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Biomedical subjects

M Miller

Publications and source records attributed to M Miller.

At least 37 records · Page 2Linked to original sources

Normal triglyceride levels and coronary artery disease events: the Baltimore Coronary Observational Long-Term Study.

OBJECTIVES: This study sought to evaluate long-term predictors of coronary events in men and women with arteriographically defined coronary artery disease (CAD). BACKGROUND: There is conflicting evidence of the role of triglycerides (TGs) as a prognosticator of CAD, and no studies have examined the long-term outcome of "normal" levels in predicting new coronary events. METHODS: This was a retrospective cohort study that evaluated 740 consecutive patients presenting for diagnostic coronary arteriography between 1977 and 1978. Beginning in 1988, patients with arteriographic CAD (n=350) were recontacted and asked to complete detailed medical questionnaires. Case and control patients were stratified by development of new coronary events, including death from ischemic heart disease, nonfatal myocardial infarction and revascularization. RESULTS: There were 199 events during the 18-year follow-up period. The mean high density lipoprotein cholesterol (HDL-C) was significantly lower (35 vs. 39 mg/dl; p=0.002) and TGs higher (160 vs. 137 mg/dl; p=0.03) in case patients than in control patients; After adjusting for age, gender and beta-adrenergic blocking agent use, multiple logistic regression analysis revealed the following independent predictors of CAD events: diabetes mellitus (relative risk [RR] 2.1, 95% confidence interval [CI] 1.4% to 3.1%), HDL-C <35 mg/dl (RR 1.5, 95% CI 1.1% to 2.00) and TGs >100 mg/dl (RR 1.5, 95% CI 1.1% to 2.1%). A Kaplan-Meier analysis revealed significantly reduced survival from CAD events in patients with baseline TG levels > or = 100 mg/dl compared with TG levels <100 mg/dl (p=0.008). CONCLUSIONS: TG levels previously considered "normal" are predictive of new CAD events. The cutpoints established by the National Cholesterol Education Program for elevated TGs (>200 mg/dl) may need to be refined.

Coronary Disease

Effects of peroxide on the fluorescence of the Ca2+ probe Fluo 3 and the pH probe BCECF.

Fluorescence probes are invaluable tools in monitoring intracellular ion concentrations. They have also been used for studying how reactive oxygen species alter these concentrations and yet there are no studies indicating how reactive oxygen species directly affect the characteristics of the probes. Our concern was that if reactive oxygen were to affect characteristics of these probes, these measurements would be inconsequential. Therefore, we examined the effects of peroxide on the Ca2+-sensitive dye Fluo 3 and the pH sensitive dye BCECF. Peroxide concentrations below 10 mM did not alter fluorescence or binding characteristics of either dye. Since the concentrations of peroxide used in most pathophysiological experiments are in the micromolar range, we conclude that these probes are appropriate for monitoring the effects of peroxide on intracellular ion concentrations.

Aniline Compounds

Determinants of rifabutin-associated uveitis in patients treated with rifabutin, clarithromycin, and ethambutol for Mycobacterium avium complex bacteremia: a multivariate analysis. Canadian HIV Trials Network Protocol 010 Study Group.

Uveitis occurred in a substantial proportion of AIDS patients receiving rifabutin, 600 mg daily, together with clarithromycin and ethambutol for treatment of Mycobacterium avium complex bacteremia. A case-control study was undertaken to examine potential risk factors for developing uveitis. Of eight parameters examined, only baseline body weight predicted the development of uveitis by both univariate and multivariate analyses (P = .001). The incidence of uveitis was 14% in patients weighing >65 kg, 45% in patients between 55 and 65 kg, and 64% in patients <55 kg. Concomitant therapy with fluconazole, a drug known to raise serum rifabutin concentrations, was not associated with an increased incidence of uveitis. The risk of uveitis was markedly reduced when rifabutin was given at 300 mg daily in combination with clarithromycin and ethambutol.

AIDS-Related Opportunistic Infections

An NCEP II diet reduces postprandial triacylglycerol in normocholesterolemic adults.

We compared the fasting and postprandial response to a National Cholesterol Education Program (NCEP) II diet with that of a diet high in total (40% of energy) and saturated fat. In free-living conditions, 17 healthy normolipidemic, normoglycemic men and women consumed a high-fat diet, a maintenance diet and the NCEP II diet, for 1 mo each. At the completion of each dietary period, an oral fat load (70 g/m2 body surface area) was administered and plasma triacylglycerol (TAG) determined every 2 h for 8 h. Compared with the high-fat phase, the NCEP II diet was associated with significantly lower energy intake (12.1 +/- 1.1 vs. 7 +/- 0.7 MJ/d) and final body weight (78 +/- 3.8 vs. 76.3 +/- 3.5 kg) (P < 0.01). Plasma high density lipoprotein cholesterol, apolipoprotein (apo) A-I and ApoB concentrations were also significantly lower when subjects consumed the NCEP II diet rather than the high-fat diet (P </= 0.004). There were no significant differences in subjects fasting TAG, glucose or insulin concentration between the high fat and NCEP II diet periods. However, the postprandial plasma TAG response to the fat load was lower after completing the NCEP II than after the high-fat diet period (P = 0.045). Under free-living conditions, a NCEP II diet was associated with weight loss and a decrease in postprandial but not fasting TAG. Because dietary alteration may not affect fasting TAG levels, thorough assessment of a dietary intervention should include measurements of postprandial TAG.

Adult

Inter-clinician agreement on clinical data abstracted from patients' medical charts.

PURPOSE: The purpose of this study was to determine the inter-observer repeatability of retrospective chart reviews. METHODS: Retrospective abstraction of corneal transplant patients' medical records by two independent observers was performed at the University of California, Davis, Department of Ophthalmology, Sacramento, CA. The sample consisted of 100 consecutive patients who underwent penetrating keratoplasty, and the primary outcome measure was the degree of agreement between the 2 independent observers on clinical ocular data abstracted from patients' medical charts. RESULTS: Even when given specific criteria for abstraction of data from patients' medical charts, inexperienced but trained observers exhibited a small degree of disagreement (range 0 to 12%) on patient demographic variables (e.g., gender, age, and date of birth) to be used for data analysis. Larger amounts of disagreement (range 3 to 26%) were found on frequently occurring variables (e.g., predisposing ocular conditions, surgical complications, and classification of corneal staining). CONCLUSIONS: Based on these data, inter-observer repeatability for retrospective chart review studies is good, but investigators using this study methodology must be quite specific about the data to be collected and should be aware of standardization techniques to enhance observer repeatability.

Abstracting and Indexing

Arginine vasopressin levels in nursing home residents with nighttime urinary incontinence.

OBJECTIVES: To examine the relationship between diurnal urine volume and plasma arginine vasopressin levels (AVP) in nursing home residents with nighttime urinary incontinence and a comparison group of frail but nondemented, continent geriatric board and care residents. DESIGN: Case series. SETTING: Four nursing homes and two board and care facilities. PARTICIPANTS: Sixty-two nursing home residents and 27 board and care residents. MEASUREMENTS: Daytime (7:00 a.m. to 7:00 p.m.) and nighttime (7:00 p.m. to 7:00 a.m.) urine volumes of incontinent nursing home residents were measured over 3 days and 3 nights by reweighing preweighed adults diapers and toileting inserts emptied by research staff for the comparison group. AVP levels were drawn in the early morning (5:00 a.m. to 7:00 a.m.) before subjects arose and in the evening after an hour of lying in bed (8:00 p.m. to 11:00 p.m.), and plasma levels were determined by radioimmunoassay. RESULTS: Half of the nursing home residents and 82% of the comparison group had night/total urine volume ratios > or = 50%. Forty-nine percent of the total of 89 subjects had undetectable morning AVP levels, 61% had undetectable evening AVP levels, and 42% had undetectable AVP levels in both morning and evening. There were no significant differences in AVP levels between those with night/total urine volume ratios > or = 50% and < 50% in either the nursing home or comparison groups though the small number of comparison group subjects with ratios < 50% may have limited our statistical power to detect differences. CONCLUSION: Our data suggest that a substantial proportion of both nursing home residents with nighttime incontinence and frail geriatric patients with a reversal of the normal diurnal pattern of urine excretion have an accompanying deficiency in AVP production and/or secretion. More detailed physiologic studies are needed to understand better the pathophysiology of geriatric nocturia and nighttime incontinence and the role that AVP deficiency may play in these conditions. Until such studies are carried out, we do not recommend the routine use of exogenous AVP for geriatric patients with unexplained nocturnal polyuria.

Aged

The use of fluorogenic substrates to measure fungal presence and activity in soil.

Our objective was to determine if 4-methylumbelliferyl-labelled enzyme substrates could be used to detect and quantify specific components of chitinase and cellulase activities as specific indicators of the presence and activity of fungal biomass. The fluorogenic substrates 4-methylumbelliferyl (MUF) N-acetyl-beta-D-glucosaminide and MUF beta-D-lactoside were used for the detection and quantification of beta-N-acetylglucosaminidase (EC 3.2.1.30) (NAGase) and endo 1,4-beta-glucanase (EC 3.2.1.4)/cellobiohydrolase (EC 3.2.1.91) (CELase), respectively. Culture screenings on solid media showed a widespread ability to produce NAGase among a taxonomically diverse selection of fungi on media with and without added chitin. NAGase activity was expressed only in a limited number of bacteria and on media supplemented with chitin. The CELase activity was observed only in a limited number of fungi and bacteria. Bacterial CELase activity was expressed on agar media containing a cellulose-derived substrate. In soil samples, NAGase activity was significantly correlated with estimates of fungal biomass, based on the content of two fungus-specific indicator molecules, 18:2 omega 6 phospholipid fatty acid (PLFA) and ergosterol. CELase activity was significantly correlated with the PLFA-based estimate of fungal biomass in the soil, but no correlation was found with ergosterol-based estimates of fungal biomass.

Acetylglucosaminidase

Actinobacillus actinomycetemcomitans leukotoxin induces apoptosis in HL-60 cells.

Actinobacillus actinomycetemcomitans leukotoxin (Ltx) is a member of the repeats-in-toxin (RTX) family of pore-forming toxins and kills human immune cells. Currently, it remains unclear whether toxin-mediated killing of target cells involves the induction of necrosis or apoptosis. Therefore, the goal of this investigation was to determine whether Ltx is capable of causing apoptotic cell death in toxin-sensitive promyelocytic HL-60 cells. Multiparameter flow cytometric analysis of toxin-treated cells stained with Hoechst 33258 (or 33342) and 7-aminoactinomycin D allowed us to identify four populations: viable cells, early apoptotic cells, late apoptotic and/or secondarily necrotic cells, and a final population that was composed of cellular debris. Compared with control cells, HL-60 cells treated with Ltx exhibited a gradual decrease in forward light scatter with a coincident increase in side light scatter, indicative of a decrease in cell size and organelle condensation, respectively. Additional experiments demonstrated that Ltx-treated cells showed evidence of internucleosomal DNA fragmentation and phosphatidylserine translocation. The results of our studies clearly demonstrate that Ltx can kill HL-60 cells by inducing apoptosis. We hypothesize that elimination of acute inflammatory cells via this mechanism plays a critical role in the pathogenesis of diseases caused by A. actinomycetemeomitans.

Aggregatibacter actinomycetemcomitans

Apolipoprotein A-I(Zavalla) (Leu159-->Pro): HDL cholesterol deficiency in a kindred associated with premature coronary artery disease.

We investigated the molecular defect causing high density lipoprotein cholesterol (HDL-C) deficiency in a male proband and his family members. Amplification and sequencing of genomic DNA disclosed a novel base-pair substitution at residue 159 in the apolipoprotein (apo) A-I gene. This substitution resulted in the loss of an AviII restriction site and a predicted substitution of leucine with proline at residue 159. Restriction enzyme analysis demonstrated absence of the AviII site in 19 of 40 biological family members. Compared with familial controls, subjects with the apoA-I(Zavalla) variant had reduced HDL-C (1.16 versus 0.27 mmol/L, P<0.0001), apoA-I (38.7 versus 124.4 mg/dL, P<0.0001), and apoA-II (14.3 versus 19.0 mg/dL, P<0.0001) levels. Two subjects who have developed coronary artery disease to date possess additional cardiovascular risk factors. Other heterozygotes for apoA-I(Zavalla) are presently without symptomatic coronary artery disease. This study identifies a monogenic cause of hypoalphalipoproteinemia, with the single base-pair substitution having a dominant effect on the low HDL-C phenotype. In addition, it extends recent observations that HDL-C deficiency states may be more prone to the development of premature coronary artery disease when accompanied by additional cardiovascular risk factors.

Adolescent

Learning with technology: use of case-based physical and computer simulations in professional education.

This presentation will clarify contemporary ideas on the role of technology in education and how it can be employed to improve student learning experiences and outcomes. The paper will emphasise RMIT's role in providing quality education that is relevant to today's world and professional practice. It will examine a specific collaborative (RMIT & ACU), interdisciplinary project 'Pregnancy Simulator: Developing and Enhancing Student Learning of Assessment Skills'. This project consist of a physical pregnancy model connected to a multi-media computer-assisted learning package for the purpose of enhancing student learning of abdominal assessment skills. Our paper outlines an innovative technology-based teaching project and includes current educational issues or problems encountered in professional education, steps already taken to address these difficulties and how this project intends to facilitate learning. It identifies expected learning outcomes for midwives, nurses and medical students, and examines pedagogical principles applied to technological applications designed to provide guided discovery for allowing students to build confidence and competence in professional education. The case-based physical and computer simulations contextualise learning to assist transfer of learning to real world situations. This paper will also discuss how technology-based projects can be evaluated and integrated into university curricula to enhance student learning.

Computer Simulation

Learning with technology: use of case-based physical and computer simulations in professional education.

This paper describes a multimedia technology project in midwifery education and how it is being developed to improve student learning experiences and outcomes. The role of the university providing quality education relevant to today's world and professional practice is emphasised. A collaborative (Royal Melbourne Institute of Technology and Australian Catholic University) interdisciplinary project 'Pregnancy Simulator: Developing and Enhancing Student Learning of Pregnancy Assessment Skills' was developed with university and direct Commonwealth support. This project consists of a physical simulation of a pregnant woman at term and case-based multimedia computer simulations designed to develop and enhance student learning of abdominal assessment skills. A key feature of the development has been to design a learning experience explicitly on an authoritative theory-based view of teaching, in this case Diana Laurillard's 'Conversational Framework'.

Computer Simulation

Hematomas and limb skeletal malformations in chicken embryos following exposure to 5-fluoro-2-deoxyuridine.

Vascular injury or interruption may play a role in vertebrate limb teratogenesis. Since 5-fluoro-2'-deoxyuridine (FdU) can cause vascular injury in the murine limb and skull prior to the appearance of skeletal malformations in these structures, we studied the effects of this chemical on skeletal development in the chick embryo and noted any vascular injury. The yolk sacs of day three chick embryos (Hamburger and Hamilton states 17-19) were injected with solutions of vary concentrations of FdU in saline. The embryos developed until the 10th day of incubation when they were fixed for study. Uninjected, saline injected, and sham injected control embryos were similarly fixed. Upon gross inspection, frequent diffuse and saccular hematomas, as well as fluid-filled blisters, were noted in the limbs of embryos treated with FdU. After the embryos were fixed and cleared, and the skeletons stained, significant skeletal malformations were observed in these limbs. Bony elements of both the upper and lower limbs were affected in at least some of the embryos. The combination of FdU-induced hematomas and blisters with associated skeletal malformations in the same regions of some embryos suggests a relationship between these phenomena.

Abnormalities, Drug-Induced

[Evaluation of diagnostic and therapeutic management in patients with bacteriologically negative pulmonary tuberculosis].

The study aimed at assessing the frequency and type of errors in the diagnosis and management of newly registered bacteriologically negative cases of pulmonary tuberculosis. Random sample of 560 out of 7272 such patients registered in 1993 was subject of detailed analysis of all available medical documentation. The analysis was performed by an independent team of three specialists: pulmonologist, radiologist and epidemiologist. The results of the analysis indicate insufficient utilization of modern available diagnostic methods. Apart from clinical assessment the main basis for diagnosis of tuberculosis was A-P radiography. Tomography examination was performed in 35.5% of patient only, bronchoscopic in 19.8% and cytologic examination of sputum in 15.9%. Bacteriological examinations during the first phase of diagnosis, usually in hospitals, were satisfactory. Error in diagnosis was found in 63 patients, i.e. 11.3% of cases. The treatment in patients considered as correctly diagnosed, was in the intensive phase correct, but in the continuation phase--too long.

Biopsy

Hyponatremia: age-related risk factors and therapy decisions.

Normal aging is accompanied by many changes in the regulatory systems that control sodium and water balance, as well as diminished capacity to withstand the challenges of illness, drugs, and physiologic stresses. Consequently, the older person is at an increased risk for clinically significant alterations in sodium and water balance, especially hyponatremia. Awareness of these risk factors allows the physician to anticipate the impact of illnesses and drugs on volume and electrolyte status of the older patient and to implement a rational approach to therapeutic intervention and management.

Acute Disease

The case study as a scientific method for researching alternative therapies.

This article argues that the case study design is a research method capable of providing valuable data and insight into alternative therapies. The background and roots of the case study in medicine and clinical practice are covered, and the status of the case study as a scientific method is examined. The highly regarded randomized controlled clinical trial--though often powerful and useful--is neither feasible nor ideal for understanding the effects of many unconventional treatment approaches. Given the complexity of the factors involved in unconventional therapeutic applications--health beliefs, changing health paradigms, patient/practitioner interactions, multiple treatment modalities, multiple symptom profiles--the case study approach offers an alternative methodological route for investigating and generating findings in this arena. Reliability and validity of data collection, data reduction, and interpretation can be enhanced through steps discussed in this article. As it continues to work with evidence that is currently unorganized, the field of alternative medicine can benefit both in clinical prowess and scientific stature from additional, carefully conducted case studies.

Complementary Therapies