Participation in cervical cancer screening by age and region--a cohort study with a 3 1/2 year follow-up on 2,223,135 women in Bavaria.

OBJECTIVE OF THE STUDY: Cervical cancer rates are higher in Germany than in comparable European countries. While other European countries have implemented invitation programs, Germany relied on annual free access only. Are sufficient screening participation rates achieved? METHODS: We analyzed data from 2,223,135 Bavarian women between 2002/3 and 2005/4 in a retrospective cohort, to evaluate screening participation, frequency, age dependencies and regional differences. RESULTS: The highest screening participation was amongst women between 20 and 29 (54.6% had at least one visit after one year, 84% within three years) and decreased progressively with increasing age. Participation was lowest for women above 70 in rural areas (in some regions less than 20% had at least one screening within three years). CONCLUSION: Poor participation rates in general are unlikely to account for the high cervical cancer rates in Germany. Low participation rates in elderly women, particularly those in rural regions might contribute to the well-known peak of cervical cancer in elderly women.

The role of active metabolites in dihydrocodeine effects.

OBJECTIVE: The metabolism of dihydrocodeine to dihydromorphine, a high affinity mu-opioid receptor ligand in membrane homogenates, is catalyzed by CYP2D6. However, it is not clear whether an active CYP2D6 enzyme is required for opioid receptor-mediated effects in man after standard dihydrocodeine doses. METHODS: Whole cell opioid-receptor affinity and effects on cAMP accumulation of dihydrocodeine and its metabolites were determined in differentiated SH-SY5Y neuroblastoma cells. In a double-blind, 2-period, placebo-controlled randomized crossover pilot study the pharmacokinetics of dihydrocodeine (60 mg single dose) and its metabolites were examined in 5 phenotyped extensive (EMs) and 4 poor metabolizers (PMs) for CYP2D6, and pharmacodynamics were evaluated using a pain threshold model and dynamic pupillometry. RESULTS: Displacement binding and cAMP accumulation experiments showed clearly higher affinities (100- and 50-fold) and activities (180- and 250-fold) of dihydromorphine and dihydromorphine-6-glucuronide, respectively, whereas the other metabolites had similar or lower affinities and activities as compared to dihydrocodeine. The clinical study revealed no significant difference in plasma or urine pharmacokinetics between EMs and PMs for dihydrocodeine and its glucuronide. Dihydromorphine and its glucuronides were detectable in EMs only. A clear reduction of initial pupil diameters was observed up to 6 hours postdose in both PMs and EMs, with no obvious differences between CYP2D6 phenotypes. In the pain threshold model no effects were observed in either group. CONCLUSION: CYP2D6 phenotype has no major impact on opioid receptor-mediated effects of a single 60 mg dihydrocodeine dose, despite the essential role of CYP2D6 in formation of highly active metabolites.