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Plant exposures: a state profile of the most common species.

Plant exposures are the fourth most common cause of poisoning and 86% of those exposures involve the pediatric population. The large number of plant-related exposures and the lack of knowledge about plant toxicity has led to plant paranoia and considerable educational efforts to reduce the number of exposures. These efforts are often dictated by misconceptions and folklore. AAPCC TESS data on all plant exposures for the years 1985-1994 were electronically analyzed by plant species and state to establish a frequency distribution in the US. Aggregate national data was also tabulated. A total of 912,534 plant exposures were analyzed to tabulate the top 30 plant exposures for each state. Philodendron species were the most common exposures, followed by Dieffenbachia species, Euphorbia pulcherrima, Capsicum annuum and Ilex species. There were considerable differences between states relating to indoor vs outdoor plants and native vs introduced varieties. Plant exposures are common and poison information centers devote significant clinical service and educational effort to manage them and to enhance public awareness. Recognition of specific plant species and exposure frequency in a poison center region can be a basis for staff education and the development of appropriate poison prevention education brochures. This can direct better utilization of poison center's resources.

Data Collection↗

Cytoskeleton/endoplasmic reticulum collapse induced by prostaglandin J2 parallels centrosomal deposition of ubiquitinated protein aggregates.

Many neurodegenerative disorders, such as Parkinson disease, exhibit inclusion bodies containing ubiquitinated proteins. The mechanisms implicated in this aberrant protein deposition remain elusive. In these disorders signs of inflammation are also apparent in the affected central nervous system areas. We show that prostaglandin J2 (PGJ2), an endogenous product of inflammation, disrupts the cytoskeleton in neuronal cells. Furthermore, PGJ2 perturbed microtubule polymerization in vitro and decreased the number of free sulfhydryl groups on tubulin cysteines. A direct effect of PGJ2 on actin was not apparent, although actin filaments were altered in cells treated with PGJ2. This cyclopentenone prostaglandin triggered endoplasmic reticulum (ER) collapse and the redistribution of ER proteins, such as calnexin and catechol-O-methyltransferase, into a large centrosomal aggregate containing ubiquitinated proteins and alpha-synuclein. The PGJ2-dependent cytoskeletal rearrangement paralleled the development of the large centrosomal aggregate. Both of these events were replicated by treating cells with colchicine, which disrupts the microtubule/ER network, but not with brefeldin A, which impairs ER/Golgi transport. PGJ2 also perturbed 26 S proteasome assembly and activity, which preceded the accumulation of ubiquitinated proteins as detergent/salt-insoluble aggregates. Our data support a mechanism by which, upon PGJ2 treatment, cytoskeleton/ER collapse coincides with the relocation of ER proteins, other potentially neighboring proteins, and ubiquitinated proteins into centrosomal aggregates. Development of these large perinuclear aggregates is associated with disruption of the microtubule/ER network. This aberrant protein deposition, triggered by a product of inflammation, may be common to other compounds that disrupt microtubules and induce protein aggregation, such as MPP+ and rotenone, found to be associated with neurodegeneration.

Actins↗

The length of polyglutamine tract, its level of expression, the rate of degradation, and the transglutaminase activity influence the formation of intracellular aggregates.

A common feature of CAG-expansion neurodegenerative diseases is the presence of intranuclear aggregates in neuronal cells. We have used a synthetic fusion protein containing at the NH2 terminus the influenza hemoagglutinin epitope (HA), a polyglutamine stretch (polyQ) of various size (17, 36, 43 CAG) and a COOH tail encoding the green fluorescent protein (GFP). The fusion proteins were expressed in COS-7 and neuroblastoma SK-N-BE cells. We found that the formation of aggregates largely depends on the length of polyglutamine tracts and on the levels of expression of the fusion protein. Moreover, transglutaminase overexpression caused an increase of insoluble aggregates only in cells expressing the mutant expanded protein. Conversely, treatment of cells with cystamine, a transglutaminase inhibitor, reduced the percentage of aggregates. We found also that the inhibition of the proteasome ubiquitin-dependent degradation increased the formation of intranuclear aggregates. These data suggest that length of polyglutamine tract, its expression, unbalance between cellular transglutaminase activity, and the ubiquitin-degradation pathway are key factors in the formation of intranuclear aggregates.

Acetylcysteine↗

Does drinking really decrease in bad times?

This paper investigates the relationship between macroeconomic conditions and drinking using individual-level data from 1987 to 1999 interview years of the "behavioral risk factor surveillance system" (BRFSS). We confirm the procyclical variation in overall drinking identified in previous research using aggregate sales data and show that this largely results from changes in consumption by existing drinkers, rather than movements into or out of drinking. Moreover, the decrease occurring during bad economic times is concentrated among heavy consumers, with light drinking actually rising. We also find no evidence that the decline in overall alcohol use masks a rise for persons becoming unemployed during contractions. These results suggest that any stress-induced increases in drinking during bad economic times are more than offset by declines resulting from changes in economic factors such as lower incomes.

Adaptation, Psychological↗

Resource costing for multinational neurologic clinical trials: methods and results.

We present the results of a multinational resource costing study for a prospective economic evaluation of a new medical technology for treatment of subarachnoid hemorrhage within a clinical trial. The study describes a framework for the collection and analysis of international resource cost data that can contribute to a consistent and accurate intercountry estimation of cost. Of the 15 countries that participated in the clinical trial, we collected cost information in the following seven: Australia, France, Germany, the UK, Italy, Spain, and Sweden. The collection of cost data in these countries was structured through the use of worksheets to provide accurate and efficient cost reporting. We converted total average costs to average variable costs and then aggregated the data to develop study unit costs. When unit costs were unavailable, we developed an index table, based on a market-basket approach, to estimate unit costs. To estimate the cost of a given procedure, the market-basket estimation process required that cost information be available for at least one country. When cost information was unavailable in all countries for a given procedure, we estimated costs using a method based on physician-work and practice-expense resource-based relative value units. Finally, we converted study unit costs to a common currency using purchasing power parity measures. Through this costing exercise we developed a set of unit costs for patient services and per diem hospital services. We conclude by discussing the implications of our costing exercise and suggest guidelines to facilitate more effective multinational costing exercises.

Australia↗

Diversity of signaling underlying responses mediated by selective activation of the platelet thromboxane A2 (TXA2) receptor; pharmacological and kinetic studies in vitro.

Selective activation of the platelet TXA2 receptor is sufficient to mediate concurrent aggregation, deaggregation and shape change (SC) responses without activation of known Gi-coupled receptors (Platelets 2003; 14: 89). However, Gi-coupled receptor activation strongly influences the hemostasis response in vivo. This study investigated the modulatory effects of two signaling pathways related to Gi-coupled receptor activation, stimulation of phosphoinositide 3-kinases (PI3Ks) and inhibition of adenylyl cyclase (AC), on the aggregation, deaggregation and SC components of the platelet activation response. A novel turbidimetric approach was applied to separate these responses and to characterize their pharmacology and kinetics. The SC response was more sensitive to TXA2 receptor activation (lower EC50 value) but less sensitive to a TXA2 receptor antagonist (higher Kd value) than the net aggregation response. Epinephrine and sulprostone, agonists of the Gi-coupled alpha2A-adrenoceptor and EP3 receptor, respectively, amplified the SC, decelerated deaggregation and enhanced net aggregation responses. SQ22536 and 2',5'-dideoxyadenosine, inhibitors of AC activity, elicited smaller but qualitatively similar effects. The PI3K inhibitor wortmannin did not affect the SC response but accelerated deaggregation and inhibited net aggregation. These data are consistent with a differential modulation of the platelet SC response by each pathway associated with Gi-coupled receptor activation, while both pathways cooperatively enhance the net aggregation response by decelerating deaggregation. We propose that the TXA2 receptor mediated concurrent platelet aggregation and SC responses, that are differentially modulated by different signaling pathways, provide a model for studying the underlying cellular pharmacology of platelet physiology.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Activation of neutral metalloprotease in human osteoarthritic knee cartilage: evidence for degradation in the core protein of sulphated proteoglycan.

The neutral, metal dependent, proteoglycan degrading enzymes (NMPEs) in human osteoarthritic knee cartilage homogenates were activated by p-aminophenylmercuric acetate (APMA). The resultant effect on the structure of newly synthesised and already existing sulphated proteoglycan was measured. Newly synthesised and already existing proteoglycan aggregated to hyaluronic acid was reduced (p less than 0.01, p less than 0.05 respectively) when measured by chromatography on Sepharose CL-2B eluted with associative buffer. The APMA activated enzyme affected both the newly synthesised and already existing proteoglycan aggregate similarly (r = 0.79, p less than 0.001). Treatment of cartilage homogenates with APMA and 1,10-phenanthroline (10 mM) showed that the amount of aggregated proteoglycan was at the control level. The hydrodynamic size of the proteoglycan monomer (A1D1) was also reduced by treatment of cartilage homogenates with APMA. Reaggregation experiments with fraction A1D1 and exogenous hyaluronic acid and link protein showed a similar defect in forming proteoglycan aggregates. These data showed that activation of the NMPEs altered the structure of proteoglycan in two ways. The most consistent change was a reduction in the ability of proteoglycan to form aggregates with hyaluronic acid. This was likely to have occurred via a cleavage of the core protein in or around the hyaluronic acid binding globular domain. A second alteration probably includes a limited proteolytic cleavage in the remainder of the core protein.

Aged↗

Reliability and validity of an interactive computer method for rating quality of life.

OBJECTIVE: The purpose of this study was to describe the reliability and validity of an interactive computer method that assesses the quality of life of patients in chronic pain and healthy individuals. METHODS: A software program to assess 21 aspects of quality of life was administered to 88 pain patients on two occasions separated by an average of 30 days. Comparison data were obtained from 105 healthy individuals retested after an average of 16 days. RESULTS: For both groups, moderate test-retest correlations occurred for mean ratings based on an aggregation of data for all variables, single global ratings, and single ratings of individual variables. Patients in chronic pain scored significantly lower on all quality of life variables than did healthy individuals. High correlations were obtained between mean ratings from the present study and those from an earlier investigation using the same method. CONCLUSIONS: The interactive computer method is both reliable and valid as a means to assess quality of life for patients in chronic pain as well as for healthy individuals.

Adult↗

The risk of hospitalization in patients with asthma switched from an inhaled corticosteroid to a leukotriene receptor antagonist.

Asthma-related hospitalization rates were compared over a 2-year period between a cohort of patients with asthma who switched from an inhaled corticosteroid in year 1 to a leukotriene modifier in year 2 (n = 285) and a matched cohort continuously treated with an inhaled corticosteroid (n = 570). During year 1, patients were well maintained, with a hospitalization rate of 1.1% to 1.4%. During year 2, 2.5% of the patients switched to a leukotriene modifier had one or more asthma-related hospitalizations compared with 0.6% of the patients continuously receiving an inhaled corticosteroid. Patients treated with a leukotriene modifier were at 7 times greater risk for an asthma-related hospitalization compared with patients who continued to receive an inhaled corticosteroid (risk-adjusted odds ratio, 7.1; 95% CI, 2.79-17.95). These data are consistent with the results of well-controlled clinical trials showing that leukotriene modifiers may be associated with deterioration of asthma control relative to inhaled corticosteroids. Considered in aggregate, the data support the conclusion that leukotriene modifiers should not be substituted for inhaled corticosteroids as a single-controller therapy for asthma.

Administration, Inhalation↗

A study of leukaemia in Glasgow in connection with chromium-contaminated land.

BACKGROUND: In 1991, soil pollution was found around the site of a former chromium-processing factory in Glasgow, Scotland. Levels of chromium in soil were above limits considered as safe, although a risk assessment concluded that population exposure was likely to be below occupational levels. As an excess incidence of leukaemia has been suspected in the area, it was decided to investigate a possible relationship between the pollutant and the illness. METHODS: The ensuing study was descriptive-geographical. In the absence of better data, levels of exposure were assumed to decrease with distance from the centre of the polluted area. Leukaemia and population figures were obtained for each of nine concentric rings by aggregation of data available at the Enumeration District level. The null study hypothesis was that relative risk (as measured by Poisson regression) would not follow a definite trend with distance from the centre. Sex, age and levels of deprivation were taken into account. RESULTS: Relative risks by variables other than distance followed previously known patterns for leukaemia. No evident pattern by distance was found. After regroupings inside the variables, a significant excess of leukaemia was found for intermediate distances from the pollutant. CONCLUSIONS: No evidence was found of a possible relationship between soil pollution by chromium and leukaemia in the general population. Nonetheless, the excess noticed by the study warrants further research.

Adolescent↗

Inhibition of N-linked glycosylation in Dictyostelium discoideum: effects of aggregate formation.

The aggregation program of Dictyostelium discoideum is extremely sensitive to the effects of tunicamycin when the drug is added to cells during the first few hours of starvation. Inhibition of development is observed with concentrations as low as 0.5 micrograms/ml, which cause only a 25%-30% inhibition of general N-linked glycosylation. However, 0.5 micrograms/ml tunicamycin can result in the total inhibition of N-linked glycosylation of specific, developmentally regulated, proteins, as exemplified by the glycoprotein 117 antigen. If added after the first hours of starvation, tunicamycin cannot inhibit aggregation even when present at 10 micrograms/ml, which maximally inhibits N-linked glycosylation. cAMP pulses can override the inhibitory effects of tunicamycin on cell aggregation. The data support the hypothesis that there is an early developmental pathway that is dependent on the N-linked glycosylation of one, or a small set of developmentally regulated proteins and that this pathway may involve the biogenesis of the chemotactic signalling system. In addition, the data raise questions as to the role of N-linked oligosaccharides in cell cohesion.

Cell Aggregation↗

Practice Audit in Gastroenterology (PAGE) program: a novel approach to continuing professional development.

BACKGROUND: Practice audit is an important component of continuing professional development that may more readily be undertaken if it were less complex. This qualitative study assessed the use of personal digital assistants to facilitate data collection and review. METHODS: Personal digital assistants programmed with standard questionnaires related to upper gastrointestinal endoscopies (Practice Audit in Gastroenterology-Endoscopy ['PAGE-Endo']) and colonoscopies (PAGE-Colonoscopy ['PAGE-Colo']) were provided to Canadian gastroenterologists, surgeons and internists. Over a three-week audit period, participants recorded indications, and the expected (E) and reported (R) findings for each procedure. Thereafter, participants recorded compliance with reporting, the ease of use and value of the PAGE program, and their willingness to perform another audit. RESULTS: Over 15 to 18 months, 173 participants completed PAGE-Endo (6168 procedures) and 111 completed PAGE-Colo (4776 procedures). Most respondents noted that PAGE was easy to use (99%), beneficial (88% to 95%), and that they were willing undertake another audit (92% to 95%). In PAGE-Endo, alarm features were prevalent (55%), but major reported findings were less common than expected: esophagitis (E 29.9%, R 14.8%), esophageal stricture (E 8.3%, R 3.6%), gastric ulcer (E 17.0%, R 4.7%), gastric cancer (E 4.3%, R 1.0%) and duodenal ulcer (E 11.5%, R 5.7%). In PAGE-Colo, more colonoscopies were performed for symptom investigation (55%) than for screening (25%) or surveillance (20%). There were marked interprovincial variations with respect to sedation, biopsies and technical aspects of colonoscopy. CONCLUSION: Secure, real-time data entry with review of aggregate and individual data in the PAGE program provided an acceptable, straightforward methodology for accredited practice audit activities. PAGE has considerable potential for continuing professional development in gastroenterology and other specialties.

Canada↗

Pharmacokinetic model of circulating covalent aggregates of insulin.

Covalent aggregates of insulin in blood of insulin-treated diabetic patients account for as much as 70% (mean 28 +/- 3.6%) of serum insulin immunoreactivity. These aggregates may originate in therapeutic insulin, because similar substances account for 0.1-3% of these preparations. Larger amounts in blood imply that aggregates accumulate as a result of delayed clearance. To test and quantify this speculation, we calculated the plasma kinetics of this material in four normal volunteers who received large intravenous doses (30 mU.kg-1.min-1) of beef-pork crystalline zinc insulin for 120 min. Insulin aggregate and monomer concentrations were measured in blood samples obtained at regular intervals throughout the infusion and during 4 h after discontinuation of insulin. Pharmacokinetic parameters were calculated from the data. Insulin aggregate and monomer serum t 1/2 were 63.6 +/- 6.9 and 34.3 +/- 2.8 min, respectively, and clearances were 101 +/- 10 and 232 +/- 47 ml/min. Volume of distribution (V beta) and volume at steady state (Vss) were 9.1 +/- 1.8 and 8.2 +/- 2.2 L for insulin aggregate and 11.6 +/- 2.8 and 12.2 +/- 3.6 L for insulin monomer, respectively. Mean residency time was 141 +/- 14 and 114 +/- 10 min for insulin aggregate and monomer, respectively [P less than .01 for all parameters except V beta (.014) and Vss (.012), aggregate vs. monomer]. Thus, in relation to insulin monomer, calculated pharmacokinetic parameters of the aggregate predict accumulation after insulin injection. Plasma t 1/2 of the aggregate was almost double that of monomeric insulin; total-body clearance and the corresponding volumes of distribution were smaller.

Adult↗

Improvement potential in Danish elderly care.

This paper examines Danish elderly care resource utilization among municipalities. The available production data are aggregated, which means that it is virtually impossible to allocate costs to specific services. We show that Multi-directional Efficiency Analysis (MEA) provides a much more subtle performance picture than Data Envelopment Analysis (DEA) because we are able to assess the input specific relative improvement potentials. The empirical results show considerable improvement potential for all inputs. The largest relative potential for improvement is found for administrative staff.

Aged↗

Effect of different concentrations of citrate on the sensitivity of an "in vitro" spontaneous platelet aggregation test.

Our data show that variations of the concentration of citrate in blood used for the "in vitro" spontaneous platelet aggregation tests, at the limits of those generally held to be without effect, have a definite influence on the results obtained. In addition, out findings suggest that a correct selection of one of the two variants of the test allows a flexibility of the sensitivity and, reciprocally, the specificity without interfering with the quality of the information which they are capable of providing. Thus, a differentiated application of Test A and Test B is possible according to different experimental or diagnostic necessities for the prevailing need of, respectively, a maximum sensitivity or of a maximum specificity.

Adult↗

Platelet aggregation may not be a prerequisite for collagen-stimulated platelet generation of nitric oxide.

By determining the sum of the supernatant concentrations of nitrite and nitrate the stimulated generation of nitric oxide (NO) by human washed platelets induced by a range of fibrillar collagen concentrations (0.0156-25 microg ml(-1)) was investigated. Platelet serotonin (5-hydroxytryptamine, 5-HT) efflux and platelet aggregation were also measured. Under resting conditions (0 microg ml(-1) collagen) platelet NO release was equivalent to 1.06+/-0.17 nmol per 10(8) platelets. Maximal NO release, equivalent to 2.1+/-0. 37 nmol per 10(8) platelets, was observed with only 0.0625 microg ml(-1) collagen (P<0.02, stimulated vs. resting release), higher collagen concentrations producing no further increases in platelet NO output. By contrast, maximal platelet aggregation and 5-HT efflux did not occur until collagen concentrations of 2.5 microg ml(-1) and 10-25 microg ml-1), respectively, had been achieved. L-NAME (1 mmol l(-1)) and L-NMMA (1 mmol l(-1)) inhibited stimulated platelet NO generation by 78+/-6% and 72%, respectively. Contrasting with fibrillar collagen, fibrillar beta-amyloid protein had no effect on platelet NO generation, or on 5-HT efflux or aggregation. These data perhaps indicate that NO generation by human platelets is stimulated by concentrations of fibrillar collagen insufficient to elicit an aggregatory response. Such a mechanism could operate in vivo to inhibit platelet aggregation which might otherwise be induced by low concentrations of circulating agonists.

Blood Platelets↗

Conformational prerequisites for alpha-lactalbumin fibrillation.

Bovine alpha-lactalbumin, a small acidic Ca(2+)-binding milk protein, formed amyloid fibrils at low pH, where it adopted the classical molten globule-like conformation. Fibrillation was accompanied by a dramatic increase in the beta-structure content and a characteristic increase in the thioflavin T fluorescence intensity. S-(Carboxymethyl)-alpha-lactalbumin, a disordered form of the protein with three out of four disulfide bridges reduced, was even more susceptible to fibrillation. Other partially folded conformations induced in the intact protein at neutral pH, either by the removal of Ca(2+) or by the binding of Zn(2+) to the Ca(2+)-protein complex, did not fibrillate, although Zn(2+)-loaded alpha-lactalbumin precipitated out of solution as amorphous aggregates. Our data suggest that the transformation of a protein into an essentially unfolded (thus, highly flexible) conformation is required for successful fibril formation, whereas more rigid (but still flexible) species may form amorphous aggregates.

Amyloid↗

The lifetime distribution of health care costs.

OBJECTIVE: To estimate the magnitude and age distribution of lifetime health care expenditures. DATA SOURCES: Claims data on 3.75 million Blue Cross Blue Shield of Michigan members, and data from the Medicare Current Beneficiary Survey, the Medical Expenditure Panel Survey, the Michigan Mortality Database, and Michigan nursing home patient counts. DATA COLLECTION: Data were aggregated and summarized in year 2000 dollars by service, age, and gender. STUDY DESIGN: We use life table models to simulate a typical lifetime's distribution of expenditures, employing cross-sectional data on age- and sex-specific health care costs and the mortality experience of the population. We determine remaining lifetime expenditures at each age for all initial members of a birth cohort. Separately, we calculate remaining expenditures for survivors at all ages. Using cross-sectional data, the analysis holds disease incidence, medical technology, and health care prices constant, thus permitting an exclusive focus on the role of age in health care costs. PRINCIPAL FINDINGS: Per capita lifetime expenditure is USD $316,600, a third higher for females (USD $361,200) than males (USD $268,700). Two-fifths of this difference owes to women's longer life expectancy. Nearly one-third of lifetime expenditures is incurred during middle age, and nearly half during the senior years. For survivors to age 85, more than one-third of their lifetime expenditures will accrue in their remaining years. CONCLUSIONS: Given the essential demographic phenomenon of our time, the rapid aging of the population, our findings lend increased urgency to understanding and addressing the interaction between aging and health care spending.

Adolescent↗