Impact of menopausal symptoms on presenteeism in Japanese women.

BACKGROUND: Menopausal symptoms are common among middle-aged women. Working women with severe menopausal symptoms are more likely to experience presenteeism-a condition where employees continue to work despite feeling unwell. However, it remains unclear as to which specific symptoms women experience during the menopausal transition and postmenopausal periods that primarily contribute to presenteeism. AIMS: To evaluate the associations between types of menopausal symptoms and presenteeism among Japanese women. METHODS: A cross-sectional study of 4000 women aged 40-59 years who were currently working was conducted in Japan in September 2022. We used an online self-administered questionnaire that included items on demographic characteristics, the Menopause Rating Scale for measuring menopausal symptoms and the Work Functioning Impairment Scale for measuring presenteeism. Logistic regression analysis was performed. RESULTS: Women with severe overall menopausal symptoms had 12.18-fold (95% confidence interval [CI] 9.09-16.33, P < 0.001) increased odds of presenteeism compared with those without symptoms. Participants with psychological symptoms also had significantly higher presenteeism (severe: odds ratio: 9.18, 95% CI 6.60-12.78, P < 0.001). However, after controlling for psychological symptoms, there were no significant associations between somatic and urogenital symptoms and presenteeism. CONCLUSIONS: The results indicate that menopausal symptoms, especially psychological symptoms, have a significant impact on presenteeism among Japanese women. Organizations need to address menopausal symptoms in the workplace, with an emphasis on reducing work-related stress for women with menopausal symptoms.

Two definitions of presenteeism: sickness presenteeism and impaired work function.

BACKGROUND: Two major definitions exist for presenteeism: sickness presenteeism and impaired work function. The evidence for comparing previous studies on presenteeism is insufficient because of the different definitions of presenteeism used. AIMS: To assess the relationship between the two major definitions of presenteeism. METHODS: This cross-sectional study analysed secondary data on 5334 respondents to an employee survey administered in a construction company in Japan. Impaired work function was measured using the Work Functioning Impairment Scale (WFun). Multiple logistic regression was performed. RESULTS: A strong linear association was observed between the number of days of sickness presenteeism and impaired work function (all P < 0.001). In contrast, the number of days of sickness absence was only partially positively associated with impaired work function. All choices for most frequent health problem were positively associated with impaired work function, beginning with mental problems (adjusted odds ratio [OR] = 20.45, 95% confidence interval [CI]: 14.94-28.01), followed by malaise (adjusted OR = 11.91, 95% CI: 9.08-15.62) and sleeping problems (adjusted OR = 8.62, 95% CI: 6.57-11.33). CONCLUSIONS: A strong relationship was observed between the two major definitions of presenteeism, even after adjusting for a variety of chronic health conditions. Although a consensus on the definition of presenteeism is yet to be reached, this study provides insight on comparing existing studies on presenteeism.

Presenteeism among workers: health-related factors, work-related factors and health literacy.

BACKGROUND: Presenteeism is an important factor in workers' health. However, few studies have examined how variables such as socio-economic status, health status, workplace status and health literacy correlate with and affect presenteeism. AIMS: To assess the correlates of presenteeism with a focus on health-related factors, work-related factors and health literacy. METHODS: We conducted a cross-sectional study of 2914 Japanese workers from one company. We used a self-administered questionnaire to assess socio-demographic characteristics, health status, work environment, presenteeism and health literacy. RESULTS: Forty-one per cent of participants were under 40 years of age and 70% were male. We found that 59% of the participants were at high risk of presenteeism. Presenteeism was associated with sex, age, household income, marital status, health-related factors (i.e. self-rated health status, dietary choices, exercise habits), work-related factors (i.e. workplace support, job demands, job control) and health literacy. Logistic regression analyses indicated that presenteeism was associated with self-rated health status, overtime hours, workplace support, job demands, job control and health literacy after adjusting for sex, age and income. CONCLUSIONS: Health-related factors, work-related factors and health literacy are all associated with presenteeism. Improving the workplace environment, especially factors such as overtime working hours, workplace support, job demands and job control, and increasing health literacy may reduce presenteeism among general office workers.

Near misses and presenteeism among paramedics.

BACKGROUND: Paramedics need to be in good physical health to be able to respond to emergencies. We hypothesized that near misses by paramedics and unanticipated incidents that cause no harm may be associated with presenteeism during emergency rescues. AIMS: To examine the association between presenteeism and near misses among paramedics. METHODS: A cross-sectional study was conducted among 254 paramedics using a self-administered questionnaire. Presenteeism was measured using the work functioning impairment scale (WFun). RESULTS: Twelve per cent of respondents experienced high work function impairment indicating presenteeism. The rate of near-miss experiences steadily increased with increasing work function impairment among paramedics (WFun score category: middle, odds ratio (OR) 3.62, 95% confidence interval (CI) 1.62-8.11; high, OR 4.36, 95% CI 1.37-13.84; very high, OR 8.62, 95% CI 2.09-35.48). CONCLUSIONS: This study demonstrated a positive relationship between impaired work function indicating presenteeism and near misses among paramedics. This suggests that presenteeism may be associated with errors that have the potential to cause serious accidents. Improved access to treatment for frequent health problems may reduce the number of incidents among paramedics.

B-RAF mutation and accumulated gene methylation in aberrant crypt foci (ACF), sessile serrated adenoma/polyp (SSA/P) and cancer in SSA/P.

BACKGROUND: Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor of colon cancer with microsatellite instability (MSI). However, the developmental mechanism of SSA/P remains unknown. We performed genetic analysis and genome-wide DNA methylation analysis in aberrant crypt foci (ACF), SSA/P, and cancer in SSA/P specimens to show a close association between ACF and the SSA/P-cancer sequence. We also evaluated the prevalence and number of ACF in SSA/P patients. METHODS: ACF in the right-side colon were observed in 36 patients with SSA/Ps alone, 2 with cancers in SSA/P, and 20 normal subjects and biopsied under magnifying endoscopy. B-RAF mutation and MSI were analysed by PCR-restriction fragment length polymorphism (RFLP) and PCR-SSCP, respectively, in 15 ACF, 20 SSA/P, and 2 cancer specimens. DNA methylation array analysis of seven ACF, seven SSA/P, and two cancer in SSA/P specimens was performed using the microarray-based integrated analysis of methylation by isochizomers (MIAMI) method. RESULTS: B-RAF mutations were frequently detected in ACF, SSA/P, and cancer in SSA/P tissues. The number of methylated genes increased significantly in the order of ACF

Demonstration of the cell clonality in canine hematopoietic tumors by X-chromosome inactivation pattern analysis.

X-chromosome inactivation pattern (XCIP) analysis has been widely used to assess cell clonality in various types of human neoplasms. In this study, a polymerase chain reaction-based canine XCIP analysis of the androgen receptor (AR) gene was applied for the assessment of cell clonality in canine hematopoietic tumors. This XCIP analysis is based on the polymorphic CAG repeats in the AR gene and the difference of methylation status between active and inactive X chromosomes. We first examined the polymorphisms of 2 CAG tandem repeats in the AR gene in 52 male and 150 female dogs of various breeds. The 2 polymorphic CAG repeats contained 9 to 12 and 10 to 14 CAGs in the first and second CAG repeats, respectively. Of the 150 female dogs, 74 (49.3%) were heterozygous for the first and/or second polymorphic CAG tandem repeats, indicating the utility of XCIP analysis in these dogs. Canine XCIP analysis was then applied to clinical samples from female dogs with canine high-grade lymphoma, chronic myelogenous leukemia, acute myelogenous leukemia, and benign lymph node hyperplasia. Of 10 lymphoma cell samples, 9 (90%) showed skewed XCIPs, indicating their clonal origins, whereas all the nonneoplastic lymph node samples showed balanced XCIPs. Moreover, bone marrow specimen from a dog with acute myelogenous leukemia and peripheral leukocyte specimens from 2 dogs with chronic myelogenous leukemia showed skewed XCIPs. XCIP analysis was successfully employed to demonstrate the cell clonality of canine hematopoietic tumors in this study and will be applicable to evaluate the clonality in various proliferative disorders in dogs.

Risk factors for early re-bleeding and associated hospitalization in patients with colonic diverticular bleeding.

AIM: The annual incidence of colonic diverticular bleeding is increasing, but treatments are not yet well established. Here we aimed to identify the risk factors for early re-bleeding and to determine the associated duration of hospitalization. METHOD: Records of 90 emergent patients with colonic diverticular bleeding between 1999 and May 2012 were retrospectively reviewed. They were divided into an early re-bleeding within 1 month group (n = 24) and a no re-bleeding group (n = 66) and we investigated the risk factors for early re-bleeding. In the former group, we calculated the time from the first haemostasis to early re-bleeding and the associated duration of hospitalization. RESULTS: Univariate analysis showed that there were significantly more patients with signs of shock (P = 0.00055) and active bleeding on the first colonoscopy after admission (P = 0.020) in the early re-bleeding group. Multivariate conditional logistic regression analysis using stepwise variable selection showed that signs of shock on admission (odds ratio, 5.23; 95% confidence interval, 1.84-14.90; P = 0.0019) remained statistically significant. All patients who re-bled without signs of shock (n = 7) and 16 of 17 with signs of shock re-bled within 126 h (5.25 days) of initial hospitalization. CONCLUSION: Shock was an independent risk factor for early re-bleeding. The associated duration of hospitalization was 6 days.

X-chromosome inactivation pattern analysis for the assessment of cell clonality in cats.

X-chromosome inactivation pattern (XCIP) analysis has been widely used to assess cell clonality in various types of neoplasms in humans. In the present study, a polymerase chain reaction-based feline XCIP analysis using the feline androgen receptor gene was developed. To construct the system of the analysis, polymorphism in CAG tandem repeats within the feline androgen receptor gene was explored using somatic DNAs from 50 male and 103 female cats. CAG tandem repeats in exon 1 of the feline androgen receptor gene were found to be polymorphic, containing 15 to 22 CAG repeats. Of the 103 female cats, 70 (68%) were heterozygous for the number of CAG repeats, indicating the possible usefulness of XCIP analysis in cats. Application of the feline XCIP analysis to 3 feline mammary gland adenocarcinoma cell lines revealed distinctly skewed XCIPs in these cell lines, indicating their clonal origins. Twelve (80%) of the 15 primary tissue/cell samples obtained from cats with various neoplastic diseases showed skewed XCIPs. Moreover, bone marrow samples from 3 cats with myelodysplastic syndrome were also found to have skewed XCIPs. The polymerase chain reaction-based XCIP analysis developed in this study can provide information on cell clonality in female cats, potentially facilitating the differential diagnosis of various disorders in cats.

Biological effect of tyrosine kinase inhibitors on three canine mast cell tumor cell lines with various KIT statuses.

Tyrosine kinase inhibitors (TKIs) can be important in the treatment of canine mast cell tumor (cMCT). Meanwhile, some TKIs have been identified as substrates for ABCB1. The inhibitory effect of four TKIs (axitinib, imatinib, masitinib, and vatalanib) for proliferation and phosphorylation of c-Kit receptor as well as the expression and function of ABCB1 were investigated in three cMCT cell lines (HRMC, VIMC1, and CMMC1). The IC(50) values of the TKIs in HRMC, the only cell line with wild-type KIT, were clearly higher than those in CMMC1 and VIMC1. In HRMC and CMMC1, both the growth and phosphorylation of c-Kit receptor were suppressed proportionally by the TKIs. VIMC1 required higher concentrations for the inhibition of c-Kit receptor phosphorylation than those in cell growth. The treatment with cyclosporine increased the effects of the TKIs on VIMC1 since ABCB1 was expressed in VIMC1. The results indicated that cMCT cell lines harboring wild-type KIT had lower sensitivity to TKIs. The growth of VIMC1 was seemingly reduced by TKIs through the inhibition of other tyrosine kinases than c-Kit receptor. There was little influence of ABCB1 on TKI effects to the proliferation of VIMC1. These results will be helpful to understand the different sensitivity to TKIs in cMCT patients.

Expression of fibrosis-related genes in canine chronic hepatitis.

Molecular regulation of fibrosis in chronic canine hepatitis is poorly understood. The authors employed quantitative polymerase chain reaction (PCR) to determine the expression levels of genes reported to be related to fibrosis in other species (human, mouse, and rat) and to elucidate the relationship of these genes with the degree of fibrosis and the presence or absence of ascites and/or jaundice in dogs with hepatitis. Nine fibrosis-related genes were assayed: PDGFB, PDGFD, MMP2, TIMP1, THBS1, COL1A1, COL3A1, TGFB1, and TGFB2. Liver samples of 15 dogs with chronic hepatitis and 4 healthy control dogs were obtained via laparoscopic biopsy and subjected to histologic and quantitative PCR analyses. The expression of all 9 genes showed significant positive correlation (P<.01, r>.70) with the degree of fibrosis. Furthermore, the expression levels of all genes except TGFB1 were significantly higher (P<.05) in dogs with hepatic failure-related symptoms (ascites/jaundice). Results suggest that these 9 genes are integral to the development of fibrosis in canine chronic hepatitis.

Propofol has anti-inflammatory effects on alveolar type II epithelial cells.

BACKGROUND: We investigated whether lipopolysaccharide (LPS) induced inflammation in alveolar epithelial type II (ATII) cells is through cluster of differentiation 14 (CD14) and Toll-like receptor 4 (TLR4) and the effect of different dosages of propofol on the inflammation in primary cultured rat ATII cells. METHODS: Cultured ATII cells were randomly assigned to one of the following five groups: Group C: untreated group (control) cultured in the absence of propofol and LPS; Group LPS: treated with 1 microg/ml LPS; Group P1: treated with 1 microg/ml LPS and 25 microM propofol; Group P2: treated with 1 microg/ml LPS and 50 microM propofol; Group P3: treated with 1 microg/ml LPS and 100 microM propofol. ATII cells in all groups were cultured at 37 degrees C for 3 h. CD14 and TLR4 mRNA was detected using real-time polymerase chain reaction. Western blot was used to detect CD14 and TLR4 protein expression. CD14 and TLR4 expression on the ATII cells was imaged using immunofluorescence. Tumor necrosis factor-alpha (TNF-alpha) production was determined using an ELISA kit. RESULTS: LPS stimulation resulted in an increased CD14 and TLR4 expression and increased TNF-alpha production in ATII cells. Propofol, at concentrations > or = 50 microM, significantly (P<0.05) and dose-dependently decreased CD14 and TLR4 mRNA expression and protein expression in ATII cells. This was accompanied by a decrease in TNF-alpha production (P<0.05). CONCLUSION: These results suggest that propofol, at clinically relevant concentrations, can reduce inflammatory responses in LPS-induced ATII cells injury through downregulation of CD14 and TLR4 expression.

Monitoring of minimal residual disease (MRD) after multidrug chemotherapy and its correlation to outcome in dogs with lymphoma: a proof-of-concept pilot study.

BACKGROUND: Tumor cell burden in dogs with lymphoma cannot be assessed accurately by diagnostic evaluation during clinical complete remission (CR). Recent advances in polymerase chain reaction (PCR)-based methods enabled us to quantify minimal residual disease (MRD) in canine lymphoma. HYPOTHESIS/OBJECTIVES: To quantify MRD in dogs with lymphoma treated with multidrug chemotherapy and to correlate it with remission duration after chemotherapy. ANIMALS: Seventeen dogs with lymphoma that achieved CR by multidrug chemotherapy. METHODS: Rearranged immunoglobulin heavy chain or T-cell receptor gamma chain gene fragments from lymphoma cells were PCR amplified and sequenced to prepare clone-specific primers and probes for real-time PCR to quantify MRD. MRD in the peripheral blood was monitored during and at the end of a 25-week multidrug chemotherapy protocol. Correlation between MRD at the end of chemotherapy and remission duration after chemotherapy was analyzed. RESULTS: MRD gradually decreased after initiation of multidrug chemotherapy, reached a nadir as low as <0.019-1.0 cells/microL at weeks 4-17, and remained low or slightly increased until week 25. MRD at the end of chemotherapy was negatively correlated with remission duration from the end of chemotherapy to relapse. CONCLUSION AND CLINICAL IMPORTANCE: MRD could be an objective marker to indicate tumor cell burden in dogs with lymphoma even in clinical CR. MRD at the end of chemotherapy could be a prognostic factor to predict remission duration after chemotherapy.

Collagenofibrotic glomerulonephropathy with fibronectin deposition in a dog.

We report herein a case of collagenofibrotic glomerulonephropathy in a 3-year-old Shiba Inu with severe proteinuria. Histologically, renal glomeruli were enlarged with massive deposition of a homogeneous eosinophilic substance within the mesangium and capillary walls. The deposits reacted weakly with periodic acid-Schiff, stained deep blue with Masson's trichrome, and were positive by immunofluorescence for type III collagen and fibronectin. Ultrastructurally, the deposits consisted of fibrils and amorphous material in the mesangial matrix and beneath the glomerular capillary endothelium. The fibrils had transverse bands analogous to those of collagen fibrils. Electron microscopy also revealed focal detachment of podocytes and foot process effacement in glomerular tufts, which suggested that podocyte injury had contributed to the development of proteinuria in this dog. The current case resembles collagenofibrotic glomerulonephropathy (CFGN) in humans in histopathologic, immunofluorescence, and electron microscopic findings. This is the first report of CFGN in a nonhuman species with glomerular deposition of fibronectin and type III collagen.

Oral symptoms predict mortality: a prospective study in Japan.

Several studies have reported positive associations between oral infections and systemic diseases. The purpose of the present study was to evaluate the effects of oral symptoms on mortality from cardiovascular disease (CVD) and pneumonia. Using data from a cohort study in Japan, we analyzed 4,139 individuals aged 40-79 years. The baseline questionnaire included the following items related to oral symptoms: 'sensitive teeth', 'difficulty in chewing tough food substances', 'bleeding gums', and 'mouth feels sticky'. We used the Cox proportional hazard model to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) for mortality, after adjustments for lifestyle, socio-economic factors, and history of diseases. Persons complaining that their 'mouth feels sticky' had a two-fold higher risk of pneumonia (HR = 2.1; 95%CI, 1.2-3.6), while those complaining of 'sensitive teeth' had a lower risk of CVD (HR = 0.4; 95%CI, 0.2-0.9). Some oral symptoms may be predictors of mortality from pneumonia and CVD.

Thermus thermophilus TMY isolated from silica scale taken from a geothermal power plant.

AIMS: To identify an extreme thermophile, strain TMY, isolated from silica scale from the geothermal electric power plant and to examine microdiversity of Thermus thermophilus strains. MATERIALS AND RESULTS: The isolated strain TMY was identified by morphological, biochemical and physiological tests. Phylogenetic comparison of the strain and other Thermus strains with 16S rDNA analysis, RAPD and ERIC-PCR fingerprinting were performed. Strain TMY was closely related to strain which was isolated from a hot spring in New Zealand and shown to belong to the Japanese Thermus cluster. However, there were considerable genetic differences between strain TMY and other Thermus species using DNA fingerprinting. CONCLUSIONS: Based on morphological, physiological and genetic properties, strain TMY could be a strain of T. thermophilus. The distinct properties of strain TMY suggest that microdiversity of T. thermophilus strains should be considered. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study have demonstrated genetic diversity within T. thermophilus strains, which were previously masked by an almost identical 16S rDNA sequence. RAPD and ERIC-PCR could be potential methods for distinguishing between Thermus strains.

Correlation between plasma milrinone concentration and renal function in patients with cardiac disease.

BACKGROUND: The dose of milrinone should be reduced in patients with renal failure. However, there is little data examining the relationship between plasma concentration of milrinone (pCmil) and renal function in intravenous infusion. METHODS: We evaluated the pCmil relative to renal function during intravenous infusion. We enrolled 10 heart failure patients. Milrinone was continuously infused at a rate of 0.2 microg/kg/min. Blood samples were collected at 6, 12, 24, and 48 h after the beginning of infusion. Urine was sampled during the first 24 h to calculate creatinine clearance (CLcr) and renal clearance of milrinone (rCLmil). RESULTS: The pCmil exhibited stability over 6 h after the beginning of infusion. During the first 24 h, CLcr and rCLmil were 62.2+/-30.6 ml/min and 1.67+/-0.77 ml/kg/min (106.2+/-60.3 ml/min), respectively. The rCLmil was highly correlated with CLcr. Y=1.77X-3.89 (X, CLcr; Y, rCLmil; R(2)=0.809, P<0.0001). Significant correlations were observed between CLcr and the plasma concentration during the continuous infusion. This correlation was expressed as the equation Y=51.1 x (BW/X)+28.2 (X; CLcr, Y; plasma concentration; BW, body weight; R(2)=0.695, P<0.01). CONCLUSION: The pCmil exhibited stability 6 h or later after the continuous infusion of milrinone 0.2 microg/kg/min. The pCmil can be estimated by the value of CLcr and BW.

Cigarette smoking, alcohol drinking, and oral and pharyngeal cancer mortality in Japan.

OBJECTIVES: To prospectively examine the association of cigarette smoking and alcohol drinking with oral and pharyngeal carcinogenesis, we analyzed data from a nation-wide large-scale cohort study in Japan. METHODS: A total of 34 136 men and 43 711 women aged 40-79 years were included in the study. The Cox proportional hazard model was used to estimate the relative risk (RR) and 95% confidence interval (95% CI) of oral and pharyngeal cancer for smoking and drinking by sex, while adjusting for age, consumption of green tea, preference for salty foods, and consumption of green yellow vegetables. RESULTS: Current smokers were found to have a higher risk of death caused by oral and pharyngeal cancer compared with non-smokers in both sexes: the RR was 2.6 (95% CI: 1.0-6.7) in men and 8.2 (95% CI: 2.1-32.1) in women. Men who drank more than 46 g ethanol per day had an approximately threefold increased risk of oral and pharyngeal cancer. Simultaneous exposure to both factors was significantly associated with an elevated risk of oral and pharyngeal cancer (RR: 3.3, 95% CI: 1.1-9.6). CONCLUSIONS: The result supports the carcinogenic effect of cigarette smoking and alcohol drinking on the oral cavity and pharynx.

Metal mesh vitrification (MMV) method for cryopreservation of porcine embryos.

The objective was to develop a simpler, more reliable vitrification method for porcine embryos. Prepubertal donor gilts were induced to ovulate with eCG and hCG, and then inseminated artificially. Morulae and expanding blastocysts approximately 200 microm in diameter were collected 6 or 7d after hCG treatment. Embryos collected from donor gilts were maintained, so as to be individually recognizable, and handled in batches of four or five. The embryos together with a minimum volume (<2 microL) of vitrification solution were placed onto stainless steel metal meshes or plastic plates, and then plunged into liquid nitrogen-metal mesh vitrification (MMV) and plastic plate vitrification (PPV), respectively. The meshes or plates were stored in 1.8-mL cryotubes submerged in liquid nitrogen. Stored embryos were subsequently removed, cultured in medium for 24 h, and then assessed for viability. The survival rate (84.4%) of expanding blastocysts cooled by MMV was higher than that (53.1%) of embryos cooled by PPV (P<0.05). There was no significant difference in total cell number between MMV and PPV. The survival rate of morulae cooled by MMV was 55.0%. Transfer of 200 expanding blastocysts cooled by MMV to 10 synchronized recipient gilts resulted in 37 live piglets from 7 recipients. In conclusion, the MMV method was an effective vitrification procedure for cryopreservation of expanding porcine blastocysts. However, there was a batch effect on embryo survival after vitrification.

Effect of tyrosine kinase inhibition by imatinib mesylate on mast cell tumors in dogs.

BACKGROUND: Imatinib mesylate is a small molecule targeted at dysregulated protein-tyrosine kinase. Mutation of c-kit exon 11, which induces constitutive phosphorylation of KIT, is one of the mechanisms for the development or progression of mast cell tumor (MCT) in dogs. The purpose of this study was to examine the therapeutic potential of imatinib mesylate in canine MCT. HYPOTHESIS: Imatinib mesylate has activity against MCT in dogs, and response to treatment can be correlated to presence of mutation within exon 11 of c-kit. ANIMALS: Twenty-one dogs with MCT with gross tumor burden and median tumor size of 7.2 cm (range, 1.0-25.3 cm) before treatment. METHODS: Tumors were analyzed for mutation of c-kit exon 11. Imatinib mesylate was administered PO to the dogs at a dose of 10 mg/kg daily for 1-9 weeks. RESULTS: Ten of 21 dogs (48%) had some beneficial response to imatinib mesylate treatment within 14 days of treatment initiation. All 5 dogs with a demonstrable c-kit mutation in exon 11 responded to the drug (1 complete remission, 4 partial remission). CONCLUSIONS AND CLINICAL IMPORTANCE: Imatinib mesylate has clinical activity against MCT in dogs. Response could not be predicted based on presence of absence of a mutation in exon 11 of c-kit.