Normal muscle fiber type distribution is recapitulated in aged ephrin-A3-/- mice that previously lacked most slow myofibers.

Individual limb muscles have characteristic representation and spatial distribution of muscle fiber types (one slow and up to three fast isoforms) appropriate to their unique anatomical location and function. This distribution can be altered by physiological stimuli such as training (i.e., for increased endurance or force) or pathological conditions such as aging. Our group previously showed that ephrin-A3 is expressed only on slow myofibers, and that adult mice lacking ephrin-A3 have dramatically reduced numbers of slow myofibers due to postnatal innervation of previously slow myofibers by fast motor neurons. In this study, fiber type composition of hindlimb muscles of aged and denervated/reinnervated C57BL/6 and ephrin-A3-/- mice was analyzed to determine whether the loss of slow myofibers persists across the lifespan. Surprisingly, fiber-type composition of ephrin-A3-/- mouse muscles at two years of age was nearly indistinguishable from age-matched C57BL/6 mice. After challenge with nerve crush, the percentage of IIa and I/IIa hybrid myofibers increased significantly in aged ephrin-A3-/- mice. While EphA8, the receptor for ephrin-A3, is present at all neuromuscular junctions (NMJs) on fast fibers in 3-6 mo old C57BL/6 and ephrin-A3-/- mice, this exclusive localization is lost with aging, with EphA8 expression now found on a subset of NMJs on some slow muscle fibers. This return to appropriate fiber-type distribution given time and under use reinforces the role of activity in determining fiber-type representation and suggests that, rather than being a passive baseline, the developmentally and evolutionarily selected fiber type pattern may instead be actively reinforced by daily living.

Analysis of lomustine drug content in FDA-approved and compounded lomustine capsules.

OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

Nature experience reduces rumination and subgenual prefrontal cortex activation.

Urbanization has many benefits, but it also is associated with increased levels of mental illness, including depression. It has been suggested that decreased nature experience may help to explain the link between urbanization and mental illness. This suggestion is supported by a growing body of correlational and experimental evidence, which raises a further question: what mechanism(s) link decreased nature experience to the development of mental illness? One such mechanism might be the impact of nature exposure on rumination, a maladaptive pattern of self-referential thought that is associated with heightened risk for depression and other mental illnesses. We show in healthy participants that a brief nature experience, a 90-min walk in a natural setting, decreases both self-reported rumination and neural activity in the subgenual prefrontal cortex (sgPFC), whereas a 90-min walk in an urban setting has no such effects on self-reported rumination or neural activity. In other studies, the sgPFC has been associated with a self-focused behavioral withdrawal linked to rumination in both depressed and healthy individuals. This study reveals a pathway by which nature experience may improve mental well-being and suggests that accessible natural areas within urban contexts may be a critical resource for mental health in our rapidly urbanizing world.

Effect of feeding a weight loss food beyond a caloric restriction period on body composition and resistance to weight gain in cats.

OBJECTIVE: To determine the effect of feeding a food with coconut oil and supplemental L-carnitine, lysine, leucine, and fiber on weight loss and maintenance in cats. DESIGN: Prospective clinical study. ANIMALS: 50 overweight cats. PROCEDURES: The study consisted of 2 trials. During trial 1, 30 cats were allocated to 3 groups (10 cats/group) to be fed a dry maintenance cat food to maintain body weight (group 1) or a dry test food at the same amount on a mass (group 2) or energy (group 3) basis as group 1. During trial 2, each of 20 cats was fed the test food and caloric intake was adjusted to maintain a weight loss rate of 1%/wk (weight loss phase). Next, each cat was fed the test food in an amount calculated to maintain the body weight achieved at the end of the weight loss phase (weight maintenance phase). Cats were weighed and underwent dual-energy x-ray absorptiometry monthly. Metabolomic data were determined before (baseline) and after each phase. RESULTS: During trial 1, cats in groups 2 and 3 lost significantly more weight than did those in group 1. During trial 2, cats lost a significant amount of body weight and fat mass but retained lean body mass during the weight loss phase and continued to lose body weight and fat mass but gained lean body mass during the weight maintenance phase. Evaluation of metabolomic data suggested that fat metabolism was improved from baseline for cats fed the test food. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that feeding overweight cats the test food caused weight loss and improvements in body condition during the weight maintenance phase, possibly because the food composition improved energy metabolism.

Effect of feeding a weight loss food beyond a caloric restriction period on body composition and resistance to weight gain in dogs.

OBJECTIVE: To determine the effect of feeding a food with coconut oil and supplemental L-carnitine, lipoic acid, lysine, leucine, and fiber on weight loss and maintenance in dogs. DESIGN: Prospective clinical study. ANIMALS: 50 overweight dogs. PROCEDURES: The study consisted of 2 trials. During trial 1, 30 dogs were allocated to 3 groups (10 dogs/group) to be fed a dry maintenance dog food to maintain body weight (group 1) or a dry test food at the same amount on a mass (group 2) or energy (group 3) basis as group 1. During trial 2, each of 20 dogs was fed the test food and caloric intake was adjusted to maintain a weight loss rate of 1% to 2%/wk (weight loss phase). Next, each dog was fed the test food in an amount calculated to maintain the body weight achieved at the end of the weight loss phase (weight maintenance phase). Dogs were weighed and underwent dual-energy x-ray absorptiometry monthly. Metabolomic data were determined before (baseline) and after each phase. RESULTS: During trial 1, dogs in groups 2 and 3 lost significantly more weight than did those in group 1. During trial 2, dogs lost a significant amount of body weight and fat mass but retained lean body mass (LBM) during the weight loss phase and continued to lose body fat but gained LBM during the weight maintenance phase. Evaluation of metabolomic data suggested that fat metabolism and LBM retention were improved from baseline for dogs fed the test food. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that feeding overweight dogs the test food caused weight loss and improvements in body condition during the weight-maintenance phase, possibly because the food composition improved energy metabolism.

Impact of cognitive behavioral therapy for social anxiety disorder on the neural dynamics of cognitive reappraisal of negative self-beliefs: randomized clinical trial.

IMPORTANCE: Cognitive behavioral therapy (CBT) for social anxiety disorder (SAD) is thought to enhance cognitive reappraisal in patients with SAD. Such improvements should be evident in cognitive reappraisal-related prefrontal cortex responses. OBJECTIVE: To determine whether CBT for SAD modifies cognitive reappraisal-related prefrontal cortex neural signal magnitude and timing when implementing cognitive reappraisal with negative self-beliefs. DESIGN Randomized clinical trial of CBT for SAD vs wait-list control group during a study that enrolled patients from 2007 to 2010. SETTING: University psychology department. PARTICIPANTS: Seventy-five patients with generalized SAD randomly assigned to CBT or wait list. INTERVENTION: Sixteen sessions of individual CBT for SAD. MAIN OUTCOME MEASURES: Negative emotion ratings and functional magnetic resonance imaging blood oxygen-level dependent signal when reacting to and cognitively reappraising negative self-beliefs embedded in autobiographical social anxiety situations. RESULTS During reactivity trials, compared with wait list, CBT produced (1) greater reduction in negative emotion ratings and (2) greater blood oxygen-level dependent signal magnitude in the medial prefrontal cortex. During cognitive reappraisal trials, compared with wait list, CBT produced (3) greater reduction in negative emotion ratings, (4) greater blood oxygen level-dependent signal magnitude in the dorsolateral and dorsomedial prefrontal cortex, (5) earlier temporal onset of dorsomedial prefrontal cortex activity, and (6) greater dorsomedial prefrontal cortex-amygdala inverse functional connectivity. CONCLUSIONS AND RELEVANCE: Modulation of cognitive reappraisal-related brain responses, timing, and functional connectivity may be important brain changes that contribute to the effectiveness of CBT for social anxiety. This study demonstrates that clinically applied neuroscience investigations can elucidate neurobiological mechanisms of change in psychiatric conditions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00380731.

Is there less to social anxiety than meets the eye? Behavioral and neural responses to three socio-emotional tasks.

BACKGROUND: Social anxiety disorder (SAD) is widely thought to be characterized by heightened behavioral and limbic reactivity to socio-emotional stimuli. However, although behavioral findings are clear, neural findings are surprisingly mixed. METHODS: Using functional magnetic resonance imaging (fMRI), we examined behavioral and brain responses in a priori emotion generative regions of interest (amygdala and insula) in 67 patients with generalized SAD and in 28 healthy controls (HC) during three distinct socio-emotional tasks. We administered these socio-emotional tasks during one fMRI scanning session: 1) looming harsh faces (Faces); 2) videotaped actors delivering social criticism (Criticism); and 3) written negative self-beliefs (Beliefs). RESULTS: In each task, SAD patients reported heightened negative emotion, compared to HC. There were, however, no SAD versus HC differential brain responses in the amygdala and insula. Between-group whole-brain analyses confirmed no group differences in the responses of the amygdala and insula, and indicated different brain networks activated during each of the tasks. In SAD participants, social anxiety symptom severity was associated with increased BOLD signal in the left insula during the Faces task. CONCLUSIONS: The similar responses in amygdala and insula in SAD and HC participants suggest that heightened negative emotion responses reported by patients with SAD may be related to dysfunction in higher cognitive processes (e.g., distorted appraisal, attention biases, or ineffective cognitive reappraisal). In addition, the findings of this study emphasize the differential effects of socio-emotional experimental tasks.

MBSR vs aerobic exercise in social anxiety: fMRI of emotion regulation of negative self-beliefs.

Mindfulness-based stress reduction (MBSR) is thought to reduce emotional reactivity and enhance emotion regulation in patients with social anxiety disorder (SAD). The goal of this study was to examine the neural correlates of deploying attention to regulate responses to negative self-beliefs using functional magnetic resonance imaging. Participants were 56 patients with generalized SAD in a randomized controlled trial who were assigned to MBSR or a comparison aerobic exercise (AE) stress reduction program. Compared to AE, MBSR yielded greater (i) reductions in negative emotion when implementing regulation and (ii) increases in attention-related parietal cortical regions. Meditation practice was associated with decreases in negative emotion and social anxiety symptom severity, and increases in attention-related parietal cortex neural responses when implementing attention regulation of negative self-beliefs. Changes in attention regulation during MBSR may be an important psychological factor that helps to explain how mindfulness meditation training benefits patients with anxiety disorders.

Emotion regulation in social anxiety disorder: behavioral and neural responses to three socio-emotional tasks.

BACKGROUND: Social anxiety disorder (SAD) is thought to involve deficits in emotion regulation, and more specifically, deficits in cognitive reappraisal. However, evidence for such deficits is mixed. METHODS: Using functional magnetic resonance imaging (fMRI) of blood oxygen-level dependent (BOLD) signal, we examined reappraisal-related behavioral and neural responses in 27 participants with generalized SAD and 27 healthy controls (HC) during three socio-emotional tasks: (1) looming harsh faces (Faces); (2) videotaped actors delivering social criticism (Criticism); and (3) written autobiographical negative self-beliefs (Beliefs). RESULTS: Behaviorally, compared to HC, participants with SAD had lesser reappraisal-related reduction in negative emotion in the Beliefs task. Neurally, compared to HC, participants with SAD had lesser BOLD responses in reappraisal-related brain regions when reappraising faces, in visual and attention related regions when reappraising criticism, and in the left superior temporal gyrus when reappraising beliefs. Examination of the temporal dynamics of BOLD responses revealed late reappraisal-related increased responses in HC, compared to SAD. In addition, the dorsomedial prefrontal cortex (DMPFC), which showed reappraisal-related increased activity in both groups, had similar temporal dynamics in SAD and HC during the Faces and Criticism tasks, but greater late response increases in HC, compared to SAD, during the Beliefs task. Reappraisal-related greater late DMPFC responses were associated with greater percent reduction in negative emotion ratings in SAD patients. CONCLUSIONS: These results suggest a dysfunction of cognitive reappraisal in SAD patients, with overall reduced late brain responses in prefrontal regions, particularly when reappraising faces. Decreased late activity in the DMPFC might be associated with deficient reappraisal and greater negative reactivity. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00380731.

Amygdala response and functional connectivity during emotion regulation: a study of 14 depressed adolescents.

BACKGROUND: Ineffective emotion regulation and abnormal amygdala activation have each been found in adolescent-onset major depressive disorder. However, amygdala activation during emotion regulation has not been studied in adolescent-onset major depressive disorder. METHOD: Fourteen unmedicated adolescents diagnosed with current depression without comorbid psychiatric disorders and fourteen well-matched controls ages 13 to 17 years underwent an emotional regulation task during functional magnetic resonance imaging. During this task, participants viewed negatively-valence images and were asked to notice how they were feeling without trying to change it and maintain their emotional reaction ("Maintain") or to interpret the image in such a way as minimize their emotional response ("Reduce"). RESULTS: Imaging analyses demonstrated that adolescents with depression showed: (1) greater right amygdala activation during the maintain condition relative to controls, (2) less connectivity during the maintain condition between the amygdala and both the insula and medial prefrontal cortex than controls, and (3) a significant positive correlation between amygdala-seeded connectivities during maintenance of emotion and psychosocial functioning. LIMITATIONS: The current study is a cross-sectional comparison and longitudinal investigations with larger sample sizes are needed to examine the association between amygdala reactivity and emotion regulation over time in adolescent MDD. CONCLUSIONS: During the maintain condition, adolescents with depression showed a heightened amygdala response and less reciprocal activation in brain regions that may modulate the amygdala. A poorly modulated, overreactive amygdala may contribute to poor emotion regulation.

Evaluation of 12- and 24-month survival rates after treatment with masitinib in dogs with nonresectable mast cell tumors.

OBJECTIVE: To evaluate the effectiveness of masitinib for the treatment of nonresectable mast cell tumors (MCTs) in dogs at 12 and 24 months after onset of treatment. ANIMALS: 132 dogs with nonresectable grade 2 or 3 MCTs. PROCEDURES: Dogs received masitinib (12.5 mg/kg/d, PO; n = 106) or a placebo (26). After 6 months, treatment was extended with tumor assessments at 3-month intervals until detection of disease progression. Endpoints were tumor response and overall survival rate and time. RESULTS: In dogs with nonresectable MCTs, masitinib significantly improved survival rate, compared with results for the placebo, with 59 of 95 (62.1%) and 9 of 25 (36.0%) dogs alive at 12 months and 33 of 83 (39.8%) and 3 of 20 (15.0%) dogs alive at 24 months, respectively. Median overall survival time was 617 and 322 days, respectively. Tumor control at 6 months had a high predictive value for 24-month survival, with high specificity (88%) and sensitivity (76%), whereas short-term tumor response (within 6 weeks) had a poor predictive value. Complete responses at 24 months were observed in 6 of 67 (9.0%) dogs with nonresectable MCTs treated with masitinib. CONCLUSIONS AND CLINICAL RELEVANCE: Masitinib significantly increased survival rates at 12 and 24 months in dogs with nonresectable MCTs. Control of disease at 6 months, but not best response at 6 weeks, was predictive of long-term survival in dogs treated with masitinib, which suggested that short-term response may be irrelevant for assessing clinical efficacy of tyrosine kinase inhibitors for treatment of MCTs.

A multicenter study of the effect of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis.

OBJECTIVE: To determine the effects of feeding a diet supplemented with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. DESIGN: Randomized, controlled, multisite clinical trial. ANIMALS: 131 client-owned dogs with stable chronic osteoarthritis examined at 33 privately owned veterinary hospitals in the United States. PROCEDURES: In all dogs, the dosage of carprofen was standardized over a 3-week period to approximately 4.4 mg/kg/d (2 mg/lb/d), PO. Dogs were then randomly assigned to receive a food supplemented with fish oil omega-3 fatty acids or a control food with low omega-3 fatty acid content, and 3, 6, 9, and 12 weeks later, investigators made decisions regarding increasing or decreasing the carprofen dosage on the basis of investigator assessments of 5 clinical signs and owner assessments of 15 signs. RESULTS: Linear regression analysis indicated that over the 12-week study period, carprofen dosage decreased significantly faster among dogs fed the supplemented diet than among dogs fed the control diet. The distribution of changes in carprofen dosage for dogs in the control group was significantly different from the distribution of changes in carprofen dosage for dogs in the test group. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in dogs with chronic osteoarthritis receiving carprofen because of signs of pain, feeding a diet supplemented with fish oil omega-3 fatty acids may allow for a reduction in carprofen dosage.

Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs.

OBJECTIVE: To assess the effect of food containing high concentrations of fish oil omega-3 fatty acids and a low omega-6-omega-3 fatty acid ratio on clinical signs of osteoarthritis in dogs. DESIGN: Randomized, double-blinded, controlled clinical trial. ANIMALS: 127 client-owned dogs with osteoarthritis in 1 or more joints from 18 privately owned veterinary clinics. PROCEDURES: Dogs were randomly assigned to be fed for 6 months with a typical commercial food or a test food containing a 31-fold increase in total omega-3 fatty acid content and a 34-fold decrease in omega-6-omega-3 ratio, compared with the control food. Dog owners completed a questionnaire about their dog's arthritic condition, and investigators performed a physical examination and collected samples for a CBC and serum biochemical analyses (including measurement of fatty acids concentration) at the onset of the study and at 6, 12, and 24 weeks afterward. RESULTS: Dogs fed the test food had a significantly higher serum concentration of total omega-3 fatty acids and a significantly lower serum concentration of arachidonic acid at 6, 12, and 24 weeks. According to owners, dogs fed the test food had a significantly improved ability to rise from a resting position and play at 6 weeks and improved ability to walk at 12 and 24 weeks, compared with control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Ingestion of the test food raised blood concentrations of omega-3 fatty acids and appeared to improve the arthritic condition in pet dogs with osteoarthritis.

Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis.

OBJECTIVE: To evaluate the effects of a food supplemented with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. DESIGN: Randomized, double-blinded, controlled clinical trial. ANIMALS: 38 client-owned dogs with osteoarthritis examined at 2 university veterinary clinics. PROCEDURES: Dogs were randomly assigned to receive a typical commercial food (n = 16) or a test food (22) containing 3.5% fish oil omega-3 fatty acids. On day 0 (before the trial began) and days 45 and 90 after the trial began, investigators conducted orthopedic evaluations and force-plate analyses of the most severely affected limb of each dog, and owners completed questionnaires to characterize their dogs' arthritis signs. RESULTS: The change in mean peak vertical force between days 90 and 0 was significant for the test-food group (5.6%) but not for the control-food group (0.4%). Improvement in peak vertical force values was evident in 82% of the dogs in the test-food group, compared with 38% of the dogs in the control-food group. In addition, according to investigators' subjective evaluations, dogs fed the test food had significant improvements in lameness and weight bearing on day 90, compared with measurements obtained on day 0. CONCLUSIONS AND CLINICAL RELEVANCE: At least in the short term, dietary supplementation with fish oil omega-3 fatty acids resulted in an improvement in weight bearing in dogs with osteoarthritis.

Evaluation of radiotherapy alone or in combination with doxorubicin chemotherapy for the treatment of cats with incompletely excised soft tissue sarcomas: 71 cases (1989-1999).

OBJECTIVE: To determine whether the addition of doxorubicin chemotherapy affected the outcome of cats with incompletely excised, nonvisceral soft tissue sarcomas undergoing postoperative radiotherapy. DESIGN: Retrospective case series. ANIMALS: 71 cats. PROCEDURES: Medical records were reviewed for clinically relevant data on cats that underwent postoperative radiotherapy for treatment of incompletely excised soft tissue sarcomas with or without concurrent doxorubicin chemotherapy. Radiotherapy was performed on an alternate-day schedule, with a total dose of 58.8 to 63 Gy delivered in 21 fractions. Doxorubicin was administered every 21 days for 3 to 5 cycles. Follow-up information was obtained by means of physical examination or through telephone conversations with refer-ring veterinarians or owners. RESULTS: Median disease-free interval with concurrent radiotherapy and doxorubicin chemotherapy (15.4 months; range, 2.4 to 44.9 months) was significantly longer than median disease-free interval with radiotherapy alone (5.7 months; range, 1.0 to 50.8 months). However, survival time was not significantly different between groups. CONCLUSION AND CLINICAL RELEVANCE: Results suggested that doxorubicin chemotherapy may play a role in extending the disease-free interval in cats undergoing radiotherapy for treatment of incompletely excised soft tissue sarcomas.

Doxorubicin and BAY 12-9566 for the treatment of osteosarcoma in dogs: a randomized, double-blind, placebo-controlled study.

BACKGROUND: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. HYPOTHESIS: Survival will be prolonged in dogs receiving BAY 12-9566. ANIMALS: The study included 303 dogs with appendicular osteosarcoma. METHODS: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. RESULTS: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.

Hematologic changes associated with half-body irradiation in dogs with lymphoma.

BACKGROUND: Reports describe the technique and efficacy of half-body irradiation (HBI) of dogs with lymphoma, but few describe the distinctive toxicoses associated with the combination of HBI and chemotherapy. HYPOTHESIS: HBI would transiently affect myelocytic and erythroid variables as assessed by serial analysis of complete blood counts. ANIMALS: Twenty-nine dogs with lymphoma treated with HBI during 2002 and 2003. METHODS: A retrospective study of medical records of 29 dogs was performed. Two HBI protocols were used, resulting in delivery of either 6 Gy or 8 Gy to each half of the body, 1 month apart. Dogs received chemotherapy before, during, or after irradiation, or at multiple times. Serial hematology was available for all dogs. Data were analyzed between collection periods by analysis of variance (ANOVA) RESULTS: The mean granulocyte count significantly (P < .01) decreased from 10,017 cells/microL (data range 3,001-20,170 cells/ microL) before the first radiation treatment to 3,250 cells/microL (820-4,400 cells/microL) at week 5 (P < .01). Three weeks after this nadir, the mean increased to 10,150 cells/microL (900-26,700 cells/microL). The hematocrit did not change (36-38%). Thrombocytopenia (<100,000/microL) occurred in 10 dogs. Two dogs died because of complications associated with thrombocytopenia. No significant difference in toxicity was found between the 6 Gy and 8 Gy group. CONCLUSIONS AND CLINICAL IMPORTANCE: HBI was myelosuppressive but effects were short term and resolved in 22 of 24 dogs. Further studies are needed to elucidate the safety and role of HBI in the treatment of dogs with lymphoma.

Single agent gemcitabine chemotherapy in dogs with spontaneously occurring lymphoma.

BACKGROUND: Gemcitabine has been shown to be effective as a single agent in a variety of tumors including nonHodgkin's lymphoma. Its use in veterinary medicine has been limited and to date this drug has not been used as a first-line therapy in dogs with lymphoma. HYPOTHESIS: Gemcitabine as a single agent may be efficacious in dogs presented for the first time with lymphoma. ANIMALS: Twenty-four dogs with spontaneously occurring lymphoma. METHODS: All dogs were clinically staged and given gemcitabine at 400 mg/m(2) over a 30-minute intravenous infusion weekly for 3 weeks and then given 1 week off treatment before starting a second cycle. RESULTS: A single dose of gemcitabine lowered both neutrophil count (decrease in mean neutrophil count from 10,640 cells/ microL to 3,140 cells/microL) and platelet count (decrease in mean platelet count from 201,290 cells/microL to 139,190 cells/microL) 7 days after administration. Consequently gemcitabine dosage was reduced at the second treatment in 8 of 21 dogs or a dose delay of 1-7 days and a reduction of dosage was used in 7 of 21 dogs. Seven dogs completed the assigned 4-week cycle. Two of these dogs had progressive disease and 5 had stable disease. No objective responses were seen in dogs treated with a second cycle of gemcitabine. CONCLUSIONS AND CLINICAL IMPORTANCE: Gemcitabine administration as a single agent resulted in hematologic toxicity and did not reduce lymphoma burden. If gemcitabine is to be used in veterinary medicine, additional prospective pharmacologic studies should be done to determine the appropriate dosage, regimen, and schedule of use before it can be recommended for use in the treatment of dogs with lymphoma as a single agent.

Ferret oncology: diseases, diagnostics, and therapeutics.

Many standard diagnostic and chemotherapeutic protocols can be adapted for use in ferrets. Unique anatomic and clinical features dictate modification of protocols, but should not prohibit diagnosis or treatment. Ferrets may be the easiest of nontraditional species to treat with chemotherapeutics. We can provide more options for our patients, with improved quality of life and longer survival times than ever before. Although clients are never happy to hear the diagnosis of "cancer," it is no longer a word that condemns their beloved pet.

Efficacy of radiation therapy for incompletely resected grade-III mast cell tumors in dogs: 31 cases (1987-1998).

OBJECTIVE: To determine the efficacy (durations of remission and survival) of an alternating-day radiation protocol for incompletely excised histologic grade-III solitary mast cell tumors (MCTs) in dogs. DESIGN: Retrospective study. ANIMALS: 31 dogs. PROCEDURE: Radiation (52 Gy in an 18-fraction alternating-day protocol) was delivered to an area bordered by margins > or = 3 cm around the surgical scar and to the associated local-regional lymph nodes. Dogs were not given chemotherapeutic agents concurrently or after radiation. Information on signalment, duration of remission, and survival time was obtained from medical records. RESULTS: Median and mean durations of remission were 27.7 and 17.0 months, respectively (range, 1 to 47 months). Median and mean durations of survival were 28 and 20 months, respectively (range, 3 to 52 months). Dogs with tumors located on the skin of the pinna, perineum, and prepuce had a median duration of remission greater than dogs with tumors located at other sites (27.7 and 14.4 months, respectively). Dogs with tumors < or = 3 cm in maximum diameter before surgery survived longer than dogs with tumors > 3 cm (31 and 24 months, respectively). The remission rate was 65% and survival rate was 71% at 1 year after treatment. Sixteen dogs that were euthanatized had complications associated with local-regional tumor progression. Systemic metastases to liver, spleen, intestine, and bone marrow were detected in 1 dog. CONCLUSIONS AND CLINICAL RELEVANCE: Without further treatment, incompletely excised grade-III mast cell tumors have high local-regional recurrence; local-regional treatment with radiation may effectively be used to manage many such tumors.