The use of CVD diamond to produce carbon K ultrasoft x-rays

Carbon K ultrasoft x-rays (278 eV) interact with biological material producing random, isolated tracks of single electrons with a range < 7 nm (cf width of DNA helix approximately2 nm). The electron tracks produced by these ultrasoft x-rays are similar to the numerous secondary electrons and 'track ends' produced by essentially all ionizing radiations. They therefore provide a unique tool in the study of mechanisms of radiation action in the cell. Conventional carbon targets used with the Medical Research Councils cold-cathode discharge tubes have a limited lifetime of 40-50 min. We have investigated the use of thin, freestanding diamond films produced using chemical vapour deposition techniques as a new transmission target for a cold-cathode tube. We present here a novel use of diamond to produce CK ultrasoft x-rays for irradiation purposes. The system described produces an entrance absorbed dose rate to attached cells of approximately 0.2 Gy min(-1) which due to the long target lifetime is usable for low dose-rate CK x-ray studies.     

Is Gender Selection an Appropriate Use of Medical Resources?

Gender selection by PGD is an appropriate use of medical resources. Children borne through PGD for gender determination would be welcome and would come into a couple's life at a planned, opportune time. If the practice were made more available through insurance coverage, the size and makeup of families could become a matter of choice rather than chance for couples favoring this approach.     

Surveying physicians: do components of the "Total Design Approach" to optimizing survey response rates apply to physicians?

BACKGROUND: Surveys serve essential roles in clinical epidemiology and health services research. However, physician surveys frequently encounter problems achieving adequate response rates. Research on enhancing response rates to surveys of the general public has led to the development of Dillman's "Total Design Approach" to the design and conduct of surveys. The impact of this approach on response rates among physicians is uncertain. OBJECTIVE: To determine the extent to which the components of the total design approach have been found to be effective in physician surveys. DESIGN: A systematic review. RESULTS: The effectiveness of prepaid financial incentives, special contacts, and personalization to enhance response rates in surveys of physicians have been confirmed by the existing research. There is suggestive evidence supporting the use of first class stamps on return envelopes and multiple contacts. The optimum amount for incentives and the number of contacts necessary have not been established. Details of questionnaire design and their impact on response rates have received almost no attention from researchers. Few studies have assessed the usefulness of combinations of components of the total design approach. CONCLUSIONS: Despite the number of surveys conducted among physicians, their cost, the level of interest in their findings, and in spite of inadequate response rates, there have been few randomized trials conducted on important aspects of enhancing response in this population. Until this gap has been filled, researchers conducting surveys of physicians should consider including all components of the total design approach whenever feasible.     

Randomized trial to evaluate indinavir/ritonavir versus saquinavir/ritonavir in human immunodeficiency virus type 1-infected patients: the MaxCmin1 Trial

This trial assessed the rate of virological failure at 48 weeks in adult human immunodeficiency virus (HIV) type 1-infected patients assigned indinavir/ritonavir (Idv/Rtv; 800/100 mg 2 times daily) or saquinavir/ritonavir (Sqv/Rtv; 1000/100 mg 2 times daily) in an open-label, randomized (1:1), multicenter, phase 4 design. Three hundred six patients began the assigned treatment. At 48 weeks, virological failure was seen in 43 (27%) of 158 and 37 (25%) of 148 patients in the Idv/Rtv and Sqv/Rtv arms, respectively. The time to virological failure did not differ between study arms (P=.76). When switching from randomized treatment was counted as failure, this was seen in 78 of 158 patients in the Idv/Rtv arm, versus 51 of 148 patients in the Sqv/Rtv arm (P=.009). A switch from the randomized treatment occurred in 64 (41%) of 158 patients in the Idv/Rtv arm, versus 40 (27%) of 148 patients in the Sqv/Rtv arm (P=.013). Sixty-four percent of the switches occurred because of adverse events. A greater number of treatment-limiting adverse events were observed in the Idv/Rtv arm, relative to the Sqv/Rtv arm. In conclusion, Rtv-boosed Sqv and Idv were found to have comparable antiretroviral effects in the doses studied.     

Cytoskeletal responsiveness to progestins is dependent on progesterone receptor A levels

Changes in the cell cytoskeleton occur in cell transformation and recent data suggest the involvement of ovarian hormones, which are implicated in cancer development and progression. In human breast and endometrial tumors, there is disrupted expression of progesterone receptor (PR) isoforms and predominance of one isoform, usually PRA. PRA predominance is an early event in carcinogenesis, and in cancers is associated with poor clinical features. Overexpression of PRA in vitro causes altered progestin regulation of cell morphology, suggesting that PRA overexpression may provoke deleterious changes in cell functioning. This study aimed to identify pathways of cytoskeleton regulation responsive to progestins and to determine whether these are perturbed when PRA is overexpressed to the levels seen in cancers. Progestin treatment of PR-positive breast cancer cells caused increased cell surface area whereas after induction of a stably integrated PRA construct, cells became rounded and the cell surface was decreased. The effect of PRA induction on cell rounding was reversed by the anti-progestin RU38486. Altered tropomyosin (Tm) isoforms were implicated in these morphological differences, as there was a PRA-mediated alteration in Tm5 isoform levels, and transfection of Tm5a mimicked progestin-mediated cell rounding in PRA-overexpressing cells. Ezrin was redistributed from the membrane to cytoplasmic locations in the presence of progestin, and discrete focal localization was evident in cells with PRA predominance. Progestin effects on the cytoskeleton in PRA-overexpressing cells provide evidence for novel endocrine regulation of aspects of actin microfilament composition, suggesting that changes in the cytoskeleton known to be associated with cancer development and progression may be regulated in part by altered PRA expression which develops early in carcinogenesis.     

Ambulatory care-sensitive conditions: clinical outcomes and impact on intensive care unit resource use

BACKGROUND: We identified risk factors and clinical outcomes associated with ambulatory care-sensitive conditions requiring intensive care unit (ICU) admission. METHODS: This prospective cohort study included 4,144 patients admitted to the medical ICU of an urban teaching hospital during a 3-year period. RESULTS: A total of 627 patients were classified as having ambulatory care-sensitive conditions (ie, potentially preventable ICU admissions). Black race, decreasing Acute Physiology and Chronic Health Evaluation II (APACHE II) score, younger age, female sex, and absence of immunodeficiency were independently associated with ambulatory care-sensitive conditions. Patients classified as having ambulatory care-sensitive conditions accounted for 2,006 ventilator days, 2,508 ICU days, and 5,392 hospital days. The hospital mortality rate was statistically lower for patients with ambulatory care-sensitive conditions than for patients without these conditions. Patients classified as having ambulatory care-sensitive conditions were also statistically more likely than other patients to lack health insurance and to sign out of the hospital against medical advice. CONCLUSION: Patients with ambulatory care-sensitive conditions account for a substantial portion of all admissions to the intensive care unit. These data suggest that interventions aimed at preventing such admissions could improve ICU bed use.