Feline and human mucopolysaccharidosis VI (MPS VI or Maroteaux-Lamy syndrome) are inherited autosomal recessive deficiencies of lysosomal enzyme arylsulphatase B. Affected cats and children exhibit lesions caused by incompetent degradation, retinal atrophy and excessive urinary excretion of dermatan facial dysmorphia, corneal stromal opacities, leukocyte granulation, retinal atrophy and excessive urinary excretion of dermatan sulphate--and usually die before adulthood. Most attempts to treat humans affected with MPS VI or other mucopolysaccharidoses have been ineffective or logistically prohibitive, but allogeneic bone marrow transplantation (BMT) offers promise for cure of certain inborn errors of metabolism. Engraftment of normal donor marrow may endow the enzyme-deficient recipient with a continuous source of enzyme-competent blood cells and tissue macrophages to facilitate degradation of stored substrate and to prevent genesis of further malformations. To test this hypothesis, we performed allogeneic BMT in a 2-year-old male Siamese cat with advanced MPS VI. Here we describe BMT-induced correction of this hereditary enzyme deficiency.

Animals↗

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Tumour cell kinetics as predictors of response in canine lymphoma treated with chemotherapy alone or combined with whole body hyperthermia.

Kinetic parameters including potential doubling time (Tpot), duration of S phase (Ts), labelling index (LI), and DNA index (DI) were obtained from 42 dogs with previously untreated lymphoma. Standard flow cytometric techniques using BrdUrd were employed. All dogs were treated with L-asparaginase and remission was induced in 26 dogs, which were then randomized to receive chemotherapy only (doxorubicin [DOX] alone or with lonidamine) or chemotherapy plus whole body hyperthermia (WBH). Dogs were treated every 3 weeks for up to five treatments and evaluated every 3 weeks for evidence of tumour recurrence. Within this subset of animals there was no difference in outcome based on treatment group. Median values for Tpot, Ts and LI were 3.4 days, 7.23 h and 12.49%, respectively. Dogs that had tumours with LI > or = 20% had a shorter time until recurrence than dogs with tumours characterized by LI < 20%. In dogs treated only with chemotherapy, dogs bearing tumours with longer than median Tpot and Ts values and lower than median LI had significantly longer remission duration than dogs with more rapidly proliferating tumours. Dogs treated only with chemotherapy, which had longer than median Tpot and Ts values and lower than median LI, had significantly longer remission duration than all other dogs in the study. The mechanisms in which kinetics are associated with response to chemotherapy are not clear and vary depending on tumour type and treatment regimen. More work is needed to understand factors involved in cell killing during in vivo hyperthermia.

Animals↗

PubMedDate not supplied

Use of whole body hyperthermia as a method to heat inaccessible tumours uniformly: a phase III trial in canine brain masses.

In this study, whole body hyperthermia (WBH) was assessed as a means of heating intracranial tumours uniformly. Twenty-five dogs received radiation therapy and 20 the combination of radiation and WBH. Total radiation dose was randomly assigned and was either 44, 48, 52, 56 or 60 Gy. Because of WBH toxicity, intercurrent disease or tumour progression, seven of the 45 dogs received less than the prescribed radiation dose. For WBH, the target rectal temperature was 42 degrees C for 2h and three treatments were planned. In five of the 20 dogs randomized to receive WBH, only one WBH treatment was given because of toxicity. WBH toxicity was severe in six dogs, and resulted in death or interruption in treatment. Most tumours did not undergo a complete response, making it impossible to differentiate tumour recurrence from brain necrosis as a cause of progressive neuropathy. Therefore, survival was the major study endpoint. There was no survival difference between groups. One-year survival probability (95% CI) for dogs receiving radiation therapy alone was 0.44 (0.25, 0.63) versus 0.40 (0.19, 0.63) for dogs receiving radiation and WBH. There was no difference in the incidence of brain necrosis in the two treatment groups. Results suggest that use of WBH alone to increase the temperature of intracranial tumours as a means to improve radiation therapy outcome is not a successful strategy.

Animals↗

PubMedDate not supplied

Billroth II gastrojejunostomy in dogs. Stapling technique and postoperative complications.

Billroth II gastrojejunostomy was performed with surgical staplers in 6 dogs that were not irradiated and in 11 dogs that subsequently received radiation to the pancreas and proximal part of the duodenum. The dogs were monitored clinically for 135 days and then euthanatized and necropsied. Each gastrojejunostomy site was preserved in formalin and the stomal diameter was measured. No mechanical complications were encountered with the use of surgical staplers and no leakage was observed at the staple closure sites before abdominal closure. All dogs vomited approximately 100 ml of coagulated blood 4 to 8 hours after surgery, and 300 to 400 ml of brown fluid after approximately 24 hours. Vomiting was the most common clinical finding after the first 24 hours. Vomiting was subjectively graded from 1 to 3 with grade 1 representing the least severe problem and grade 3 the most severe. Grade 1 vomiting occurred in 12 of 16 dogs that survived 135 days; in the other four dogs, vomiting was classified as grade 2 or 3. All dogs with grade 1 vomiting had stomal diameters of 1.7 to 2.9 cm (mean, 2.2 +/- 0.4 cm standard deviation). Dogs with grade 2 or 3 vomiting had stomal diameters of 2.2 to 4.0 cm (mean, 3.2 +/- 0.8 cm standard deviation). The difference was statistically significant (p less than 0.005). The percentage of weight gained or lost was recorded for each dog. Two nonirradiated dogs gained body weight, whereas the other nonirradiated dogs and all irradiated dogs lost body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

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Intraoperative irradiation of 16 spontaneously occurring canine neoplasms.

Sixteen dogs with malignant neoplasms were treated with intraoperative radiation therapy after surgical debulking. Fractionated external beam radiation therapy was given postoperatively to 11 dogs. Healing of surgical incisions was uncomplicated in 14 dogs. When the ureters or urinary bladder were included in the irradiation field, they became stenotic and fibrotic. Urinary incontinence and secondary renal injury were common. Local tumor control was poor regardless of site or tumor type.

Animals↗

PubMedDate not supplied

Whole body hyperthermia in dogs using a radiant heating device: effect of surface cooling on temperature uniformity.

Rectal and subcutaneous temperatures were measured during a total of 10 whole body hyperthermia treatments conducted in six dogs. During five of the treatments skin cooling, by means of initiating air flow through the radiant heating device, was necessary during the plateau phase because rectal temperature exceeded the target value. Skin cooling was not necessary in the other five treatments. Although the rectal temperatures were similar in all 10 treatments, extensive and rapid subcutaneous temperature non-uniformity, of approximately 4 degrees C, developed during treatments where skin cooling was necessary. During the treatments where skin cooling was not necessary, the subcutaneous temperature remained approximately equal to the rectal temperature. These data indicate that the environment in the radiant heating device during the plateau phase can have a profound effect on the temperature at superficial sites, which is not reflected by the temperature measured at deeper sites. The temperature at superficial sites should be measured during whole body hyperthermia to assure that the prescribed heat dose is administered to the largest percentage of body mass possible. Active skin cooling during whole body hyperthermia should be avoided if possible.

Animals↗

PubMedDate not supplied

Response of canine soft tissue sarcomas to radiation or radiation plus hyperthermia: a randomized phase II study.

Sixty-four dogs with spontaneous soft tissue sarcomas without evidence of metastases were stratified by tumour volume and randomized to receive graded doses of radiotherapy (XRT) alone or radiotherapy plus hyperthermia (HT). An improvement in duration of local control was achieved with the addition of hyperthermia as compared with XRT alone (Wilcoxon, p = 0.040; log rank, p = 0.064). Overall frequency of late complications was not different for the two treatment arms when comparing across equivalent XRT dose groups. Frequency of distant metastases after therapy completion was not significantly different for the two treatment arms at 1 year (7.4% for XRT versus 20% for HT plus XRT) or 2 years (11.5% for XRT versus 25% for HT plus XRT) post therapy. These results suggest that a therapeutic gain was achieved for this group of tumour-bearing animals. Uni- and multivariate analyses were performed to examine the potential for various factors to influence treatment outcome. Patient related variables included tumour stage, histologic subtype and grade and tumour site. Treatment related variables included total radiation dose and 15 descriptors of temperature distributions achieved during hyperthermia. When considering patient related factors, tumour histology, grade and location were important predictors of time to minimum volume, but only tumour location influenced time to tumour regrowth. When considering treatment related factors, radiation dose was not significantly correlated with time to minimum volume or time to local regrowth, but it was correlated with probability for late normal tissue damage in the XRT alone group (p = 0.005). For the hyperthermia treatments, 13 of 15 tumour temperature distribution descriptors were correlated with time to minimum volume, but none were correlated with time to local regrowth. These results suggest that caution should be used in interpreting the value of temperature distribution descriptors in predicting for long-term local control after hyperthermia and radiotherapy, based on analysis of short-term responses.

Animals↗

PubMedDate not supplied

Whole-body hyperthermia combined with hyperfractionated irradiation of the thorax in dog: acute physiological response.

Whole-body hyperthermia has potential as an adjuvant treatment with chemotherapy and radiation therapy for diseases such as lung cancer which require both local and systemic control. The acute toxicity of whole-body hyperthermia combined with whole-thorax irradiation was studied in dogs. Twenty-eight dogs received three 2-h whole-body hyperthermia (WBH) treatments at 42.0 degrees C deep rectal temperature. Twenty-four of these dogs were also randomized to receive radiation doses of 18, 22.5, 27, 31.5, 40.5 or 45 Gy. Irradiation was given in 1.5 Gy fractions over 6 weeks. Three WBH treatments were given to 28 dogs with all dogs surviving treatment. WBH was given on days 1, 22 and 40 of the 6-week interval. Thirty-one dogs received radiation doses of 18-49.5 Gy without WBH. Deep rectal temperature was maintained at 41.9 +/- 0.3 degrees C over 2 h with an average of 20 min outside the chamber for irradiation. Two dogs required intervention with emergency medications during WBH treatment. One of the two dogs developed permanent neurological injury. Continuous physiological monitoring was necessary for successful WBH. WBH plus thoracic irradiation was well tolerated. All dogs survived all treatments. A significant but transient increase in peripheral blood leucocytes and a decrease in platelet counts occurred after each WBH treatment. The addition of thoracic irradiation up to 45 Gy in 1.5 Gy fractions did not appear to alter the acute toxicity of WBH with the exception of an increase in the protein content of lung lavage fluids. In conclusion, multiple WBH treatments of 2 h at a target temperature of 42 degrees C in addition to thoracic irradiation up to 45 Gy in 1.5 Gy fractions was administered with only mild acute toxicities occurring. Core temperature could be maintained for up to 20 min outside of the WBH chamber which allowed irradiation to be given concurrently with hyperthermia at a core temperature of 42 degrees C +/- 0.1 degree C.

Animals↗