Cytotoxic chemotherapy: new players, new tactics

Veterinary clients often seek the same new and innovative cancer treatment options for their companion animals that they read about in the press or on the Internet. It is, therefore, necessary for the practitioner to have an understanding of the development of new and innovative cytotoxic drugs and delivery techniques. This article describes the drug development process and how a new product eventually finds its way into clinical use. Some of the newer drugs and delivery techniques applied to small animals are reviewed.     

Excretion and residues of the herbicides benzoylprop-ethyl flamprop-isopropyl and flamprop-methyl in cows,pigs and hens

Two wild oat herbicides, benzoylprop-ethyl and flamprop-methyl were administered to lactating cows at low dose levels (0.3–3.0 mg/kg in total diet) and the excretion of total metabolites in milk, urine and faeces was measured. Total residues in tissues were also determined. Similarly a third and related herbicide flamprop-isopropyl was fed to cows, pigs and hens (at 0.5 mg/kg in total diet) and the residues were determined in excreta and tissues, including eggs. The amounts of the compounds fed were equivalent to approximately 10–300 times the total residue found in cereal treated in the field. Residues in milk in most cases were well below 0.001 mg/kg; in muscle samples <0.003 mg/kg; and in eggs, 0.0008 mg/kg, decreasing by 50% in approximately 3 days to 0.0001 mg/kg 4 days after the termination of treatment. Elimination of the herbicides from the animals was rapid in every case and this, together with the low residue levels, was attributed to very efficient metabolic de-esterification to the parent carboxylic acid metabolites (benzoylprop and flamprop). These metabolites possess physical properties ideally suited for excretion via the kidneys and bile into urine and faeces and, conversely, unsuited for transport into milk and eggs.     

The successful use of work oxen in agricultural development of tsetse infested land in Ethiopia

Summary For the past five years a herd of work oxen, now numbering some 450 individuals, has been maintained under the protection of trypanocidal drugs on a settlement scheme in an area of western Ethiopia infested with tsetse. This paper describes the environmental conditions and the epizootiology of trypanosomiasis in the oxen and in the vector, Glossina morsitans. It is concluded that with the strategic use of drugs, oxen can be kept alive and perform useful agricultural work, in areas of high tsetse challenge, provided reasonable standards of veterinary supervision and management are maintained.

---

El Uso Exitoso De Bueyes En El Desarrollo Agricola De Tierras Infestadas De Tsetse En Etiopia

Resumen Se ha mantenido un número aproximado de 450 bueyes, bajo el efecto de drogas contra la tripanosomiasis (quimioprofiláxis), en una concentración rural bajo el flagelo de la mosca tsetse, en el oeste de Etiopía. Este trabajo describe las condiciones ambientales y epizootiológicas de la tripanosomiasis en bueyes y vectores (Glossina morsitans). Se concluye, que el uso estrátegico de drogas preventivas proteje a los bueyes en áreas infestadas por tsetse, siempre y cuando se mantenga una supervisión veterinaria y de manejo animal aceptable.

---

Succes De L'Utilisation Des Boeufs De Travail Dans Le Developpement De L'Agriculture D'Une Region D'Ethiopie Infestee De Tse-Tse

Résume Au cours des cinq dernières années, un troupeau de boeufs de travail, maintenant au nombre de quelque 450 têtes, a été maintenu sous protection de produits trypanocides à l'occasion d'un essai d'implantation du bétail dans une région de l'Ouest de l'Ethiopie infestée de tsé-tsé. Ce document traite des conditions de l'environnement, de l'épizootologie des trypanosomoses du bétail ainsi que du vecteur:Glossina morsitans. La conclusion est qu'avec l'utilisation des trypanocides, les boeufs peuvent vivre et donner les performances habituelles au niveau des travaux agricoles dans les zones à haute infestation glossinaire pourvu du'un encadrement vétérinaire et de gestion suffisant soit maintenu.

     

Thiobases in Escherchia coli Transfer RNA: 2-Thiocytosine and 5-Methylaminomethyl-2-thiouracil

Two new sulfur-containing pyrimidine nucleotides have been isolated from hydrolyzates of Escherichia coli transfer RNA. The structures, 2-thiocytosine and 5-methylaminomethyl-2-thiouracil, have been assigned to the bases as a result of study of ultraviolet and mass spectra. An acid-degradation product, S-methylamino-methyluracil, has been synthesized and is identical to that derived from the natural product.     

Benzimidazole pesticides: Analysis and transformations

Some properties, analysis and transformations by plants, animals, soil and light of benomyl, carbendazim, thiabendazole, fuberidazole, cypendazole and fenazaflor are discussed.     

Hematologic Toxicosis Associated with Doxorubicin Administration in Cats

The hematologic toxicity of doxorubicin, 30 mg/m2 body surface area (BSA) every 21 days to a cumulative dose of 300 mg/m2, was evaluated in six cats. Complete blood and platelet counts were performed daily during the first treatment cycle. They were monitored before treatment for all remaining cycles, and at the average neutrophil nadir (day 8) starting with cycle 4. Significant poikilocytosis developed after the first treatment and remained throughout the study, although anemia did not occur. No other red blood cell abnormalities were seen. Platelet counts remained within the reference range throughout the first treatment cycle, but mild thrombocytopenia (88,000-288,000/uL) was found in 11.3% of subsequent complete blood counts (CBCs). Thrombocytosis was seen in 30.9% of CBCs. Neutropenia did not occur during the first treatment cycle although neutrophil counts did decrease, with the nadir occurring between days 8 and 11. All neutrophil counts returned to pretreatment values by day 14. Neutropenia was documented after 14 of 46 (30.4%) doxorubicin treatments, and was associated with fever in 5 cats (10.9%). All fevers responded to oral antibiotic therapy. Neutropenia that lasted more than 14 days developed in two cats, necessitating dosage reduction to 25 mg/m2 BSA. At the dose used in this study, doxorubicin administration was associated with acceptable hematologic toxicosis in most cats.     

COMPARISON OF UPPER GASTROINTESTINAL RADIOGRAPHIC FINDINGS TO HISTOPATHOLOGIC OBSERVATIONS: A RETROSPECTIVE STUDY OF 41 DOGS AND CATS WITH SUSPECTED SMALL BOWEL INFILTRATIVE DISEASE (1985 to 1990)

It was the intent of this study to define which, if any, radiographic observations corresponded with specific causes of diffuse infiltrative small bowel disease and if radiographic findings could differentiate inflammatory disease from neoplastic disease and either of them from normal. Bowel spasticity, luminal narrowing, and thumbprinting tend to indicate the presence of tumor more often than inflammatory disease. Increased bowel gas in cats and barium adhesion in dogs and cats suggest that a component of enteritis is present. Decreased bowel gas in dogs is more often associated with obstructive disease, but is not helpful in differentiating diffuse inflammatory disease from diffuse neoplastic disease. While several observations that can foster differentiation of neoplastic from inflammatory disease were found, this study also indicated that the UGI lacks a high degree of predictive value other than to indicate the presence of infiltrative small bowel disease.     

Efficacy of fenbendazole against inhibited larvae of Ostertagia ostertagi in yearling cattle

Efficacy of fenbendazole, at doses of 7.5 and 10.0 mg/kg of body weight, against inhibited early 4th-stage larvae of Ostertagia ostertagi and other nematodes of the abomasum and intestinal tract, was investigated in naturally infected yearling heifers in late May 1982. In Louisiana, this is near the end of the period (March to May) in which maximal numbers of inhibition-prone larvae are acquired. The mean numbers of O ostertagi in 10 untreated control cattle were: adults, 4,880; developing 4th-stage larvae, 12,546; and inhibited early 4th-stage larvae, 167,931. At the 7.5 mg/kg dose level (10% liquid suspension) in 10 cattle, percentage reduction of O ostertagi in comparison with controls was: adults, 95.7%; developing 4th stages, 91.1%; and inhibited 4th stage, 55.0%. Percentage reductions of other genera were as follows: abomasum--Trichostrongylus axei, 99.6%; Haemonchus sp, 95.1%; intestinal tract--Cooperia spp, 97.8%; Trichostrongylus colubriformis, 100.0%; and Oesophagostomum radiatum 4th stage and adults, 100.0%. At the 10.0 mg/kg dose (10% liquid suspension) in 11 cattle, the percentage reduction of O ostertagi in comparison with controls was: adults, 98.6%; developing 4th stages, 92.9%; and inhibited 4th stage, 80.0%. Percentage reductions of other genera were: abomasum--T axei, 99.9%; Haemonchus sp, 98.8%; intestinal tract--Cooperia spp, 99.3%; T colubriformis, 100.0%; and Oes radiatum 4th stage and adults, 100.0%. Variability of efficacy against inhibited larvae was observed, particularly at the 7.5 mg/kg dose; at this dose, 7 of the 10 heifers in the group yielded in excess of 54,000 surviving larvae.(ABSTRACT TRUNCATED AT 250 WORDS)