Treatment of ocular squamous cell carcinomas in cattle with interleukin-2.

In total, 174 bovine ocular squamous cell carcinomas of varying sizes (20 to 2800 mm(2) in area) were treated daily with peritumoural injections of solvent, or solvent containing 5000 U, 20,000 U, 200,000 U, 500,000 U, 1 million U or 2 million U interleukin-2 (IL-2) for 10 days. The tumours were measured and clinically staged before treatment and at one, three, four, nine and 20 months after treatment. After 20 months, 14 per cent of the tumours treated with the solvent had regressed completely, a significantly smaller proportion than the 55 per cent treated with 5000 U IL-2, 52 per cent treated with 20,000 U IL-2, 58 per cent treated with 200,000 U IL-2, 50 per cent treated with 500,000 U IL-2, 69 per cent of tumours treated with 1 million U IL-2, 52 per cent treated with 2 million U IL-2. The tumours on the third eyelid and limbus were the most responsive.

Low doses of interleukin-2 can cure large bovine ocular squamous cell carcinoma.

Four cows bearing large Ocular Squamous Cell Carcinomas (BOSCC) were treated by 10 intratumoral injections (Monday-Friday for 2 consecutive weeks) of 200,000 U Interleukin-2 (Cetus). Tumors regressed in 2 out of 4 cases. This result shows that even large tumors may regress after local IL-2 treatment.

Hereditary cancer and its clinical implications: a view.

In hereditary cancers the responsible inherited cancer genes are defective (mutated) anti-oncogenes (tumour suppressor genes). This inherited mutation is present in all cells of the organism, and only leads to cancer if in a somatic cell a complete set of specific cancer mutations is accumulated. Since one defective anti-oncogene has been inherited, only three additional somatic cancer mutations are required, according to our previously published view (Anticancer Res 10:1990). The number of de novo arising tumour cells in such a person is thus multiplied by a factor equal to the reverse of the mutant frequency, that is about 10(4)-10(5). This can be observed e.g. in retinoblastoma. Mutations occur in proliferating cells only. Consequently cancer mutations also depend on cell proliferation. If an inherited cancer mutation predisposes to cancer formation in certain organs, then the cancer risk in these organs is enhanced by 10(4)-10(5) times. Tumours in these organs will appear simultaneously if the number of cells and the growth kinetics are similar. This is of course observed in paired organs, like the retina and the female breast. In cancer family syndromes different organs may be affected at the same time. Examples are type I and type II cancer family syndrome and multiple endocrine neoplasia type 1 2a, and 2b. The secondly diagnosed tumours are not caused by metastatic spread. Tumours in two organs will arise at difference times if the number of end cells per organ and the growth kinetics differ. In this case the second tumour is called a second primary malignancy and is not caused by metastatic spread. A good example are the second primary malignancies in hereditary retinoblastoma. The inherited defective anti-oncogene is a recessive gene. This defective inherited gene causes a 10(4)-10(5) fold increase of the normal tumour incidence. This means that nearly always one or more tumours will arise. Evidently, this pattern of inheritance has led to the erroneous conclusion that the genetic abnormality is dominant at the level of the chromosome. The 10(4)-10(5) times enhanced tumour incidence in hereditary cancer is helpful for the clinical recognition of hereditary cancer. That is, hereditary cancer can be recognized not only by family history, but also by early occurrence, the multifocal and bilateral localisation, its occurrence as cancer family syndrome or by second primary malignancies. It is thus recommended to screen patients and families with hereditary cancer for first and second primary tumours. Treatment of patients with hereditary tumours requires extra care to avoid additional cancer mutations.(ABSTRACT TRUNCATED AT 400 WORDS)

Phenotypic characterization of Zimbabwean isolates of Pasteurella multocida.

The phenotypic characteristics of 60 Zimbabwean isolates of Pasteurella multocida sensu stricto, from disease syndromes in different host species were studied. A number of representative strains were also serotyped. Consistent results were obtained in the tests for; catalase, oxidase, urease, indole, acid in glucose, inositol, salicin and sucrose. There was no obvious relationship between serotype, host or disease and the pattern of utilization of certain substrates by an isolate. This has been discussed in the context of recent proposals to reclassify Pasteurella and P. multocida on genotypic and phenotypic studies. It is suggested that notwithstanding the relevance of genetic studies in circumscribing P. multocida, the phenotype and disease significance of the taxon should not be ignored. A case of bronchitis in a dog which was simultaneously colonized by three different strains of Pasteurella is described. Also septicaemic pasteurellosis in a Nile crocodile (Crocodylus niloticus) is reported and for the first time prevalence of various serotypes in pasteurellosis of animals in Zimbabwe.

Phenotype and serotype of Pasteurella multocida isolates from diseases of dogs and cats in Zimbabwe.

A variety of disease manifestations, comprising skin bite wounds, pyothorax, respiratory and genitourinary tract infections, in 202 dogs and cats presented to the University Clinic, were investigated for the presence of Pasteurella multocida. Of these, 25-42% of various cases (69) were found to be infected with P. multocida. P. multocida-associated respiratory tract infections were more common than bite wounds or genitourinary tract infections. The regimen of treatment consisted of those antibiotics, sensitivity to which had been confirmed in vitro. Following detailed characterization of the isolates of P. multocida, in order to assign them to the reclassified taxa of Pasteurella, a preponderance of P. multocida subspecies multocida and septica were recorded. There did not appear to be a correlation between the reclassified taxa and their serotypes. Certain strains of different species or subspecies belonged to a common serotype and vice versa. However, the strains which were serotyped belonged to capsular type A, except for a solitary isolate from a cat which was capsular type D. Type D is known to cause atrophic rhinitis and does not appear to have been isolated either from a dog or a cat. Two strains, one from a dog and another from a cat, were identified as group EF-4 bacteria. This group of organisms has been incriminated in human wounds resulting from dog/cat bites, and has so far not been reported in Africa. Three different species, P. stomatis, P. dagmatis and P. multocida subspecies multocida were simultaneously isolated from a case of chronic bronchitis in a dog. There was no evidence of any relationship between disease manifestation in a host and the isolation of a particular taxon of Pasteurella, except that P. canis and Pasteurella taxon 16 were only isolated from dogs.

Antitumor effect of locally injected low doses of recombinant human interleukin-2 in bovine vulval papilloma and carcinoma.

In many human clinical trials and in various animal tumor models, the antitumor effect of high doses of systemically applied interleukin-2 (IL-2) is tested. Our studies focused on the effects of low doses of locally injected IL-2. In this paper, the effect of local injection of low doses of IL-2, i.e. a total dose of 25,000-50,000 units, into papillomas or carcinomas of the bovine vulva is described. In 19 out of 23 (83%) cows treated with IL-2 an effect on the tumor load was observed; in three of these animals, complete regression was obtained. In the majority of cases, regression was not restricted to the tumors injected with IL-2.

Toxocara vitulorum in beef calves kept on effluent-irrigated pastures in Zimbabwe.

Faeces from 20 calves aged 13 +/- 5 days were examined for Toxocara vitulorum eggs fortnightly for a period of 20 weeks. The age of calves when eggs were first detected varied from 24 to 110 days (mean 41 +/- 20 days). The mean egg count varied from 257 to 19,821 g-1 of faeces with a highest count of 68,400. The patency period of T. vitulorum lasted from 14 to 112 days (mean 65 +/- 30 days). None of the calves showed clinical signs of illness.

Local low-dose IL-2 therapy.

Interleukin-2 (IL-2) is a powerful drug for treating cancer. However, it is only powerful if it is properly applied. That is, IL-2 should be applied at the tumor site, because at the transition of normal and malignant tissue are the tumor infiltrating cells. These should be activated by IL-2. Local application implies that IL-2 can be used in relatively low doses. It is becoming clear that even a single injection of IL-2 can cure cancer. IL-2 can also enhance the therapeutic effects of irradiation and Cisplatin. Locally applied IL-2 therapy is virtually non-toxic.

Metastatic malignant mesothelioma in a dog.

A case of malignant mesothelioma in a 5 1/2-year-old St Bernard dog is described. The distribution of the neoplasm was to the pericardium and peritoneum and not the pleura. Distant metastases were found in the bronchial lymph node and bone marrow.

Mycoplasma ovipneumoniae infection in Zimbabwean goats and sheep.

The prevalence of Mycoplasma ovipneumoniae (MO) in three Communal Lands flocks of goats on the outskirts of Harare is described. In a single sampling of nasal swabs from 172 randomly selected, apparently healthy goats, 112 animals were identified as carriers of MO. The three flocks had a history of occasional deaths, following chronic and subacute pneumonia associated with isolation of MO as the only identifiable pathogen. Attempts to induce clinical pneumonia in groups of 6 to 8-week-old kids and lambs with local isolates of MO were not successful. However, MO was consistently cultured from the trachea, lungs, lymph node and thymus of some test animals. Cuffing interstitial pneumonia was also observed in these animals. Infection of the thymus occurred; this has not previously been reported with any Mycoplasma sp. The animals did not produce detectable serum antibodies to MO nor were they reactive to MO antigen in a tuberculin-type hypersensitivity test. The possibility that a state of immunotolerance may have been responsible for failure to develop clinical pneumonia is discussed.

Concurrent systemic cryptococcosis and haemangiosarcoma in a dog.

A young dog with progressive neurological signs was humanely killed by the injection of barbiturate for postmortem examination. Lesions in the nose, lung, pancreas, lymph nodes, kidneys and the meninges were heavily infiltrated with Cryptococcus neoformans. In addition, haemangiosarcoma was detected in the right atrium. The finding of systemic mycosis and neoplasia together in a young dog suggests an immunosuppressed state.

Ocular squamous cell carcinoma in Simmental cattle in Zimbabwe.

In Zimbabwe, ocular squamous cell carcinoma (OSCC) was frequently observed in 5 breeding herds of Simmental cattle, a Bos taurus breed originating from Switzerland. In these herds, initial signs of OSCC were already noticeable in cattle about 3 years old. Gradually, OSCC prevalence increased, and 36 to 53% of cattle over 7 years old had 1 or more tumors. More tumors developed in Simmental cattle with periorbital white skin than in cattle with periorbital pigmented skin. Other breeds of cattle (eg, Friesian) also are partly white-faced and live in Zimbabwe in a comparable environment; yet, OSCC prevalence was lower in those breeds.

Efficacy of SAD (Berne) rabies vaccine given by the oral route in two species of jackal (Canis mesomelas and Canis adustus).

Eight black-backed jackals (Canis mesomelas) and seven side-striped jackals (Canis adustus) were given SAD (Berne) rabies vaccine by direct oral instillation. Three different vaccine doses were used: 10(6.3), 10(6.8) and 10(7.5) median tissue culture infectious doses. Two additional jackals were given vaccine in chicken heads. One group of jackals was challenged with a lethal dose of jackal-derived rabies virus 1 mo after vaccination and a second group 12 mo after vaccination. All 17 vaccinated jackals developed high and persistent serum neutralizing antibody titers. All challenged jackals resisted a lethal dose of rabies virus, whereas three control jackals given the same challenge succumbed to rabies.

The epidemiology of rabies in Zimbabwe. 1. Rabies in dogs (Canis familiaris).

The epidemiology of rabies in dogs in Zimbabwe is described using data from 1950, when rabies was re-introduced after a 37-year absence, to 1996. Dogs constituted 45.7% of all laboratory-confirmed rabies cases and were the species most frequently diagnosed with the disease. Slightly more cases were diagnosed from June to November than in other months. From 1950 to the early 1980s, most dog cases were recorded from commercial farming areas, but since the early 1980s most have been recorded from communal (subsistence farming) areas. This change appears to be due to improved surveillance in communal areas and not to any change in the prevalence of rabies. Dog rabies therefore appears to be maintained mainly in communal area dog populations, particularly the large communal area blocks. Urban rabies was not important except in the city of Mutare. Where dog rabies prevalence was high, the disease was cyclic with periods between peak prevalence ranging from 4-7 years. Dog rabies cases were, on the whole, independent of jackal rabies and rabies in other carnivores. There was a significant negative relationship between the annual number of rabies vaccine doses administered nationally to dogs and the annual number of dog rabies cases lagged by one year, indicating that the past levels of immunisation coverage have had a significant effect on the number of rabies cases. However, dog vaccination coverage has clearly not been adequate to prevent the regular occurrence of rabies in dogs.

The epidemiology of rabies in Zimbabwe. 2. Rabies in jackals (Canis adustus and Canis mesomelas).

The epidemiology of rabies in Canis adustus (the side-striped jackal) and Canis mesomelas (the black-backed jackal) in Zimbabwe is described using data collected from 1950-1996. Cases in the two species made up 25.2% of all confirmed cases, second only to domestic dogs. Since the species of jackal cases was not recorded on rabies submission forms, the country was divided into areas according to species dominance and jackal cases were assigned to either C. adustus or C. mesomelas dominant zones or a sympatric zone where the relative status of the species is not known. Jackal rabies in both species is maintained in the commercial farming sector. Jackal rabies in the C. adustus zone occurs as dense epidemics, which begin at a single focus and spread centrifugally. The foci were initiated by rabid dogs, but once initiated the epidemic is maintained by C. adustus independently of other species. The extent of outbreaks in the C. adustus zone was limited by geographical (landuse type and jackal species interface) boundaries. Jackal rabies in C. adustus zones showed two seasonal peaks with the main peak occurring during late summer and the second peak during winter. In the C. mesomelas zone jackal rabies was more sparse but it occurred during most years. C. mesomelas is also able to maintain rabies independently of other species, although the epidemiology of the disease in this species is unclear. Transmission of rabies cycles between the two jackal species zones does not appear to occur as epidemics terminate when crossing the C. adustus and C. mesomelas interface boundaries.

Biochemical and haematological values in abattoir pigs with and without subclinical lesions.

The biochemical and haematological profiles of 379 pigs with or without various gross pathological lesions in an abattoir in Zimbabwe were studied to see whether there were any differences between the levels of haematological and biochemical values, and health status (with and without pathological lesions). On the basis of observable gross pathology, 134 pigs were classified as having one or more subclinical lesions (liver milk spot, pneumonia, pleurisy, pericarditis, abscesses and arthritis). Seventy-six of these were males and 58 females. There were observable sex differences in the mean haematological and biochemical values obtained. Erythrocyte counts showed significant differences in mean values (P < 0.05) among groups of pigs found with various pathological lesions. The biochemical values showed significant group differences for ALP, ALT, AST, and LDH.

Repair of a diaphragmatic hernia in a horse.

One month after falling heavily a four-year-old horse developed acute colic while being exercised. A tentative diagnosis of diaphragmatic hernia was reached on the basis of the clinical findings and confirmed at laparotomy. The defect was repaired and the horse made an uneventful recovery.

Naturally occurring tetracycline-like fluorescence in sections of femur from jackals in Zimbabwe.

In assessing the potential of the tetracycline compounds as biomarkers in oral rabies vaccination campaigns in jackals in Zimbabwe, the natural prevalence of fluorescent compounds in bone tissue from jackals was investigated. Femur samples were taken from unbaited jackals received for routine rabies diagnosis, and thin undecalcified sections were cut and viewed under an ultraviolet microscope. Of 131 femur samples examined, 49 (37 per cent) had fluorescent markings indistinguishable from those of tetracycline. The result implies that the tetracycline compounds, which are commonly used in rabies baiting campaigns in Europe and North America, cannot be used as biomarkers in jackals in Zimbabwe.

Intrahepatic cholestasis in a dog: a clinicopathological study.

The paper describes a case of jaundice in a three-year-old bassett hound. The illness was accompanied by hyperbilirubinaemia and raised serum levels of alkaline phosphatase and glutamic pyruvic transaminase, indicating the presence of both biliary obstruction and hepatocellular damage. Examination of liver biopsies on two occasions showed intrahepatic cholestasis and mild inflammatory change. The dog was treated with corticosteroid. The jaundice regressed after three months, hepatic functions returned to normal and the dog recovered. The cause of the jaundice was not determined.

A baiting system suitable for the delivery of oral rabies vaccine to dog populations in Zimbabwe.

A baiting system suitable for the delivery of oral rabies vaccine to dog populations in developing countries was studied in Zimbabwe. In a field trial, 369 sponge baits containing a placebo liquid, rhodamine B as a biomarker and a pungent attractant were distributed over an area of 60 sq km in a communal land in Manicaland with a dog population of over 500. Twenty-four hours later 21 per cent of the baits were recovered and 79 per cent of these had been significantly bitten or chewed. Twenty-five per cent of the dogs examined showed evidence of superficial staining by rhodamine B indicating that they had chewed baits or ingested their contents. It was concluded that the system would deliver an oral vaccine to dog populations more efficiently than had been the case in comparable studies in wildlife populations, but that the number of baits per unit area should in future studies be increased.