Biomedical subjects
B Williams
Publications and source records attributed to B Williams.
The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial.
Second primary tumors (SPTs) develop at an annual rate of 3-7% in patients with head and neck squamous cell cancer (HNSCC). In a previous Phase III study, we observed that high doses of 13-cis-retinoic acid reduced the SPT rate in this disease. In 1991, we launched an intergroup, placebo-controlled, double-blind study to evaluate the efficacy of low-dose 13-cis-retinoic acid in the prevention of SPTs in patients with stage I or II squamous cell carcinoma of the larynx, oral cavity, or pharynx who had been previously successfully treated with surgery, radiotherapy, or both, and whose diagnoses had been established within 36 months of study entry. As of September 16, 1999, the Retinoid Head and Neck Second Primary (HNSP) Trial had completed accrual with 1384 registered patients and 1191 patients randomized and eligible. All of the patients were followed for survival, SPT development, and index cancer recurrence. Smoking status was assessed at study entry and during study. Smoking cessation was confirmed biochemically by measurement of serum cotinine levels. The annual rate of SPT development was analyzed in terms of smoking status and tumor stage. As of May 1, 2000, SPTs have developed in 172 patients. Of these, 121 (70.3%) were tobacco-related SPTs, including 113 in the aerodigestive tract (57 lung SPTs, 50 HNSCC SPTs, and 6 esophageal SPTs) and 8 bladder SPTs. The remaining 51 cases included 23 prostate adenocarcinomas, 8 gastrointestinal malignancies, 6 breast cancers, 3 melanomas, and 11 other cancers. The annual rate of SPT development observed in our study has been 5.1%. SPT development related to smoking status was marginally significant (active versus never, 5.7% versus 3.5%; P = 0.053). Significantly different smoking-related SPT development rates were observed in current, former, and never smokers (annual rate = 4.2%, 3.2%, and 1.9%, respectively, overall P = 0.034; current versus never smokers, P = 0.018). Stage II HNSCC had a higher overall annual rate of SPT development (6.4%) than did stage I disease (4.3%; P = 0.004). When evaluating the development of smoking-related SPTs, stage was also highly significant (4.8% for stage II versus 2.7% for stage I; P = 0.001). Smoking-related SPT incidence was significant for site as well (larynx versus oral cavity, P = 0.015; larynx versus pharynx, P = 0.011). Primary tumors recurred at an annual rate of 2.8% in a total of 97 patients. The rate of recurrence was higher in patients with stage II disease (4.1% versus 2.2%, P = 0.004) as well as oral cavity site when compared with larynx (P = 0.002). This is the first large-scale prospective chemoprevention study evaluating smoking status and its impact on SPT development and recurrence rate in HNSCC. The results indicate significantly higher SPT rates in active smokers versus never smokers and significantly higher smoking-related SPT rates in active smokers versus never smokers, with intermediate rates for former smokers.
Tennessee medical schools: are we educating today's medical students for tomorrow's practices?
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Laughter as medicine: Tennessee doctors explore the humor-health connection.
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Improving data collection in four easy steps.
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The Conduit Artery Functional Endpoint (CAFE) study in ASCOT.
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TennCare 2002. Where do we go from here?
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Bioterrorism: are we prepared?
Since the horrific events of September 11, and subsequent retaliations by the United States, Americans have struggled with the impact of terrorism and worried about where, when, and how the next strike would come. Tennessee's medical community has raised its expectation and readiness for the worst-case scenario, including the use of biological agents as weapons.
How much information can physicians actually assimilate?
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December depression: holidays blues may be intensified by terrorist fears.
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Orthodontic treatment standards in a public group practice in Sweden.
The aim was to assess the orthodontic treatment service provided by 6 orthodontists in a group practice in Malmö. One hundred cases were randomly selected from the model store. The Index of Complexity, Outcome and Need (ICON) was used to assess the need, complexity of the problem, outcome, the degree of improvement and whether the completed case was acceptable or not. The reliability of the examiner using the ICON was assessed using Root Mean Square. Logistic regression analysis was employed to explore the variables related to acceptability of the finish and duration of treatment. The younger the patient at the start of treatment the lower initial ICON score, with short treatment duration were associated with an acceptable finish. Three out of 100 cases were deemed as not requiring orthodontic treatment and 36 cases were classified as very difficult to treat. Nevertheless, 71 cases out of the 100 exhibited acceptable finishes with 27 indicating substantial or great improvement. 6 cases finished treatment with ICON scores greater than 43 indicating need for orthodontic treatment. The treatment on average took 22 months. An objective appraisal of the quality of orthodontic care in a group practice in Malmö has been undertaken. Seventy-one cases were completed with acceptable occlusions. The Index of Complexity, Outcome and Need appears to be a valuable tool to assess the multiple facets of orthodontic provision.
Targeted disruption of the three Rb-related genes leads to loss of G(1) control and immortalization.
The retinoblastoma protein, pRB, and the closely related proteins p107 and p130 are important regulators of the mammalian cell cycle. Biochemical and genetic studies have demonstrated overlapping as well as distinct functions for the three proteins in cell cycle control and mouse development. However, the role of the pRB family as a whole in the regulation of cell proliferation, cell death, or cell differentiation is not known. We generated embryonic stem (ES) cells and other cell types mutant for all three genes. Triple knock-out mouse embryonic fibroblasts (TKO MEFs) had a shorter cell cycle than wild-type, single, or double knock-out control cells. TKO cells were resistant to G(1) arrest following DNA damage, despite retaining functional p53 activity. They were also insensitive to G(1) arrest signals following contact inhibition or serum starvation. Finally, TKO MEFs did not undergo senescence in culture and do possess some characteristics of transformed cells. Our results confirm the essential role of the Rb family in the control of the G(1)/S transition, place the three Rb family members downstream of multiple cell cycle control pathways, and further the link between loss of cell cycle control and tumorigenesis.
Factors associated with severe manifestations of histoplasmosis in AIDS.
We report factors associated with severe manifestations of histoplasmosis (such as shock, respiratory failure, and death) in patients with AIDS during an outbreak. Severe disease was present in 28 of 155 patients (17.9%). The following factors were associated with severe disease: black race (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.2-6.2); hemoglobin level <9.5 g/dL (OR, 2.7; 95% CI, 1.2-6.4), partial thromboplastin time >45 s (OR, 3.1; 95% CI, 1.1-9.3); alkaline phosphatase level >2.5 times normal (OR, 3.4; 95% CI, 1.3-8.7); aspartate aminotransferase level >2.5 times normal (OR, 4.2; 95% CI, 1.7-10.0); bilirubin level concentration >1.5 mg/dL (OR, 9.2; 95% CI, 2.5-34.3); creatinine concentration >2.1 mg/dL (OR, 8.3; 95% CI, 2.2-31.9); and albumin concentration <3.5 g/dL (OR, 4.6; 95% CI, 1.3-16.4). Zidovudine use was associated with decreased risk of severe disease (OR, 0.3; 95% CI, 0.1-0.7). Multivariate analysis showed that a creatinine value >2.1 mg/dL (OR, 9.5; 95% CI, 1.7-52) and an albumin value <3.5 g/dL (OR, 4.8; 95% CI, 1.0-22) were associated with an increased risk of severe disease, and zidovudine therapy remained associated with a decreased risk (OR, 0.2; 95% CI, 0.1-0.6). Findings associated with severe histoplasmosis should be recognized early and the cases managed aggressively.
High HIV incidence and prevalence among young women in rural South Africa: developing a cohort for intervention trials.
OBJECTIVE: To measure prevalence and model incidence of HIV infection. SETTING: 2013 consecutive pregnant women attending public sector antenatal clinics in 1997 in Hlabisa health district, South Africa. Historical seroprevalence data, 1992-1995. METHODS: Serum remaining from syphilis testing was tested anonymously for antibodies to HIV to determine seroprevalence. Two models, allowing for differential mortality between HIV-positive and HIV-negative people, were used. The first used serial seroprevalence data to estimate trends in annual incidence. The second, a maximum likelihood model, took account of changing force of infection and age-dependent risk of infection, to estimate age-specific HIV incidence in 1997. Multiple logistic regression provided adjusted odds ratios (OR) for risk factors for prevalent HIV infection. RESULTS: Estimated annual HIV incidence increased from 4% in 1992/1993 to 10% in 1996/1997. In 1997, highest age-specific incidence was 16% among women aged between 20 and 24 years. In 1997, overall prevalence was 26% (95% confidence interval [CI], 24%-28%) and at 34% was highest among women aged between 20 and 24 years. Young age (<30 years; odds ratio [OR], 2.1; p = .001), unmarried status (OR 2.2; p = .001) and living in less remote parts of the district (OR 1.5; p = .002) were associated with HIV prevalence in univariate analysis. Associations were less strong in multivariate analysis. Partner's migration status was not associated with HIV infection. Substantial heterogeneity of HIV prevalence by clinic was observed (range 17%-31%; test for trend, p = .001). CONCLUSIONS: This community is experiencing an explosive HIV epidemic. Young, single women in the more developed parts of the district would form an appropriate cohort to test, and benefit from, interventions such as vaginal microbicides and HIV vaccines.
Private funding of elective hospital treatment in England and Wales, 1997-8: national survey.
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Funding of long term care for older people needs to be publicly debated.
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Conflicts regarding decisions to limit treatment: a differential diagnosis.
Conflicts between physicians and families about end-of-life decisions create challenging and emotionally difficult situations. In this article, we propose a "differential diagnosis" of such conflicts, distinguishing and describing the characteristics of families, physicians, and organizations and society that contribute to the "etiology" of the situation, as well as strategies for "diagnosing" the dominant factors. As a medical model, the differential diagnosis can be a useful tool to help physicians understand and manage conflicts about end-of-life care.