Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study.

BACKGROUND: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. OBJECTIVES: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. ANIMALS: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. METHODS: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. RESULTS: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

Effect of Body Weight on Echocardiographic Measurements in 19,866 Pure-Bred Cats with or without Heart Disease.

BACKGROUND: Echocardiography is a cost-efficient method to screen cats for presence of heart disease. Current reference intervals for feline cardiac dimensions do not account for body weight (BW). OBJECTIVE: To study the effect of BW on heart rate (HR), aortic (Ao), left atrial (LA) and ventricular (LV) linear dimensions in cats, and to calculate 95% prediction intervals for these variables in normal adult pure-bred cats. ANIMALS: 19 866 pure-bred cats. METHODS: Clinical data from heart screens conducted between 1999 and 2014 were included. Associations between BW, HR, and cardiac dimensions were assessed using univariate linear models and allometric scaling, including all cats, and only those considered normal, respectively. Prediction intervals were created using 95% confidence intervals obtained from regression curves. RESULTS: Associations between BW and echocardiographic dimensions were best described by allometric scaling, and all dimensions increased with increasing BW (all P<0.001). Strongest associations were found between BW and Ao, LV end diastolic, LA dimensions, and thickness of LV free wall. Weak linear associations were found between BW and HR and left atrial to aortic ratio (LA:Ao), for which HR decreased with increasing BW (P<0.001), and LA:Ao increased with increasing BW (P<0.001). Marginal differences were found for prediction formulas and prediction intervals when the dataset included all cats versus only those considered normal. CONCLUSIONS AND IMPORTANCE: BW had a clinically relevant effect on echocardiographic dimensions in cats, and BW based 95% prediction intervals may help in screening cats for heart disease.

Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study.

BACKGROUND: Myxomatous mitral valve disease (MMVD) is an important cause of morbidity and mortality in dogs. OBJECTIVES: To compare, throughout the period of follow-up of dogs that had not yet reached the primary endpoint, the longitudinal effects of pimobendan versus benazepril hydrochloride treatment on quality-of-life (QoL) variables, concomitant congestive heart failure (CHF) treatment, and other outcome variables in dogs suffering from CHF secondary to MMVD. ANIMALS: A total of 260 dogs in CHF because of MMVD. METHODS: A prospective single-blinded study with dogs randomized to receive pimobendan (0.4-0.6 mg/kg/day) or benazepril hydrochloride (0.25-1.0 mg/kg/day). Differences in outcome variables and time to intensification of CHF treatment were compared. RESULTS: A total of 124 dogs were randomized to pimobendan and 128 to benazepril. No difference was found between groups in QoL variables during the trial. Time from inclusion to 1st intensification of CHF treatment was longer in the pimobendan group (pimobendan 98 days, IQR 30-276 days versus benazepril 59 days, IQR 11-121 days; P = .0005). Postinclusion, dogs in the pimobendan group had smaller heart size based on VHS score (P = .013) and left ventricular diastolic (P = .035) and systolic (P = .0044) dimensions, higher body temperature (P = .030), serum sodium (P = .0027), and total protein (P = .0003) concentrations, and packed cell volume (P = .030). Incidence of arrhythmias was similar in treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan versus benazepril resulted in similar QoL during the study, but conferred increased time before intensification of CHF treatment. Pimobendan treatment resulted in smaller heart size, higher body temperature, and less retention of free water.

[NT-proBNP as a diagnostic marker in dogs with dyspnea and in asymptomatic dogs with heart murmur]. / NT-proBNP in der Diagnostik bei Hunden mit Dyspnoe und asymptomatischen Hunden mit Herzgeräusch.

OBJECTIVE: The cardiac biomarker NT-proBNP indicates cardiac load in terms of myocardial wall stress. The objective of the study was to compare the results of NT-proBNP measurements in healthy dogs and dogs with dyspnea as well as asymptomatic dogs with heart murmur with the literature. MATERIAL AND METHODS: Between April 2007 and December 2007 dogs with dyspnea of non-cardiac origin (n=11), dogs with dyspnea of cardiac origin (n=18) and asymptomatic dogs with heart murmur (n=22) were included. Twelve clinically healthy dogs served as a control group. All animals underwent cardiologic examination including echocardiography and measurement of serum NT-proBNP concentration. Serum was centrifuged and frozen within 30 minutes and was stored frozen until analysis was performed. RESULTS: Median NT-proBNP concentration in healthy dogs was 240 pmol/l (range 131-546 pmol/l). Dogs with dyspnea and primary respiratory disease displayed a median NT-proBNP concentration of 876 pmol/l (range 97-2614 pmol/l). In patients with dyspnea of non-cardiac origin, there was a difference in the values of NT-proBNP of dogs with and without pulmonary hypertension diagnosed by echocardiography. Dogs with dyspnea of cardiac origin displayed a median NT-proBNP concentration of 2000 pmol/l (range 137-2614 pmol/l). Low normal NT-proBNP values were only found in patients with pericardial effusion. Median NT-proBNP concentration in asymptomatic dogs with heart murmur was 698.5 pmol/l (range 121-2614 pmol/l). Considerably increased values were particularly measured in asymptomatic patients with severe congenital heart disease. CONCLUSION AND CLINICAL RELEVANCE: NT-proBNP represents a useful additional diagnostic parameter in veterinary clinical cardiology to assess the severity of cardiac disease. Interpretation must take into consideration the clinical picture of the patient, as dogs with severe arrhythmias, sepsis and pulmonary thromboembolism may display high NT-proBNP levels without congestive heart failure. Our results indicate the following cut-off values: <500 pmol/l: no relevant cardiac load; 500-900 pmol/l: moderate cardiac load; >900 pmol/l: severe cardiac load.

Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: the QUEST study.

BACKGROUND: Myxomatous mitral valve disease (MMVD) continues to be an important cause of morbidity and mortality in geriatric dogs despite conventional therapy. HYPOTHESIS: Pimobendan in addition to conventional therapy will extend time to sudden cardiac death, euthanasia for cardiac reasons, or treatment failure when compared with conventional therapy plus benazepril in dogs with congestive heart failure (CHF) attributable to MMVD. ANIMALS: Two hundred and sixty client-owned dogs in CHF caused by MMVD were recruited from 28 centers in Europe, Canada, and Australia. METHODS: A prospective single-blinded study with dogs randomized to PO receive pimobendan (0.4-0.6 mg/kg/d) or benazepril hydrochloride (0.25-1.0 mg/kg/d). The primary endpoint was a composite of cardiac death, euthanized for heart failure, or treatment failure. RESULTS: Eight dogs were excluded from analysis. One hundred and twenty-four dogs were randomized to pimobendan and 128 to benazepril. One hundred and ninety dogs reached the primary endpoint; the median time was 188 days (267 days for pimobendan, 140 days for benazepril hazard ratio = 0.688, 95% confidence limits [CL]=0.516-0.916, P= .0099). The benefit of pimobendan persisted after adjusting for all baseline variables. A longer time to reach the endpoint was also associated with being a Cavalier King Charles Spaniel, requiring a lower furosemide dose, and having a higher creatinine concentration. Increases in several indicators of cardiac enlargement (left atrial to aortic root ratio, vertebral heart scale, and percentage increase in left ventricular internal diameter in systole) were associated with a shorter time to endpoint, as was a worse tolerance for exercise. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan plus conventional therapy prolongs time to sudden death, euthanasia for cardiac reasons, or treatment failure in dogs with CHF caused by MMVD compared with benazepril plus conventional therapy.

Occupational skin-protection products--a review.

Skin-protection products are used in the occupational field to protect the skin against hazards from the workplace. They are only to be used for non-toxic, non-cancerogenous and non-sensitizing low-grade irritants such as water, detergents, and cutting fluids and cannot replace other protective measures such as gloves. The recommendation of products mainly focuses on the physico-chemical properties of the irritant and the protective cream. More in vivo studies and intervention studies are needed to prove the efficacy of skin-protection products under real-life conditions.

Multicentre study for the development of an in vivo model to evaluate the influence of topical formulations on irritation.

Although skin protective products to prevent irritant skin reactions are in wide use, neither standardized test models to prove differences in efficacy exist, nor has the quality or the reproducibility of results been evaluated in a multicentre approach. This should be mandatory when developing or testing skin care products. Therefore, we have designed a multicentre study in an approach to find a standardized test procedure for the evaluation of skin protective products. In this irritation study, a repeated short-time occlusive irritation test (ROIT) with a standardized protocol has been evaluated in 2 phases (12 days and 5 days protocol) in 4 (n=20) respectively 6 (n=33) skilled centres. The skin reaction was induced by 2 irritants (0.5% aq. SLS and toluene, 2x a day for 30 min). Its modification by 3 different cream bases with different hydrophilicity was analyzed. The irritation was monitored by bioengineering methods (TEWL measurement, colorimetry) and by clinical scoring. The evaluation showed that significant results could already be achieved with the 5-day protocol. Furthermore, in spite of the expected inter-centre variations due to heterogeneity of the individual threshold of irritation, interpretation of clinical score, and inter-instrumental variability, the ranking of the vehicles regarding reduction of the irritant reaction was consistent in all centres.

[Nuclear spin tomography, magnetic resonance tomography (MRT), nuclear magnetic resonance imaging (NMR). Technical and methodical hypotheses for the use of nuclear spin tomography on the hip joint of the dog]. / Kernspintomographie, Magnet-Resonanz-Tomographie (MRT), Nuclear Magnetic Resonance Imaging (NMR). Technische und methodische Voraussetzungen zur Anwendung der Kernspintomographie am Hüftgelenk des Hundes.

The theoretical principles of nuclear magnetic resonance imaging and its application in human medicine are described. The most important parameters to produce informative images are explained. The tomographic examination of the canine hip joints demands a precise choice of section planes and measuring parameters. The resulting images of the hip joints of eight beagle puppies are evaluated and discussed.

[Further Helenanolides from the Flowers of Arnica chamissonis subsp. foliosa]. / Weitere Helenanolide aus den Blüten von Arnica chamissonis subsp. foliosa.

A phytochemical study of the flowers of ARNICA CHAMISSONIS Less. subsp. FOLIOSA (Nutt.) Maguire (Asteraceae) has resulted in the identification of a further 23 helenanolides. Six of them, 2alpha-hydroxy-6- O-angelicoyl-2,3-dihydrohelenalin ( 3B), 2alpha-hydroxy-6- O-senecioyl-2, 3-dihydrohelenalin ( 3C), 2alpha-hydroxy-6- O-tigloyl-2,3,11alpha,13-tetrahydrohelenalin ( 4A), 2alpha-hydroxy-6- O-isovaleryl-2, 3,11alpha,13-tetrahydrohelenalin ( 4D), 6- O-acetylchamissonolide ( 5C), and 4,6-di- O-acetylchamissonolide ( 5D), were isolated for the first time as natural compounds. Their structures were established by GLC-MS studies and IR, (1)H- and (13)C-NMR spectroscopy.

[Evaluating skin tolerance. Study of skin cleansing agents in modifications of the Duhring chamber test]. / Zur Problematik von Hautverträglichkeitsprüfungen. Untersuchung von Hautreinigungsmitteln in Modifikationen des Duhring-Kammer-Tests.

Towards Elucidation of the Problems of Skin-compatibility Testing/An investigation of hand-cleansing products using a modified Duhring chamber test The irritant potential of commercially available liquid syndets was investigated in a repetitive Duhring chamber test using a modified test procedure. Instead of regularly testing over a period of five days, the test was conducted only as long as it took for the first signs of irritation to appear. Among those products tested, substantial differences were found with respect to irritation and possible application time, and, as a result, to skin compatibility. Some of them produced skin irritation with the same intensity and just as quickly as the control substance, sodium lauryl sulfate (0.5%). These differences are not observed in a simple 24-hour epicutaneous test. For this reason, the latter, as opposed to the repetitive Duhring chamber test, appears to be unsuitable for comparative skin compatibility studies of syndets. The skin compatibility of special hand cleaners containing solvents was also investigated in a modified Duhring chamber test. In addition to the modification introduced above for the liquid syndets, here the maximum cumulative application time was reduced from 48 to 30 h. In this manner different degrees of skin compatibility to various special hand cleaners can be ascertained and taken into account when developing new products.

Sesquiterpenlactone aus Arnica chamissonis IV.1,2 Ivalin und andere Sesquiterpenlactone aus den Blütenkörbchen der Subspecies genuina.

The flowers of ARNICA CHAMISSONIS ssp. GENUINA afforded in addition to 8 helenanolides ivalin, the first eudesmanolide found in the genus ARNICA.

[Sesquiterpenlactone aus Arnica chamissonis].

From the flowers of Arnica chamissonis Less, sub-sp. foliosa (Nutt.) Maguire and its variety incana (Gray) Hulten two new naturally occuring pseudoguaianolides were isolated and their structures established by spectroscopic methods. They are shown to be 4-O-acetyl-6-desoxychamissonolide ( 3) and the propionylic ester of 11,13-dihydrohelenalin which was named arnicolide G ( 6).