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Biomedical subjects

L Benton

Publications and source records attributed to L Benton.

12 recordsLinked to original sources

Early pregnancy termination with mifepristone and misoprostol in the United States.

BACKGROUND: Mifepristone and a prostaglandin have been used successfully to terminate pregnancy in Europe and China. We report the results of a large U.S. study of mifepristone and misoprostol in women with pregnancies of up to nine weeks' duration. METHODS: We administered 600 mg of mifepristone and then 400 microg of misoprostol two days later to 2121 women seeking termination of their pregnancies at 17 centers. The women were observed for four hours after the administration of misoprostol and returned on day 15 for final assessment. RESULTS: Two thousand fifteen women completed the final assessment. Among them, pregnancy was terminated in 762 of the 827 women pregnant for < or =49 days (92 percent), 563 of the 678 women pregnant for 50 to 56 days (83 percent), and 395 of the 510 women pregnant for 57 to 63 days (77 percent) (P<0.001). Termination occurred within 4 hours after the administration of misoprostol in 49 percent of the women and within 24 hours in 75 percent. Failures, defined as cases requiring surgical intervention for medical reasons or because the patient requested it, the abortion was incomplete, or the pregnancy was ongoing, increased with increasing duration of pregnancy. The largest increase was in failures representing ongoing pregnancy, which increased from 1 percent in the < or =49-days group to 9 percent in the 57-to-63-days group (P<0.001). Abdominal pain, nausea, vomiting, diarrhea, and vaginal bleeding also increased with advancing gestational age. Two percent of the women in the < or =49-days group, as compared with 4 percent in each of the other two groups, were hospitalized, underwent surgical interventions, and received intravenous fluids (P=0.008). CONCLUSIONS: This mifepristone-misoprostol regimen is effective in terminating pregnancies, especially in women with pregnancies of 49 days' duration or less.

Abortifacient Agents, Nonsteroidal↗

Operative outcomes of minimally invasive saphenous vein harvest.

BACKGROUND: The longest incision used in surgery is the standard incision for harvesting the greater saphenous vein for arterial grafting. This long incision is associated with significant pain and morbidity. We present a comparative study between two relatively less invasive techniques: the standard bridge technique (BT) and the endoscopic saphenous vein harvest (ESVH). PATIENTS AND METHODS: This is a prospective, nonrandomized, case-matched study of contemporaneous minimally invasive saphenous vein harvest in patients undergoing multiple vessel coronary artery bypass grafting (CABG). Data points include operative time, total wound length, length of vein harvested, intraoperative complications, conversions to open, injury to the graft, postoperative complications and hospital length of stay. Follow-up continued for 8 weeks postdischarge. RESULTS: Within a 10-month period (July 1996 to May 1997), 60 saphenous vein harvests were performed, with 29 by BT and 31 by ESVH. Patient demographics were well matched, except for a larger number of patients with peripheral vascular disease in the ESVH group. ESVH only required 2.3 incisions versus 5 for the BT (P = 0.000001), whereas ESVH produced on average longer veins of 53.9 cm versus 47.7 cm for BT (P = 0.05). Harvest times were comparable in the two groups. However, mean vein preparation times, incision closure times, and total vein operative times for the BT were, respectively, 18.5 minutes, 35.1 minutes, and 94 minutes versus significantly less times of 11.3 minutes (P = 0.009), 10.6 minutes (P = 0.000001), and 73 minutes (P = 0.0001), respectively, for ESVH. The early, minor wound complication rate was 32% for the ESVH group versus 3% for the BT group (P = 0.0048). However, excluding small wound hematomas, the wound complication rate in the ESVH group fell to 13%. Graft quality was acceptable in both groups. CONCLUSIONS: ESVH was demonstrated to be a useful procedure to harvest saphenous veins for CABG surgery. The ESVH technique allowed the harvesting of a longer vein, via shorter and fewer incisions and in less time. However, for maximum operating room efficiency with the new technology, staff education is essential. There was a greater incidence of minor wound complications in the ESVH group; however, the majority of these ESVH complications were small wound hematomas, which did not occur as surgeon experience with the technique increased.

Aged↗

Impact of the introduction of new medical methods on therapeutic abortions at the Royal Infirmary of Edinburgh.

OBJECTIVE: To assess the impact of the introduction of new medical methods on the provision of therapeutic abortions at the Royal Infirmary Edinburgh. DESIGN: A review of the total number of abortions performed by medical and surgical means between 1989 and 1995 (inclusive); a prospective survey of the terminations of pregnancy (< or = 9 weeks of gestation) performed over the six-month period of January to June 1994; and a questionnaire of the reasons why women chosen a particular method. SETTING: Large teaching hospital in Scotland. SUBJECTS: One thousand and seven women seeking early pregnancy termination between January and June 1994. MAIN OUTCOME MEASURES: Proportion of pregnancies terminated by medical means; comparison of complete abortion rate, incidence of complications and morbidity following both medical and surgical methods (< or = 9 weeks of gestation); reasons for preference of the method of abortion. RESULTS: Since 1991 there has been a progressive increase in the number of medical abortions performed at the Royal Infirmary of Edinburgh, and by 1994 the majority of women (57%) seeking abortion at < or = 9 weeks chose a medical method. Women who chose medical abortion had more years at full-time education and were less likely to smoke (P < 0.04). Both medical and surgical methods were highly effective (> 96% complete abortion) with a low incidence of complications and morbidity. However, women who had chosen the medical method were less likely to receive antibiotics for suspected endometritis than their surgical counterparts (chi 2, P = 0.0001). CONCLUSIONS: If this trend towards medical methods in Edinburgh is repeated elsewhere, it will inevitably have an impact on gynaecological services by releasing staff and operating time for other purposes.

Abortifacient Agents, Steroidal↗

Differentiation of adult Leydig cells.

Adult Leydig cells originate within the testis postnatally. Their formation is a continuous process involving gradual transformation of progenitors into the mature cell type. Despite the gradual nature of these changes, studies of proliferation, differentiation and steroidogenic function in the rat Leydig cell led to the recognition of three distinct developmental stages in the adult Leydig cell lineage: Leydig cell progenitors, immature Leydig cells and adult Leydig cells. In the first stage, Leydig cell progenitors arise from active proliferation of mesenchymal-like stem cells in the testicular interstitium during the third week of postnatal life and are recognizable by the presence of Leydig cell markers such as histochemical staining for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and the present of luteinizing hormone (LH) receptors. They proliferate actively and by day 28 postpartum differentiate into immature Leydig cells. In the second stage, immature Leydig cells are morphologically recognizable as Leydig cells. They have an abundant smooth endoplasmic reticulum and are steroidogenically active, but primarily produce 5 alpha-reduced androgens rather than testosterone. Immature Leydig cells divide only once, giving rise to the total adult Leydig cell population. In the third and final stage, adult Leydig cells are fully differentiated, primarily produce testosterone and rarely divide. LH and androgen act together to stimulate differentiation of Leydig cell progenitors into immature Leydig cells. Preliminary data indicate that insulin like growth factor-1 (IGF-1) acts subsequently in the transformation of immature Leydig cells into adult Leydig cells.

Androgens↗

Endothelial cells adherent to expanded polytetrafluoroethylene express the intercellular adhesion molecule-1.

BACKGROUND: The foreign body reaction caused by implanted biomaterials is not fully characterized. To evaluate the effect of an expanded polytetrafluoroethylene (ePTFE) surface on the binding of monoclonal antibodies against the intercellular adhesion molecule (ICAM-1) by adherent endothelial cells, an in vitro bioassay was developed. STUDY DESIGN: Human saphenous vein endothelial cells (HSVEC) and human umbilical vein endothelial cells (HUVEC) were grown to confluency on fibronectin-pretreated ePTFE and on fibronectin-pretreated polystyrene culture flasks used as controls. Cells were assayed for size, density, viability, and binding of anti-ICAM-1 antibodies. Human peripheral blood leukocytes (PBLs) were then cocultured with HUVEC adherent to ePTFE and control polystyrene and HUVEC were assayed for the binding of anti-ICAM-1 antibodies. RESULTS: The adherence of HSVEC and HUVEC to ePTFE resulted in a twofold increase in the binding of monoclonal antibodies against ICAM-1 compared with controls at 48 hours (p < 0.005). The addition of PBLs to the adherent HUVEC resulted in a four- to eightfold increase in anti-ICAM-1 antibody binding on ePTFE and polystyrene, respectively, at 24 hours. CONCLUSIONS: Adherence of endothelial cells to ePTFE results in an increase in the binding of anti-ICAM-1 antibodies. Coculture of adherent HUVEC and PBLs results in a marked increase in the number of cells binding ICAM-1 antibodies. These data support the conclusion that ePTFE is associated with the activation of adherent cells, which is one aspect of a multicellular inflammatory response.

Adult↗

Role of adhesion molecules in leukocyte binding to endothelial cells adherent to vascular grafts.

BACKGROUND: The localization of leukocytes to vascular grafts is an essential part of healing and infection resistance. The mechanisms involved in this process are only partly understood. STUDY DESIGN: Human saphenous vein endothelial cells (HSVEC) were grown on control polystyrene culture ware and expanded polytetrafluoroethylene (ePTFE). The binding of monoclonal antibodies against the intercellular adhesion molecule (ICAM-1) and the E-selectin by adherent HSVEC was determined by flow cytometry. Peripheral blood leukocytes (PBL) were cocultured with HSVEC adherent to ePTFE and leukocyte binding was determined with and without the addition of a protein kinase C inhibitor. RESULTS: HSVEC adherent to ePTFE constitutively bound anti-ICAM-1 antibodies, which were attenuated by the protein kinase C inhibitor, H-7. HSVEC adherent to ePTFE bound significantly greater numbers of leukocytes than those on control (58 versus 41 percent, p < 0.05). Incubation with H-7 decreased leukocyte binding to HSVEC significantly (p < 0.005). Coculture of PBL with HSVEC adherent to ePTFE caused a tenfold increase in binding of anti-E-selectin antibodies (p < 0.0005). CONCLUSIONS: These data indicate that PBL binding to HSVEC adherent to ePTFE is, at least in part, ICAM-1 to HSVEC adherent to ePTFE is, at least in part, ICAM-1 and E-selection dependent.

Blood Vessel Prosthesis↗

Treatment of primary Sjögren's syndrome with hydroxychloroquine.

Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of the salivary/lacrimal glands, autoantibody production, and polyclonal hyperglobulinemia. In view of the efficacy and relative safety of hydroxychloroquine in other autoimmune disorders, the potential benefit of hydroxychloroquine (200 mg per day for 12 months) in 10 patients with Sjögren's syndrome was evaluated. Changes in levels of total immunoglobulin, antibody against Sjögren's syndrome-associated antigen B, rheumatoid factor, and in vitro production of immunoglobulin in the serum were evaluated. For comparison, 10 patients matched according to age and sex, who did not receive hydroxychloroquine were studied. In the hydroxychloroquine-treated group, the following observations were made: (1) significantly decreased total immunoglobulin G (IgG) and IgA levels with little change in IgM levels; (2) significant decrease in IgA-rheumatoid factor with a smaller decrease in IgM-rheumatoid factor; (3) decreased IgG anti-Sjögren's syndrome-associated antigen B autoantibody; and (4) decreased erythrocyte sedimentation rate and increased hemoglobin level. Further, a specific idiotype present on their rheumatoid factor (defined by monoclonal antibody 17-109) was significantly decreased, with disappearance of detectable circulating paraprotein in two hydroxychloroquine-treated patients. Finally, rheumatoid factor production in vitro by lymphocytes from hydroxychloroquine-treated patients using a T cell-dependent mitogen was significantly decreased. These results suggest that hydroxychloroquine modulates lymphoproliferation in patients with Sjögren's syndrome and may prevent progression to extraglandular sites of neoplastic transformation.

Autoantibodies↗

Potential role of Epstein-Barr virus in Sjögren's syndrome.

Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration and destruction of salivary and lacrimal glands. This condition may occur as a primary condition or may be associated with other autoimmune disorders such as rheumatoid arthritis or systemic lupus. Because the environmental factors that initiate SS are unknown, we have investigated the potential role of EBV, CMV, and other viruses. We observed that epithelial cells in salivary gland biopsies of patients with SS contained antigens reactive with monoclonal antibodies against EBV-associated antigens. These antigens were not found in other tissues of patients with SS and were not detectable in salivary gland biopsies from normal persons and patients with other autoimmune diseases lacking SS. The molecular weight of the antigens present in the SS salivary gland extracts was similar to that expressed in cells containing reactivated EBV. Also, the content of EBV DNA in the saliva of patients with SS was significantly greater than in age-, sex-matched controls or persons with other autoimmune disorders. These studies provide one of the first examples where a specific viral agent may be implicated in perpetuating a chronic autoimmune disease. These results also may provide insight into other autoimmune diseases where the target organ is less accessible to biopsy.

Antigens, Viral↗

Dynamic assessment of cognitive and cardiovascular performance in the elderly.

Dynamic measures of cardiovascular and cognitive performance have been used as a preliminary step toward developing predictors of decline in functional performance in older persons. Both batteries use multiple measures to examine the cooperativity of various aspects of performance, and both examine the subject's response to naturally occurring stresses. In these two senses, the measures are dynamic. For the cardiovascular measure we conducted ambulatory monitoring of blood pressure and pulse at 7.5-min intervals over a 24-h period. These parameters were analyzed simultaneously to examine changes in one relative to the others, using spectroscopy. After appropriate filtering, several dominant ultradian rhythms were noted, with periods of 47 min, 180 min and 6 to 8 h, the latter rhythm being present only in subjects aged greater than or equal to 60. A battery of computer-administered cognitive tests was developed to assess reaction time, visual recognition memory and word recognition memory. This testing allows for both a time and performance level grading. The results of the computer battery correspond well with those for standard neuropsychological tests. In general, performance declined with age, and reaction time increased. The computerized tests are faster, more consistently administered, and do not rely on a skilled professional for administration or analysis. They also provide a wide variety of measures that can be used in isolating components of performance. Once the acceptability and tolerance of older subjects toward such testing was established, attention shifted to questions of measurement stability and discriminant validity. Since the project's primary purpose is to predict subtle measures of decline in function, the battery's ultimate test is in its ability to correctly identify those about to change functional status. However, many different measures of status change are possible, and the predictive accuracy will depend on the outcome chosen. Subsequent work will focus on the predictors to refine measures and compare data collected at one point in time with the predictive power of change scores that reflect the individual subject's "signature." By-products of this work include a wealth of longitudinal physiologic and neuropsychologic data on older persons and tools that may be useful to the practicing physician.

Aged↗