[Show abstract][Hide abstract] ABSTRACT: Sequential half-body irradiation (HBI) combined with chemotherapy is feasible in treating canine lymphoma, but prolonged interradiation intervals may affect efficacy. A 2-week interradiation interval is possible in most dogs receiving low-dose rate irradiation (LDRI) protocols at 6 Gy dose levels.
LDRI incorporated into a cyclophosphamide, doxorubicin, vincritine, and prednisone (CHOP)-based chemotherapy protocol is effective for the treatment of lymphoma in dogs.
Thirty-eight client-owned animals diagnosed with multicentric lymphoma.
Retrospective study evaluating the efficacy and prognostic factors for the treatment of canine lymphoma with sequential HBI and chemotherapy.
The median 1st remission was 410 days (95% confidence interval [CI] 241-803 days). The 1-, 2-, and 3-year 1st remission rates were 54, 42, and 31%. The median overall survival was 684 days (95% CI 334-1,223 days). The 1-, 2-, and 3-year survival rates were 66, 47, and 44%.
Results of this study suggest that treatment intensification by a 2-week interradiation treatment interval coupled with interradiation chemotherapy is an effective treatment for dogs with lymphoma.
Journal of Veterinary Internal Medicine 08/2009; 23(5):1064-70. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thirteen dogs with previously untreated multicentric lymphoma were enrolled in a prospective study investigating the effects of low-dose rate total body irradiation (TBI) and chemotherapy. Dogs received either 6 or 8 Gy TBI in half-body fractions, 2 weeks apart. Toxicity consisted of mild to moderate haematological and gastrointestinal (GI) signs. One dog died from treatment complications. Anorexia was noted independent of dose. Haematological toxicity was more common and more severe after 8 Gy treatment. GI toxicity was more likely postcaudal half-body irradiation with 8 Gy. Other than leukotrichia, late effects from radiation were not observed. Results indicated that haematological and nonhaematological toxicity was dose dependent. However, the protocol was well tolerated and treatment intensification using a 2-week inter-radiation interval was possible in all dogs treated with 6 Gy. Preliminary survival data for these dogs were very encouraging, providing a strong rationale to analyse the efficacy of low-dose rate irradiation (LDRI) in canine lymphoma.
Veterinary and Comparative Oncology 01/2008; · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine progression-free and overall survival times of cats with squamous cell carcinoma (SCC) of the nasal planum following treatment with a single fraction of strontium Sr 90 ((90)Sr).
Retrospective case series.
49 cats with SCC of the nasal planum.
Information including FIV infection status, diagnosis of SCC vs SCC in situ (ie, evidence that the tumor did or did not penetrate the epidermal basement membrane, respectively), (90)Sr dose and number of probe applications, treatment-related response and complications, and recurrence of SCC and new lesion development was obtained from medical records. The relationships of these variables with calculated progression-free and overall survival times were assessed.
Of 49 cats that underwent (90)Sr plesiotherapy (median dose, 128 Gy), 48 (98%) had a response to treatment and 43 (88%) had a complete response. Median progression-free and overall survival times were 1,710 and 3,076 days, respectively. Treatment complications were infrequent (4 [8%] cats) and mild. Following treatment, the SCC recurrence rate was 20% (10/49 cats); 16 (33%) cats developed new lesions in other locations. Overall survival time was significantly longer for cats with a complete response to treatment than for those with a partial response. None of the other variables evaluated had a significant effect on progression-free or overall survival time.
Treatment of cats with SCC of the nasal planum with a single fraction of (90)Sr appeared to be effective and well tolerated. Initial response to treatment was predictive of overall survival time.
Journal of the American Veterinary Medical Association 10/2007; 231(5):736-41. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine outcome associated with cutaneous tumors treated via intratumoral chemotherapy with cisplatin and identify risk factors affecting local tumor control and complications in equidae.
Retrospective case series.
573 equidae with 630 cutaneous tumors.
Medical records of horses, mules, donkeys, and ponies with cutaneous tumors treated via intratumoral chemotherapy with cisplatin were analyzed.
549 horses, 13 mules, 8 donkeys, and 3 ponies with 630 histologically confirmed cutaneous tumors were included. Tumors included sarcoids (n = 409), squamous cell carcinomas (151), soft tissue sarcomas (28), cutaneous lymphomas (26), and melanomas (16). Overall cure rate, defined as local control at 4 years, was 93.3%. For all tumor stages combined, cure rates after 1 course of treatment were 96.3% for sarcoids, 96% for lymphomas, 88% for squamous cell carcinomas, 85% for soft tissue sarcomas, and 81% for melanomas. Treatment protocol, tumor stage, and prior treatment were significant prognostic factors for tumor control. Treatment efficacy was lower for large tumors, those with gross postoperative residual disease, and those that had been treated previously with other modalities. Treatment was well tolerated. Local reactions were more likely to occur and to be more severe after the third and fourth treatment sessions.
Results confirmed the value of intratumoral chemotherapy with cisplatin for treatment of cutaneous tumors in equidae. The results cannot be extrapolated to other formulations of cisplatin or other protocols that might be used.
Journal of the American Veterinary Medical Association 06/2007; 230(10):1506-13. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The records of 19 cats treated for stage I nasal lymphoma with radiation therapy and chemotherapy were reviewed to determine response to therapy, treatment outcome and possible prognostic indicators. All cats were treated with megavoltage radiation therapy to a total dose ranging from 22 to 48 Gy (median dose = 42 Gy). All cats were prescribed at least 6 months of multiagent chemotherapy. The median progression-free interval for all cats was 945 days (31 months). Two cats did not achieve clinical remission. Of 17 cats evaluable for relapse, 10 (58.8%) were progression free during the entire follow-up period. Four cats (23.5%) suffered local recurrence, while three (17.6%) experienced distant relapse. The median survival time was 955 days (31.4 months). The only variable found to have a significant negative impact on survival was destruction of the cribriform plate before therapy (P= 0.002). The long progression free and survival times reported here indicate that cats with stage I nasal lymphoma treated with aggressive local and systemic therapy can have a favorable outcome when compared with other anatomic forms of lymphoma. Despite strong clinical responses to the multimodality therapy used, the fact that three (17.6%) cats relapsed distantly supports the recommendation that treatment with radiation therapy alone is insufficient until further prospective studies can be performed.
[Show abstract][Hide abstract] ABSTRACT: Pituitary masses in dogs are not uncommon tumors that can cause endocrine and neurologic signs and, if left untreated, can decrease life expectancy.
Dogs with pituitary masses that received radiation therapy (RT) have more favorable neurologic outcomes and longer survival times compared with untreated dogs.
Nineteen dogs with a pituitary mass identified on CT or MR imaging were irradiated with 48 Gy given in 3 Gy daily-dose fractions. Twenty-seven untreated control dogs had pituitary masses.
Medical records of dogs with pituitary masses were retrospectively reviewed for clinical signs, mass size, and outcome.
Median survival time was not reached in the treated group. Mean survival time in the treated group was 1,405 days (95% confidence interval [CI], 1,053-1,757 days) with 1-, 2-, and 3-year estimated survival of 93, 87, and 55%, respectively. Median survival in the nonirradiated group was 359 days (95% CI, 48-916 days), with a mean of 551 days (95% CI, 271-829 days). The 1-, 2-, and 3-year estimated survival was 45, 32, and 25%, respectively. Dogs that received RT for their pituitary tumors had significantly longer survival times than untreated dogs (P = .0039). Treated dogs with smaller tumors (based on maximal pituitary-to-brain height ratio or area of tumor to area of brain) lived longer than those with larger tumors (P < .001).
When compared with untreated dogs, RT increased survival and controlled neurologic signs in dogs with pituitary masses.
Journal of Veterinary Internal Medicine 01/2007; 21(5):1027-33. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A feasibility study of the treatment of advanced superficial human malignant tumors utilizing direct intralesional injections of cisplatin mixed with purified bovine collagen was performed. The purpose of using intralesional injection of cisplatin mixed with collagen was to limit the drug exposure to normal tissues while increasing the dose and duration of exposure to the tumor. Fourteen evaluable superficial tumors in four patients (melanoma, breast CA, squamous CA from larynx) received a total of 65 treatments in the outpatient clinic setting. All patients had failed prior treatment with systemic intravenous cisplatin. Lesions were treated at least three times at two-week intervals. After intramuscular meperidine premedication, multiple injections of cisplatin mixed with collagen were made into the tumors. There was minimal normal tissue toxicity and minimal systemic toxicity. Tumor regression or stabilization occurred in 86% (12/14) of tumors; 50% (7/14) of lesions regressed more than 50% in size. This study suggests that intralesional colloidal cisplatin can overcome resistance to systemic intravenous cisplatin.
[Show abstract][Hide abstract] ABSTRACT: An activating mutation in codon 599 of BRAF has been identified in approximately 60% of human cutaneous nevi and melanomas, but not melanomas of mucosal origin. The purpose of this study was to determine if BRAF mutations occur in canine oral malignant melanomas. The canine BRAF gene was first cloned from normal canine testicular cDNA, and a novel previously unreported splice variant involving exon 5 was identified during this process. To screen canine melanoma samples for BRAF mutation in codon 599, cDNA and genomic DNA were isolated from canine malignant melanoma cell lines and primary tumor samples respectively, all from cases seen at the Veterinary Medical Teaching Hospital at the University of California, Davis. Polymerase chain reaction (PCR) was performed for exon 15 using primers based at the 5' end of exon 15 and the 5' end of intron 15 and the resultant products were directly sequenced. No mutations in codon 599 or exon 15 were identified in any of the 17 samples evaluated. However, all of the melanoma cell lines expressed BRAF and demonstrated high levels of basal ERK phosphorylation suggesting that dysregulation of this pathway is present. Therefore, similar to the case with human mucosal melanomas, canine oral malignant melanomas do not possess codon 599 BRAF mutations commonly identified in human cutaneous melanomas. This finding supports the notion that melanomas arising from non-sun-exposed sites exhibit distinct mechanisms of molecular transformation.
[Show abstract][Hide abstract] ABSTRACT: To determine the clinical outcome and factors affecting cutaneous or mucosal flaps in dogs treated with radiation therapy (RT).
Longitudinal clinical study.
Twenty-six client-owned dogs.
Dogs entered in the study had a flapping procedure and RT as part of their treatment. The sequence of flapping and RT included: (1) planned preoperative RT, (2) postoperative RT, and (3) flapping as a salvage procedure for management of complications or local tumor recurrence after RT. Flap complications were defined as necrosis, local infection, dehiscence, and ulceration. The risk and severity of flap complication were analyzed independently.
Twenty (77%) dogs had a complication; 6 dogs required an additional flapping procedure; and 4 dogs had an unresolved complication. Flapping procedures performed to correct a complication, or failure of RT, had a significantly greater risk for complication; however, postoperative RT decreased the severity of complication. A dose per fraction of 4 Gy compared with 3 Gy was prognostic for increased severity of complications, whereas the head and neck location was prognostic for decreased severity of complication.
Although morbidity was substantial, cutaneous or mucosal flaps were used successfully in an RT field in 85% of the dogs. Flaps that were part of the planned therapy as opposed to those used to correct a complication or failure of RT had a better clinical outcome.
Cutaneous or mucosal flaps can be part of the treatment of dogs with tumor when adjuvant or neoadjuvant RT is to be used.
Veterinary Surgery 01/2005; 34(3):214-22. · 1.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The majority of information on oncology therapies has been reported in humans, canine, and feline patients, and laboratory animals with experimentally induced tumors. A variety of treatments,including radiation therapy, chemotherapy, photodynamic therapy, and others have been used with exotic animals. There are many species of exotic pets, and anatomic differences, as well as husbandry and nutritional requirements, must be taken into account to provide optimal care. By providing a broad overview of therapies and considerations for treatment, this article is intended to provide the practitioner with an overview of approach and options when addressing oncology cases in exotic animals.
Veterinary Clinics of North America Exotic Animal Practice 10/2004; 7(3):757-81, vii.
[Show abstract][Hide abstract] ABSTRACT: In this retrospective study of 57 dogs irradiated for oral acanthomatous epulis, 2 (3.5%) dogs developed a second tumor (sarcoma, osteosarcoma) in the radiation treatment field at 5.2 and 8.7 years after the end of radiation therapy. As opposed to previous reports, no second epithelial tumors developed in the radiation treatment field. There is a risk of radiation-induced carcinogenesis, but it appears that it is a relatively low risk and an event that occurs years after radiation therapy. Radiation-induced tumors are of more concern in younger dogs that undergo radiation therapy for tumors that are radioresponsive, such as acanthomatous epulis, where long-term survival is expected. The only statistically significant variable in the survival analysis was age, with dogs less than 8.3 years old having a significantly longer median overall survival (2322 days) than dogs older than 8.3 years (1106 days; P<0.0001).
[Show abstract][Hide abstract] ABSTRACT: The medical records of 24 dogs with histologically confirmed mast cell tumors (MCT) of the muzzle were retrospectively evaluated to determine their biologic behavior and prognostic factors. Information on signalment, tumor grade and stage, treatment methods, and pattern of and time to failure and death was obtained from the medical record. Twenty-three dogs were treated with combinations of radiotherapy, surgery, and chemotherapy; 1 dog received no treatment. There were 2 Grade 1, 15 Grade 11, and 7 Grade III tumors. Tumors were stage 0 (n = 8), stage 1 (5), stage 2 (6), stage 3 (4), and stage 4 (1). Mean and median survival times of treated dogs were 36 and 30 months, respectively. Prognostic factors affecting survival time included tumor grade and presence of metastasis at diagnosis. Dogs with Grade I and II tumors survived longer than dogs with Grade III tumors. Variables, including sex, age, gross versus microscopic disease, and treatment type were not found to affect survival. Local control rate was 75% at 1 year and 50% at 3 years. Tumor grade was the only variable found to affect local control. Dogs with Grade I tumors had longer disease-free intervals than those with Grade II tumors, and dogs with Grade II tumors had longer disease-free intervals than dogs with Grade III tumors. Eight of 9 dogs dying of MCT had local or regional disease progression. Muzzle MCT a rebiologically aggressive tumors with higher regional metastatic rates than previously reported for MCT in other sites.
Journal of Veterinary Internal Medicine 01/2003; 17(5):687-92. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine expression of a transforming gene (E5) of bovine papillomavirus in sarcoids, other tumors, and normal skin samples collected from horses with and without sarcoids.
23 sarcoids and 6 samples of normal skin obtained from 16 horses with sarcoids, 2 samples of normal skin and 2 papillomas obtained from horses without sarcoids, and 1 papilloma obtained from a cow.
Protein was extracted from tissue samples collected from horses and incubated with agarose beads covalently coupled to Staphylococcus aureus protein A and an anti-E5 polyclonal antibody. Following incubation, proteins were eluted from the beads and electrophoresed on a 14% polyacrylamide gel and transferred to a polyvinylidene difluoride membrane. The E5 protein was detected by use of western blot analysis, using a chemiluminescence detection system.
All 23 sarcoids had positive results for expression of E5 protein. Quantity of viral protein appeared to vary among sarcoids. All other tissues examined had negative results for E5 protein. Highest expression for E5 protein was observed in biologically aggressive fibroblastic variants of sarcoids, compared with expression in quiescent tumors.
This study documented that activation and expression of the E5 gene is evident in sarcoids obtained from horses. These data support the conclusion that infection with bovine papillomavirus is important in the initiation or progression of sarcoids in horses. Treatment strategies designed to increase immune recognition of virally infected cells are warranted.
American Journal of Veterinary Research 09/2001; 62(8):1212-7. · 1.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the incidence of bovine papillomavirus (BPV) type 1 or 2 in sarcoids and other samples of cutaneous tissues collected from horses in the western United States.
55 horses with sarcoids and 12 horses without sarcoids.
Tissue samples (tumor and normal skin from horses with sarcoids and normal skin, papillomas, and nonsarcoid cutaneous neoplasms from horses without sarcoids) were collected. Tissue samples were analyzed for BPV-1 or -2 DNA, using a polymerase chain reaction (PCR) and restriction fragment length polymorphism. The PCR products from 7 sarcoid-affected horses were sequenced to evaluate percentage homology with expected sequences for BPV-1 or-2.
Most (94/96, 98%) sarcoids contained BPV DNA. Sixty-two percent of the tumors examined had restriction enzyme patterns consistent with BPV-2. Thirty-one of 49 (63%) samples of normal skin obtained from horses with sarcoids contained BPV DNA. All samples subsequently sequenced had 100% homology with the expected sequences for the specific viral type. All tissues from healthy horses, nonsarcoid neoplasms, and papillomas were negative for BPV DNA.
Bovine papillomaviral DNA was detected in essentially all sarcoids examined. There appears to be regional variation in the prevalence of viral types in these tumors. The fact that we detected viral DNA in normal skin samples from horses with sarcoids suggests the possibility of a latent viral phase. Viral latency may be 1 explanation for the high rate of recurrence following surgical excision of sarcoids.
American Journal of Veterinary Research 06/2001; 62(5):741-4. · 1.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Basal cell tumors are rare benign tumors in horses. Over a 15-year period, 6 horses were diagnosed with basal cell tumors. The tumors were well-circumscribed. freely moveable, firm, raised papules, nodules, or masses that ranged from 0.6 to 5 cm in diameter. Five of the 6 tumors were ulcerated. Based on gross appearance, the tumors were diagnosed as sarcoids, and 1 was diagnosed as a melanoma. The range of age of affected horses was 6-26 years. The tumors were identified clinically 1 week to 3 years before excision. In 4 horses for which information was available, complete surgical excision was curative with no recurrence 4 months to 2 years after removal.
Journal of Veterinary Internal Medicine 01/2001; 15(1):43-6. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine quality and duration of progression-free survival (PFS) time in dogs with unresectable thyroid carcinomas treated with definitive megavoltage irradiation and analyze prognostic factors of PFS and patterns of failure (local recurrence vs metastasis).
Prospective clinical trial.
25 dogs with locally advanced thyroid carcinomas and no evidence of metastasis.
Dogs were treated with 48 Gy during 4 weeks on an alternate-day schedule of 4 Gy/fraction.
Irradiation was safe and effective for treatment of large unresectable thyroid carcinomas. Progression-free survival rates were 80% at 1 year and 72% at 3 years. Time to maximum tumor size reduction ranged from 8 to 22 months. Factors affecting PFS were not found. Twenty-eight percent (7/25) of dogs developed metastasis. Dogs with bilateral tumors had 16 times the risk of developing metastases, compared with dogs with a single tumor. Dogs with no evidence of tumor progression had 15 times less risk of developing metastases. Radiation-induced hypothyroidism was suspected in 2 dogs 13 and 29 months after irradiation.
Irradiation is effective for local control of thyroid tumors, despite their slow regression rate. Results provided evidence that local tumor control affects metastatic outcome in dogs with thyroid carcinomas and is a strong basis for the development of new approaches that include irradiation in the management of dogs with advanced thyroid carcinomas. Improvements in local tumor control alone may be insufficient to improve survival times because of the high risk of metastatic spread before an initial diagnosis is made, which warrants initiation of early systemic treatment.
Journal of the American Veterinary Medical Association 07/2000; 216(11):1775-9. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To characterize the long-term effects of therapeutic doses of ionizing radiation on the uptake and distribution of percutaneously delivered particulate contrast media in normal lymph nodes.
Two milliliters of an iodinated nanoparticle suspension (76 mg I/mL) was injected subcutaneously or submucosally into nine normal adult beagles. Region of interest analysis was used to estimate the volume, attenuation, and iodine concentration of opacified targeted lymph nodes and nonopacifled contralateral nodes on 24-hour postinjection CT images. All lymph nodes were then irradiated with 50 Gy in 25 fractions of 2 Gy/d. Contrast-enhanced quantitative CT was repeated 12 months after irradiation.
Contrast-enhanced nodes averaged 2.3+/-0.8 times the volume of nonenhanced contralateral nodes before irradiation. The mean attenuation of contrast-enhanced nodes increased to 305 to 380 Hounsfield units from a pre-enhancement value of approximately 25 Hounsfield units. Opacified node volumes after irradiation averaged 61% to 86% of preirradiation volumes but were generally not statistically different. Contrast uptake assessed by average attenuation and iodine concentration decreased significantly by an average of 17% to 22% after irradiation and was significantly less than preirradiation uptake. Qualitatively, irradiated nodes generally appeared smaller than nonirradiated nodes, but the distribution pattern of contrast media did not appear to be appreciably altered.
Lymph node irradiation resulted in only minimal decreases in contrast media uptake and node volume at 12 months. These effects presumably would not appreciably alter the potential clinical value of indirect lymphography for evaluating patients undergoing radiation therapy.
[Show abstract][Hide abstract] ABSTRACT: To assess the influence of tumor cell proliferation and sex-hormone receptors on the efficacy of megavoltage irradiation for dogs with incompletely resected meningiomas.
Longitudinal clinical trial.
20 dogs with incompletely resected intracranial meningiomas.
Dogs were treated with 48 Gy of radiation administered 3 times per week on an alternate-day schedule of 4 Gy/fraction for 4 weeks, using bilateral parallel-opposed fields.
Tumor proliferative fraction measured by immunohistochemical detection of proliferating cell nuclear antigen (PFPCNA index) ranged from 10 to 42% (median, 24%). Progesterone receptor immunoreactivity was detected in 70% of tumors. Estrogen receptor immunoreactivity was not detected. An inverse correlation was found between detection of progesterone receptors and the PFPCNA index. The overall 2-year progression-free survival (PFS) rate was 68%. The only prognostic factor that significantly affected PFS rate was the PFPCNA index. The 2-year PFS was 42% for tumors with a high PFPCNA index (value > or = 24%) and 91% for tumors with a low PFPCNA index (value < 24%). Tumors with a high PFPCNA index were 9.1 times as likely to recur as were tumors with a low PFPCNA index.
This study confirms the value of irradiation for dogs with incompletely resected meningiomas. Prognostic value of the PFPCNA index suggests-that duration of treatment and interval from surgery to start of irradiation may affect outcome. Loss of progesterone receptors in some tumors may be responsible for an increase in PFPCNA index and may indirectly affect prognosis after radiation therapy.
Journal of the American Veterinary Medical Association 03/2000; 216(5):701-7, 684-5. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the benefits of reducing the interval between surgical cytoreduction and intratumoral administration of cisplatin.
Randomized clinical study.
70 horses with 89 incompletely resected T2- and T3-stage sarcoids (n = 64) and squamous cell carcinomas (25).
Horses were given 4 intratumoral treatments of cisplatin at 2-week intervals. The first treatment was given at the time of, or immediately after, surgical resection for horses treated in accordance with the perioperative protocol (group 1). Horses in group 2 were treated with cisplatin after the skin healed following surgical resection in accordance with the postoperative protocol.
A difference was not found in duration of overall local tumor control between the 2 groups. Patterns of treatment failures and interval to failure differed between the 2 groups. Length of the surgical scar was the only factor that affected prognosis; an increase in length was associated with a poorer prognosis. A detrimental effect of postoperative treatment was only found in tumors with a high tumor proliferative fraction. Local reactions were similar for the 2 treatment groups, and chronic reactions were not observed.
Intratumoral administration of cisplatin is beneficial for treatment of cutaneous tumors in horses. Tumor repopulation during the interval between surgery and intratumoral administration of cisplatin decreases treatment efficacy. These results provide evidence of rapid tumor repopulation following surgical resection without a lag period for tumors with a high proliferation index. When tumor proliferation index is not known, it may be prudent to use the perioperative protocol.
Journal of the American Veterinary Medical Association 01/2000; 215(11):1655-60. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine effects of glutamine-supplemented and glutamine-free amino acid-based purified diets, compared with a dry expanded diet, on intestinal structure and function in a model that used cats with methotrexate-induced enteritis.
18 adult specific-pathogen-free cats.
12 cats were given intragastric feedings of an amino acid-based purified diet supplemented with glutamine (7% [wt:wt]) or an isonitrogenous amount of glycine and alanine; 6 cats consumed a dry expanded diet. After 21 days, cats received methotrexate (MTX; 11 mg/kg of body weight, IV). Intestinal permeability testing was performed immediately before and 66 hours after MTX administration. Celiotomy was performed 72 hours after MTX administration for aseptic removal of mesenteric lymph nodes, collection of full-thickness intestinal biopsy specimens, determination of intestinal cellular proliferation, and collection of aortic and portal venous blood samples for determination of arteriovenous amino acid concentrations across the intestine.
Administration of MTX was associated with severe enterotoxicosis manifested as diarrhea (8/12 cats), vomiting (12/12), and positive results for bacterial culture of mesenteric lymph nodes (12/12) in cats receiving the purified diets, independent of glutamine supplementation. Diet did not affect villus tip length and villus surface area in the small intestine or cellular proliferation. Administration of MTX was associated with significantly increased intestinal permeability, which was not attenuated by glutamine supplementation.
Feeding of a glutamine-supplemented amino acid-based purified diet was unable to preserve intestinal function in cats with MTX-induced enteritis.
Intestinal morphologic alterations correlate poorly with intestinal function as measured by means of bacterial translocation and intestinal permeability.
American Journal of Veterinary Research 07/1999; 60(6):755-63. · 1.35 Impact Factor