Jutta Engel

In cochlea inner hair cells (IHCs), L-type Ca(2+) channels (LTCCs) formed by alpha1D subunits (D-LTCCs) possess biophysical and pharmacological properties distinct from those of alpha1C containing C-LTCCs. We investigated to which extent these differences are determined by alpha1D itself by analyzing the biophysical and pharmacological properties of cloned human alpha1D splice variants in tsA-201 cells. Variant alpha1D(8A,) containing exon 8A sequence in repeat I, yielded alpha1D protein and L-type currents, whereas no intact protein and currents were observed after expression with exon 8B. In whole cell patch-clamp recordings (charge carrier 15-20 mm Ba(2+)), alpha1D(8A) - mediated currents activated at more negative voltages (activation threshold, -45.7 versus -31.5 mV, p < 0.05) and more rapidly (tau(act) for maximal inward currents 0.8 versus 2.3 ms; p < 0.05) than currents mediated by rabbit alpha1C. Inactivation during depolarizing pulses was slower than for alpha1C (current inactivation after 5-s depolarizations by 90 versus 99%, p < 0.05) but faster than for LTCCs in IHCs. The sensitivity for the dihydropyridine (DHP) L-type channel blocker isradipine was 8.5-fold lower than for alpha1C. Radioligand binding experiments revealed that this was not due to a lower affinity for the DHP binding pocket, suggesting that differences in the voltage-dependence of DHP block account for decreased sensitivity of D-LTCCs. Our experiments show that alpha1D(8A) subunits can form slowly inactivating LTCCs activating at more negative voltages than alpha1C. These properties should allow D-LTCCs to control physiological processes, such as diastolic depolarization in sinoatrial node cells, neurotransmitter release in IHCs and neuronal excitability.

OBJECTIVE: To assess long-term quality of life in a population-based sample of rectal cancer patients. SUMMARY BACKGROUND DATA: Quality of life in rectal cancer patients who suffer reduced bowel and sexual function is very important. Few studies, however, have long term follow-up data or sufficient sample sizes for reliable comparisons between operation groups. PATIENTS AND METHODS: A 4-year prospective study of rectal cancer patients' quality of life was assessed by using the European Organization for Research and Treatment of Cancer QLQ-30 and CR38 questionnaires. RESULTS: A total of 329 patients returned questionnaires. Overall, anterior resection patients had better quality of life scores than abdominoperineal extirpation patients. High-anterior resection patients had significantly better scores than both low-anterior resection and abdominoperineal extirpation patients. Low-anterior resection patients, however, overall had a better quality of life than abdominoperineal extirpation patients, especially after 4 years. Abdominoperineal extirpation patients' quality of life scores did not improve over time. Stoma patients had significantly worse quality of life scores than nonstoma patients. Quality of life improved greatly for patients whose stoma was reversed. CONCLUSIONS: Anterior resection and nonstoma patients, despite suffering micturition and defecation problems, had better quality of life scores than abdominoperineal extirpation and stoma patients. Comparisons between abdominoperineal extirpation and anterior resection patients should consider the effect of temporary stomas. Improvements in quality of life scores over time may be explained by reversal of temporary stomas or physiologic adaptation.

There are many conflicting results in the literature comparing quality of life following breast-conserving therapy (BCT) and mastectomy. This study compared long-term quality of life between breast cancer patients treated by BCT or mastectomy in three age groups. Patients (n = 990) completed a quality of life survey, including the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), at regular intervals over 5 years. In the cross-sectional data, mastectomy patients had significantly (p < 0.01) lower body image, role, and sexual functioning scores and their lives were more disrupted than BCT patients. Emotional and social functioning and financial and future health worries were significantly (p < 0.01) worse for younger patients. There were no differences in body image and lifestyle scores between age groups. There was also no interaction between age and surgery method. Even patients > or =70 years of age reported higher body image and lifestyle scores when treated with BCT. The repeated measures analysis indicated that four functioning scores, half the symptom scores, future health, and global quality of life improved significantly (p < 0.01) over time. All these variables increased significantly for BCT patients and those 50 to 69 years of age. Body image, sexual functioning, and lifestyle disruption scores did not improve over time. BCT should be encouraged in all age groups. Coping with appearance change should be addressed in patient interventions.