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Biomedical subjects

C Sams

Publications and source records attributed to C Sams.

14 recordsLinked to original sources
PubMed2005

Exposure to antineoplastic drugs in two UK hospital pharmacy units.

STUDY OBJECTIVES: To carry out an environmental and biological monitoring study in two UK hospital pharmacy units involved in the preparation of antineoplastic drugs. PARTICIPANTS AND METHODS: The two units studied used isolators for drug preparation. One used isolators operating at positive pressure relative to external atmospheric pressure, whereas the other used negative pressure isolators. Monitoring utilized the measurements of methotrexate, ifosfamide, cyclophosphamide and platinum reflecting the platino-coordinated drugs, such as cisplatin and carboplatin. Personal and static atmospheric and floor wipe samples were collected together with preshift and post-shift urine samples over a 4-day consecutive monitoring period. During the study period both units operated to their normal procedures. RESULTS: Measurable amounts of cytotoxic drugs were detected on the floors of both units and on the disposable gloves worn by staff preparing the drugs. There was also evidence in both units of some very low-level drug absorption from urine measurements, using the most sensitive analytical technique of platinum analysis. The absorption of platinum containing drugs in the unit using negative-pressure isolators was significantly higher, even though less platinum containing drug was prepared per day. Urine measurements in both units were below the detection limit for the other measured drugs. Although the unit using positive-pressure isolators handled daily approximately five times the drug quantities handled with the negative pressure unit, the general levels of external contamination and urine measurements did not reflect this difference. Comparison of the relative levels of glove and floor contamination between the two units was not clear-cut and appeared to depend on the specific cytotoxic drug being monitored. CONCLUSIONS: The levels of external contamination on the floor and gloves, and absorbed dose from urine measurements found in this study showed considerable improvement over many earlier, non-UK studies using comparable exposure measurements. These earlier studies were in facilities using laminar flow/microbiological safety cabinets and where staff were likely to be involved in both drug preparation and administration. Our data did not suggest that the differential pressure of the isolator to the pharmacy atmosphere was an overarching factor in the risk of operator exposure under normal operation. There remains a need to investigate the sources of the low-level drug contamination found in the pharmacies even when using isolators to prepare cytotoxic drugs. This study, and related studies of hospital oncology ward staff, appear to be the only recent UK studies of occupational cytotoxic drug exposure using environmental and biological monitoring techniques.

Air Pollution, Indoor↗
PubMed2004

Biotransformation of chlorpyrifos and diazinon by human liver microsomes and recombinant human cytochrome P450s (CYP).

The cytochrome P450 (CYP)-mediated biotransformation of the organophosphorothioate insecticides chlorpyrifos and diazinon was investigated. Rates of desulphuration to the active oxon metabolite (chlorpyrifos-oxon and diazinon-oxon) and dearylation to non-toxic hydrolysis products were determined in human liver microsome preparations from five individual donors and in recombinant CYP enzymes. Chlorpyrifos and diazinon underwent desulphuration in human liver microsome with mean Km = 30 and 45 microM and V(max) = 353 and 766 pmol min(-1) mg(-1), respectively. Dearylation of these compounds by human liver microsome proceeded with Km = 12 and 28 microM and V(max) = 653 and 1186 pmol min(-1) mg(-1), respectively. The apparent intrinsic clearance (V(max)/Km) of dearylation was 4.5- and 2.5-fold greater than desulphuration for chlorpyrifos and diazinon, respectively. Recombinant human CYP2B6 possessed the highest desulphuration activity for chlorpyrifos, whereas CYP2C19 had the highest dearylation activity. In contrast, both desulphuration and dearylation of diazinon were catalysed at similar rates, in the rank order CYP2C19 > CYP1A2 > CYP2B6 > CYP3A4. Both organophosphorothioates were more readily detoxified (dearylation) than bioactivated (desulphuration) in all human liver microsome preparations. However, the role of individual CYP enzymes in these two biotransformation pathways varied according to the structure of the organophosphorothioate, which was reflected in different activation/detoxification ratios for chlorpyrifos and diazinon. Variability in activity of individual CYP enzymes may influence interindividual sensitivity to the toxic effects of chlorpyrifos and diazinon.

Aged↗
PubMed2001

NASA/American Cancer Society High-Resolution Flow Cytometry Project-I.

BACKGROUND: The NASA/American Cancer Society (ACS) flow cytometer can simultaneously analyze the electronic nuclear volume (ENV) and DNA content of cells. This study describes the schematics, resolution, reproducibility, and sensitivity of biological standards analyzed on this unit. METHODS: Calibrated beads and biological standards (lymphocytes, trout erythrocytes [TRBC], calf thymocytes, and tumor cells) were analyzed for ENV versus DNA content. Parallel data (forward scatter versus DNA) from a conventional flow cytometer were obtained. RESULTS: ENV linearity studies yielded an R value of 0.999. TRBC had a coefficient of variation (CV) of 1.18 +/- 0.13. DNA indexes as low as 1.02 were detectable. DNA content of lymphocytes from 42 females was 1.9% greater than that for 60 males, with a noninstrumental variability in total DNA content of 0.5%. The ENV/DNA ratio was constant in 15 normal human tissue samples, but differed in the four animal species tested. The ENV/DNA ratio for a hypodiploid breast carcinoma was 2.3 times greater than that for normal breast tissue. CONCLUSIONS: The high-resolution ENV versus DNA analyses are highly reliable, sensitive, and can be used for the detection of near-diploid tumor cells that are difficult to identify with conventional cytometers. ENV/DNA ratio may be a useful parameter for detection of aneuploid populations.

American Cancer Society↗
PubMed2001

Immune responsiveness following academic stress in first-year medical students.

Many studies illustrate that physical or psychologic stressors can alter human immune function, which might predispose one to an increased susceptibility to infections. In the present study, we monitored immune responsiveness in 16 first-year medical students (age 23.8 +/- 2.2 years) during the first examination session. Baseline blood samples were collected 30 days prior to the first examination session. Subsequently, subjects were randomly assigned to two groups, and blood samples were collected at 24 h (POST24h) or 48 h (POST48h) after an examination. The percentage of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(+)CD45RO(+), CD3(+)CD45RA(+), CD3(-)CD16(+)56(+), CD19(+), and CD14(+) cells in whole blood was examined to determine changes in circulating immune cell populations. Activation of peripheral blood mononuclear cells (PBMC) with a mixture of phorbol myristate acetate (PMA) and ionomycin or lipopolysaccharide (LPS) for 4 h was used to assess the distribution of interleukin-2 (IL-2)-secreting or interferon-gamma (IFN-gamma)-secreting CD4(+) and CD8(+) cells, as well as IL-1alpha-secreting CD14(+) cells. Activation with a combination of phytohemagglutinin (PHA) and LPS was used to assess secretion of IL-2, IFN-gamma, IL-4, IL-10, soluble IL-2 receptor-alpha (sIL-2Ralpha), IL-1beta, and IL-1R antagonist (IL-1Ra) by PBMC in 48-h cell culture. A significantly higher level of total T cells was found at POST24h, and CD14(+) was elevated at both POST24h and POST48h. The percentage of CD4(+) and CD8(+) cells significantly declined at POST24 and POST48h. A significant elevation in the percentage of memory T cells was observed at POST48h, whereas the percentage of naive T cells was elevated at POST24h and POST48h. These changes were accompanied by a significant decline in percentage of natural killer (NK) cells 24 h after the examination. The percentage of IL-2-producing CD4(+) and CD8(+) cells was significantly lower at POST24h, and the percentage of CD8(+)IFN-gamma(+) cells significantly declined at POST48h. The percentage of CD14(+)IL-1alpha(+) significantly declined at both POST24 and POST48h. A significant decrease was observed in IL-2 secretion 24 h after the examinations, and the secretion of IL-4 and IL-1beta significantly declined at POST48h. No changes in IFN-gamma, IL-10, sIL-2Ralpha, and IL-1Ra secretion were observed. We conclude that the stress outcomes of academic examinations in first-year medical students can significantly alter immune cell distribution and in vitro production and secretion of specific cytokines.

Adult↗
PubMed2000

Evidence for the activation of organophosphate pesticides by cytochromes P450 3A4 and 2D6 in human liver microsomes.

The role of specific cytochrome P450 isoforms in catalysing the oxidative biotransformation of the organophosphorothioate pesticides parathion, chlorpyrifos and diazinon into structures that inhibit cholinesterase has been investigated in human liver microsomes using chemical inhibitors. Pesticides were incubated with human liver microsomes and production of the anticholinergic oxon metabolite was investigated by the inhibition of human serum cholinesterase. Quinidine and ketoconazole at 10 micromol/l inhibited oxidative biotransformation. Compared to control incubations (no inhibitor) where cholinesterase activity was inhibited to between 1 and 4% of control levels, incorporation of the CYP2D6 inhibitor quinidine into the microsomal incubation resulted in cholinesterase activity of 50% for parathion, 38% for diazinon and 30% for chlorpyrifos. Addition of the CYP3A4 inhibitor ketoconazole to microsomal incubations resulted in 66% cholinesterase activity with diazinon, 20% with parathion and 5% with chlorpyrifos. The unexpected finding that CYP2D6, as well as CYP3A4, catalysed oxidative biotransformation was confirmed for chlorpyrifos and parathion using microsomes prepared from a human lymphoblastoid cell line expressing CYP2D6. While parathion has been investigated only as a model compound, chlorpyrifos and diazinon are both very important, widely used pesticides and CYP2D6 appears to be an important enzyme in their bioactivation pathway. CYP2D6 is polymorphic and hence may influence individual susceptibility to exposure to chlorpyrifos and diazinon as well as other structurally similar pesticides.

Biotransformation↗
PubMed2000

Rates of spontaneous reactivation and aging of acetylcholinesterase in human erythrocytes after inhibition by organophosphorus pesticides.

The in vitro rates of spontaneous reactivation and aging in human erythrocyte acetylcholinesterase were studied after inhibition by a dimethoxy (R1R2) and diethoxy substituted (R1R2) organophosphate pesticide (OP) of general structure R1R2P(O)X. These have been compared with data for human plasma cholinesterase previously reported using a similar methodology. A significantly slower rate of aging for erythrocyte acetylcholinesterase was found compared to plasma cholinesterase, whether inhibited by dimethoxy or diethoxy substituted OPs. For diethoxy OPs the rate of spontaneous reactivation of the inhibited plasma enzyme was significantly slower than for the inhibited red cell enzyme. This acetylcholinesterase, and previously published plasma cholinesterase, data suggest that in practise a blood sample taken 30-40 h after significant acute OP exposure will still show inhibition in either plasma or erythrocyte cholinesterase when analysed, but that any inhibited plasma enzyme is more likely to be in the aged form. In contrast a substantial proportion of the erythrocyte acetylcholinesterase is found unaged and therefore sensitive to reactivation by oximes. Samples from an occupational exposure where depressions in plasma or erythrocyte cholinesterase activity from baseline measurements were reactivated ex vivo using the oxime 2-PAM support this hypothesis. These data also confirm that the plasma enzyme is a more sensitive than erythrocyte acetylcholinesterase as an indicator of OP exposure and thus the potential value of ex vivo oxime reactivation of erythrocyte acetylcholinesterase in a blood sample to indicate subclinical OP exposure may be limited. However, this study is too small to draw conclusions on the sensitivity of ex vivo oxime reactivation of acetylcholinesterase as a novel biomarker of excessive OP absorption. Given that there is a better relationship between anticholinergic symptoms and red cell acetylcholinesterase inhibition, and that the slower resynthesis rate of any aged or inhibited red cell enzyme may be interpretatively useful when venepuncture is delayed, it is suggested that red cell acetylcholinesterase activity does have a place in monitoring potential OP exposure.

Acetylcholinesterase↗
PubMed2000

Laboratory outreach: student assessment of flow cytometer fluidics in zero gravity.

Due to the the clinical utility of the flow cytometer, the National Aeronautics and Space Administration (NASA) is interested in the design of a space flight-compatible cytometer for use on long-duration space missions. Because fluid behavior is altered dramatically during space flight, it was deemed necessary to validate the principles of hydrodynamic focusing and laminar flow (cytometer fluidics) in a true microgravity environment. An experiment to validate these properties was conducted by 12 students from Sweetwater High School (Sweetwater, TX) participating in the NASA Reduced Gravity Student Flight Opportunity, Class of 2000. This program allows high school students to gain scientific experience by conducting an experiment on the NASA KC-135 zero gravity laboratory aircraft. The KC-135 creates actual zero-gravity conditions in 30-second intervals by flying a highly inclined parabolic flight path. The experiment was designed by their mentor in the program, the Johnson Space Center's flow cytometrist Brian Crucian, PhD, MT(ASCP). The students performed the experiment, with the mentor, onboard the NASA zero-gravity research aircraft in April 2000.

Aircraft↗
PubMed1999

Detoxification of organophosphates by A-esterases in human serum.

1. In vitro detoxification of the organophosphate (OP) insecticides paraoxon, chlorpyrifos-oxon and malaoxon has been investigated in human serum. 2. Specific A-esterase activity to each OP substrate was measured in the serum of 100 individuals using established spectrophotometric methods for paraoxonase and chlorpyrifos-oxonase and a novel assay for malaoxonase activity. 3. Dose-effect inhibition of serum cholinesterase by the three OPs was measured in pooled human serum. Inhibition of calcium dependent A-esterases by addition of EDTA resulted in increased inhibition of cholinesterase at a given OP concentration. 4. Data from both the direct spectrophotometric measurement of A-esterase activity and inhibition of serum cholinesterase in the presence and absence of A-esterase activity indicated that human serum A-esterase catalysed detoxification of chlorpyrifos-oxon> paraoxon> malaoxon. Our data also confirms the wide variation in potency to inhibit cholinesterase between the three OPs. 5. Malaoxonase activity in human serum does not appear to be polymorphic, however, there is large inter-individual variation as has been previously found for other A-esterases. 6. This study has demonstrated two approaches to investigate the inter-individual variation towards specific OPs and the relative ability of human serum A-esterase to detoxify specific OP compounds.

Aryldialkylphosphatase↗
PubMed1999

A comparative analysis of individuals with spinal cord injury who differ in unplanned utilization of health services.

The purpose of this descriptive study is to describe the profile of individuals with spinal cord injuries (SCI) who frequently use health care services in an unplanned manner so that nursing interventions could be designed to decrease utilization. The medical records of 78 subjects with SCI were reviewed for demographic and injury-related variables, comorbid health conditions, discharge disposition, and health care utilization for five years. Based on the rate of unplanned utilization of health care services, three groups of users were identified: non-user, low-user, and high-user groups. Results indicated that high users, compared to non-users and low users, had a higher substance-use rate, a higher unemployment rate at the time of the most recent health care visit, and more violent causes of their SCI. Findings suggest four clinically meaningful trends that have practical implications for nurses related to marital status, substance use, employment status, and etiology of injury. Results of this study laid the foundation for future research aimed at devising a more in-depth risk profile of high users of health care services in the SCI population.

Adult↗
PubMed1993

The role of psychoneuroendocrine factors on spaceflight-induced immunological alterations.

This paper summarizes previous in-flight infections and novel conditions of spaceflight that may suppress immune function. Granulocytosis, monocytosis, and lymphopenia are routinely observed following short duration orbital flights. Subtle changes within the monocyte and T cell populations can also be noted by flow cytometric analysis. The similarity between the immunological changes observed after spaceflight and other diverse environmental stressors suggest that most of these alterations may be neuroendocrine-mediated. Available data support the hypothesis that spaceflight and other environmental stressors modulate normal immune regulation via stress hormones, other than exclusively glucocorticoids. It will be essential to simultaneously collect in-flight endocrine, immunologic, and infectious illness data to determine the clinical significance of these results. Additional research that delineates the neuroendocrine mechanisms of stress-induced changes in normal immune regulation will allow clinicians in the future to initiate prophylactic immunomodulator therapy to restore immune competence altered by the stress of long-duration spaceflight and therefore reduce morbidity from infectious illness, autoimmune disease, or malignancy.

Humans↗
PubMed1993

Polygalacturonase isozymes from Botrytis cinerea grown on apple pectin.

Five isozymes (four acidic and one basic) of polygalacturonase were separated by chromatofocusing from the culture filtrate of Botrytis cinerea grown on apple pectin. The isozymes, designated as Polygalacturonase I to V, have isoelectric points of 9.7, 4.9, 4.6, 3.7, and 2.7, respectively, with Polygalacturonase III exhibiting the highest specific activity. Polygalacturonase I appeared to function as an endo-polygalacturonase while the other four isozymes act as exo-polygalacturonases. The pH optima of the isozymes range from pH 4.5 to 5.5 with Polygalacturonase V being less sensitive to higher pH compared with the rest of the isozymes.

Chromatography, Thin Layer↗