Anticoagulation: assessment of benefits and risks

Thromboembolism is a frequent complication of atrial fibrillation. As could be demonstrated by several placebo-controlled prospective studies in the recent years the rate of thromboembolism was reduced significantly by anticoagulation of nearly all kinds of atrial fibrillation. These results are challenging to weigh risks and benefits in every patient. The principles which have to consider in this calculation are discussed with regard to the knowledge derived from the controlled studies.     

Lymphoblastoid interferon therapy in chronic hepatitis C: biochemical, virological and histological evaluation of two different doses

Sixty patients of both sexes with biopsy-proven chronic hepatitis C were randomized to receive lymphoblastoid interferon 3 MU or 6 MU three times weekly for 6 months. A follow-up period of 3 months at the end of the therapy was scheduled. Thirty-two patients (53.3%) normalized alanine aminotransferase at the end of the therapy. Of these, 17 received 3 MU (56.7%) and 15 (50%) received 6 MU. Eighteen of the 32 patients (56.2%) relapsed in the follow-up period after treatment. No significant difference in relapse rate was observed between the two groups. The overall percentage of the non-responder patients was 36.6%. The treatment was discontinued because of non-compliance and/or side effects in six patients (10%): three in the 3-MU group and three in the 6-MU group. An improvement in liver histology was observed in about a quarter of chronic active hepatitis patients whose overall diagnosis changed to chronic persistent hepatitis. Knodell's score system showed a significant improvement (p < 0.05) with regard to peripheral necrosis, fibrosis and total score. HCV-RNA was positive at the beginning in all patients and it became undetectable in almost all responder patients. In some cases there was no correlation between viraemia and biochemical signs of liver disease. Our study shows that 6 MU does not increase the response rate compared to 3 MU. Moreover, the lower dose is able to improve the liver histology and to abolish the HCV viraemia in responder patients.     

Cesarean section: medical benefits and costs

Cesarean section rates have risen dramatically in the U.S. over the past 20 years. Although infant mortality has declined during the same period, there is little evidence that more frequent cesarean surgery is the cause. Cesareans save lives or benefit health in certain circumstances, but the incidence of those indications has not increased. Cesarean section also has risks, the most significant for the infant being iatrogenic prematurity or respiratory disease. Maternal mortality is 2-4 times higher and morbidity is 5-10 times higher after a cesarean compared to vaginal birth. The four indications responsible for most of the rise in cesarean rates--previous cesarean, dystocia, breech presentation, and fetal distress--are those conferring the least clear-cut benefit. Demographically, women who are most likely to experience pregnancy complications, low birth weight births, or infant mortality are least likely to have a cesarean. Social, economic, and other factors seem to have a greater influence on the decision to perform a cesarean than does expected medical benefit. The development of neonatal intensive care, expanded access to prenatal care, and greater availability of abortion and family planning have contributed more to falling infant mortality. It has been estimated that approximately half the cesareans currently performed in the U.S. are medically unnecessary, resulting in considerable avoidable maternal mortality and morbidity, and a cost of over $1 billion each year.     

Cost evaluation of therapeutic management of patients with chronic hepatitis C]

The enzymatic activity of many ribonucleases (RNases) depends on two histidines, as in RNase A, or one histidine and/or glutamate, as in microbial RNases belonging to the T1 family. In RNase T1, substitution of either one or both of the two histidines at positions 40 and 92 by a variety of other amino acids reduces the activity more than 100-fold. However, the double variant His40-->Asp/His92-->Asp retains a significant residual enzymatic activity towards RNA and guanylyl-3',5'-cytidine, indicating that a pair of substituted side chains in these positions, both with acid functionality, can confer enzymatic activity. It was shown that the substitution of histidine with glutamate in the variant His40-->Glu yields an enzyme with drastically reduced activity and leads to inactivation in the His92-->Glu, His40-->Glu/His92-->Glu variants. For the variants where histidine is substituted with aspartate we found measurable activity from 1% (His40-->Asp) to 6% (His40-->Glu/His92-->Asp) towards RNA.     

Health services research clinical trials: issues in the evaluation of economic costs and benefits

The endoplasmic reticulum chaperone glucose-regulated protein 78 (GRP78) is essential for the proper glycosylation, folding and assembly of many membrane bound and secreted proteins. GRP78 mRNA is well known to be induced in cultured cells by lowering medium glucose concentrations from 4.5 to 0 mg/ml. Here we report a study designed to determine the effects of intermediate concentrations of glucose on GRP78 mRNA abundance. Progressive reduction in culture medium glucose from 4.5 to 1.0 mg/ml progressively reduced GRP78 mRNA to approximately 30% of the initial level. Induction of GRP78 mRNA by glucose starvation was observed in medium containing less than 1 mg/ml glucose. Determination of the amount of glucose consumed in these cultures showed that reduction of glucose concentrations led first to repression of GRP78 mRNA abundance, followed by induction of the mRNA only when glucose is nearly exhausted. Caloric restriction in mice both reduces fasting and mean 24 h glucose blood concentrations and GRP78 mRNA abundance in the liver. Thus, it is possible that negative regulation of GRP78 mRNA in the liver is due directly to reduced blood glucose concentrations.     

Nanotechnology: Scientific challenges and societal benefits and risks

The field of nanotechnology is developing rapidly, as are its practical application in society. In this article, we give examples that demonstrate the enormous potential that exists for this new class of materials, and for devices with critical dimensions of less than 100 nm. We also identify some of the challenges that need to be faced in order to fully realize the practical benefits of nanotechnology, and discuss possible risks that may come with this new technology. In all cases, the unique advantage of nanotechnology can be traced back to nanoscale physical and chemical properties that are quite different from those encountered in more traditional microscopic (micro) or macroscopic (macro) materials and devices. Unique nanoscale properties and behaviors are already being used to increase energy efficiency, improve healthcare, and strengthen national security. However, while progress is rapid, many challenges remain. These include manufacturing at the nanoscale, integration of nanoscale materials and devices with more conventional technology, and predictive modeling that will allow nanotechnology to be engineered reliably into useful applications and products. Nanotechnology can be expected to have an increasing impact on human lives and society at large. As we strive to use nanotechnology to improve human life through better healthcare, cleaner environment, and improved national security, we must also work to detect and assess the negative impacts that nanotechnology science (or any new technology) might bring. We suggest that the conduct of should be allowed to proceed unimpeded, so that we can fully understand and appreciate the rules of nature at the nanometer scale. That said, scientific pursuits that involve self-replication in synthetic systems, encryption, defense technology, or the enhancement of human intelligence should be reviewed. The development of new technology from fundamental science and the process of deciding what new technology is to be created for what purpose are topics for reasoned debate among the general public as well as in the forums of scientific peer review and political decision making. Dr. Alton D. Romig, Jr., is currently Vice President, Nonproliferation and Assessments, at Sandia National Laboratories (Albuquerque, NM). His responsibilities include the leadership and management of the development and engineering activities that provide systems, science, technology, and expertise in support of national objectives to reduce the threat to the United States from proliferation of and use of weapons of mass destruction. Program areas include remote sensing, proliferation assessment, technology assessment, international security, physical security, and nuclear/chemical/biological nonproliferation and counterintelligence. Dr. Romig is a member of the National Academy of Engineering and is active on a number of National Academy of Engineering/National Research Council Committees and Boards. He is a Fellow of the American Association for the Advancement of Science (AAAS) and member of Science, Engineering and Public Policy Committee and TMS (Fellow Class of 2005) (The Metals, Minerals and Materials Society). Dr. Romig is also Fellow and former President of ASM INTERNATIONAL (formerly American Society for Metals). He also serves on the Boards of Atomic Weapons Establishment Management Limited, a Lockheed Martin joint venture company in the United Kingdom, and Technology Ventures Corporation, a Lockheed Martin subsidiary dedicated to technology commercialization. For his pioneering work in analytical electron microscopy and solidstate diffusion, Dr. Roming has received several awards, including the Burton Medal (1988), awarded by the Electron Microscopy Society of America to an Outstanding Young Scientist; the K.F.J. Heinrich Award (1991), given by the Microbeam Analysis Society to an Outstanding Young Scientist; the ASM Silver Medal for Outstanding Materials Research (1992); and the Acta Metallurgica International Lectureship (1993–1994). Dr Roming has also been named the 2003 ASM-TMS Distinguished Lecturer in Materials and Society. He received his B.S., M.S., and Ph.D. degrees in materials science and engineering from Lehigh University in 1975, 1977, and 1979, respectively. In 1979, he joined Sandia National Laboratories as a member of the technical staff, Physical Metallurgy Division. After a variety of management assignments, he was named Director, Materials and Process Sciences, in 1992. From 1995 to 1999, he was Director of Microsystems Science, Technology, and Components. In 1999, he was named Chief Technology Officer and Vice President for Science, Technology, and Partnerships. In that role, he was Chief Scientific Officer for the Nuclear Weapons program, accountable for Sandia’s interactions with industry and the Laboratories’ Campus Executive program. In addition, he was responsible for the Laboratory Directed Research & Development program. He served in this capacity until attaining his present position in 2003. With Terry A. Michalske and R.J. Floran     

Nanotechnology: Scientific challenges and societal benefits and risks

The field of nanotechnology is developing rapidly, as are its practical application in society. In this article, we give examples that demonstrate the enormous potential that exists for this new class of materials, and for devices with critical dimensions of less than 100 nm. We also identify some of the challenges that need to be faced in order to fully realize the practical benefits of nanotechnology, and discuss possible risks that may come with this new technology. In all cases, the unique advantage of nanotechnology can be traced back to nanoscale physical and chemical properties that are quite different from those encountered in more traditional microscopic (micro) or macroscopic (macro) materials and devices. Unique nanoscale properties and behaviors are already being used to increase energy efficiency, improve healthcare, and strengthen national security. However, while progress is rapid, many challenges remain. These include manufacturing at the nanoscale, integration of nanoscale materials and devices with more conventional technology, and predictive modeling that will allow nanotechnology to be engineered reliably into useful applications and products. Nanotechnology can be expected to have an increasing impact on human lives and society at large. As we strive to use nanotechnology to improve human life through better healthcare, cleaner environment, and improved national security, we must also work to detect and assess the negative impacts that nanotechnology (or any new technology) might bring. We suggest that the conduct of science should be allowed to proceed unimpeded, so that we can fully understand and appreciate the rules of nature at the nanometer scale. That said, scientific pursuits that involve self-replication in synthetic systems, encryption, defense technology, or the enhancement of human intelligence should be reviewed. The development of new technology from fundamental science and the process of deciding what new technology is to be created for what purpose are topics for reasoned debate among the general public as well as in the forums of scientific peer review and political decision making. Dr. Alton D. Romig, Jr., is currently Vice President, Nonproliferation and Assessments, at Sandia National Laboratories (Albuquerque, NM). His responsibilities include the leadership and management of the development and engineering activities that provide systems, science, technology, and expertise in support of national objectives to reduce the threat to the United States from proliferation of and use of weapons of mass destruction. Program areas include remote sensing, proliferation assessment, technology assessment, international security, physical security, and nuclear/chemical/biological nonproliferation and counterintelligence. Dr. Romig is a member of the National Academy of Engineering and is active on a number of National Academy of Engineering/National Research Council Committees and Boards. He is a Fellow of the American Association for the Advancement of Science (AAAS) and member of Science, Engineering and Public Policy Committee and TMS (Fellow Class of 2005) (The Metals, Minerals and Materials Society). Dr. Romig is also Fellow and former President of ASM INTERNATIONAL (formerly American Society for Metals). He also serves on the Boards of Atomic Weapons Establishment Management Limited, a Lockheed Martin joint venture company in the United Kingdom, and Technology Ventures Corporation, a Lockheed Martin subsidiary dedicated to technology commercialization. For his pioneering work in analytical electron microscopy and solid-state diffusion, Dr. Romig has received several awards, including the Burton Medal (1988), awarded by the Electron Microscopy Society of America to an Outstanding Young Scientist; the K.F.J. Heinrich Award (1991), given by the Microbeam Analysis Society to an Outstanding Young Scientist; the ASM Silver Medal for Outstanding Materials Research (1992); and the Acta Metallurgica International Lectureship (1993–1994). Dr. Romig has also been named the 2003 ASM-TMS Distinguished Lecturer in Materials and Society. He received his B.S., M.S., and Ph.D. degrees in materials science and engineering from Lehigh University in 1975, 1977, and 1979, respectively. In 1979, he joined Sandia National Laboratories as a member of the technical staff, Physical Metallurgy Division. After a variety of management assignments, he was named Director, Materials and Process Sciences, in 1992. From 1995 to 1999, he was Director of Microsystems Science, Technology, and Components. In 1999, he was named Chief Technology Officer and Vice President for Science, Technology, and Partnerships. In that role, he was Chief Scientific Officer for the Nuclear Weapons program, accountable for Sandia’s interactions with industry and the Laboratories’ Campus Executive program. In addition, he was responsible for the Laboratory Directed Research & Development program. He served in this capacity until attaining his present position in 2003. With Terry A. Michalske and R.J. Floran     

Snake and spider antivenin: risks and benefits of therapy

A case of hepatic mesenchymal hamartoma, found after sudden onset clinical and biological cholestasis, is reported in a 18-year-old man. Abdominal ultrasound examination and computed tomography showed a intrahepatic cystic tumor. The diagnosis of hepatic mesenchymal hamartoma was made by the pathological examination of the resected specimen. This rare tumor is found in most cases in children less than 2 years old. Thirteen cases in adulthood were already reported, five of them in Japanese patients. Our case is peculiar because no hepatic tumor was shown by ultrasound examination, 2 years before, the large size of cysts and presence of smooth muscle fibers in the wall.     

Hemofiltration and double high flux dialysis: risks and benefits

Patients with systemic lupus erythematosus require adequate information (sun avoidance, fair compliance, smoking discontinuation, adequate contraception and diet, pregnancy planning). Nonsteroidal antiinflammatory drugs and antimalarials are effective in patients presenting with skin and articular involvement. Visceral lesions and hemocytopenias require the use of steroids, alone or in association with immunosuppressive agents. Long-term anticoagulation with an INR of 3-3.5 achieves the prevention of recurrent thrombotic events. Experimental data suggest that more specific treatments and even regimens aimed at eradication of human lupus might soon arise.     

Therapy concepts in chronic hepatitis C

Patients with persistently normal transaminases and without inflammatory changes or fibrosis in liver biopsy have a low risk for progression, respond poorly to antiviral therapy and should thus not be treated for the present. Patients with significant histologic activity or advanced stage of fibrosis are at risk for progression towards cirrhosis. The risk is significantly increased with chronic alcohol consumption even in moderate doses. Treatment with interferon alone results in sustained virological remission in less than 20% of these patients. Treatment success, however, is 2 to 6 times higher under combined treatment with interferon plus ribavirin. The response rate may be further increased with high-dose and daily interferon administration (inductive dosing). The best treatment option for patients with chronic hepatitis C, therefore, is their inclusion in one of the study protocols (examining combinations and induction) currently active in Switzerland.     

Effects of mood states, costs, and benefits on helping.

263 college students participated in a factorial experiment designed to test the hypotheses that mood states interact with costs and with benefits in determining helping. Positive and negative mood states were induced by varying the difficulty of a bogus aptitude test; neutral-mood (control) Ss did not take the test. Benefits for helping were manipulated by asking Ss to collect donations for a worthwhile charity (the American Cancer Society) or to a less worthwhile charity (Little League baseball). In the high-costs-for-helping condition, Ss were asked to collect donations by going door to door, whereas in the low-cost condition, Ss were asked to sit at donations desks. Pretests indicated that the manipulations effectively induced the intended mood states, costs, and benefits. The results generally support the hypotheses. Positive-mood Ss volunteered more than neutral-mood Ss, and whether negative-mood Ss volunteered more or less than neutral-mood Ss depended on the costs and benefits. It is suggested that the seemingly conflicting results of previous investigations of negative mood and helping can be explained by interactions of mood states with costs and with benefits. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prognosis of chronic hepatitis C: results of a large, prospective cohort study

The prognosis of chronic hepatitis C virus (HCV) infection is still ill-defined. The present study prospectively evaluated mortality and complications in a large cohort of patients with chronic hepatitis C. The study included 838 anti-HCV and HCV-RNA-positive patients who were followed for 50.2 +/- 26.9 months (mean +/- SD; range, 6-122 months) in a prospective protocol. During follow-up, 62 patients died (31 from liver disease and 31 from other causes), and 12 patients needed liver transplantation. When compared with a matched general population, hepatitis C increased mortality mainly when cirrhosis was present and in patients who were less than 50 years old at study entry. During follow-up, a further 30 patients developed nonlethal complications of cirrhosis. By multivariate regression, survival was decreased by cirrhosis, long disease duration, history of intravenous drug abuse, and excessive alcohol consumption, whereas interferon therapy improved survival. Alanine transaminase (ALT), bilirubin, sex, and genotype had no effect on survival. The risk of hepatocellular carcinoma (HCC) (n = 17) was increased by cirrhosis and to a lesser degree by long disease duration and high bilirubin, whereas interferon therapy, genotype, and other factors had no effect. Chronic hepatitis C is a disease with considerable mortality and morbidity when cirrhosis is present at diagnosis. Patients who acquire the infection early in life have a markedly increased mortality even when cirrhosis is absent at diagnosis. The age at diagnosis therefore should play a major role in therapeutic considerations. The present data also suggest that interferon therapy has a long-term clinical benefit, although it did not reduce the risk of liver cancer.     

Risks, benefits and costs of hormone replacement therapy in menopause

OBJECTIVE: To gain insight into whether ondansetron treatment induces changes in total cholecystokinin (CCKT) plasma levels before and after administration of the cholecystokinin tetrapeptide (CCK-4) panic challenge procedure in healthy men. METHODS: Thirty-eight volunteers received a 50-microgram bolus of CCK-4 60 minutes after a single oral dose (acute treatment) and multiple oral doses (chronic treatment) of ondansetron or placebo. RESULTS: Results showed no difference in CCKT plasma levels of CCKT elimination rate constant between the ondansetron and the placebo groups after either acute or chronic treatment. CONCLUSION: Results from this study suggest that total CCK plasma levels are not influenced by either acute or chronic treatment with ondansetron. However, the effect of ondansetron on the different CCK component fractions still needs exploration.