Risk factors for equine glandular and squamous gastric disease in show jumping Warmbloods.

BACKGROUND: Prevalence of, and risk factors for, equine squamous gastric disease (ESGD) are well established. Limited data exists on risk factors for equine glandular gastric disease (EGGD). OBJECTIVES: To identify management factors associated with EGGD in show jumping Warmbloods in training. A secondary objective was to identify management factors associated with ESGD. STUDY DESIGN: Cross-sectional. METHODS: Gastroscopies were performed in horses following a 12-16 h fast. Management questionnaires were collected for each horse. Risk factors were determined using multivariable logistic regression modelling. RESULTS: Eighty-three horses were included in the final analysis. Exercising ≥6 days per week increased the odds of EGGD grade ≥1/4 (odds ratio [OR] = 3.5; 95% confidence interval [CI] 1.2-10.7) compared to less frequent exercise. Currently showing increased the risk of EGGD grade ≥2/4 (OR = 10.2; 95% CI, 1.04-100), while competing at the international level decreased the odds of EGGD grade ≥2/4 (OR = 0.11; 95% CI, 0.01-0.97). Exercise intensity increased the odds of grade ≥1/4 ESGD (OR = 2.8; 95% CI, 1.03-7.8) and feeding beet pulp decreased odds (OR = 0.22; 95% CI, 0.07-0.7). Exercise intensity (OR = 3.8; 95% CI, 1.1-12.8) increased the likelihood of grade ≥2/4 ESGD and feeding beet pulp decreased the odds of grade ≥2/4 ESGD (OR = 0.1; 0.02-0.64) respectively. MAIN LIMITATIONS: This study used a convenience sample of horses within a relatively small (approximately 200 km) geographic radius. The sample size was relatively small, particularly within the international competition level group. CONCLUSIONS: Training and feeding strategies and competition level appear to influence the occurrence of EGGD and ESGD. Prospective studies evaluating the impact of training frequency, duration, and intensity on gastric physiology may clarify the role of exercise in gastric disease.

Phenylbutazone induces equine glandular gastric disease without decreasing prostaglandin E2 concentrations.

In equids, phenylbutazone at high doses induces gastric disease, primarily in the glandular portion of the stomach. However, the mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric disease in horses has yet to be determined. While phenylbutazone-associated ulceration is often attributed to a decrease in basal gastric prostaglandins, this has not been demonstrated in the horse. Twelve horses were randomly assigned to treatment (n = 6; 4.4 mg/kg phenylbutazone PO in 20 ml molasses q 12 hr for 7 days) or placebo (n = 6; 20 ml molasses PO q 12 hr for 7 days) groups. Before treatment and 3 and 7 days after initiation of treatment, gastroscopy was performed and glandular gastric biopsies were collected and frozen at -80°C. Glandular disease was assessed on a scale of 0-4. Prostaglandin E2 concentrations in biopsies were measured using a commercially available enzyme-linked immunosorbent assay. All phenylbutazone-treated horses developed grade ≥2 glandular disease. Prostaglandin concentrations increased over time (p = .0017), but there was no effect of treatment (p = .49). These findings indicate that despite induction of glandular disease grade ≥2, phenylbutazone did not decrease basal glandular gastric prostaglandin E2 concentration.

Cervical carcinogenesis, bacterial vaginosis, HPV-mRNA test and relapse of CIN2+ after loop electrosurgical excision procedure (LEEP).

OBJECTIVE: The aim of the study was to evaluate the relationship between bacterial vaginosis (BV) and relapse of cervical intraepithelial neoplasia grade 2 or more (CIN2+) after Loop electrosurgical excision procedure (LEEP). PATIENTS AND METHODS: One hundred four patients who underwent LEEP for CIN2+ were followed up every six months for three years. Fifty-three were negative for BV and fifty-one were positive. Each clinical control included Pap test, colposcopy, Amsel criteria test, HPV-DNA, and HPV-mRNA test. RESULTS: Patients' age, presence of BV, positivity to HPV-DNA and HPV-mRNA tests were analyzed. The average age of patients was 42.5 ± 8.92 years (median: 42.5; range from 27 to 58 years). The minimum follow-up was 6 months and maximum 36 months (average: 22.8 ± 4.53; median: 24). The 10% of the patients with HPV-mRNA test negative had relapsed, compared to 45% of patients with HPV-mRNA test positive. Among the 53 patients without BV the 20% had relapsed compared with 23% of 51 patients with diagnosis of BV. CONCLUSIONS: There is no evidence for higher percentage of relapse in patients with BV, submitted to excisional procedure for CIN2+ associated to HPV-m-RNA test positivity. There is only a correlation among BV and relapse of CIN2+ lesions after LEEP.

Expression of E6/E7 HPV-DNA, HPV-mRNA and colposcopic features in management of CIN2/3 during pregnancy.

OBJECTIVE: The incidence of abnormal cervical cytology in pregnancy is similar to that reported for non-pregnant women. Furthermore, 1% of pregnant women annually screened for cervical cancer will be diagnosed with cervical intraepithelial neoplasia (CIN) of various degrees. For this reason, Pap smear should be performed in the first trimester of pregnancy. The persistence of HR-HPV infection is related to the development of CIN. However, the relationship between CIN and HR-HPV infection during pregnancy and postpartum can hardly be found. The aim of this work was to assess the proper management of abnormal cytology during and after pregnancy evaluating regression rate, persistence rate and risk of progression and the predictive role of HPV molecular tests. PATIENTS AND METHODS: Patients with abnormal cervical cytology were followed-up using colposcopy and colposcopy-directed biopsies every 12 weeks. Molecular tests were performed at the moment of the cytological diagnosis. Patients not treated in pregnancy were re-evaluated with cytology, colposcopy, biopsies, HPV-DNA test and HPV-mRNA test for a final diagnosis 8 weeks postpartum. Women with a persistent CIN 2-3 lesion at this follow-up check, underwent an excisional procedure by LEEP and then re-evaluated every 6 months for a year. RESULTS: HPV-DNA test showed a sensitivity of 90.5% and a negative predictive value of 96.4%. Specificity and positive predictive values were 67.9% and 43.2%, respectively. For HPV-mRNA test, a sensitivity of 76.2% and a NPV of 93.9% were found; specificity and PPV were 98.7% and 94.1% respectively. CONCLUSIONS: An observational management based on the use of molecular test and particularly HPV-mRNA test for its higher specificity, is a reasonable possibility in the follow-up of CIN2/3 lesions during pregnancy.

Human papilloma virus infection and cervical cytomorphological changing among intrauterine contraception users.

OBJECTIVE: The increased use of the intrauterine contraception (IUC) in female population and its probable relationship with cervical squamous intraepithelial lesions and cervical cancer make necessary clarify the possible interaction between the device and the pre-neoplastic lesions. PATIENTS AND METHODS: Seven hundred and eighty-nine patients users of IUC and 1491 patients ever users of IUC were followed every 6 months for 3 years. Each clinical control included Papanicolau test, colposcopy, HPV-DNA test and HPV-mRNA test. Also, in patients IUC users we analyzed the type of device, years of use and average age. RESULTS: Cytological sampling, histological examination, HPV-DNA test and HPV-mRNA test showed that there are not significantly differences between patients with or without IUC. CONCLUSIONS: None difference arose regarding persistence and progression between patients IUC users and IUC no users, for this reason, intrauterine contraception does not seem to be a co-causal factor in the possible development of cervical cancer.

Judicious use of prophylactic antimicrobials to reduce abdominal surgical site infections in periparturient cows: part 1 - a risk factor review.

Surgical site infections (SSI) are an uncommon, but significant, consequence of surgical interventions. There are very few studies investigating SSI risk in veterinary medicine, and even fewer in cattle, despite the fact that major surgeries are commonly conducted on livestock. Furthermore, the suboptimal conditions under which such surgeries are frequently performed on livestock could be considered an important risk factor for the development of SSIs. With increasing public concern over the contribution of veterinary-prescribed antimicrobials to the emergence of antimicrobial-resistant bacteria in people, there is widespread scrutiny and criticism of antimicrobial use in livestock production medicine systems. While the causal link between antimicrobial resistance in livestock and people is heavily debated, it is clear that the prevalence of antimicrobial resistance, in any population, is closely correlated with the antimicrobial 'consumption' within that population. As the veterinary profession explores ways of addressing the emergence and selection of antimicrobial-resistant bacteria in food-producing animals, there is a need for veterinarians and producers to carefully consider all areas of antimicrobial use, and employ an evidence-based approach in designing appropriate clinical protocols. This paper aims to review current knowledge regarding the risk factors related to abdominal SSI in periparturient cows, and to encourage practitioners to judiciously evaluate both their standard operating procedures and their use of antimicrobials in these situations. In a second paper, to be published in a subsequent issue of Veterinary Record, these principles will be used to provide specific evidence-based recommendations for antimicrobial use in bovine abdominal surgery.

Evaluation of E6 and E7 mRNA expression in HPV DNA positive breast cancer.

Several studies have suggested a possible role for HPV in the pathogenesis of the breast cancer. We investigated the presence of the HPV DNA in breast cancers and non malignant disease breast tissues by the use of a standard HPV detection method (INNO-Lipa HPV), in order to detect HPV DNA in metastatic nodes, to investigate a possible cervical HPV co-infection, and to evaluate the E6/E7 mRNA expression in HPV DNA positive breast cancer tissues. The rate of HPV infection was significantly higher in the cancer group than in controls (9/31 vs. 0/12, p = 0.04). One out of eight metastatic axillary nodes was positive for HPV infection; 2/3 of the positive HPV breast cancer patients were co-infected at the cervical site. The role of the virus in breast oncogenesis is still unclear, since our analysis failed in demonstrating the expression of viral E6 and E7 in positive HPV positive breast tumor tissues.

Prognostic implication of high risk human papillomavirus E6 and E7 mRNA in patients with intraepithelial lesions of the cervix in relationship to age.

Since the introduction of the cytological screening programs, a significant reduction in the incidence of cervical cancer has been achieved. Almost all of these cancers are related to high-risk (HR) Human Papillomavirus (HPV) cervical infections. However, the natural history of HPV infection seems to be different in younger patients, resulting in a higher rate of regression. There is, therefore, the need to identify HPV-related biomarkers in order to enhance the effectiveness of screening of high-risk cytological lesions, in particular in women over 35 years of age. This study aims to evaluate the prognostic value of the HR HPV E6 and E7 mRNA expression in women with intraepithelial lesions of the cervix, older or younger than 35 years of age. One hundred and eighty-four HR HPV DNA positive patients with a low squamous intraepithelial lesion (LSIL) were tested for mRNA expressions, included in an observational study, and evaluated at follow-up with standard cytology up to 24 months from the mRNA test. The frequency of HSIL/LSIL cytology in the older cohort of mRNA positive patients was significantly higher compared to mRNA-negative patients, both at 1 and 2 years of follow-up (Chi-square: p 0.007 and p 0.009), but this difference was not found in the younger cohort. According to our results, the E6/E7 mRNA test could be a biomarker for viral activity, useful in identifying patients at higher risk of abnormal cytology, and in implementing the management of HR HPV DNA-positive women over 35 years of age.

Predictors of anxiety and depression among people attending diabetes screening: a prospective cohort study embedded in the ADDITION (Cambridge) randomized control trial.

OBJECTIVE: This study aimed to identify factors predicting anxiety and depression among people who attend primary care-based diabetes screening. DESIGN: A prospective cohort study embedded in the ADDITION (Cambridge) randomized control trial. METHODS: Participants (N= 3,240) at risk of diabetes were identified from 10 primary care practices and invited to a stepwise screening programme as part of the ADDITION (Cambridge) trial. Main outcome measures were anxiety and depression at 12 months post-screening assessed using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Hierarchical linear regressions showed that demographic, clinical, and psychological variables collectively accounted for 52% of the variance in HADS anxiety scores and 53% of the variance in HADS depression scores 12 months after diabetes screening. Screening outcome (positive or negative for diabetes) was not related to differences in anxiety or depression at 12 months. Higher number of self-reported (diabetes) symptoms after first attendance was associated with higher anxiety and depression at 12-month follow-up, after controlling for anxiety and depression after first attendance. CONCLUSION: Participants in a diabetes screening programme showed low scores on anxiety and depression scales after first appointment and 1 year later. Diagnosis of diabetes was shown to have a limited psychological impact and may be less important than symptom perception in determining emotional outcomes after participation in diabetes screening.

Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia.

The influence of genetic polymorphism in inosine triphosphate pyrophosphatase (ITPA) on thiopurine-induced adverse events has not been investigated in the context of combination chemotherapy for acute lymphoblastic leukemia (ALL). This study investigated the effects of a common ITPA variant allele (rs41320251) on mercaptopurine metabolism and toxicity during treatment of children with ALL. Significantly higher concentrations of methyl mercaptopurine nucleotides were found in patients with the nonfunctional ITPA allele. Moreover, there was a significantly higher probability of severe febrile neutropenia in patients with a variant ITPA allele among patients whose dose of mercaptopurine had been adjusted for TPMT genotype. In a cohort of patients whose mercaptopurine dose was not adjusted for TPMT phenotype, the TPMT genotype had a greater effect than the ITPA genotype. In conclusion, genetic polymorphism of ITPA is a significant determinant of mercaptopurine metabolism and of severe febrile neutropenia, after combination chemotherapy for ALL in which mercaptopurine doses are individualized on the basis of TPMT genotype.

The ovariectomized, mature rat model of postmenopausal osteoporosis: an assessment of the bone sparing effects of curcumin.

Identification of natural health products that might benefit skeletal health could reduce the negative impact of osteoporotic bone fractures upon society. The objectives of this study were to evaluate an animal model of postmenopausal osteoporosis and to search for evidence that curcumin reduces bone mineral losses in a dose-dependent manner when endogenous estrogen levels are reduced. Bone mineral density was measured at the spine, femur and whole body before and at 2, 4 and 6 months after ovariectomy in each of 40 mature rats. Serum osteocalcin and C-telopeptide were measured as indicators of bone formation and resorption rates. Femoral compressive strength was measured at 6 months. Ovariectomy alone resulted in loss of mineral from the spine (p<0.005) and an increase in osteocalcin levels (p<0.05). At the same time, there was an increase in energy to fracture (p<0.01) due to an increased bone size. When ovariectomized animals were given etidronate there was no loss of mineral from the spine, the size of the femur increased (p<0.005), C-telopeptide levels were reduced (p<0.001) and femoral compressive strength increased (p<0.025). Administration of curcumin to ovariectomized animals resulted in changes that were intermediate between those produced by etidronate and by ovariectomy alone. The increase in femur size produced by the highest dose of curcumin was statistically significant (p< 0.01) and curcumin administration resulted in a significant, dose dependent, increase in energy to fracture. Curcumin produces beneficial changes in bone turnover and increases in bone strength using the ovariectomized mature rat model of postmenopausal osteoporosis.

Hormonal responses to a 160-km race across frozen Alaska.

BACKGROUND: Severe physical and environmental stress seems to have a suppressive effect on the hypothalamic-pituitary-gonadal (HPG) axis in men. Examining hormonal responses to an extreme 160-km competition across frozen Alaska provides a unique opportunity to study this intense stress. OBJECTIVE: To examine hormonal responses to an ultra-endurance race. METHODS: Blood samples were obtained from 16 men before and after racing and analyzed for testosterone, interleukin-6 (IL-6), growth hormone (GH) and cortisol. Six subjects (mean (SD) age 42 (7) years; body mass 78.9 (7.1) kg; height 1.78 (0.05) m raced by bicycle (cyclists) and 10 subjects (age 35 (9) years; body mass 77.9 (10.6) kg; height, 1.82 (0.05) m) raced by foot (runners). Mean (SD) finish times were 21.83 (6.27) and 33.98 (6.12) h, respectively. RESULTS: In cyclists there were significant (p< or =0.05) mean (SD) pre-race to post-race increases in cortisol (254.83 (135.26) to 535.99 (232.22) nmol/l), GH (0.12 (0.23) to 3.21 (3.33) microg/ml) and IL-6 (2.36 (0.42) to 10.15 (3.28) pg/ml), and a significant decrease in testosterone (13.81 (3.19) to 5.59 (3.74) nmol/l). Similarly, in runners there were significant pre-race to post-race increases in cortisol (142.09 (50.74) to 452.21 (163.40) ng/ml), GH (0.12 (0.23) to 3.21 (3.33) microg/ml) and IL-6 (2.42 (0.68) to 12.25 (1.78) pg/ml), and a significant decrease in testosterone (12.32 (4.47) to 6.96 (3.19) nmol/l). There were no significant differences in the hormonal levels between cyclists and runners (p>0.05). CONCLUSIONS: These data suggest a suppression of the hypopituitary-gonadal axis potentially mediated by amplification of adrenal stress responses to such an ultra-endurance race in environmentally stressful conditions.

Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models.

Although fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice its involvement in human cancer is not well characterized. Here we report that FGF19 and its cognate receptor FGF receptor 4 (FGFR4) are coexpressed in primary human liver, lung and colon tumors and in a subset of human colon cancer cell lines. To test the importance of FGF19 for tumor growth, we developed an anti-FGF19 monoclonal antibody that selectively blocks the interaction of FGF19 with FGFR4. This antibody abolished FGF19-mediated activity in vitro and inhibited growth of colon tumor xenografts in vivo and effectively prevented hepatocellular carcinomas in FGF19 transgenic mice. The efficacy of the antibody in these models was linked to inhibition of FGF19-dependent activation of FGFR4, FRS2, ERK and beta-catenin. These findings suggest that the inactivation of FGF19 could be beneficial for the treatment of colon cancer, liver cancer and other malignancies involving interaction of FGF19 and FGFR4.

Prediction of persistent vaginal intraepithelial neoplasia in previously hysterectomized women by high-risk HPV DNA detection.

AIM: To estimate the incidence and latency of Vaginal Intraepithelial Neoplasia (VAIN) in women previously hysterectomized for benign/malign pathology and to evaluate the role of high risk HPVs in the prediction of persistent or recurrent disease. SUBJECTS AND METHODS: 830 women with prior hysterectomy for benign/malign pathologies followed by cytological scraping and vaginal colposcopy. Forty-four patients presented VAIN lesions confirmed by histopathological diagnosis. HPV DNA test was performed at the time of diagnosis. Patients were treated by Laser CO(2) vaporization and underwent follow-up by cytology, colposcopy for a mean period of 3 years. HPV DNA test was performed at 6 months after treatment and every years. Persistent or relapsed disease was confirmed by histopathology. RESULTS: Incidence of VAIN in women hysterectomized for benign pathologies did not differ significantly from the malign group. VAIN degree was more severe in the hysterectomized patients with cervical malignancy and subsequently radiated respect to non-radiated patients. The HPV DNA test at 6 months after VAIN treatment showed fifteen positive cases: twelve HPV 16 (80%) and three HPV 18 (20%). In five cases HPV DNA test was positive with a persistent negative cytological smear during the years. Positivity to high-risk HPV (either 16 or 18) was significantly higher in the patients with relapse to VAIN (10/44, p<0.002). CONCLUSIONS: We suggest to include HPV DNA test in addition to cytology in the follow-up of patients previously treated for VAIN, in order to predict VAIN persistence or progression in vaginal carcinoma before cytology becomes abnormal.

Modelling predictions of cancer deaths in Northern Ireland.

BACKGROUND: An ageing population has service planners concerned about future levels of disease which are age dependent. Predictions of mortality for colorectal, lung and breast cancers, which account for 30% of cancer cases and 40% of cancers deaths, were calculated for 2010 and 2015, based on trends in death rates and the predicted change in the demography of the Northern Ireland population. METHODS: The U.S. National Cancer Institute's "Joinpoint" program was used to check for structural breaks in the time series of cancer death rates from 1984 to 2004. The prediction models applied to the data allowed variations in trends across age groups to be taken into account. A linear model was used for increasing or constant trends and a log linear model was used where the trend was decreasing. The models assume the number of deaths in each stratum, defined by age-sex and time-period, is Poisson distributed, with the average value determined by a log or linear function. RESULTS: Recent trends in rates of cancers studied were downwards except for female lung. Predictions include decreased colorectal cancer deaths in females and lung cancer deaths in males. In females, lung cancer deaths are predicted to more than double by the year 2015 (473 deaths), based on the 1984 level. Colorectal death rates in males are predicted to drop, but the number of deaths will increase by more than 10%, due to demographic change. Numbers of breast cancer deaths are likely to rise slightly, despite falling age standardised death rates, due to an ageing population. CONCLUSIONS: This work has provided estimates of early future trends, useful to service planners, and highlights the need for tobacco control, to reduce numbers of lung cancer deaths in females. The recently announced control of environmental tobacco legislation is one welcome development which should reduce lung cancer mortality in Northern Ireland.

Genome-wide approach to identify risk factors for therapy-related myeloid leukemia.

Using a target gene approach, only a few host genetic risk factors for treatment-related myeloid leukemia (t-ML) have been defined. Gene expression microarrays allow for a more genome-wide approach to assess possible genetic risk factors for t-ML. We assessed gene expression profiles (n=12 625 probe sets) in diagnostic acute lymphoblastic leukemic cells from 228 children treated on protocols that included leukemogenic agents such as etoposide, 13 of whom developed t-ML. Expression of 68 probes, corresponding to 63 genes, was significantly related to risk of t-ML. Hierarchical clustering of these probe sets clustered patients into three groups with 94, 122 and 12 patients, respectively; 12 of the 13 patients who went on to develop t-ML were overrepresented in the latter group (P<0.0001). A permutation test indicated a low likelihood that these probe sets and clusters were obtained by chance (P<0.001). Distinguishing genes included transcription-related oncogenes (v-Myb, Pax-5), cyclins (CCNG1, CCNG2 and CCND1) and histone HIST1H4C. Common transcription factor recognition elements among similarly up- or downregulated genes included several involved in hematopoietic differentiation or leukemogenesis (Maz, PU.1, ARNT). This approach has identified several genes whose expression distinguishes patients at risk of t-ML, and suggests targets for assessing germline predisposition to leukemogenesis.

A two-year prospective study of the health-related quality of life of children with chronic illness--the parents' perspective.

The aim of this study was to assess prospectively changes in the health-related quality of life (HRQL) of children and adolescents with diabetes, asthma or cystic fibrosis (CF). One hundred and twenty-two parents of children aged 10-16 years with asthma, diabetes, or CF were recruited from specialist paediatric clinics. Parents described their children's HRQL using the Child Health Questionnaire (PF98) at baseline, 6, 12, 18 and 24 months post-baseline. They reported that the general health of children with CF was significantly worse than that of children with asthma and diabetes at baseline. In other domains there were few differences between the HRQL of children in the three groups. In several domains, the HRQL of children with asthma or diabetes improved over the 2 years of the study. This improvement was less evident for children with CF.

Psychological costs of inadequate cervical smear test results.

The purpose of the study is to investigate, for the first time, the psychological impact of an inadequate smear test result. A prospective questionnaire design was used, and the setting was a single English cervical screening laboratory. Two groups of women receiving either a normal test result (n=226) or either a first or nonconsecutive inadequate smear test result (n=180) participated. The main outcome measures included State anxiety (STAI) and concern about test result, assessed within 4 weeks of receipt of results, and attendance for a repeat cervical smear within 3 months. Compared to women with normal test results, women with inadequate smear test results had higher state anxiety (P=0.025), were more concerned about their results (P<0.001), perceived themselves to be at higher risk of cervical cancer (P=0.016), and felt less satisfied with the information they had received about their test results (P<0.001). The only predictor of attendance for a repeat smear test following an inadequate smear test result was state anxiety (P=0.011): nonattenders had higher levels of state anxiety in response to their initial test results. In conclusion, in this first study to assess the psychological impact of receiving an inadequate smear test result, we have shown that it raises state anxiety and concern to levels similar to those found in women with abnormal smear test results. Of particular concern is that anxious women are less likely to attend for a repeat smear test within the recommended time frame. Given the millions of women each year receiving this test result, research is now needed to ascertain how the anxiety associated with this result can be avoided.