[Song to today's and tomorrow's nurse. Interview by Mette-Marie Davidsen].
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Biomedical subjects
Publications and source records attributed to V Henderson.
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When 1-beta-D-arabinofuranosylcytosine (ara-C), 25 mg/m2, is infused over 3 h together with tetrahydrouridine (THU) at 10 to 350 mg/m2 to heavily pretreated patients with solid tumors, Michaelis-Menten type kinetic values are observed with leveling off of delta area under the curve, delta ara-C levels at 3 h, and delta total body clearance after 150 mg/m2 of THU. When the ara-C dose was increased to 50, 75, and 100 mg/m2 coinfusion of 250 or 350 mg/m2 of THU significantly increased plasma ara-C at peak and area under the curve. In contrast, total body clearance and volume of distribution decreased significantly. At 100 mg/m2 of ara-C coinfused with high doses of THU, i.e., at 350 mg/m2, the pharmacokinetics of plasma ara-C was changed from a biphasic decay of plasma ara-C at peaks (control) to a curve similar or identical to a monophasic curve, indicating that THU not only inhibits deamination but also changes the distribution of ara-C. This combination provides plasma ara-C levels (greater than or equal to 10 microM) comparable to high dose ara-C at 1 g/m2. Such plasma ara-C levels are considered to be sufficient for saturation of the kinases catalyzing the production of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate. This reduced ara-C dose necessary to achieve saturation of kinases also reduces plasma 1-beta-D-arabinofuranosyluracil levels substantially. Toxicity of this combination was predominantly confined to bone marrow and gastrointestinal toxicity.
Many occupational epidemiology studies require complete and accurate information on tobacco use to control for confounding by smoking and to assess interactions of smoking with workplace exposures. This paper reviews and evaluates the availability, reliability, validity, and efficiency of the various data sources and techniques for obtaining individual smoking data, including existing records, biological markers, and surveys. Emphasis is placed on the highly problematic issue of obtaining retrospective smoking histories. In general, the survey technique is currently deemed the most feasible approach for obtaining lifetime smoking histories. Both theoretical and practical aspects of smoking surveys are discussed in detail and are illustrated with a review of the recent literature and with data from two recent retrospective cohort studies conducted at the University of Pittsburgh. Several recommendations involving both the use of smoking data and areas for future methodologic research are presented. These include (1) justification for collecting smoking data in occupational studies based primarily on the potential for smoking to act as an effect modifier rather than solely as a confounder, (2) checks for reliability and validity in all studies which involve the collection of smoking data, (3) more methodologic research to better understand the impact that missing, unreliable, and invalid smoking data may have on the ability to detect and quantify important smoking-exposure interactions, and (4) an assessment of the correlation between biological markers and cigarette carcinogen exposure.
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The mortality experience of 1074 white men who retired from a United States asbestos company during the period 1941-67 and who were exposed to asbestos working as production and maintenance employees for the company is reported to the end of 1980 when 88% of this cohort was known to be dead. As noted in earlier reports the mortality for respiratory and gastrointestinal cancer was raised. A more detailed examination of causes of death shows that the excess in gastrointestinal cancer was largely due to a statistically significant excess in stomach cancer. A statistically significant excess was also noted for kidney cancer, cancer of the eye, and non-malignant respiratory disease. Eight deaths from malignant mesothelioma were observed, two of which were peritoneal. Asbestos exposures for these mesothelioma cases were low relative to other members of the cohort. Continuing follow up of this cohort shows a dose response relation for respiratory cancer that has become increasingly linear. Standardised mortality ratios peaked 10 to 15 years after retirement and were relatively constant at around 250 in each five year interval starting in 1950. This excess might have been detected as early as 1960 but certainly by 1965. The mortality experience of this cohort reflects the ultimate effects of asbestos since nearly all of the cohort has now died.
The records of 100 patients who had cataract surgery were reviewed to compare preoperative potential acuity meter (PAM) results with postoperative visual acuity. A PAM acuity was obtainable in 95 patients. In 82 of the 95 patients (86%), the PAM levels were within three lines of the outcome. Potential acuity meter results substantially lower (less than or equal to four Snellen lines) than outcome generally occurred when posterior subcapsular (PSC) or PSC plus diffuse cortical or nuclear changes were present. We believe that the PAM projection can usually go around or through the nuclear sclerosis to give an accurate prediction. However, with PSC or mixed type, one may not always find a window in the cataract. Also, PSC or diffuse cortical cataracts may be particularly disruptive to the paracentral diffracted light that is an important factor in PAM acuity.
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