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Biomedical subjects

D K Miller

Publications and source records attributed to D K Miller.

At least 127 records · Page 7Linked to original sources

Time and financial analysis of an academic general internal medicine unit.

A detailed time and financial analysis of an academic general internal medicine unit was used to examine financial, educational, and research issues. The residents' outpatient service possessed the greatest patient visit and revenue capacity, but revenue recovery was limited by low productivity and collection rate. Outpatient revenue production could be improved but would still be less than current inpatient revenues. Full financial self-sufficiency would require improvements in several aspects of revenue production and would severely limit faculty time for teaching, personal study, and research. Indirect financial contributions to the medical center through hospitalizations and referrals dwarfed direct revenues. Several strategies for academic general internal medicine units to achieve financial and academic survival are possible, each with its own set of trade-offs. Because local circumstances differ, strategies and outcomes are likely to vary among units.

Efficiency↗

Serological prevalence of bovine babesiosis in Mali.

A serological survey of cattle in Mali was carried out to determine the prevalence of antibody activity to Babesia bovis and B. bigemina. It was found that the level of B. bovis infection as indicated by antibody activities was too low to be of immediate concern. However, the serological prevalence of B. bigemina was high and this may indicate a potential disease problem. It was also found that when zebu and N'Dama cattle grazed together the N'Dama were twice as likely to have positive titres to Babesia as were the zebus.

Age Factors↗

Effects of DEAE-dextran on infection and hemolysis by VSV. Evidence that nonspecific electrostatic interactions mediate effective binding of VSV to cells.

The polycation DEAE-dextran increased the binding of VSV to BHK cells about fourfold over a wide range of VSV concentrations. The same proportion of bound virions was internalized by the cell in the presence or absence of DEAE-dextran. Viral primary RNA production was increased to the equivalent of a 4- to 4.5-fold increase in multiplicity of infection in the presence of DEAE-dextran, closely paralleling the increase in total VSV binding to the cell. Viral secondary RNA production was increased only to the equivalent of about twofold increase in multiplicity. The kinetics of both primary and secondary RNA production were indistinguishable in the presence or absence of DEAE-dextran. DEAE-dextran had to be present simultaneously with the input virions in order to enhance RNA production; addition even 30 min after infection was ineffective. Addition of the polycation DEAE-dextran was also required for appreciable VSV-induced hemolysis of human erythrocytes; erythrocytes of several other species were hemolyzed in the absence of DEAE-dextran, but hemolysis was enhanced by its presence. Maximal binding and hemolysis occurred at pH 5.0 and 37 degrees. Vesicles containing only G protein and viral lipid were 40% as hemolytic as intact virions at pH 5.0, but were inactive at pH 6.0; "spikeless" virions lacking G, or protein-free viral lipid vesicles were not hemolytic, showing that G protein is necessary for hemolysis. These results, together with other recent observations, suggest that multiple electrostatic interactions between VSV and the cell surface, rather than an affinity for specific surface molecules, mediated the productive (infection producing) binding of VSV to the cell surface.

Animals↗

Measurement of the global and functional dimensions of health status in the elderly.

Data from a two-stage random sample of 401 noninstitutionalized elderly individuals residing in 18 census tracts in south-central metropolitan St. Louis were used to examine the relationships among seven measures of health status. Factor analyses revealed two pristine dimensions: (a) a global health status dimension, on which perceived health status, nutritional risk, perceived sensory functions, and mental health all load significantly; and, (b) a functional dimension on which the Activities of Daily Living, Instrumental Activities of Daily Living, and mental orientation measures all load significantly. These two factors explain 56% of the variance in the seven health status measures, and, using an oblique rotational procedure, they were found to be correlated only modestly (r = .37). The implications for the measurement of health status of elderly adults as well as the use of such measures in predicting health services utilization are discussed, and recommendations for the inclusion of items tapping both dimensions in future studies are presented.

Activities of Daily Living↗

Abetalipoproteinemia. Report of an unusual patient.

Abetalipoproteinemia (Bassen-Kornzweig syndrome, acanthocytosis) was diagnosed at age 13 months in a black male. At age 13 months, the electroretinogram was nonrecordable and a pigmentary retinopathy was obvious with ophthalmoscopy. Following dietary modification and vitamin supplementation, the scotopic electroretinogram improved to about 30% of normal.

Abetalipoproteinemia↗

Cell killing by lysosomotropic detergents.

We have studied the mechanism by which lysosomotropic detergents kill baby hamster kidney cells. Lysosomotropic detergents are lysosomotropic amines (compounds with pK between 5 and 9, such as imidazole or morpholine) containing straight-chain hydrocarbon "tails" of 9-14 carbon atoms (Firestone, R. A., J. M. Pisano, and R. J. Bonney. 1979, J. Med. Chem., 22:1130-1133). Using lucifer yellow CH as a specific fluorescent label for lysosomes, it was shown by light microscopy that N-dodecyl (C12)-imidazole acted rapidly to damage lysosomes, causing leakage of dye into the cytoplasm. This was followed at later times by vacuolization, blebbing of the plasma membrane, cell rounding, and cell death. 3H-labeled C12-imidazole rapidly diffused into cells where much of it was trapped in lysosomes as shown by its co-migration with lysosomes in Percoll gradients. Cells preincubated with C12-imidazole released it slowly into C12-imidazole-free media, permitting the cells to be killed by the preincubation dose. Cell killing by the lysosomotropic detergents exhibited strongly sigmoidal dose-response curves. The sensitivity of baby hamster kidney cells to killing by C12-imidazole was density dependent, the cells being most sensitive at lowest cell densities, and relatively resistant at confluence. The amount of 3H-C12-imidazole taken up by the cells was also density dependent, with highest specific uptake occurring at the lowest cell density. A rise in lysosomal pH, measured in fluoresceinated dextran-labeled cells, commenced immediately upon addition of C12-imidazole to cells, and continued for over an hour. This was followed after a lag of 1-2 h by inhibition of protein and RNA synthesis and by lactate dehydrogenase release. Ionophores or lysosomotropic amines, such as methylamine, that raise intralysosomal pH provided substantial protection of the cells from killing by lysosomotropic detergents. These findings provide strong support for the idea that lysosomotropic detergents kill cells by disrupting lysosomes from within.

Animals↗

Rocky Mountain Spotted Fever. Ultrastructural findings.

A case of Rocky Mountain Spotted Fever in a human is presented with special emphasis on ultrastructural aspects of the disease. Electron microscopic examination of the tick bite site demonstrated the presence of rickettsial organisms both within the cytoplasm and nucleus of endothelial cells, as well as within the periendothelial cell environment. Several ultrastructural reports of rickettsia localization and morphology within experimental animal and tissue culture models have been reviewed. This report, to our knowledge, represents the first documented demonstration of rickettsial organisms in an acute human disease case. The size, location and morphologic features of the organisms in our case compare closely with the previously reported experimental results.

Cell Nucleus↗

Ultraviolet-irradiated vesicular stomatitis virus and defective-interfering particles are similar non-specific inhibitors of virus infection.

The way in which ultraviolet-irradiated vesicular stomatitis virus (VSV) inhibits the early events in VSV infection has been further characterized. Comparison of several different u.v.-irradiated thermolabile, temperature-sensitive mutants before and after heat inactivation established a requirement for inhibitory activity of functional G, N and L proteins, but not M protein. Defective-interfering (DI) particles, whether irradiated or not, inhibited VSV primary transcription as efficiently as UV-VSV, suggesting that virus proteins rather than transcription products are responsible for inhibition. Addition of inhibitory UV-VSV at different times after infection established that inhibition results from an action at an intracellular site, rather than at the cell surface or in the process of internalization. A similar inhibition by UV-VSV of infection by Sendai virus, Semliki Forest virus, Sindbis virus and influenza virus suggests that UV-VSV is acting by inducing a general change in the intracellular environment.

Animals↗

pH dependence of influenza A virus-induced haemolysis is determined by the haemagglutinin gene.

The pH-dependent profiles of haemolysis by influenza viruses AHK/8/68 (HK virus) and APR/8/34 (PR8 virus) were found to possess characteristic differences. Both viruses were highly haemolytic at pH 5.0, but while HK virus-induced haemolysis was undetectable above pH 5.5 to 5.6,, PR8 virus-induced haemolysis persisted at higher pH values, becoming undetectable above pH 5.7 to 5.8. In order to determine whether these haemolysis profiles were genetically determined, we studied the pH dependence of haemolysis by eight recombinants of HK and PR8 viruses. The pH profile of each recombinant clearly resembled that of one parent or the other, showing that it is an inherited trait. The pH profile was found to be conferred exclusively by the haemagglutinin (HA) gene.

Hemagglutinins, Viral↗

Faculty resources for teaching geriatric medicine.

Self-administered questionnaires were sent to all faculty and staff members of the departments of internal medicine and psychiatry in a school of medicine. The questionnaires asked for information about personal characteristics, practice characteristics, and interest in teaching geriatrics. Included also were measures of knowledge about aging and attitudes toward the elderly. Responses were received from 25 per cent of the faculty. Results indicated that 40 per cent wanted no involvement in teaching geriatrics. Of the remainder, most preferred a consultant's role on a clinical service. Despite extensive experience with elderly patients, respondents showed modest scores on knowledge, but there was little stereotyping of elderly patients. Implications for establishing a training program in geriatrics are discussed.

Adult↗

Attitudes and health promoting behavior of medical and law students.

An entering class of medical students is compared with an entering class of law students on attitudes toward self-responsibility for health and reported health behaviors. Students' health behavior patterns are contrasted with those of practicing physicians and lawyers. Data were collected by self-administered questionnaires. Results indicated that medical students were stronger on self-responsibility and also reported more often engaging in health promoting behavior than law students. The same pattern of differences was reported for practicing physicians and lawyers.

Adult↗

Cost-effectiveness of thyroid function tests.

The cost-effectiveness of thyroid function tests (serum thyroxine concentration, triiodothyronine [T3]-resin uptake, free thyroxine index, serum T3, and serum thyrotropin concentration) was assessed in 135 ambulatory patients suspected of hypothyroidism or hyperthyroidism who did not have a history of thyroid disease requiring medication or thyroid surgery within the preceding two years. Of patients with five or more signs and symptoms compatible with thyroid dysfunction, 50.0% had biochemical abnormalities substantiating hypothyroidism or hyperthyroidism, while only 1.5% of patients with fewer than two signs and symptoms had either disease. The cost of thyroid function tests was twice as much per patient evaluated by residents as for those evaluated by faculty physicians. These results suggest that interventions to reduce the number and type of tests in patients without multiple signs and symptoms of thyroid disease could improve the cost-effective use of these tests.

Cost-Benefit Analysis↗