Biomedical subjects
Publications and source records attributed to R Smith.
Landomycin A was found to inhibit the uptake of [3H]thymidine into DNA in murine smooth muscle cells indicating decreased DNA synthesis. Subsequent studies showed that landomycin A inhibits cell cycle progression.
Explore the source record for details and available documents.
BACKGROUND: We have shown previously that lumpectomy with radiation therapy was more effective than lumpectomy alone for the treatment of ductal carcinoma in situ (DCIS). We did a double-blind randomised controlled trial to find out whether lumpectomy, radiation therapy, and tamoxifen was of more benefit than lumpectomy and radiation therapy alone for DCIS. METHODS: 1804 women with DCIS, including those whose resected sample margins were involved with tumour, were randomly assigned lumpectomy, radiation therapy (50 Gy), and placebo (n=902), or lumpectomy, radiation therapy, and tamoxifen (20 mg daily for 5 years, n=902). Median follow-up was 74 months (range 57-93). We compared annual event rates and cumulative probability of invasive or non-invasive ipsilateral and contralateral tumours over 5 years. FINDINGS: Women in the tamoxifen group had fewer breast-cancer events at 5 years than did those on placebo (8.2 vs 13.4%, p=0.0009). The cumulative incidence of all invasive breast-cancer events in the tamoxifen group was 4.1% at 5 years: 2.1% in the ipsilateral breast, 1.8% in the contralateral breast, and 0.2% at regional or distant sites. The risk of ipsilateral-breast cancer was lower in the tamoxifen group even when sample margins contained tumour and when DCIS was associated with comedonecrosis. INTERPRETATION: The combination of lumpectomy, radiation therapy, and tamoxifen was effective in the prevention of invasive cancer.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A parenterally administered rotavirus vaccine composed of virus-like particles (VLPs) is being evaluated for human use. VLPs composed of bovine VP6 and simian VP7 (SA11, G3) proteins (6/7-VLPs) or of bovine VP2, bovine VP6, and simian VP7 (SA11, G3) proteins (2/6/7-VLPs) were synthesized and purified from Sf9 insect cells co-infected with recombinant baculoviruses. 6/7- and 2/6/7-VLP administered parenterally (i.m.) in mice had comparable immunogenicity, but the 2/6/7-VLPs were more homogeneous and stable. The inclusion of the VP2 capsid contributed to particle formation and stability. The adjuvant QS-21 significantly enhanced the immunogenicity of 2/6/7-VLPs over A10H or saline alone. Equivalent serum neutralizing antibody responses were induced over the range of 1-15 microg/dose of 2/6/7-VLPs administered with the range of 5-20 microg/dose of QS-21. The immunogenicity of 2/6/7-VLPs and inactivated SA11 virus were comparable. 2/6/7-VLPs are a promising candidate for a parenterally delivered rotavirus subunit vaccine.
Explore the source record for details and available documents.
Mutations in Jagged1 cause Alagille syndrome (AGS), a pleiotropic disorder with involvement of the liver, heart, skeleton, eyes, and facial structures. Cardiac defects are seen in more than 95% of AGS patients. Most commonly these are right-sided defects ranging from mild peripheral pulmonic stenosis to severe forms of tetralogy of Fallot. AGS demonstrates highly variable expressivity with respect to all of the involved systems. This leads us to hypothesize that defects in Jagged1 can be found in patients with presumably isolated heart defects, such as tetralogy of Fallot or pulmonic stenosis. Two patients with heart defects of the type seen in AGS and their relatives were investigated for alterations in the Jagged1 gene. Jagged1 was screened by a combination of cytogenetic and molecular techniques. Patient 1 was studied because of a four-generation history of pulmonic stenosis. Molecular analysis showed a point mutation in Jagged1 in the patient and her mother. Patient 2 was investigated owing to the finding of tetralogy of Fallot and a "butterfly" vertebra on chest radiograph first noted at age 5 years. She was found to have a deletion of chromosome region 20p12 that encompassed the entire Jagged1 gene. The identification of these two patients suggests that other patients with right-sided heart defects may have subtle findings of AGS and Jagged1 mutations.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Health care delivery in many countries has expanded over the past 150 years from a largely social service delivered by individual practitioners to an intricate network of services provided by teams of professionals. The problems of increasing resource consumption, financial constraints, complexity, and poor system design that have emerged as consequences of these changes have exacerbated many of the ethical tensions inherent in health care and have created new ones. Many groups of professionals that give and affect health care have established separate codes of ethics for their own disciplines, but no shared code exists that might bring all stakeholders in health care into a more consistent moral framework. A multidisciplinary group therefore recently met at Tavistock Square in London in an effort to prepare such a shared code. The result was not a code but a more basic and generic statement of ethical principles. The intent and hope is that it will offer clear guidance for tough calls in real world settings. It is presented here not as a finished work, but as a draft to elicit comment, critique, suggestions for revision, and, especially, ideas for implementation.