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2.
Dis Esophagus ; 21(8): 757-64, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18522636

RESUMEN

Dilated intercellular spaces (DIS) within esophageal epithelium (EE) is a histopathologic feature of non-erosive reflux disease and early lesion in acid-damaged rabbit EE associated with increased paracellular permeability. Its cause remains unknown, but the lesion's morphology suggests a significant fluid shift into the intercellular spaces (ICS). Since water follows osmotic forces and consequently ion movements, we explored the role of active (ion) transport and ion gradients in its pathogenesis. This was done by quantifying the effect of inhibited active transport and altered ion gradients on electrical resistance (R(T)) and ICS diameter in acid-exposed Ussing-chambered rabbit EE. Compared with normal Ringer, pH 7.5, 30 minutes of luminal HCl (100 mmol/L), pH 1.1, increased permeability (R(T): +5 +/- 4% vs-52 +/- 4%) and ICS diameter (0.25 +/- 0.01 microm vs 0.42 +/- 0.02 microm), but had no effect on cell morphology or diameter. Ouabain pretreatment significantly reduced active transport but had no effect on the acid-induced changes. However, negating the chloride gradient created by luminal HCl either by adding choline chloride, 100 mmol/L, serosally or by replacing luminal HCl, pH 1.1, with luminal H(2)SO(4), pH 1.1, prevented the development of DIS while maintaining the increase in permeability. DIS was also prevented in the presence of a 100 mmol/L (choline) chloride gradient by luminal exposure at neutral pH. DIS in HCl-damaged EE is caused by an H(+)-induced increase in epithelial permeability; this enables Cl(-) to diffuse along its gradient into the ICS, creating an osmotic force for water movement into and (hydrostatic) dilation of the ICS.


Asunto(s)
Esófago/metabolismo , Esófago/ultraestructura , Espacio Extracelular , Reflujo Gastroesofágico/metabolismo , Reflujo Gastroesofágico/patología , Membrana Mucosa/ultraestructura , Animales , Transporte Biológico Activo/fisiología , Dilatación Patológica/etiología , Reflujo Gastroesofágico/complicaciones , Ácido Clorhídrico , Transporte Iónico/fisiología , Masculino , Conejos , Técnicas de Cultivo de Tejidos
3.
Free Radic Biol Med ; 42(12): 1826-37, 2007 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-17512462

RESUMEN

It is unknown whether nutritional deficiencies affect the morphology and function of structural cells, such as epithelial cells, and modify the susceptibility to viral infections. We developed an in vitro system of differentiated human bronchial epithelial cells (BEC) grown either under selenium-adequate (Se+) or selenium-deficient (Se-) conditions, to determine whether selenium deficiency impairs host defense responses at the level of the epithelium. Se- BECs had normal SOD activity, but decreased activity of the selenium-dependent enzyme GPX1. Interestingly, catalase activity was also decreased in Se- BECs. Both Se- and Se+ BECs differentiated into a mucociliary epithelium; however, Se- BEC demonstrated increased mucus production and increased Muc5AC mRNA levels. This effect was also seen in Se+ BEC treated with 3-aminotriazole, an inhibitor of catalase activity, suggesting an association between catalase activity and mucus production. Both Se- and Se+ were infected with influenza A/Bangkok/1/79 and examined 24 h postinfection. Influenza-induced IL-6 production was greater while influenza-induced IP-10 production was lower in Se- BECs. In addition, influenza-induced apoptosis was greater in Se- BEC as compared to the Se+ BECs. These data demonstrate that selenium deficiency has a significant impact on the morphology and influenza-induced host defense responses in human airway epithelial cells.


Asunto(s)
Bronquios/efectos de los fármacos , Virus de la Influenza A/efectos de los fármacos , Gripe Humana/inmunología , Selenio/deficiencia , Adulto , Alantoína/metabolismo , Animales , Bronquios/citología , Bronquios/metabolismo , Catalasa/antagonistas & inhibidores , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Células Cultivadas/efectos de los fármacos , Células Cultivadas/metabolismo , Células Cultivadas/ultraestructura , Quimiocina CXCL10 , Quimiocinas CXC/metabolismo , Pollos , Perros , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/ultraestructura , Glutatión/metabolismo , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Humanos , Virus de la Influenza A/inmunología , Virus de la Influenza A/patogenicidad , Gripe Humana/metabolismo , Interleucina-6/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Selenio/administración & dosificación , Tasa de Supervivencia , Virulencia/efectos de los fármacos
6.
Cochrane Database Syst Rev ; (2): CD002042, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12076437

RESUMEN

BACKGROUND: Most clinical practice guidelines recommend restrictive red cell transfusion practices with the goal of minimising exposure to allogeneic blood (from an unrelated donor). The purpose of this review is to compare clinical outcomes in patients randomised to restrictive versus liberal transfusion thresholds (triggers). OBJECTIVES: To examine the evidence on the effect of transfusion thresholds, on the use of allogeneic and/or autologous blood, and the evidence for any effect on clinical outcomes. SEARCH STRATEGY: Trials were identified by: computer searches of OVID Medline (1966 to December 2000), Current Contents (1993 to Week 48 2000), and the Cochrane Controlled Trials Register (2000 Issue 4). References in identified trials and review articles were checked and authors contacted to identify any additional studies. SELECTION CRITERIA: Controlled trials in which patients were randomised to an intervention group or to a control group. Trials were included where the intervention groups were assigned on the basis of a clear transfusion "trigger", described as a haemoglobin (Hb) or haematocrit (Hct) level below which a RBC transfusion was to be administered. DATA COLLECTION AND ANALYSIS: Trial quality was assessed using criteria proposed by Schulz et al. (1995). Relative risks of requiring allogeneic blood transfusion, transfused blood volumes and other clinical outcomes were pooled across trials using a random effects model. MAIN RESULTS: Ten trials were identified that reported outcomes for a total of 1780 patients. Restrictive transfusion strategies reduced the risk of receiving a red blood cell (RBC) transfusion by a relative 42% (RR=0.58: 95%CI=0.47,0.71). This equates to an average absolute risk reduction (ARR) of 40% (95%CI=24% to 56%). The volume of RBCs transfused was reduced on average by 0.93 units (95%CI=0.36,1.5 units). However, heterogeneity between these trials was statistically significant (p<0.00001) for these outcomes. Mortality, rates of cardiac events, morbidity, and length of hospital stay were unaffected. Trials were of poor methodological quality. REVIEWER'S CONCLUSIONS: The limited published evidence supports the use of restrictive transfusion triggers in patients who are free of serious cardiac disease. However, most of the data on clinical outcomes were generated by a single trial. The effects of conservative transfusion triggers on functional status, morbidity and mortality, particularly in patients with cardiac disease, need to be tested in further large clinical trials. In countries with inadequate screening of donor blood the data may constitute a stronger basis for avoiding transfusion with allogeneic red cells.


Asunto(s)
Transfusión de Eritrocitos/normas , Guías como Asunto , Humanos , Trasplante Autólogo , Trasplante Homólogo
8.
Thorax ; 57(4): 363-5, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11923559

RESUMEN

BACKGROUND: The airway cilia of patients with primary ciliary dyskinesia (PCD) exhibit several anomalies when studied by transmission electron microscopy, but little is known about the ultrastructural organisation of ciliary membranes in these patients. Freeze fracture replication of airway epithelium from patients with PCD provides a means of achieving high resolution views of cell membrane structure. Ciliary necklaces are a specialised structural feature of ciliary membranes thought to serve as a timing mechanism for ciliary beat, and their characterisation in the cilia of patients with PCD may contribute new insights into the pathophysiology of this syndrome. METHODS: The nasal epithelium of three patients with PCD was freeze fractured and replicated with platinum and carbon shadowing. The resultant preparations were examined by transmission electron microscopy and the ciliary necklaces were compared with similar preparations of nasal biopsy specimens from normal healthy subjects. RESULTS: The ciliary necklaces of the three patients with PCD were normal with no overt differences from those of healthy individuals. CONCLUSIONS: The defective ciliary motility observed in patients with PCD does not appear to result from membrane dysfunction associated with overt disorganisation of ciliary necklace structure.


Asunto(s)
Trastornos de la Motilidad Ciliar/patología , Mucosa Respiratoria/ultraestructura , Técnica de Fractura por Congelación , Humanos , Microscopía Electrónica/métodos
9.
Am J Respir Cell Mol Biol ; 25(5): 577-83, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11713099

RESUMEN

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal recessive disorder caused by abnormal ciliary ultrastructure and function, characterized clinically by oto-sino-pulmonary disease. Mutations in an intermediate chain dynein (DNAI1; IC78) have recently been described in PCD patients, with outer dynein arm (ODA) defects. The aims of the current study were to test for novel DNAI1 mutations in 13 PCD patients with ODA defects (from 7 unrelated families) and to assess genotype/phenotype correlations in patients and family members. A previously reported mutation (219+3insT) was detected in three PCD patients from two families. The opposite allele had the novel missense mutation G1874C (W568S) in both affected individuals from one family, and a nonsense mutation G1875A (W568X) in an affected individual from another family. The tryptophan at position 568 is a highly conserved residue in the WD-repeat region, and a mutation is predicted to lead to abnormal folding of the protein and loss of function. None of these mutations were found in 32 other PCD patients with miscellaneous ciliary defects. Mutations in DNAI1 are causative for PCD with ODA defects, and are likely the genetic origin of clinical disease in some PCD patients with ultrastructural defects in the ODA.


Asunto(s)
Dineínas/genética , Mutación de Línea Germinal , Síndrome de Kartagener/genética , Adolescente , Adulto , Dineínas Axonemales , Niño , Preescolar , Cilios/patología , Estudios de Cohortes , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Ligamiento Genético , Humanos , Síndrome de Kartagener/patología , Masculino , Óxido Nítrico/análisis , Linaje , Fenotipo
10.
Am J Respir Crit Care Med ; 164(8 Pt 1): 1514-8, 2001 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-11704605

RESUMEN

Epidemiological investigation has established an association between exposure to particulate matter (PM) and both human mortality and diverse indices of human morbidity. However, attributing adverse health effects of specific individuals to PM exposure in these studies is not possible. Consequently, their clinical presentation remains ill-defined. We describe a 42-yr-old male with both respiratory damage, abnormal blood end points, and cardiac effects following an exposure to an emission source air pollution particle aerosolized during the cleaning of his domestic oil-burning stove. Early symptoms of shortness of breath and wheezing progressed over 2 wk to hypoxic respiratory failure necessitating mechanical ventilation. Blood indices were abnormal. Thoracoscopic biopsy demonstrated particle-laden macrophages and diffuse alveolar damage. Symptomatic and objective improvement rapidly followed initiation of corticosteroids. He developed typical anginal symptoms within 2 wk of discharge; however, coronary angiography did not identify any significant narrowing of the epicardial coronary arteries. This patient presents with the aggregate of potential injuries described by epidemiological methods to be associated with air pollution particle exposure.


Asunto(s)
Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Alveolos Pulmonares , Adulto , Humanos , Enfermedades Pulmonares/etiología , Masculino , Aceites
11.
J Am Coll Cardiol ; 37(5): 1297-302, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11300438

RESUMEN

OBJECTIVES: To determine if nicotine patches, both as prescribed and used over-the-counter, increase the risk of first myocardial infarction (MI). BACKGROUND: Although nicotine patches improve smoking cessation rates, case reports have raised the hypothesis that they may increase the risk of MI. METHODS: A population-based case-control study among 68 hospitals in an eight-county region surrounding Philadelphia was performed to determine if nicotine patches increase the risk of first MI. Cases were smokers (current or within the prior year) admitted to all hospitals in the region with a first MI. Controls were smokers (current or within the prior year) without prior MI selected from the same region using random-digit dialing. Data were collected by telephone interviews and chart reviews. The study had 80% power to detect an odds ratio (OR) of 2.5. RESULTS: A total of 653 cases and 2,990 controls were interviewed. There was no association between nicotine patches and MI (OR 0.46; 95% CI: 0.09, 1.47), and the confidence interval (CI) excluded an effect from nicotine patches equal to that from cigarette smoking itself (OR < 2.5). Among those who abstained from smoking, the OR for use of nicotine patches was 0.25 (95% CI: 0.01, 1.67); among those who smoked concomitantly, the OR for patch use was 0.83 (95% CI: 0.09, 3.81). Adjustment for confounding did not alter the study's findings (OR adjusted for confounders that could mask a harmful effect of patches: 0.70; 95% CI: 0.20, 2.46). CONCLUSIONS: Nicotine patches, as used in actual practice, do not appear to be associated with an increased risk of MI.


Asunto(s)
Infarto del Miocardio/inducido químicamente , Nicotina/efectos adversos , Cese del Hábito de Fumar , Administración Cutánea , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Nicotina/administración & dosificación , Philadelphia , Factores de Riesgo , Fumar/efectos adversos
12.
Am J Respir Cell Mol Biol ; 24(2): 132-8, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11159046

RESUMEN

Southwest Metropolitan Mexico City (SWMMC) children are repeatedly exposed to a complex mixture of air pollutants, including ozone, particulate matter, and aldehydes. Nasal biopsies taken from these children exhibit a wide range of histopathologic alterations: marked changes in ciliated and goblet cell populations, basal cell hyperplasia, squamous metaplasia, and mild dysplasias. We studied the ultrastructural features of 15 nasal biopsies obtained from clinically healthy children 4 to 15 yr of age, growing up in SWMMC. The results were compared with nasal biopsies from 11 children growing up in Veracruz and exposed to low pollutant levels. Ultrathin sections of nasal biopsies revealed an unremarkable mucociliary epithelium in control children, whereas SWMMC children showed an epithelium comprised of variable numbers of basal, ciliated, goblet, and squamous metaplastic as well as intermediate cells. Nascent ciliated cells, as evidenced by the presence of migratory kinetosomes, were common, as were ciliary abnormalities, including absent central microtubules, supernumerary central and peripheral tubules, ciliary microtubular discontinuities, and compound cilia. Dyskinesia associated with these abnormal cilia was suggested by the altered orientation of the central microtubules in closely adjacent cilia. A transudate was evident between epithelial cells, suggesting potential deficiencies in epithelial junction integrity. Particulate matter was present in heterolysosomal bodies in epithelial cells and it was also deposited in intercellular spaces. The severe structural alteration of the nasal epithelium together with the prominent acquired ciliary defects are likely the result of chronic airway injury in which ozone, particulate matter, and aldehydes are thought to play a crucial role. The nasal epithelium in SWMMC children is fundamentally disordered, and their mucociliary defense mechanisms are no longer intact. A compromised nasal epithelium has less ability to protect the lower respiratory tract and may potentially leave the distal acinar airways more vulnerable to reactive gases. Impairment of mucociliary clearance has the potential to increase the contact time between deposited mutagenic particulate matter and the epithelial surface, thus increasing the risk for nasal carcinogenesis. Chronic exposures to air pollutants affect the whole respiratory tract; the nasal epithelium is an accessible and valuable sentinel to monitor exposures to toxic or carcinogenic substances.


Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Mucosa Nasal/ultraestructura , Adolescente , Biopsia , Niño , Femenino , Humanos , Masculino , México , Mucosa Nasal/efectos de los fármacos , Sistema Respiratorio/efectos de los fármacos , Sistema Respiratorio/ultraestructura
13.
Am J Respir Cell Mol Biol ; 23(6): 734-41, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11104725

RESUMEN

The most conspicuous evidence of airway epithelial maturation and vitality is the presence of motile cilia. In an effort to generate genetic and antigenic markers of airway maturation, injury, and repair, we characterized airway epithelial expression of a gene identified by two human expressed sequence tags that encoded peptides with sequence similarity to an invertebrate ciliary dynein heavy chain (DHC). Molecular analyses showed that the gene has a very large RNA transcript that encodes a very high molecular weight polypeptide with biochemical properties that are characteristic of a dynein heavy chain. Expression of the gene transcript correlated with the presence of ciliated cells in tissues, and immunohistochemical localization of the gene product confirmed its presence in the cilia of mature airway epithelium. In epithelium undergoing ciliogenesis ex vivo, expression of the gene transcript preceded ciliation of the epithelium and the gene product was present in the cytoplasm and at the apical border of nonciliated cells. These data suggested that the gene encodes an axonemal DHC that is expressed early during ciliogenesis, before the appearance of cilia.


Asunto(s)
Dineínas/genética , Epitelio/metabolismo , Tráquea/metabolismo , Secuencia de Aminoácidos , Anticuerpos Monoclonales/análisis , Northern Blotting , Bronquios/metabolismo , Línea Celular , Cilios/metabolismo , Cilios/ultraestructura , ADN Complementario/química , ADN Complementario/genética , Dineínas/inmunología , Femenino , Regulación de la Expresión Génica , Humanos , Inmunohistoquímica , Microscopía Inmunoelectrónica , Datos de Secuencia Molecular , ARN Mensajero/genética , ARN Mensajero/metabolismo , Alineación de Secuencia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Distribución Tisular
14.
Ultrastruct Pathol ; 24(3): 169-74, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10914428

RESUMEN

The ultrastructural analysis of cilia and diagnosis of primary ciliary dyskinesia (PCD) in biopsies of airway epithelium is sometimes confounded by poor sampling, inconsistencies in tissue quality and processing, and other technical problems. Although clinical findings may lead to a presumptive diagnosis, ultrastructural analysis of ciliary axonemes is the standard for confirmation of PCD. The ultrastructural features of the cilium when viewed in cross section by transmission electron microscopy confer a radial symmetry to the axoneme. Current digital image processing techniques can be applied to such images to reinforce signal, diminish noise, and confirm consistency of position of axonemal structures, a process that can augment ultrastructural analysis for PCD. In this study, computer-assisted digital image processing was used to evaluate cross sections of cilia in airway epithelial biopsies from patients previously diagnosed with PCD as well as in control subjects with normal cilia. These studies supported the original diagnoses and provided some new insights into axonemal organization in PCD. This technique is simple and may be useful in providing a supporting means for confirming or ruling out a diagnosis of PCD in cases that appear equivocal.


Asunto(s)
Cilios/ultraestructura , Procesamiento de Imagen Asistido por Computador , Síndrome de Kartagener/patología , Mucosa Respiratoria/ultraestructura , Enfermedad Crónica , Humanos , Enfermedades Respiratorias/patología
15.
Anesthesiology ; 92(4): 947-57, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10754613

RESUMEN

BACKGROUND: The impact of anesthetic choice on postoperative mortality and morbidity has not been determined with certainty. METHODS: The authors evaluated the effect of type of anesthesia on postoperative mortality and morbidity in a retrospective cohort study of consecutive hip fracture patients, aged 60 yr or older, who underwent surgical repair at 20 US hospitals between 1983 and 1993. The primary outcome was defined as death within 30 days of the operative procedure. The secondary outcomes were postoperative 7-day mortality, postoperative myocardial infarction, postoperative pneumonia, postoperative congestive heart failure, and postoperative change in mental status. Numerous comorbid conditions were controlled for individually and by several comorbidity indices using logistic regression. RESULTS: General anesthesia was used in 6,206 patients (65.8%) and regional anesthesia in 3,219 patients (3,078 spinal anesthesia and 141 epidural anesthesia). The 30-day mortality rate in the general anesthesia group was 4.4%, compared with 5.4% in the regional anesthesia group (unadjusted odds ratio = 0.80; 95% confidence interval = 0.66-0.97). However, the adjusted odds ratio for general anesthesia increased to 1.08 (0.84-1.38). The adjusted odds ratios for general anesthesia versus regional anesthesia for the 7-day mortality was 0.90 (0.59-1.39) and for postoperative morbidity outcomes were as follows: myocardial infarction: adjusted odds ratio = 1.17 (0.80-1.70); congestive heart failure: adjusted odds ratio = 1.04 (0.80-1.36); pneumonia: adjusted odds ratio = 1.21 (0.87-1.68); postoperative change in mental status: adjusted odds ratio = 1.08 (0.95-1.22). CONCLUSIONS: The authors were unable to demonstrate that regional anesthesia was associated with better outcome than was general anesthesia in this large observational study of elderly patients with hip fracture. These results suggest that the type of anesthesia used should depend on factors other than any associated risks of mortality or morbidity.


Asunto(s)
Anestesia de Conducción , Anestesia General , Fracturas de Cadera/cirugía , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Fracturas de Cadera/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/mortalidad , Estudios Retrospectivos , Resultado del Tratamiento
16.
Gastroenterol Clin North Am ; 29(1): 169-87, vii, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10752021

RESUMEN

The hematologic management of gastrointestinal (GI) bleeding requires evaluation of the underlying cause of bleeding, associated diseases that can exacerbate the bleeding, and identification of related and unrelated coagulation abnormalities. Erythrocyte transfusions are given to increase oxygen carrying capacity; however, there is limited information on the level of anemia that places a patient at increased risk of adverse events after a GI bleed and when patients should receive erythrocyte transfusion. Isolated thrombocytopenia is uncommon in patients with GI bleeding, and there is little evidence documenting the degree of thrombocytopenia associated with an increased risk of bleeding. Platelets are often administered when the count is 50,000 per cu/mL in a bleeding patient. The coagulopathy of liver disease is the most common abnormality seen in the setting of GI bleeding. Fresh-frozen plasma (FFP) should be given in a dose equivalent to the underlying abnormality and the common practice of administering 2 units of FFP is often insufficient in a bleeding patient.


Asunto(s)
Transfusión de Eritrocitos/métodos , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Transfusión de Plaquetas/métodos , Ensayos Clínicos como Asunto , Transfusión de Eritrocitos/efectos adversos , Femenino , Hemorragia Gastrointestinal/diagnóstico , Humanos , Masculino , Transfusión de Plaquetas/efectos adversos , Pronóstico , Resultado del Tratamiento
17.
Am J Physiol ; 277(5): L960-7, 1999 11.
Artículo en Inglés | MEDLINE | ID: mdl-10564181

RESUMEN

We hypothesized that the reduction in hospital respiratory admissions in the Utah Valley during closure of a local steel mill in 1986-1987 was attributable in part to decreased toxicity of ambient air particles. Sampling filters for particulate matter < 10 micrometer (PM(10)) were obtained from a Utah Valley monitoring station for the year before (year 1), during (year 2), and after (year 3) the steel mill closure. Aqueous extracts of the filters were analyzed for metal content and oxidant production and added to cultures of human respiratory epithelial (BEAS-2B) cells for 2 or 24 h. Year 2 dust contained the lowest concentrations of soluble iron, copper, and zinc and showed the least oxidant generation. Only dust from year 3 caused cytotoxicity (by microscopy and lactate dehydrogenase release) at 500 microgram/ml. Year 1 and year 3, but not year 2, dust induced expression of interleukin-6 and -8 in a dose-response fashion. The effects of ambient air particles on human respiratory epithelial cells vary significantly with time and metal concentrations.


Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Células Epiteliales/efectos de los fármacos , Pulmón/citología , Acero , Citotoxinas/farmacología , Células Epiteliales/inmunología , Células Epiteliales/ultraestructura , Filtración , Expresión Génica/efectos de los fármacos , Expresión Génica/inmunología , Humanos , Interleucina-6/genética , Interleucina-6/inmunología , Interleucina-8/genética , Interleucina-8/inmunología , Metales Pesados/farmacología , Microscopía Electrónica de Rastreo , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/inmunología , Enfermedades Profesionales/patología , Estrés Oxidativo/efectos de los fármacos , ARN Mensajero/análisis , Utah , Ventilación , Agua
18.
Anat Rec ; 256(3): 242-51, 1999 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-10521783

RESUMEN

The tracheal epithelium of infant ferrets undergoes rapid postnatal maturation over the first month of life to achieve the pseudostratified columnar configuration characteristic of the large airways of other mammals. We have used in vivo pulsing with tritiated thymidine ((3)HT) to elicit autoradiographic labeling of cells synthesizing nucleic acids in order to characterize more fully the contribution to development of different cell types comprising the nascent epithelial layer during this period of rapid growth. These studies indicate that two distinct populations of epithelial cells possess proliferative potential and contribute to the establishment of the mature adult epithelial layer. These investigations further confirm the mitotic potential of basal cells during a period of rapid postnatal growth and development of the tracheal epithelial layer. These studies also document the contribution to early airway development by non-ciliated cells, which predominate on the luminal border of the ferret trachea at birth. The temporal and histologic patterns of airway epithelial maturation during post-natal life in the ferret as contained in this study exhibit similarities to those which occur with recovery from injury by infection and irritant exposure in mature airways. Thus, the characterization of epithelial cell compartments having proliferative potential may provide insights into the mechanisms whereby normal airway epithelial organization is established and maintained during development as well as the possible recapitulation of these mechanisms during times of epithelial regeneration following injury.


Asunto(s)
Células Epiteliales/citología , Hurones/crecimiento & desarrollo , Tráquea/citología , Animales , Animales Recién Nacidos , Autorradiografía , División Celular , Epitelio , Femenino , Mitosis/fisiología , Embarazo , Tráquea/crecimiento & desarrollo
19.
Transfusion ; 39(8): 808-17, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10504114

RESUMEN

BACKGROUND: Previous analyses have found autologous transfusion to be very expensive but have not considered avoidance of postoperative bacterial infections as one of its benefits. STUDY DESIGN AND METHODS: A cost-utility analysis using a Markov cohort simulation model compared autologous blood transfusion to allogeneic transfusion in a hypothetical cohort of patients undergoing elective total hip replacement with respect to discounted quality-adjusted life years (QALYs) and health-care system costs. RESULTS: Assuming a base case rate of serious infection of 3.7 percent, a relative risk of infection of 1.85, and additional costs of $12,980 per infection, autologous transfusion has a cost-effectiveness of $2,470 per QALY. If the relative risk of bacterial infection following allogeneic transfusion exceeds 1.1, the cost-effectiveness of autologous transfusion is less than $50,000 per QALY and if the relative risk exceeds 2.4, autologous transfusion is dominant, resulting in both lower costs and greater QALYs. If there were no increased risk of transfusion, the cost-effectiveness of autologous transfusion would be $3,400,000 per QALY. CONCLUSIONS: If there is only a modest increase in the risk of bacterial infection following allogeneic transfusion, autologous transfusion would result in improved outcomes at a cost of less than $50,000 per QALY. Autologous transfusion would be dominant above a relative risk of infection that is within the range of values observed in randomized controlled trials. However, if there is no increased risk of bacterial infection, autologous transfusion would be a very expensive strategy. Until more definitive data are available on the magnitude and costs of this risk, we advise against prematurely closing the debate about the cost-effectiveness of autologous transfusion.


Asunto(s)
Transfusión de Sangre Autóloga/economía , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Infecciones Bacterianas/transmisión , Análisis Costo-Beneficio , Humanos , Cadenas de Markov , Persona de Mediana Edad , Factores de Riesgo , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/terapia , Trasplante Homólogo/efectos adversos
20.
Transfusion ; 39(7): 694-700, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10413276

RESUMEN

BACKGROUND: The relationship between allogeneic blood transfusion and bacterial infection remains uncertain. An increased risk of bacterial infection would represent the most important risk of allogeneic transfusion, because viral disease transmission has become so rare. STUDY DESIGN AND METHODS: A retrospective cohort study of 9598 consecutive hip fracture patients at least 60 years old who underwent surgical repair was performed. The primary outcome was serious bacterial infection, defined as bacteremia, pneumonia, deep wound infection, or septic arthritis or osteomyelitis. Secondary outcomes included two individual infections, pneumonia and urinary tract infection (UTI), and the cost of infection. Hospital cost of infection was assessed by linking the study population to Medicare data. RESULTS: Fifty-eight percent of patients received at least one transfusion. Serious bacterial infection occurred in 437 patients (4.6%); 28.8 percent of this group died during the hospital stay. Pneumonia occurred in 361 patients (3.8%) and UTI occurred in 1157 patients (12.1%). The adjusted risk of serious bacterial infection associated with transfusion was 1.35 (95% CI, 1.10-1.66). The adjusted risk for pneumonia was 1.52 (95% CI, 1.21-1.91), and that for UTI was 1.03 (95% CI, 0.91-1.17). A dose-response relationship was present for serious bacterial infection (p = 0.001) and pneumonia (p = 0.001). The cost of hospitalization was $14,000 greater for patients with serious infection than for patients without infection. CONCLUSION: Blood transfusion is associated with a 35-percent greater risk of serious bacterial infection and a 52-percent greater risk of pneumonia. Postoperative infections are costly. The risk of bacterial infection may be the most common life-threatening adverse effect of allogeneic blood transfusion.


Asunto(s)
Infecciones Bacterianas/etiología , Transfusión Sanguínea , Fracturas de Cadera/cirugía , Anciano , Anciano de 80 o más Años , Infecciones Bacterianas/economía , Infecciones Bacterianas/epidemiología , Estudios de Cohortes , Costos y Análisis de Costo , Femenino , Fijación de Fractura , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo
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