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Biomedical subjects

T Miller

Publications and source records attributed to T Miller.

At least 109 records · Page 6Linked to original sources

Accuracy of self-reported educational attainment among diverse patient populations: a preliminary investigation.

Despite speculation concerning the accuracy of self-reported information, particularly from certain patient populations, many neuropsychologists continue to estimate premorbid intellectual functioning on the basis of self-reported educational attainment. This study examined 116 individuals with diverse diagnoses [i.e., alcoholism, posttraumatic stress disorder (PTSD), schizophrenia or schizoaffective, and dementia] to determine the accuracy of their self-reported high school educational attainment. Results suggest that at least half of all participants were inaccurate as defined by discrepancies between actual and estimated GPA greater than.5 on a traditional 4-point grading scale. Most patients were inaccurate in the direction of overestimating their educational attainment. Patients diagnosed with alcoholism and PTSD were significantly less accurate in recalling their educational history when compared to a group of normal-control subjects. Several subjects, whose records could not be verified, were found to have not attended high school as they had claimed. These results underscore the potential inaccuracy that exists when estimating premorbid intelligence using self-reported information.

Journal Article↗

Are rice chromosomes components of a holocentric chromosome ancestor?

Comparative genomics reveals that cereal genomes are composed of similar genomic building blocks (linkage blocks). By stacking these blocks in a unique order, it is possible to construct a single ancestral 'chromosome' which can be cleaved to give the basic structure of the 56 different chromosomes found in wheat, rice, maize, sorghum, millet and sugarcane. The borders of linkage blocks are defined by cereal centromeric and telomeric sites. However, a number of studies have shown that telomeric heterochromatin has neocentromeric activity, implying that linkage blocks are in fact defined by centromeric-like sites with conserved sequences. The structure of the ancestral cereal genome thus resembles a holocentric chromosome, which is the chromosome structure shared by the closest relatives of the Gramineae, the Cypericeae and Juncaceae.

Biological Evolution↗

Changes in diagnostic decision-making after a computerized decision support consultation based on perceptions of need and helpfulness: a preliminary report.

We examined the degree to which attending physicians, residents, and medical students' stated desire for a consultation on difficult-to-diagnose patient cases is related to changes in their diagnostic judgments after a computer consultation, and whether, in fact, their perceptions of the usefulness of these consultations are related to these changes. The decision support system (DSS) used in this study was ILIAD (v4.2). Preliminary findings based on 16 subjects' (6 general internists, 4 second-year residents in internal medicine, and 6 fourth-year medical students) workup of 136 patient cases indicated no significant main effects for 1) level of experience, 2) whether or not subjects indicated they would seek a diagnostic consultation before using the DSS, or 3) whether or not they found the DSS consultation in fact to be helpful in arriving at a diagnosis (p > .49 in all instances). Nor were there any significant interactions. Findings were similar using subjects or cases as the unit of analysis. It is possible that what may appear to be counter-intuitive, and perhaps irrational, may not necessarily be so. We are currently examining potential explanatory hypotheses in our ongoing current, larger study.

Attitude to Computers↗

The role of the four Ca2+ binding sites of troponin C in the regulation of skeletal muscle contraction.

In order to study the role of the Ca2+-specific sites (I and II) and the high affinity Ca2+-Mg2+ sites (III and IV) of TnC in the regulation of muscle contraction, we have constructed four mutants and the wild type (WTnC) of chicken skeletal TnC, with inactivated Ca2+ binding sites I and II (TnC1,2-), site III (TnC3-), site IV (TnC4-), and sites III and IV (TnC3,4C-). All Ca2+ binding site mutations were generated by replacing the Asp at the X-coordinating position of the Ca2+ binding loop with Ala. The binding of these mutated proteins to TnC-depleted skinned skeletal muscle fibers was investigated as well as the rate of their dissociation from these fibers. The proteins were also tested for their ability to restore steady state force to TnC-depleted fibers. We found that although the NH2-terminal mutant of TnC (TnC1,2-) bound to the TnC-depleted fibers (with a lower affinity than wild type TnC (WTnC)), it was unable to reactivate Ca2+-dependent force. This supports earlier findings that the low affinity Ca2+ binding sites (I and II) in TnC are responsible for the Ca2+-dependent activation of skeletal muscle contraction. All three COOH-terminal mutants of TnC bound to the TnC-depleted fibers, had different rates of dissociation, and could restore steady state force to the level of unextracted fibers. Although both high affinity Ca2+ binding sites (III and IV) are important for binding to the fibers, site III appears to be the primary determinant for maintaining the structural stability of TnC in the thin filament. Moreover, our results suggest an interaction between the NH2- and COOH-terminal domains of TnC, since alteration of sites I and II lowers the binding affinity of TnC to the fibers, and mutations in sites III and IV affect the Ca2+ sensitivity of force development.

Animals↗

A cereal centromeric sequence.

We report the identification of a family of sequences located by in situ hybridisation to the centromeres of all the Triticeae chromosomes studied, including the supernumerary and midget chromosomes, the centromeres of all maize chromosomes and the heterochromatic regions of rice chromosomes. This family of sequences (CCS1), together with the cereal genome alignments, will allow the evolution of the cereal centromeres and their sites to be studied. The family of sequences also shows homology to the CENP-B box. The centromeres of the cereal species and the proteins that interact with them can now be characterised.

Autoantigens↗

Irradiated uveal melanomas: cytopathologic correlation with prognosis.

PURPOSE: We analyzed the additional prognostic information from cytopathologic data obtained at the time of uveal melanoma irradiation. METHODS: Fine-needle aspiration biopsies (FNABs) were performed and reviewed in a masked manner. These data and standard prognostic variables were correlated with survival and local tumor recurrence using Kaplan-Meier and Cox model statistical techniques. RESULTS: Cytopathologic assessment of cell type added to prognostic accuracy. In 116 patients, the percentage of epithelioid cells on FNAB and ciliary body involvement were most strongly correlated with melanoma-related mortality. CONCLUSIONS: FNAB data improved our prognostic accuracy in irradiated uveal melanoma patients.

Biopsy, Needle↗

Effects of some components of the essential oil of chamomile, Chamomilla recutita, on histamine release from rat mast cells.

The influence of three compounds of the essential oil of Chamomilla recutita (L.) Rauschert on the protamine sulphate-provoked degranulation of mast cells from Lewis-1a rats was investigated. The effect was determined by measuring histamine liberation fluorometrically. Chamazulene and (-)-alpha-bisabolol had no distinct effects. The en-yne dicycloether partly inhibited the degranulation in concentrations above 10(-4) M.

Animals↗

The development of the Functional Capacity Index.

OBJECTIVE: This paper describes the development of the Functional Capacity Index (FCI) and compares it to the Abbreviated Injury Scale (AIS) and the Injury Impairment Scale (IIS). METHODS: The FCI maps 1990 AIS injury descriptions into scores that reflect expected levels of reduced functional capacity at 1 year after injury. Its development involved three steps. First, an expert clinical panel identified 10 relevant dimensions of function and defined levels of capacity within each dimension. A group of 114 individuals then rated the relative severity of different levels of function in terms of their impact on daily living. The third step involved clinical experts assigning FCI scores to AIS '90 injury descriptions based on their knowledge of the likely 1-year consequences associated with each injury. As a first step in validating the FCI, 1 year postinjury levels of impairment (based on range of motion and strength) were correlated with FCI, IIS, and AIS scores derived for 301 patients with severe lower extremity fractures. RESULTS: Consistency of FCI scores derived within and across dimensions of function argue for the conceptual integrity of the index. Non-zero FCI scores were assigned to only 26% of the 1,272 AIS injury descriptions, indicating that, for most of the injuries in the AIS dictionary, very little or no residual impairment is expected for the average person at 1 year. FCI scores derived for 301 patients with lower extremity fractures ranged from 0 to 63 (out of a possible 100 points). A modest correlation was found between FCI scores and actual levels of impairment observed at 1 year. Compared with the AIS and the IIS, the FCI appeared to discriminate somewhat better among different levels of function. CONCLUSIONS: Although further empirical validation of the FCI is essential before it can be broadly applied, its development represents an important first step in the generation of an AIS-based measure of expected functional outcome. Its validation is encouraged across a variety of settings and injury types.

Abbreviated Injury Scale↗

Renin regulation in cultured proximal tubular cells.

Recent studies have documented the presence of a complete renin-angiotensin system in the proximal tubule of the kidney: however, little is known about the regulation of renin in this proximal tubular system. Therefore, we performed the present studies to learn whether the behavior of the renin system in cultured proximal tubule is similar to that of the juxtaglomerular renin system. Basal renin secretion from rabbit proximal tubular cells in primary culture was low and not affected by isoproterenol (10(-5) mol/L), diltiazem (10(-5) mol/L), or a zero-calcium bath (O nmol/L). Only the calcium ionophore A23187 (10(-4) mol/L) significantly reduced renin secretion in these cells (from 2.44 +/- 0.37 to 1.14 +/- O.08 ng angiotensin I/mg protein per hour, P<.05). When the proximal tubular cells were lysed so the effects of the test agents on intracellular renin content could be assessed, isoproterenol caused a significant twofold (107 percent) increase (from 2.02 +/- 0.56 to 4.18 +/- 0.81 ng angiotensin I/mg protein per hour, P<.05), whereas diltiazem, A23187, and zero- and high-calcium baths did not produce a significant change. The effects of these agents on renin mRNA were examined in rabbit and rat proximal tubular cells in primary culture with the use of an S1 nuclease protection assay. Densitometry analysis of renin mRNA and either GAPDH mRNA (rat) or alpha-actin (rabbit) showed no significant alterations in renin mRNA abundance. In summary, these results confirm the presence of renin mRNA in cultured proximal tubular cells and suggest that a low-level, constitutive secretion of renin occurs in this system that is decreased by A23187. Moreover, the results also suggest that proximal tubular renin is regulated, albeit differently from the juxtaglomerular renin system. Finally, short-term increments in proximal tubular renin occur without a change in renin mRNA.

Animals↗

ABT-431: the diacetyl prodrug of A-86929, a potent and selective dopamine D1 receptor agonist: in vitro characterization and effects in animal models of Parkinson's disease.

(-)-Trans 9,10-hydroxy-2-propyl-4,5,5a,6,7,11b-hexahydro-3-thia-5- azacyclopent-1-ena[c]phenanthrene hydrochloride (A-86929) is a potent and selective full agonist at the dopamine (DA) D1-like receptor. Judging by its binding affinities to the D1 and D2 classes of receptors, the compound is approximately 20-fold D1 receptor-selective, whereas relative potencies based on functional in vitro assays indicate that A-86929 is greater than 400-fold D1-selective. A-86929 has moderate to weak (Ki > 1 microM) affinity at other monoaminergic and peptidergic receptors, at ion channels and at monoamine uptake sites. The catechol of A-86929 was bis-acetylated to produce the prodrug, (-)-trans 9,10-acetoxy-2-propyl-4,5,5a,6,7,11-b-hexahydro-3-thia- 5-azacyclopent-1-ena[c]phenanthrene hydrochloride (ABT-431), which is more chemically stable yet is rapidly converted to the parent compound with a half-life of less than 1 min in plasma. Both A-86929 and ABT-431 produced contralateral rotation in rats bearing unilateral 6-hydroxydopamine lesions, with ED50 values of 0.24 mumol/kg s.c. and 0.54 mumol/kg s.c., respectively. A-86929 and ABT-431 improved behavioral disability scores and increased locomotor activity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmoset model of Parkinson's disease in a dose-dependent manner (the minimum effective dose was 0.10 mumol/kg s.c.). When administered three times daily for 30 consecutive days to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned marmosets, A-86929 significantly improved disability scores throughout the duration of the study. Current Parkinson's disease therapy includes L-dopa, which stimulates both classes of DA receptors by virtue of its conversion to DA in vivo, and direct-acting D2-selective agonists. Stimulation of the D2 receptor, which is associated with all current DA agonist-based therapies, may contribute to their dose-limiting side effects. An agent such as A-86929 (or its prodrug ABT-431), which selectively stimulates the D1 receptor, may represent a novel mechanism for Parkinson's disease therapy with the potential for an improved side-effect profile and, consequently, improved patient compliance.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Apoptosis induced by tumor necrosis factor-alpha in rat hepatocyte cell lines expressing hepatitis B virus.

Three well differentiated SV40-immortalized rat hepatocyte cell lines, CWSV1, CWSV2, and CWSV14, and Hepatitis B Virus (HBV)-producing cell lines derived from them were examined for sensitivity to tumor necrosis factor (TNF)-alpha. CWSV1, CWSV2, and CWSV14 cells were co-transfected with a DNA construct containing a dimer of the HBV genome and the neo gene and selected in G418 to generate stable cell lines. Characterization of these cell lines indicated that they contain integrated HBV DNA, contain low molecular weight HBV DNA compatible with the presence of HBV replication intermediates, express HBV transcripts, and produce HBV proteins. The viability of CWSV1, CWSV2, and CWSV2 cells was not significantly altered when they were treated with TNF-alpha at concentrations as high as 20,000 U/ml. The HBV-expressing CWSV1 cell line, SV1di36, and the HBV-expressing CWSV14 cell line, SV14di208, were also not killed when treated with TNF-alpha. However, the HBV-expressing CWSV2 cell line, SV2di366, was extensively killed when treated with TNF-alpha at concentrations ranging from 200 to 20,000 U/ml. Analysis of several different HBV-producing CWSV2 cell lines indicated that TNF-alpha killing depended upon the level of HBV expression. The TNF-alpha-induced cell killing in high HBV-producing CWSV2 cell lines was accompanied by the presence of an oligonucleosomal DNA ladder characteristic of apoptosis.

Animals↗

The influence of a decision support system on the differential diagnosis of medical practitioners at three levels of training.

As computer-based diagnostic consultation systems become, available, their influence and usefulness need to be evaluated. This report, based on partial data from a larger study, examines the influence of Iliad, a diagnostic consultation system, on the differential diagnosis of fourth year medical students, residents in medicine, and attendings in general internal medicine. Our results show that when faced with difficult diagnostic cases, medical students add significantly more diagnoses from Iliad's differential than do residents or attendings. However, the quality of Iliad's diagnostic advice in terms of the presence of the correct diagnosis, is no better for consultations done by students or residents compared to attendings.

Clinical Competence↗

Factors promoting completion of advance directives in the hospital.

BACKGROUND: The 1991 Patient Self-Determination Act required health care providers to give patients information about advance directives. OBJECTIVES: To investigate whether the requirement to distribute information to hospital patients increased completion of the health care proxy. To also explore factors that might influence use of advance directives, including demographic variables and methods of informing patients about the directives. PATIENTS AND METHODS: We interviewed 419 randomly selected patients who were admitted for a planned admission to two tertiary care, teaching hospitals. Patients at one hospital received proxy information before the day of admission, at a pretesting visit, or by mail. The other hospital distributed the proxy information only on the day of admission. RESULTS: Before receiving hospital materials, 17% of all patients had completed proxies. After receiving hospital proxy forms, an additional 40% completed proxies at the hospital that distributed forms before the day of admission. Only 4% of the patients completed proxies at the hospital that distributed information only on the day of admission. The most frequently cited barrier to completion of a proxy was not seeing the form. Few patients said they did not want to think about the subject. CONCLUSIONS: Completion rates for advance directives may be markedly improved by altering the time for distributing information to patients admitted to the hospital for a planned admission. Patients were more likely to complete a proxy in the hospital that distributed the form in advance of the day of admission, a result that was unexplained by other variables in the study. Although many patients would prefer to receive information about advance directives during an office visit with a physician, hospitalization can provide a valuable opportunity for many patients to complete directives.

Adult↗