Analysis of microRNA expression in brush cytology specimens improves the diagnosis of pancreatobiliary cancer.

BACKGROUND/OBJECTIVES: Malignant pancreatobiliary strictures are in many cases clinically indistinguishable and present a major problem to endoscopy specialists. Intraductal sampling procedures such as brush cytology are commonly used for diagnosis with a sensitivity that is low for a diagnostic test used in daily clinical practice. MicroRNA (miR) alterations detected in many cancers are disease-specific, which can be utilized in clinical applications. The aim of the present study was to analyze whether determination of miR expression levels in intraductal brush cytology specimens is a feasible approach to improve the diagnosis of pancreatobiliary cancer. METHODS: Brush cytology specimens have been collected during endoscopic retrograde cholangio-pancreatography (ERCP) and analyzed by routine cytology and ancillary miR assays. Total RNA was extracted using the miRNeasy Mini Kit and the expression of miRs frequently dysregulated in pancreatobiliary cancer (miR-16, miR-21, miR-196a, miR-221) were analyzed by quantitative real-time PCR using RNU6B as internal control. RESULTS: Routine cytology resulted in no false positive diagnoses, however, the combined sensitivity remained at 53.8%. Expression (ΔCt values) of miR-16 (p = 0.0039), miR-196a (p = 0.0003) and miR-221 (p = 0.0049) showed a clear statistical significance between malignant and benign pancreatobiliary specimens (n = 35). Malignancy could be detected combining routine cytology and the miR-196a single marker expression levels with a sensitivity of 84.6% (92.9% in biliary strictures) with no false positives. CONCLUSIONS: The results offer the first direct demonstration that microRNAs are readily detectable in brush cytology specimens obtained during ERCP, and have the potential to help the cytological diagnosis of pancreatobiliary malignancy.

Reversal of gene expression changes in the colorectal normal-adenoma pathway by NS398 selective COX2 inhibitor.

BACKGROUND AND AIMS: Treatment of colorectal adenomas with selective cyclooxygenase-2 inhibitors can contribute to the chemoprevention of colorectal cancer (CRC), but the molecular background of their effect is not fully understood. We analysed the gene expression modulatory effect of N-(2-cyclohexyloxy-4-nitrophenyl)-methanesulfonamide (NS398) on HT29 cells to be correlated with expression data gained from biopsy samples. METHODS: HT29 colon adenocarcinoma cells were treated with NS398, and global mRNA expression was analysed on HGU133Plus2.0 microarrays. Discriminatory transcripts between normal and adenoma and between adenoma and CRC biopsy samples were identified using HGU133Plus2.0 microarrays. The results were validated using RT-PCR and immunohistochemistry. RESULTS: Between normal and adenoma samples, 20 classifiers were identified, including overexpressed cadherin 3, KIAA1199, and downregulated peptide YY, glucagon, claudin 8. Seventeen of them changed in a reverse manner in HT29 cells under NS398 treatment, 14 (including upregulated claudin 8, peptide YY, and downregulated cadherin 3, KIAA1199) at a significance of P<0.05. Normal and CRC could be distinguished using 38 genes, the expression of 12 of them was changed in a reverse manner under NS398 treatment. CONCLUSION: NS398 has a reversal effect on the expression of several genes that altered in colorectal adenoma-carcinoma sequence. NS398 more efficiently inverted the expression changes seen in the normal-adenoma than in the normal-carcinoma transition.

[Implementation and testing of a multifunctional electronic patient record for routine practice and evaluation of patient care]. / Implementierung und Erprobung einer multifunktionalen elektronischen Patientenakte für Routine und Evaluation der Patientenversorgung.

"Medical Monitoring" is a software produced for everyday medical practice in order to document data of history, physical and functional status, interventions and outcomes. The electronic patient record has been developed for research purpose within a network of hospitals and primary care physicians specialized in integrative medicine. It should help to realize a comprehensive documentation-system for long-term observations of patients concerning effectiveness, cost, risk and safety. Important components of the program are: a) health record for routine documentation in medicine and nursing b) tools for formal assessment in special indications c) user-support in service and decision-making d) user-support for advising and teaching patients in self-treatment and lifestyle-techniques e) archive-function for diverse findings f) tools for quality assurance g) tools for reimbursement and billing.

[Infant mortality among children of 35-39 year-old mothers. An analysis of development of death cause categories and among multiple pregnancies during the period 1980-1993]. / Den perinatale dødelighed blandt børn af 35-39-årige mødre. En analyse af udviklingen i dødsårsagskategorier og blandt flerfoldsfødte i perioden 1980-1993.

The perinatal mortality in Denmark decreased significantly from the late 1980's to 1990-1993 but increased among births by mothers aged 35-39 years, from 9.7 in 1985-1989 to 11.0 per 1000 born in 1990-1993. No increase was observed among infants of teen-age mothers or mothers older than 40 years. Based upon data from the Danish National Register of Causes of Death and the Birth Register all perinatal deaths in 1980-1993 were classified in nine categories including pathoanatomical, obstetrical and paediatric criteria. The increase in perinatal mortality in infants born to mothers aged 35-39 years was because of more deaths due to congenital birth defects, intra-partum events and foeto-placental dysfunction, while mortality due to prematurity decreased. The rate of multiple pregnancies and of primiparas increased significantly among 35-39 year-old mothers. With reference to international literature, the article discusses the possible impact of in-vitro fertilisation and other fertility treatments upon the special trend in perinatal mortality in this mother age-group. A national Danish IVF-register was first established in 1994 and will in the future allow concrete analyses of the outcome of IVF-pregnancies.

[Abortions and prevention of pregnancies in 1992]. / Aborter og svangerskabsforebyggelse i 1992.

PIP: In January 1994, the Health Service published its statistics about pregnancy prevention and abortion in 1991 and 1992. The number of legal abortions was 19,729 in 1991 and 18,833 in 1992, which was the lowest figure since the law was introduced about elective abortion in 1973. 2623 fewer abortions were carried out in 1992 than five years before. The general abortion rate decreased from 15.8 in 1990 to 14.9 in 1992 (it was the highest in 1975 with 23.7). The age-specific abortion rate fell mostly in the 18-29 age group, with fewer in the 15-19 and 30-34 age groups. The number of children who were born to women over 40 increased from 390 in 1982 to 864 in 1992, while the birth rate of women under 20 decreased to almost half. The abortion rate was the highest in large cities, it was about 2.5 times higher than in the county of Ringkobing, which had the lowest rate, especially in the age groups under 25 years. The combined abortion rate (per 1000 women of reproductive age) was 578 in 1982, 540 in 1990, and 505 in 1992. 97.5% of abortions were performed within 12 weeks of pregnancy in accordance with the abortion law. 2% of abortions were carried out because of the woman's health or for social indications. 80% of abortions were performed in the 10th week of pregnancy mostly with vacuum aspiration. Complications decreased compared to previous years, and made up 2.6% of all abortions in 1992, mainly bleeding and, for 1/5 of them, inflammatory conditions. Half of the women who underwent an abortion in 1992 had given birth to at least one living child, 8% to more than three. Half of the 20% of women who could given birth but chose abortion had given birth in the previous two years and 27% within less than a year before abortion. The number of spontaneous abortions was 10,717 in 1991 and 10,605 in 1992, about 1000 fewer than in 1990. The number of male sterilizations fell from 2784 in 1991 to 1722 in 1992, and female sterilizations from 4777 to 4429. About 13 million condoms and 16,000 IUDs were sold, and about 250,000 Danish women used oral contraceptives.^ieng

Mortality from chronic interstitial nephritis and phenacetin consumption in Denmark.

After 1950, a pronounced increase in the mortality from chronic interstitial nephritis among women was registered in Denmark. This was suspected to be caused by a contemporary increase in the consumption of drugs containing phenacetin. Restrictions were therefore imposed on the sale of such drugs in 1961 and consumption decreased sharply. This report, based upon death certificates from 1941--76, shows that the mortality rate from chronic interstitial nephritis has decreased gradually among women in Denmark since 1960, and has now reached the same level in younger women as in the 1940's.

[Treatment of bradycardia with an atropine ester]. / Therapie der Bradykardie mit einem Atropinester

In view of the unsatisfying drug treatment of bradycardias in most cases, clinical studies with new compounds seem to be urgent. A report is given on experiences with a derivative of atropine (gen. Ipratropiumpromid) in 34 cases suffering from various types of bradycardias. Comparing heart rate following intravenous injections of 0.5 to 1.0 mg, the new drug proved to be definitely more effective than atropine sulfate. Side effects were limited to diminution of salivary glands function.