Local interleukin-2 and interleukin-12 therapy of bovine ocular squamous cell carcinomas

Interleukin-2 and interleukin-12 have been used independently to successfully treat the induced and the spontaneous tumours in animals. This trial was done to determine if a combination of IL-2 and IL-12 in the treatment of spontaneous bovine ocular squamous cell carcinomas (BOSCC) would be more successful than IL-2 or IL-12 therapy by themselves. For this trial, we selected 25 BOSCC tumours seen on Holstein Fresian cows in Beatrice, Zimbabwe. The cows were randomly assigned to a treatment group of 5 days of IL-2 (200,000 U/day), 5 days of IL-12 (0.5 microg/day) or 5 days of IL-2 (200,000 U/day) and IL-12 (0.5 microg/day). At 20 months after treatment, the IL-2 therapy group had 63% complete regressions; the combination group had 38% complete regressions, which were significantly higher than the IL-12 group, which had 0% complete regressions at 20 months, despite having 29% complete regressions at 6 months. These results show that IL-2 therapy by itself and in combination with IL-12 is more successful than IL-12 by itself. However, combination therapy does not improve the outcome in comparison to IL-2 as a single therapy. It also proves that IL-2 is consistently successful in the therapy of BOSCC with over 60% complete regression, which corresponds to a number of other studies we have done on IL-2 therapy of BOSCC [Rutten, V.P.M.G., Klein, W.R., De Jong, W.A., Misdorp, W., Den Otter, W., Steerenberg, P.A., De Jong, W.H., Ruitenberg, E.J., 1989. Local interleukin-2 therapy in bovine ocular squamous cell carcinoma. A pilot study. Cancer Immunol. Immunother. 30, 165--169; Stewart, R.J.E., Hill, F.W.G., Masztalerz, A., Jacobs, J.J.L., Koten, J.W., Den Otter, W., 2003. Local low dose interleukin-2 therapy of bovine ocular squamous cell carcinomas in cattle in Zimbabwe, submitted for publication; Den Otter, W., Hill, F.W.G., Klein, W.R., Koten, J.W., Steerenberg, P.A., De Mulder, P.H.M., Rutten, V.P.M.G., Ruitenberg, E.J., 1993. Low doses of interleukin-2 can cure large bovine ocular squamous cell carcinoma. Anticancer Res. 13, 2453-2455; Den Otter, W., Hill, F.W.G., Klein, W.R., Koten, J.W., Steerenberg, P.A., De Mulder, P.H., Rhode, C., Stewart, R., Faber, J.A., Ruitenberg, E.J., 1995. Therapy of bovine ocular squamous cell carcinoma with local doses of interleukin-2: 67% complete regressions after 20 months of follow-up. Cancer Immunol. Immunother. 41, 10-14].     

Imprint and brush cytology in the diagnosis of canine intranasal tumours

Fifty-four dogs with nasal tumours were included in this study. Based on histopathology, 52 tumours were malignant (36 epithelial and 16 mesenchymal) and two were benign (one oncocytoma and one pleiomorphic adenoma). Malignancy was significantly more frequently diagnosed by imprint cytology (81 per cent of the cases) than by brush cytology (56 per cent). Brush cytology was a significantly more sensitive technique in epithelial than in mesenchymal tumours, while the sensitivity of imprint cytology was not affected by the histological type. Brush cytology determined an epithelial origin in 88 per cent of epithelial tumours, and imprint cytology in 90 per cent. In mesenchymal tumours, the scores were significantly lower, the histological type being determined in only 20 per cent and 50 per cent, using brush and imprint cytology, respectively.     

An economic justification of "blitz" therapy to eradicate Streptococcus agalactiae from a dairy herd

Streptococcus agalactiae was identified as the cause of mastitis in a 240-cow dairy herd. Forty-five per cent of the herd had cell counts over 500,000/ml, and 28 per cent had cell counts over 1,000,000/ml. Dry cow therapy was used regularly but teat dipping had not been used for three years. The procedures at milking were modified, teat dipping was introduced, and the herd was divided into two according to cell count. The 120 cows with higher cell counts were treated with 300 mg erythromycin (Erythrocin intramammary; Sanofi Animal Health) preparation per quarter at two consecutive milkings. Towards the end of lactation, all the 90 lactating cows in the herd were again treated with erythromycin. Milk samples were collected from all the cows in the herd 12 months after the initial treatment, and S agalactiae was isolated from only one replacement heifer which had been purchased after the treatments with erythromycin. The butterfat and protein levels in the milk were compared with those of a similar, but untreated, herd for 12 months before and after therapy. The butterfat levels rose sharply after treatment, and financial assessment showed a 41 per cent return on investment in the 12 months following the treatment.     

Effects of radiotherapy alone and surgery and radiotherapy on survival of dogs with nasal tumours

The case records of 26 dogs with nasal tumours, treated either with radiation alone or surgery and radiation, were compared. One- and two-year actuarial survival rates for 12 dogs treated with radiotherapy were 58 and 13 per cent, respectively, compared to 71 and 38 per cent, respectively, for 14 dogs which were treated with surgery before radiotherapy. Sixty-seven per cent of the dogs treated with radiotherapy had recurrent clinical signs by 52 weeks compared to 36 per cent of the dogs treated with surgery and radiotherapy. The longer disease-free interval of the dogs treated with surgery and radiotherapy was statistically significant. When dogs with sarcomas were compared to those with carcinomas, there was no significant difference in disease-free interval or survival time.     

Effect of injecting collagenase into the uterine artery during a caesarean section on the placental separation of cows induced to calve with dexamethasone

A caesarean section was performed on 30 cows before normal term and 16 to 20 hours after the induction of parturition with dexamethasone. During the surgical procedure, 20,000 U of bacterial collagenase was injected into the uterine artery of 15 of the cows. The average periods of retention of the fetal membranes were 40 hours in the treated cows and 114 hours in the control cows (P<0.001). At 36 hours after the surgery six of the treated cows (40 per cent) but all 15 of the control cows had retained fetal membranes. The collagenase-treated cows showed no abnormal clinical signs during the 10 days after the operation.     

Evaluation of excision, cryosurgery and local BCG vaccination for the treatment of equine sarcoids.

Ninety-five horses with sarcoids were subjected to three types of treatment: surgical excision (conventional or carbon dioxide laser), cryotherapy or local BCG vaccination. The type of treatment was selected on the basis of the size, location and clinical appearance of the tumours. The choice between conventional and laser excision was empirical. A successful outcome was obtained in 11 of 14 (79 per cent) of the horses treated by cryosurgery, 18 of 27 (67 per cent) treated by BCG vaccination, 18 of 22 (82 per cent) treated by conventional excision, and 20 of 28 (71 per cent) treated with a carbon dioxide laser. For both excision methods, rigorous measures were taken to avoid autoinoculation and to ensure a wide margin of normal skin. The probability of local recurrence after excision was significantly higher for large sarcoids and sarcoids which had previously failed to respond to treatment. In 10 of the 31 horses with remaining sarcoids, some or all of the untreated sarcoids were observed to regress spontaneously.     

Hyperthermia and radiation in the management of canine tumours

Fifty-one dogs bearing a variety of naturally occurring tumours were treated with combined radiation and hyperthermia. The treatment regime consisted of four, weekly fractions of radiation to a total dose of 3600–4000 cGys and one or two treatments with local microwave hyperthermia, heating the tumour to 44°C for 30 minutes on each occasion. Twenty-six (51 per cent) of the tumours showed a complete response to this treatment and a further eighteen (35 per cent) tumours underwent significant regression giving a total response rate of 86 per cent. Sixteen tumours later recurred at intervals of 11–50 weeks post treatment. The majority of tumours were in the oral cavity (35 cases) and in this group the survival rate compares favourably with figures for surgical treatment and radiotherapy alone. These findings support published results from other centres, indicating that hyperthermia combined with radiotherapy is a potentially useful technique for the management of certain canine malignant tumours.     

Monthly application of 10 per cent moxidectin and 2{middle dot}5 per cent imidacloprid spot-on to prevent relapses in generalised demodicosis: a pilot study

Canine generalised demodicosis (GD) can be difficult to cure, with some dogs requiring life-long treatment. The aim of this pilot study was to evaluate the effectiveness of monthly 10 per cent moxidectin/2·5 per cent imidacloprid spot-on in maintaining long-term (12 months) clinical and parasitological remission in dogs with relapsing GD. Fourteen dogs were included: 10 with juvenile-onset GD (JOGD) and four with adult-onset GD (AOGD). All?dogs had been treated previously and relapsed (1-4 times). Each dog was treated again with either milbemycin oxime 2 mg/kg or ivermectin 400 μg/kg orally once daily, until two consecutive negative skin scrapings at one-month intervals (total 4-7 months of treatment). After treatment discontinuation, 10 per cent moxidectin/2·5 per cent imidacloprid spot-on was applied monthly for 12 months. Dogs were rechecked after 1, 2, 3, 6 and 12 months, and multiple skin scrapings were taken. Twelve dogs completed the study and were clinically normal and parasitologically negative at each recheck (four dogs with AOGD and eight with JOGD). One dog died suddenly for unrelated reasons, and one dog relapsed. Results of this pilot study suggest that monthly application of 10 per cent moxidectin/2·5 per cent imidacloprid spot-on may be effective as maintenance therapy in relapsing cases of GD.     

Duration of immunity and absorption of cysticerci in calves after treatment of Taenia saginata cysticercosis with praziquantel

Calves were first infected with 5000 Taenia saginata eggs at six to 10 weeks old and treated with praziquantel 12 weeks later. Complete immunity against challenge lasted for at least 12 weeks following anthelmintic treatment. Six months after drug treatment over 90 per cent of the cysticerci had been completely absorbed but some were still detectable especially in the heart. An increase was observed in the ELISA values of sera from infected calves following treatment with praziquantel, but no such rise was detected in sera from resistant calves after challenge infection.     

Effect of copper oxide wire particle treatment on establishment of major gastrointestinal nematodes in lambs

Eighty-four 10-week-old lambs were used to investigate the effect of copper oxide wire particle treatment on the establishment of major gastrointestinal nematodes. They were maintained on pasture previously treated to minimise larval contamination. Five grams of uniform sized copper oxide wire particles were given orally five days before infection with either 20,000 Trichostrongylus colubriformis larvae, 20,000 Ostertagia circumcincta larvae or 3000 Haemonchus contortus larvae given as three doses at three-day intervals. The animals were slaughtered 21 or 22 days after the last infective dose. Parasite burdens in the lambs treated with copper oxide wire particles were reduced by 96 per cent in the case of H contortus and by 56 per cent in the case of O circumcincta compared to burdens in controls. There was no significant effect of copper particles on the establishment of T colubriformis.     

Clinical staging for oropharyngeal malignancies in the dog

One hundred dogs bearing malignancies of the oropharyngeal region were examined over a three-year period and prospectively staged using the World Health Organisation TNM Classification of Tumours of Domestic Animals. Primary tumours were characterized by their large size or local infiltration (71 per cent, T3 status) and invasion into adjacent bone (60 per cent, Tb status). Regional lymph node metastasis was less common (17 per cent, N1b, N2b or N3 status) and distant metastasis was an unusual presenting feature (5 per cent, M1 status). The early Stage I and II tumours together accounted for 8 per cent of the total series whilst the more advanced Stage III group were by far the most frequent, representing 84 per cent. The remaining 8 per cent being classified as Stage IV because of extensive regional or distance metastatic deposits. Prognoses by stage showed actuarial survival rates at 12 months of 100 per cent for Stage I, 71 per cent for Stage II, 31 per cent for Stage III with no survivors in the Stage IV group. Survival rates for the major histological types were 44 per cent for the non-tonsillar squamous cell carcinoma, 22 per cent for the tonsillar squamous cell carcinoma and fibrosarcomas, 17 per cent for mastocytomas whilst none of the malignant melanomata survived 12 months.     

Local current field radiofrequency hyperthermia for the treatment of superficial skin tumours in cats

Local current field radiofrequency (LCF-RF) hyperthermia was used to treat 38 superficial skin tumours (predominantly squamous cell carcinomas) of the nose, face and ears in 35 cats. LCF-RF hyperthermia was applied at 50°C for 60 seconds at single or multiple sites depending on the tumour size. Each cat was observed over a four-month period after treatment and 14 out of 35 cases were also available for re-evaluation eight months after treatment. Tumours which had not resolved completely within one month after the initial treatment were re-treated.

LCF-RF hyperthermia is most suited for the treatment of superficial skin tumours (<5 mm diameter). Ninety-two per cent (12/13) of tumours of this dimension showed some regression and 69% (9/13) completely resolved. Larger tumours >5 mm diameter) were also successfully treated. 54% (8/14) regressed but only 14% (2/14) completely resolved. LCF-RF hyperthermia is not recommmended for the treatment of tumours of the pinnae as 5 of the 6 tumours at this site failed to respond.     

Local current field radio frequency hyperthermia for the treatment of superficial skin tumours in cats

Local current field radiofrequency (LCF-RF) hyperthermia was used to treat 38 superficial skin tumours (predominantly squamous cell carcinomas) of the nose, face and ears in 35 cats. LCF-RF hyperthermia was applied at 50 degrees C for 60 seconds at single or multiple sites depending on the tumour size. Each cat was observed over a four-month period after treatment and 14 out of 35 cases were also available for re-evaluation eight months after treatment. Tumours which had not resolved completely within one month after the initial treatment were re-treated. LCF-RF hyperthermia is most suited for the treatment of superficial skin tumours (<5 mm diameter). Ninety-two per cent (12/13) of tumours of this dimension showed some regression and 69% (9/13) completely resolved. Larger tumours >5mm diameter) were also successfully treated. 54% (8/14) regressed but only 14% (2/14) completely resolved. LCF-RF hyperthermia is not recommended for the treatment of tumours of the pinnae as 5 of the 6 tumours at this site failed to respond.     

A retrospective evaluation of four surgical methods of treating canine transmissible venereal tumour

A total of 109 lesions were treated in a total of 109 dogs and bitches using simple surgical excision or diathermy, with or without the simultaneous removal of the gonads. Evaluation of the case, 49 months after surgery, showed that 35 (32.1 per cent) of the tumours had regressed completely whilst 74 (67.9 per cent) had recurred. Excision using diathermy was the more effective treatment irrespective of whether the gonads were removed. There was a significant difference in the frequency of recurrence and the time interval for it to recur (P < 0.05 and P < 0.25 respectively) when the methods of treatment were compared, however castration of either males or females had no significant effect upon the frequency of recurrence.     

Effect of experimental Ostertagia circumcincta infection on the performance of grazing lambs

Groups of 10 three-and-a-half-month-old Suffolkcross lambs were infected daily, five times a week, for 12 weeks with either zero, 500, 1500, 3000 or 5000 larvae of Ostertagia circumcincta and grazed together on a series of 'clean' paddocks. All the lambs were moved at seven to 10 day intervals to a fresh paddock to prevent autoinfection and were killed after 14 weeks. Another group was killed at the outset as a control for carcase analysis. Mean O circumcincta populations were 34 (grazing control) and 1224, 473, 1092 and 4331 for the groups receiving 500, 1500, 3000 and 5000 larvae per day respectively. The percentage of fourth stage larvae increased with increasing larval intake. Extensive abomasal damage with mucosal hypertrophy and depletion of parietal cells occurred in the lambs receiving 3000 and 5000 O circumcincta larvae per day. Intakes of 1500 larvae per day and above depressed growth rate by 24 to 37 per cent, reduced the deposition of protein in the carcase by 34 to 52 per cent and lowered calcium/phosphorus deposition by 23 to 48 per cent. Plasma pepsinogen concentrations were consistently elevated in lambs receiving 3000 or 5000 larvae per day and may be a useful aid to recognising abomasal damage sufficient to affect productivity.     

Effects of stage and number of tumours on prognosis of dogs with cutaneous mast cell tumours

Between 1997 and 1999, 280 dogs with mast cell tumours were identified, of which 59 (21 per cent) had multiple tumours. Follow-up data for survival analysis were available for 145 dogs with single tumours and 50 dogs with multiple tumours. There was no significant difference between the survival times of the two groups; the survival rates after 12 and 24 months were 88 per cent and 83 per cent, respectively, for the dogs with single tumours, and 86 per cent at both intervals for the dogs with multiple tumours. Eight of the dogs with single tumours had lymph node metastases (stage II disease) and these dogs had a median survival time of 431 days, whereas the 50 dogs with multiple tumours (classified as stage III disease) and the dogs with single tumours (classified as stage I disease) had not reached their median survival times. Golden retrievers appeared to be predisposed to developing multiple tumours in the population studied, with an odds ratio of 3.8. This study found no evidence that dogs with multiple tumours had different survival times than those with single tumours, although there was evidence that the presence of lymph node metastasis generally carried a poorer prognosis.     

Hemilaminectomy for the treatment of thoracolumbar disc disease in the dog: a follow-uo studv of 40 cases

A study was made of dogs with Hansen type I thoracolumbar disc extrusions that had been treated by hemilaminectomy and fenestration of the affected disc. Follow-up information was available for 40 dogs undergoing treatment over a five-year period. The follow-up period ranged from 12 to 72 months (mean 34 months). The case details and the results of treatment of these 40 dogs are presented. All dogs were graded according to the degree of neurological dysfunction at the time of initial presentation and at the conclusion of the study period. Twenty-seven dogs (68 per cent) had no detectable signs of neurological dysfunction or thoracolumbar pain at the final assessment and a further eight dogs (20 per cent) had mild ambulatory paraparesis but were regarded by their owners as functional pets. Recurrence of neurological signs consistent with thoracolumbar disc disease was seen in five dogs (13 per cent) and was successfully resolved completely in one of three dogs that were treated.     

Evaluation of measurements of the conductivity of quarter milk samples for the early diagnosis of mastitis

Measurements of the conductivity of quarter milk samples were made in 31 cows in a 70-cow herd in southeast England, for a period of 15 weeks. Over this period, 42 per cent of cow-weeks and 20 per cent of quarter-weeks had an increase in quarter milk conductivity of 10 per cent of more compared with the mean conductivity of the previous 14 milkings. Fourteen per cent of quarter-weeks had an increase in conductivity of 15 per cent or more. The geometric mean somatic cell count (cell count) was higher in quarter-weeks with a 10 per cent or greater increase in conductivity than in quarter-weeks with a conductivity change of less than 10 per cent. At a conductivity threshold of 10 or 15 per cent and a cell count threshold of 200,000 or 400,000 cells/ml the specificity of this system was estimated to be 85 to 92 per cent, the sensitivity 40 to 54 per cent, the negative predictive value 87 to 93 per cent and the positive predictive value 33 to 55 per cent. The positive predictive value of the individual quarter milk conductivity was insufficiently accurate to be used as the sole criterion for the selection of quarters for early antibiotic treatment.     

Histopathological survey of neoplasms in flat-coated retrievers, 1990 to 1998

Over the period from March 1990 to December 1998, veterinary surgeons in general practice were invited to submit tissues suspected of being neoplastic which had been removed from flat-coated retrievers. When possible, pedigree details were obtained from the owners. In addition, data were collected from flat-coated retrievers known to have suffered from a neoplastic condition and for which a histopathological report was available. A total of 1023 submissions was obtained from 782 dogs. These included 165 non-neoplastic lesions (16 per cent), 447 benign samples (44 per cent) and 411 malignant samples (40 per cent). Soft tissue sarcomas accounted for 55 per cent of the malignant samples (26 per cent of all tumour samples and 22 per cent of all submissions) with 63 per cent of them being diagnosed as undifferentiated. Carcinomas accounted for 20 per cent of malignant samples (8 per cent of all submissions). Of the benign tumours, cutaneous histiocytoma was the most common diagnosis (48 per cent of benign tumours, 25 per cent of all tumours and 21 per cent of all submissions).     

Cyclosporine treatment of anal furunculosis in 26 dogs

OBJECTIVES: To evaluate the effect of cyclosporine on anal furunculosis lesions in 26 dogs. METHODS: Lesions were graded as mild in 11 dogs, moderate in eight and severe in seven. Each dog was treated with approximately 4 mg/kg cyclosporine orally every 12 hours until the lesions resolved or showed no further improvement. Residual lesions were resected surgically. RESULTS: Eighteen dogs (69 per cent) experienced complete resolution, seven (27 per cent) improved but had residual lesions and one (4 per cent) showed no improvement. The mean duration of treatment until resolution or no further improvement was 8.8 weeks (range four to 24 weeks). Nine dogs (35 per cent) experienced recurrence. Six were from the group that had shown complete resolution and three were from the group that had surgery. Fifteen dogs (58 per cent) developed side effects to cyclosporine, although none required treatment to be discontinued. Mean duration of follow-up was 6.8 months (range one to 20 months). CLINICAL SIGNIFICANCE: Cyclosporine was effective at resolving or reducing anal furunculosis lesions in 25 of 26 dogs (96 per cent). However, residual or recurrent lesions remain a potential problem, and surgical resection or long-term cyclosporine treatment may be necessary in some dogs.