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Biomedical subjects

M Miller

Publications and source records attributed to M Miller.

At least 289 records · Page 16Linked to original sources

Structural Analysis of Photosystem II: Comparative Study of Cyanobacterial and Higher Plant Photosystem II Complexes

Oxygen evolving photosystem II (PSII-OEC) complexes and PSII core complexes were isolated from spinach and the thermophilic cyanobacterium Synechococcus sp. OD24 and characterized by gel electrophoresis, immunoblotting, and absorbance spectroscopy. The mass of the core complexes was determined by scanning transmission electron microscopy (STEM) and found to be 281 ± 65 kDa for spinach and 313 ± 52 kDa for Synechococcus sp. OD24. The mass of the spinach PSII-OEC complex was 327 ± 64 kDa. Digital images of negatively stained PSII-OEC and PSII core complexes were recorded by STEM and analyzed by single particle averaging. All monomeric complexes showed similar morphologies and were of comparable length (14 nm) and width (10 nm). The averages revealed a pseudo-twofold symmetry axis, which is a prominent structural element of the monomeric form. Difference maps between the averaged projections of the oxygen evolving complexes and the core complexes from both species indicated where the 33-kDa extrinsic manganese stabilizing protein is bound. A symmetric organization of the PSII complex, with the PsbA and the PsbD proteins in the center and symmetrically arranged PsbB and PsbC proteins at the periphery of the monomeric complex, is proposed.

Journal Article↗

Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group.

A randomized trial was conducted to compare the efficacy and safety of fluconazole versus that of amphotericin B in the treatment of candidemia in non-neutropenic adults. Enrollment was stratified by disease severity (APACHE II score). Patients were randomized (1:1) to receive amphotericin B 0.6 mg/kg/day (cumulative dose 8 mg/kg) or fluconazole 800 mg intravenous loading dose, then 400 mg daily for four weeks (intravenous for at least 10 days). Patients were monitored for six months. A total of 106 patients were enrolled. A protocol amendment implemented midway through the trial required patients to be removed from the study and treated with amphotericin B if species identification indicated candidemia due to Candida glabrata or Candida krusei. Baseline characteristics were similar for the two groups; 103 patients (fluconazole, 50; amphotericin B, 53) met the major enrollment criteria. The intention-to-treat analysis indicated successful therapy in 50% of fluconazole recipients compared to 58% of the amphotericin B group (p = 0.39; one-sided 95% CI, -8 to 24%). The efficacy analysis included 84 patients (fluconazole, 42; amphotericin B, 42); successful outcomes were observed in 57% and 62% of cases in the fluconazole and amphotericin B groups, respectively (p = 0.66: one-sided 95% CI, -12 to 22%). The mortality at day 14 for the fluconazole group was 26% and for the amphotericin B group 21% (p = 0.52; chi-square test) and remained similar throughout the course of follow-up, Drug-related adverse events were more frequent with amphotericin B than with fluconazole and prompted switching of therapy for two (4%) and zero cases, respectively. Fluconazole and amphotericin B were associated with similar clinical response rates and survival in the treatment of candidemia among non-neutropenic patients; however, drug-related adverse events were more frequent with amphotericin B.

Adult↗

Multiple metabolic abnormalities in normal glucose tolerant relatives of NIDDM families.

Non-diabetic first degree relatives of non-insulin-dependent diabetic (NIDDM) families are at increased risk of developing diabetes mellitus, and have been studied to identify early metabolic abnormalities. Hormone concentrations measured by specific enzyme immunoassays were assessed in non-diabetic relatives of North European extraction, and control subjects with no family history of diabetes were matched for age, sex and ethnicity. A 75-g oral glucose tolerance test was conducted and those with newly diagnosed NIDDM were excluded. Basal insulin resistance was determined by homeostasis model assessment (HOMA), and hepatic insulin clearance by C-peptide:insulin molar ratio. Relatives (n = 150) were heavier (BMI: p < 0.0001) than the control subjects (n = 152), and had an increased prevalence of impaired glucose tolerance (15 vs 3%, p < 0.01). The relatives had increased fasting proinsulin levels and decreased C-peptide levels following the glucose load, while insulin levels were increased at all time points. To examine whether the differences in hormone levels were secondary to the differences in glucose tolerance and adiposity, we studied 100 normal glucose tolerant relatives and control subjects pair-matched for age, sex, waist-hip ratio and BMI. The differences in proinsulin levels were no longer apparent. However, the relatives remained more insulin resistant, and had decreased C-peptide levels and C-peptide:insulin ratios at all time points. In conclusion, we have identified several metabolic abnormalities in the normal glucose tolerant relatives, and propose that the decreased hepatic insulin clearance helps to maintain normoglycaemia in the face of combined insulin resistance and decreased insulin secretion.

Adult↗

Epidemic Bacillus endophthalmitis after cataract surgery I: acute presentation and outcome.

OBJECTIVE: The purpose of the study is to report the clinical outcome of acute Bacillus endophthalmitis after cataract surgery. DESIGN: The study design is a cohort study. PARTICIPANTS: Fourteen eyes of 14 patients with epidemic acute postoperative inflammation after exposure to bacteria-contaminated viscoelastic material were studied. INTERVENTION: Three patients with milder clinical presentations were treated without vitrectomy or antibiotics. Eleven patients with more severe infection were treated with vitrectomy as well as intravitreous and topical fortified antibiotics. MAIN OUTCOME MEASURES: Final visual acuities were obtained in all 14 study patients. Results of microbiologic studies of aqueous and vitreous specimens from 11 vitrectomized eyes also were analyzed. RESULTS: One patient with late presentation had severe inflammation and had phthisis bulbi develop with no light perception. The remaining 13 patients had successful resolution of inflammation after treatment by 1 month of follow-up. Twelve of these 13 patients, including 1 nonvitrectomized patient, had final visual acuities of 20/100 or better at 6 months' follow-up. Six patients, including two patients with nonvitrectomized eyes, had outcomes of 20/40 or better visual acuity. Bacillus species were grown from all 11 (100%) vitreous and 7 (88%) of 8 aqueous specimens obtained from vitrectomized patients, as well as from the contaminated viscoelastic material remaining in the operating room. CONCLUSIONS: Postoperative Bacillus endophthalmitis need not result in poor outcome. Results depend on factors including bacterial load, specific bacterial species, timing of treatment, and immune status of the patient.

Acute Disease↗

Fluid and electrolyte homeostasis in the elderly: physiological changes of ageing and clinical consequences.

Characteristic of the normal ageing process are changes in the renal, hormonal and thirst regulatory systems involved in the control of sodium and water balance. In the presence of disease or drug use, the ageing changes put the elderly person at increased risk of either sodium retention or loss and of water retention or loss. Clinically, these alterations in water and sodium balance are commonly expressed as either hyponatraemia or hypernatraemia with central nervous system dysfunction as the symptomatic expression. Thus, the impaired homeostasis of the many systems affecting fluid balance in the elderly is readily influenced by many of the disease states and medications which are often present in the elderly with resultant adverse clinical consequences. Awareness of these age-associated circumstances can allow the physician to anticipate the impact of illnesses and drugs and to implement a rational approach to therapeutic intervention and management.

Aged↗

Maintenance of employment on dialysis.

This article describes the components of a multidisciplinary effort focused on promoting, among other goals, continued employment during end-stage renal disease (ESRD) treatment. The education and guidance of the patient begin during the pre-ESRD period, intensify through dialysis treatment, and continue even through posttransplantation follow-up. Such focused programs support patients in retaining their usual lifestyle, staying in their current jobs where possible, and maximizing self-esteem and quality of life.

Employment↗

Myeloproliferative disease and myelodysplastic syndrome induced by transplantation of bone marrow cells expressing mutant p53.

p53 mutations are the most common genetic alterations observed in human cancers including lymphomas and leukemias. We have previously shown that transduction of normal murine hematopoietic cells with mutant p53 alone in vitro results in an enhanced proliferative capacity and modified differentiation potential of transduced cells. In order to investigate further the role of mutant p53 in hematopoietic cell transformation, mutant p53-transduced bone marrow cells were used to reconstitute the hematopoietic system of lethally irradiated mice. The results show that overexpression of mutant p53 can initiate the transformation of immature murine hematopoietic cells in vivo and induce two types of hematopoietic disorders, myeloproliferative disease and myelodysplastic syndrome.

Animals↗

Younger versus older gay men: risks, pleasures and dangers of anal sex.

This study reports on the practice and the pleasure and danger perceptions of protected and unprotected anal sex of young adult gay men (< or = 30) and older gay men (30+). It is assumed that, if prevention efforts were successful, younger gay men-sexually socialized during the AIDS era-should have more favourable perceptions of anal sex with a condom. Data from a cohort of gay men in Flanders, Belgium (1993, n = 553) are used in this analysis. The results indicate that younger gay men do not differ from older gay men in the riskiness/safety of their actual sexual behaviour. However, younger men hold different valuations regarding anal sex. They report a higher appraisal for both insertive and receptive anal sex with a condom. The perceived safety of protected anal sex is also higher among the younger men. We also found that younger men with a steady partner report more gratification from insertive anal sex with a condom than do older partnered men. We interpret these findings as evidence of the effectiveness of HIV prevention efforts.

Adolescent↗

An outbreak of Enterobacter hormaechei infection and colonization in an intensive care nursery.

Enterobacter hormaechei was first identified as a unique species in 1989. Between 29 November 1992 and 17 March 1993, an outbreak of E. hormaechei occurred among premature infants in the intensive care nursery (ICN) at The Hospital of the University of Pennsylvania. The 10 infants whose cultures were positive for E. hormaechei (six were infected and four were colonized) had a lower median estimated gestational age and birth weight than did other ICN infants; other risk factors for infection or colonization with E. hormaechei were not identified. Cultures from three isolettes and a doorknob in the ICN were positive for E. hormaechei. Pulsed-field gel electrophoresis of isolates from six patients and two isolettes were identical. Observations of health care workers revealed breaks in infection control techniques that may have allowed transmission of this organism. We found that E. hormaechei is a nosocomial pathogen that can infect vulnerable hospitalized patients and that can be transmitted from patient to patient when infection control techniques are inadequate.

Disease Outbreaks↗

Computer-assisted self-interviewing: a multimedia approach to dietary assessment.

Currently available dietary assessment tools have limited ability to obtain valid data within the resource constraints of large-scale studies. Many obstacles to gathering data can be overcome with computer-assisted self-interviewing (CASI). Computers can conduct personalized, in-depth interviews without interviewers; provide standardized data collection with appropriate levels of probing; automate data entry; encourage subjects to review and correct inconsistent data; and ensure that responses are complete. Interactive multimedia tools can motivate subjects and improve participation. Visual and aural cues may stimulate recall and improve data quality. CASI is appropriate for use in populations in which literacy is low and in multiple ethnic groups. A prototype CASI diet-history program was developed for use in the United States. The diet-history approach was selected to improve cognitive support and capture information on usual diet. Scripts were based on recorded interviews with dietitians and interviewers from the National Health and Nutrition Examination Survey. At the end of the interview, participants are given information on how their reported nutrient intakes compare with current recommendations for their age and sex. The prototype was tested in focus groups of mixed age, sex, ethnicity, and education, with encouraging results. The development of multimedia-based dietary assessment tools seems a logical next step in improving dietary assessment methods.

Computers↗

Benzo[a]pyrene coated ferric oxide and aluminum oxide particles: uptake, metabolism and DNA binding in hamster pulmonary alveolar macrophages and tracheal epithelial cells in vitro.

Ferric oxide (Fe2O3) and aluminum oxide (Al2O3) particles are widely encountered in occupational settings. Benzo[a]pyrene (B[a]P), a well-characterized environmental carcinogen, is frequently adsorbed onto particles. It has been shown that B[a]P-coated Fe2O3 particles (B[a]P-Fe2O3) significantly increased lung tumors in the hamster in contrast to B[a]P-coated Al2O3 (B[a]P-Al2O3) or B[a]P alone. In order to determine the genotoxic effects of these particles on the metabolism of B[a]P, pulmonary alveolar macrophages (AM) from male Syrian golden hamsters were incubated with 5 microg (19.8 nmol) B[a]P-coated respirable size (99% < 5 microm) Fe2O3 and Al2O3 particles with loads from 0.5 to 2.0 mg. Intracellular uptake of B[a]P by AM at 24 h was higher with B[a]P-Fe2O3 than that of B[a]P alone (P < 0.05) or B[a]P-Al2O3 (P < 0.05). Total B[a]P metabolism was significantly greater in AM exposed to B[a]P-coated Fe2O3 at 1.0 and 1.5 mg than in the AM exposed to B[a]p-al2O3 (0.5, 1.0 and 1.5 mg) (P < 0.05) or B[a]P alone (P < 0.05). Similar significant differences for Fe2O3 relative to Al2O3 and B[a]P alone were also apparent for total dihydrodiols, quinones and phenolic metabolites. Co-administration of 5 microg alpha-naphthoflavone (alpha-NF, an inhibitor of cytochrome P-4501A1 and P-4501A2) and 10(-3) M cyclohexene oxide (CO, an inhibitor of epoxide hydrolase) significantly reduced B[a]P metabolism in B[a]P-Fe2O3 (P < 0.05) and B[a]P-Al2O3 (P < 0.05) treated groups relative to B[a]P alone. AM were co-cultured with hamster tracheal epithelial cells (HTE) and treated as described above for metabolism studies to assess the DNA binding of B[a]P metabolites in the target cells, using 32P-postlabeling techniques. Two adducts were observed that had chromatographic behavior similar to 7R,8S,9S-trihydroxy-10R-(N2-deoxyguanosyl-3'-phosphate)-7,8,9,10-t etrahydrobenzo[a]pyrene [(+)-anti-BPDE-dG, adduct 1, major adduct representing 70-80% of total adducts] and 7S,8R,9R-trihydroxy-10S-(N2-deoxyguanosyl-3'-phosphate)-7,8,9,10-t etrahydrobenzo[a]pyrene [(-)-anti-BPDE-dG, adduct 2, representing 20-30% of total adducts]. B[a]P-Fe2O3 treatment enhanced the levels of the two B[a]P-DNA adducts in the HTE compared with B[a]P-Al2O3 (P < 0.05) or B[a]P alone. The inhibitors alphaNF and CO significantly reduced total adduct levels in the HTE (P < 0.05) in the B[a]P and B[a]P-Fe2O3 treatments as well as adduct 1 and adduct 2 levels. Our data suggest that the cocarcinogenic effect of B[a]P-Fe2O3 relative to B[a]P-coated Al2O3 can be due to: (i) the enhancement of B[a]P metabolism in AM by Fe2O3 associated with the increased uptake of B[a]P; and (ii) augmentation of DNA adduct formation in epithelial cells.

Aluminum Oxide↗

Ethanol endovascular management of brain arteriovenous malformations: initial results.

OBJECTIVE: The goal was to determine the safety and efficacy of absolute ethyl alcohol treatment in the management of intra-axial brain arteriovenous malformations (AVMs). METHODS: Seventeen patients (eight female and nine male patients; mean age, 41 yr) underwent ethanol endovascular therapy for treatment of their brain AVMs. Superselective amytal testing preceded all procedures. Neuroleptic intravenous anesthesia was used for 16 patients, and general anesthesia was used for 1 patient. Follow-up monitoring consisted of clinical evaluations, magnetic resonance imaging, and arteriography. RESULTS: In follow-up evaluations (mean follow-up period, 13 mo) after embolization of brain AVMs, neither vascular recanalization nor the neovascular recruitment phenomenon was observed in any patient. Progressive AVM thrombosis at arteriographic follow-up evaluation was a constant feature. Seven patients were cured of their AVMs with ethanol endovascular therapy alone. Three patients were cured of their lesions with ethanol embolization plus surgical resection. One patient was cured of his lesion with ethanol embolization and radiation therapy of the residual nidus. Three patients underwent only partial therapy, with significant improvement in symptoms. Three patients are currently undergoing ethanol endovascular therapy. Complications occurred with 8 of 17 patients, most of which were transient. Two patients died because of late subarachnoid hemorrhages, one patient 4 months and one patient 14 months after partial therapy. CONCLUSION: Progressive and permanent AVM occlusion is a common finding in arteriographic follow-up evaluations. In no patients did arterial recanalization or the neovascular recruitment phenomenon occur. Our initial results indicate that ethanol has a permanence that is seldom encountered with other embolic agents. With aggressive decadron therapy, the complications related to swelling in the brain are largely reversible.

Adult↗

Fellowship training.

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Fellowships and Scholarships↗

The effects of physician in-migration to rural Colorado (1992 to 1995).

This paper reports the results of an analysis of the American Medical Association Masterfile. The purpose of this study was to examine changes in health care accessibility in rural Colorado from 1992 to 1995, and to describe the pattern of in-migration of physicians to nonmetropolitan statistical area counties of the state during that period. The number of direct patient care providers increased from 532 to 700 (31.6%) during the three-year period vs. a growth of 11.2 percent in the general population of nonmetropolitan statistical area counties. Of the 700 physicians serving residents of Colorado's 52 rural counties, 308 (44%) had been practicing in their community since 1992. The rate of departure from nonmetropolitan statistical area practice sites in 1992 was 26.4 percent (140 of 532). Physicians new to their rural practice locations were younger and proportionally more female, but they were similar in primary medical specialty to doctors who had remained in their 1992 sites. Population to physician and to primary care physician ratios were much more favorable for 1995 than for 1992. Accessibility to care was most improved in counties with fewer than 10,000 inhabitants.

American Medical Association↗

Statistical methods in computational anatomy.

This paper reviews recent developments by the Washington/Brown groups for the study of anatomical shape in the emerging new discipline of computational anatomy. Parametric representations of anatomical variation for computational anatomy are reviewed, restricted to the assumption of small deformations. The generation of covariance operators for probabilistic measures of anatomical variation on coordinatized submanifolds is formulated as an empirical procedure. Populations of brains are mapped to common coordinate systems, from which template coordinate systems are constructed which are closest to the population of anatomies in a minimum distance sense. Variation of several one-, two- and three-dimensional manifolds, i.e. sulci, surfaces and brain volumes are examined via Gaussian measures with mean and covariances estimated directly from maps of templates to targets. Methods are presented for estimating the covariances of vector fields from a family of empirically generated maps, posed as generalized spectrum estimation indexed over the submanifolds. Covariance estimation is made parametric, analogous to autoregressive modelling, by introducing small deformation linear operators for constraining the spectrum of the fields.

Algorithms↗