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Biomedical subjects

D Anderson

Publications and source records attributed to D Anderson.

At least 127 records · Page 7Linked to original sources
PubMed2000

Do characteristics of HIV/AIDS education and training affect perceived training quality? Lessons from the evaluation of seven projects.

Initial and continuing HIV/AIDS education and training has been a critical way to bring the nation's health providers up to date on emerging developments and approaches. This study reports cross-cutting findings from seven HIV/AIDS education and training projects. Trainers described over 600 training sessions from these projects in terms of their structural characteristics and design elements, while trainees described these sessions on several dimensions related to training quality. Training characteristics were compared to trainee assessments of training quality. Using a decision-tree analytic approach for major training attributes, considerable support emerged for links between training characteristics and perceived quality of the HIV/AIDS training experience. More favorable quality ratings were associated with certain projects, the training setting, the types of trainees served by the training, the intended training impact, discussion of special populations, and training methods involving interactive learning. With increased knowledge regarding how these educational experiences relate to the ways they are perceived and processed, more targeted approaches to training design on HIV/AIDS can be developed.

Adult↗
PubMed2000

Abusive behavior is barrier to high-reliability health care systems, culture of patient safety.

Addressing abusive behavior in the medical workplace presents an important opportunity to deliver on the national commitment to improve patient safety. Fundamentally, the issue of patient safety and the issue of abusive behavior in the workplace are both about harm. Undiagnosed and untreated, abusive behavior is a barrier to creating high reliability service delivery systems that ensure patient safety. Health care managers and clinicians need to improve their awareness, knowledge, and understanding of the issue of workplace abuse. The available research suggests there is a high prevalence of workplace abuse in medicine. Both administrators at the blunt end and clinicians at the sharp end should consider learning new approaches to defining and treating the problem of workplace abuse. Eliminating abusive behavior has positive implications for preventing and controlling medical injury and improving organizational performance.

Agonistic Behavior↗
PubMed1999

Cytogenetic damage and ras p21 oncoprotein levels from patients with chronic obstructive pulmonary disease (COPD), untreated lung cancer and healthy controls.

The purpose of the present communication was to determine in patients with chronic obstructive pulmonary disease (COPD), untreated lung cancer and healthy controls if there was a possible association between the disease state and biomarkers of cytogenetic damage and ras p21 oncoprotein levels, and if various exogenous confounding factors such as smoking habit and endogenous ones (sex, cancer in the immediate family) could affect these biomarkers. The individuals in all groups were as well-matched as possible for age to determine if this could be eliminated as a confounder. Peripheral blood and plasma were collected from 20 COPD patients, 31 cancer patients and 20 healthy controls. Chromosomal aberrations (CA), sister chromatid exchanges (SCE) and high frequency SCE cells (HFC) were examined from the blood and ras p21 oncoproteins from the plasma. These parameters were used as biomarkers of genotoxic anomalies. All the biomarkers were examined for their relationship to the confounding factors. Results were analysed by a t-test, analysis of variance (ANOVA) and stepwise multivariate regression analysis. There was an increase in CA, although not statistically so, in COPD and cancer patients by comparison with healthy controls, but there was a statistically significant increase in SCE, HFC and ras p21 oncoproteins. There was also a statistically significant difference between respiratory volume parameters in COPD patients and controls. Respiratory parameters were not measured in cancer patients. Ras p21 oncoproteins were also statistically significantly increased in the COPD and cancer patients, suggesting that the disease state alone might be sufficient to increase the oncoproteins, or that some of the COPD patients were in the process of developing cancer or perhaps some would die from COPD before cancer developed. Smoking was shown to have a marked effect on all parameters investigated. Ex-smokers showed less effects. Since age was very well controlled, there was little effect due to age. There was an effect due to sex, but cancer in the immediate family had little effect on any of the parameters.

Adult↗
PubMed1999

IL-2 plasmid therapy of murine ovarian carcinoma inhibits the growth of tumor ascites and alters its cytokine profile.

We have evaluated whether i.p. murine ovarian tumors could be treated with an IL-2 plasmid DNA complexed with the cationic lipid, (+/-)-N-(2-hydroxyethyl)-N,N-dimethyl-2, 3-bis(tetradecyloxy)-1-propanaminium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). Reporter gene studies were initially conducted in which mice bearing i.p. murine ovarian teratocarcinoma (MOT) were injected i.p. with reporter gene plasmid DNA (pDNA):DMRIE/DOPE. Histochemical analyses revealed that transfection occurred primarily in the tumor cells of the ascites, with only a minority of other ascitic cells or surrounding tissues transfected. IL-2 levels in the MOT ascites were determined after i. p. injection of either IL-2 pDNA:DMRIE/DOPE or recombinant IL-2 protein. IL-2 was detected in tumor ascites for up to 10 days after a single i.p. injection of IL-2 pDNA:DMRIE/DOPE, but was undetectable 24 h after a single i.p. injection of IL-2 protein. In an antitumor efficacy study, MOT tumor-bearing mice injected i.p. with IL-2 pDNA:DMRIE/DOPE on days 5, 8, and 11 after tumor cell implant had a significant inhibition of tumor ascites (p = 0.001) as well as a significant increase in survival (p = 0.008). A cytokine profile of the MOT tumor ascites revealed that mice treated with IL-2 pDNA:DMRIE/DOPE had an IL-2-specific increase in the levels of IFN-gamma and GM-CSF. Taken together, these findings indicate that i. p. treatment of ovarian tumors with IL-2 pDNA:DMRIE/DOPE can lead to an increase in local IL-2 levels, a change in the cytokine profile of the tumor ascites, and a significant antitumor effect.

Animals↗
PubMed1999

Examination of ras oncoproteins in human plasma from healthy controls and workers exposed to petroleum emissions, including benzene-related compounds.

Ras oncoproteins in blood plasma from workers exposed to petroleum emissions and unexposed controls were examined from Polish and Estonian samples. Twenty-four workers and 35 unexposed controls were examined from Poland and 97 exposed and 40 unexposed controls from Estonia. Of the Estonian workers, 50 were exposed to benzene in a benzene production plant and 47 to polyaromatic hydrocarbons and benzene in a cokery. Blood plasma proteins were separated by gel electrophoresis, transferred to a nitrocellulose membrane by Western blotting and detected by chemiluminescence using a monoclonal antibody as the primary antibody. There were no statistically significant differences between the exposed and the control groups in either the Polish or the Estonian samples.

Air Pollutants, Occupational↗
PubMed1999

Therapeutic plasma exchange: an update from the Canadian Apheresis Group.

In 1997, the Canadian Apheresis Group reviewed data on 103,416 plasma exchange procedures that had been collected since 1980. Although the number of plasma exchanges gradually increased (from 3189 to 8208 per year), the pattern changed. In 1981, the five most frequent indications for plasma exchange resulted in 55% of all such procedures; by 1997, the five most frequent indications for plasma exchange resulted in 81.1% of all such procedures. During this period, three conditions that were originally among the most frequent indications for plasma exchange became among the least frequent. This paper reviews the published evidence that supports or refutes the use of plasma exchange in the category of the five most frequent indications from 1981 to 1997: thrombotic thrombocytopenic purpura, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, Waldenstrom macroglobulinemia, the Guillain-Barre syndrome, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. For most disorders, use of plasma exchange procedures is correlated with published evidence, and the changing patterns of plasma exchange use by members of the Canadian Apheresis Group reflect published evidence. Annual center-by-center reviews of use of plasma exchange may also have influenced practice patterns.

Acute Disease↗
PubMed1999

RANK is essential for osteoclast and lymph node development.

The physiological role of the TNF receptor (TNFR) family member, RANK, was investigated by generating RANK-deficient mice. RANK(-/-) mice were characterized by profound osteopetrosis resulting from an apparent block in osteoclast differentiation. RANK expression was not required for the commitment, differentiation, and functional maturation of macrophages and dendritic cells from their myeloid precursors but provided a necessary and specific signal for the differentiation of myeloid-derived osteoclasts. RANK(-/-) mice also exhibited a marked deficiency of B cells in the spleen. RANK(-/-) mice retained mucosal-associated lymphoid tissues including Peyer's patches but completely lacked all other peripheral lymph nodes, highlighting an additional major role for RANK in lymph node formation. These experiments reveal that RANK provides critical signals necessary for lymph node organogenesis and osteoclast differentiation.

Animals↗
PubMed1999

High-performance liquid chromatographic method for sensitive determination of the alkylating agent CB1954 in human plasma.

A high-performance liquid chromatography (HPLC) method is described for the measurement of the weak alkylating agent CB1954 in human plasma. CB1954 can be used as an innocuous prodrug designed for activation by bacterial nitroreductases in strategies of gene-directed enzyme-prodrug therapy, and becomes activated to a potent bifunctional alkylating agent. The HPLC method involves precipitation and solvent extraction and uses Mitomycin C (MMC) as an internal standard, with a retention time for MMC of 5.85 +/- 0.015 min, and for CB1954 of 10.72 +/- 0.063 min. The limit of detection for CB1954 is 2.9 ng/ml, and this compares favourably with systems involving direct analysis of plasma (limit of detection 600 ng/ml, approximately). The method is now being used for pharmacokinetic measurements in plasma samples from cancer patients entering phase I clinical trials of CB1954. Results using serial plasma samples from one patient are presented. The patient was treated intravenously with CB1954 (6 mg/m2), and plasma clearance of the drug showed biphasic kinetics with alpha half-life 14.6 min, and beta half-life 170.5 min.

Antineoplastic Agents, Alkylating↗
PubMed1999

Factors contributing to biomarker responses in exposed workers.

"...[Th]e proper study of mankind is man" (Pope, circa 1733/1734). Human monitoring fits this notion and monitoring after exposure to genotoxic agents is now an established discipline. It is possible in many situations to identify humans exposed to potentially toxic materials in the workplace and the environment. Responses are often measured in peripheral lymphocytes because these cells can be acquired by a generally socially and ethically acceptable, minimally invasive route. In the early 1960s, chromosome damage in these cells was one of the first endpoints to be used as a biomarker and benzene was one of the first chemicals investigated. Although a causal relationship between chromosome damage and cancer has not been proven, it has been suggested to have some prognostic significance for future cancer onset. With other genetic biomarkers this is as yet not the case, but there are now many biomarkers for different areas of toxicology. Other well-established genetic biomarkers include the detection of hprt mutations, micronuclei and sister chromatid exchanges. However, for interpretation of responses, the issue of confounding factors must be addressed. As in most human studies, there tends to be a high degree of interindividual variability in response to chemical insults. Some non-exposed control individuals exhibit as high a level of damage as some exposed individuals and some of these have levels of damage as low as many of the controls. Thus, it is only the mean values of the groups that can substantiate an exposure related-problem; the data on an individual basis are still of limited use. While human lymphocytes remain the most popular cell type for monitoring purposes, sperm, buccal, nasal, epithelial and placental cells are also used. Confounding factors affect responses in all cell types. There are endogenous confounding factors such as age, sex, genetic make-up and exogenous confounding factors including lifestyle habits such as smoking, drinking, etc. There are biomarkers of exposure, effect and susceptibility and the last may be influenced by the genotype and polymorphism genes existing in a population. From our own studies, confounding effects will be considered in relation to workers exposed to vinyl chloride and petroleum emissions. The relationship between the biomarkers and various factors which influence them is complex. Sometimes the variables are not completely independent of one another.

Biomarkers↗
PubMed1999

Examination of various biomarkers measuring genotoxic endpoints from Barcelona airport personnel.

Three different biomarkers: sister-chromatid exchanges (SCE), micronuclei (MN), and the Comet assay, were used to evaluate different kinds of genetic damage in peripheral blood lymphocytes from 34 male workers at Barcelona airport, exposed to low levels of hydrocarbons and jet fuel derivatives. The control group consisted of 11 unexposed men. We also investigated the ras p21 protein levels in plasma, in order to evaluate whether the ras gene could serve as a suitable potential marker of carcinogenic pollution in occupationally exposed cohorts. SCE and MN analyses failed to detect any statistically significant increase in the airport workers when compared with the controls, and in fact, the frequency of binucleated cells with MN in the exposed group was significantly lower than that obtained in the control. However, slight but significant differences in the mean comet length and genetic damage index were observed between the exposed and control groups when using the Comet assay. There were no statistically significant differences between both groups in p21 plasma levels. Smoking was shown to affect significantly both SCE and high frequency cells (HFC) in the exposed group.

Air Pollutants↗
PubMed1999

Preliminary clinical study of the distribution of HPMA copolymers bearing doxorubicin and galactosamine.

Galactose-targeted delivery of macromolecules and drug conjugates to asialoglycoprotein receptor (ASGPR) positive cells has been widely documented in animals, although targeting in humans has never been demonstrated. In this study we report the pharmacokinetics and imaging determined in the first patient enrolled in a phase I clinical study of the poly[N-(2-hydroxypropyl)methacrylamide] copolymer bearing doxorubicin and galactosamine, known as PK2. Gradient high performance liquid chromatography (HPLC) evaluation of plasma and urine has been combined with 123I-based imaging to show biphasic clearance of the drug from the plasma (half-lives of 78+/-1 and 990+/-15), and approximately 30% delivery of the drug to the hepatic region, as determined by planar whole body imaging at 24 h. This patient has a multifocal hepatoma, and single photon emission computed tomography (SPECT) analysis showed a ratio of tumour tissue to normal liver uptake of approximately 1:3, at 24 h. On the basis of this patient, effective hepatic targeting can be achieved following an intravenous dose of 20 mg/m2 doxorubicin as PK2, however the therapeutic usefulness of this targeted drug has yet to be established.

Antibiotics, Antineoplastic↗
PubMed1999

A gene therapy for cancer using intramuscular injection of plasmid DNA encoding interferon alpha.

A cancer treatment is described in which i.m. injection of plasmid DNA (pDNA) encoding murine interferon alpha (mIFN-alpha) leads to potent antitumor effects on primary and metastatic tumors in mice. Mice bearing s.c. B16F10 melanoma, Cloudman melanoma, or glioma 261 tumors were injected i.m. with mIFN-alpha pDNA. In all three tumor models, a significant reduction in tumor volume and enhancement of survival was found after IFN pDNA therapy. The mIFN-alpha pDNA could be injected as infrequently as once every other week and still produce a significant antitumor effect, and, in a metastatic tumor model, the therapy markedly reduced the number of lung tumor metastases. Depletion of immune cell subsets indicated that CD8(+) T cells were required for the antitumor response. These studies demonstrate that primary and metastatic tumors can be treated systemically by i.m. injection of a plasmid encoding a cytokine gene.

Animals↗
PubMed1999

Immunohistochemical analysis of the activation of NF-kappaB and expression of associated cytokines and adhesion molecules in human models of allergic inflammation.

To investigate the role of NF-kappaB in regulating allergic inflammation, a monoclonal antibody directed to the activated form of NF-kappaB has been developed and immunohistochemistry has been employed to study the pro-inflammatory transcriptive function of NF-kappaB and the adhesion molecules and cytokines that it regulates. Human umbilical vein endothelial cells (HUVECs) exposed to physiological levels of TNFalpha demonstrated dose- and time-dependent cytoplasmic and nuclear activation of NF-kappaB, followed by up-regulation of ICAM-1. This was suppressed by the selective inhibitors of NF-kappaB activation, calpain and gliotoxin. Using monoclonal antibodies directed to NF-kappaB and associated cytokines and adhesion molecules, immunohistochemistry was applied to bronchial explants stimulated ex vivo with TNFalpha, and to nasal polyp tissue, embedded in glycol methacrylate. Stimulation of the bronchial explants increased expression of NF-kappaB, IL-8, and GM-CSF in the epithelium and endothelium and ICAM-1 in the endothelium. In nasal polyp, expression of NF-kappaB was in the epithelium, the endothelium and in submucosal mast cells, eosinophils, T and B lymphocytes, and macrophages. Thus, immunohistochemistry can be used to determine the cellular provenance of NF-kappaB and its activation status in single cell and complex tissue systems, in parallel with appropriate inflammatory markers.

Animals↗
PubMed1999

Antimutagenic activity of chemical fractions isolated from a commercial soybean processing by-product.

Commercial products of agronomic crop plants may become a reliable and inexpensive source of phytonutrients, such as antimutagenic food supplements. We previously demonstrated that PCC, an ethanol extract of a commercial soybean processing by-product, was able to repress induced genomic DNA damage, whole cell clastogenicity, and point mutation in mammalian cells. In this paper we separated PCC into a series of chemically defined fractions and determined their ability to repress induced mutagenic damage in Chinese hamster lung cells, Chinese hamster ovary cells and human lymphocytes. Fraction PCC70 (PCC 70% methanol eluate) contained the flavonoids from PCC and daidzin and genistin repressed 2-acetoxyacetylaminofluorene (2AAAF)-induced DNA damage measured with single cell gel electrophoresis. Genistein, however, enhanced the genotoxic impact of 2AAAF. Fraction PCC100 (PCC 100% methanol eluate) had the greatest level of antigenotoxic activity against 2AAAF in CHO cells and repressed the genotoxic capacity of the dietary carcinogen 2-amino-3-methylimidazo-(4,5-f)quinoline (IQ) in human lymphocytes. These data indicate that commercial soybean products and by-products may be a source of chemoprotective food additives.

Animals↗
PubMed1999

The effect of potassium diazoacetate on human peripheral lymphocytes, human adenocarcinoma Colon caco-2 cells, and rat primary colon cells in the comet assay.

In previous studies, N-(N'-acetyl-L-propyl)-N-nitrosoglycine (APNG) has been shown to be a potent mutagen in a variety of genotoxicity assays and a carcinogen in a limited cancer study. APNG decomposes to a carboxymethyldiazonium ion, which can also be generated from potassium diazoacetate (KDA). KDA is particularly interesting because it is a stable nitrosated derivative of glycine, one of the most common dietary amino acids. KDA has been shown to produce more O6 carboxymethyl- and O6 methyl-adducts than APNG, so it was anticipated that it might also be a potent genotoxic agent. Thus in the present study KDA has been investigated in the single cell gel electrophoresis (Comet) assay, which primarily measures DNA strand breakage. Since KDA has been shown to be formed in the gut, the genotoxic effects of KDA were investigated in vitro in human adenocarcinoma colon Caco-2 cells, and in rat primary colon cells and compared to responses from human peripheral lymphocytes. KDA induced DNA damage in the three cell types, confirming that KDA is genotoxic in a range of mammalian cells.

Adult↗
PubMed1999

Effect of some phthalate esters in human cells in the comet assay.

Phthalate esters are among the most extensively used industrial chemicals and are widely distributed in the environment. Di-(2-ethylhexyl)phthalate (DEHP) and its hydrolysis product mono-(2-ethylhexyl)phthalate (MEHP) have been examined for genotoxic activity on previous occasions. Only MEHP was found to cause chromosome damage in CHO cells but was without effect in the sister chromatid exchange and hypoxanthine guanine phosphoribosyl assay. DEHP was found to be a weak direct acting mutagen in Salmonella typhimurium strain TA100, the mutagenic activity of which could be abolished by rat liver microsomes (S9 mix). The clastogenicity and weak mutagenicity suggest a possible contributory role for these compounds in the observed carcinogenicity of the phthalates, which have been thought predominantly to be linked to cancer pathology through proliferation of hepatic peroxisomes. The present study showed that these compounds could produce DNA damage in human blood cells in the Comet assay and also, that rat liver microsomes could abolish the effect of DEHP. Thus in the intact animal, no response may be observed.

Animals↗