Esterified estrogens with and without methyltestosterone decrease arterial LDL metabolism in cynomolgus monkeys

OBJECTIVES: To assess retinal complications and to identify risk factors for retinal complications following aqueous shunt procedures. MATERIALS AND METHODS: Records of 38 consecutive aqueous shunt procedures that were performed on 36 patients at the Eye Institute of the Medical College of Wisconsin, Milwaukee, from June 1993 to March 1995 (minimum follow-up, 6 months) were reviewed. The mean +/- SD follow-up was 11.4 +/- 5.2 months (median, 10.5 months). RESULTS: Twelve patients (32%) had the following retinal complications: 4 serous choroidal effusions (10%) that required drainage, 3 suprachoroidal hemorrhages (8%), 2 vitreous hemorrhages (5%), 1 rhegmatogenous retinal detachment (3%), 1 endophthalmitis (3%), and 1 scleral buckling extrusion (3%). Surgical procedures for retinal complications were required in 8 (67%) of these 12 patients. Visual acuity decreased 2 lines or more in 9 (75%) of these 12 patients. The median onset of a postoperative retinal complication was 12.5 days, with 10 patients (83%) experiencing complications within 35 days. Serous choroidal effusions developed in 10 other patients (26%), and these effusions resolved spontaneously. Visual acuity decreased 2 lines or more in 2 (20%) of these additional 10 patients. Patients who experienced serious retinal complications were significantly older, had a higher rate of hypertension, and postoperative ocular hypotony. Serious retinal complications were distributed evenly among patients with Krupin valves with discs and Molteno and Baerveldt devices. Experience with the Ahmed glaucoma valve implant was limited. CONCLUSION: Aqueous shunt procedures may be associated with significant retinal complications and subsequent visual loss.     

Tissue culture surface characteristics influence the expansion of human bone marrow cells

Human cell therapy applications in tissue engineering, such as the ex vivo production of hematopoietic cells for transplantation, have recently entered the clinic. Although considerable effort has been focused on the development of biological processes to generate therapeutic cells, little has been published on the design and manufacture of devices for implementation of these processes in a robust and reproducible fashion at a clinical scale. In this study, the effect of tissue culture surface chemistry and texture was assessed in human bone marrow (BM) mononuclear cell (MNC) and CD34-enriched cell cultures. Growth and differentiation was assessed by total, progenitor (CFU-GM), stromal (CFU-F), and primitive (LTC-IC) cell output. Tissue culture treated (TCT) plastic significantly increased MNC culture output as compared with non-TCT plastic, whereas CD34-enriched cell cultures gave lower output (than MNC cultures) that was unaffected by TCT plastic. Interestingly, the level of MNC culture output was significantly different on four commercial TCT surfaces, with the best performing surface giving output that was 1.6- to 2.8-fold greater than the worst one. The surface giving the highest output was the best at supporting development of a distinct morphological feature in the adherent layer (i.e. cobblestone area) indicative of primitive cells, and X-ray photoelectron spectroscopy (XPS) was used to characterize this surface. For custom injection molding of culture devices, the use of three different resins resulted in MNC culture output that was equivalent to commercial cultureware controls, whereas CD34-enriched cell cultures were highly sensitive to resins containing additives. When the texture of molded parts was roughened by sandblasting of the tool, MNC culture output was significantly reduced and higher spikes of IL-6 and G-CSF production were observed, presumably due to macrophage activation. In conclusion, the manufacture of BM MNC culture devices for clinical applications was optimized by consideration of plastic resin, surface treatment, and texture of the culture substratum. Although CD34-enriched cells were insensitive to surface treatment, they were considerably more sensitive to biocompatibility issues related to resin selection. The development of robust systems for BM MNC expansion will enable clinical trials designed to test the safety and efficacy of cells produced in this novel tissue engineering application.     

Effects of age, breast density, ethnicity, and estrogen replacement therapy on screening mammographic sensitivity and cancer stage at diagnosis: review of 183,134 screening mammograms in Albuquerque, New Mexico

PURPOSE: To examine how common patient factors affect screening mammographic sensitivity and cancer stage at diagnosis. MATERIALS AND METHODS: The authors used a population-based database of 183,134 screening mammograms and a statewide tumor registry to identify 807 breast cancers detected at screening mammography. RESULTS: Sensitivity varied significantly with ethnicity, use of estrogen replacement therapy, mammographic breast density, and age. Sensitivity was 54% (13 of 24) in women younger than 40 years, 77% (121 of 157) in women aged 40-49 years, 78% (224 of 286) in women aged 50-64 years, and 81% (277 of 340) in women older than 64 years. Sensitivity was 68% (162 of 237) for dense breasts and 85% (302 of 356) for nondense breasts and 74% (180 of 244) in estrogen replacement therapy users and 81% (417 of 513) in nonusers. Sensitivity was most markedly reduced with the combination of dense breasts and estrogen replacement therapy use; there was little difference when only one factor was present. Median cancer size and the percentage of early cancers showed little change with any factors. CONCLUSION: Age is a minor determinant of mammographic sensitivity in women aged 40 years or older. Sensitivity is substantially decreased with the combination of higher breast density and estrogen replacement therapy use. There was not a notable shift in cancer outcomes in the groups with lower mammographic sensitivity. These data do not support different screening recommendations in women aged 40-49 years or in estrogen replacement therapy users.     

Proliferating cell nuclear antigen (PCNA) immunostaining--a prognostic factor in ovarian cancer?

The measurement of tumour cell proliferation is becoming increasingly recognised in defining prognostic groups. Proliferating cell nuclear antigen (PCNA) immunolocalisation can be used as an index of cell proliferation and may define the extent of departure from normal growth control. The monoclonal antibody PC10 stains PCNA in archival paraffin-embedded tissue. This study investigates its potential as a prognostic marker in early and advanced ovarian cancer. A three-stage immunoperoxidase technique was developed to detect the monoclonal antibody PC10. Archival paraffin-embedded tissue from 19 stage I ovarian tumours (13 malignant and six borderline) and 79 advanced (stage IIb-IV) ovarian tumours (patients entered into the Third North-West Thames Ovarian Cancer Trial) was immunostained with PC10. PC10 immunostaining was performed successfully in 91.8% of cases. The PC10 labelling index (PC10 LI) ranged from 1.5% to 88% with a mean value of 47.4%. Stage I borderline tumours had significantly lower PCNA labelling indexes than stage I malignant tumours (P < 0.048). In advanced disease there was an inverse correlation between PC10 and overall survival, and in those patients who underwent good debulking surgery (37 patients with disease < 2 cm diameter) a low PC10 value (< 36.5%) correlated with improved survival (log-rank trend test for survival, chi 2 = 5.75, P = 0.017). PCNA immunostaining defines a good prognostic subgroup in adequately debulked patients with ovarian cancer.     

Metaheuristics for the waste collection vehicle routing problem with time windows,driver rest period and multiple disposal facilities

In this problem there is a set of waste disposal facilities, a set of customers at which waste is collected and an unlimited number of homogeneous vehicles based at a single depot. Empty vehicles leave the depot and collect waste from customers, emptying themselves at the waste disposal facilities as and when necessary. Vehicles return to the depot empty. We take into consideration time windows associated with customers, disposal facilities and the depot. We also have a driver rest period. The problem is solved heuristically. A neighbour set is defined for each customer as the set of customers that are close, but with compatible time windows. A procedure that attempts to fully utilise a vehicle is used to obtain an initial solution, with this initial solution being improved using an interchange procedure. We present two metaheuristic algorithms using tabu search and variable neighbourhood search that are based around the neighbour sets. We also present a metaheuristic based on variable neighbourhood tabu search, where the variable neighbourhood is searched via tabu search. Computational results are presented for publicly available waste collection problems involving up to 2092 customers and 19 waste disposal facilities, which indicate that our algorithms produce better quality solutions than previous work presented in the literature.     

Toward a theoretical approach to medical error reporting system research and design

The release of the Institute of Medicine (Kohn et al., 2000) report "To Err is Human", brought attention to the problem of medical errors, which led to a concerted effort to study and design medical error reporting systems for the purpose of capturing and analyzing error data so that safety interventions could be designed. However, to make real gains in the efficacy of medical error or event reporting systems, it is necessary to begin developing a theory of reporting systems adoption and use and to understand how existing theories may play a role in explaining adoption and use. This paper presents the results of a 9-month study exploring the barriers and facilitators for the design of a statewide medical error reporting system and discusses how several existing theories of technology acceptance, adoption and implementation fit with many of the results. In addition we present an integrated theoretical model of medical error reporting system design and implementation.     

Xenogeneic spermatogenesis following transplantation of hamster germ cells to mouse testes

It was recently demonstrated that rat spermatogenesis can occur in the seminiferous tubules of an immunodeficient recipient mouse after transplantation of testis cells from a donor rat. In the present study, hamster donor testis cells were transplanted to mice to determine whether xenogeneic spermatogenesis would result. The hamster diverged at least 16 million years ago from the mouse and produces spermatozoa that are larger than, and have a shape distinctly different from, those of the mouse. In four separate experiments with a total of 13 recipient mice, hamster spermatogenesis was identified in the testes of each mouse. Approximately 6% of the tubules examined demonstrated xenogeneic spermatogenesis. In addition, cryopreserved hamster testis cells generated spermatogenesis in recipients. However, abnormalities were noted in hamster spermatids and acrosomes in seminiferous tubules of recipient mice. Hamster spermatozoa were also found in the epididymis of recipient animals, but these spermatozoa generally lacked acrosomes, and heads and tails were separated. Thus, defects in spermiogenesis occur in hamster spermatogenesis in the mouse, which may reflect a limited ability of endogenous mouse Sertoli cells to support fully the larger and evolutionarily distant hamster germ cell. The generation of spermatogenesis from frozen hamster cells now adds this species to the mouse and rat, in which spermatogonial stem cells also can be cryopreserved. This finding has immediate application to valuable animals of many species, because the cells could be stored until suitable recipients are identified or culture techniques devised to expand the stem cell population.