Cancer incidence of persons with Down syndrome in Finland: a population-based study

Individuals with Down syndrome (DS) have a predisposition to leukaemia and testicular cancer, but data on the incidence of cancers are yet sparse. A cohort of 3,581 persons with DS was identified from a National Registry of Finnish persons with intellectual disability collected between 1978 and 1986 and followed-up for cancer incidence until 2002. Standardised incidence ratios (SIRs) were defined as ratios of observed number of cancer cases to those expected from the national cancer incidence rates, by age and sex. The overall cancer risk was equal to that of the general population, but a significantly high risk of leukaemia (SIR 10.5, CI 95% 6.6-15.8) and testicular cancer (SIR4.8, CI 95% 1.8-10.4) was found.     

Are there socioeconomic differences in myocardial infarction event rates and fatality among patients with angina pectoris?

BACKGROUND: Systematic socioeconomic differences in mortality have been reported among myocardial infarction (MI) patients in many countries, including Finland. The findings have been similar irrespective of country, study period, age group, or length of follow up, but few studies have examined the disparities among other groups of coronary patients. This study examined whether similar socioeconomic differences in outcomes exist among patients with angina pectoris (AP). METHODS: The data were based on individual register linkages among a population based 40-79 year-old cohort of 61,350 patients with incident AP or MI during 1995-1998 in Finland. Two year coronary heart disease mortality and one year MI incidence and its 28 day case fatality was studied among AP patients using Cox's and logistic regression analysis, and the results compared with those of the MI patient group. RESULTS: A clear socioeconomic pattern was found in two year coronary heart disease (CHD) mortality: the lower the socioeconomic group the higher the mortality risk. The socioeconomic patterning of mortality was similar to that found among MI patients. Controlling for comorbidity or disease severity did not change the results. Among AP patients a similar pattern was also found in MI incidence during the follow up, but no systematic socioeconomic differences were detected in its 28 day case fatality. CONCLUSIONS: Socioeconomic differences in CHD outcomes also exist among angina patients. These results suggest that targeted measures of secondary prevention are needed among CHD patients with lower socioeconomic status to reduce socioeconomic disparities in fatal and non-fatal coronary events.     

Utilization of fluorescence in situ hybridization with cytokeratin discriminators in TOP2A assessment of chemotherapy-treated patients with breast cancer

Tumor biomarkers increasingly provide information for predicting outcomes with chemotherapeutic regimens (personalized medicine). Topo2A is a DNA helicase targeted by anthracyclines, cytotoxic therapeutics used in both adjuvant and palliative treatments of breast cancer. TOP2A gene amplification/deletion is implicated in response to anthracycline-based chemotherapy. We describe an approach for analyzing formalin-fixed, paraffin-embedded breast tumors on tissue microarrays with TOP2A fluorescence in situ hybridization coupled with cytokeratin immunofluorescence to target tumor cells. Stained tissue from patient specimens was imaged and analyzed using Metafer/Metacyte (Metasystems, Waltham, MA, USA), including customized image classifiers. TOP2A/CEN17 ratios of 2.0 or greater (amplified) and 0.8 or less (deleted) were observed for 10.0% and 6.1% of the patients, respectively. Patient outcomes for adjuvant chemotherapy (cyclophosphamide-epirubicin-fluorouracil, cyclophosphamide-methotrexate-fluorouracil, no chemotherapy) were evaluated. No statistical significance was achieved for clinical end points regarding TOP2A status in anthracycline-treated patients. However, patients with TOP2A aberrations receiving methotrexate-based therapy exhibited a significant decrease in 5-year distant disease-free survival and breast cancer-specific overall survival, especially for patients with TOP2A deletions (disease-free survival: hazard ratio, 5.31 [P = .001], and breast cancer-specific overall survival: hazard ratio, 6.45 [P ≤ .001]). No significant differences were seen in patients included in the no-chemotherapy group. Topo2A protein levels were assessed by immunohistochemistry with no correlative statistical relevance to immunofluorescence/fluorescence in situ hybridization-based prognosis for cyclophosphamide-epirubicin-fluorouracil or cyclophosphamide-methotrexate-fluorouracil groups. Interestingly, aberrant (under)expressing patients in the no-chemotherapy group exhibited better 5-year distant disease-free survival (hazard ratio, 0.39; P = .004), trending toward more favorable breast cancer-specific overall survival (hazard ratio, 0.61; P = .11). Our results indicate a strategy by which fluorescence in situ hybridization scoring targeted to cytokeratin-positive tumor cells may provide a tool for added precision and efficiency in TOP2A evaluation from tumor tissue.     

High HIV prevalence among injecting drug users in Estonia: implications for understanding the risk environment

We found a high prevalence of HIV among injecting drug users (IDU) 54% in Tallinn and 90% in Kohtla Jarve, Estonia. Risk factors for HIV in Tallinn included use of the drug 'china white', being registered as an IDU at a drug treatment clinic, and sharing injecting equipment with sex partners. Differences existed in risk behaviour between the cities. An urgent scale-up of HIV prevention is needed. It is also important to explore how local 'risk environments' mediate the risk of HIV transmission.     

Segmental stem fracture of a cemented femoral prosthesis

We report an unusual case of segmental stem fracture in 4 places of a cemented femoral prosthesis in a 43-year-old man 4 years after total hip arthroplasty. To our knowledge, this is the first reported case of segmental stem fracture. Detailed analysis of the prosthesis was performed at an independent testing laboratory. Initiation of all the cracks occurred on the medial aspect on the stem where the manufacturer's identification lettering was present, and the fractures occurred sequentially along the stem from distal to proximal. Laser etching is likely to have caused the microstructural alterations found on the surface of the stem, which, in turn, predisposed to fatigue cracking. Proximal debonding of the cement-bone interface observed in prefracture radiographs suggests that cantilever-bending stresses represented the initial mode of failure.     

Comparison of the inhibitory effects of interferon alfacon-1 and ribavirin on yellow fever virus infection in a hamster model

Antiviral compounds were evaluated for efficacy against yellow fever virus (YFV) in a hamster model of YFV-induced liver disease. Challenge with a 10(2) 50% cell culture infectious doses of YFV resulted in a 50-80% mortality rate in female hamsters. Virus was detected by quantitative real-time RT-PCR (QRT-PCR) in liver, kidney, spleen and serum with peak titers on 4-6 days post-viral challenge (dpi). Serum levels of alkaline phosphatase, alanine aminotransferase (ALT), bilirubin, blood urea nitrogen, potassium and creatinine were significantly elevated, while serum levels of albumin, amylase, glucose, calcium, globulin, phosphorus, sodium and total protein were significantly reduced. Packed cell volume and white blood cell count were significantly elevated during the course of the infection. Intraperitoneal treatment of hamsters with 0.5-5 microg/kg/day interferon (IFN) alfacon-1, 100mg/kg/day viramidine or 50 mg/kg/day ribavirin, initiated 4h prior to YFV challenge, resulted in significant improvement in survival and serum ALT levels. Treatment with IFN alfacon-1 or ribavirin starting 2dpi, also significantly improved survival and serum ALT levels in hamsters challenged with YFV. Pre- and post-virus exposure treatment with IFN alfacon-1 was efficacious in improving disease in YFV-infected hamsters.     

Pharmacophore modelling of 17beta-HSD1 enzyme based on active inhibitors and enzyme structure

The 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) enzyme regulates the conversion of estrone (E1) to the biologically active estradiol (E2). Due to its role as a key enzyme in female hormone production, it has emerged as an attractive drug target for inhibitor development in relation to hormone-dependent breast cancer. Herein, we report four pharmacophore models of 17beta-HSD1 based on a crystal structure, a relaxed crystal structure, a library of 17beta-HSD1 inhibitors and on a docked complex of 17betaHSD1 enzyme and a potent inhibitor. The models were used in screening two databases, which produced novel compounds to be used as leads in our drug design project. The results were validated by docking the compounds to the active site of the 17beta-HSD1 enzyme. With the help of our 3D-QSAR model, these results will be used to develop new inhibitors of 17beta-HSD1 as drug candidates.