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Biomedical subjects

David Miller

Publications and source records attributed to David Miller.

54 records · Page 3Linked to original sources
PubMed2003

Influence of thrombolytic therapy, with or without intra-aortic balloon counterpulsation, on 12-month survival in the SHOCK trial.

BACKGROUND: The enhancement of diastolic coronary blood flow by the combination of thrombolytic therapy (TT) and intra-aortic balloon counterpulsation (IABP) in experimental studies provides a rationale for their combined use in acute myocardial infarction (MI) complicated by cardiogenic shock. We examined the relation between TT (with and without IABP) and 12-month survival in the SHould We Emergently Revascularize Occluded Coronaries for Cardiogenic ShocK (SHOCK) Trial. METHODS AND RESULTS: Among 302 patients with myocardial infarction and cardiogenic shock who were randomized in the SHOCK Trial, 16 had absolute contraindications to TT. Among 150 patients randomly assigned to initial medical stabilization (IMS), 63% received TT, as recommended per protocol, compared with 49% of 152 patients randomly assigned to emergency revascularization, in whom TT was not recommended if immediate angiography was available. IABP deployment, which was protocol-recommended, was used in 86% of patients. The rate of severe bleeding was similar in patients receiving TT and in those not receiving TT (31% vs 26%, P =.37). Among patients randomly assigned to IMS, TT was associated with improved 12-month survival (unadjusted mortality hazard ratio, 0.59; P =.01; mortality hazard ratio adjusted for age and prior MI, 0.62; P =.02). TT was not associated with improved 12-month survival among patients randomly assigned to emergency revascularization (unadjusted mortality hazard ratio, 0.93; P =.76; mortality hazard ratio adjusted for age and prior MI, 1.06, P =.81). The test for interaction of TT and randomization group P value was.16, and there was insufficient statistical power to demonstrate a differential effect of TT on 12-month survival by treatment group assignment. CONCLUSIONS: Among patients randomly assigned to IMS in the SHOCK Trial, TT was associated with improved 12-month survival and did not significantly increase the risk of severe bleeding.

Aged↗
PubMed2003

A rapid method for determining recent sunscreen use in field studies.

The role of sunscreens in preventing skin cancer and melanoma is the focus of ongoing research. Currently, there is no objective measure which can be used in field studies to determine whether a person has applied sunscreen to their skin, and researchers must use indirect assessments such as questionnaires. We sought to develop a rapid, non-invasive method for identifying sunscreen on the skin for use in epidemiological studies. Our basic method is to swab the skin, elute any residues which have been adsorbed onto the swab by rinsing in ethanol, and submit the eluted washings for spectrophotometric analysis. In a controlled study, we applied 0.1 ml of sunscreen to a 50 cm(2) grid on both forearms of 21 volunteers. Each forearm was allocated one of 10 different sunscreen brands. The skin was swabbed after intervals of 20 min, 1 h, 2 h and 4 h. In a field study conducted among 12 children aged 2-4 years attending a child care centre, sunscreen was applied to the faces of half the children. Swabs were then taken from the face and back of all children without knowledge of sunscreen status. In the controlled study, sunscreen was clearly detectable up to 2 h after application for all brands containing organic sunscreen, and marginally detectable at 4 h. In the field study, this method correctly identified all children with and without sunscreen. We conclude that spectrophotometric analysis of skin swabs can reliably detect the presence of sunscreen on the skin for up to 2 h after application.

Adult↗
PubMed2003

Purification and characterization of recombinant Streptomyces griseus aminopeptidase.

Recombinant Streptomyces griseus aminopeptidase (SGAP) was produced using Cangene's expression system, CANGENUS. This heat-stable aminopeptidase with an N-terminal Ala-Pro-Asp-Ile-Pro-Leu-Ala-Asn-Val-Lys-Ala sequence was purified from 16L of Streptomyces lividans fermentation supernatant with high purity and 19.5% recovery rate. This was achieved by the combination of hydrophobic-interaction and size-exclusion chromatographic procedures. The calcium-activated zinc metalloprotein demonstrated no loss of activity at -20 degrees C for at least 8 weeks in both liquid and freeze-dried formulations. The recombinant SGAP showed an apparent molecular mass of 31 kDa by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and 26.8 kDa by gel filtration. The simple, high-yield, inexpensive purification method with few intermediate steps provides a novel and practical procedure for large-scale production of active recombinant S. griseus aminopeptidase.

Aminopeptidases↗
PubMed2003

Spinal-cord MRI in multiple sclerosis.

The potential of MRI of the spinal cord as a diagnostic tool in MS has recently gained much interest. Dual echo spin echo MRI is most sensitive for the detection of spinal-cord abnormalities, which range from multiple focal lesions to confluent areas of high signal intensity. In some patients, commonly those with primary progressive disease, diffuse areas of slightly increased signal intensity are found. Disappointingly, the relation between MRI findings and clinical disability is weak. Studies relating MRI findings with histopathology have revealed substantial axonal loss in the spinal cords of patients with MS, whether focal lesions are present of not. Further, diffuse cord atrophy is found in advanced MS, which may reflect axonal loss. In the diagnostic setting, spinal-cord imaging is valuable. First, asymptomatic spinal-cord lesions are very rare in disorders other than MS. For example, in a patient with equivocal brain findings such as an elderly patient with vascular-ischaemic lesions, a normal spinal-cord examination can help rule out MS. Second, presence of asymptomatic spinal lesions may help confirm a diagnosis of MS when few or no brain lesions are present.

Adult↗
PubMed2003

A field investigation of Bacillus anthracis contamination of U.S. Department of Agriculture and other Washington, D.C., buildings during the anthrax attack of October 2001.

In response to a bioterrorism attack in the Washington, D.C., area in October 2001, a mobile laboratory (ML) was set up in the city to conduct rapid molecular tests on environmental samples for the presence of Bacillus anthracis spores and to route samples for further culture analysis. The ML contained class I laminar-flow hoods, a portable autoclave, two portable real-time PCR devices (Ruggedized Advanced Pathogen Identification Device [RAPID]), and miscellaneous supplies and equipment to process samples. Envelopes and swab and air samples collected from 30 locations in the metropolitan area once every three days were subjected to visual examination and DNA extraction, followed by real-time PCR using freeze-dried, fluorescent-probe-based reagents. Surface swabs and air samples were also cultured for B. anthracis at the National Veterinary Service Laboratory (NVSL) in Ames, Iowa. From 24 October 2001 to 15 September 2002, 2,092 pieces of mail were examined, 405 real-time PCR assays were performed (comprising 4,639 samples), and at the NVSL 6,275 samples were subjected to over 18,000 platings. None of the PCR assays on DNA extracted from swab and air samples were positive, but viable spores were cultured from surface swabs taken from six locations in the metropolitan area in October, November, and December 2001 and February, March, and May 2002. DNA extracted from these suspected B. anthracis colonies was positive by real-time and conventional PCRs for the lethal factor, pXO1, and for capA and vrr genes; sequence analysis of the latter amplicons indicated >99% homology with the Ames, vollum, B6273-93, C93022281, and W-21 strains of B. anthracis, suggesting they arose from cross-contamination during the attack through the mail. The RAPID-based PCR analysis provided fast confirmation of suspect colonies from an overnight incubation on agar plates.

Anthrax↗
PubMed2002

Spermatozoal RNA profiles of normal fertile men.

BACKGROUND: Findings from several studies support the conclusion that spermatozoa contain a complex repertoire of mRNAs. Even though these mRNAs are thought to provide an insight into past events of spermatogenesis, their complexity and function have yet to be established. Our aim was to determine whether we could use spermatozoal mRNAs to generate a genetic fingerprint of normal fertile men. METHODS: We used a suite of microarrays containing 27016 unique expressed sequence tags (ESTs) to investigate cDNAs from a pool of 19 testes, cDNAs from a pool of nine individual ejaculate spermatozoal mRNAs, and cDNAs constructed from spermatozoal mRNAs from a single ejaculate. We also used ontological data mining to determine the function of the genes identified in each EST profile. FINDINGS: The cDNAs from the testes, pooled ejaculate, and single ejaculate hybridised to 7157, 3281, and 2780 ESTs, respectively. The testicular population contained all of the ESTs identified by the cDNAs from the pooled and individual ejaculate. The pooled ejaculate population contained all but four ESTs identified from the individual ejaculate. A subset of the spermatozoal mRNAs was associated with embryo development. INTERPRETATION: The microarray data from testes and spermatozoa (pooled and individual) were concordant, supporting the view that a spermatozoal mRNA fingerprint can be obtained from normal fertile men. Thus, profiling can be used to monitor past events-ie, gene expression of spermatogenesis. Moreover, the data suggest that, in addition to delivering the paternal genome, spermatozoa provide the zygote with a unique suite of paternal mRNAs. Ejaculate spermatozoa can now be used as a non-invasive proxy for investigations of testis-specific infertility.

Adolescent↗
PubMed2002

The serpin SQN-5 is a dual mechanistic-class inhibitor of serine and cysteine proteinases.

SQN-5 is a mouse serpin that is highly similar to the human serpins SCCA1 (SERPINB3) and SCCA2 (SERPINB4). Previous studies characterizing the biochemical activity of SQN-5 showed that this serpin, like SCCA2, inhibited the chymotrypsin-like enzymes mast cell chymase and cathepsin G. Using an expanded panel of papain-like cysteine proteinases, we now show that SQN-5, like SCCA1, inhibited cathepsins K, L, S, and V but not cathepsin B or H. These interactions were characterized by stoichiometries of inhibition that were nearly 1:1 and second-order rate constants of >10(4) M(-1) s(-1). Reactive site loop (RSL) cleavage analysis showed that SQN-5 employed different reactive centers to neutralize the serine and cysteine proteinases. To our knowledge, this is the first serpin that serves as a dual inhibitor of both chymotrypsin-like serine and the papain-like cysteine proteinases by employing an RSL-dependent inhibitory mechanism. The ability of serpins to inhibit both serine and/or papain-like cysteine proteinases may not be a recent event in mammalian evolution. Phylogenetic studies suggested that the SCCA and SQN genes evolved from a common ancestor approximately 250-280 million years ago. When the fact that mammals and birds diverged approximately 310 million years ago is considered, an ancestral SCCA/SQN-like serpin with dual inhibitory activity may be present in many mammalian genomes.

Amino Acid Sequence↗
PubMed2002

Comparison of detrending methods for optimal fMRI preprocessing.

Because of the inherently low signal to noise ratio (SNR) of fMRI data, removal of low frequency signal intensity drift is an important preprocessing step, particularly in those brain regions that weakly activate. Two known sources of drift are noise from the MR scanner and aliasing of physiological pulsations. However, the amount and direction of drift is difficult to predict, even between neighboring voxels. Further, there is no concensus on an optimal baseline drift removal algorithm. In this paper, five voxel-based detrending techniques were compared to each other and an auto-detrending algorithm, which automatically selected the optimal method for a given voxel time-series. For a significance level of P < 10(-6), linear and quadratic detrending moderately increased the percentage of activated voxels. Cubic detrending decreased activation, while a wavelet approach increased or decreased activation, depending on the dataset. Spline detrending was the best single algorithm. However, auto-detrending (selecting the best algorithm or none, if detrending is not useful) appears to be the most judicious choice, particularly for analyzing fMRI data with weak activations in the presence of baseline drift.

Adult↗
PubMed2002

Brain activation during smooth-pursuit eye movements.

A potential application of studying eye movements with functional MRI (fMRI) is to examine patient populations with known eye movement dysfunction, but the reliability with which normal subjects demonstrate activity in specific brain regions has not been established. To date, fMRI studies of smooth-pursuit eye movements have used relatively small numbers of subjects and have been restricted to fixed-effects analyses. We extend these studies to whole brain imaging at 1.5 T, properly accounting for intersubject variation using random effects analysis. Smooth-pursuit eye movements elicited activation consistently in dorsal cortical eye fields and cerebellum. Subcortical activation was greatly attenuated, but not eliminated, with the random-effects second-level analysis. In addition, session-dependent changes in activation were greater in some regions than others and may indicate areas of brain, such as the supplementary eye fields, that are sensitive to attentional modulation of eye movements.

Adult↗
PubMed2002

Gene-drug interaction: additive influence of mutant APOA1 and testosterone on plasma HDL-cholesterol.

OBJECTIVES: Factors associated with decreased plasma high-density lipoprotein (HDL) cholesterol concentration, or hypoalphalipoproteinemia, include androgenic steroids and mutations in APOA1, encoding apolipoprotein (apo) A-I, the main structural protein of HDL. However, there is little information regarding the extent of plasma HDL lowering when exogenous testosterone is used in subjects with monogenic low HDL. DESIGN AND METHODS: A man with coronary heart disease (CHD) had been receiving exogenous testosterone post-orchidectomy. He had marked hypoalphalipoproteinemia, which was not responsive to diet or medication. To identify a possible genetic contribution to his biochemical phenotype, we sequenced the LCAT and APOA1 genes. RESULTS: There were no sequence abnormalities in LCAT, but we found that he was a heterozygote for a novel APOA1 mutation in codon 107 (AAG->TGG), which predicted the replacement of lysine by tryptophan (K107W). Serial biochemical measurements over 11 years showed that plasma HDL cholesterol on either intramuscular or oral testosterone was 0.19 +/- 0.06 mmol/L, while plasma HDL cholesterol on transdermal testosterone was significantly higher at 0.52 +/- 0.18 mmol/L (p = 0.015, unpaired t-test). CONCLUSIONS: The findings suggest that the low plasma HDL cholesterol associated with heterozygosity for mutant APOA1 can become extremely depressed during treatment with oral or intramuscular androgens. The findings also suggest that transdermal testosterone may perturb HDL to a lesser extent than other routes of delivery in such patients.

Aged↗
PubMed2002

Changes in human knee ligament stiffness secondary to osteoarthritis.

Stiffness of the medial (MCL) and lateral (LCL) collateral ligaments was compared between a group of 10 patients undergoing total knee arthroplasty for varus degenerative osteoarthritis (OAP), a group of 10 osteoarthritic cadaveric knees (OAC), and a group of 10 non-osteoarthritic cadaveric knees (NOA). A load-elongation curve was obtained for the medial and lateral compartments of each knee using an instrumented Moreland spreader. A strain gage (SG) was attached to the spreader handle and strain was calibrated to load applied against the spread distance. In extension, medial compartment stiffness of the OAP, OAC, and NOA groups was 60.7+/-16, 52.8+/-9.3 and 21.4+/-5.0 N/mm, respectively. Lateral compartment stiffness in extension was 29.2+/-9.2, 33.3+/-10.3 and 19.5+/-5.3 N/mm, for OAP, OAC, and NOA, respectively. Differences in stiffness between the OAP and OAC groups were not statistically significant (p > 0.05). However, the osteoarthritic groups (OAP and OAC) demonstrated a statistically significantly (p < 0.05) increase in ligament stiffness when compared to the NOA group. Following knee arthroplasty, stiffer medial structures in extension may lead to flexion contracture and accelerated polyethylene wear. Adequate bone resection, in conjunction with soft tissue release may alleviate the threefold increase in stiffness observed in the medial compartment secondary to OA without jeopardizing joint stability.

Aged↗
PubMed2002

Ergonomic program effectiveness: ergonomic and medical intervention.

The implementation of a successful ergonomic and medical intervention program designed to reduce the number and severity of injuries and illnesses and the associated levels of discomfort in the workplace is presented. Because of the recent activity concerning the on-again-off-again Occupational Safety and Health Administration (OSHA) Ergonomic Program Standard questions have been raised as to the value and effectiveness of an organization's ergonomics program. In light of these concerns, the immense cost associated with work-related injury and illness, and the related pain and suffering associated with such injuries and illnesses, it is important to present a workable and effective ergonomic and medical intervention program. The results of this applied study demonstrate that through the application of an ergonomic and medical intervention program, workplace-related injuries and illnesses can be reduced or eliminated.

Ergonomics↗
PubMed1995

Cloning of a Candida albicans peptide transport gene.

A Candida albicans peptide transport gene, CaPTR2, was cloned from a C. albicans genomic library by functional complementation of a peptide transport deficient mutant (strain ptr2-2) of Saccharomyces cerevisiae. CaPTR2 restored peptide transport to transformants as determined by uptake of radiolabelled dileucine, growth on dipeptides as sources of required amino acids, and restoration of growth inhibition by toxic peptides. Plasmid curing experiments demonstrated that the peptide transport phenotype was plasmid borne. CaPTR2 was localized to chromosome R of C. albicans by contour-clamped homologous electric field gel chromosome blots. Deletion subclones and frameshift mutagenesis were used to narrow the peptide transport complementing region to a 5.1 kb DNA fragment. DNA sequencing of the complementing region identified an ORF of 1869 bp containing an 84 nucleotide intron. The deduced amino acid sequence predicts a protein of 70 kDa consisting of 623 amino acids with 12 hydrophobic segments. A high level of identity was found between the predicted protein and peptide transport proteins of S. cerevisiae and Arabidopsis thaliana. This study represents the first steps in the genetic characterization of peptide transport in C. albicans and initiates a molecular approach for the study of drug delivery against this pathogen.

Amino Acid Sequence↗
PubMedDate not supplied

Regulatory issues for health-related quality of life--PhRMA Health Outcomes Committee workshop, 1999.

INTRODUCTION: Health-related quality-of-life (HRQL) can be defined as the impact of disease and treatment across the physical, psychological, social and somatic domains of functioning and well-being. Health-related quality-of-life measures are included in clinical trials of drug treatment to assess the impact of therapy on the patient's functioning. HRQL guidance could allow for use of this data in drug labeling and promotion. OBJECTIVES: The aim of our study was to provide recommendations with respect to regulatory issues important to the development of guidelines for HRQL research. METHODS: The HRQL workshop was planned jointly by members of the Pharmaceutical Research and Manufacturers of America Health Outcomes Committee and the Division of Drug Marketing, Advertising, and Communications of the Food and Drug Administration. The workshop was limited to six regulatory issues related to HRQL research in clinical trials of pharmaceutical therapies. These six issues were: instrument selection and validation, study design, data analysis, HRQL and safety, clinical meaning, and promotional use. Before the meeting, a consensus was reached that HRQL does not measure, nor should it be used to measure, safety. Therefore, five work groups discussed HRQL issues and made recommendations. RESULTS: Overall, the workshop recommended that HRQL measures be treated as any other clinical end point. The workshop recognized that research in HRQL methods is ongoing and that any guidance should be flexible to allow for changes in this developing research area. CONCLUSIONS: HRQL provides a patient perspective on the impact of disease and therapy on patients' daily life and functioning. Including HRQL information in promotion could be beneficial to decision making on the use of therapies. HRQL is a measure of effectiveness, not safety, and should be treated as any other clinical end point.

Clinical Trials as Topic↗
PubMedDate not supplied

Effect of sharp debridement using curette on recalcitrant nonhealing venous leg ulcers: a concurrently controlled, prospective cohort study.

The objective of this study was to evaluate the effect of sharp debridement on the progression of recalcitrant chronic venous leg ulcers (CVLU) and to assess the feasibility of performing this procedure in an outpatient setting. We performed a prospective study of 55 CVLU (53 patients) over a 12-month period. The study group, which underwent debridement, contained 28 CVLU whose wound beds had slough, nonviable tissue, and no granulation tissue. The control group was 27 CVLU with minimal (15-20%) granulation tissue, but no slough or nonviable tissue. Treatments were otherwise similar. Age, body mass index, mean ulcer surface area (MSA) and mean ulcer duration were comparable in both groups. Ulcer measurements were taken at 4 weeks before debridement, at the time of debridement, and 4 and 20 weeks post-debridement. There was no change in the MSA from 4 weeks before to the time of debridement in either group. At 4 weeks post-debridement, the study ulcers showed a 6 cm(2) reduction in the MSA vs. a 1 cm(2) reduction in controls (P = 0.02). By week 20 post-debridement, the study ulcers achieved a 7.4 cm(2) reduction in the MSA vs. an increase of 1.3 cm(2) in controls (P = 0.008). Between weeks 8 and 20 post-debridement, 16% of study ulcers vs. 4.3% of control ulcers achieved complete healing. Infection rates and antimicrobial usage were similar. We conclude that sharp debridement is effective in stimulating healing of recalcitrant CVLU. It is safe, well tolerated, and can be performed in an outpatient setting.

Aged↗
PubMedDate not supplied

Comparison of ante- and post-mortem PSA levels for epidemiological studies.

BACKGROUND: Valuable correlations could be made between serum prostate specific antigen (PSA) and prostate histopathology by the use of autopsy sampling if post-mortem PSA data were informative. However, PSA forms and levels in autopsy sera have not been investigated. MATERIALS AND METHODS: Paired ante- and post-mortem sera were collected for a series of cases. Total and free PSA levels in each were determined and compared. These PSA data were correlated with corresponding changes in serum electrolyte levels. RESULTS: Total PSA levels were similar in ante- and post-mortem sera if autopsy blood was drawn by approximately 24 hours following the time of death. Free PSA levels, however, were increased approximately two-fold in most post-mortem sera analyzed. Increases in the serum electrolytes potassium, magnesium and phosphate correlated positively with increases in free PSA. CONCLUSION: Total PSA levels in ante- and post-mortem sera were comparable. Free PSA levels had approximately doubled by autopsy, but may be normalized in relation to increases in serum electrolyte levels. The use of autopsy prostates and PSA data would avoid diagnostic bias from use of clinical material and permit extensive analysis to be carried out, which is not normally feasible with live subjects.

Aged↗