Biomedical subjects

C D Brown

Publications and source records attributed to C D Brown.

At least 19 recordsLinked to original sources

PubMed2006

Adsorption of ionisable pesticides in soils.

Understanding the fate of a pesticide in soil is fundamental to the accurate assessment of its environmental behaviour and vital in ensuring the safe use of new and existing products. Ionisable pesticides comprise a significant proportion of both existing and new active substances registered for use in agriculture worldwide. This group of pesticides includes chemicals that are frequently found in groundwater and surface waters in many different countries. Despite this, approaches to predict the influence of soil properties on the behaviour of ionisable pesticides in soils are poorly developed. Current regulatory assessments frequently default to methods developed for nonionic chemicals, although it is evident that ionisable compounds do not often react like neutral molecules. This review presents the state of knowledge on the adsorption of ionisable pesticides in soils. It first introduces the issues concerning adsorption and the characteristics of this particular kind of chemical. The mechanisms postulated for the adsorption of ionisable pesticides are then described: these are hydrophobic partitioning, ionic exchange, charge transfer, ligand exchange, cation or water bridging, and the formation of bound residues. Relatively little experimental evidence is available, and we are still unable to determine the quantitative contribution of each process in a particular situation. Knowledge is still lacking concerning phenomena occurring at the surfaces of soil particles. Measurements do not allow determination of the operative pH at the surface of soil particles or in microenvironments, and the influence of ionic strength or competition effects is difficult to assess. Subsequently, the review focuses on the influence of soil properties on adsorption and on potential to predict the behaviour of ionisable pesticides in soils. Unlike hydrophobic compounds, adsorption of ionisable pesticides is highly sensitive to variation in pH. This relationship mainly derives from the different proportion of ionic and neutral forms of the pesticide present at each pH level but also from the presence of surfaces with pH-dependent charges in soils. Soil organic matter generally promotes adsorption, although a negative influence has sometimes been reported. Clay and oxides can also play a significant role in some cases. So far, no modelling approach has been applied successfully to a range of ionisable pesticides to predict their adsorption in soils. The standardization of experimental settings and the application of approaches specific to a particular class of pesticide or different type of soil might be necessary to describe the complexity of interactions among ionisable molecules. Degradation of ionisable pesticides is influenced by soil pH in a particular way that relates to changes in sorption, changes in composition and activity of the microbial community, and to shifts in the balance between different degradative mechanisms.

Adsorption↗

PubMed2005

Clinical assessment of near-infrared spectroscopy for noninvasive diabetes screening.

BACKGROUND: Current diabetes screening techniques comprise the fasting plasma glucose (FPG) and oral glucose tolerance tests. Both tests demand patient compliance, and neither test has ideal performance. Near-infrared (NIR) spectroscopy is a noninvasive means of interrogating characteristics of a sample and is evaluated as a novel screening method for type 2 diabetes. METHODS: One hundred fifty-four patients with and without type 2 diabetes were recruited. Their forearm skin was measured with the NIR spectroscopic system, and a capillary blood glucose measurement was also taken. Sixty-six patients returned for a second visit at a later date. A multivariate model, generated from a separate training study, was employed to produce a quantitative risk marker of disease for each NIR spectrum. Sensitivity and specificity (the probabilities that the NIR method will correctly identify a subject as having diabetes or as not having diabetes, respectively) were calculated. As the NIR method produces a continuous rather than categorical classification, various thresholds were evaluated to give several sensitivity and specificity pairs. Test reproducibility was also determined. RESULTS: At a false-positive rate of 70%, the NIR test had a sensitivity of 77.7%, which is comparable to the 77.3% sensitivity for the FPG test as reported for the Third National Health and Nutrition Examination Survey (NHANES III) study. The reproducibility of the NIR test was also similar to the FPG test (inter-day agreement rates of 84.2% and 79.2%, respectively). CONCLUSIONS: A noninvasive NIR spectroscopic measurement of the volar forearm was shown to have comparable performance characteristics with the FPG test. The source of the spectroscopic signal is still uncertain and is the subject of ongoing research.

Adult↗

PubMed2005

Noninvasive alcohol testing using diffuse reflectance near-infrared spectroscopy.

A diffuse reflectance near-infrared (NIR) spectrometer was evaluated as a noninvasive alternative to breath and blood measurements for in vivo alcohol testing. A hybrid partial least squares (PLS) calibration was constructed using a combination of in vivo and in vitro spectral data. This model was subsequently evaluated for its performance in quantifying alcohol concentrations in vivo using a prospective validation study involving subjects who did not participate in the calibration. The validation study entailed induction of alcohol excursions in ten human subjects and comparison of the noninvasive NIR alcohol measurements to blood and breath alcohol measurements. Blood and breath alcohol measurements were performed at the time of each noninvasive NIR measurement (N = 372), establishing the noninvasive NIR measurement standard error relative to blood alcohol at 4.9 mg/dL (0.0049%). Assessment of the hybrid calibration model's sensitivity and selectivity provided strong evidence that the hybrid calibration yielded measurements that were both sensitive to alcohol and independent of other absorbing analytes in human tissue.

Algorithms↗

PubMed2004

Using a linked soil model emulator and unsaturated zone leaching model to account for preferential flow when assessing the spatially distributed risk of pesticide leaching to groundwater in England and Wales.

Although macropore flow is recognized as an important process for the transport of pesticides through a wide range of soils, none of the existing spatially distributed methods for assessing the risk of pesticide leaching to groundwater account for this phenomenon. The present paper presents a spatially distributed modelling system for predicting pesticide losses to groundwater through micro- and macropore flow paths. The system combines a meta version of the mechanistic, dual porosity, preferential flow pesticide leaching model MACRO (the MACRO emulator), which describes pesticide transport and attenuation in the soil zone, to an attenuation factor leaching model for the unsaturated zone. The development of the emulator was based on the results of over 4000 MACRO model simulations. Model runs describe pesticide leaching for the range of soil types, climate regimes, pesticide properties and application patterns in England and Wales. Linking the MACRO emulator to existing spatial databases of soil, climate and compound-specific loads allowed the prediction of the concentration of pesticide leaching from the base of the soil profile (at 1 m depth) for a wide range of pesticides. Attenuation and retardation of the pesticide during transit through the unsaturated zone to the watertable was simulated using the substrate attenuation factor model AQUAT. The MACRO emulator simulated pesticide loss in 10 of 12 lysimeter soil-pesticide combinations, for which pesticide leaching was shown to occur and also successfully predicted no loss from 3 soil-pesticide combinations. Although the qualitative aspect of leaching was satisfactorily predicted, actual pesticide concentrations in leachate were relatively poorly predicted. At the national scale, the linked MACRO emulator/AQUAT system was found to predict the relative order of, and realistic regional patterns of, pesticide leaching for atrazine, isoproturon, chlorotoluron and lindane. The methodology provides a first-step assessment of the potential for pesticide leaching to groundwater in England and Wales. Further research is required to improve the modelling concept proposed. The system can be used to refine regional groundwater monitoring system designs and sampling strategies and improve the cost-effectiveness of the measures needed to achieve 'good status' of groundwater quality as required by the Water Framework Directive.

Journal Article↗

PubMed2004

A lysimeter experiment to investigate temporal changes in the availability of pesticide residues for leaching.

Leaching of three pesticides (isoproturon, chlorotoluron and triasulfuron) and a tracer (bromide) were determined in four contrasting soils ranging in texture from sandy loam to clay. The compounds were applied to undisturbed columns of soil and four columns for each soil were randomly selected and leached with 24-mm equivalent of water at prescribed time intervals (3, 9, 24, 37 and 57 d after application). A rapid decline in leached loads of isoproturon and chlorotoluron as time from application to irrigation increased was observed in all soils. In contrast, triasulfuron and bromide loads only decreased rapidly in the clay soil. Bromide losses decreased with decreasing clay contents of the soil and therefore with a decrease in structural development. Magnitudes of pesticide losses varied from soil to soil, depending on structural development and the organic carbon content. Pesticide degradation experiments on disturbed and undisturbed soil samples showed that the rapid decline of leached loads with time was faster than could be explained by degradation alone. Five physico-chemical processes are put forward to explain the different patterns of pesticide leached loads observed in the soils: (1) relative extent of preferential flow, (2) sorption capacity of the compounds to the different soils, (3) extent of degradation of the compounds in the soil, (4) variation in sorption kinetics between compounds associated with pesticide diffusion into soil aggregates, and (5) protection of the compounds by a combination of intra-aggregate diffusion and the presence of preferential flow pathways.

Diffusion↗

PubMed2002

Anti-cholinergic bronchodilators versus beta2-sympathomimetic agents for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Inhaled bronchodilators form the mainstay of treatment for acute exacerbations of COPD. Two types of agent are used routinely, either singly or in combination: anticholinergic agents and beta2-sympathomimetic agonists. OBJECTIVES: To assess the effect of anti-cholinergic agents on lung function and dyspnea in patients with acute exacerbations of COPD, compared with placebo or short-acting beta-2 agonists. SEARCH STRATEGY: A comprehensive search of the literature was carried out on MEDLINE, EMBASE, CINAHL and the Cochrane COPD Trials Register, using the terms: bronchodilator* OR ipratropium OR oxitropium. References listed in each included trial were searched for additional trial reports. SELECTION CRITERIA: Studies were included if the participants were adult patients with a known diagnosis of COPD and had symptoms consistent with criteria for acute exacerbation of COPD. All randomized controlled trials that compared inhaled ipratropium bromide or oxitropium bromide to appropriate controls were considered. Appropriate control treatments included placebo, other bronchodilating agents, or combination therapies. Studies of acute asthma or ventilated patients were excluded. DATA COLLECTION AND ANALYSIS: All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus. MAIN RESULTS: Four trials compared the short-term effects of ipratropium bromide vs. a beta2-agonist. Short-term changes in FEV1 (up to 90 minutes) showed no significant difference between beta2-agonist and ipratropium bromide treated patients. The differences were similar among the studies and when combined: Weighted Mean Difference (WMD) 0.0 liters (95% Confidence Interval (95% CI) -0.19, 0.19). There was no significant additional increase in change in FEV1 on adding ipratropium to beta2-agonist: WMD 0.02 liter (95% CI -0.08, 0.12). Long-term effects (24 hours) of the ipratropium bromide and beta2-agonist treatment combination were similar: WMD 0.05 liters (95%CI -0.14, 0.05). Neither of two studies found significant changes in PaO2, either short- or long-term, with ipratropium vs. beta-agonist, although one showed an increase in PaO2 in subjects receiving ipratropium bromide at 60 minutes. Adverse drug reactions included dry mouth and tremor. REVIEWER'S CONCLUSIONS: There was no evidence that the degree of bronchodilation achieved with ipratropium bromide was greater than that using a short-acting beta2-agonist. The combination of a beta2-agonist and ipratropium did not appear to increase the effect on FEV1 more than either used alone.

Bronchodilator Agents↗

PubMed2001

A physiologically based pharmacokinetic model for ethylene oxide in mouse, rat, and human.

Ethylene oxide (EO) is widely used as a gaseous sterilant and industrial intermediate and is a direct-acting mutagen and carcinogen. The objective of these studies was to develop physiologically based pharmacokinetic (PB-PK) models for EO to describe the exposure-tissue dose relationship in rodents and humans. We previously reported results describing in vitro and in vivo kinetics of EO metabolism in male and female F344 rats and B6C3F1 mice. These studies were extended by determining the kinetics of EO metabolism in human liver cytosol and microsomes. The results indicate enzymatically catalyzed GSH conjugation via cytosolic glutathione S-transferase (cGST) and hydrolysis via microsomal epoxide hydrolase (mEH) occur in both rodents and humans. The in vitro kinetic constants were scaled to account for cytosolic (cGST) and microsomal (mEH) protein content and incorporated into PB-PK descriptions for mouse, rat, and human. Flow-limited models adequately predicted blood and tissue EO levels, disposition, and elimination kinetics determined experimentally in rats and mice, with the exception of testis concentrations, which were overestimated. Incorporation of a diffusion-limited description for testis improved the ability of the model to describe testis concentrations. The model accounted for nonlinear increases in blood and tissue concentrations that occur in mice on exposure to EO concentrations greater than 200 ppm. Species differences are predicted in the metabolism and exposure-dose relationship, with a nonlinear relationship observed in the mouse as a result of GSH depletion. These models represent an essential step in developing a mechanistically based EO exposure-dose-response description for estimating human risk from exposure to EO.

Animals↗

PubMed2001

Release of PEGylated granulocyte-macrophage colony-stimulating factor from chitosan/glycerol films.

We have prepared a new formulation for mucosal delivery of GM-CSF or PEGylated GM-CSF based on a chitosan carrier plus added glycerol to control the rate of release of the protein. Thin dry films comprised of various weight ratios of chitosan to glycerol and containing either granulocyte-macrophage colony-stimulating factor (GM-CSF) or PEGylated GM-CSF, PEG-(GM-CSF), were prepared. The amount of GM-CSF or PEG-(GM-CSF) released from the chitosan/glycerol films was determined using size exclusion high performance liquid chromatography (HPLC-SEC). The amount of PEG-(GM-CSF) released from the films decreased with an increase in the amount of glycerol present in the film. In parallel with this, films with higher glycerol content exhibited a lower degree of equilibrium swelling when immersed in release media. pH measurements of the release media and analysis of the dried films by Fourier-transform infrared spectroscopy (FTIR) suggested that the amount of residual acetic acid in the dry films decreased as the glycerol content increased. This indicates that glycerol may act by displacing and releasing bound acetic acid from the chitosan molecules, resulting in chitosan--glycerol hydrogen bond formation as the film dries. Further, it was found that the release rate and the amount of PEG-(GM-CSF) released decreased with increasing molecular weight of the conjugated PEG. This effect was not observed with films containing physical mixtures of PEG and GM-CSF. The decrease in the fraction of PEG-(GM-CSF) released with increasing PEG molecular weight is believed to be due to the increased steric hindrance of the PEGylated protein molecule during its diffusion out of the swollen chitosan/glycerol film.

Biocompatible Materials↗

PubMed2001

Inhaled short-acting beta2-agonists versus ipratropium for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Inhaled short acting beta2 adrenergic agonists and ipratropium bromide are both used in the treatment of acute exacerbations of chronic obstructive pulmonary disease. OBJECTIVES: In patients with acute exacerbations of COPD to: 1. To assess the efficacy of short-acting beta-2 agonists against placebo; 2. Compare the efficacy of short-acting beta-2 agonists and ipratropium. SEARCH STRATEGY: A comprehensive search of the literature was carried out of EMBASE, MEDLINE, CINAHL and the Cochrane COPD trials register was carried out using the terms: bronchodilator* OR albuterol OR metaproterenol OR terbutaline OR isoetharine OR pirbuterol OR salbutamol OR beta-2 agonist. SELECTION CRITERIA: All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus. DATA COLLECTION AND ANALYSIS: All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus. References listed in each included trial were searched for additional trial reports. Trials were combined using Review Manager using a fixed effects model. The size of the treatment effects were tested for heterogeneity. MAIN RESULTS: We identified no placebo-controlled comparisons of beta-2 agonists. Three studies permitted comparison of ipratropium to an inhaled beta-2 agonist. These studies included a total of 103 patients. The beta2-agonists used were: fenoterol and metaproterenol. One study was a parallel group trial of regular therapy for seven days. The other two were cross over studies of single dose treatments, with efficacy measured 90 min post dose. There was no washout period between treatments. Both treatments produced an improvement in forced expiratory volume (FEV1) after 90 min in the range 150-250 ml. The was no difference between treatments, mean difference in FEV1 10 ml; 95% CI -220, 230 ml. In one small crossover study (n=10) there was a significant improvement in arterial PaO2 after 30 minutes with ipratropium (+5.8 mm Hg +/- 3.0 (SEM)) compared to metaproterenol (-6.2 +/- 1.2 mm Hg), but this was not significant at 90 min. There were no data concerning respiratory symptoms. The crossover studies showed no evidence of an additive effect of the two treatments, although they were not designed specifically to test this. REVIEWER'S CONCLUSIONS: There are few controlled trial data concerning the use of inhaled beta2-agonist agents in acute exacerbations of COPD and none that have compared these agents directly with placebo. None of the studies used the more modern beta2-agonists used most widely in this setting (salbutamol and terbutaline). Beta2-agonists and ipratropium both produce small improvements in FEV1, but beta2-agonists may worsen PaO2 for a period. We could not draw conclusions concerning possible additive effects.

Administration, Inhalation↗

PubMed2001

Evaluation of uncalibrated preferential flow models against data for isoproturon movement to drains through a heavy clay soil.

The uncalibrated predictive ability of four preferential flow models (CRACK-NP, MACRO/MACRO_DB, PLM, SWAT) has been evaluated against point rates of drainflow and associated concentrations of isoproturon from a highly structured and heterogeneous clay soil in the south of England. Data were available for four plots for a number of storm events in each of three successive growing seasons. The mechanistic models CRACK-NP and MACRO generally gave reasonable estimates of drainflow over the three seasons, but under-estimated concentrations of isoproturon over a prolonged period in the first season and over-estimated them in the two remaining seasons. CRACK-NP simulated maximum concentrations of isoproturon over the first two events of each of the three seasons of 156, 527 and 24.4 micrograms litre-1, respectively, and matched the observed data (465, 65.1 and 0.65 micrograms litre-1) slightly better than MACRO (69.1, 566 and 58.5 micrograms litre-1). Automatic selection of parameters from soils information within MACRO_DB reduced the emphasis on preferential flow relative to the stand-alone version of MACRO. This gave a poor simulation of isoproturon breakthrough and simulated maximum concentrations were 0, 50.1 and 35.1 micrograms litre-1, respectively. The capacity model PLM gave the best overall simulation of total drainflow for the first two events in each season, but over-estimated concentrations of isoproturon (967, 808 and 51.3 micrograms litre-1). The simple model SWAT represented total drainflow reasonably well and gave the best simulation of maximum isoproturon concentrations (140, 80.2 and 8.2 micrograms litre-1). There was no clear advantage here in using the mechanistic models rather than the simpler models. None of the models tested was able to simulate consistently the data set, and uncalibrated modelling cannot be recommended for such artificially drained heavy clay soils.

Aluminum Silicates↗

PubMed2001

Influence of topsoil tilth and soil moisture status on losses of pesticide to drains from a heavy clay soil.

Twelve lysimeters with a surface area of 0.5 m2 and a length of 60 cm were taken over mole drains from a Denchworth heavy clay soil and divided into two groups with either a standard agricultural tilth or a finer topsoil tilth. The influence of topsoil tilth on leaching of the herbicide isoproturon and a bromide tracer was evaluated over a winter season. The effect of variations in soil moisture status in the immediate topsoil on leaching of isoproturon, chlorotoluron and linuron was investigated in the following winter season. Here, water inputs were controlled such that lysimeters received 50 mm at a maximum intensity of 2 mm h-1 over a 4-week period with herbicides applied on day 15. Three treatments received the water either all prior to application, all after application, or evenly spread over the 4-week period. Leaching losses of the three herbicides were monitored for a subsequently drainage event. Analysis of covariance showed a significant effect of topsoil tilth and total flow on both the maximum concentrations (P = 0.034) and total losses (P = 0.012) of isoproturon in drainflow. Both concentrations and losses were c 35% smaller from lysimeters with the finer tilth. However, generation of the fine tilth in the field was restricted by a wet autumn and this is not considered a reliable management option for reducing pesticide losses from heavy clay soils. In the second experiment, variation in soil moisture content prior to and after application did not have any significant effect (P < 0.05) upon subsequent losses of the three herbicides to drains.

Aluminum Silicates↗

PubMed2001

Regulation of 15-lipoxygenase isozymes and mucin secretion by cytokines in cultured normal human bronchial epithelial cells.

OBJECTIVE AND DESIGN: To study the effects of IL-4, IL-13, IL-1beta, IL-8 and TNFalpha on 15-lipoxygenase(15-LO) isozyme expression and mucin secretion in normal human bronchial epithelial cells. MATERIAL AND METHODS: The effects of IL-4, IL-13, IL-1beta, IL-8 and TNFalpha on 15-LO isoenzyme mRNA and protein expression, total 15-LO enzyme activity and mucin secretion were examined in cultures of normal human bronchial epithelial cells. In addition, in order to determine whether the observed effects on mucin secretion were due to lipoxygenase (LO) products, the effect of the non-selective LO inhibitor nordihydroguaiaretic acid was examined. RESULTS: IL-4 and IL- 13 selectively enhanced 15-LOa mRNA and protein levels, and total 15-LO enzyme activity. In contrast, no changes were observed in 15-LOb mRNA or protein levels. IL-4 and IL-13 both reduced mucin secretion in this cell type, however the non-selective LO inhibitor nordihydroguaiaretic acid had no effect on this action of IL-4. CONCLUSIONS: These data demonstrate that IL-4 and IL-13 selectively regulate the expression of the 15-LOa isozyme. However, 15LOa products do not mediate the IL-4-induced reduction in mucin secretion observed in this cell type.

Arachidonate 15-Lipoxygenase↗

PubMed2001

Effects of erythropoietin and aminoguanidine on red blood cell deformability in diabetic azotemic and uremic patients.

Impaired red blood cell-deformability (RBC-df) is noted in patients with diabetes and may play a role in the pathogenesis of microvasculopathy and nephropathy. We report the effects of erythropoietin (EPO) alone and combined with aminoguanidine (AG) for 1 year on RBC-df in predialysis patients (P-DPs) with renal insufficiency and in end-stage renal disease (ESRD) patients on maintenance hemodialysis (DPs). Nine P-DPs who received EPO 50 U/kg by subcutaneous injection 3 times per week are compared with 5 P-DPs treated without EPO (mean serum creatinine 4.1 +/- 0.1 versus 4.2 +/- 0.6 mg/dL, respectively). Twelve DPs (Kt/V = 1.5 +/- 0.1) were studied. Six DPs received AG 200 mg/every other day by mouth and EPO 50 U/kg by intravenous (IV) injection, and 6 DPs received EPO (50 U/kg) and placebo and served as control. RBC-df improved significantly in 9 P-DPs treated with EPO at 6 months (from 2.7 +/- 0.1 to 1.6 +/- 0.2, P = 0.005). This positive effect was sustained at 12 months (P = 0.005); there was no change in RBC-df in P-DPs receiving usual care without EPO. RBC-df improved significantly and progressively at 6 and 12 months in DPs treated with EPO and AG (from 2.2 +/- 0.2 to 1.8 +/- 0.2; P = 0.01; 1.2 +/- 0.1; P = 0.001, respectively); there was limited improvement in RBC-df in DPs treated with EPO and placebo. We conclude that EPO treatment significantly improved RBC-df in diabetic P-DPs, but EPO alone has no significant effect on RBC-df after 12 months in diabetic DPs. The combination of EPO and AG restores RBC-df to near-normal levels in diabetic DPs. We speculate that the effect of EPO on RBC-df seen in P-DPs and DPs is related to increased synthesis and influx of new and younger RBCs. AG may confer protection of RBCs in DPs by blocking advanced glycosylated end-product (AGE) formation.

Area Under Curve↗

PubMed2001

Prior exposure to aged and diluted sidestream cigarette smoke impairs bronchiolar injury and repair.

The bronchiolar injury/repair response to naphthalene (NA) in mice includes acute distal airway epithelial injury that is followed by epithelial proliferation and redifferentiation, which result in repair of the epithelium within 14 days. To test whether prior exposure to aged and diluted sidestream cigarette smoke (TS) would alter the injury/repair response of the airway epithelium, adult mice were exposed to either filtered air (FA) or smoke for 5 days before injection with either corn oil carrier (CO) or naphthalene. Mice were killed 1 and 14 days after naphthalene injury. Lung and lobar bronchus were examined and measured using high-resolution epoxyresin sections. The control group (FACOFA) that was exposed to filtered air/corn oil/filtered air contained airway epithelium similar to untreated controls at all airway levels. The group exposed to tobacco smoke/corn oil/filtered air (TSCOFA) contained some rounded cells in the small airways and some expansion of the lateral intercellular space in the larger airways. Necrotic or vacuolated cells were not observed. As expected, the epithelium in the group exposed to filtered air/naphthalene/filtered air (FANAFA) contained many light-staining vacuolated Clara cells and squamated ciliated cells within distal bronchioles during the acute injury phase. Repair (including redifferentiation of epithelial cells and restoration of epithelial thickness) was nearly complete 14 days after injury. The extent of Clara cell injury, as assessed in lobar bronchi, was not different between the four groups. Although the FANAFA group contained greater initial injury in the distal airways at 1 day, the group exposed to tobacco smoke/naphthalene/filtered air (TSNAFA) had the least amount of epithelial repair at 14 days after naphthalene treatment; many terminal bronchioles contained abundant squamated undifferentiated epithelium. We conclude that tobacco smoke exposure prior to injury (1) does not change the target site or target cell type of naphthalene injury, since Clara cells in terminal bronchioles are still selectively injured; (2) results in slightly diminished acute injury from naphthalene in distal bronchioles; and (3) delays bronchiolar epithelial repair.

Acute Disease↗

PubMed2001

Coping with a MEDLIB-L service outage.

OBJECTIVE: The study assessed the coping strategies of MEDLIB-L subscribers during an unexpected disruption in the list's service. METHODS: An online survey of MEDLIB-L subscribers was performed following a six-day service outage in August 1999. RESULTS: Respondents' information needs resulted in two distinct coping strategies. Subscribers without a recognized information need or an information need determined to be not pressing coped by waiting out the interruption. Subscribers with pressing information needs turned to alternative methods of resolving these needs. CONCLUSIONS: While most respondents missed the list and the assistance that it provided, many did not feel that the outage required significant coping strategies. The outage was viewed as a "minor stressor" and did not require secondary-level assessment of the availability and suitability of alternative resources.

Anecdotes as Topic↗

PubMed2000

The neprilysin family in health and disease.

The mammalian neprilysin (NEP) family comprises at least seven members: NEP itself, Kell blood group antigen (KELL), the endothelin-converting enzymes (ECE-1 and ECE-2), the enzyme PEX, associated with X-linked hypophosphataemia, "X-converting enzyme" (XCE) a CNS-expressed orphan peptidase and a soluble, secreted endopeptidase (SEP). These zinc metallopeptidases are all type II integral membrane proteins. Where identified, these enzymes have roles in the processing or metabolism of regulatory peptides and therefore represent potential therapeutic targets. A distinct feature of ECE-1 species is their existence as distinct isoforms differing in their N-terminal cytoplasmic tails. These tails play a role in enzyme targeting and turnover with di-leucine and tyrosine-based motifs affecting localization. Additional anchorage of these enzymes can also occur through palmitoylation. Bacterial homologues of the neprilysin family exist, for example the products of the pepO genes from L. lactis and S. parasanguis, and a recently described gene product of P. gingivalis which is an ECE-1 homologue that can catalyse the conversion of big endothelin to endothelin. A genomics based approach to understanding the functions of this proteinase family is aided by the completion of the C. elegans and Drosophila genomes, both of which encode multiple copies of NEP-like enzymes.

Acylation↗

PubMed2000

Pesticides in rainfall in Europe.

Papers and published reports investigating the presence of pesticides in rainfall in Europe were reviewed. Approximately half of the compounds that were analysed for were detected. For those detected, most concentrations were below about 100 ng/l, but larger concentrations, up to a few thousand nanograms per litre, were detected occasionally at most monitoring sites. The most frequently detected compounds were lindane (gamma-HCH) and its isomer (alpha-HCH), which were detected on 90-100% of sampling occasions at most of the sites where they were monitored. For compounds developed more recently, detection was usually limited to the spraying season. A classification of pesticides according to their deposition pattern is proposed.

Journal Article↗

PubMed2000

Body mass index and the prevalence of hypertension and dyslipidemia.

OBJECTIVE: To describe and evaluate relationships between body mass index (BMI) and blood pressure, cholesterol, high-density lipoprotein-cholesterol (HDL-C), and hypertension and dyslipidemia. RESEARCH METHODS AND PROCEDURES: A national survey of adults in the United States that included measurement of height, weight, blood pressure, and lipids (National Health and Nutrition Examination Survey III 1988-1994). Crude age-adjusted, age-specific means and proportions, and multivariate odds ratios that quantify the association between hypertension or dyslipidemia and BMI, controlling for race/ethnicity, education, and smoking habits are presented. RESULTS: More than one-half of the adult population is overweight (BMI of 25 to 29.9) or obese (BMI of > or =30). The prevalence of high blood pressure and mean levels of systolic and diastolic blood pressure increased as BMI increased at ages younger than 60 years. The prevalence of high blood cholesterol and mean levels of cholesterol were higher at BMI levels over 25 rather than below 25 but did not increase consistently with increasing BMI above 25. Rates of low HDL-C increased and mean levels of HDL-C decreased as levels of BMI increased. The associations of BMI with high blood pressure and abnormal lipids were statistically significant after controlling for age, race or ethnicity, education, and smoking; odds ratios were highest at ages 20 to 39 but most trends were apparent at older ages. Within BMI categories, hypertension was more prevalent and HDL-C levels were higher in black than white or Mexican American men and women. DISCUSSION: These data quantify the strong associations of BMI with hypertension and abnormal lipids. They are consistent with the national emphasis on prevention and control of overweight and obesity and indicate that blood pressure and cholesterol measurement and control are especially important for overweight and obese people.

Adult↗