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1.
J Clin Rheumatol ; 24(6): 302-307, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29708516

RESUMEN

OBJECTIVE: The aims of this study were to evaluate the prevalence of metabolic syndrome (MetS) in psoriatic arthritis (PsA) patients according to the most recent definition in a Mediterranean population and to determine its association with biomarkers of inflammation and serum adipocytokine levels. METHODS: Demographic, clinical, and laboratory data were collected on 74 patients with PsA and 82 control subjects. The presence of MetS was determined according to the current "harmonization" definition. Serum adipocytokines were analyzed. Continuous variables were compared by t test and discrete variables by χ test. Multivariate regression models compared the association between the presence of MetS and the blood levels of adipocytokines. RESULTS: The prevalence of MetS was higher in PsA patients compared with the control group: 54.8% versus 36.6%, respectively (P = 0.02; odds ratio, 2.33; 95% confidence interval, 1.16-4.69). The main difference between the 2 groups was waist circumference. No association was found between MetS and parameters of articular and skin disease activity or treatment. Leptin levels and leptin/adiponectin ratio were higher in PsA patients compared with control subjects: 83.4 versus 51.7 ng/mL (P = 0.001) and 6.3 × 10 versus 4.1 × 10 (P = 0.015), respectively. There was no significant difference in the adiponectin levels between the groups. CONCLUSIONS: The prevalence of MetS was higher in PsA patients compared with non-PsA control subjects in this Mediterranean population. Clinicians caring for PsA patients ought to be aware of the increased risk of MetS in PsA patients, confirmed in different regions worldwide. The increased MetS seems to be linked to central obesity in these patients, and appropriate treatment recommendations are advised.


Asunto(s)
Adipoquinas/sangre , Artritis Psoriásica , Síndrome Metabólico , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Antirreumáticos/clasificación , Antirreumáticos/uso terapéutico , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/epidemiología , Artritis Psoriásica/metabolismo , Biomarcadores/sangre , Glucemia/análisis , HDL-Colesterol/sangre , Correlación de Datos , Femenino , Humanos , Israel/epidemiología , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Factores de Riesgo , Triglicéridos/sangre , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Circunferencia de la Cintura
2.
BMC Infect Dis ; 16(1): 569, 2016 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-27737630

RESUMEN

BACKGROUND: Acute reduction in hemoglobin levels is frequently seen during sepsis. Previous studies have focused on the management of anemia in patients with septic shock admitted to intensive care units (ICU's), including aggressive blood transfusion aiming to enhance tissue oxygenation. AIM: To study the changes in hemoglobin concentrations during the first week of sepsis in the setting of Internal Medicine (IM) units, and their correlation to survival. DESIGN: Observational prospective study. METHODS: We recorded hemoglobin values upon admission and throughout the first week of hospital stay in a consecutive cohort of septic patients admitted to IM units at a community hospital, the patients were enrolled into a prospective registry. Data on blood transfusions was also collected, we examined the correlation between hemoglobin concentrations during the first week of sepsis and survival, the effect of blood transfusion was also assessed. RESULTS: Eight hundred and fifteen patients (815) with sepsis were enrolled between February 2008 to January 2009. More than 20 % of them had hemoglobin levels less than 10g/dL on admission, a rate that was doubled during the first week of sepsis. Overall, 68 (8.3 %) received blood transfusions, 14 of them (20.6 %) due to bleeding. Typically, blood transfusion was given to older patients with a higher rate of malignancy and lower hemoglobin levels. While hemoglobin concentration on admission had strong correlation with in-hospital mortality (O.R-0.83 [95 % C.I. 0.74-0.92], blood transfusion was not found to be an independent predicting factor for mortality. CONCLUSION: Anemia is very common in sepsis. While hemoglobin level on admission exhibit independent correlation with survival, blood transfusion do not.


Asunto(s)
Transfusión Sanguínea/estadística & datos numéricos , Hemoglobinas/análisis , Sepsis/sangre , Sepsis/terapia , Adulto , Anciano , Anciano de 80 o más Años , Anemia/sangre , Anemia/mortalidad , Anemia/terapia , Femenino , Departamentos de Hospitales , Mortalidad Hospitalaria , Humanos , Medicina Interna , Israel/epidemiología , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Sepsis/mortalidad , Choque Séptico/sangre , Choque Séptico/mortalidad , Choque Séptico/terapia
3.
Harefuah ; 155(5): 296-8, 322, 321, 2016 May.
Artículo en Hebreo | MEDLINE | ID: mdl-27526558

RESUMEN

INTRODUCTION: The southern district of Clalit Health Services and Soroka University Medical Center are combined in an organizational configuration: the Southern Region. The Region has developed joint programs in order to advance the quality of medical care whilst optimizing the utilization of available resources. An objective continuous method of assessment was needed to evaluate the continuity of care between the community and the hospital. AIMS: To produce objective tools for quantification based on pre-existing data systems, which enable ongoing assessment of the quality of continuity of care between the community and hospital, and the impact of the introduction of novel means of improvement. METHODS: We defined a set of measurements that exemplify continuity of care in different areas of transition between community and hospital, all directly retrievable from existing computerized data sources. RESULTS: About forty different measurements have been defined, in different clinical areas. Of these, a dozen have already been implemented by mapping the process and the main obstacles that the patient goes through, followed by implementation of appropriate solutions. CONCLUSIONS: The application of an objective system of assessment of the results of continuity of care, utilizing pre-existing data sources, is essential for advancing the initiative, and is a breakthrough in the quantification of continuity of care. DISCUSSION: Continuity of care between community and hospital has been applied in the Southern Region to dozens of quality measurements. This is a novel project developing an objective system of measurement, directly assessing the quality of continuity of care for the individual patient.


Asunto(s)
Centros Médicos Académicos/organización & administración , Servicios de Salud Comunitaria/organización & administración , Continuidad de la Atención al Paciente/normas , Humanos , Israel , Objetivos Organizacionales , Evaluación de Resultado en la Atención de Salud , Garantía de la Calidad de Atención de Salud , Mejoramiento de la Calidad
4.
Med Care ; 53(3): 283-9, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25634089

RESUMEN

BACKGROUND: Readmission prevention should begin as early as possible during the index admission. Early identification may help target patients for within-hospital readmission prevention interventions. OBJECTIVES: To develop and validate a 30-day readmission prediction model using data from electronic health records available before the index admission. RESEARCH DESIGN: Retrospective cohort study of admissions between January 1 and March 31, 2010. SUBJECTS: Adult enrollees of Clalit Health Services, an integrated delivery system, admitted to an internal medicine ward in any hospital in Israel. MEASURES: All-cause 30-day emergency readmissions. A prediction score based on before admission electronic health record and administrative data (the Preadmission Readmission Detection Model-PREADM) was developed using a preprocessing variable selection step with decision trees and neural network algorithms. Admissions with a recent prior hospitalization were excluded and automatically flagged as "high-risk." Selected variables were entered into multivariable logistic regression, with a derivation (two-thirds) and a validation cohort (one-third). RESULTS: The derivation dataset comprised 17,334 admissions, of which 2913 (16.8%) resulted in a 30-day readmission. The PREADM includes 11 variables: chronic conditions, prior health services use, body mass index, and geographical location. The c-statistic was 0.70 in the derivation set and of 0.69 in the validation set. Adding length of stay did not change the discriminatory power of the model. CONCLUSIONS: The PREADM is designed for use by health plans for early high-risk case identification, presenting discriminatory power better than or similar to that of previously reported models, most of which include data available only upon discharge.


Asunto(s)
Registros Electrónicos de Salud/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Adulto , Anciano , Estudios de Cohortes , Técnicas de Apoyo para la Decisión , Predicción , Humanos , Pacientes Internos/estadística & datos numéricos , Israel/epidemiología , Persona de Mediana Edad , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud , Estudios Retrospectivos , Medición de Riesgo/métodos
5.
Acta Oncol ; 54(2): 164-70, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25350524

RESUMEN

BACKGROUND: After a decade of extensive use, the actual contribution of bevacizumab in first-line treatment of metastatic colorectal cancer (mCRC) is still unclear. OBJECTIVE: To evaluate 'real-life' outcomes of patients with mCRC before and after the introduction of bevacizumab to standard mCRC first-line practice. METHODS: Using the computerized administrative database of Clalit Health Services' (CHS), Israel's largest health care provider, we retrospectively compared two cohorts (n = 1739): (A) all CHS' patients diagnosed with mCRC between January 2000 and December 2004 that received first-line irinotecan or oxaliplatin-based combination chemotherapy (before bevacizumab was introduced) (n = 1052), and (B) all patients that started first-line irinotecan or oxaliplatin combination chemotherapy together with bevacizumab between September 2006 and December 2009 (after bevacizumab was fully reimbursed in Israel for mCRC first-line therapy) (n = 687). The primary endpoint was overall survival (OS) and secondary endpoints were first-line progression-free survival (PFS) and metastatectomy rates. RESULTS: Median OS was longer in Cohort B than in Cohort A [23.0 months vs.15.0, adjusted hazard ratio (HR), 0.75]. Secondary outcomes were also better; PFS of 14.0 months vs. 9.8 in the earlier period (HR, 0.75) and metastatectomy rate of 8.1% versus 3.9%. The longer OS in Cohort B was preserved even after controlling for latter-line epidermal growth factor receptor (EGFR) inhibitor use (HR = 0.77). CONCLUSION: In this analysis, OS, PFS and metastatectomy rates of first-line treatment of mCRC were significantly higher in the later period of the study. These results, derived from 'real-life' practice, suggest that the use of bevacizumab, among other alterations in the clinical management of mCRC between the two periods, might have had a significant contribution to these outcomes, and may therefore support the current practice of adding bevacizumab to first-line treatment of mCRC.


Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Bevacizumab , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Estudios de Cohortes , Neoplasias Colorrectales/irrigación sanguínea , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Receptores ErbB/antagonistas & inhibidores , Femenino , Humanos , Irinotecán , Israel/epidemiología , Masculino , Metastasectomía , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Estudios Retrospectivos
6.
Respiration ; 84(6): 492-500, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22986339

RESUMEN

BACKGROUND: The routine use of multidetector computed tomography has led to increased detection of unsuspected pulmonary embolism (UPE), with questionable benefit for diagnosis and treatment. OBJECTIVE: The purpose of this work was to compare the clinical characteristics and prognosis of patients with UPE to patients with suspected PE (SPE). METHODS: We retrospectively reviewed the charts of patients diagnosed with PE in a community-based university hospital between the years 2002 and 2007. UPE was defined as PE detected on CT scans performed for indications other than suspicion of PE. We compared patients with UPE to patients with SPE for differences in clinical features, electrocardiogram, imaging and echocardiographic findings. We also assessed the long-term outcomes using electronic patient records. RESULTS: Of 500 patients with PE, 408 had SPE and 92 had UPE. Patients with UPE were similar to patients with SPE regarding age and sex distribution. Malignancy was more prevalent in UPE patients (39 vs. 23%, p < 0.0068). UPE patients had significantly less tachypnea (37 vs. 57%, p = 0.0005), dyspnea (47 vs. 87%, p < 0.0001), chest pain (19 vs. 42%, p < 0.0001) and hypoxemia (36 vs. 55%, p = 0.0011). Mortality was higher in UPE patients (70.3 vs. 53%, p = 0.0029). The hazard ratio after adjustment for confounders including age, sex and malignancy was 1.546 (95% CI: 1.139-2.099, p = 0.0052). CONCLUSIONS: We suggest that UPE is more prevalent in patients with a malignancy and is associated with higher mortality despite a less severe clinical presentation. UPE may be a marker of poor prognosis.


Asunto(s)
Neoplasias/epidemiología , Embolia Pulmonar , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Pronóstico , Modelos de Riesgos Proporcionales , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidad , Embolia Pulmonar/fisiopatología , Estudios Retrospectivos
7.
Rheumatol Int ; 32(3): 595-600, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21120489

RESUMEN

Disease patterns and manifestations may vary among different populations and change over time. The purpose of our study was to define the demographic, clinical, roentgenologic, and laboratory findings in a recent cohort of psoriatic arthritis patients followed up in rheumatology clinics in northern Israel. We conducted a cross-sectional study of 149 psoriatic arthritis patients. Demographic, clinical, laboratory, and radiological data, with emphasis on the pattern of arthritis, treatment regimens, and co-morbidities were obtained from patient interviews and rheumatology file reviews. The mean age of our patients was 58.2, with a female preponderance (57.3%). Skin involvement preceded the arthritis or was diagnosed simultaneously in 90.1% of cases. The most common joint involvement was an RA-like arthritis (49.7% of the patients) correlating positively with age, female gender, and disease duration. Dactylitis and nail involvement were observed in 33.6 and 36.2% of the patients, respectively. Radiographic bone erosions were noted in a third of the patients, correlating with DIP and RA-like arthritis patterns. Most patients were treated with methotrexate (73.8%) and a combination therapy (41.4%). An increased incidence of hypertension, hyperlipidemia, and diabetes mellitus was noted in our cohort compared to the general Israeli population. Our survey, the first of its kind conducted in Israel, noted a relative increase in the polyarticular manifestation of PsA and a decrease in spondyloarthropathy, compared to historic series, with more aggressive disease found in women above the age of sixty. These findings are in line with recent surveys.


Asunto(s)
Artritis Psoriásica/diagnóstico , Artritis Psoriásica/epidemiología , Diabetes Mellitus/epidemiología , Hiperlipidemias/epidemiología , Hipertensión/epidemiología , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Pruebas de Química Clínica , Comorbilidad , Estudios Transversales , Demografía , Quimioterapia Combinada , Salud de la Familia , Femenino , Humanos , Inmunosupresores/uso terapéutico , Israel/epidemiología , Articulaciones/patología , Articulaciones/fisiopatología , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos
8.
Isr Med Assoc J ; 14(2): 115-8, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22693794

RESUMEN

BACKGROUND: Extended-spectrum beta-lactamase (ESBL) resistance is a growing concern in and outside hospitals. Physicians often face a true clinical dilemma when initiating empirical antibiotic treatment in patients admitted to internal medicine departments. OBJECTIVES: To determine the prevalence of risk factors for ESBL resistance in patients with urinary tract infection (UTI) admitted to internal medicine departments. METHODS: We conducted a retrospective analysis of the medical records of patients with UTI admitted to an internal medicine division in a community-based academic hospital over a 1 year period. We collected clinical, laboratory and imaging data that were available to the treating physician at admission. Outcome measures included ESBL resistance and death. RESULTS: Of the 6754 admissions 366 patients were included in the study. Hospitalization during the previous 3 months (odds ratio 3.4, P < 0.0001), residency in a long-term-care facility (OR 2.4, P = 0.004), and the presence of a permanent urinary catheter (OR 2.2, P = 0.015) were correlated to ESBL resistance with statistical significance. These risk factors were extremely prevalent in our patient cohort. CONCLUSIONS: ESBL resistance is becoming prevalent outside hospital settings, and patients admitted to an internal medicine department with UTI frequently carry risk factors for harboring resistant bacteria. In such patients a high index of suspicion and early targeted antibiotic treatment for ESBL-producing Enterobacteriaceae may be justified.


Asunto(s)
Antibacterianos/farmacología , Infecciones por Enterobacteriaceae/epidemiología , Enterobacteriaceae/efectos de los fármacos , Infecciones Urinarias/epidemiología , Resistencia betalactámica , beta-Lactamas/farmacología , Anciano de 80 o más Años , Estudios de Cohortes , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/microbiología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Medicina Interna/métodos , Israel/epidemiología , Masculino , Oportunidad Relativa , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología
9.
Harefuah ; 151(7): 388-92, 437, 2012 Jul.
Artículo en Hebreo | MEDLINE | ID: mdl-23002687

RESUMEN

Technological advances combined with the aging of the population bring about an increasingly growing number of patients with chronic conditions and multi-morbidity. Multi-morbidity, the co-occurrence of chronic and/or non-chronic conditions in an individual, is the norm among elderly patients, and is becoming increasingly common among younger adults. The Israeli health system, like other systems worldwide, is faced with the challenges posed by the increase in complex multi-morbidity, in an era of growing fiscal constraints, a situation that can induce financial and organizational crises. To effectively cope with such circumstances, a paradigm shift is needed. Health systems need to focus on overall morbidity burden and multi-morbidity (rather than the prevailing one disease at a time approach) and on better care integration. The Israeli health system entails many of the essential elements for addressing the challenges of integrated care, including universal health coverage and advanced health information technology systems. Yet, like other health systems, there is a need for care management support mechanisms that are more effectively tailored to meet the needs of the highly multimorbid patients. This review outlines the organizational approach required to better align care for the main customers of health care in the 21st century: patients with multi-morbidity. We focus on four domains: assessment of morbidity burden according to measures that account for the interaction and synergism amongst conditions; integration across the care continuum; enhancement of primary care and self-management support approaches; and provision of uniquely tailored care management solutions for the highest risk multi-morbid patients.


Asunto(s)
Prestación Integrada de Atención de Salud/organización & administración , Atención Primaria de Salud/organización & administración , Autocuidado/métodos , Adulto , Anciano , Envejecimiento , Enfermedad Crónica , Comorbilidad , Costo de Enfermedad , Humanos , Cobertura del Seguro , Israel/epidemiología , Informática Médica/organización & administración
10.
Am J Physiol Cell Physiol ; 300(3): C557-66, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21148412

RESUMEN

Hypoxia, which characterizes ischemia, trauma, inflammation, and solid tumors, recruits monocytes, immobilizes them, and alters their function, leading to an anti-inflammatory and proangiogenic phenotype. Monocyte extravasation from the circulation and their migration in tissues are partially mediated by the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The mechanisms evoked by hypoxia that regulate monocyte migration and activation are not entirely clear. Specifically, the effect of hypoxia on TIMPs in these cells has hardly been investigated. We show that hypoxia reduces TIMP-2 secretion from human primary monocytes and from the monocyte-like cell lines U937 and THP-1 by three- to fourfold (P < 0.01), by inhibiting TIMP-2 transcription through mechanisms that involve the transcription factor SP-1. Hypoxia also lowers TIMP-2 protein secretion from human endothelial cells (by 2-fold, P < 0.05). TIMP-2 levels do not influence the reduced migration of THP-1 cells in hypoxia; however, low TIMP-2 levels enhance endothelial cell migration/proliferation, their ability to form tubelike structures in vitro, and the appearance of mature blood vessels in a Matrigel plug assay in vivo. Thus we conclude that reduced TIMP-2 levels secreted from both hypoxic monocytes and endothelial cells are proangiogenic.


Asunto(s)
Regulación hacia Abajo , Hipoxia/metabolismo , Monocitos/metabolismo , Neovascularización Fisiológica , Inhibidor Tisular de Metaloproteinasa-2/antagonistas & inhibidores , Regulación hacia Arriba , Animales , Secuencia de Bases , Línea Celular , Inhibición de Migración Celular/genética , Movimiento Celular/genética , Proliferación Celular , Células Cultivadas , Regulación hacia Abajo/genética , Células Endoteliales/metabolismo , Células Endoteliales/patología , Humanos , Hipoxia/patología , Hipoxia/fisiopatología , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Monocitos/patología , Neovascularización Fisiológica/genética , Neovascularización Fisiológica/fisiología , Factor de Transcripción Sp1/fisiología , Inhibidor Tisular de Metaloproteinasa-2/biosíntesis , Inhibidor Tisular de Metaloproteinasa-2/genética , Células U937 , Regulación hacia Arriba/genética
11.
Am J Physiol Lung Cell Mol Physiol ; 301(1): L23-30, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21478253

RESUMEN

Widespread vascular endothelial injury is the major mechanism for multiorgan dysfunction in sepsis. Following this process, the permeability of the alveolar capillaries is augmented with subsequent increase in water content and acute respiratory distress syndrome (ARDS). Nevertheless, the role of alveolar epithelium is less known. Therefore, we examined alveolar fluid clearance (AFC) using isolated perfused rat lung model in septic rats without ARDS. Sepsis was induced by ligating and puncturing the cecum with a 21-gauge needle. AFC was examined 24 and 48 h later. The expression of Na-K-ATPase proteins was examined in type II alveolar epithelial cells (ATII) and basolateral membrane (BLM). The rate of AFC in control rats was 0.51 ± 0.02 ml/h (means ± SE) and decreased to 0.3 ± 0.02 and 0.33 ± 0.03 ml/h in 24 and 48 h after sepsis induction, respectively (P < 0.0001). Amiloride, significantly decreased AFC in sepsis; conversely, isoproterenol reversed the inhibitory effect of sepsis. The alveolar-capillary barrier in septic rats was intact; therefore the finding of increased extravascular lung water in early sepsis could be attributed to accumulation of protein-poor fluid. The expression of epithelial sodium channel and Na-K-ATPase proteins in whole ATII cells was not different in both cecal ligation and puncture and control groups; however, the abundance of Na-K-ATPase proteins was significantly decreased in BLMs of ATII cells in sepsis. Early decrease in AFC in remote sepsis is probably related to endocytosis of the Na-K-ATPase proteins from the cell plasma membrane into intracellular pools, with resultant inhibition of active sodium transport in ATII cells.


Asunto(s)
Regulación hacia Abajo , Alveolos Pulmonares/enzimología , Alveolos Pulmonares/patología , Sepsis/enzimología , Sepsis/fisiopatología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Amilorida/farmacología , Animales , Western Blotting , Líquido del Lavado Bronquioalveolar , Catecolaminas/sangre , Regulación hacia Abajo/efectos de los fármacos , Canales Epiteliales de Sodio/metabolismo , Agua Pulmonar Extravascular/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Inmunohistoquímica , Masculino , Tamaño de los Órganos/efectos de los fármacos , Permeabilidad/efectos de los fármacos , Alveolos Pulmonares/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Sepsis/sangre
12.
Am J Pathol ; 177(4): 2046-54, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20709800

RESUMEN

Tumor-associated macrophages can potentially kill tumor cells via the high concentrations of nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS); however, tumor-associated macrophages actually support tumor growth, as they are skewed toward M2 activation, which is characterized by low amounts of NO production and is proangiogenic. We show that the mouse renal cell carcinoma cell line, RENCA, which, on stimulation, expresses high levels of iNOS mRNA, loses its ability to express the iNOS protein. This effect is mediated by the microRNA miR-146a, as inhibition of RENCA cells with anti-miR- 146a restores iNOS expression and NO production (4.8 ± 0.4 versus 0.3 ± 0.1 µmol/L in uninhibited cells, P < 0.001). In vivo, RENCA tumor cells do not stain for iNOS, while infiltrating tumor-associated macrophages showed intense staining, and both cell types expressed iNOS mRNA. Restoring iNOS protein expression in RENCA cells using anti-miR-146a increases macrophage-induced death of RENCA cells by 73% (P < 0.01) in vitro and prevents tumor growth in vivo. These results suggest that, in addition to NO production by macrophages, tumor cells must produce NO to induce their own deaths, and some tumor cells may use miR-146a to reduce or abolish endogenous NO production to escape macrophage-mediated cell death. Thus, inhibiting miR-146a may render these tumor cells susceptible to therapeutic strategies, such as adoptive transfer of M1-activated macrophages.


Asunto(s)
Carcinoma de Células Renales/patología , Neoplasias Renales/patología , MicroARNs/farmacología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/metabolismo , Animales , Apoptosis , Western Blotting , Carcinoma de Células Renales/enzimología , Carcinoma de Células Renales/genética , Movimiento Celular , Proliferación Celular , Femenino , Hibridación in Situ , Neoplasias Renales/enzimología , Neoplasias Renales/genética , Macrófagos/enzimología , Macrófagos/patología , Ratones , Ratones Endogámicos BALB C , MicroARNs/antagonistas & inhibidores , Neovascularización Patológica , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Biosíntesis de Proteínas , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
13.
Transpl Int ; 24(10): 1018-26, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21806687

RESUMEN

Transplantation involves preoperative ischemic periods that contribute to endothelial cell (EC) dysfunction and T-cell activation, leading to graft rejection. As hypoxia is a major constituent of ischemia, we evaluated its effect on the ability of ECs to express HLA-DR, which is required for presentation of antigens to T cells, and by itself serves as an important target for allogeneic T cells. Primary human umbilical vein ECs (HUVEC) and the human endothelial cell line EaHy926 were incubated in normoxia or hypoxia (PO(2) < 0.3%). Hypoxia increased the membranal expression (by 4-6 fold, P < 0.01) and secretion (by sixfold, P < 0.05) of HLA-DR protein, without influencing the accumulation of its mRNA. Alternative splicing, attenuated trafficking, or shedding from the plasma membrane were not observed, but the lysosomal inhibitor bafilomycin A1 reduced HLA-DR secretion. Hypoxia-induced endothelial HLA-DR elevated and diminished the secretion of IL-2 and IL-10, respectively, from co-cultured allogeneic CD4(+) T cells in a HLA-DR-dependent manner, as demonstrated by the use of monoclonal anti-HLA-DR. Our results indicate a yet not fully understood post-translational mechanism(s), which elevate both membranal and soluble HLA-DR expression. This elevation is involved in allogeneic T-cell activation, highlighting the pivotal role of ECs in ischemia/hypoxia-associated injury and graft rejection.


Asunto(s)
Células Endoteliales/citología , Antígenos HLA-DR/biosíntesis , Hipoxia , Activación de Linfocitos , Linfocitos T/citología , Linfocitos T CD4-Positivos/inmunología , Línea Celular , Rechazo de Injerto , Antígenos HLA-DR/metabolismo , Humanos , Hipoxia/metabolismo , Inflamación , Oxígeno/metabolismo , Radioinmunoensayo/métodos
14.
Crit Care ; 15(2): R95, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21401927

RESUMEN

INTRODUCTION: Due to the increasing burden on hospital systems, most elderly patients with non-surgical sepsis are admitted to general internal medicine departments. Disease-severity scoring systems are used for stratification of patients for utilization management, performance assessment, and clinical research. Some widely used scoring systems for septic patients are inappropriate when rating non-surgical patients in a non-intensive care unit (ICU) environment mainly because their calculations require types of data that are frequently unavailable. This study aimed to assess the fitness of four scoring systems for septic patients hospitalized in general internal medicine departments: modified early warning score (MEWS), simple clinical score (SCS), mortality in emergency department sepsis (MEDS) score, and rapid emergency medicine score (REMS). METHODS: We prospectively collected computerized data of septic patients admitted to general internal medicine departments in our community-based university hospital. We followed 28-day in-hospital mortality, overall in-hospital mortality, and 30- and 60-day mortality. Using a logistic regression procedure we calculated the area under ROC curve (AUC) for every scoring system. RESULTS: Between February 1st, 2008 and April 30th, 2009 we gathered data of 1,072 patients meeting sepsis criteria on admission to general internal medicine departments. The 28-day mortality was 19.4%. The AUC for the MEWS was 0.65-0.70, for the SCS 0.76-0.79, for the MEDS 0.73-0.75, and for the REMS, 0.74-0.79. Using Hosmer-Lemeshow statistics, a lack of fit was found for the MEDS model. All scoring systems performed better than calculations based on sepsis severity. CONCLUSIONS: The SCS and REMS are the most appropriate clinical scores to predict the mortality of patients with sepsis in general internal medicine departments.


Asunto(s)
Departamentos de Hospitales , Medicina Interna/métodos , Sepsis/mortalidad , Índice de Severidad de la Enfermedad , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Departamentos de Hospitales/estadística & datos numéricos , Mortalidad Hospitalaria , Hospitales Comunitarios , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo/métodos
15.
Harefuah ; 150(7): 578-82, 617, 2011 Jul.
Artículo en Hebreo | MEDLINE | ID: mdl-21874767

RESUMEN

BACKGROUND: The incidence of invasive pneumococcal infections in industrialized countries is above 50/100,000 annuaty in adults over the age of 65 years. The Israel Ministry of Health recommends 23-valent polysaccharide anti-pneumococcaL vaccination for patients with immune suppression or chronic diseases and citizens above the age of 65 years. METHODS: in 1.1.2008 pneumococcal vaccination for adults was introduced as a quality measure in CLalit Health Services (CHS). At the time of the introduction of pneumococcaL vaccination as a new quality measure in CHS, as one of 70 quality measures in community medicine, the target population included all CHS enrollees over 65 years of age and patients with specific chronic diseases. The relative weight of this quality measure within the set of CHS quality measures was set at 3.19%. The goal for the measure was set at 75%. Pneumococcal vaccination was paired with the influenza vaccination campaign. Mandatory copayment was reduced from NIS 57 to NIS 25 for enroLLees without supplementary medical insurance, and from NIS 11 to NIS 5 for enrollees with supplementary insurance. An alert for performing pneumococcaL vaccination for the target population was introduced into the medical software used by all CHS physicians. RESULTS: During a period of two years foLLowing the introduction of pneumococcaL vaccination as a quality measure in CHS, approximately 400,000 CHS enrollees within the target population received pneumococcaL vaccination, and the rate of immunization increased 10-fold (with respect to August 2007). CONCLUSION: The introduction of pneumococcal vaccination as a quality measure in CHS, coupled by other managerial and service-related actions, substantially increased the vaccination rates.


Asunto(s)
Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Indicadores de Calidad de la Atención de Salud , Anciano , Seguro de Costos Compartidos , Humanos , Programas de Inmunización/estadística & datos numéricos , Seguro de Servicios Farmacéuticos/economía , Israel/epidemiología , Infecciones Neumocócicas/epidemiología , Vacunas Neumococicas/economía , Garantía de la Calidad de Atención de Salud , Programas Informáticos , Vacunación/estadística & datos numéricos
16.
Am J Physiol Cell Physiol ; 298(4): C942-51, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20071690

RESUMEN

Detachment of endothelial cells (ECs) from the extracellular matrix (ECM) is required not only for angiogenesis, but also for EC apoptosis. Matrix metalloproteinase (MMP)-2 plays a major role in the degradation of the ECM, supporting an essential role for this enzyme in both survival (angiogenesis) and death of ECs. Our aim was to study these seemingly paradoxical effects of MMP-2. We rationalized that inhibiting apoptosis would drive MMP-2 toward a prosurvival activity, clarifying the mechanisms involved. By employing specific inhibitors to two major apoptotic pathways in ECs, caspases and p38 MAPK (p38), we demonstrated that they differently affected EC behavior as well as MMP-2 expression. The p38 pathway appears to enhance MMP-2 synthesis, its partial ("intermediate") and its full activation, probably via membrane type (MT)1-MMP, while caspases enhance MMP-2 synthesis and full activation but reduce MT1-MMP and MMP-2 intermediate form. Evaluation of the reciprocal influences of MMP-2 on ECs showed that the intermediate form supported survival and migration, and the fully active form led to cell death. In addition, a pro- and intermediate form-rich environment, even in the presence of the fully active form, exerted protective effects. Thus the seemingly conflicting effects of MMP-2 on EC survival may be explained by the ratio between the MMP-2 activation forms. A regulatory loop between active MMP-2 and p38 but not between MMP-2 and caspases was also observed, suggesting that MMP-2 is downstream to caspases where it serves as an "exterminator" molecule. Altogether, modification of caspase and p38 pathways, via changes of local MMP-2, affect survival and angiogenic steps in ECs.


Asunto(s)
Apoptosis/fisiología , Células Endoteliales/fisiología , Metaloproteinasa 2 de la Matriz/metabolismo , Clorometilcetonas de Aminoácidos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Caspasa 3/metabolismo , Inhibidores de Caspasas , Movimiento Celular/fisiología , Forma de la Célula , Células Cultivadas , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Matriz Extracelular/metabolismo , Humanos , Imidazoles/farmacología , Metaloproteinasa 2 de la Matriz/genética , Piridinas/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
17.
Telemed J E Health ; 16(7): 799-806, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20815747

RESUMEN

OBJECTIVE: Our aim was to evaluate visualization methods for specific tasks performed with personal healthcare e-record systems for lay adults and older patients. We investigated common visualization methods for data entry and follow-up of personal and clinical information for self-control of blood coagulation functions. METHODS: Twenty-five old (72.2 +/- 5.5 years) and 25 young (30.4 +/- 4.9 years) participants completed tasks based on common scenarios, on experimental Web sites with hidden tracking programs. Functional parameters (time, accuracy), subjective parameters (preference, satisfaction), and physiological parameters (heart rate, skin temperature, sweat, respiratory rate, and muscle tension) monitored with miniature sensors were used. RESULTS: Total time for data entry and information follow-up were significantly longer for older compared with younger participants, with no significant differences in accuracy (errors), in stress-related physiological parameters, in preferences, or in satisfaction between age group. The Menu display was the significantly preferred configuration for data entry in both age groups, based on functional, physiological, and subjective criteria (p < 0.05, Duncan test). The Calendar configuration was significantly preferred for mixed tasks of follow-up and information retrieval, in both age groups, based on functional, physiological, and subjective criteria (p < 0.05, Duncan test). CONCLUSIONS: Our study supports equal capabilities of old and young people to use interactive healthcare systems for management of chronic diseases and further encourages using physiological, functional, and subjective methods for evaluating personal healthcare records.


Asunto(s)
Anticoagulantes , Presentación de Datos , Sistemas de Registros Médicos Computarizados , Estrés Fisiológico/fisiología , Estrés Psicológico/fisiopatología , Acceso a la Información , Adulto , Factores de Edad , Anciano , Análisis de Varianza , Actitud hacia los Computadores , Electromiografía , Femenino , Respuesta Galvánica de la Piel , Indicadores de Salud , Frecuencia Cardíaca , Humanos , Masculino , Monitoreo Fisiológico/instrumentación , Temperatura Cutánea/fisiología , Encuestas y Cuestionarios , Factores de Tiempo
18.
Isr Med Assoc J ; 12(1): 10-5, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20450122

RESUMEN

BACKGROUND: Parallel to increased life expectancy, the number of very elderly patients hospitalized in internal medicine departments is growing rapidly, although clinical data on hospital care are lacking. OBJECTIVES: To investigate the sociodemographic data, hospitalization characteristics and outcomes of nonagenarian patients, as these measures are necessary for evaluating prognostic information and predictors of mortality. METHODS: We reviewed the medical records of all patients aged > or = 90 hospitalized in our institute's Department of Internal Medicine. The data comprised 482 admissions of 333 patients hospitalized over a one year period. RESULTS: Half of the study patients were residents of nursing institutions. A high rate of atrial fibrillation was documented (106 patients, 32%). Acute infectious diseases constituted the leading diagnosis (276/482 admissions, 57%), followed by acute coronary syndrome (17% of admissions). In-hospital mortality occurred in 74 patients (22%). Chronic therapy with statins or acetylsalicylic acid was inversely related to mortality (P<0.05). The main predictors for in-hospital death of nonagenarians were pressure sores, older age, atrial fibrillation, malignant disease, and admission due to an acute infection, especially Clostridium difficile-associated diseases in addition, mental decline, permanent urinary catheter, leukocytosis, renal failure and hypoalbuminemia predicted post-discharge mortality. Admission due to an infectious disease but not acute coronary syndrome was significantly correlated to in-hospital and post-discharge mortality (P<0.001). CONCLUSIONS: Hospitalized nonagenarians comprise a growing group with distinct characteristics and increasing significance in the daily practice of internal medicine departments. Comprehensive assessment of the elderly at admission together with identification of the above clinical and laboratory risk factors for mortality will help determine in-hospital management, discharge planning and rehabilitation programs.


Asunto(s)
Estado de Salud , Hospitalización/estadística & datos numéricos , Medicina Interna , Factores de Edad , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Evaluación Geriátrica , Mortalidad Hospitalaria , Humanos , Israel , Masculino , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
19.
Crit Care Med ; 37(3): 1054-61, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19237917

RESUMEN

OBJECTIVE: Inhalation of oxygen improves the hemodynamic status and attenuates the inflammatory response after intestinal ischemia-reperfusion (IR). Yet, the use of hyperoxia is hindered by concerns that it could exacerbate reperfusion injury by increasing free radical formation. We examined the effect of hyperoxia on enterocyte turnover and intestinal preservation and rehabilitation following IR injury in rats. DESIGN: Animal study. SETTING: Research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Animals were assigned to four experimental groups: 1) Sham rats underwent laparotomy without vascular occlusion and breathed air, 2) Sham-oxygen rats underwent laparotomy without vascular occlusion and breathed 100% oxygen, 3) IR rats underwent occlusion of the superior mesenteric artery and portal vein for 30 minutes and breathed air, and 4) IR group treated with oxygen (IR-O2)rats underwent IR and breathed 100% oxygen starting 10 minutes before and continued for the first 6 hours after reperfusion. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 hours after IR. MEASUREMENTS AND MAIN RESULTS: In IR rats, breathing 100% oxygen resulted in a significant decrease in Park's injury score in the ileum (p < 0.05 from untreated IR rats). Rats treated with oxygen also demonstrated a significant increase in mucosal weight (p < 0.05) and mucosal DNA (p < 0.05) in the jejunum and ileum, and an increase in villus height (p < 0.01), and crypt depth (p < 0.05) in the ileum. Enterocyte proliferation (assessed by bromodeoxyuridine uptake) was significantly decreased in the jejunum and ileum in untreated IR rats. Oxygen therapy increased enterocyte proliferation in the ileum, and diminished both the apoptosis index and Bax gene expression in the jejunum and ileum (p < 0.05). Plasma thermochemiluminescence oxidizability assay revealed significantly higher thermochemiluminescence ratios in IR group treated with oxygen than in untreated IR rats (p < 0.05) at 6 hours postreperfusion suggesting a significantly lower prior in vivo molecular oxidation. CONCLUSIONS: Hyperoxia reduces small bowel injury, accelerates enterocyte turnover, and improves intestinal rehabilitation after IR.


Asunto(s)
Enterocitos/fisiología , Intestinos/irrigación sanguínea , Terapia por Inhalación de Oxígeno , Oxígeno/administración & dosificación , Daño por Reperfusión/terapia , Animales , Enterocitos/efectos de los fármacos , Mucosa Intestinal/metabolismo , Masculino , Oxígeno/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Daño por Reperfusión/rehabilitación
20.
Crit Care ; 13(1): 205, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19291278

RESUMEN

Oxygen is one of the most commonly used therapeutic agents. Injudicious use of oxygen at high partial pressures (hyperoxia) for unproven indications, its known toxic potential, and the acknowledged roles of reactive oxygen species in tissue injury led to skepticism regarding its use. A large body of data indicates that hyperoxia exerts an extensive profile of physiologic and pharmacologic effects that improve tissue oxygenation, exert anti-inflammatory and antibacterial effects, and augment tissue repair mechanisms. These data set the rationale for the use of hyperoxia in a list of clinical conditions characterized by tissue hypoxia, infection, and consequential impaired tissue repair. Data on regional hemodynamic effects of hyperoxia and recent compelling evidence on its anti-inflammatory actions incited a surge of interest in the potential therapeutic effects of hyperoxia in myocardial revascularization and protection, in traumatic and nontraumatic ischemicanoxic brain insults, and in prevention of surgical site infections and in alleviation of septic and nonseptic local and systemic inflammatory responses. Although the margin of safety between effective and potentially toxic doses of oxygen is relatively narrow, the ability to carefully control its dose, meticulous adherence to currently accepted therapeutic protocols, and individually tailored treatment regimens make it a cost-effective safe drug.


Asunto(s)
Oxígeno/uso terapéutico , Sistemas de Atención de Punto/tendencias , Animales , Investigación Biomédica/métodos , Investigación Biomédica/tendencias , Hemodinámica/fisiología , Humanos , Oxigenoterapia Hiperbárica/métodos , Oxigenoterapia Hiperbárica/tendencias , Hiperoxia/tratamiento farmacológico , Hiperoxia/metabolismo , Oxígeno/administración & dosificación
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