Platelet function in dogs treated for lymphoma and hemangiosarcoma and supplemented with dietary n-3 fatty acids

A prospective randomized, double-blind clinical trial was performed to test the hypothesis that dogs with malignancies that are supplemented with n-3 fatty acids do not have clinical or laboratory evidence of coagulation disorders or altered platelet function when compared with unsupplemented dogs with similar malignancies. Thirteen dogs with hemangiosarcoma and 66 dogs with lymphoma were evaluated. Coagulation status of the dogs with lymphoma and hemangiosarcoma was evaluated with prothrombin time, partial thromboplastin time, platelet count, and in vitro platelet aggregometry using the whole-blood method. These tests were performed at 5 time points: before beginning the diet (week 0), at weeks 3, 15, and 21, and at 1 year or when progressive disease was evident. Alterations in platelet function in dogs receiving a diet supplemented with dietary n-3 fatty acids were not identified when compared to dogs fed a control diet. Dietary n-3 fatty acid supplementation using this dosage and ratio in dogs with lymphoma or hemangiosarcoma did not induce clinically significant hemorrhage in these animals. Therefore, supplementation with n-3 fatty acids did not result in clinical or laboratory evidence relating to uncontrolled hemorrhage in these dogs.     

Comparison of the effects of asparaginase administered subcutaneously versus intramuscularly for treatment of multicentric lymphoma in dogs receiving doxorubicin

OBJECTIVE: To determine the effectiveness and safety of asparaginase administered s.c. versus i.m. for treatment of multicentric lymphoma in dogs receiving doxorubicin. DESIGN: Prospective study. ANIMALS: 49 dogs with multicentric lymphoma. PROCEDURE: Dogs were treated with doxorubicin every 3 weeks, for a total of 5 treatments, and were given 3 weekly treatments of asparaginase, s.c. or i.m. Using high-performance liquid chromatography, mean plasma asparagine, aspartic acid, glutamine, and glutamic acid concentrations were determined in dogs before and during treatment with asparaginase (10,000 U/m2 of body surface area, once a week for 3 weeks). Asparaginase was administered s.c. in 23 dogs and i.m. in 26 dogs. Variables evaluated included time to response to chemotherapy, remission and survival times, and clinical and serum biochemical indicators of toxicoses. RESULTS: Using the World Health Organization's staging system for lymphoma, 30 dogs were in clinical stage III and 19 were in clinical stage IV. One week after asparaginase treatment, plasma asparagine concentrations were low and plasma aspartic acid, glutamine, and glutamic acid concentrations were high. Differences in plasma amino acid concentrations were not found between s.c. and i.m. groups. For dogs in clinical stage IV, i.m. administration of asparaginase significantly decreased the number of days to complete remission, compared with s.c. administration (8 vs 17 days, respectively). For dogs in clinical stage III, i.m. administration favorably increased the duration of first remission (191 vs 103 days) and survival time (289 vs 209 days). Overall, dogs treated i.m. had a faster response to chemotherapy (9 vs 15 days), a longer remission (191 vs 109 days), and a longer survival time (286 vs 198 days), compared with all dogs treated s.c. Asparaginase toxicoses were not observed regardless of the route of administration. CLINICAL IMPLICATIONS: For dogs with multicentric lymphoma that are receiving doxorubicin, i.m. treatment with asparaginase is more effective than s.c. treatment.     

Efficacy of a continuous, multiagent chemotherapeutic protocol versus a short-term single-agent protocol in dogs with lymphoma

OBJECTIVE: To compare response rates and remission and survival times in dogs with lymphoma treated with a continuous, multiagent, doxorubicin-based chemotherapeutic protocol or with a short-term single-agent protocol incorporating doxorubicin. DESIGN: Nonrandomized controlled clinical trial. ANIMALS: 114 dogs with lymphoma. PROCEDURES: Dogs were treated with a chemotherapeutic protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate, and prednisolone (n=87) or doxorubicin alone (27). RESULTS: 63 of 86 (73%) dogs treated with the multiagent protocol (data on response was unavailable for 1 dog) and 14 of 27 (52%) dogs treated with the single-agent protocol had a complete remission. Dogs with lymphoma classified as substage相似文献   

Is Maintenance Chemotherapy Appropriate for the Management of Canine Malignant Lymphoma?

A retrospective study was conducted between two groups of dogs with histopathologically diagnosed multicentric malignant lymphoma to determine if treatment with either short-term or continuous chemotherapy resulted in a significant difference in first-remission length or survival time. One group was treated with single agent, short-term (three cycles) of doxorubicin. Dogs obtaining complete remission while receiving doxorubicin were given no further chemotherapy. The other group received combination agent, long-term chemotherapy consisting of cyclophosphamide, vincristine sulfate, and prednisone (COP). Dogs obtaining complete remission on COP by the end of 6 weeks were given maintenance chemotherapy of cyclophosphamide, prednisone and methotrexate. One hundred and five dogs were treated. Thirty-eight dogs received doxorubicin and 67 received COP. All dogs were evaluated at 6 weeks for response to chemotherapy and followed until death. No significant differences were observed in first-remission length or survival time when comparing dogs treated with either short-term doxorubicin or long-term COP (P greater than 0.05). Sex, weight, age, clinical stage, performance status, histopathologic cell type, and grade were not significant factors for determining the responsiveness to either chemotherapy protocol. However, within either treatment group, significant differences in first-remission length were observed in dogs evaluated histopathologically by the Keil and NCI working formulation and in survival time when evaluated by performance status (P less than 0.05).     

Evaluation of a Multidrug Chemotherapy Protocol (ACOPA II) in Dogs With Lymphoma

A chemotherapeutic protocol using cyclophosphamide, vincristine, prednisone, doxorubicin, and L-asparaginase (ACOPA II) was evaluated in dogs with lymphoma. The response rate for 68 dogs treated with ACOPA II (complete remission [CR] 65%, partial remission [PR] 10%) was lower than that for 41 dogs treated with a related protocol previously evaluated (ACOPA I; CR 76%, PR 12%). Initial treatment with doxorubicin and prednisone did not decrease the prevalence or severity of toxicity during induction. The mortality during induction was 22%. The median duration of CR for dogs treated with ACOPA II was 9 months, with 40% still in remission at 1 year and 21% at 2 years. The rate of CR was lower for dogs with signs of illness at presentation (substage b ) and for dogs weighing less than 15 kg. Age was negatively correlated with survival time and duration of remission. Dogs with immunoblastic lymphoma had a more favorable prognosis than did those with lymphoblastic lymphoma. Survival times were also longer for dogs in substage a at presentation. Seven dogs in which treatment was discontinued while in remission had comparable remission duration to that achieved by dogs receiving long-term maintenance chemotherapy.     

Effect of age, breed and dietary omega-6 (n-6): omega-3 (n-3) fatty acid ratio on immune function, eicosanoid production, and lipid peroxidation in young and aged dogs.

The focus of this study was to examine the influence of age and diet on various parameters of immune function in young and old Fox Terriers and Labrador Retrievers. Eighteen young and old dogs were utilized for this study. Young and old dogs were fed a basal diet containing an (n-6):(n-3) ratio of 25:1 for sixty days (Phase I). Half of the dogs were then switched to a diet with an (n-6):(n-3) ratio of 5:1, and all were maintained on their respective diets for an additional sixty days (Phase II). Results from these studies revealed an age-associated decline in several immune parameters measured. Both these breeds demonstrated a reduction in sheep red blood cell titers, as well as in their ability to respond to different mitogens. Interestingly, this decline was greater in Fox Terriers, suggesting a decrease in cellular proliferative capacity in lymphocytes isolated from the larger breed. Neither cytokine production or DTH response was affected by age. Diet and breed interactions resulted in a significant increase in T- and B-cell mitogen responsiveness. In contrast, supplementation with n-3 fatty acids did not affect IL-1, IL-6 or TNF-alpha production. Supplementation with n-3 fatty acids resulted in increased PGE3 production from peritoneal macrophages but had no effect on PGE2 production from peripheral blood mononuclear cells or peritoneal macrophages. The n-3 fatty acid supplementation did not influence alpha-tocopherol status although older dogs had significantly lower serum alpha-tocopherol concentrations. Oxidative status of these dogs was assessed by serum levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Feeding an n-3-enriched diet did not affect 4-HNE levels but significantly decreased MDA levels in old dogs. In summary, this study indicates that feeding a diet containing an (n-6):(n-3) fatty acid ratio of 5:1 had a positive, rather than a negative, effect on the immune response of young or geriatric dogs.     

Evaluation of a discontinuous treatment protocol (VELCAP-S) for canine lymphoma

Eighty-two dogs with lymphoma received a single 15-week course of chemotherapy, after which treatment was ceased until relapse. Fifty-six dogs (68%) achieved complete remission for a median 1st remission duration of 20 weeks. Forty-eight dogs relapsed, of which 30 repeated the induction cycle. In 22 of these dogs, 1st remission had been short, and they received maintenance chemotherapy; the other 8 dogs received 2 or 3 cycles of induction chemotherapy. Second remission rate for these 30 dogs was 87% (26 dogs). Overall disease control for the 38 dogs that remained on protocol was 44 weeks, which was not markedly shorter than for dogs treated with a previously reported protocol in which maintenance chemotherapy was instituted in all dogs after an identical 1st induction (VELCAP-L). Dogs that were febrile and dogs that were dyspneic were less likely to achieve a complete remission to induction chemotherapy. Of dogs that achieved a complete remission, those that were thrombocytopenic at entry had a shorter 1st remission, and dogs that were anorexic at entry had shorter overall disease control. There was a correlation between 1st remission duration and length of any subsequent remission obtained. The incidence of toxicity was high, particularly after the combination of doxorubicin and vincristine. Dose reductions because of toxicity did not markedly reduce remission duration. We conclude that discontinuous chemotherapy may reduce patient visits in a small number of patients because of long-term disease control. Delaying maintenance chemotherapy until after 2nd remission is achieved does not markedly affect overall disease control.     

A Combination Chemotherapy Protocol (VELCAP-L) for Dogs with Lymphoma

Ninety-eight dogs with lymphoma treated with a 5-drug combination chemotherapy regimen (vincristine, L-asparaginase. cyclophosphamide, doxorubicin, prednisone [VELCAP-L]) were evaluated for pretreatment characteristics predictive for response and remission duration. The complete remission rate was 69%, with a median remission duration of 55 weeks. Dogs with advanced stage of disease, constitutional signs, dogs that were older, and dogs that were dyspneic were less likely to achieve remission. Once in remission, small dogs and dogs without pretreatment thrombocytopenia were likely to have longer remission duration. Toxicoses were frequent, but rarely fatal, and no predictitive factors were found for a dog developing toxicoses. VELCAP-L is an effective treatment for dogs in stage I-III lymphoma, particularly in young, small animals.     

Chemotherapy and remission status do not alter pre-existing innate immune dysfunction in dogs with lymphoma

Dogs with lymphoma have altered innate immunity and little is known about the effects of chemotherapy on innate immune function in dogs. Lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PG) – induced leukocyte cytokine production capacity, and phagocytosis and respiratory burst were evaluated in dogs prior to and following 6 weeks of chemotherapy. Dogs had decreased TNF production following LPS stimulation and increased IL-10 production following PG stimulation, which did not improve following remission of lymphoma. Dogs also had reduced E. coli-induced respiratory burst function after chemotherapy induced complete or partial remission. Dogs with lymphoma have an imbalance in pro-and anti-inflammatory cytokine production which did not improve with remission, and, following treatment, a decrease in respiratory burst function. Altered immune responses following exposure to bacterial pathogen associated molecular pattern motifs and bacteria may have many implications in the management of canine lymphoma.     

Effect of n-3 fatty acid ratio and dose on clinical manifestations,plasma fatty acids and inflammatory mediators in dogs with pruritus

The use of n-3 fatty acids is often recommended to manage pruritus. The purpose of this study was to determine the effect of various doses of n-3 fatty acids at different n-6:n-3 ratios on plasma fatty acids, clinical response and inflammatory mediators in pruritic dogs. After baseline assessment, dogs were randomly assigned to receive diets varying in both total n-3 and n-6 fatty acid dose and n-6:n-3 ratio. The total clinical score decreased significantly in all four diet groups after 8 weeks with no difference between groups. Plasma fatty acid changes generally mirrored the fatty acid content of the test diets, although alterations appeared to depend on both the dose of n-3 fatty acids and the n-6:n-3 ratio. In this clinical trial, which controlled dietary intake of fatty acids, n-3 fatty acid supplementation did not appear to have an added benefit on clinical signs over thorough clinical management.     

Effects of dietary n-6 and n-3 fatty acids and vitamin E on the immune response of healthy geriatric dogs

OBJECTIVE: To determine the effect of dietary n-6 to n-3 fatty acid ratios and alpha-tocopheryl acetate concentration on immune functions andT cell subpopulations in healthy dogs. ANIMALS: Thirty-two 7- to 10-year old female Beagles. PROCEDURE: For 17 weeks, dogs were fed food that contained low (1.4:1) or high (40:1) ratios of n-6 to n-3 fatty acids in combination with 3 concentrations of all rac-alpha-tocopheryl acetate (low, 17 mg/kg of food; medium, 101 mg/kg; high, 447 mg/kg). Dogs were inoculated twice with a keyhole limpet hemocyanin suspension at 13 and 15 weeks. RESULTS: After 12 weeks, dogs consuming low concentrations of alpha-tocopheryl acetate had lower percentages of CD8+ T cells, compared with dogs consuming medium or high alpha-tocopheryl acetate concentrations. Also, dogs consuming low alpha-tocopheryl acetate concentrations had higher CD4+ to CD8+ T cell ratios. On day 4 of week 15, the percentage of CD8+ T cells was highest in dogs fed medium concentrations of alpha-tocopheryl acetate, compared with other dogs; however, the CD4+ to CD8+ T cell ratio was higher only in dogs fed low concentrations of alpha-tocopheryl acetate with high concentrations of n-3 fatty acids. Dogs consuming low concentrations of n-3 fatty acids with medium concentrations of alpha-tocopheryl acetate had the largest delayed-type hypersensitivity (DTH) skin test response. CONCLUSIONS AND CLINICAL RELEVANCE: An optimum amount of dietary alpha-tocopheryl acetate concentration, regardless of the dietary n-6 to n-3 fatty acid ratio, stimulates the CD8+ T cell population. Effects of an optimum amount of dietary alpha-tocopheryl acetate concentration on the DTH response are blunted by dietary n-3 fatty acids.     

Sequential Low-Dose Rate Half-Body Irradiation and Chemotherapy for the Treatment of Canine Multicentric Lymphoma

Background: 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.
Hypothesis: LDRI incorporated into a cyclophosphamide, doxorubicin, vincritine, and prednisone (CHOP)-based chemotherapy protocol is effective for the treatment of lymphoma in dogs.
Animals: Thirty-eight client-owned animals diagnosed with multicentric lymphoma.
Methods: Retrospective study evaluating the efficacy and prognostic factors for the treatment of canine lymphoma with sequential HBI and chemotherapy.
Results: 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%.
Conclusions and Clinical Relevance: 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.     

Clinical characteristics, treatment, and outcome of dogs with presumed primary hepatic lymphoma: 18 cases (1992-2008)

OBJECTIVE-To determine outcome of dogs with presumed primary hepatic lymphoma treated with various multiagent, doxorubicin-based chemotherapeutic protocols and identify factors associated with prognosis. DESIGN-Retrospective case series. ANIMALS-18 dogs with presumed primary hepatic lymphoma. PROCEDURES-Medical records were reviewed for information on signalment, treatment, and outcome. RESULTS-8 dogs had a complete remission (CR), with a median remission duration of 120 days. Dogs with leukocytosis, neutrophilia, hypoalbuminemia, hyperbilirubinemia, or a combination of hypoalbuminemia and hyperbilirubinemia were less likely to achieve a CR. Overall median survival time (MST) was 63 days (range, 2 to 402 days). In a multivariate analysis, response to treatment and serum albumin concentration were associated with MST. Dogs that did not achieve a CR had a significantly shorter MST than did dogs that did achieve a CR (13 vs 283 days, respectively). Dogs with serum albumin concentration < 2.5 g/dL at the time treatment was initiated had a significantly shorter MST than did dogs with serum albumin concentration within reference limits (10 vs 128 days, respectively). There was also a positive correlation between serum albumin concentration and survival time (r = 0.74). CONCLUSIONS AND CLINICAL RELEVANCE-Results suggested that dogs with primary hepatic lymphoma that underwent chemotherapy had a poor prognosis, with a low response rate. Dogs that responded to treatment had a better prognosis, and dogs with hypoalbuminemia had a poorer prognosis.     

Evaluation of Single-Agent Mitoxantrone as Chemotherapy for Relapsing Canine Lymphoma

Many chemotherapeutic regimens will induce remission in dogs with lymphoma, but almost all dogs suffer relapse. Mitoxantrone was selected for evaluation as single-agent chemotherapy for relapsing canine lymphoma based on its use in humans undergoing salvage chemotherapy for non-Hodgkin's lymphoma and its tumoricidal effect against canine lymphoma. Dogs entered into study had multicentric lymphoma, and all had been treated solely with a standard combination chemotherapy protocol. At 1st relapse, all dogs were again staged and underwent lymph node biopsy. Mitoxantrone was administered IV at 6 mg/m² every 21 days. Dogs were evaluated for lymphadenopathy before each dose of mitoxantrone. Fifteen dogs were entered into study. The average age (±SEM) of the dogs studied was 7.7 ± 0.91 years, and most dogs were large (mean ± SEM weight, 24.44 ± 2.15 kg). Twelve dogs (80%) had B-cell lymphoma, and 3 had T-cell lymphoma. Dogs were staged IV (n = 12) or V (n = 3). The median duration of chemotherapy before entry into the study was 98 days. Overall median duration of response after mitoxantrone chemotherapy was 21 days. Complete responses were attained in 7 of 15 dogs (47%) with a median response duration of 84 days. Nine of 15 (60%) dogs attained a complete remission with additional chemotherapy after failing mitoxantrone chemotherapy. Mild toxicities were observed after mitoxantrone administration. No adverse reactions were observed during mitoxantrone infusions. The results of this study demonstrate that mitoxantrone, as a single agent, has limited value for dogs with lymphoma at 1st relapse after conventional multidrug chemotherapy.     

Impact of chemotherapeutic dose intensity and hematologic toxicity on first remission duration in dogs with lymphoma treated with a chemoradiotherapy protocol

BACKGROUND: Dose intensity has proven to be critical in maximizing chemotherapeutic efficacy for numerous human cancers. To date, the impact of dose intensity and toxicity on first remission duration has not been thoroughly assessed in dogs with lymphoma. HYPOTHESIS: Dogs that receive maximal dose intensity will have prolonged first remission duration. ANIMALS: Sixty-two dogs with lymphoma that were treated according to a standardized chemoradiotherapy regimen and achieved durable complete remissions were identified from the medical records database of North Carolina State University. METHODS: Dosage reductions and treatment delays resulting from chemotherapy-related neutropenia were evaluated retrospectively, and each patient's actual summation dose intensity and frequency of myelotoxicity were calculated. Impact of dose intensity and frequency of neutropenia on first remission duration were evaluated by Cox proportional hazards regression. RESULTS: Development of grade III or IV neutropenia during chemotherapy was found to be associated with prolonged first remission duration (P < .01). Dose intensity did not have a significant impact on remission duration (P = .07). CONCLUSIONS AND CLINICAL IMPORTANCE: Results of this study suggest that dosage reductions and treatment delays instituted to avoid repeated neutropenic episodes do not reduce first remission duration. Prolonged remission duration in patients that developed grade III or IV neutropenic episodes indicates the need for further optimization of dosing strategies for canine lymphoma patients undergoing chemotherapy.     

Autologous marrow transplantation as consolidation therapy for canine lymphoma: efficacy and toxicity of various regimens of total body irradiation

Dogs with malignant lymphoma were given chemotherapy consisting of nitrogen mustard, vincristine sulfate, prednisone, L-asparaginase, and 6-mercaptopurine (MOPA-6) for 14 days. Among 62 dogs that completed treatment with MOPA-6, 47 (76%) had complete remission, and 13 (21%) had partial remission and 2 had no response to chemotherapy. Twenty-two of the 62 dogs were not returned by their owners for additional therapy and died 15 to 391 (median 21) days after MOPA-6 from infections or recurrent disease. A median of 1 month after starting MOPA-6 therapy, 40 dogs (35 in complete remission, 5 in partial remission) were given total body irradiation (TBI), followed by infusion of fresh autologous marrow. Twenty dogs were given 13.5 Gray (Gy) of TBI at 4 centi-Gray (cGy)/min. Among 16 evaluable dogs, 7 had recurrence of lymphoma at a median of 169 days. Two dogs died with veno-occlusive disease of the liver, 3 with pneumonia, 3 with hemorrhage, and 1 was killed. Twenty dogs were given 11.8 to 14.7 Gy of TBI at 2 cGy/min. Among 14 evaluable dogs, 9 had recurrence of lymphoma at a median of 117 days. The remaining 5 dogs were killed at 110 to 680 days; lymphoma was not present at necropsy. The results indicated that doses of TBI of 11.8 to 14.7 Gy did not reduce the recurrence of lymphoma, compared with results obtained in a previous study with 8.4 Gy of TBI. Furthermore, increased doses of TBI increased acute and delayed toxicities. Alternatively, recurrent disease may have been due to lymphoma cells contained in the infused remission marrow.     

Histologic classification as an indication of therapeutic response in malignant lymphoma of dogs

In retrospective evaluation of treatment of canine malignant lymphoma, 12 of 13 dogs that had received doxorubicin alone or in combination with dacarbazine attained complete remission. Doxorubicin had been given alone, with combination chemotherapy being used only when complete remission could not be achieved and maintained with doxorubicin. The response to single or combined chemotherapy was correlated with histologic cell type of the malignant lymphoma. Histiocytic cell types did not respond to doxorubicin alone, but lymphoblastic types did respond. Combination chemotherapy was effective against histiocytic types. A mixed-cell type, which was initially responsive to doxorubicin alone, but not responsive after relapse, was observed to be histiocytic on rebiopsy.     

Antioxidant Status and Biomarkers of Oxidative Stress in Dogs with Lymphoma

Background: Oxidative stress might play a role in carcinogenesis, as well as impacting morbidity and mortality of veterinary cancer patients. The purpose of this study was to evaluate antioxidant concentrations and biomarkers of oxidative stress in dogs with newly diagnosed lymphoma before treatment and once in remission, with comparison with healthy controls.
Hypothesis: Dogs with lymphoma have increased oxidant and reduced antioxidant concentrations compared with healthy controls, and that these abnormalities normalize once remission is achieved.
Animals: Seventeen dogs with lymphoma and 10 healthy controls.
Methods: Prospective, observational study. Measures of oxidative stress [malondialdehyde and total isoprostanes (isoP)] and antioxidants [α-tocopherol, γ-tocopherol, oxygen radical absorbance capacity (ORAC), and glutathione peroxidase (GSHPx)] were assessed in dogs with newly diagnosed lymphoma before treatment compared with healthy control dogs. The same parameters were measured in the dogs with lymphoma on week 7 of the chemotherapy protocol when all dogs were in remission.
Results: At baseline, dogs with lymphoma had significantly lower α-tocopherol ( P <.001) and γ-tocopherol ( P = .003) but higher GSHPx ( P = .05), ORAC ( P = .001), and isoP ( P < .001) compared with healthy controls. In the dogs with lymphoma, α-tocopherol concentrations were higher ( P = .005) and ascorbic acid were lower ( P = .04) after treatment.
Conclusions and Clinical Importance: Results suggest that dogs with lymphoma have alterations in oxidant and antioxidant concentrations and that the status of some of these biomarkers normalize after remission. Further studies are warranted to determine whether antioxidant interventions to correct these are beneficial in the treatment of canine lymphoma.     

Effects of carnitine and taurine on fatty acid metabolism and lipid accumulation in the liver of cats during weight gain and weight loss

OBJECTIVE: To determine the effects of carnitine (Ca) or taurine (Ta) supplementation on prevention of lipid accumulation in the liver of cats. ANIMALS: 24 adult cats. PROCEDURE: Cats were fed a weight-gaining diet sufficient in n-6 polyunsaturated fatty acids (PUFAs), low in long-chain n-3 PUFAs (n-3 LPUFA), and containing corn gluten for 20 weeks. Cats gained at least 30% in body weight and were assigned to 4 weight-reduction diets (6 cats/diet) for 7 to 10 weeks (control diet, control plus Ca, control plus Ta, and control plus Ca and Ta). RESULTS: Hepatic lipids accumulated significantly during weight gain and weight loss but were not altered by Ca orTa after weight loss. Carnitine significantly increased n-3 and n-6 LPUFAs in hepatic triglycerides, decreased incorporation of 13C palmitate into very-low-density lipoprotein and hepatic triglycerides, and increased plasma ketone bodies. Carnitine also significantly increased weight loss but without altering the fat to lean body mass ratio. Taurine did not significantly affect any variables. Diets low in n-3 LPUFAs predisposed cats to hepatic lipidosis during weight gain, which was further exacerbated during weight loss. Mitochondrial numbers decreased during weight gain and weight loss but were not affected by treatment. Carnitine improved fatty acid oxidation and glucose utilization during weight loss without correcting hepatic lipidosis. CONCLUSIONS AND CLINICAL RELEVANCE: The primary mechanism leading to hepatic lipidosis in cats appears to be decreased fatty acid oxidation. Carnitine may improve fatty acid oxidation but will not ameliorate hepatic lipidosis in cats fed a diet low in n-3 fatty acids.     

Comparison of 3 protocols for treatment after induction of remission in dogs with lymphoma

BACKGROUND: The optimal treatment after inducing complete remission (CR) in dogs with lymphoma has not been established. HYPOTHESIS: After inducing CR with L-asparaginase, vincristine, cyclophosphamide, doxorubicin, prednisone (L-CHOP); consolidation with either half-body radiation therapy (HBRT); or lomustine (CCNU) and mechlorethamine, vincristine, procarbazine, prednisone (MOPP) would improve first remission duration compared with continuing a CHOP-based protocol for an additional 4 months. ANIMALS: Dogs with stage III-V lymphoma. METHODS: Prospective clinical trial in which dogs initially were treated with an 8-week induction protocol that consisted of L-CHOP. Dogs in CR after induction were then allocated to 1 of 2 consolidation arms. A chemotherapy consolidation arm consisted of 2 treatments with CCNU and 1 cycle of MOPP. A HBRT arm consisted of 2 sequential 8.0-Gy fractions to the cranial and caudal half-body separated by 30 days. Vincristine was given between fractions. Results of the consolidation arms also were compared with a historical group treated with the same 8-week induction protocol followed by CHOP therapy until week 24. RESULTS: Overall, 67% of the dogs were in CR after 8 weeks of induction chemotherapy and were compared. Fifty-two dogs were in the historical arm, 23 in the CCNU/MOPP arm, and 27 in the HBRT arm. No difference in first remission duration was found among groups. Median first remission duration for the historical, CCNU/MOPP, and HBRT arms were 307, 274, and 209 days, respectively (P = .28). Overall second CR rate was 82% and was not different among groups (all P > or = .58). Overall remission duration (P = .28) and survival time (P = .48) were not different among groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Consolidation with either CCNU/MOPP or HBRT showed no advantage over a standard CHOP-based protocol.