones. Filling the aneurysm and blocking or displacing the inflow zone can produce thrombosis of an aneurysm with preservation of the parent artery.

Quantitative determination of acid-labile DNA in cervical intraepithelial neoplasia.

Using a modified Feulgen hydrolysis procedure and integrating microdensitometry, the acid-labile nuclear DNA in exfoliated cervical epithelial cells was quantified in a range of histologically confirmed cervical intraepithelial neoplasia (CIN), invasive cancer, and normal controls. The mean relative optical densities obtained for each sample group showed an increase from normal epithelium, through CIN grades, to invasive cancer. Although there was some overlap between groups, the difference in the overall mean values between the adjacent groups was statistically significant. The sensitivity of the test was 87.1% with a specificity of 99.2% and a predictive value of 99.5%, with no false negatives in the severe dysplasia and cancer groups. Quantitative data allows the threshold value to be altered to vary the sensitivity and specificity according to prevailing requirements. This suggests the possibility of using quantitative acid-labile DNA measurements to improve existing screening for cervical precancer.

Delayed visual loss due to trauma of the internal carotid artery.

The group of six patients in this study experienced delayed visual loss following head trauma. Visual loss occurred from 1 day to 13 years after the initial injury. All patients suffered indirect trauma to the internal carotid artery resulting in formation of either an aneurysm or pseudoaneurysm or a carotid-cavernous fistula. Review of the radiologic and clinical findings was performed in six patients. The diagnosis was established by computed tomography, magnetic resonance imaging, and angiography. All patients had follow-up clinical evaluation and imaging studies. Treatment by neurosurgical or interventional neuroradiologic procedures resulted in significant visual improvement in five patients. Different pathophysiologic mechanisms could be correlated with the delayed visual loss produced by the two types of lesions. The pathologic changes associated with the aneurysms/pseudoaneurysms included direct compression of optic nerves and/or chiasm and intracranial hematoma. A carotid-cavernous fistula caused delayed visual loss by either hematoma at the orbital apex or compression of the chiasm and/or optic nerves by saccular dilatation of the cavernous sinus. The delayed onset of decreased vision following head trauma should alert the physician to the possibility of a traumatic aneurysm/pseudoaneurysm or a carotid-cavernous fistula. Different neuro-ophthalmologic symptoms can usually be correlated with the pathologic changes demonstrated by neuroimaging procedures.

Magnetic resonance imaging of central nervous system lesions in patients with lupus erythematosus. Correlation with clinical remission and antineurofilament and anticardiolipin antibody titers.

Clinical, magnetic resonance imaging (MRI), and serologic studies were performed on 11 patients with diffuse central nervous system (CNS) systemic lupus erythematosus and 8 patients with focal CNS lupus. MRI of patients with diffuse clinical disease showed symmetrically distributed areas of increased signal intensity in the subcortical white matter; these resolved after treatment with high-dose methylprednisolone. These patients' sera contained elevated levels of antineurofilament antibodies. Patients with focal CNS lupus had areas of increased signal intensity and atrophic changes in regions corresponding to the major cerebral vessels. These MRI abnormalities did not improve after treatment with high-dose steroids. The sera of patients with focal CNS lupus had elevated levels of cardiolipin and lupus anticoagulant but normal levels of antineurofilament antibody. Our findings suggest that results of a combined clinical, MRI, and serologic evaluation of patients with CNS lupus may predict the response of patients to high-dose steroid therapy.