ECG changes after rabbit coronavirus infection.

This study examines the electrocardiographic (ECG) changes following rabbit coronavirus (RbCV) infection. We have shown that infection with RbCV results in the development of myocarditis and congestive heart failure and that some survivors of RbCV infection go on to develop dilated cardiomyopathy in the chronic phase. Serial ECGs were recorded on 31 RbCV-infected rabbits. Measurements of heart rate; P-R interval; QRS duration; QTc interval; and P-, QRS-, and T-wave voltages were taken. The recordings were also examined for disturbances of conduction, rhythm, and repolarization. The acute and subacute phases were characterized by sinus tachycardia with depressed R- and T-wave voltages as well as disturbances of conduction, rhythm, and repolarization. In most animals in the chronic phase, the sinus rate returned to near-baseline values with resolution of the QRS voltage changes. The ECG changes observed during RbCV infection are similar to the spectrum of interval/segment abnormalities, rhythm disturbances, conduction defects, and myocardial pathology seen in human myocarditis, heart failure, and dilated cardiomyopathy. Because animals often died suddenly in the absence of severe clinical signs of congestive heart failure during the acute phase, RbCV infection may increase ventricular vulnerability, resulting in sudden cardiac death. RbCV infection may provide a rare opportunity to study sudden cardiac death in an animal model in which the ventricle is capable of supporting ventricular fibrillation, and invasive techniques monitoring cardiac function can be performed.

Electrocardiographic changes following rabbit coronavirus-induced myocarditis and dilated cardiomyopathy.

Rabbit Coronavirus (RbCV) infection was divided into two phases based upon day of death and pathologic findings. During the acute phase (days 2-5) heart weights (HW) and heart weight-to-body weight (HW/BW) ratios were increased with striking dilation of the right ventricle. These changes as well as increased dilation of the left ventricle were especially pronounced during the subacute phase (days 6-12). Myocytolysis, pulmonary edema, and degeneration and necrosis of myocytes, were seen during both phases. Myocarditis, pleural effusion, calcification of myocytes, and congestion in the liver and lungs were seen in the subacute phase. Electrocardiograms (ECGs) exhibited low voltage, nonspecific ST-T wave changes, sinus tachycardia, occasional ventricular and supraventricular premature complexes and 2(0) AV block consistent with myocarditis and heart failure. Forty-one percent of the survivors exhibited increased HW and HW/BW ratios, biventricular dilation, interstitial and replacement fibrosis, myocyte hypertrophy and myocarditis. ECGs exhibited nonspecific ST-T wave changes, sinus arrhythmia, occasional ventricular and supraventricular premature complexes and 2(0) AV block. These data suggest that RbCV infection may result in viral myocarditis and heart failure with a proportion of survivors progressing into DCM.

An experimental model for dilated cardiomyopathy after rabbit coronavirus infection.

A rabbit model for coronavirus-induced dilated cardiomyopathy is described. Acute rabbit coronavirus infection results in virus-induced myocarditis and congestive heart failure. Of the survivors of rabbit coronavirus infection, 41% had increased heart weight and heart weight-to-body weight ratios, biventricular dilation, myocyte hypertrophy, myocardial fibrosis, and myocarditis consistent with the development of dilated cardiomyopathy. These changes were also seen in the remaining 59% of the survivors, except that the degree of myocyte hypertrophy was reduced and only right ventricular dilation was present. In most survivors, myocarditis was usually mild (1-5 foci/transverse section), but in some cases it was severe (> 20 foci/transverse section). Interstitial and replacement fibrosis was more pronounced in the papillary muscles. These data suggest that rabbit coronavirus infection may progress to dilated cardiomyopathy.

Adenoid cystic carcinoma of Cowper's gland.

We report an additional case of primary adenoid cystic carcinoma of Cowper's gland in an otherwise healthy asymptomatic 66-year-old man. Based on a review of similar lesions presenting in the head and neck, our treatment plan entailed pelvic exenteration followed by radiation therapy. Whether adenoid cystic carcinoma of Cowper's gland behaves as aggressively as it does in the head and neck remains unclear. However, in view of the extensive local invasion in our patient and a previously successful outcome, a combined surgical and radiation approach appears to be the most appropriate therapy.

An experimental model for myocarditis and congestive heart failure after rabbit coronavirus infection.

In a model for virus-induced myocarditis and congestive heart failure, rabbit coronavirus infection was divided into acute (days 2-5) and subacute (days 6-12) phases on the basis of day of death and pathologic findings. During the acute phase, the principal histologic lesions were degeneration and necrosis of myocytes, myocytolysis, interstitial edema, and hemorrhage. The severity of these changes increased in the subacute phase. Pleural effusion and congestion of the lungs and liver were also present at this time. Myocarditis was detected by day 9 and peaked by day 12. Heart weights and heart weight-to-body weight ratios were increased, and dilation of the right ventricular cavity became prominent early in infection and persisted. In contrast, dilation of the left ventricle occurred late in the subacute stage. Virus was isolated from infected hearts between days 2 and 12. These data suggest that rabbit coronavirus infection progresses to myocarditis and congestive heart failure.

Relatedness of rabbit coronavirus to other coronaviruses.

Rabbit coronavirus (RbCV) was apparently first encountered in 1961 when Scandinavian investigators observed occasional mortality in rabbits used to propagate the Nichols strain of Treponema pallidum. Mortality rates reached 50 percent by 1968 and 75 percent by 1970. Contaminated samples of T. pallidum were brought to the Johns Hopkins University School of Medicine, a World Health Organization center for the study of treponematoses. There it was established that the causative agent was filterable, the heart was the target organ, and the agent was determined by electron microscopy to be a coronavirus. Also, complement fixing antibodies to the human coronaviruses 229E (two way cross) and 0C43 (one way cross) were demonstrated in surviving rabbits. Immunofluorescent staining with anti-229E serum localized fluorescence in the interstitial tissue of the myocardium. Antiserum to RbCV cross reacted with coronaviruses of three other diseases, feline infectious peritonitis (FIPV), canine coronavirus diarrhea (CCV), and transmissible gastroenteritis (TGEV) by radioimmunoassay. In plaque neutralization tests, a slight reduction was observed against TGE and CCV but not against FIP. Antiserum to 229EV, CCV, FIPV and to a lesser degree TGEV partially blocked the clinical course of the disease and reduced mortality. Slight protection was afforded rabbits by vaccination with, in descending order of survivors, CCV, FIPV, and TGEV. Vaccination with calf diarrhea coronavirus (CDCV) provided no protection.

Similarities and differences in behaviour between mentally handicapped and normal preschool children during play.

When 12 normal preschool children and 12 mentally handicapped children of similar mental age were individually observed during peer group play, more similarities than differences were found in the incidence of 28 behaviours. However, the behaviours for which significant differences were found included those likely to be most relevant to social acceptance. Mutual social involvement of normal and handicapped children during integrated play may require not only attention to the constitution of the group but also manipulation of the conditions and environment.

Clinical manifestations of mousepox in an experimental animal holding room.

A study of the clinical aspects of mousepox was conducted during the 1979-80 outbreak at the National Institutes of Health. The disease was detected serologically in a room located adjacent to the index room. The index room received animals prior to this outbreak from a noncommercial colony which later was found to be infected with mousepox. The infection was present in the room for at least 6 weeks prior to the completion of the study. The paucity of clinical signs and low mortality were striking when compared to previous descriptions of mousepox in the United States. Only 27 of the 939 mice in the room were infected, and only one of these had typical skin lesions. A few of the mice had non-specific signs such as ruffled hair coat and hunched appearance. Minimal spread of the disease was evidenced by clustering of infected cages on one of five animal racks in the room.

Prevention and control of mousepox.

The prevention and control of mousepox begins with investigators being aware of the disease's existence and its serious nature for users of mice and mouse tissues. Every institution must include as part of its management policy, provisions to ascertain that mice and mouse tissues entering its facilities are free of ectromelia virus. Policy must encompass the entire institution, be clearly stated, and must be workable. The provisions of this policy include the establishment of a disease surveillance program which actively searches for disease or virus in incoming mice and mouse tissues from untested sources. Complete records of receipts of animals and animal tissues must be maintained. There must be open and honest communication among investigators concerning the presence of mousepox (and other diseases) in their mice and tumors. Decisions must be based on accurate information. The elimination of mousepox within an institution may be difficult, and a single plan applicable to all situations cannot be given. However, the basics of all control measures include the following: recognition that mousepox represents an institutional problem, not the problem of only a single or a few investigators; rapid notification of all investigators involved, including those who may have received infected mice; confirmation of the diagnosis and notification of the scientific community of the disease's existence. Strategies for dealing with mousepox depend on the nature of the mice infected. Euthanasia of mice which can be replaced and vaccination of extremely valuable breeding stock are suggested.

Subclinical scurvy in the guinea pig.

Twenty-eight guinea pigs from nine episodes of subclinical scurvy had diarrhea, weight loss and dehydration. The classical signs of scurvy were not seen. Microscopically the epiphyses were attenutated and irregular. The amount of osteoid was less than normal. Many guinea pigs had acute enteritis. In some there were many hemosiderin-laden macrophages in the intestinal lamina propria. All episodes were associated with either autoclaving food without adequate supplementation or other inadequate feed management practices.

Rabbit cardiomyopathy associated with a virus antigenically related to human coronavirus strain 229E.

A new disease of rabbits is described. Following an acute febrile course, animals die or recover by the 11th day postinoculation. The characteristic pathologic finding is multifocal myocardial degeneration and necrosis. The disease can be transmitted by various routes with tissue filtrates or with infectious sera diluted to 10(-6) and passed through 0.1 micron filters. Virus particles with morphologic features characteristic of a coronavirus are present in infectious but not in normal rabbit serums. The antigen(s) in the infectious serums cross-reacts with the 229E and the OC43 strains of human coronavirus. Antigen cross-reacting with the 229E virus is detectable by immunofluorescent staining in frozen sections of heart tissue from sick but not from healthy animals. Animals surviving infection seroconvert to coronavirus specificity, as demonstrated by the presence in convalescent serums of antibody capable of reacting with the 339E virus. Susceptibility to infection has not been demonstrated in mice, hamsters, or guinea pigs, and the virus was not adapted for growth in tissue culture. It is uncertain whether the agent is a natural pathogen of rabbits or a coronavirus contaminant from another species, possibly human. The name rabbit infectious cardiomyopathy is suggested for this disease.