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Biomedical subjects

L Anderson

Publications and source records attributed to L Anderson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Health effects of depleted uranium on exposed Gulf War veterans.

A small group of Gulf War veterans possess retained fragments of depleted uranium (DU) shrapnel, the long-term health consequences of which are undetermined. We evaluated the clinical health effects of DU exposure in Gulf War veterans compared with nonexposed Gulf War veterans. History and follow-up medical examination were performed on 29 exposed veterans and 38 nonexposed veterans. Outcome measures employed were urinary uranium determinations, clinical laboratory values, and psychiatric and neurocognitive assessment. DU-exposed Gulf War veterans with retained metal shrapnel fragments are excreting elevated levels of urinary uranium 7 years after first exposure (range 0.01-30.7 microg/g creatinine vs 0.01- 0.05 microg/g creatinine in the nonexposed). The persistence of the elevated urine uranium suggests on-going mobilization from a storage depot which results in a chronic systemic exposure. Adverse effects in the kidney, a presumed target organ, are not present at this time, though other effects are observed. Neurocognitive examinations demonstrated a statistical relationship between urine uranium levels and lowered performance on computerized tests assessing performance efficiency. Elevated urinary uranium was statistically related to a high prolactin level (>1.6 ng/ml; P=0.04). More than 7 years after first exposure, DU-exposed Gulf War veterans with retained metal fragments continue to excrete elevated concentrations of urinary uranium. Effects related to this are subtle perturbations in the reproductive and central nervous systems.

Adult↗
PubMed2000

Rapid molecular epidemiologic studies of human parainfluenza viruses based on direct sequencing of amplified DNA from a multiplex RT-PCR assay.

Sequencing studies of limited regions of the human parainfluenza viruses (HPIVs) genomes have helped describe patterns of virus circulation and characterize institutional outbreaks of HPIVs-associated respiratory illness. In this study, we sequenced reverse transcription polymerase chain reaction (RT-PCR)-amplified HPIVs RNA obtained from a multiplex RT-PCR assay described previously for simultaneous detection of HPIV-1, 2 and 3. Differences in the nucleotide sequences of limited regions of the HN gene allowed us to distinguish temporally and geographically diverse HPIV isolates (43 HPIV-1, 7 HPIV-2, 12 HPIV-3 isolates from this and previously published studies). In addition, an outbreak of HPIV-3-associated illness among infants on a pediatric ward was investigated by comparing sequences of three ward isolates with three matched community controls. Sequences of all ward isolates were identical and differed from those of the community controls, suggesting a single introduction and nosocomial transmission of the virus. Combining multiplex reverse transcription polymerase chain reaction (RT-PCR) assays with direct sequencing of the PCR products can provide an integrated system for rapid diagnosis and characterization of HPIVs.

Child↗
PubMed2000

Developing an evidence-based Guide to Community Preventive Services--methods. The Task Force on Community Preventive Services.

Systematic reviews and evidence-based recommendations are increasingly important for decision making in health and medicine. Over the past 20 years, information on the science of synthesizing research results has exploded. However, some approaches to systematic reviews of the effectiveness of clinical preventive services and medical care may be less appropriate for evaluating population-based interventions. Furthermore, methods for linking evidence to recommendations are less well developed than methods for synthesizing evidence. The Guide to Community Preventive Services: Systematic Reviews and Evidence-Based Recommendations (the Guide) will evaluate and make recommendations on population-based and public health interventions. This paper provides an overview of the Guide's process to systematically review evidence and translate that evidence into recommendations. The Guide reviews evidence on effectiveness, the applicability of effectiveness data, (i.e., the extent to which available effectiveness data is thought to apply to additional populations and settings), the intervention's other effects (i.e., important side effects), economic impact, and barriers to implementation of interventions. The steps for obtaining and evaluating evidence into recommendations involve: (1) forming multidisciplinary chapter development teams, (2) developing a conceptual approach to organizing, grouping, selecting and evaluating the interventions in each chapter; (3) selecting interventions to be evaluated; (4) searching for and retrieving evidence; (5) assessing the quality of and summarizing the body of evidence of effectiveness; (6) translating the body of evidence of effectiveness into recommendations; (7) considering information on evidence other than effectiveness; and (8) identifying and summarizing research gaps. Systematic reviews of and evidence-based recommendations for population-health interventions are challenging and methods will continue to evolve. However, using an evidence-based approach to identify and recommend effective interventions directed at specific public health goals may reduce errors in how information is collected and interpreted, identify important gaps in current knowledge thus guiding further research, and enhance the Guide users' ability to assess whether recommendations are valid and prudent from their own perspectives. Over time, all of these advantages could help to increase agreement regarding appropriate community health strategies and help to increase their implementation.

Decision Making↗
PubMed2000

Data collection instrument and procedure for systematic reviews in the Guide to Community Preventive Services. Task Force on Community Preventive Services.

INTRODUCTION: A standardized abstraction form and procedure was developed to provide consistency, reduce bias, and improve validity and reliability in the Guide to Community Preventive Services: Systematic Reviews and Evidence-Based Recommendations (the Guide). DATA COLLECTION INSTRUMENT: The content of the abstraction form was based on methodologies used in other systematic reviews; reporting standards established by major health and social science journals; the evaluation, statistical and meta-analytic literature; expert opinion and review; and pilot-testing. The form is used to classify and describe key characteristics of the intervention and evaluation (26 questions) and assess the quality of the study's execution (23 questions). Study procedures and results are collected and specific threats to the validity of the study are assessed across six categories (intervention and study descriptions, sampling, measurement, analysis, interpretation of results and other execution issues). DATA COLLECTION PROCEDURES: Each study is abstracted by two independent reviewers and reconciled by the chapter development team. Reviewers are trained and provided with feedback. DISCUSSION: What to abstract and how to summarize the data are discretionary choices that influence conclusions drawn on the quality of execution of the study and its effectiveness. The form balances flexibility for the evaluation of papers with different study designs and intervention types with the need to ask specific questions to maximize validity and reliability. It provides a structured format that researchers and others can use to review the content and quality of papers, conduct systematic reviews, or develop manuscripts. A systematic approach to developing and evaluating manuscripts will help to promote overall improvement of the scientific literature.

Data Collection↗
PubMed2000

Identification of HIV-1 integrase inhibitors via three-dimensional database searching using ASV and HIV-1 integrases as targets.

Integration of viral DNA into the host cell genome is a critical step in the life cycle of HIV. This essential reaction is catalyzed by integrase (IN) through two steps, 3'-processing and DNA strand transfer. Integrase is an attractive target for drug design because there is no known cellular analogue and integration is essential for successful replication of HIV. A computational three-dimensional (3-D) database search was used to identify novel HIV-1 integrase inhibitors. Starting from the previously identified Y3 (4-acetylamino-5-hydroxynaphthalene-2,7-disulfonic acid) binding site on the avian sarcoma virus integrase (ASV IN), a preliminary search of all compounds in the nonproprietary, open part of the National Cancer Institute 3-D database yielded a collection of 3100 compounds. A more rigorous scoring method was used to rescreen the 3100 compounds against both ASV IN and HIV-1 IN. Twenty-two of those compounds were selected for inhibition assays against HIV-1 IN. Thirteen of the 22 showed inhibitory activity against HIV-1 IN at concentrations less than 200 microM and three of them showed antiviral activities in HIV-1 infected CEM cells with effective concentrations (EC50) ranging from 0.8 to 200 microM. Analysis of the computer-generated binding modes of the active compounds to HIV-1 IN showed that simultaneous interaction with the Y3 site and the catalytic site is possible. In addition, interactions between the active compounds and the flexible loop involved in the binding of DNA by IN are indicated to occur. The structural details and the unique binding motif between the HIV-1 IN and its inhibitors identified in the present work may contribute to the future development of IN inhibitors.

Avian Sarcoma Viruses↗
PubMed2000

The role of cardiovascular magnetic resonance in heart failure.

Cardiovascular Magnetic Resonance (CMR) is an accepted gold standard for non-invasive, accurate, and reproducible assessment of cardiac mass and function. The interest in its use for viability, myocardial perfusion and coronary artery imaging is also widespread and growing rapidly as the hardware and expertise becomes available in more centres, and the scans themselves become more cost effective. In patients with heart failure, accurate and reproducible serial assessment of remodelling is of prognostic importance and the lack of exposure to ionizing radiation is helpful. The concept of an integrated approach to heart failure and its complications using CMR is fast becoming a reality, and this will be tested widely in the coming few years, with the new generation of dedicated CMR scanners.

Heart Failure↗
PubMed2000

Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium.

Severe psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder are brain diseases of unknown origin. No biological marker has been documented at the pathological, cellular, or molecular level, suggesting that a number of complex but subtle changes underlie these illnesses. We have used proteomic technology to survey postmortem tissue to identify changes linked to the various diseases. Proteomics uses two-dimensional gel electrophoresis and mass spectrometric sequencing of proteins to allow the comparison of subsets of expressed proteins among a large number of samples. This form of analysis was combined with a multivariate statistical model to study changes in protein levels in 89 frontal cortices obtained postmortem from individuals with schizophrenia, bipolar disorder, major depressive disorder, and non-psychiatric controls. We identified eight protein species that display disease-specific alterations in level in the frontal cortex. Six show decreases compared with the non-psychiatric controls for one or more diseases. Four of these are forms of glial fibrillary acidic protein (GFAP), one is dihydropyrimidinase-related protein 2, and the sixth is ubiquinone cytochrome c reductase core protein 1. Two spots, carbonic anhydrase 1 and fructose biphosphate aldolase C, show increase in one or more diseases compared to controls. Proteomic analysis may identify novel pathogenic mechanisms of human neuropsychiatric diseases.

Amino Acid Sequence↗
PubMed2000

Effects on nursing workload of different methicillin-resistant Staphylococcus aureus (MRSA) control strategies.

Nursing staff workload may influence hospital-acquired staphylococcal transmission. Closure of wards to new admissions is used in some institutions as part of methicillin-resistant Staphylococcus aureus (MRSA) outbreak control, and we postulated that it worked by reducing staff workload, allowing more time for good infection control practices. We have used the GRASPCopyright workload system to compare nursing workload during six MRSA outbreaks. Two outbreaks occurred while an aggressive control policy ('old'; 1994-1995) was in place, with a low threshold for ward closure. Control measures had been relaxed before the later four outbreaks, with wards remaining fully or partially open unless MRSA transmission proved intractable ('new'; 1995-1996). To standardize the analysis we compared GRASP and epidemiological data for periods while MRSA transmission was occurring on each ward ('during'), and four week periods 'before' and 'after'. Closing wards to admissions reduces staff workload towards a quality environment, although the nursing requirements of remaining patient rises. Workload pressures may rise during outbreaks if wards are not closed quickly and fully, and patients are not transferred to specialist isolation facilities. Changes in nursing workload need to be assessed during comparative studies of outbreak control measures and the GRASP(c) system appears to be a sensitive way to measure these.

Cross Infection↗
PubMed2000

Biomechanical evaluation of dual-energy X-ray absorptiometry for predicting fracture loads of the infant femur for injury investigation: an in vitro porcine model.

OBJECTIVE: The purpose of this study was to determine the ability of bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) and geometry measured by biplanar x-ray to predict fracture mechanics in vitro in an immature femur model. DESIGN: Prospective analysis of radiographic and biomechanical data was performed. SETTING: In vitro experimentation. INTERVENTIONS: Bone geometry and DXA data were obtained before mechanical testing. Twenty-two porcine femora from males and females (age 3 to 12 months; body weight 3.6 to 7.0 kilograms) were fractured. Mechanical tests were performed on the diaphysis of the femora in two loading configurations: (a) three-point bending to simulate loads that result in transverse fractures; and (b) torsion to simulate twisting injuries that result in spiral fractures. MAIN OUTCOME MEASURES: Correlation of radiographic data with the experimentally determined bone strength. RESULTS: Three-point bending consistently resulted in transverse fractures. Femoral diaphysis BMD (mean, 0.304 grams per square centimeter; SD, 0.028 grams per square centimeter) strongly correlated (r2 = 0.938) to fracture load in bending. Load at failure ranged from 530 to 1,024 N (mean, 726 N; SD, 138 N), consistent with the findings of Miltner. Empirically derived strength parameters coupling BMD with geometry accurately predicted bending loads (r2 = 0.84, p < 0.001) and energy to failure (r2 = 0.88, p < 0.05). Torsional loading failed to generate spiral fractures consistently, resulting in either end plate or diaphyseal fractures. Load at failure for torsion ranged from 1,383 to 3,559 Newton-millimeters (mean, 2,703 Newton-millimeters; SD, 826 Newton-millimeters). Because of these inconsistent fracture results, empirical strength parameters for torsion could not be derived. CONCLUSION: BMD coupled with geometry is a strong predictor of bending fracture loads in the immature femoral diaphysis. A similar relationship could not be shown for torsion because of inconsistent failure results. This study represents an initial attempt at developing a methodology for predicting the strength of young bones from radiographic measures. Further research is required to establish this methodology and to show the necessary correlation with immature human bone.

Absorptiometry, Photon↗
PubMed2000

Purification of a jojoba embryo fatty acyl-coenzyme A reductase and expression of its cDNA in high erucic acid rapeseed.

The jojoba (Simmondsia chinensis) plant produces esters of long-chain alcohols and fatty acids (waxes) as a seed lipid energy reserve. This is in contrast to the triglycerides found in seeds of other plants. We purified an alcohol-forming fatty acyl-coenzyme A reductase (FAR) from developing embryos and cloned the cDNA encoding the enzyme. Expression of a cDNA in Escherichia coli confers FAR activity upon those cells and results in the accumulation of fatty alcohols. The FAR sequence shows significant homology to an Arabidopsis protein of unknown function that is essential for pollen development. When the jojoba FAR cDNA is expressed in embryos of Brassica napus, long-chain alcohols can be detected in transmethylated seed oils. Resynthesis of the gene to reduce its A plus T content resulted in increased levels of alcohol production. In addition to free alcohols, novel wax esters were detected in the transgenic seed oils. In vitro assays revealed that B. napus embryos have an endogenous fatty acyl-coenzyme A: fatty alcohol acyl-transferase activity that could account for this wax synthesis. Thus, introduction of a single cDNA into B. napus results in a redirection of a portion of seed oil synthesis from triglycerides to waxes.

Aldehyde Oxidoreductases↗
PubMed2000

Immunohistochemical detection of steroid receptors in breast cancer: a working protocol. UK Receptor Group, UK NEQAS, The Scottish Breast Cancer Pathology Group, and The Receptor and Biomarker Study Group of the EORTC.

The biochemical assay for the oestrogen receptor has shown the clinical value of knowing the concentration of the receptor within tissue. The immunohistochemical assay is rapidly taking over from the biochemical assay. Therefore, it is vital to have an equivalent scoring system that will have the same predictive value. This paper reports both a practical protocol and a scoring system that should achieve this aim. This approach should be applicable to many more biomarkers detected by immunohistochemistry.

Biomarkers, Tumor↗
PubMed2000

Workshop to identify critical windows of exposure for children's health: cancer work group summary.

We considered whether there are discrete windows of vulnerability in the development of cancer and which time periods may be of the greatest importance. Cancer was considered broadly, including cancers in childhood as well as adult cancers that may have an in utero or childhood origin. We concluded that there was evidence from animal and epidemiologic studies for causal relationships for preconceptional, in utero, and childhood exposures and cancer occurrence in children and adults. However, the evidence is incomplete and all relevant critical windows may not have been identified. The comprehensive evaluation of the relative importance of specific time windows of exposure is limited. Improvements in the design of epidemiologic studies and additional animal studies of mechanisms are warranted.

Adolescent↗
PubMed2000

Pharmacokinetics and metabolism of the methotrexate metabolite 2, 4-diamino-N(10)-methylpteroic acid.

The novel methotrexate (MTX) rescue agent carboxypeptidase-G(2) (CPDG(2)) converts >98% of plasma MTX to 2, 4-diamino-N(10)-methylpteroic acid (DAMPA) and glutamate in patients with MTX-induced renal failure and delayed MTX excretion. DAMPA is eliminated more rapidly than MTX in these patients, suggesting nonrenal elimination. The pharmacokinetics and metabolism of DAMPA were studied in four nonhuman primates with reverse-phase HPLC with UV, photodiode array detection, and mass spectroscopy. The mean peak plasma DAMPA concentration was 51 microM and the plasma disposition was described by a three-compartment open model with first order elimination. The mean clearance of DAMPA was 1.9 l/kg/h and the mean terminal half-life was 51 min. Forty-six percent of the dose was excreted in the urine as parent compound. Three DAMPA metabolites, hydroxy-DAMPA, DAMPA-glucuronide, and hydroxy-DAMPA-glucuronide, were identified in plasma and urine. These metabolites also were identified in plasma from patients who received CPDG(2) as an MTX rescue agent. The cytotoxicity of DAMPA and its effect on MTX cytotoxicity were assessed in the Molt-4 human leukemic cell line. DAMPA was not cytotoxic and did not significantly alter the cytotoxicity of MTX. In nonhuman primates metabolism of DAMPA is a major route of DAMPA elimination, and metabolism underlies the more rapid elimination of DAMPA versus MTX in patients with MTX-induced renal dysfunction after administration of CPDG(2).

Animals↗
PubMed1999

Lead: male-mediated effects on reproduction and development in the rat.

The present study was designed to determine the effect of relatively low levels of lead acetate (25 and 250 ppm) exposure on fertility and offspring viability in male Sprague-Dawley rats. Protein synthesis in 2-cell embryos was monitored by [35S] methionine labeling and two-dimensional SDS gel electrophoresis. Fertility was reduced in males with blood lead levels in the range 27-60 microg/dL. Lead was found to affect initial genomic expression in embryos fathered by male rats with blood lead levels as low as 15-23 microg/dL. Dose-dependent increases were seen in an unidentified set of proteins with a relative molecular weight of approximately 70 kDa (Mr). These results indicate that male-mediated effects of lead may be observed in the 2-cell embryo. The alteration observed in embryonic gene expression with paternal lead exposure may be useful for studying the role of the paternal contribution to the activation of the embryonic genome and protein synthesis in the early embryo.

Animals↗
PubMed1999

A comparison of the effect of rocuronium and vecuronium on heart rate during gynaecological laparoscopy.

The effect on intra-operative heart rate of two nondepolarising muscle relaxants, rocuronium and vecuronium, was compared in 116 fit out-patients undergoing gynaecological laparoscopic procedures. Both groups received an anaesthetic technique which differed only in the choice of muscle relaxant. Intra-operatively it was noted that patients given rocuronium (20 mg) had significantly fewer episodes of bradycardia (heart rate < 50 beat.min-1) than patients given vecuronium 4 mg (p < 0.05). Profound bradycardias (heart rate < 30 beat.min-1) did not occur in any of the patients in the rocuronium study group, whereas 5% of patients receiving vecuronium had a period of transient asystole. We conclude that, at the doses stated, rocuronium results in significantly fewer episodes of bradycardia than vecuronium when used as a muscle relaxant for laparoscopic gynaecological procedures.

Adult↗
PubMed1999

Antegrade visceral revascularisation via a thoracoabdominal approach for chronic mesenteric ischaemia.

OBJECTIVES: It has been suggested that patients with chronic visceral ischaemia are elderly and emaciated hence they may not tolerate antegrade visceral revascularisation via a thoracoabdominal approach. There are no studies to support this assumption. The purpose of this study is to assess the efficacy of this approach for the treatment of chronic visceral ischaemia. METHODS: Between 1988 and 1996, 10 patients underwent antegrade visceral revascularisation for chronic visceral ischaemia via a thoracoabdominal approach and were followed-up for a mean of 40 months. Eight patients were treated with aorto superior mesenteric artery bypass and implantation of the coeliac axis in the graft and two patients with aorto superior mesenteric bypass alone. Graft patency was monitored with duplex scanning. RESULTS: There were no postoperative deaths in this series. Two patients developed postoperative pulmonary infections and required intubation for a short period of time. All patients were discharged after a mean of 17 days (range 7-38). Follow up with duplex scanning revealed that all grafts were patent. One patient developed a high grade anastomotic stenosis which was followed by recurrence of the symptoms. This was dilated on three occasions by balloon angioplasty within a period of 17 months. On the last occasion a stent was placed and since the patient remains asymptomatic. CONCLUSIONS: Antegrade visceral revascularisation via a thoracoabdominal approach is a durable and effective method of relieving symptoms of chronic visceral ischaemia. The low morbidity in this series justifies larger studies in order to establish the true incidence of complications.

Aged↗