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1.
Cardiovasc Revasc Med ; 57: 82-90, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37400345

RESUMEN

BACKGROUND: The optimal parameters for defining stages of cardiogenic shock (CS) are not yet known. The Cardiogenic Shock Working Group-defined Society for Cardiovascular Angiography and Interventions (CSWG-SCAI) staging of CS was developed to provide simple and specific parameters for risk-stratifying patients. OBJECTIVES: The purpose of this study was to test whether the Cardiogenic Shock Working Group-defined Society for Cardiovascular Angiography and Interventions (CSWG-SCAI) staging is associated with in-hospital mortality, using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. METHODS: We utilized the open-access MIMIC-IV database, which includes >300,000 patients admitted between 2008 and 2019. We extracted the clinical profile of patients admitted with CS and stratified them into different SCAI stages at admission based on the CSWG criteria. We then tested the association between in-hospital mortality and parameters of hypotension, hypoperfusion, and overall CSWG-SCAI stage. RESULTS: Of the 2463 patients, CS was predominantly caused by heart failure (HF; 54.7 %) or myocardial infarction (MI; 26.3 %). Mortality was 37.5 % for the total cohort, 32.7 % for patients with HF, and 40 % for patients with MI (p < 0.001). Mortality was higher among patients with mean arterial pressure < 65 mmHg, lactate >2 mmol/L, ALT >200 IU/L, pH ≤ 7.2, and more than one drug/device support at baseline. Increasing CSWG-SCAI stages at baseline and maximum CSWG-SCAI stage achieved were significantly associated with in-hospital mortality (p < 0.05). CONCLUSIONS: The CSWG-SCAI stages are significantly associated with in-hospital mortality and may be used to identify hospitalized patients at risk of worsening cardiogenic shock severity. CONDENSED ABSTRACT: We analyzed data from 2463 patients with cardiogenic shock using the MIMIC-IV database to investigate the relationship between the Cardiogenic Shock Working Group-defined Society for Cardiovascular Angiography and Interventions (CSWG-SCAI) staging and in-hospital mortality. The main causes of cardiogenic shock were heart failure (54.7 %) and myocardial infarction (26.3 %). The overall mortality rate was 37.5 %, with a higher rate among patients with myocardial infarction (40 %) compared to those with heart failure (32.7 %). Mean arterial pressure < 65 mmHg, lactate >2 mmol/L, ALT >200 IU/L, and pH ≤ 7.2 were significantly associated with mortality. Increasing CSWG-SCAI stages at baseline and maximum achieved stages were strongly associated with higher mortality (p < 0.05). Therefore, the CSWG-SCAI staging system can be used to risk-stratify patients with cardiogenic shock.


Asunto(s)
Insuficiencia Cardíaca , Infarto del Miocardio , Humanos , Choque Cardiogénico/diagnóstico por imagen , Choque Cardiogénico/etiología , Angiografía Coronaria/efectos adversos , Insuficiencia Cardíaca/complicaciones , Cuidados Críticos , Mortalidad Hospitalaria , Lactatos
2.
Environ Pollut ; 318: 120848, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36563990

RESUMEN

The extensive use of antibiotics in food animal production and disposal of untreated wastewater from food animal slaughter facilities may create a shift in microbiomes of different ecosystems by generating reservoirs of antimicrobial resistance along the human-animal-environmental interface. This epidemiological problem has been studied, but its magnitude and impact on a global scale is poorly characterised. A systematic review was done to determine global prevalence and distribution patterns of antimicrobial resistance in effluent wastewater from animal slaughter facilities. Extracted data were stratified into rational groups for secondary analyses and presented as percentages. Culture and sensitivity testing was the predominant method; Escherichia spp., Enterococcus spp., and Staphylococcus aureus were the most targeted isolates. Variable incidences of resistance were detected against all major antimicrobial classes including reserved drugs such as ceftazidime, piperacillin, gentamicin, ciprofloxacin, and chloramphenicol; the median frequency and range in resistant Gram-negative isolates were: 11 (0-100), 62 (0-100), 8 (0-100), 14 (0-93) and 12 (0-62) respectively. Ciprofloxacin was the most tested drug with the highest incidences of resistance in livestock slaughterhouses in Iran (93%), Nigeria (50%) and China (20%), and poultry slaughterhouses in Germany (21-81%) and Spain (56%). Spatial global distribution patterns for antimicrobial resistance were associated with previously reported magnitude of antibiotic use in livestock or poultry farming and, the implicit existence of jurisdictional policies to regulate antibiotic use. These data indicate that anthropogenic activities in farming systems are a major contributor to the cause and dissemination of antimicrobial resistance into the environment via slaughterhouse effluents.


Asunto(s)
Antibacterianos , Aguas Residuales , Animales , Humanos , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Ecosistema , Prevalencia , Aves de Corral , Ciprofloxacina , Pruebas de Sensibilidad Microbiana
3.
Inhal Toxicol ; 34(9-10): 275-286, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35724235

RESUMEN

Objective: Stainless steel welding creates fumes rich in carcinogenic metals such as chromium (Cr). Welding consumables devoid of Cr are being produced in an attempt to limit worker exposures to toxic and carcinogenic metals. The study objective was to characterize a copper-nickel (Cu-Ni) fume generated using gas metal arc welding (GMAW) and determine the pulmonary deposition and toxicity of the fume in mice exposed by inhalation. Materials and Methods: Male A/J mice (6-8 weeks of age) were exposed to air or Cu-Ni welding fumes for 2 (low deposition) or 4 (high deposition) hours/day for 10 days. Mice were sacrificed, and bronchoalveolar lavage (BAL), macrophage function, and histopathological analyses were performed at different timepoints post-exposure to evaluate resolution. Results and Discussion: Characterization of the fume indicated that most of the particles were between 0.1 and 1 µm in diameter, with a mass median aerodynamic diameter of 0.43 µm. Metal content of the fume was Cu (∼76%) and Ni (∼12%). Post-exposure, BAL macrophages had a reduced ability to phagocytose E. coli, and lung cytotoxicity was evident and significant (>12%-19% fold change). Loss of body weight was also significant at the early timepoints. Lung inflammation, the predominant finding identified by histopathology, was observed as a subacute response early that progressively resolved by 28 days with only macrophage aggregates remaining late (84 days). Conclusions: Overall, there was high acute lung toxicity with a resolution of the response in mice which suggests that the Cu-Ni fume may not be ideal for reducing toxic and inflammatory lung effects.


Asunto(s)
Contaminantes Ocupacionales del Aire , Soldadura , Contaminantes Ocupacionales del Aire/análisis , Contaminantes Ocupacionales del Aire/toxicidad , Animales , Cromo , Cobre/toxicidad , Escherichia coli , Gases/análisis , Gases/farmacología , Pulmón , Masculino , Metales , Ratones , Níquel/toxicidad , Soldadura/métodos
4.
J Card Fail ; 27(10): 1082-1089, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34625128

RESUMEN

OBJECTIVE: Elevated blood lactate levels are strongly associated with mortality in patients with cardiogenic shock. Recent evidence suggests that the degree and rate at which blood lactate levels decrease after the initiation of treatment may be equally important in patient prognosis. We performed a systematic review and meta-analysis to evaluate the usefulness of lactate clearance as a prognostic factor in cardiogenic shock. METHODS AND RESULTS: We performed searches of Ovid MEDLINE, Elsevier EMBASE, EBM Reviews-Cochrane Central Register of Controlled Trials, and Web of Science to identify studies comparing lactate clearance between survivors and nonsurvivors at one or more timepoints. Both prospective and retrospective studies were eligible for inclusion. Two study investigators independently screened, extracted data, and assessed the quality of all included studies. Twelve studies were included in the meta-analysis. The median lactate clearance at 6-8 hours was 21.9% (interquartile range [IQR] 14.6%-42.1%) in survivors and 0.6% (IQR -3.7% to 14.6%) in nonsurvivors. At 24 hours, the median lactate clearance was 60.7% (IQR 58.1%-76.3%) and 40.3% (IQR 30.2%-55.8%) in survivors and nonsurvivors, respectively. Accordingly, the pooled mean difference in lactate clearance between survivors and nonsurvivors at 6-8 hours was 17.3% (95% CI 11.6%-23.1%, P < .001) at 6-8 hours and 27.9% (95% CI 14.1%-41.7%, P < .001) at 24 hours. CONCLUSIONS: Survivors had significantly greater lactate clearance at 6-8 hours and at 24 hours compared with nonsurvivors, suggesting that lactate clearance is an important prognostic marker in cardiogenic shock.


Asunto(s)
Insuficiencia Cardíaca , Choque Cardiogénico , Humanos , Ácido Láctico , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/terapia
5.
Toxicol Appl Pharmacol ; 427: 115652, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34298059

RESUMEN

Exposure to phosphine (PH3) presents with a host of diverse, non-specific symptoms that span multiple organ systems and is characterized by a high mortality rate. While a comprehensive mechanism for PH3 poisoning remains inconclusive, prior studies have implicated cardiac failure and circulatory compromise as potential pathways central to PH3-induced mortality. In this study, milrinone (MLR), a phosphodiesterase-3 inhibitor used to treat cardiac failure, was investigated as a potential countermeasure for PH3 poisoning. Lethality, physiological responses, and behavioral changes were evaluated in telemetrized female rats pretreated with water (sham) or one of three doses of MLR (40, 200, or 600 µg/kg) and exposed to PH3 (660 ppm for 25-40 min; 16,500-26,400 ppm × min). Animals receiving prophylactic administration of 600 µg/kg of MLR had nominally improved survivability compared to sham animals, although median lethal concentration-time and time of death did not differ substantially between treatment groups. Changes in respiration and behavior induced by PH3 appeared largely unaffected by MLR pretreatment, regardless of dose. Conversely, MLR pretreatment alleviated some aspects of PH3-induced cardiac function impairment, with slight dose-dependent effects observed for cardiac contractility, mean arterial pressure, and QRS duration. Together, these results illustrate the importance of circulatory compromise in PH3 poisoning and highlight the potential viability of MLR as a potential countermeasure option or part of a countermeasure regimen when administered prophylactically at 600 µg/kg.


Asunto(s)
Gasto Cardíaco/efectos de los fármacos , Cardiotónicos/administración & dosificación , Insecticidas/envenenamiento , Milrinona/administración & dosificación , Fosfinas/envenenamiento , Mecánica Respiratoria/efectos de los fármacos , Animales , Gasto Cardíaco/fisiología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Femenino , Exposición por Inhalación/efectos adversos , Dosificación Letal Mediana , Profilaxis Pre-Exposición/métodos , Ratas , Ratas Sprague-Dawley , Mecánica Respiratoria/fisiología , Tasa de Supervivencia/tendencias
6.
Sensors (Basel) ; 20(20)2020 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-33092311

RESUMEN

Dynamic elastic strain in ~1.8 and 1.0 m diameter containment vessels containing a high explosive detonation was measured using an array of fiber Bragg gratings. The all-optical method, called real-time localized strain measurement, recorded the strain for 10 ms after detonation with additional measurements being sequentially made at a rate of 1.7 MHz. A swept wavelength laser source provided the repetition rate necessary for such high-speed measurements while also providing enough signal strength and bandwidth to simultaneously measure 8 or more unique points on the vessel's surface. The data presented here arethen compared with additional diagnostics consisting of a fast spectral interferometer and an optical backscatter reflectometer to show a comparison between the local and global changes in the vessel strain, both dynamically and statically to further characterize the performance of the localized strain measurement. The results are also compared with electrical resistive strain gauges and finite element analysis simulations.

7.
Toxicol Rep ; 7: 1350-1355, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33102138

RESUMEN

It is estimated that greater than 1 million workers are exposed to welding fume (WF) by inhalation daily. The potentially toxic metals found in WF are known to cause multiple adverse pulmonary and systemic effects, including cardiovascular disease, and these metals have also been shown to translocate to the liver. This occupational exposure combined with a high fat (HF) Western diet, which has been shown to cause hyperlipidemia and non-alcoholic fatty liver disease (NAFLD), has the potential to cause significant mixed exposure metabolic changes in the liver. The goal of this study was to use matrix assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) to analyze the spatial distribution and abundance changes of lipid species in Sprague Dawley rat liver maintained on a HF diet combined with WF inhalation. The results of the MALDI-IMS analysis revealed unique hepatic lipid profiles for each treatment group. The HF diet group had significantly increased abundance of triglycerides and phosphatidylinositol lipids, as well as decreased lysophosphatidic lipids and cardiolipin. Ceramide-1-phosphate was found at higher abundance in the regular (REG) diet WF-exposed group which has been shown to regulate the eicosanoid pathway involved in pro-inflammatory response. The results of this study showed that the combined effects of WF inhalation and a HF diet significantly altered the hepatic lipidome. Additionally, pulmonary exposure to WF alone increased lipid markers of inflammation.

8.
Toxicol Rep ; 7: 1112-1120, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32864344

RESUMEN

Carfentanil is a powerful synthetic opioid that is approximately 100 times more potent than fentanyl and 10,000 times more potent than morphine. Carfentanil was originally intended to be used as a sedative for big game animals in a veterinary setting, but it is becoming increasingly recognized as a public health concern. We set out to investigate the effectiveness of naloxone against a potentially lethal dose of inhaled carfentanil in male ferrets. Ferrets were implanted with telemetry devices to study cardiac parameters and exposed to aerosolized carfentanil in a whole-body plethysmography chamber to record respiratory parameters. We observed profound respiratory depression in exposed animals, which led to apneic periods constituting 24-31 % of the exposure period. Concomitant with these apneic periods, we also observed cardiac abnormalities in the form of premature junctional contractions (PJCs). At our acute exposure dose, lethal in 3 % of our animals, naïve ferrets were unresponsive and incapacitated for a total of 126.1 ± 24.6 min. When administered intramuscularly at human equivalent doses (HEDs) of either 5 mg or 10 mg, naloxone significantly reduced the time that ferrets were incapacitated following exposure, although we observed no significant difference in the reduction of time that the animals were incapacitated between the treatment groups. Naloxone was able to quickly resolve the respiratory depression, significantly reducing the frequency of apneic periods in carfentanil-exposed ferrets. Our results suggest that naloxone, when administered via intramuscular injection following incapacitation, is a viable treatment against the effects of a potentially lethal dose of inhaled carfentanil.

9.
Ann N Y Acad Sci ; 1479(1): 196-209, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32285953

RESUMEN

Fluoroacetate (FA) is a tasteless, odorless, water-soluble metabolic poison with severe toxicological effects. Characterized in the mid-1900s, it has been used as a rodenticide but is comparably lethal to all mammals. Many countries have restricted its use, and modern-day accidental human exposures are rare, but recently, concerns have been raised about its application as a chemical weapon with no known antidote. A combined treatment of methylene blue (MB), an antioxidant, and monosodium glutamate (MSG), a precursor of the citric acid cycle substrate alpha-ketoglutarate, has been recommended as an effective countermeasure; however, no peer-reviewed articles documenting the efficacy of this therapy have been published. Using a rodent model, we assessed the effects of MB and MSG on the neurologic, cardiac, and pulmonary systems. Transcriptomic analysis was used to elucidate inflammatory pathway activation and guide bioassays, which revealed the advantages and disadvantages of these candidate countermeasures. Results show that MB and MSG can reduce neurologic signs observed in rats exposed to sodium FA and improve some effects of intoxication. However, while this strategy resolved some signs of intoxication, ultimately it was unable to significantly reduce lethality.


Asunto(s)
Fluoroacetatos/envenenamiento , Azul de Metileno/farmacología , Sistema Nervioso , Glutamato de Sodio/farmacología , Animales , Perfilación de la Expresión Génica , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Pulmón/metabolismo , Pulmón/patología , Masculino , Miocardio/metabolismo , Miocardio/patología , Sistema Nervioso/metabolismo , Sistema Nervioso/patología , Ratas , Ratas Sprague-Dawley
10.
Infect Dis Clin Pract (Baltim Md) ; 28(2): 61-63, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34012223

RESUMEN

A 51 year old man with active follicular lymphoma presented with several days of erythematous skin nodules on all extremities two weeks after a self-limited diarrheal illness. All serum immunoglobulin levels were found to be low. Blood cultures grew Campylobacter jejuni. The patient was given one week of azithromycin with complete resolution of his skin nodules. The literature of skin manifestations seen in active Campylobacter jejuni infection are reviewed. The majority of cases occur in immunocompromised hosts, many with low or no serum immunoglobulin levels. Postulated mechanisms include a lack of secretory IgA in intestinal mucosa predisposing susceptible patients to translocated enteric pathogens however the precise pathogenesis underlying cutaneous manifestations are unknown.

11.
Toxicol Sci ; 174(1): 100-111, 2020 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-31868906

RESUMEN

The exposome is the measure of all exposures of an individual in a lifetime and how those exposures relate to health. The goal was to examine an experimental model integrating multiple aspects of the exposome by collecting biological samples during critical life stages of an exposed animal that are applicable to worker populations. Genetic contributions were assessed using strains of male rats with different genetic backgrounds (Fischer-344, Sprague Dawley, and Brown-Norway) maintained on a regular or high-fat diet for 24 weeks. At week 7 during diet maintenance, groups of rats from each strain were exposed to stainless steel welding fume (WF; 20 mg/m3 × 3 h/d × 4 days/week × 5 weeks) or air until week 12, at which time some animals were euthanized. A separate set of rats from each strain were allowed to recover from WF exposure until the end of the 24-week period. Bronchoalveolar lavage fluid and serum were collected at 7, 12, and 24 weeks to assess general health indices. Depending on animal strain, WF exposure and high-fat diet together worsened kidney toxicity as well as altered different serum enzymes and proteins. Diet had minimal interaction with WF exposure for pulmonary toxicity endpoints. Experimental factors of diet, exposure, and strain were all important, depending on the health outcome measured. Exposure had the most significant influence related to pulmonary responses. Strain was the most significant contributor regarding the other health indices examined, indicating that genetic differences possibly drive the exposome effect in each strain.


Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Dieta Alta en Grasa/efectos adversos , Exposoma , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Soldadura , Animales , Exposición por Inhalación , Riñón/metabolismo , Riñón/patología , Hígado/metabolismo , Hígado/patología , Masculino , Exposición Profesional , Ratas Endogámicas BN , Ratas Endogámicas F344 , Ratas Sprague-Dawley , Medición de Riesgo , Especificidad de la Especie , Factores de Tiempo
12.
Cogent Biol ; 5(1)2019.
Artículo en Inglés | MEDLINE | ID: mdl-31595219

RESUMEN

Sodium fluoroacetate (1080) is a highly toxic metabolic poison that has the potential because of its lack of defined color, odor, and taste and its high water solubility to be intentionally or unintentionally ingested through food adulteration. Although the mechanism of action for 1080 has been known since the 1950's, no known antidote exists. In an effort to better understand the cardiopulmonary impacts of 1080, we utilized whole-body plethysmography and telemeterized Sprague-Dawley rats which allowed for the real-time measurement of respiratory and cardiac parameters following exposure using a non-invasive assisted-drinking method. Overall, the animals showed marked depression of respiratory parameters over the course of 24 hours post-exposure and the development of hemorrhage in the lung tissue. Tidal volume was reduced by 30% in males and 60% in females at 24 hours post-exposure, and respiratory frequency was significantly depressed as well. In telemeterized female rats, we observed severe cardiac abnormalities, highlighted by a 50% reduction in heart rate, 75% reduction in systolic blood pressure, and a 3.5-fold lengthening of the QRS interval over the course of 24 hours. We also observed a reduction in core body temperature of nearly 15°C. Our study was able to describe the severe and pronounced effects of sodium fluoroacetate poisoning on cardiopulmonary function, the results of which indicate that both tissue specific and systemic deficits contribute to the toxicological progression of 1080 intoxication and will need to be accounted for when developing any potential countermeasure for 1080 poisoning.

13.
Am J Infect Control ; 47(9): 1102-1106, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31005345

RESUMEN

BACKGROUND: No single strategy is more effective than proper hand hygiene (HH) in reducing the spread of nosocomial infections. Unfortunately, health care worker compliance with HH is imperfect. We sought to improve HH compliance using an electronic hand hygiene monitoring system (EHHMS) in 2 units to collect unbiased data and provide feedback. METHODS: In this prospective, quasi-experimental study, the Hyginex EHHMS was installed in 2 units at Tufts Medical Center. Ninety-one bracelets were assigned, and electronic data were collected over 8 months. Human observations continued. We compared HH compliance as measured by human observation before, during, and after EHHMS implementation. Pre- and post-implementation surveys were distributed to staff. RESULTS: The number of electronically captured HH compliance observations was small due to infrequent bracelet use after month 2 of the intervention. HH compliance, as determined by human observation, increased by an average of 1.3 percentage points per month (P = .0005). Survey responses revealed negative attitudes about the EHHMS before and after its implementation. CONCLUSIONS: Despite poor EHHMS participation and negative attitudes toward its implementation, HH compliance, as measured by human observation, significantly improved. Hospitals considering implementing an EHHMS should look to refine the intervention to encourage health care worker participation.


Asunto(s)
Técnicas de Observación Conductual/métodos , Electrónica/métodos , Adhesión a Directriz/estadística & datos numéricos , Higiene de las Manos/estadística & datos numéricos , Control de Infecciones/métodos , Boston , Infección Hospitalaria/prevención & control , Transmisión de Enfermedad Infecciosa/prevención & control , Higiene de las Manos/métodos , Hospitales Universitarios , Humanos , Ensayos Clínicos Controlados no Aleatorios como Asunto , Estudios Prospectivos
14.
Arch Toxicol ; 91(8): 2953-2962, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28054104

RESUMEN

Epidemiologic studies suggest an increased risk of lung cancer with exposure to welding fumes, but controlled animal studies are needed to support this association. Oropharyngeal aspiration of collected "aged" gas metal arc-stainless steel (GMA-SS) welding fume has been shown by our laboratory to promote lung tumor formation in vivo using a two-stage initiation-promotion model. Our objective in this study was to determine whether inhalation of freshly generated GMA-SS welding fume also acts as a lung tumor promoter in lung tumor-susceptible mice. Male A/J mice received intraperitoneal (IP) injections of corn oil or the chemical initiator 3-methylcholanthrene (MCA; 10 µg/g) and 1 week later were exposed by whole-body inhalation to air or GMA-SS welding aerosols for 4 h/d × 4 d/w × 9 w at a target concentration of 40 mg/m3. Lung nodules were enumerated at 30 weeks post-initiation. GMA-SS fume significantly promoted lung tumor multiplicity in A/J mice initiated with MCA (16.11 ± 1.18) compared to MCA/air-exposed mice (7.93 ± 0.82). Histopathological analysis found that the increased number of lung nodules in the MCA/GMA-SS group were hyperplasias and adenomas, which was consistent with developing lung tumorigenesis. Metal deposition analysis in the lung revealed a lower deposited dose, approximately fivefold compared to our previous aspiration study, still elicited a significant lung tumorigenic response. In conclusion, this study demonstrates that inhaling GMA-SS welding fume promotes lung tumorigenesis in vivo which is consistent with the epidemiologic studies that show welders may be at an increased risk for lung cancer.


Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Exposición por Inhalación/efectos adversos , Neoplasias Pulmonares/inducido químicamente , Soldadura , Administración por Inhalación , Animales , Modelos Animales de Enfermedad , Neoplasias Pulmonares/patología , Masculino , Metilcolantreno/administración & dosificación , Ratones , Ratones Endogámicos , Enfermedades Profesionales/etiología , Enfermedades Profesionales/patología , Exposición Profesional/efectos adversos , Acero Inoxidable/toxicidad
15.
J Clin Epidemiol ; 84: 61-69, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28063913

RESUMEN

OBJECTIVES: To provide a perspective on the current practice of randomized clinical trials (RCTs) of diagnostic strategies focusing on patient-important outcomes. STUDY DESIGN AND SETTING: We conducted a comprehensive search of MEDLINE and included RCTs published in full-text reports that evaluated alternative diagnostic strategies. RESULTS: Of 56,912 unique citations, we sampled 7,500 and included 103 eligible RCTs, therefore suggesting that MEDLINE includes approximately 781 diagnostic RCTs. The 103 eligible trials reported on: mortality (n = 41; 39.8%); morbidities (n = 63; 61.2%); symptoms/quality of life/functional status (n = 14; 13.6%); and on composite end points (n = 10; 9.7%). Of the studies that reported statistically significant results (n = 12; 11.6%), we judged 7 (58.3%) as at low risk of bias with respect to missing outcome data and 4 (33.3%) as at low risk of bias regarding blinding. Of the 41 RCTs that reported on mortality, only one (2.4%) reported statistically significant results. Of 63 RCTs addressing morbidity outcomes, 11 (17.5%) reported statistically significant results, all of which reported relative effects of greater than 20%. CONCLUSION: RCTs of diagnostic tests are not uncommon, and sometimes suggest benefits on patient-important outcomes but often suffer from limitations in sample size and conduct.


Asunto(s)
Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Evaluación del Resultado de la Atención al Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Humanos , MEDLINE
16.
J Occup Environ Hyg ; 13(7): 501-18, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26873639

RESUMEN

Direct-reading instruments have been widely used for characterizing airborne nanoparticles in inhalation toxicology and industrial hygiene studies for exposure/risk assessments. Instruments using electrical mobility sizing followed by optical counting, e.g., scanning or sequential mobility particle spectrometers (SMPS), have been considered as the "gold standard" for characterizing nanoparticles. An SMPS has the advantage of rapid response and has been widely used, but there is little information on its performance in assessing the full spectrum of nanoparticles encountered in the workplace. In this study, an SMPS was evaluated for its effectiveness in producing "monodisperse" aerosol and its adequacy in characterizing overall particle size distribution using three test aerosols, each mimicking a unique class of real-life nanoparticles: singlets of nearly spherical titanium dioxide (TiO2), agglomerates of fiber-like multi-walled carbon nanotube (MWCNT), and aggregates that constitutes welding fume (WF). These aerosols were analyzed by SMPS, cascade impactor, and by counting and sizing of discrete particles by scanning and transmission electron microscopy. The effectiveness of the SMPS to produce classified particles (fixed voltage mode) was assessed by examination of the resulting geometric standard deviation (GSD) from the impactor measurement. Results indicated that SMPS performed reasonably well for TiO2 (GSD = 1.3), but not for MWCNT and WF as evidenced by the large GSD values of 1.8 and 1.5, respectively. For overall characterization, results from SMPS (scanning voltage mode) exhibited particle-dependent discrepancies in the size distribution and total number concentration compared to those from microscopic analysis. Further investigation showed that use of a single-stage impactor at the SMPS inlet could distort the size distribution and underestimate the concentration as shown by the SMPS, whereas the presence of vapor molecules or atom clusters in some test aerosols might cause artifacts by counting "phantom particles." Overall, the information obtained from this study will help understand the limitations of the SMPS in measuring nanoparticles so that one can adequately interpret the results for risk assessments and exposure prevention in an occupational or ambient environment.


Asunto(s)
Contaminantes Ocupacionales del Aire/análisis , Nanotubos de Carbono/análisis , Tamaño de la Partícula , Titanio/análisis , Soldadura , Aerosoles , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión
17.
J Occup Environ Hyg ; 13(1): 1-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26267301

RESUMEN

Nine gas metal arc welding (GMAW) processes for stainless steel were assessed for fume generation rates, fume generation rates per g of electrode consumed, and emission rates for hexavalent chromium (Cr(6+)). Elemental manganese, nickel, chromium, iron emissions per unit length of weld, and labor plus consumables costs were similarly measured. Flux-cored arc welding and shielded metal arc (SMAW) processes were also studied. The objective was to identify the best welding processes for reducing workplace exposures, and estimate costs for all processes. Using a conical chamber, fumes were collected, weighed, recovered, and analyzed by inductively coupled atomic emission spectroscopy for metals, and by ion chromatography for Cr(6+). GMAW processes used were Surface Tension Transfer, Regulated Metal Deposition, Cold Metal Transfer, short-circuit, axial spray, and pulsed spray modes. Flux-cored welding used gas shielding; SMAW used E308 rods. Costs were estimated as dollars per m length of a » in (6.3 mm) thick horizontal butt weld; equipment costs were estimated as ratios of new equipment costs to a 250 ampere capacity SMAW welding machine. Results indicate a broad range of fume emission factors for the processes studied. Fume emission rates per g of electrode were lowest for GMAW processes such as pulsed-spray mode (0.2 mg/g), and highest for SMAW (8 mg fume/g electrode). Emission rates of Cr(6+) ranged from 50-7800 µg/min, and Cr(6+) generation rates per g electrode ranged from 1-270 µg/g. Elemental Cr generation rates spanned 13-330 µg/g. Manganese emission rates ranged from 50-300 µg/g. Nickel emission rates ranged from 4-140 µg/g. Labor and consumables costs ranged from $3.15 (GMAW pulsed spray) to $7.40 (SMAW) per meter of finished weld, and were measured or estimated for all 11 processes tested. Equipment costs for some processes may be as much as five times the cost of a typical SMAW welding machine. The results show that all of the GMAW processes in this study can substantially reduce fume, Cr(6+), manganese and costs relative to SMAW, the most commonly used welding process, and several have exceptional capabilities for reducing emissions.


Asunto(s)
Contaminantes Ocupacionales del Aire/análisis , Cromo/análisis , Exposición Profesional/análisis , Acero Inoxidable , Soldadura/métodos , Lugar de Trabajo , Contaminantes Ocupacionales del Aire/economía , Gases/análisis , Metales/análisis , Exposición Profesional/prevención & control , Soldadura/economía
18.
Toxicology ; 328: 168-78, 2015 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-25549921

RESUMEN

Welding fumes (WF) are a complex mixture of toxic metals and gases, inhalation of which can lead to adverse health effects among welders. The presence of manganese (Mn) in welding electrodes is cause for concern about the potential development of Parkinson's disease (PD)-like neurological disorder. Consequently, from an occupational safety perspective, there is a critical need to prevent adverse exposures to WF. As the fume generation rate and physicochemical characteristics of welding aerosols are influenced by welding process parameters like voltage, current or shielding gas, we sought to determine if changing such parameters can alter the fume profile and consequently its neurotoxic potential. Specifically, we evaluated the influence of voltage on fume composition and neurotoxic outcome. Rats were exposed by whole-body inhalation (40 mg/m(3); 3h/day × 5 d/week × 2 weeks) to fumes generated by gas-metal arc welding using stainless steel electrodes (GMA-SS) at standard/regular voltage (25 V; RVSS) or high voltage (30 V; HVSS). Fumes generated under these conditions exhibited similar particulate morphology, appearing as chain-like aggregates; however, HVSS fumes comprised of a larger fraction of ultrafine particulates that are generally considered to be more toxic than their fine counterparts. Paradoxically, exposure to HVSS fumes did not elicit dopaminergic neurotoxicity, as monitored by the expression of dopaminergic and PD-related markers. We show that the lack of neurotoxicity is due to reduced solubility of Mn in HVSS fumes. Our findings show promise for process control procedures in developing prevention strategies for Mn-related neurotoxicity during welding; however, it warrants additional investigations to determine if such modifications can be suitably adapted at the workplace to avert or reduce adverse neurological risks.


Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Encéfalo/efectos de los fármacos , Exposición por Inhalación/prevención & control , Intoxicación por Manganeso/prevención & control , Manganeso/toxicidad , Enfermedad de Parkinson Secundaria/prevención & control , Soldadura/métodos , Aerosoles , Contaminantes Ocupacionales del Aire/química , Animales , Carga Corporal (Radioterapia) , Encéfalo/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Diseño de Equipo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Exposición por Inhalación/efectos adversos , Masculino , Manganeso/química , Intoxicación por Manganeso/etiología , Intoxicación por Manganeso/genética , Intoxicación por Manganeso/metabolismo , Enfermedad de Parkinson Secundaria/etiología , Enfermedad de Parkinson Secundaria/genética , Enfermedad de Parkinson Secundaria/metabolismo , Tamaño de la Partícula , Ratas Sprague-Dawley , Medición de Riesgo , Solubilidad , Factores de Tiempo , Soldadura/instrumentación
19.
Ann Occup Hyg ; 58(4): 403-12, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24515891

RESUMEN

To provide quantitative information to choose the best welding processes for minimizing workplace emissions, nine gas metal arc welding (GMAW) processes for mild steel were assessed for fume generation rates, normalized fume generation rates (milligram fume per gram of electrode consumed), and normalized generation rates for elemental manganese, nickel, and iron. Shielded metal arc welding (SMAW) and flux-cored arc-welding (FCAW) processes were also profiled. The fumes were collected quantitatively in an American Welding Society-type fume chamber and weighed, recovered, homogenized, and analyzed by inductively coupled atomic emission spectroscopy for total metals. The processes included GMAW with short circuit, globular transfer, axial spray, pulsed spray, Surface Tension Transfer™, Regulated Metal Deposition™, and Cold Metal Transfer™ (CMT) modes. Flux-cored welding was gas shielded, and SMAW was a single rod type. Results indicate a wide range of fume emission factors for the process variations studied. Fume emission rates per gram of electrode consumed were highest for SMAW (~13 mg fume g(-1) electrode) and lowest for GMAW processes such as pulsed spray (~1.5mg g(-1)) and CMT (~1mg g(-1)). Manganese emission rates per gram of electrode consumed ranged from 0.45 mg g(-1) (SMAW) to 0.08 mg g(-1) (CMT). Nickel emission rates were generally low and ranged from ~0.09 (GMAW short circuit) to 0.004 mg g(-1) (CMT). Iron emission rates ranged from 3.7 (spray-mode GMAW) to 0.49 mg g(-1) (CMT). The processes studied have significantly different costs, and cost factors are presented based on a case study to allow comparisons between processes in specific cost categories. Costs per linear meter of weld were $31.07 (SMAW), $12.37 (GMAW short circuit), and $10.89 (FCAW). Although no single process is the best for minimizing fume emissions and costs while satisfying the weld requirements, there are several processes that can minimize emissions. This study provides information to aid in those choices. Suggestions for overcoming barriers to utilizing new and less hazardous welding processes are also discussed.


Asunto(s)
Contaminantes Ocupacionales del Aire/análisis , Contaminantes Ocupacionales del Aire/economía , Exposición Profesional/análisis , Soldadura/economía , Lugar de Trabajo , Monitoreo del Ambiente/estadística & datos numéricos , Gases/química , Humanos , Metales/análisis , Tamaño de la Partícula , Acero/análisis , Soldadura/métodos
20.
Artículo en Inglés | MEDLINE | ID: mdl-23162799

RESUMEN

Shiga toxin producing Escherichia coli (STEC) are a major cause of food-borne illness worldwide. However, a consensus regarding the role Shiga toxins play in the onset of diarrhea and hemorrhagic colitis (HC) is lacking. One of the obstacles to understanding the role of Shiga toxins to STEC-mediated intestinal pathology is a deficit in small animal models that perfectly mimic human disease. Infant rabbits have been previously used to study STEC and/or Shiga toxin-mediated intestinal inflammation and diarrhea. We demonstrate using infant rabbits that Shiga toxin-mediated intestinal damage requires A-subunit activity, and like the human colon, that of the infant rabbit expresses the Shiga toxin receptor Gb(3). We also demonstrate that Shiga toxin treatment of the infant rabbit results in apoptosis and activation of p38 within colonic tissues. Finally we demonstrate that the infant rabbit model may be used to test candidate therapeutics against Shiga toxin-mediated intestinal damage. While the p38 inhibitor SB203580 and the ZAK inhibitor DHP-2 were ineffective at preventing Shiga toxin-mediated damage to the colon, pretreatment of infant rabbits with the drug imatinib resulted in a decrease of Shiga toxin-mediated heterophil infiltration of the colon. Therefore, we propose that this model may be useful in elucidating mechanisms by which Shiga toxins could contribute to intestinal damage in the human.


Asunto(s)
Benzamidas/metabolismo , Intestinos/efectos de los fármacos , Intestinos/patología , Piperazinas/metabolismo , Inhibidores de Proteínas Quinasas/metabolismo , Proteínas Quinasas/administración & dosificación , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirimidinas/metabolismo , Toxina Shiga II/toxicidad , Animales , Animales Recién Nacidos , Apoptosis , Mesilato de Imatinib , Quinasas Quinasa Quinasa PAM , Subunidades de Proteína/toxicidad , Conejos , Escherichia coli Shiga-Toxigénica/patogenicidad , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
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