RESUMEN
An inflammatory microenvironment has been shown to increase risk for malignant melanoma, suggesting that melanoma may be related to a pro-inflammatory state. Though Hashimoto's thyroiditis is one of the most common autoimmune diseases, there are no investigations of its relationship with melanoma. We aim to determine if Hashimoto's increases risk of developing melanoma. A retrospective, validated cohort of patients with a diagnosis of Hashimoto's between 2005 and 2020 were identified using the Olmsted County database. Patients were age and sex matched to controls without a Hashimoto's diagnosis. The primary outcomes were development of melanoma and time to first melanoma diagnosis. 4805 patients were included in the study, with 1726 (36%) having a diagnosis of Hashimoto's. Hashimoto's patients had no significant difference in risk of melanoma (relative risk 0.96, 95% CI 0.78-1.17) or nonmelanoma skin cancer (relative risk 0.95, 95% CI 0.86-1.06) compared with matched controls. This suggests that the local proinflammatory environment present in Hashimoto's does not contribute significantly to melanoma risk. Larger studies may be needed to further characterize the relationship between these diseases.
Asunto(s)
Enfermedad de Hashimoto , Melanoma , Humanos , Estudios Retrospectivos , Estudios de Cohortes , Enfermedad de Hashimoto/epidemiología , Riesgo , Melanoma/epidemiología , Microambiente TumoralRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-infected individuals. We compared host and tumour characteristics between HIV-infected and HIV-uninfected Nigerians with HCC and examined the impact of HIV on survival. METHODS: This prospective observational study was conducted at Jos University Teaching Hospital in Jos, Nigeria, among adults (>18 years) with HCC enrolled between September 2015 and September 2017 and followed until April 2019. Demographics, tumour characteristics and survival were compared between HCC subjects with and without HIV. RESULTS: 101 (10 HIV-infected and 91 HIV-uninfected) subjects were enrolled [male 72%; median age 48 (IQR 35-60)]. 60% HIV-infected subjects were receiving ART; 90% had CD4 counts ≥ 200/mm3 at HCC diagnosis, and 20% had HIV RNA levels < 20 copies/mL. 57.4% were infected with chronic HBV (HBsAg+). The duration of symptoms was shorter in HIV-infected vs. HIV-uninfected subjects [93 (IQR 54-132) vs. 155 (93-248] days; p = 0.02]. At the end of follow-up, 99 of 101 (98.0%) subjects were confirmed to have died: 9 of 10 (90.0%) HIV-infected and 90 of 91 (98.9%) HIV-uninfected. The probability of survival at three months was 22% and 47% in HIV-infected and HIV-uninfected subjects, respectively (P = 0.02). Median time to death was significantly shorter in HIV-infected vs. HIV-uninfected subjects [24 days (IQR 16-88) vs. 85 days (IQR 34-178), respectively (P = 0.03)]. CONCLUSIONS: High early mortality was observed in this cohort of Nigerian adults with HCC. HIV infection was associated with a faster clinical presentation and shorter survival. More aggressive HCC surveillance may be warranted in HIV-infected subjects, particularly if they are co-infected with chronic HBV.
CONTEXTE: Le carcinome hépatocellulaire (CHC) est une cause croissante de mortalité chez les personnes infectées par le VIH. Nous avons comparé les caractéristiques de l'hôte et de la tumeur entre les Nigérians avec le CHC infectés par le VIH et non infectés et avons examiné l'impact du VIH sur la survie. MÉTHODES: Cette étude observationnelle prospective a été menée au Jos University Teaching Hospital à Jos, au Nigéria, chez des adultes (>18 ans) avec CHC inscrits entre septembre 2015 et septembre 2017 et suivis jusqu'en avril 2019. Les données démographiques, les caractéristiques tumorales et la survie ont été comparées entre les sujets CHC avec et sans VIH. RÉSULTATS: 101 sujets (10 infectés par le VIH et 91 non infectés par le VIH) ont été recrutés [hommes 72%; âge médian de 48 ans (IQR 35-60)]. 60% des sujets infectés par le VIH recevaient une ART; 90% avaient des taux de CD4 ≥200/mm3 au moment du diagnostic de CHC et 20% avaient des taux d'ARN du VIH <20 copies/ml. 57,4% étaient chroniquement infectés par le VHB (HBsAg +). La durée des symptômes était plus courte chez les sujets infectés par le VIH que ceux non infectés [93 (IQR 54-132) vs 155 (93-248] jours; p = 0,02]. A la fin du suivi, 99/101 (98,0 %) des sujets ont été confirmés décédés: 9/10 (90,0%) sujets infectés par le VIH et 90/91 (98,9%) non infectés par le VIH. La probabilité de survie à trois mois était de 22% et 47% chez les personnes infectées par le VIH et celles non infectées par le VIH, respectivement (p = 0,02). Le délai médian au décès était significativement plus court chez les sujets infectés par le VIH par rapport aux sujets non infectés par le VIH [24 jours (IQR 16-88) contre 85 jours (IQR 34-178), respectivement (p = 0,03)]. CONCLUSIONS: Une mortalité précoce élevée a été observée dans cette cohorte d'adultes nigérians atteints de CHC. L'infection par le VIH était associée à une présentation clinique plus rapide et à une survie plus courte. Une surveillance plus étroite du CHC peut être justifiée chez les sujets infectés par le VIH, particulièrement s'ils sont coinfectés chroniquement par le VHB.
Asunto(s)
Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/mortalidad , Infecciones por VIH/complicaciones , Hepatitis B/complicaciones , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/mortalidad , Adulto , Estudios de Cohortes , Coinfección , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nigeria/epidemiología , Prevalencia , Pronóstico , Estudios Prospectivos , Análisis de SupervivenciaAsunto(s)
Brazo , Astrocitoma/diagnóstico por imagen , Encefalopatías Metabólicas/diagnóstico por imagen , Lóbulo Parietal/diagnóstico por imagen , Tomografía de Emisión de Positrones , Temblor/etiología , Astrocitoma/complicaciones , Astrocitoma/fisiopatología , Encefalopatías Metabólicas/complicaciones , Encefalopatías Metabólicas/fisiopatología , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Lóbulo Parietal/fisiopatología , Radiofármacos , Resultado del Tratamiento , Temblor/fisiopatologíaRESUMEN
Supervised dosing is a cornerstone of tuberculosis treatment. HIV treatment strategies that use directly administered antiretroviral therapy (DAART) are increasingly being assessed. In a prospective single-arm clinical trial, we enrolled methadone-maintained, HIV-infected participants to receive supervised doses of antiretroviral therapy (ART) on days when they received methadone. Other ART doses were self-administered. In this analysis we examined factors associated with retention to DAART, adherence to supervised doses, and virologic failure. Factors associated with retention to DAART were assessed with the Kaplan-Meier method and Cox proportional hazards models. Factors associated with nonadherence with supervised dosing and with virologic failure were assessed by logistic regression and techniques for longitudinal data analysis. A total of 16,453 supervised doses were administered to 88 participants over a median follow-up of 9.4 months. The median participant adherence with supervised dosing was 83%. Active drug use, determined by urine drug screens, was associated twofold increased risks of both intervention dropout and nonadherence with supervised doses. Adherence with supervised doses was strongly associated with virologic failure. Because DAART was administered only on methadone dosing days, fewer than half of the total ART doses were scheduled to be supervised in most participants. The percent of doses that was scheduled to be supervised was not associated with either adherence or with virologic failure. Given that a relatively small proportion of the total ART doses were supervised in many patients, future studies should assess how DAART affects adherence with nonsupervised doses and retention to ART.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Terapia por Observación Directa , Infecciones por VIH/tratamiento farmacológico , Metadona/uso terapéutico , Cooperación del Paciente , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Trastornos Relacionados con Sustancias/tratamiento farmacológico , Adulto , Instituciones de Atención Ambulatoria , Fármacos Anti-VIH/administración & dosificación , Recuento de Linfocito CD4 , Quimioterapia Combinada , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Humanos , Masculino , Metadona/administración & dosificación , Persona de Mediana Edad , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Trastornos Relacionados con Sustancias/complicaciones , Insuficiencia del Tratamiento , Resultado del Tratamiento , Carga ViralRESUMEN
BACKGROUND: Directly administered antiretroviral therapy (DAART) in methadone clinics has the potential to improve treatment outcomes for human immunodeficiency virus (HIV)-infected injection drug users (IDUs). METHODS: DAART was provided at 3 urban methadone clinics. Eighty-two participants who were initiating or reinitiating highly active antiretroviral therapy (HAART) received supervised doses of therapy at the clinic on the mornings on which they received methadone. Treatment outcomes in the DAART group were compared with outcomes in 3 groups of concurrent comparison patients, who were drawn from the Johns Hopkins HIV Cohort. The concurrent comparison patients were taking HAART on a self-administered basis. The 3 groups of concurrent comparison patients were as follows: patients with a history of IDU who were receiving methadone at the time HAART was used (the IDU-methadone group; 75 patients), patients with a history of IDU who were not receiving methadone at the time that HAART was used (the IDU-nonmethadone group; 244 patients), and patients with no history of IDU (the non-IDU group; 490 patients). RESULTS: At 12 months, 56% of DAART participants achieved an HIV type 1 RNA level <400 copies/mL, compared with 32% of participants in the IDU-methadone group (P=.009), 33% of those in the IDU-nonmethadone group (P=.001), and 44% of those in the non-IDU group (P=.077). The DAART group experienced a median increase in the CD4 cell count of 74 cells/mm3, compared with 21 cells/mm3 in the IDU-methadone group (P=.04), 33 cells/mm3 in the IDU-nonmethadone group (P=.09), and 84 cells/mm3 in the non-IDU group (P=.98). After adjustment for other covariates in a logistic regression model, DAART participants were significantly more likely to achieve viral suppression than were patients in each of the 3 comparison groups. CONCLUSIONS: These results suggest that methadone clinic-based DAART has the potential to provide substantial clinical benefit for HIV-infected IDUs.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Terapia por Observación Directa , Infecciones por VIH/tratamiento farmacológico , Metadona/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Abuso de Sustancias por Vía Intravenosa/rehabilitación , Factores de Tiempo , Carga ViralRESUMEN
Hereditary haemorrhagic telangiectasia, HHT, is an autosomal dominant disorder that affects approximately 1 in 8000 people. HHT1 is associated with mutations in the ENG (Endoglin) gene and with haploinsufficiency. The disorder is characterized by focally dilated vessels, which can lead to arteriovenous malformations and serious complications even in young children. In the current study, umbilical cord and placenta samples from newborns with ENG mutations were analyzed to estimate the level of corresponding protein and look for potential vascular dysplasia. We confirmed, using metabolic labelling and flow cytometry, that endoglin levels were significantly reduced to median values of 47 per cent (range 32-56 per cent) and 58 per cent (46-90 per cent), respectively, in human umbilical vein endothelial cells derived from newborns with ENG mutations (HHT1 group; n=18) relative to samples from newborns shown not to have the familial mutation (non-HHT group). We also quantified the relative expression of endoglin by estimating the endoglin/PECAM-1 staining ratio in tissue sections. We observed significantly lower values in the HHT1 group, compared to the non-HHT group for the umbilical vein (n=9; median 0.6 vs 0.9; ranges 0.2-1.0 and 0.5-1.5) and for placental stem villus vessels (n=9 and 10; median 0.42 vs 0.93; ranges 0.24-0.58 and 0.56-1.18). No differences in the estimated umbilical vein cross-sectional area and in the proportion of vessels present in placental villi were observed in sections from the HHT1 group relative to the non-HHT group. Thus, blood vessels from HHT1 individuals are maintained intact in the umbilical vein and placenta during pregnancy and delivery, despite a significant reduction in endoglin expression.
Asunto(s)
Endotelio Vascular/metabolismo , Hiperbilirrubinemia Hereditaria/metabolismo , Placenta/irrigación sanguínea , Venas Umbilicales/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Antígenos CD , Células Cultivadas , Análisis Mutacional de ADN , Endoglina , Endotelio Vascular/citología , Humanos , Hiperbilirrubinemia Hereditaria/genética , Hiperbilirrubinemia Hereditaria/patología , Procesamiento de Imagen Asistido por Computador , Recién Nacido , Mutación , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Receptores de Superficie Celular , Venas Umbilicales/citología , Molécula 1 de Adhesión Celular Vascular/genéticaRESUMEN
The objective of this work was to synthesize and characterize a novel series of biodegradable cyclic carbonate polyester copolymers based on lactide and 5-methyl-5-benzyloxy-carbonyl-1,3-dioxan-2-one (MBC). Two compositions were selected for characterization. One copolymer was based on a racemic mixture of 1-lactide with 15.4 mole % MBC and the other was based on 1-lactide with 8.2 mole % MBC. These polymers contain carboxylic acid moieties along the backbone that may be used for tethering bioactive agents, forming ionic crosslinks or be reacted with vinyl containing monomers to allow free radical crosslinking. The initial materials evaluated have the carboxylic acid functionalities blocked with benzene. These polymers and the de-blocked versions may have potential applications for hard and soft tissue scaffolds, control drug delivery matrixes or a variety of other applications in medicine. The copolymer samples were pressed into 7.0-mm diameter disk using a KBr press. The disks were then sterilized using U.V radiation under a laminar flow hood. After sterilization, the copolymer disks were submerged in 2 ml of media and placed in a CO2 regulated incubator at 37 degrees C. A total of six groups per phase (n = 7 test tubes per group) were used in this study. Test tubes in groups I and III were plated with MRC-5 and subsequently treated with media alone (controls). Test tubes in groups II and IV were plated with MRC-5 and subsequently treated with media before being introduced to copolymer samples. Cell number, as well as, biochemical markers such as protein and malondialdehyde (MDA) were determined at the end of the 24, 48 and 72-hour time periods. Representative test tubes were subjected to an H&E staining procedure for microscopic morphological evaluation. The results of this evaluation suggest that the exposure of both copolymers produced a non-cytotoxic environment with the MRC-5 cell line. Although both copolymers are non-cytotoxic, the sample having the higher MBC content is the preferred composition based upon MDA levels and morphological evaluations.
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Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Poliésteres/síntesis química , Poliésteres/toxicidad , Implantes Absorbibles , Apoptosis/efectos de los fármacos , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/toxicidad , Adhesión Celular , Recuento de Células , Línea Celular , Anticonceptivos/síntesis química , Anticonceptivos/toxicidad , Dioxanos/química , Dioxanos/toxicidad , Humanos , Poliésteres/química , Polímeros/síntesis química , Polímeros/toxicidadRESUMEN
The grazing trial at Kidston Gold Mine, North Queensland, was aimed specifically to assess the uptake of metals from the tailing and the potential for unacceptable contamination of saleable meat. Further aims included estimating metal dose rates and identifying potential exposure pathways including plant uptake of heavy metals, mine tailings adhered to plants and direct ingestion of mine tailing. It was found that of the 11 metals analysed (As, Zn, Co, Cd, Cr, Sn, Pb, Sb, Hg, Se and Ni) in the animal's liver, muscle and blood during the 8-month trial period, only accumulation of arsenic and zinc occurred. A risk assessment including these two metals was conducted to determine the potential for chronic metal toxicity and long-term contamination, using the estimates of metal dose rate. It was concluded that no toxicity or long-term contamination in cattle was likely at this site. Management procedures were therefore not required at this site; however, the results highlight percent ground cover and standing dry matter (DM) as important factors in decreasing metal exposure from direct ingestion of tailings and dust adhered to plants.
Asunto(s)
Arsénico/farmacocinética , Residuos Industriales , Minería , Contaminantes del Suelo/farmacocinética , Zinc/farmacocinética , Crianza de Animales Domésticos , Animales , Arsénico/sangre , Intoxicación por Arsénico , Disponibilidad Biológica , Bovinos , Conducta Alimentaria , Contaminación de Alimentos/análisis , Oro , Residuos Industriales/análisis , Hígado/efectos de los fármacos , Hígado/metabolismo , Carne/análisis , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Poaceae/química , Medición de Riesgo , Contaminantes del Suelo/análisis , Zinc/sangreRESUMEN
Two studies were conducted to test a model of the distinctiveness-based illusory correlation (IC) phenomenon that suggests there are two components operating with ICs: cognitive memorial, and affective. In Expt 1 (N = 118), two stimulus arrays were developed that were equivalent in regards to valence (good or bad extremity) but differed in regards to the affect dimension (high or low emotional intensity). Consistent with predictions drawn from the proposed model, the magnitude of the IC effect was higher in the high emotional intensity than in the low emotional intensity condition, but only significantly so on the measures (estimation and general evaluation) that have been hypothesized to be most sensitive to the affective component. In Expt 2 (N = 52), the affective qualities were matched and the valence properties varied in two stimulus arrays. As predicted, the IC effect differed significantly between conditions only on the measure (assignment) thought to be most sensitive to the memorial component. The results are discussed in terms of the implications of the findings for the proposed mechanisms of illusory correlation.
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Afecto , Ilusiones , Recuerdo Mental , Percepción Social , Estereotipo , Adulto , Nivel de Alerta , Femenino , Humanos , Masculino , Personalidad , Retención en Psicología , Identificación SocialRESUMEN
High concentrations of neutrophil defensins from airway and blood have been reported in patients with inflammatory lung diseases, but their exact role is unclear. We investigated the direct effect of defensins on the lungs of mice. Intratracheal instillation of purified defensins (5-30 mg/kg) induced a progressive reduction in peripheral arterial O(2) saturation, increased lung permeability, and enhanced the lung cytochrome c content. These indexes of acute lung dysfunction were associated with an increased total cell number and a significant neutrophil influx into the lung [5.1 +/- 0.04% in control vs. 48.6 +/- 12.7% in the defensin (30 mg/kg) group, P < 0.05]. Elastase concentrations in the bronchoalveolar lavage (BAL) fluids increased from 38 +/- 11 ng/ml (control) to 80 +/- 4 ng/ml (defensins, P < 0.05). Five hours after defensin instillation, concentrations of tumor necrosis factor-alpha and macrophage inflammatory protein-2 in BAL fluid were significantly increased. High levels of monocyte chemoattractant protein-1 in BAL fluid and plasma were also found after defensin stimulation. We conclude that intratracheal instillation of defensins causes acute lung inflammation and dysfunction, suggesting that high concentrations of defensins in the airways may play an important role in the pathogenesis of inflammatory lung diseases.
Asunto(s)
Defensinas/metabolismo , Neutrófilos/metabolismo , Neumonía/metabolismo , Animales , Arterias , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Quimiocina CCL2/metabolismo , Quimiocina CXCL2 , Quimiocinas/metabolismo , Grupo Citocromo c/metabolismo , Defensinas/administración & dosificación , Relación Dosis-Respuesta a Droga , Instilación de Medicamentos , Masculino , Ratones , Infiltración Neutrófila/efectos de los fármacos , Infiltración Neutrófila/inmunología , Neutrófilos/inmunología , Oximetría , Elastasa Pancreática/metabolismo , Permeabilidad/efectos de los fármacos , Neumonía/inducido químicamente , Neumonía/inmunología , Tráquea/efectos de los fármacos , Tráquea/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
What happens when people discover that they are members of a group about which they have previously formed some stereotype? To address this question, procedures previously shown to induce negative stereotypes of minority groups were combined with a social categorization manipulation. Participants in a distinctiveness-based illusory correlation paradigm (Hamilton & Gifford, 1976) either knew nothing about their group membership, or learned that they were a member of the minority group or the majority group either before or after being presented the stereotype-engendering stimulus materials. Results revealed that social categorization into the minority group before stimulus presentation eliminated the perceived stereotype and reversed the evaluative bias, whereas social categorization into the minority group after stimulus presentation had no effect on the perceived stereotype and only a weak effect in reducing the evaluative bias. Social categorization into the majority group either before or after stimulus presentation had little effect on the perceived stereotype and evaluative bias. These results clarify the process underlying the influence of social categorization on stereotype formation, underscore the distinction between affective and cognitive influences on stereotype formation and stereotype change, and offer insights into 'autostereotyping' among members of minority groups.
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Identificación Social , Percepción Social , Estereotipo , Humanos , AutoimagenRESUMEN
OBJECTIVE: Assessment of alcohol-related problems is essential in psychiatric settings. The Michigan Alcoholism Screening Test (MAST) has been the most commonly evaluated self-report alcohol assessment tool in psychiatric settings. However, due to a large variation in reports of findings and conclusions, a clear understanding of the utility of the MAST in psychiatric settings continues to be elusive. Therefore, the major goals of this investigation were (1) to integrate the available information pertaining to the validity of the MAST when used in psychiatric settings, and (2) to investigate factors that may moderate the performance of the MAST. METHOD: Using clinically determined alcohol-related diagnosis as a criterion, a meta-analytic integration of nine published studies investigating the criterion validity of the MAST in psychiatric settings is presented. RESULTS: Findings revealed that the MAST is significantly valid when used in psychiatric settings. However, sensitivity estimates were found to be of greater magnitude than specificity estimates. Further, validity estimates of the MAST were found to be higher in psychiatric samples that had a greater proportion of women and in samples that exhibited higher base rates of alcohol-use disorder. CONCLUSIONS: Results of this integration support the continued use of the MAST in psychiatric settings as a screening instrument and suggest that those who administer the MAST must be attentive to particular characteristics of respondents.
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Alcoholismo/diagnóstico , Admisión del Paciente , Inventario de Personalidad/estadística & datos numéricos , Adulto , Alcoholismo/psicología , Femenino , Humanos , Masculino , Psicometría , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVES: Ventilation with positive end-expiratory pressure (PEEP) above the inflection point (P(inf)) has been shown to reduce lung injury by recruiting previously closed alveolar regions; however, it carries the risk of hyperinflating the lungs. The present study examined the hypothesis that a new strategy of recruiting the lung with a sustained inflation (SI), followed by ventilation with small tidal volumes, would allow the maintenance of low PEEP levels (
P(inf). MEASUREMENTS AND MAIN RESULTS: In groups 2 and 4, static compliance decreased after ventilation (p < .01). Histologically, group 2 (PEEP < P(inf) without SI) showed significantly greater injury of small airways, but not of terminal respiratory units, compared with group 1. Group 3 (PEEP < P(inf) after a SI), but not group 4, showed significantly less injury of small airways and terminal respiratory units compared with group 2. CONCLUSIONS: We conclude that small tidal volume ventilation after a recruitment maneuver allows ventilation on the deflation limb of the pressure/volume curve of the lungs at a PEEP < P(inf). This strategy a) minimizes lung injury as well as, or better than, use of PEEP > P(inf), and b) ensures a lower PEEP, which may minimize the detrimental consequences of high lung volume ventilation.
Asunto(s)
Ventilación con Presión Positiva Intermitente/métodos , Síndrome de Dificultad Respiratoria/terapia , Mecánica Respiratoria , Análisis de Varianza , Animales , Insuflación , Rendimiento Pulmonar , Respiración con Presión Positiva , Estudios Prospectivos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Síndrome de Dificultad Respiratoria/patología , Capacidad Pulmonar TotalRESUMEN
OBJECTIVES: To examine the clinical value of six seminal plasma components in the evaluation of sperm quality and in the differential diagnosis of men with infertility. METHODS: We analyzed 202 seminal plasmas for prostate-specific antigen, glucose, pepsinogen C, insulin-like growth factor binding protein-3, prostaglandin D synthase (PGDS), and BRCA1-like immunoreactive protein (BRCA1-LIP) using quantitative immunofluorometric procedures. The semen donors were categorized in four clinical groups: normal, oligospermic, azoospermic, and vasectomy patients. We then evaluated whether any of these biochemical markers were associated with other parameters of sperm quality, including patient age, total cell concentration, percentage of motility, and percentage of normal morphology. RESULTS: We found that only PGDS concentration was significantly associated with other parameters of sperm quality. PGDS concentration correlated positively with total cell concentration (r = 0.55), percentage of motility (r = 0.31), and percentage of normal morphology (r = 0.31). Median PGDS concentration in seminal plasma decreased progressively from normal to oligospermic to azoospermic to vasectomy patients (P <0.001). There was no overlap between seminal plasma PGDS concentration of normal subjects versus vasectomy patients. The only other parameter that was moderately decreased in vasectomy patients was BRCA1-LIP. The source of PGDS in seminal plasma was determined with various techniques, including immunohistochemistry. This protein is produced and secreted by the Sertoli cells. CONCLUSIONS: Our findings suggest that PGDS concentration in seminal plasma correlates with other known indicators of semen quality and is a new marker of post-testicular obstruction. This biochemical parameter could be used to aid in the differential diagnosis of obstructive and nonobstructive azoospermia in men with infertility.
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Infertilidad Masculina/diagnóstico , Semen/química , Adulto , Biomarcadores/análisis , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The lung relies upon epithelial active transport of Na+ to aid in the clearance of fluid from its air spaces. Because it is unknown whether the rate of active Na+ transport by the distal lung epithelium varies during early postnatal age, we performed studies in young guinea pigs (7 and 30 days after birth). We used a single pass isolated perfused lung model in which a Krebs Ringer bicarbonate solution containing 22Na+, [14C]sucrose, and FITC-dextran was placed into the air spaces of the lungs, and apparent permeability-surface area (PS) products were calculated after determining the changes in lung weight and the concentrations of the isotopes in the vascular effluent. The PS product for 22Na+, but not [14C]sucrose, decreased significantly at both ages when amiloride was infused (final concentration of 10(-4) M). Amiloride also decreased the rate of fluid clearance, as assessed by changes in organ weight, at both ages. Although the absolute rate of amiloride-sensitive 22Na+ transport increased with age, morphometric measurement of the alveolar region demonstrated that the rate of amiloride-sensitive 22Na+ transport per unit alveolar surface area was similar. These data indicate that although the guinea pig lung undergoes significant growth shortly after birth, the rate of amiloride-sensitive active Na+ transport per unit surface area remains constant. Since a component of weight loss was insensitive to amiloride, these in vivo studies suggest that the amiloride-insensitive Na+ transport pathways previously identified in cultured lung epithelium exist in the intact lung.
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Amilorida/farmacología , Pulmón/metabolismo , Radioisótopos de Sodio/metabolismo , Animales , Animales Recién Nacidos , Epitelio/crecimiento & desarrollo , Epitelio/metabolismo , Cobayas , Transporte Iónico/efectos de los fármacos , Pulmón/crecimiento & desarrollo , Edema Pulmonar/metabolismoRESUMEN
The authors have shown previously that in addition to its survival effects on neurons and glia, ciliary neurotrophic factor (CNTF) induced potent cachectic effects and acute phase proteins when present in the peripheral circulation at concentrations of < or = 10 ng/ml. These effects did not depend upon the induction of other cytokine family members. Described here are the specific physiological effects which systemic administration of CNTF can induce in somatic tissue. Mice implanted with C6 glioma cells, genetically modified to secrete CNTF, exhibited rapid catabolism of adipose tissue and skeletal muscle, depressed steady-state levels of glucose and triglycerides, elevations in red blood cell content, gall bladder hypertrophy and thymic atrophy, with a disproportionate loss of CD4+/CD8+ T cells. This cachectic wasting resulted in death over a period of 7-10 days. Implantation of the parental C6 line, or C6 cells which express a non-secreted form of CNTF, did not result in overt effects over this time period. These findings have implications both for the biology of CNTF family members, and the therapeutic use of factors such as CNTF in vivo.
Asunto(s)
Factores de Crecimiento Nervioso/farmacología , Proteínas del Tejido Nervioso/farmacología , Síndrome Debilitante/inducido químicamente , Tejido Adiposo/metabolismo , Animales , Glucemia/metabolismo , Relación CD4-CD8 , Línea Celular , Factor Neurotrófico Ciliar , Femenino , Citometría de Flujo , Vesícula Biliar/efectos de los fármacos , Interleucina-11/farmacología , Interleucina-6/farmacología , Ratones , Músculo Esquelético/metabolismo , Ratas , Triglicéridos/sangre , Células Tumorales CultivadasRESUMEN
Because an increase in biliary deoxycholate levels seems to be a risk factor for cholesterol gallstone formation, we determined the relationship between deoxycholate levels and levels of the pronucleating protein, immunoglobulin G (Ig) in human gallbladder bile. Patients with cholesterol gallstones had a higher concentration of biliary IgG compared with a pigmented stone group and control patients. This was associated with the simultaneous presence of two conditions in the cholesterol stone group, supersaturated bile and a high deoxycholate/cholate ratio. The other patient groups met only one of the two conditions. Next, animal studies were performed to determine if model biles mimicking the two conditions could affect IgG secretion by the gallbladder. Gallbladders were exposed in vivo and then in an Ussing chamber to model biles. The voltage clamp technique was used to monitor functional integrity of the preparation. Three different model biles were tested: (1) taurodeoxycholate (TDC), 80%; taurocholate (TC), 20%; and cholesterol saturation index (CSI), 1.2; (2) TDC, 20%; TC, 80%; and CSI, 1.2; and (3) TDC, 80%; TC, 20%; and CSI, 0.6. IgG concentrations became significantly higher in group 1 than in the other two groups. The concentration of mucous glycoprotein was also significantly greater in group 1 when compared with group 2. Plasma cells were increased in number in mucosal and submucosal layers in group 1. We conclude that cholesterol supersaturated model bile with high content of TDC induces gallbladder epithelial alterations, which increase the luminal concentration of IgG and mucous glycoprotein.
Asunto(s)
Bilis/metabolismo , Ácido Desoxicólico/farmacología , Inmunoglobulina G/metabolismo , Animales , Colelitiasis/clasificación , Colelitiasis/metabolismo , Colelitiasis/fisiopatología , Colesterol/metabolismo , Femenino , Glicoproteínas/metabolismo , Humanos , Concentración Osmolar , Pigmentación , Valores de Referencia , Porcinos , Ácido Taurocólico/metabolismo , Ácido Taurodesoxicólico/metabolismoRESUMEN
This analysis summarizes studies comparing attained heights with expected heights of children with asthma treated with inhaled or oral corticosteroids. The possible moderating effects of treatment duration, and dosage and asthma severity are also examined. A preliminary database of 95 articles rendered 21 includable studies representing 810 patients with asthma, which yielded 29 tests of the corticosteroid-growth effect. Statistical integration of the results of these studies revealed a significant but small tendency for corticosteroid therapy in general to be associated with diminished final height (Z = 2.328, p = 0.01, mean r = -0.023). However, this effect varied for the specific drugs under consideration. As expected, significant weak growth impairment was observed for prednisone (Z = 2.137, p = 0.0164, mean r = -0.295) and "other oral corticosteroids" (Z = 9.107, p = 2.44E-18, mean r = -0.260). On the other hand, a significant moderate tendency was observed for inhaled beclomethansone dipropionate therapy to be associated with attaining normal stature (Z = 7.395, p = 2.17E-13, mean r = +0.432). There was no statistical evidence for beclomethasone dipropionate therapy to be associated with growth impairment at higher doses, for longer therapy durations, or among patients with more severe asthma. This meta-analytic integration indicates that available studies of inhaled beclomethasone dipropionate therapy do not show an association between its use and the adverse effect of diminished stature.
Asunto(s)
Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Crecimiento/efectos de los fármacos , Administración por Inhalación , Administración Oral , Factores de Edad , Asma/tratamiento farmacológico , Beclometasona/efectos adversos , Niño , HumanosRESUMEN
The purpose of this research was to explore the interviewees' perceptions of the major factors that contributed to their alcohol abuse. The research was carried out by interviewing seven women who were identified by community mental health professionals. The research was qualitative and exploratory. The semi-structured tape-recorded interview technique was used as an enquiry tool. The tapes were then transcribed and coded, and the findings were scrutinized and scanned for emerging themes and concepts using an interactive and cyclical process of data-reduction techniques, data display and verification of findings. The findings suggest that the majority of the interviewees could identify and isolate specific life events and past-life crises that contributed to an increase in their alcohol intake. Results also indicate that there is a need to consider the efficacy of the current models of primary, secondary and tertiary care as well as relapse-prevention programmes of care in order to facilitate women to have every opportunity to make informed and rational health choices about their drinking behaviours, and to maintain abstinence, for the promotion of positive mental health and for enhancing the quality of their lives.