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Biomedical subjects

W Stewart

Publications and source records attributed to W Stewart.

At least 73 records · Page 4Linked to original sources

Estimating age incidence from survey data with adjustments for recall errors.

In this paper we propose a method and discuss the type of data required to estimate age incidence rates from population survey data. While surveys are typically designed to estimate the prevalence of a disease or medical condition, they can also be used to estimate incidence rates. A limitation of survey data, however, is that recall is prone to errors. Three types of errors are common: telescopic, false negative, and false positive reports. Telescopic reports are thought to be the most common. We propose a method to adjust for recall errors by modeling the reported age of onset (ONST) and the time interval since the reported first occurrence of the medical condition (LAG). A number of models were examined using migraine headache data from over 10,000 subjects in Washington County, Maryland. Population surveys should be considered as a relatively inexpensive means for estimating the age incidence of medical conditions, especially for symptom based problems like back pain, asthma, mental illness, and serious headache. We recommend that data be collected on variables which can be used as surrogates for the different types of recall errors. Specifically, the age at interview, the date when the condition was cured or in remission, the severity of the condition, and possibly a specific inquiry as to how certain the respondent is in reporting the date of medical events, should be considered for this purpose.

Adolescent↗

Role of oxygen radicals in induction of DNA damage by metabolites of benzene.

Benzene is strongly suspected of being an animal and human carcinogen, but the mechanisms by which benzene induces tumors of lymphoid and hematopoietic organs are unknown. Binding studies in vivo suggest a very low level of covalent binding to the DNA of bone marrow elements. Since several metabolites of benzene have the potential to undergo autooxidation and thereby generate reactive oxygen intermediates, we have tested the hypothesis that benzene metabolites can induce DNA damage through the generation of oxygen radicals. Hydroquinone (HQ), benzoquinone (BQ), catechol, and 1,2,4-benzenetriol (BT) were first tested for their ability to generate O2-. at a physiological pH. BT, and to a lesser extent HQ, were autooxidized and produced significant quantities of O2-.. No detectable O2-. was produced by catechol or BQ. Similarly, BT was very efficient at degrading DNA, and this degradation was inhibited by scavengers of O2-., H2O2 and .OH. HQ did not degrade DNA but did induce single- and double-strand breaks. In contrast to the action of BT, the breakage of DNA by HQ was not inhibited by scavengers of reactive oxygen intermediates. The metabolites which did not produce O2-. (catechol and BQ) did not induce significant breakage of DNA. Taken together, the data support the hypothesis that certain benzene metabolites can induce DNA damage through the production of oxygen radicals; they further suggest that other metabolites may act, via another mechanism, to damage DNA.

Benzene↗

Mortality odds ratio, proportionate mortality ratio, and healthy worker effect.

The standardized proportionate mortality ratio (PMRi) and the mortality odds ratio (MORi) are two statistics used to approximate the cause specific standardized mortality ratio (SMRi) when death data are available but the population at risk is not known. When there is a healthy worker effect, the MORi will always overestimate the SMRi and will always be greater than the PMRi. The PMRi is influenced by the relative frequency of the cause of death. For rare causes, such as brain cancer or leukemia, the PMRi will overestimate the SMRi to essentially the same degree as the MORi. For more common conditions, such as lung cancer, the PMRi will overestimate or underestimate the SMRi depending on the magnitude of the healthy worker effect. When the SMRi = 1 and there is a healthy worker effect, both the PMRi and MORi are in excess of one (1) regardless of the disease rate. As the SMRi increases it is more likely to be bounded by the PMRi (lower) and the MORi (upper). We therefore recommend that each statistic be derived when death certificates are the only source of data used to assess risk due to occupational exposures.

Environmental Exposure↗

Residential mobility during pregnancy: implications for environmental teratogenesis.

Although most teratogens are suspected to act early in the first trimester of pregnancy, birth defects monitoring programs and etiologic studies usually use residence at birth as a proxy measure for residence in the first trimester in searching for environmental teratogens. Because of the high mobility of the U.S. population, residence misclassification can potentially alter inferences concerning environmental teratogens. To evaluate this potential bias, data from the population-based Maryland Birth Defects Reporting and Information System were analyzed. In 1984, the system ascertained 295 infants with one or more of 12 sentinel defects. Of these cases, 59 (20%) mothers reported they have changed address between the time of conception and the time of birth, and 22 have moved to a different county. The residential mobility rate varied by demographic variables and was highest among white women, in the age group 20-24 years. If residence at birth is used as a screening test for residence at conception, it can be shown that in the presence of an environmental teratogenic exposure, misclassification of exposure increases with increasing mobility rate, and population exposure frequency. Such misclassification tends to weaken associations between residence and birth defects and may lead to missing environmental teratogens. This analysis emphasizes the need to use residence information early in pregnancy rather than exclusively at birth.

Abnormalities, Drug-Induced↗

Interferon induction by endotoxin-derived nontoxic polysaccharides.

Polysaccharide-rich preparations from Serratia marcescens-derived endotoxin and components thereof, including Lipid A, were studied in terms of their ability to induce interferon (IFN) activity in murine spleen cell cultures in vitro. Although the polysaccharide-rich derivatives, similar to intact endotoxin, were only weak stimulators for IFN induction, pretreatment of splenocyte cultures with recombinant interleukin-2 (IL-2) significantly increased IFN-inducing activity. Both an endotoxin-derived polysaccharide and a "White type" polysaccharide prepared from intact Serratia had similar ability to induce IFN in vitro, but only when spleen cells were first treated with IL-2. The polysaccharide preparations were nontoxic as compared with the high degree of toxicity of the intact endotoxin, yet induced similar IFN levels as whole endotoxin. Much of the IFN induced by these preparations was of the gamma type, since activity was either not neutralized or only incompletely neutralized by treatment with anti-alpha/beta interferon antibody.

Animals↗

Distinctive immunomodulatory effects of endotoxin and nontoxic lipopolysaccharide derivatives in lymphoid cell cultures.

Endotoxin derived from Serratia marcescens, as well as a hydrolyzed polysaccharide-rich derivative from the bacteria similar to the White-type polysaccharide (WPS), and hydrolyzed split products of endotoxin, including Lipid A and the nontoxic polysaccharide (PS), were studied in terms of their ability to induce mitogenic proliferation of murine spleen cells in vitro and enhancement of antibody formation to sheep erythrocytes. The intact endotoxin and the Lipid A component induced marked proliferative activity of normal lymphoid cells, but the PS components obtained after a 30 min or longer mild hydrolysis of the endotoxin had much less mitogenic activity. The WPS preparation retained mitogenic activity after 30 min but lost it during continued hydrolysis. Nevertheless, all of the components were marked adjuvants for murine spleen cells in vitro in terms of enhancing the antibody response to sheep red cells. Both the intact endotoxin as well as the Lipid A component induced interleukin-1 and interferons, including alpha/beta and gamma, following stimulation of spleen cell cultures for 24 h in vitro. Although only the endotoxin and Lipid A, but not the PS components, were mitogenic for murine splenocytes, all of these preparations had immune adjuvant effects and induced spleen cells to produce or release interferons. However, the PS-rich derivative did not induce tumor necrosis factor. These distinct properties of components of endotoxin indicate that the nontoxic PS-rich derivative, as compared to the toxic endotoxin or Lipid A, has some immunostimulatory activities but lacks others.

Adjuvants, Immunologic↗

Limbus-based versus fornix-based conjunctival flaps in trabeculectomy.

Forty consecutive trabeculectomies were performed by one surgeon, utilizing a limbus-based conjunctival flap in the first 20 eyes and a fornix-based flap in the remaining 20. A success rate of 90% was achieved in both groups, although eyes with limbus-based flaps had slightly better postoperative intraocular pressure control.

Adult↗

The assessment of the beta-blocking activity of urapidil: a new method.

Urapidil is an antihypertensive vasodilator agent whose pharmacological action in man has not yet been fully defined. We have assessed the beta blocking activity of urapidil 15 mg and 30 mg i.v. in a single blind study of 10 healthy male volunteers. Urapidil at plasma concentrations in the same range as those shown to have antihypertensive affect did not significantly attenuate the chronotropic effect of isoproterenol. Propranolol 5 mg iv, the positive control, significantly shifted the isoproterenol dose-response curve to the right. We describe a new method of analyzing incomplete dose response curves whereby a linear terminal segment can be reproducibly defined.

Adrenergic beta-Antagonists↗

Season of birth: schizophrenia and bipolar disorder.

Studies investigating the association between the risk of schizophrenia and season of birth are reviewed and the association clearly established. This association cannot be explained on the basis of age-incidence or age-prevalence artifacts. Other studies suggest there may be an association between bipolar disorder and season of birth. The leading theory in explaining the season of birth phenomenon is that a seasonal factor (such as viral infection, malnutrition, vitamin deficiency, prenatal or obstetrical complications, or ambient temperature) can damage an infant's brain and thereby predispose the child to later development of psychosis. Evidence suggests that the seasonal effect is associated with a subgroup of schizophrenics who have early onset of psychosis, less genetic loading than other schizophrenics, and better prognosis. Case-control studies are needed comparing winterborn to nonwinter-born schizophrenics.

Adolescent↗

Digital subtraction fluoroscopy: a new method of detecting coronary calcifications with improved sensitivity for the prediction of coronary disease.

The association between calcification of the coronary arteries and coronary artery narrowing is well established. However, fluoroscopic visualization of coronary calcifications has been insufficiently sensitive to be useful as a screening test. Since digitization of radiographic images permits the subtraction of noncardiac structures from moving cardiac structures, such subtraction might increase the sensitivity of coronary fluoroscopy. To determine whether coronary calcifications were better visualized with digital subtraction fluoroscopy than with conventional fluoroscopy, we taped diseased human coronary arteries to a pulsating water balloon inside the thorax of a dog cadaver and studied this model with both fluoroscopic techniques. Calcific atherosclerotic plaques were more easily identified with digital subtraction fluoroscopy than with conventional fluoroscopy. We tested the method clinically by submitting 191 subjects without history or electrocardiographic evidence of previous myocardial infarction who were referred for coronary arteriography to both fluoroscopic studies. For at least one, at least two, and three calcified coronary arteries, digital fluoroscopy was more sensitive (92%, 66%, and 40%) than conventional fluoroscopy (63%, 21%, and 2%) (all p less than .001) for the prediction of significant coronary obstructions (greater than 50%). Although digital fluoroscopy was less specific than conventional fluoroscopy (digital: 65%, 89%, and 97%; conventional: 81%, 98%, and 100%) (all but last, p less than .01), receiver operating curve analysis revealed a significantly larger area under the curve, indicating higher accuracy for the digital technique (p = .03). Digital subtraction fluoroscopy was more accurate in younger than in older patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Rib perichondrial grafts for the repair of full-thickness articular-cartilage defects. A morphological and biochemical study in rabbits.

The purpose of this study was to investigate the use of perichondrial grafts in articular cartilage defects and to characterize the newly formed cartilage. In a rabbit model, rib perichondrium was used to repair full-thickness defects in the femoral condyle. The quality of repair was then evaluated histologically and biochemically at six and twelve weeks after grafting. Unacceptable results were obtained in 50 per cent of the rabbits. These failures were due to condylar fracture in 20 per cent, failure of graft attachment in 20 per cent, and infection in 10 per cent. The technique of grafting must be improved to increase the percentage of successful grafts in which neocartilage with a relatively normal chemical composition fills the articular cartilage defect. Successful grafts proliferate to fill the full-thickness defect with neocartilage, which has biochemical characteristics that are similar to those of hyaline cartilage.

Animals↗