To support the licensure of a new and safer vaccine to protect people against smallpox, a monkeypox model of infection in cynomolgus macaques, which simulates smallpox in humans, was used to evaluate two vaccines, Acam2000 and Imvamune, for protection against disease. Animals vaccinated with a single immunization of Imvamune were not protected completely from severe and/or lethal infection, whereas those receiving either a prime and boost of Imvamune or a single immunization with Acam2000 were protected completely. Additional parameters, including clinical observations, radiographs, viral load in blood, throat swabs, and selected tissues, vaccinia virus-specific antibody responses, immunophenotyping, extracellular cytokine levels, and histopathology were assessed. There was no significant difference (P > 0.05) between the levels of neutralizing antibody in animals vaccinated with a single immunization of Acam2000 (132 U/ml) and the prime-boost Imvamune regime (69 U/ml) prior to challenge with monkeypox virus. After challenge, there was evidence of viral excretion from the throats of 2 of 6 animals in the prime-boost Imvamune group, whereas there was no confirmation of excreted live virus in the Acam2000 group. This evaluation of different human smallpox vaccines in cynomolgus macaques helps to provide information about optimal vaccine strategies in the absence of human challenge studies.
Squamous cell carcinoma of the vulva is a disease of significant clinical importance, which arises in the presence or absence of human papillomavirus. We used comparative genomic hybridisation to document non-random chromosomal gains and losses within human papillomavirus positive and negative vulvar cancers. Gain of 3q was significantly more common in human papillomavirus-positive cancers compared to human papillomavirus-negative cancers. The smallest area of gain was 3q22–25, a chromosome region which is frequently gained in other human papillomavirus-related cancers. Chromosome 8q was more commonly gained in human papillomavirus-negative compared to human papillomavirus-positive cancers. 8q21 was the smallest region of gain, which has been identified in other, non-human papillomavirus-related cancers. Chromosome arms 3p and 11q were lost in both categories of vulvar cancer. This study has demonstrated chromosome locations important in the development of vulvar squamous cell carcinoma. Additionally, taken together with previous studies of human papillomavirus-positive cancers of other anogenital sites, the data indicate that one or more oncogenes important in the development and progression of human papillomavirus-induced carcinomas are located on 3q. The different genetic changes seen in human papillomavirus-positive and negative vulvar squamous cell carcinomas support the clinicopathological data indicating that these are different cancer types.
British Journal of Cancer (2002) 86, 924–928. DOI: 10.1038/sj/bjc/6600112 www.bjcancer.com
© 2002 Cancer Research UK
comparative genomic hybridisation; vulva; neoplasm; squamous cell carcinoma; human papillomavirus
Genetic changes orchestrated by human papillomaviruses are the most important known factors in carcinogenesis of the uterine cervix. However, it is clear that additional genetic events are necessary for tumour progression. We have used comparative genomic hybridization to document non-random chromosomal gains and losses within a subset of 37 cervical carcinomas matched for clinical stage Ib, but with different lymph node status. There were significantly more chromosomal changes in the primary tumours when the lymph nodes were positive for metastases. The most frequent copy number alterations were loss of 3p, 11q, 6q and 10q and gain of 3q. The smallest areas of loss and gain on chromosome 3 were 3p14–22 and 3q24–26. The study identifies progressive DNA copy number changes associated with early-stage invasive cervical cancers with and without lymph node metastases, a factor of potential prognostic and therapeutic value. © 2000 Cancer Research Campaign http://www.bjcancer.com
comparative genomic hybridization; cervix cancer; lymph node metastasis; human papillomavirus
Cardiopulmonary function was assessed in healthy cats premedicated with intramuscular acepromazine, meperidine, atropine combination (premix), followed by induction and maintenance with intravenous thiopental for 30 min. Cardiac output by thermodilution, heart rate, blood pressure and blood gas analysis were evaluated over 120 min. A minor degree of respiratory depression was noted in the cats. Cardiac index (cardiac output/kg) was significantly depressed following thiopental induction and for the entire 120 min studied. Stroke volume was significantly reduced after premix administration and for 90 min posthiopental induction. No significant change in heart rate, systemic vascular resistance or blood pressure was observed. Significant cardiovascular depression was produced by the premedicant, and this persisted following thiopental anesthesia.
Cardiopulmonary function was assessed in healthy cats given a xylazine-ketamine hydrochloride combination intramuscularly. Cardiac output, heart rate, stroke volume and cardiac index were significantly decreased. Systolic, diastolic and mean arterial blood pressure were also significantly decreased. Systemic vascular resistance and central venous pressure were significantly increased. Blood gas values remained stable. In conclusion, significant cardiovascular depression was noted in normal cats given the xylazine-ketamine combination at the dosages listed.
Heart sound recordings were taken from cats. The heart sounds were recorded directly from the chest wall and through an esophageal tube. The phono transducer and the esophageal tube were both placed over the base of the heart. Ultrasound M-mode, or motion-mode, recordings were taken to study the mitral valve dynamics. After analogue to digital conversion, electrocardiogram gated first heart sounds of each phono record were analyzed by the fast Fourier transform to obtain a frequency spectrum. Relative energies in 15 Hz bandwidths up to 150 Hz were correlated with the mitral valve closing velocity of the anterior mitral leaflet, obtained from the M-mode echocardiograms. The closing velocity correlated best with the energy in the 30-45 Hz bandwidth and 60-75 Hz bandwidth for the externally and internally monitored phonocardiogram respectively. The chest wall acted as a low pass filter, that is, the wall favoured the transmission of low frequencies and the energy transmitted decreased as wall thickness increased.
The prevalence of gross and/or histological cardiac lesions was found to be much greater in Doberman pinscher dogs (16/26 or 62%) than in non-Doberman dogs (124/417 or 30%). At least some of the affected Dobermans were unrelated. Middle aged (mean age 4.7 yr) Dobermans of both sexes (11 M:5F) were affected. Four of the Dobermans with heart lesions had congestive cardiomyopathy; three of these four had congestive heart failure and the other one died suddenly. Prominent gross lesions were ventricular dilation and atrioventricular valvular endocardiosis. Histological lesions noted were prominent myocardial fibrosis, myofiber degeneration with fatty replacement, myofiber vacuolation and arterial intimal cushion formation. A spectrum of myocardial disease exists in Dobermans and clinically overt congestive cardiomyopathy represents one end of this spectrum.
The response of the heart to disease can be detected by assessing myocardial electrical activity. The electrocardiograph is a useful diagnostic tool which is widely available to the veterinary clinician. However, interpretation of the tracing often requires considerable experience.
Regularly, electrocardiograms (ECG) of clinical cases will appear in this column. Each tracing will be preceeded by the history and the pertinent ancillary data. Interpretation and discussion of the ECG will follow. The purpose of this column is to present clinicians with examples of common electrocardiographic abnormalities.
Left ventricular echocardiographic parameters in cats were recorded, measured and analyzed to study the effects of a combination of xylazine and sodium pentobarbital on left ventricular function. The depressant effects of a combination of xylazine and sodium pentobarbital on the left ventricular dimension at end diastole, the percent change in minor diameter and the velocity of circumferential fibre shortening were compared to echocardiographic values of unanesthetized cats. No change in heart rate was noted. Stroke volume and cardiac output were depressed.
A technique for the determination of cardiac output in the cat by the thermal dilution method is described. The values of cardiac output assessed by thermal dilution and the values of left ventricular function assessed echocardiographically are compared. Values of cardiac output obtained by thermal dilution compare favourably with values obtained by other investigators by indicator dye dilution, the Fick method and electromagnetic flowmeter technique. The technique of thermal dilution in the cat was consistent and simple to perform. The calculation of ventricular volumes and cardiac output echocardiographically using formulae suggested in man was unsuccessful. Such formulae based on assumptions of cardiac shape and contractility do not appear valid in the cat. Statistical analysis demonstrated a positive correlation between the cardiac output determined by thermodilution and the left ventricular diastolic and systolic dimensions determined echocardiographically. A positive correlation was also shown between the cardiac output and the cardiac index, the left ventricular diastolic dimension and the left ventricular systolic dimension and the percent change in minor diameter and the velocity of circumferential fibre shortening. A negative correlation existed between the left ventricular systolic dimension and the velocity of circumferential fibre shortening and the ejection time and the velocity of circumferential fibre shortening.
Echocardiography is the accepted term for the study of cardiac ultrasound. Although a relatively new tool for the study of the heart in man it has already found wide acceptance in the area of cardiac research and in the study of clinical cardiac disease. Animals had often been used in the early experiments with cardiac ultrasound, but only recently has echocardiography been used as a research and clinical tool in veterinary medicine. In this report echocardiography is used in the research of anesthetic effects on ventricular function and clinically in the diagnosis of congestive cardiomyopathy in a cat, ventricular septal defect in a calf, and pericardial effusion in a dog. Echocardiography is now an important adjunct to the field of veterinary cardiology.
Echocardiographic parameters were recorded, measured and statistically analyzed on a population of normal cats under pentobarbital anesthesia. Results of the study are similar to those obtained by previous investigators. However, this investigation demonstrates the depressant effect of pentobarbital anesthesia on cardiac contractility and the percent change in the left ventricular minor diameter. Analysis by correlation indices shows a positive relationship between the left ventricular diastolic and systolic dimensions, the left ventricular diastolic dimension and the E to F slope of the anterior mitral valve, the left ventricular systolic dimension and the E to F slope, the percent change in left ventricular minor diameter and the velocity of circumferential fibre shortening of the left ventricle and the left atrial dimension and body weight. A negative correlation exists between the left ventricular dimension at systole and the percent change in minor diameter of the left ventricle and the velocity of circumferential fibre shortening.
Patent ductus arteriosus is the most common shunting congenital cardiac anomaly in the cat. If it is treated surgically, early in the course of the disease, the prognosis is good.
A standardised behaviour rating scale, the Shortened Stockton Rating Scale, was completed by care staff for each of 903 residents in old people's homes. In an attempt to validate the four subscales suggested by the authors of the published scale, the data were subjected to factor analysis. The results indicate the existence of three factors reflecting physical, mental, and social impairment. They offer only partial support for the published subscales and the need for such scales to be validated on the intended target population is discussed.
The clinical, pathological and virological findings in puppies affected with myocarditis are reported. A parvo-like virus was isolated from pooled heart specimens, which is similar to the virus isolated from gastroenteritis cases.
Phenobarbital was administered orally to seven healthy cats at a dose of 5 mg/kg once a day for 21 days. Serum phenobarbital concentrations were determined using a commercial immunoassay technique. A one-compartment model was used to describe the final elimination curve. The elimination half-life (t1/2 b) after the final day of treatment was 43.3 +/- 2.92 h. The large apparent volume of distribution of 695.0 +/- 43.9 mL/kg suggests that the drug was widely distributed within the body. The t1/2 b following multiple oral administration was significantly shorter than previously reported for a single oral dose of phenobarbital in the cat. Analysis of pharmacokinetic results after days 1 and 21 of treatment suggested that the elimination kinetics of phenobarbital did not change significantly with multiple oral administration. It appears that differences in elimination kinetics can exist between populations of cats. These differences emphasize the need for individual monitoring of cats receiving phenobarbital.
Phenobarbital was administered to eight healthy cats as a single intravenous dose of 10 mg/kg. Serum phenobarbital concentrations were determined using an immunoassay technique. The intravenous data were fitted to one-, two- and three-compartment models. After statistical comparison of the three models, a two-compartment model was selected. Following intravenous administration, the drug was rapidly distributed (distribution half-life = 0.046 +/- 0.007 h) with a large apparent volume of distribution (931 +/- 44.8 mL/kg). Subsequent elimination of phenobarbital from the body was slow (elimination half-life = 58.8 +/- 4.21 h). Three weeks later, a single oral dose of phenobarbital (10 mg/kg) was administered to the same group of cats. A one-compartment model with an input component was used to describe the results. After oral administration, the initial rapid absorption phase (absorption half-life = 0.382 +/- 0.099 h) was followed by a plateau in the serum concentration (13.5 +/- 0.148 micrograms/mL) for approximately 10 h. The half-life of the terminal elimination phase (76.1 +/- 6.96 h) was not significantly different from the half-life determined for the intravenous route. Bioavailability of the oral drug was high (F = 1.20 +/- 0.120). Based on the pharmacokinetic parameters determined in this study, phenobarbital appears to be a suitable drug for use as an anticonvulsant in the cat.