DNA measurement,proliferation markers,and other factors in pituitary adenomas

To assess the proliferative activity of pituitary adenomas, 36 surgically removed adenomas were studied by light microscopical parameters; mitotic count; expression of PCNA, Ki-67, cathepsin D, and EGF; and image cytometry. Three adenomas (9%) showed high, 11 (34%) medium, 17 (53%) moderate, and 1 (3%) low structural differentiation. In 10 adenomas (31%), no mitosis was observed. The average was 2.4 mitoses/100 HPF; the highest count was 7.1 mitoses/100 HPF. Eleven adenomas (33.3%) were PCNA-negative; in 20 adenomas (60.6%), between 0.05 and 3.9, and in 2 adenomas (6.0%), between 10.5 and 16.4 PCNA-positive nuclei were observed. Only a recurrent null-cell adenoma (9%) was Ki-67-negative. Three adenomas (9.1%) were EGF-negative, 28 (84.8%) showed up to 10% positive cells, and 2 (6.1 %) showed between 10 and 30% positive cells; 19 adenomas (68%) were cathepsin D-negative, including all endocrine-inactive adenomas. Half the adenomas had an euploid DMA stem line. Endocrine-inactive adenomas displayed a higher rate of euploid DNA stem lines than endocrine-active adenomas. The S-phase fraction varied between 2.97 and 28%, with a mean value of 14.4%. Half the adenomas showed an S-phase fraction of 11.65% or lower.     

Distribution of the [3H]-label from low doses of radioactive ochratoxin a ingested by rats,and evidence for DNA single-strand breaks caused in liver and kidneys

The distribution of a single low dose of [³H]ochratoxin A (OTA) in different tissues of male Wistar rats, after administration by intubation, was investigated after 5 h, 24 h and 48 h. This dose corresponds to concentrations encountered in naturally contaminated feed (4 ppm). The distribution of [³H]-label varied with the time elapsed after administration; at 5 h the highest specific label was found in the stomach contents and in decreasing order in: intestinal contents, lung, liver, kidney, heart, fat, intestine, testes, and the lowest in muscles, spleen and brain. With exception of brain, fat, stomach and lung, all tissues showed maximum levels at 24 h, after which time the label decreased steadily, whereas in fat it increased.After a 12-week feeding experiment, with doses of 288.8 g/kg corresponding to an intake of 4 ppm in feed each 48 h, the DNA in liver and kidneys was investigated for damage. By the alkaline elution method combined with micro-spectrofluorimetric determinations of DNA, evidence for DNA single-strand breaks was obtained. These findings support reports on the carcinogenic action of OTA.     

Highlights in experimental therapeutics

The past two decades have seen a dramatic change in cancer treatment paradigms. Anticancer agents are no longer being developed based on empiricism and serendipity, but are now being aimed to inhibit a validated target that is relatively specific for tumours rather than normal cells. The vast majority of cancers arise from multiple genetic lesions; thus, sophisticated drug cocktails, or single drugs acting on multiple downstream targets will be needed for successful cancer therapy. Three emerging concepts that are addressing these therapeutic needs and that are key to blocking steps in tumourigenesis will be highlighted in this review: (a) attacking cancer cell immortality by targeting the telomere/telomerase complex; (b) targeting oncogene activation by inhibiting the molecular chaperone Hsp90; and (c) stabilizing tumour suppressor proteins by modulating the ubiquitin-proteasome system.     

Tick-born encephalitis (TBE) vaccination in children: advantage of the rapid immunization schedule (i.e., days 0, 7, 21)

Tick-borne encephalitis (TBE) is an important, vaccine-preventable arthropod-borne disease, causing severe illness in children too. In order to evaluate the immune response to different licensed primary immunization schedules, a total of 294 children aged 1 to 11 years of age were enrolled in a randomized, controlled, multi-center trial. The subjects were vaccinated with the pediatric formulation of a TBE vaccine (Encepur children) according to the conventional schedule (Group C; N = 73, vaccination on days 0, 28 and 300), the modified conventional schedule (Group M; N = 139, vaccination on days 0, 21 and 300), or the rapid schedule (Group R; N = 82, vaccination on Days 0, 7 and 21). Antibody titers as measured by neutralization-test (NT) and ELISA were determined on Days 0, 42, 180, 300, and 321. The demographic data of the study groups were similar. Most subjects (97%-100%) reached an NT titer of at least 1:10 on Day 42. On Day 42, the highest NT geometric mean titers (GMTs) were reached in Group C. In Group C and Group M, titers declined up to Day 300. Until Day 300, the highest NT-GMTs were maintained in Group R, notably without a decline compared to Day 42. Group M reached titers similar to Group R on Day 42, but these titers declined by 50% up to Day 180. Similar to the NT, on Day 42 highest geometric mean concentrations (GMCs) as measured by ELISA across all groups were reached in Group C. In all groups, titers declined until Day 300. On Day 300, GMC ELISA of Group R was higher compared to Group C and Group M. To conclude, the rapid immunization schedule in children not only provides fast protection but also leads to stable titers as measured by NT for at least 300 days after vaccination.     

The Mosque Campaign: a cardiovascular prevention program for female Turkish immigrants

BACKGROUND: The Women's Health Office of the State of Tyrol, Austria, provides cardiovascular disease (CVD) prevention programs for women. However, local Turkish women have not participated in our programs. The aim of the so-called Mosque Campaign was to conduct a Turkish-language, culture-sensitive CVD prevention program tailored to the needs of Turkish women to improve their knowledge of CVD risk factors and to minimize ethnic differences in participation rates for preventive programs. METHODS: The pilot program was conducted in all 28 mosques in Tyrol during the years 1999/00, 2000/01 and 2001/02. A Turkish educational lecture and the opportunity for a private medical consultation were provided, and 2,446 Turkish women completed a questionnaire on their personal knowledge of CVD. In addition a total of 1,992 blood pressure readings were taken. RESULTS: Most of the women belonged to the first generation of female immigrants and reported not using German-language media. About one-third of the women considered themselves to be obese. More than 13 % had raised systolic and/or diastolic blood pressure. We observed a significant decrease in unawareness of the main CVD risk factors from 1999/00 to 2001/02: unawareness of cholesterol level decreased from 57.4 % to 32.4 % (p < 0.001), of blood pressure from 41.3 % to 29.6 % (p < 0.001) and of blood glucose from 49.7 % to 25.2 % (p < 0.001). CONCLUSIONS: Even though Austria provides free access to healthcare services, a large number of Turkish women were not aware of their CVD risk factors. The Mosque Campaign reached female Turkish migrants and was effective in reducing their level of unawareness about CVD. Language-adapted and culture-sensitive programs are necessary to ensure greater equality for ethnic minority groups.     

Three-dimensional color Doppler sonography in carotid artery stenosis

BACKGROUND AND PURPOSE: Color Doppler sonography (CDS) suffers from such disadvantages as high interobserver variability and problems with data presentation and storage. We therefore performed a prospective trial to assess the role of three-dimensional CDS (3D-CDS) in the evaluation of internal carotid artery stenosis (ICAS). METHODS: We included 32 consecutive patients with sonographically verified ICAS (30-99%) and 16 asymptomatic volunteers. All underwent CDS and 3D-CDS, and 23 patients also underwent intraarterial angiography. The sensitivity, specificity, positive predictive value, and negative predictive value for the detection of high-grade ICAS were analyzed by three blinded readers, who also graded the percentage of ICAS. RESULTS: CDS revealed 14 patients with mild to moderate ICAS and 18 patients with high-grade ICAS. Mean sensitivity of 3D-CDS was 81.5%, mean specificity was 98.9%, mean positive predictive value was 97.9%, and mean negative predictive value was 89.9%. 3D-CDS correlated significantly with CDS (mean r=0.85; P<.001) and angiography (mean r=0.57; P=.01). CONCLUSION: 3D-CDS findings correlate with those obtained by CDS and angiography; 3D-CDS also offers excellent interobserver correlation, positive predictive value, and specificity, approaching 100% for the detection of high-grade ICAS.