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Biomedical subjects

G Chase

Publications and source records attributed to G Chase.

At least 19 recordsLinked to original sources

Use of short-term assays to evaluate the potential toxicity of two new biosoluble glasswool fibers.

Two new glasswools were developed for optimal biosolubility in the lung: JM 902, for insulation and filtration; and JM 901F, for standard thermal and acoustical insulation. Both were tested for lung biopersistence and their potential to induce persistent pulmonary inflammation in rats. Their dissolution rate constants (k(dis)) were estimated in vitro. Results for 902 were: in vitro k(dis) (pH 7.4) = 150 ng/cm2/h; after 5 days of fiber inhalation (IH), lung clearance of fibers > 20 microm length (F > 20 microm) indicated a weighted half-time (WT(1/2)) of 6.8 days and 90% clearance time (T90) of 33 days; following intratracheal instillation (IT), lung clearance half-time (T(1/2)) for F > 5 microm was 20 days. Results for 901F were: k(dis) (pH 7.4) = 500-560; after 5 days of fiber inhalation exposure, WT(1/2) (F > 20 microm) = 8.1 days and T90 = 38 days. After 5 days of fiber inhalation, both fibers induced initial pulmonary inflammation followed by return to normal within 3 wk postexposure. Lung clearance half-times for 902 and 901F passed the European Union (EU) criteria for noncarcinogenic fibers (IH WT(1/2) F > 20 microm was < 10 days); 902 passed the noncarcinogenic criterion of the German government (IT T(1/2) F > 5 microm was < 45 days). Thus, carcinogenicity labeling is not required for either fiber in the EU. Short-term test results for 902 and 901F were similar to results for synthetic vitreous fibers (SVFs) that were innocuous in rodent chronic inhalation studies, but short-term test results for 902 and 901F differed sharply from results for other SVFs that were pathogenic in chronic studies. Thus, these short-term tests indicate that 902 and 901F are biosoluble fibers and would be nonpathogenic in the rat exposed by inhalation.

Animals↗

Biopersistence of synthetic vitreous fibers and amosite asbestos in the rat lung following inhalation.

Fiber biopersistence as a major mechanism of fiber-induced pathogenicity was investigated. The lung biopersistence of 5 synthetic vitreous fibers (SVFs) and amosite asbestos was evaluated using the rat inhalation model. In contrast to several previous studies, this study examined fibers that dissolve relatively slowly in vitro at pH 7.4. Fisher rats were exposed for 5 days by nose-only inhalation to refractory ceramic fiber (RCF1a), rock (stone) wool (MMVF21), 2 relatively durable special application fiber glasses (MMVF32 or MMVF33), HT stonewool (MMVF34), amosite asbestos, or filtered air. Lung burdens were analyzed during 1 year post-exposure. Fiber aerosols contained 150-230 fibers/cc longer than 20 micrometer (>20 micrometer). On post-exposure Day 1, long-fiber lung burdens for the 6 test fibers were similar (12-16 x 10(5) fibers/lung >20 micrometer). After 1 year, the percentage of fibers >20 micrometer remaining in the lung was 0.04-10% for SVFs but 27% for amosite. Lung clearance weighted half-times (WT1/2) for fibers >20 micrometer were 6 days for MMVF34, 50-80 days for the other 4 SVFs, and >400 days for amosite. This study and 3 previous studies demonstrate a broad range of biopersistences for 19 different SVFs and 2 asbestos types. Ten of these fibers also have been (or are being) tested in chronic inhalation studies; in these studies, the very biopersistent fibers were carcinogenic (amosite, crocidolite, RCF1, MMVF32, and MMVF33), while the more rapidly clearing fibers were not (MMVF10, 11, 21, 22, and 34). These studies demonstrate the importance of biopersistence as an indicator of the potential pathogenicity of a wide range of fiber types.

Aerosols↗

Radiographic and spirometric findings in diatomaceous earth workers.

Diatomaceous earth is a noncrystalline form of silica; in processing, calcining leads to formation of cristobalite, a form of crystalline silica. Four hundred ninety-two currently employed diatomaceous earth workers in a large mine and processing facility had chest radiographs performed and interpreted by the International Labour Office (ILO) system. Two hundred sixty-seven subjects underwent spirometry testing. Exposure indices for total dust (largely diatomaceous earth) and cristobalite were reconstructed for each individual based upon personnel records. Analysis demonstrated the following prevalences of radiographic findings: 5% had ILO scores > or = 1/0, and 25% had scores of 0/1 or higher. Regression analyses showed that there was a relationship between both total cristobalite exposure and total dust (largely diatomaceous earth) exposure and the ILO score. Radiographic patterns are not typical of those of classic silicosis. Linear regression analyses for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio did not demonstrate a relationship between cumulative exposure and lung function. Such analyses were performed using all subjects and stratified by smoking status. There were differences in spirometric data according to radiographic ILO category, but the results were inconsistent and did not permit determining if physiologic changes are associated with radiographic change or if this is due to confounding. Overall, the study suggests that diatomaceous earth pneumoconiosis (radiographically defined) is an entity distinct from silicosis. Recent exposure levels may produce radiographic abnormalities but do not lead to demonstrable physiologic effect. The prevalence of the disorder has diminished markedly in response to modern dust control measures. Ongoing medical surveillance is recommended in workers with potential exposure to significant quantity of material.

Adult↗

ApoE-4 and age at onset of Alzheimer's disease: the NIMH genetics initiative.

OBJECTIVE: To explore the impact of apoE-4 on Alzheimer's disease (AD) and its age at onset. DESIGN: A genetic linkage study using affected relative pairs, predominantly siblings. SETTING: Three academic medical centers ascertained subjects from memory disorder clinics, nursing homes, and the local community. SUBJECTS: 310 families including 679 subjects with AD by NINCDS/ADRDA and/or Khachaturian criteria and 231 unaffected subjects. OUTCOME MEASURE: ApoE genotype. ANALYTIC METHODS: Association, affected pedigree member, sibling pair, and lod score analyses. RESULTS: ApoE-4 was strongly associated with AD in this sample (allele frequency = 0.46 vs. 0.14 in controls, p < 0.000001). Results of lod score, affected pedigree member analysis, and sib-pair analysis also supported apoE-4 as a risk factor for AD. When the sample was stratified on family mean age at onset, the risk conferred by apoE-4 was most marked in the 61 to 65 age group. Individuals with two copies of apoE-4 had a significantly lower age at onset than those with one or no copies (66.4 vs. 72.0, p < 0.001), but individuals with one copy did not differ from those with none. Within families, the individual with the earliest age at onset had, on average, significantly more apoE-4 alleles (p < 0.0001) than the individual with the latest onset. DISCUSSION: This work supports previous reports of an association between apoE-4 and the development of AD and demonstrates that apoE-4 exerts its maximal effect before age 70. These findings have important implications for the potential use of apoE genotyping for diagnosis and prediction of disease. They also underscore the need to identify additional genetic factors involved in AD with onset beyond age 70 years.

Age of Onset↗

The steam connection.

Explore the source record for details and available documents.

Maintenance and Engineering, Hospital↗

Plasma cholesterol and triglyceride distributions in 13,665 children and adolescents: the Prevalence Study of the Lipid Research Clinics Program.

The age-, race-, sex-specific distributions for plasma cholesterol (CH) and triglyceride (TG) are described for the 13,655 individuals under 20 years of age who were examined at the first visit (visit I) of the Prevalence Study of the Lipid Research Clinics (LRC) Program. Composite findings are presented from the seven North American LRC's where children were included in the target population. Cholesterol values are higher for blacks than for whites, but triglyceride values are higher for whites than for blacks. In both the CH and TG distributions for the combined races, the mean values for females are generally higher than for males. For cholesterol, consistent age-associated differences occur. On average, the CH values peak in late childhood and decline during adolescence. The decrease in mean values for CH is most marked for white males. The values for TG tend to increase in early adolescence. This report expands the available information about lipid distributions in young populations and describes the extent of the variation in plasma lipids associated with race and sex for each year of age, 0 to 19 years.

Adolescent↗

Prophylactic transfusions of normal red blood cells during pregnancies complicated by sickle cell hemoglobinopathies.

Prophylactic transfusions of normal donor red cells were administered during 37 pregnancies to women with sickle cell anemia, sickle cell-hemoglobin C disease, or sickle cell-beta thalassemia disease. Once the diagnosis was confirmed, the transfusions were administered intermittently throughout the rest of the pregnancy in such amounts and at such frequencies that no more than 60% of the circulating red cells contained hemoglobin S and the hematocrit was above 25. The maternal mortality rate was zero and maternal morbidity as the consequence of the sickle cell hemoglobinopathy was minimal. The perinatal mortality rate was appreciably reduced when compared to that previously observed without prophylactic transfusions but perinatal morbidity was still excessive. Evidence that the intrauterine environment was compromised, in spite of the transfusions consisted of an increased frequency of growth-retarded fetuses, of meconium staining of amnionic fluid, and of ominous decelerations of fetal heart rate. Morbidity from the transfusions was troublesome. Nonetheless, it is concluded tentatively that both the mother with a sickle cell hemoglobinopathy and her fetus are likely to benefit from prophylactic transfusions of normal donor red cells administered during one pregnancy according to the protocol employed in this study.

Anemia, Sickle Cell↗

Implementing a human services program: how hard will it be?

A framework is presented for examining obstacles to the implementation of human services delivery programs. These obstacles appear to arise from three basic sources: (1) from the operational demands implied by a particular program concept, (2) from the nature and availability of the resources required to run the program, and (3) from the need to share authority with, or retain support of, other bureaucratic and political actors in the implementation process. Within these three broad categories, fifteen areas deserve special attention: the people to be served, the nature of the service, the likelihood of distortions or irregularities, the controllability of the program, money, personnel, space, supplies and technical equipment, and intersections with overhead agencies, other line agencies, elected politicians, higher levels of government, private-sector providers, special-interest groups, and the press. By searching each of these fifteen areas diligently and systematically--with the aid of some 44 "factors for consideration"--it appears possible to make relatively powerful predictions about the obstacles that the implementation of a given human services program will entail. In addition, the framework can be used as a comparative instrument in allocating scarce political, managerial, and financial resources among human services programs, and as an aid to decision-making within particular programs and to identifying obstacles that cut across programs. Finally, some general guidance is offered on how implementing agency managers might deal with one of the more important and difficult dimensions of program implementation--namely, getting the cooperation of players in the implementation game whom the managers do not control, and who have different interests and agendas.

Community Health Services↗

Drug utilization review in an HMO. I. Introduction and examples of methodology.

An experimental drug utilization review program was developed for a health maintenance organization (HMO). The objectives of the program were to develop and implement an ongoing mechanism for reviewing drug use using criteria based on the scientific literature, and to evaluate the effect of the drug use review program on physician precribing patterns. Seven therapeutic categories of drugs, accounting for over 65 per cent of prescribing, were selected and criteria developed for their use. The drug use review prcedure is described briefly. The evaluation of the drug use review program is based on a comparison of rates of prescription use for specific therapeutic categories before and after the criteria were ceveloped and approved. As an example, data for the antihistamine therapeutic category are presented. Criteria for prescribing antihistamines suggested restricting use of combination cold preparations and refraiming from antihistamine use in viral upper respiratory tract infections. After the criteria were adopted, prescribing of antihistamines for viral URIs declined, particularly in pediatrics. In general, prescribing of combination antihistamine preparations did not change; where one combination preparation was deleted from the formulary, prescribers appeared to substitute another combination preparation.

Adolescent↗

Reproductive performance of male and female phenotypes in three sex chromosomal genotypes(XX, XY, YY) in the killifish, Oryzias latipes.

The present study investigates the juvenile and adult reproductive performance of Japanese killifish, Oryzias latipes, which were successfully sex-reversed by feeding them male or female sex hormones during the fry stage. Sexual maturation of these laboratory grown fish of three known genotypes (XX, SY, YY) occurred earliest in untreated genotypes, next in genotypes treated with male hormone (methyl testosterone) and female hormone (estrone), respectively. The delay in sexual maturation caused by early exogenous, sex-hormone treatment may represent a disturbance in the delicate neural-gonadal axis. However, the degree of response was also strongly influenced by the animal's sex chromosomal genotype. XX fish, normally phenotypic females, were affected more by the male hormone than by the female hormone. XY and YY fish, normally phenotypic males, were delayed more by the female hormone than by the male hormone. This specific sex hormone-sex genotype interaction also influenced adult reproductive performance (sperm or egg production). Differences in the metabolism of male and female sex hormones by the XX, XY, and YY fish are probably responsible for these interesting findings.

Age Factors↗

A computer-oriented linkage analysis scheme.

A comprehensive, computer-oriented scheme for genetic linkage analysis is described. It computes the likelihood of a complex pedigree allowing for many non-standard features including multiple alleles (up to four per locus), multiple mates, more than one mating in the eldest generation, consanguinity, missing or partially tested persons, and different recombination fractions between males and females. The program works by computing weighted likelihoods in a vertical, descending fashion. First, the set of possible genotypes for the members of the eldest generation is determined and prior probabilities assigned to these states of nature (based on gene frequency calculations). Phenotypic information is used to modify these probabilities in the standard manner. Then, for a particular set of genotypes, the conditional likelihood of the remainder of the pedigree is computed. This calculation may itself be many-branched and therefore a computer is necessary to keep track of the stages of the process. When the youngest generation has been taken into account, a final likelihood is determined, reflecting all information in the pedigree. The current version of the program successfully calculates the exact likelihood of a complex pedigree which was designed to exploit the non-standard features of the program. It has also computed likelihoods for a published pedigree, and the results are essentially equal to those obtained by the other authors using a previously available computer scheme for linkage analysis.

Diagnosis, Computer-Assisted↗

A longitudinal study of total body potassium in normal children.

Most investigators studying changes in body composition during growth agree to the desirability of having longitudinal data. A group of 110 boys and 126 girls, studied annually for 4-5 years with 880 measurements of total body K in a 2pi liquid scintillation whole body counter, had total body K vs. height and total body K vs. weight data that fit previously described regression lines.

Adolescent↗

Cyclophosphamide protection in NZB/NZW disease. Mechanisms and therapeutic regimens.

Regular administration of cyclophosphamide to NZB/NZW female mice effectively protects against the nephritis that is thought to be a model for human SLE nephritis. Reductions in serologic, histologic, and immunogluorescent parameters of the disease are correlated. Intermittent as well as continuous administration of the drug is effective without the development of leukopenia. Possible mechanisms of drug action and a modified approach to therapy of immune complex disease are discussed.

Animals↗