Lack of CD44 variant 6 expression in rectal cancer invasive front associates with early recurrence

AIM: To investigate the prognostic value of CD44 variant 6 (CD44v6), a membranous adhesion molecule, in rectal cancer.METHODS: Altogether, 210 rectal cancer samples from 214 patients treated with short-course radiotherapy (RT, n = 90), long-course (chemo) RT (n = 53) or surgery alone (n = 71) were studied with immunohistochemistry for CD44v6. The extent and intensity of membranous and cytoplasmic CD44v6 staining, and the intratumoral membranous staining pattern, were analyzed.RESULTS: Membranous CD44v6 expression was seen in 84% and cytoplasmic expression in 81% of the cases. In 59% of the tumors with membranous CD44v6 expression, the staining pattern in the invasive front was determined as “front-positive” and in 41% as “front-negative”. The latter pattern was associated with narrower circumferential margin (P = 0.01), infiltrative growth pattern (P < 0.001), and shorter disease-free survival in univariate survival analysis (P = 0.022) when compared to the “front-positive” tumors.CONCLUSION: The lack of membranous CD44v6 in the rectal cancer invasive front could be used as a method to identify patients at increased risk for recurrent disease.     

Benefits and risks of long-term low-dose oral continuous combined hormone therapy

OBJECTIVES: Current recommendations for hormone therapy (HT) are mainly based on findings from studies using standard dose regimens in older women who had a different health profile from those who start HT soon after the onset of menopause. METHODS: We, therefore, reviewed controlled trials assessing the efficacy, safety and tolerability of low-dose oral continuous combined HT (cc-HT) started for treatment of climacteric symptoms. This review is limited to oral cc-HT regimens over sequential regimens as most postmenopausal women prefer not to have a return of uterine bleeding, and to studies of at least 2 years in duration. RESULTS: Low-dose cc-HT is effective in alleviating climacteric symptoms and in maintaining bone density over prolonged periods, although no data were available regarding fracture risk. No increased risk of coronary heart disease, venous thrombo-embolism or stroke during the use of low-dose cc-HT was reported in the long-term studies and no definitive evidence for an increased risk of breast cancer was found. Breakthrough bleeding during the first months of use is less common than with standard dose HT and amenorrhoea is achieved in most women over time. These regimens are safe for the endometrium and are well tolerated, with a low incidence of adverse events compared with standard doses. CONCLUSIONS: Current evidence from controlled trials indicates that low-dose oral cc-HT appears effective and safe. This makes it a good choice for the alleviation of climacteric symptoms, and for this purpose long-term administration of low-dose cc-HT does not seem to impose serious health risks. However, more long-term study data and direct head-to-head comparisons between various low-dose preparations are needed to support or rectify the safety aspects.     

Human variation and CYP enzyme contribution in benfuracarb metabolism in human in vitro hepatic models

Human responses to the toxicological effects of chemicals are often complicated by a substantial interindividual variability in toxicokinetics, of which metabolism is often the most important factor. Therefore, we investigated human variation and the contributions of human-CYP isoforms to in vitro metabolism of benfuracarb. The primary metabolic pathways were the initial sulfur oxidation to benfuracarb-sulfoxide and the nitrogen-sulfur bond cleavage to carbofuran (activation). The K_m, V_max, and CL_int values of carbofuran production in ten individual hepatic samples varied 7.3-, 3.4-, and 5.4-fold, respectively. CYP2C9 and CYP2C19 catalyzed benfuracarb sulphur oxidation. Carbofuran formation, representing from 79% to 98% of the total metabolism, was catalyzed predominantly by CYP3A4. The calculated relative contribution of CYP3A4 to carbofuran formation was 93%, while it was 4.4% for CYP2C9. The major contribution of CYP3A4 in benfuracarb metabolism was further substantiated by showing a strong correlation with CYP3A4-selective markers midazolam-1′-hydroxylation and omeprazole-sulfoxidation (r = 0.885 and 0.772, respectively). Carbofuran formation was highly inhibited by the CYP3A inhibitor ketoconazole. Moreover, CYP3A4 marker activities were relatively inhibited by benfuracarb. These results confirm that human CYP3A4 is the major enzyme involved in the in vitro activation of benfuracarb and that CYP3A4-catalyzed metabolism is the primary source of interindividual differences.     

Psychiatric nursing staffs’ attitudes towards the use of containment methods in psychiatric inpatient care: An integrative review

One of the international objectives in psychiatric care is reducing the use of coercion. Containment methods are meant to keep patients safe, yet usually include coercion. Nurses play a key role in deciding whether or not containment should be used and, as such, their attitudes towards containment can significantly impact the extent to which these methods are applied. The aim of this integrative review was to identify, analyse, and synthesize the available research on psychiatric nursing staffs’ attitudes towards containment methods in inpatient psychiatric care. An electronic search was conducted using the CINAHL, Scopus, and PsycINFO databases. In addition, the citations of identified studies were screened for relevant research. A total of 24 relevant papers published between 2002 and 2017 were selected for further analysis. These studies revealed variation in nursing staffs’ attitudes towards the use of containment methods. The use of containment methods seems to be widely accepted and nurses reported rarely considering alternative measures. It appears that attitudes towards containment have continuously become more negative, although the change has not been very pronounced. The concept of attitude was only defined in two studies. Thus, future research should strive to clarify this concept, as a generally accepted definition for attitude within nursing research and the utilization of all dimensions of this concept are both essential to the nursing field. Currently, it would be important to focus on changing attitudes among psychiatric nursing staff to reduce the use of containment methods; this calls for more research on nursing staffs’ attitudes.     

Lowered vision as a risk factor for injurious accidents in older people

BACKGROUND AND AIMS: Poor vision in older people is often related to increased fall risk. However, the association of the severity between visual deficit and risk for all kind of injurious accidents has not been widely studied. The aim of this study was to examine whether visual loss is associated with higher incidence of injurious accidents and whether walking speed or physical activity play a mediating role in the association. METHODS: 416 persons aged 75 and 80 years at baseline underwent visual acuity measurements. Visual acuity (VA) <0.3 in the better eye, with spectacle correction when necessary, was defined as visual impairment, VA >or=0.3 but 0.5 as normal VA. Hospital records of accidents resulting in injury were monitored for 10 years after baseline. RESULTS: During the 10-year follow-up, 239 (58%) participants suffered at least one injurious accident. The risk for injurious accidents in a multivariate model adjusted for age, gender, eye-related diseases, diabetes and cardiovascular diseases among participants with lowered vision was 1.45 (95% CI 1.08- 1.94), compared with that for people with normal visual acuity. Participants with visual impairment did not have an increased risk for injurious accidents (HR 1.20, 95% CI 0.82-1.75). Furthermore, neither walking speed nor physical activity had a mediating effect on the relationship between visual loss and accidents. CONCLUSIONS: Lowered vision is a risk factor for injurious accidents in older people independent of mobility and physical activity. Interestingly, more severe visual impairment did not increase the risk. Early intervention strategies, for example, proper correction of refractive errors or cataract extraction, may potentially prevent injurious accidents in older people.     

Characterization of 17B-hydroxysteroid dehydrogenase isoenzyme expression in benign and malignant human prostate

In the present study, expressions of 17B-hydroxysteroid dehydrogenase (17HSD) types 1, 2 and 3, 5α-reductase type 2 and human androgen receptor mRNAs were determined in 12 benign prostatic hyperplasia and 17 prostatic carcinoma specimens. 17HSD type 2 was found to be the principal isoenzyme expressed in the prostate. Significantly higher expressions of 17HSD type 2 and 5α-reductase type 2 were detected in benign prostatic hyperplasia compared with the carcinoma specimens. Expression of the androgen receptor in the 2 groups was not significantly different. 17HSD type 3 mRNA was not detected in any of the specimens investigated. Only low constitutive expression of the 2.3 kb mRNA of 17HSD type I was seen. Immunohistochemical analyses indicated that this did not lead to significant enzyme expression, only faint staining for the enzyme protein being detected, mainly in uroepithelial cells. No significant correlation was found between any of the mRNAs analyzed, but the data on 5α-reductase type 2 mRNA support the presence of an increased proportion of 5α-dihydrotesterone in the hyperplastic prostate. In cultured PC-3 prostatic cancer cells and in transiently transfected human embryonic kidney 293 cells, 17HSD type 2 was found exclusively to convert 5α-dihydrotestosterone and testosterone into the less potent 17-keto compounds 5α-androstanedione and 4-androstenedione, respectively. We suggest that the 17HSD type 2 isoenzyme plays a part in the metabolic pathway, resulting in the inactivation of testosterone and 5α-dihydrotestosterone locally in the prostate. The enzyme expressed in the prostate could, therefore, protect cells from excessive androgen action. © 1996 Wiley-Liss, Inc.     

Maternal origin of transferrin receptor positive cells in venous blood of pregnant women

We studied the origin of transferrin receptor (CD71) positive cells in blood from seven women pregnant with a male fetus in order to explore if fetal cells could be detected among them. We used a technique that allows direct chromosomal analysis by in situ hybridization on immunologically and morphologically classified cells. Enrichment was performed by magnetic activated cell sorting (miniMACS)® using an anti-CD71 monoclonal antibody. The cells were immunophenotyped by alkaline phosphatase anti-alkaline phosphatase immunostaining with the same antibody. The origin of the immunophenotyped cells was studied by in situ hybridization using an X cosmid Y repeat chromosome specific probe cocktail. CD71 positive cells were found in six of the seven women at the range of 4 to 43 in respective samples. Over 90% of the CD71 positive cells were nucleated erythrocytes. None of the detected positive cells were shown to be fetal. Thus, the use of transferrin receptor antigen alone in combination with the miniMACS® may not be sufficient for enrichment of fetal cells.