GB virus C/hepatitis G virus infection among patients with hepatocellular carcinoma in the inshore area of the Yangtze River, China

The latest meeting of the AAMC's Forum on the Future of Academic Medicine, on April 29, 1998, opened with a talk by Francis S. Collins, MD, PhD, director of the National Human Genome Research Institute, who reviewed the significant progress that the Human Genome Project (HGP) has made and speculated on how genetic discoveries and technologies would transform health-related research and ultimately the practice of medicine. The HGP's findings will offer clear improvements in diagnosis and prevention, and eventually in treatments, and the relationship between the academic medical center and the pharmaceutical industry will change--but remain good--as that industry applies the findings of the HGP. He stressed the need for the public and health care providers to develop a greater understanding of genetic issues, and urged changes in medical education to accomplish this. Forum members and Dr. Collins discussed the ethics and economics in patient care resulting from genetic research; forum members also asked whether academic medical centers could profit from genetic research findings. The second speaker was John Eisenberg, MD, administrator of the Agency for Health Care Policy and Research, which fosters health care research and disseminates to clinicians and others the findings of such research. Among other topics, Dr. Eisenberg described the new emphasis on health care outcomes and quality and described how his agency promotes research in these areas. Forum members asked who would pay for the information systems needed to communicate the findings of health services research and also noted that there is an expanding definition of health that places new pressures on already stressed academic medical centers, their missions, and their curricula, which must change. Michael Whitcomb, MD, of the AAMC, noted that the view that medical schools can't change their curricula has been proved wrong, and that 24 medical schools are working with the AAMC's Medical Schools Objectives Project on curricular reform. The forum closed with discussion of a few broader issues affecting academic medical centers.     

Role of glutathione modulation in acrylonitrile-induced gastric DNA damage in rats

Acrylonitrile (VCN) or its reactive metabolites irreversibly interact with gastric DNA in vivo and cause DNA damage. The effect of glutathione (GSH) modulation on VCN-induced genotoxicity and unscheduled DNA repair synthesis (UDRS) in DNA of gastric mucosal tissues was investigated. VCN-induced UDRS was determined: in control rats, rats with depleted gastric GSH contents, and rats treated with sulfhydryl compounds. A single oral dose (23 mg/kg) of VCN induced a time- and dose-dependent increase in gastric UDRS and decrease in GSH levels. While maximal UDRS in gastric mucosa was observed 2 h following oral administration of 23 mg/kg VCN, maximal GSH depletion (50% of control) was detected 4 h following treatment. Increasing the VCN dose to 46 mg/kg caused a further decrease in gastric GSH level (27% of control), while UDRS was elevated. Inhibition of VCN oxidation by treatment of the animals with the cytochrome P450 inhibitor, SKF 525-A, prior to VCN administration caused 65% reduction in VCN-induced UDRS. Treatment of rats with the GSH depletor diethylmaleate (DEM) prior to VCN administration caused 167% increase in UDRS in gastric mucosal tissues. Treatment of the animals with the sulfhydryl compounds, cysteine and penicillamine, prior to VCN administration protected against VCN-induced UDRS. The results demonstrated an inverse and highly significant correlation between gastric GSH levels and VCN-induced UDRS (r = -0.873, P < 0.0001). In conclusion, our study indicates that VCN bioactivation and the homeostasis of gastric GSH may play a major, role in the initial processes underlying VCN-induced gastric carcinogenesis.     

Prospective study of exogenous hormones and risk of pulmonary embolism in women

BACKGROUND: Current use of oral contraceptives (OCs) is a well-recognised risk factor for venous thrombosis and consequent pulmonary embolism (PE). Little is known about residual effects of past OC use. Furthermore, few epidemiological studies have assessed the relation between postmenopausal use of hormones and thrombotic disease. METHODS: In this prospective study information was obtained through questionnaires sent every 2 years (1976-92) to 1125,93 women aged 30-55 in 1976. We excluded women with previously diagnosed cardiovascular disease or cancer in 1976 and at the beginning of each subsequent 2-year follow-up period. FINDINGS: From self-reports and medical records, we documented 123 cases of primary PE (no identified antecedent cancer, trauma, surgery, or immobilisation). Current users of postmenopausal hormones had an increased risk of primary PE (relative risk adjusted for multiple risk factors 2.1 [95% CI 1.2-3.8]). However, past use showed no relation to PE (1.3 [0.7-2.4]). In current users of OCs the risk of primary PE was about twice that in non-users (2.2 [0.8-5.9]), but this finding was based on only five cases who were current OC users. Users of OCs in the past had no increase in risk of PE (0.8 [0.5-1.2]). These relations were consistent irrespective of cigarette-smoking status. INTERPRETATION: Primary PE was uncommon in this cohort. The risk was increased by current though not past use of postmenopausal hormones or OCs.     

Pharmacokinetic parameters of sisomicin

Sisomicin in doses of 1 mg/kg was administered intramuscularly to 10 healthy volunteers, and 1 week later the same volunteers received sisomicin at the same dose intravenously. A peak serum concentration of sisomicin of 3.08 mug/ml was obtained 1 h after intramuscular injection, and a peak serum concentration of 7.12 mug/ml was achieved 30 min after a 30-min intravenous infusion. The sisomicin elimination data were analyzed according to a two-compartment model. Pharmacokinetic parameters derived from the intramuscular and intravenous studies were quite similar.     

Vicryl-mesh wrap for the implantation of hydroxyapatite orbital implants: an animal model

OBJECTIVE: To evaluate host fibrovascularization of hydroxyapatite orbital implants wrapped in sclera or in Vicryl (polyglactin 910) mesh in a rabbit model. NUMBERS: Eight adult New Zealand white rabbits that received hydroxyapatite orbital implants wrapped in homologous donor sclera (four animals) or Vicryl mesh (four animals). INTERVENTIONS: The rabbits had one eye enucleated and then received a 12-mm hydroxyapatite implant wrapped in sclera or Vicryl mesh. Magnetic resonance imaging (MRI) and bone scintigraphy were done to assess host fibrovascularization of the implant 4, 8, 12 and 20 weeks after implantation. Two animals (one in each group) were killed at each of these times, and the implant was removed for histopathological examination. MAIN OUTCOME MEASURES: Enhancement on MRI, uptake on bone scintigraphy, fibrovascularization seen on histopathological examination. RESULTS: The degree of fibrovascularization was substantial in all the specimens but appeared greater in the Vicryl-mesh-wrapped implants in the first 12 weeks after implantation on both histopathological and MRI studies. At 20 weeks these findings were similar in the two groups. A granulomatous foreign-body giant-cell reaction to both the Vicryl mesh and the implant itself was present up to 8 weeks after implantation. Bone scans showed only grade 1+ activity in all the implants. CONCLUSIONS: Host fibrovascularization in the rabbit appears to occur to a greater degree in Vicryl-mesh-wrapped hydroxyapatite implants than in those wrapped in donor sclera during the first 12 weeks after implantation. Vicryl mesh appears to be an acceptable alternative wrap for the hydroxyapatite implant, eliminating the need for donor sclera and its potential risks of transmissible diseases.