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Platelet-rich plasma (PRP) is an autologous biologic product used in several fields of medicine for tissue repair due to the regenerative capacity of the biomolecules of its formulation. PRP consists of a plasma with a platelet concentration higher than basal levels but with basal levels of any biomolecules present out of the platelets. Plasma contains extraplatelet biomolecules known to enhance its regenerative properties. Therefore, a PRP containing not only a higher concentration of platelets but also a higher concentration of extraplatelet biomolecules that could have a stronger regenerative performance than a standard PRP. Considering this, the aim of this work is to develop a new method to obtain PRP enriched in both platelet and extraplatelet molecules. The method is based on the absorption of the water of the plasma using hydroxyethyl acrylamide (HEAA)-based hydrogels. A plasma fraction obtained from blood, containing the basal levels of platelets and proteins, was placed in contact with the HEAA hydrogel powder to absorb half the volume of the water. The resulting plasma was characterized, and its bioactivity was analyzed in vitro. The novel PRP (nPRP) showed a platelet concentration and platelet derived growth factor (PDGF) levels similar to the standard PRP (sPRP), but the concentration of the extraplatelet growth factors IGF-1 (p < 0.0001) and HGF (p < 0.001) were significantly increased. Additionally, the cells exposed to the nPRP showed increased cell viability than those exposed to a sPRP in human dermal fibroblasts (p < 0.001) and primary chondrocytes (p < 0.01). In conclusion, this novel absorption-based method produces a PRP with novel characteristics compared to the standard PRPs, with promising in vitro results that could potentially trigger improved tissue regeneration capacity.
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BACKGROUND: Surgery and stereotactic body radiotherapy (SBRT) are two of the options available as local treatments for pulmonary oligometastases from colorectal cancer (CRC). We hypothesized that SBRT would have, at least, a similar local control rate to surgery. METHODS: We identified an initial cohort of 100 patients with CRC who received SBRT or surgery for lung metastases. This was then narrowed down to 75 patients: those who underwent surgery (n = 50) or SBRT (n = 25) as their first local thoracic treatment between 1 January 2004 and 29 December 2017. The Kaplan-Meier method was used to calculate lung-progression-free survival (L-PFS) and overall survival (OS). RESULTS: The 1 and 2-year L-PFS was 85% and 70% in the surgical group and 87% and 71% in the SBRT group, respectively (p = 0.809). No significant differences were found between the two groups in terms of OS. The biologically effective dose (BED), age and initial CRC stage did not have a significant effect on local control or survival. No grade 3 or above acute- or late-toxicity events were reported. CONCLUSIONS: These results add retrospective evidence that SBRT and surgery have similar results in terms of OS and local control in patients with lung oligometastases from CRC.
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Leprosy is a chronic, neglected tropical infectious disease, currently endemic in Formosa, a province in northwestern Argentina. To analyze the performance, distribution, and effectiveness of the health system in leprosy diagnosis in Formosa, we estimated the trend of the number of new cases of leprosy diagnosed between 2002 and 2019 and estimated a forecast for 2022 at the primary health care centers (PHCCs) of at the first level of care (1stLC), at district hospitals (DHs) of the second level of care (2ndLC), high-complexity hospitals at the third level of care (3rdLC), and in rural and urban areas. The general trend was calculated based on the new cases detection rate (NCDR) using the autoregressive-moving average model (ARMA). The 1stLC, 2ndLC, and 3rdLC and the rural/urban variables were assessed using a proportional Bayesian trend ARMA (TrARMA) model. A predictive model was used for estimated forecasts. Markov-Monte Carlo chains were applied with A Metropolis-Hastings's algorithm. The highest median proportion (Mp) of new cases of leprosy was diagnosed at the 2ndLC (Mp, 0.67; 97.5% credibility interval [CI] [0.56-0.77]), at the 3rdLC (Mp, 0.11; 97.5% CI [0.08-0.15]), and in urban areas (urban median proportion (uMp), 0.86; 97.5% CI [0.83- 0.88]), whereas the lowest proportion of new cases was diagnosed at the 1stLC (Mp, 0.082; 97.5% CI [0.061-0.108]) and in rural areas (rural median proportion (rMp), 0.13; 97.5% CI [0.11-0.16]). Our model predicts for 2022 that a median number of new cases of leprosy of 19.70 will be diagnosed in urban areas (97.5% CI [15.94-23.80]), and will continue to be diagnosed at the 2ndLC (median number of cases, 15.33; 97.5% CI [12.40-10.52]) and 3rdLC (median number of cases, 2.43; 97.5% CI [1.97-2.94]).
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Lepra , Humanos , Argentina/epidemiología , Taiwán , Teorema de Bayes , Lepra/diagnóstico , Lepra/epidemiología , Programas de GobiernoRESUMEN
BACKGROUND: The province of Formosa, Argentina, is endemic for leprosy. In the present paper, we assessed the trend (T, 2002-2016 time series) and the forecast for 2022 of new case detection rate (NCDR) and determined the spatial distribution of new cases detected (NCD) of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: This is a descriptive observational study of 713 NCD of leprosy from provincial medical records between January 2002 and December 2016. The whole dataset from the provincial medical record was used to independently estimate the NCDR trends of the general population, age groups, sexes and Departments. This same database was used to estimate the NCDR forecast of the general population for 2022, applying a dynamic linear model with a local linear trend, using the MCMC algorithm. The NCDR was higher in men (p<0.05), increased with age (0.20, 8.17, 21.04, and 29.49 for the 0-14, 15-44, 45-64 and over 65-year-old age groups, respectively; p<0.05) and showed a downward trend (negative values) of estimated slopes for the whole province and each Department. Bermejo Department showed the highest (T:-1.02, 95%CI: [-1.42, -0.66]) and Patiño the lowest decreasing trend (T:-0.45, 95%CI: [-0.74, -0.11]). The NCDR trend for both sexes was similar (T:-0.55, 95%CI: [-0.64, -0.46]), and age groups showed a decreasing trend (S15-44:-103, S45-64:-81, S>65:-61, p<0.05), except for the 0-14 age group (S:-3, p>0.05), which showed no trend. Forecasts predicted that leprosy will not be eliminated by 2022 (3.64, 95%CI: [1.22, 10.25]). CONCLUSIONS/SIGNIFICANCE: Our results highlight the status of leprosy in Formosa and provide information to the provincial public health authorities on high-risk populations, stressing the importance of timely detection of new cases for further elimination of the disease in the province.
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Lepra/epidemiología , Adolescente , Adulto , Anciano , Algoritmos , Argentina/epidemiología , Niño , Preescolar , Predicción , Humanos , Incidencia , Lactante , Recién Nacido , Modelos Lineales , Masculino , Persona de Mediana Edad , Prevalencia , Adulto JovenRESUMEN
BACKGROUND: Diabetes is related with increased cancer mortality across multiple cancer types. Its role in lung cancer mortality is still unclear. We aim to determine the prognostic value of fasting plasma glucose (FPG) and diabetes mellitus in patients with locally advanced non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy. METHODS: One-hundred seventy patients with stage III NSCLC received definitive concurrent chemoradiotherapy from 2010 to 2014. Clinico-pathological data and clinical outcome was retrospectively registered. Fifty-six patients (33%), met criteria for type 2 diabetes mellitus (T2DM) at baseline. The prognostic value of FPG and other clinical variables was assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and Cox proportional models and log-rank test were used. RESULTS: With a median follow-up of 36 months, median PFS was 8.0 months and median OS was 15.0 months in patients with FPG ≥7 mmol/L compared to 20 months (HR 1.13; 95% CI 1.07-1.19, p < 0.001) and 31 months (HR 1.09; 95% CI 1.04-1.15; p < 0.001) respectively, for patients with FPG < 7 mmol/L. In the multivariate analysis of the entire cohort adjusted by platinum compound and comorbidities, high levels of FPG as a continuous variable (HR 1.14; 95% CI 1.07-1.21; p < 0.001), the presence of comorbidity (HR 1.72; 95% CI 1.12-2.63; p = 0.012), and treatment with carboplatin (HR 1.95; 95% CI 1.26-2.99; p = 0.002) were independent predictors for shorter OS. In additional multivariate models considering non-diabetic patients as a reference group, diabetic patients with poor metabolic control (HbA1c > 8.5%) (HR 4.53; 95% CI 2.21-9.30; p < 0.001) and those receiving insulin (HR 3.22; 95% CI 1.90-5.46 p < 0.001) had significantly independent worse OS. CONCLUSION: Baseline FPG level is an independent predictor of survival in our cohort of patients with locally advanced NSCLC treated with concurrent chemoradiotherapy. Studies in larger cohorts of patients are warranted to confirm this relevant association.
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Biomarcadores/análisis , Glucemia/análisis , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Quimioradioterapia , Neoplasias Pulmonares/diagnóstico , Platino (Metal)/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Although concurrent chemoradiotherapy (cCRT) increases survival in patients with inoperable, locally advanced non-small-cell lung cancer (NSCLC), there is no consensus on the treatment of elderly patients. The aim of this study was to determine the prognostic value of the comprehensive geriatric assessment (CGA) and its ability to predict toxicity in this setting. METHODS: We enrolled 85 consecutive elderly (⩾75 years) participants, who underwent CGA and the Vulnerable Elders Survey (VES-13). Those classified as fit and medium-fit by CGA were deemed candidates for cCRT (platinum-based chemotherapy concurrent with thoracic radiation therapy), while unfit patients received best supportive care. RESULTS: Fit (37%) and medium-fit (48%) patients had significantly longer median overall survival (mOS) (23.9 and 16.9 months, respectively) than unfit patients (15%) (9.3 months, log-rank P=0.01). In multivariate analysis, CGA groups and VES-13 were independent prognostic factors. Fit and medium-fit patients receiving cCRT (n=54) had mOS of 21.1 months (95% confidence interval: 16.2, 26.0). In those patients, higher VES-13 (⩾3) was associated with shorter mOS (16.33 vs 24.3 months, P=0.027) and higher risk of G3-4 toxicity (65 vs 32%, P=0.028). CONCLUSIONS: Comprehensive geriatric assessment and VES-13 showed independent prognostic value. Comprehensive geriatric assessment may help to identify elderly patients fit enough to be treated with cCRT.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia/métodos , Evaluación Geriátrica/métodos , Neoplasias Pulmonares/terapia , Cuidados Paliativos/métodos , Anciano , Anciano de 80 o más Años , Consenso , Toma de Decisiones , Femenino , Humanos , Masculino , Platino (Metal)/uso terapéutico , Estudios Prospectivos , España , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCCIÓN La lepra es una enfermedad endémica en la provincia de Formosa, del noroeste Argentino. OBJETIVOS En este trabajo estudiamos la tendencia de los Indicadores Epidemiológicos en la serie temporal 2002-2016 y las proyecciones al 2022 de; los nuevos casos de lepra (NCL) en la provincia en general, en áreas rurales y urbanas y según el Nivel de Complejidad de Atención en Áreas Programáticas (AP) y Distritos Sanitarios (DS) en que fueron diagnosticados. MÉTODOS Se estudiaron 698 NCL diagnosticados por el Programa de Control de Leishmaniasis y Lepra de Formosa (PCLyLF). A partir de la tasas de detección de nuevos casos (TDNC) se evaluó la tendencia general mediante un modelo Autorregresivo de Media Móvil (TrARMA) y para las variables sexo, urbanización, forma clínica, área programática y distrito sanitario, un modelo Bayesiano TrARMA proporcional. Para todos los modelos se utilizaron cadenas de Markov-Montecarlo con el algoritmo de Metropolis-Hastings. RESULTADOS En el período 2002-2016, hubo una tendencia general decreciente de los NCL 66.029 [62.14 70.518] con una pendiente de 0.948 [0.938 0.957], que significó un descenso de 5.2% anual. Para el 2022, se estima 18.35 [23.18 27.41] NCL, siendo de 13.52 [10.94 16.34] para hombres y de 9.06 [7.33 10.94] para mujeres. En las áreas urbanas el número de NCL será de 19.70 [15.94 23.80] y en las rurales de 2.88 [2.33 3.48]. El mayor número de NCL se diagnosticó en las AP "B" 2do Nivel de Atención (n=459) y el menor en las AP "A" 1er Nivel de Atención (n=5) y será de 15.33 [12.40 18.52] y de 0.55 [0.44 0.66] en el 2022. Los DS-V (3.30 [2.67 3.99]), VII (2.79 [2.25 3.37]) y XII (2.43 [1.97 2.94]) serán los que diagnostiquen mayor número de casos. DISCUSIÓN La lepra es una enfermedad urbana, diagnosticada en el 2do Nivel de Atención, los DS VII y XII serán los más efectivos en el diagnóstico y si bien tiene una franca tendencia a decrecer, no se eliminará en el 2022
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LepraRESUMEN
BACKGROUND: Corrientes, a province of northeastern Argentina with endemic leprosy, has improved its epidemiological indicators, however, a study of the dynamics over time is lacking. OBJECTIVES: We analysed data of 1308 leprosy patients between 1991 to 2014, and the forecast for 2020. METHODS: Descriptive statistics and stepwise Bayesian model selection were performed. Forecasts were made using the median of 100,000 projections using the parameters calculated via Monte Carlo methods. RESULTS: We found a decreasing number of new leprosy cases (-2.04 cases/year); this decrease is expected to continue by an estimated 20.28 +/- 10.00 cases by 2020, evidenced by a sustained decline in detection rate (from 11 to 2.9/100,000 inhabitants). Age groups that were most affected were 15-44 (40.13%) and 45-64 (38.83%) year olds. Multibacillary forms (MB) predominated (70.35%) and while gradually declining, between 10 and 30% developed disability grade 2 (DG2) (0.175 (0.110 - 0.337) DG2/MB cases), with a time delay between 0 to 15 years (median = 0). The proportion of MB clinic forms and DG2 increased and will continuously increase in the short term (0.036 +/- 0.018 logit (MB/total of cases). MAIN CONCLUSIONS: Corrientes is on the way to eliminating leprosy by 2020, however the increased proportion of MB clinical forms and DG2 signals a warning for disease control efforts.
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Lepra/epidemiología , Adolescente , Adulto , Argentina/epidemiología , Teorema de Bayes , Erradicación de la Enfermedad/tendencias , Femenino , Humanos , Lepra/prevención & control , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND Corrientes, a province of northeastern Argentina with endemic leprosy, has improved its epidemiological indicators, however, a study of the dynamics over time is lacking. OBJECTIVES We analysed data of 1308 leprosy patients between 1991 to 2014, and the forecast for 2020. METHODS Descriptive statistics and stepwise Bayesian model selection were performed. Forecasts were made using the median of 100,000 projections using the parameters calculated via Monte Carlo methods. RESULTS We found a decreasing number of new leprosy cases (-2.04 cases/year); this decrease is expected to continue by an estimated 20.28 +/- 10.00 cases by 2020, evidenced by a sustained decline in detection rate (from 11 to 2.9/100,000 inhabitants). Age groups that were most affected were 15-44 (40.13%) and 45-64 (38.83%) year olds. Multibacillary forms (MB) predominated (70.35%) and while gradually declining, between 10 and 30% developed disability grade 2 (DG2) (0.175 (0.110 - 0.337) DG2/MB cases), with a time delay between 0 to 15 years (median = 0). The proportion of MB clinic forms and DG2 increased and will continuously increase in the short term (0.036 +/- 0.018 logit (MB/total of cases). MAIN CONCLUSIONS Corrientes is on the way to eliminating leprosy by 2020, however the increased proportion of MB clinical forms and DG2 signals a warning for disease control efforts.
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Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Lepra/prevención & control , Lepra/epidemiología , Argentina/epidemiología , Estudios RetrospectivosRESUMEN
Establishing the putative links between sylvatic and domestic transmission cycles of Trypanosoma cruzi, the etiological agent of Chagas disease, is of public health relevance. We conducted three surveys to assess T. cruzi infection in wild mammals from a rural and a preserved area in Misiones Province, Northeastern Argentina, which had recently been declared free of vector- and blood-borne transmission of human T. cruzi infection. A total of 200 wild mammals were examined by xenodiagnosis (XD) and/or polymerase chain reaction (PCR) amplification of the hyper-variable region of kinetoplast DNA minicircles of T. cruzi (kDNA-PCR). The overall prevalence of T. cruzi infection was 8%. Nine (16%) of 57 Didelphis albiventris opossums and two (7%) of 29 Desmodus rotundus vampire bats were positive by both XD and kDNA-PCR. Additionally, one D. rotundus positive for T. cruzi by kDNA-PCR tested positive by satellite-DNA-PCR (SAT-DNA-PCR). The T. cruzi-infected bats were captured indoors and in the yard of a vacant dwelling. All D. albiventris were infected with TcI and both XD-positive D. rotundus by TcII. Fifty-five opossum cubs within the marsupium were negative by XD. The mean infectiousness to the vector was 62% in D. albiventris and 50% in D. rotundus. Mice experimentally infected with a parasite isolate from a vampire bat displayed lesions typically caused by T. cruzi. Our study documents the presence of the genotype TcII in a sylvatic host for the first time in Argentina, and the occurrence of two transmission cycles of T. cruzi in a district free of domestic vector-borne transmission.
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Enfermedad de Chagas/veterinaria , Quirópteros/parasitología , Reservorios de Enfermedades , Mamíferos/parasitología , Trypanosoma cruzi/aislamiento & purificación , Animales , Animales Salvajes/parasitología , Argentina/epidemiología , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/transmisión , ADN Protozoario/genética , Vectores de Enfermedades , Zarigüeyas/parasitología , Reacción en Cadena de la Polimerasa , Prevalencia , XenodiagnósticoRESUMEN
OBJECTIVES: The long-term impact of stereotactic body radiotherapy (SBRT) on respiratory function in patients with inoperable non-small cell lung cancer (NSCLC) has not been well studied. The aim of this phase II trial was to assess local control, survival, and lung function at 36 months after treatment. METHODS: From July 2008 to February 2012, 42 patients in whom inoperable NSCLC with peripheral lesions was diagnosed were consecutively enrolled. Lung function testing included measurement of forced expiratory vital capacity, forced expiratory volume in 1 second, and diffusing capacity for carbon monoxide. All lung function parameters were registered at baseline and evaluated prospectively after SBRT every 6 months for 2 years and annually thereafter. RESULTS: Of the 42 initial patients, four were excluded. At 36 months after SBRT, 22 patients were still evaluable (12 deaths and four patients lost to follow-up). At 36 months, the rate of local control was 94%. At 1, 2, and 3 years, respectively, overall survival rates were 92%, 75%, and 66%. Median overall survival was 57 months. Grade (G) 3 acute toxicity was observed in four patients (10%). Chronic G1 toxicity was observed in all 38 cases (100%), with the most common type being pneumonitis (26 patients [68%]). The mean lung function parameters at baseline and at 36 months after treatment were as follows: forced expiratory vital capacity 83% versus 79%; forced expiratory volume in 1 second 62% versus 57%; and diffusing capacity for carbon monoxide 54% versus 54%. These changes were not significant. CONCLUSIONS: In this trial, local control and survival rates after SBRT were very good. Treatment with SBRT had no significant impact on lung function at 36 months. These findings provide further support for the use of SBRT as a radical treatment for NSCLC. Lung toxicity is minimal, even in patients with poor pulmonary function before treatment.
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Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Pulmón/efectos de la radiación , Radiocirugia , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Femenino , Volumen Espiratorio Forzado/efectos de la radiación , Humanos , Pulmón/fisiopatología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neumonitis por Radiación/etiología , Radiocirugia/efectos adversosRESUMEN
The objective of this article is to discuss the meanings that health professionals and patients in treatment attribute to obesity. The research consisted of a qualitative survey in health, based on in-depth interviews with patients and professionals at an out-patient clinic at the University Hospital in Barcelona, Spain. Here, we discuss the concept of obesity, the meanings of diagnoses, the singularities involved in managing treatment, and the process of becoming ill, all in the light of the anthropology of health that has a sociocultural orientation. Obesity is usually seen by the professionals as a risk-factor disease. For patients, the incorporation of this rationality is procedural and is mixed in with other meanings attributed to being overweight/obese that have been gradually developed throughout life. A patient's autonomy in choosing to be fat, or obese, and to adhere to treatment, is defined as a process that requires support in order to come to joint proposals in caring for these problems.
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Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Sobrepeso/psicología , Adulto , Humanos , Obesidad/psicología , Investigación CualitativaRESUMEN
The optimal schedule and regimen of chemotherapy (CT) in association with chemoradiation has not been established in stage III non-small-cell lung cancer (NSCLC). We have compared three schedules of non-platinum-based CT plus either radiotherapy or chemoradiation. From May 2001 to June 2006, 158 patients with unresectable stage III NSCLC were enrolled in a randomized phase II trial with overall response rate (ORR) as the primary endpoint. The initial design included three arms: sequential CT followed by thoracic radiation (TRT); concurrent CT/TRT followed by consolidation CT; and induction CT followed by concurrent CT/TRT. However, based on the preliminary results of the RTOG 9410 trial, the sequential arm was closed when 19 patients had been enrolled. All patients received two cycles of docetaxel 40 mg/m(2) days 1 and 8 plus gemcitabine 1200 mg/m(2) days 1 and 8, as either induction or consolidation therapy. Concurrent CT/TRT consisted of docetaxel 20 mg/m(2) and carboplatin AUC 2 weekly plus 60 Gy TRT. No differences were found in ORR between the two arms (56% and 57%). Hematological toxicity was mild but significantly superior with consolidation CT; the esophagitis rate was similar in both arms (16% and 15%). With a median follow-up of 57 months, no differences were found in median survival (13.07 and 13.8 months) or 5-year survival (16.4% and 22%). This regimen cannot be recommended as an alternative to platinum-based CT/TRT although it has an acceptable toxicity profile and encouraging long-term survival data (ClinicalTrials.gov NCT01652820).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Quimioradioterapia , Quimioterapia de Consolidación , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Docetaxel , Femenino , Humanos , Quimioterapia de Inducción , Masculino , Persona de Mediana Edad , Taxoides/administración & dosificación , Taxoides/efectos adversos , Resultado del Tratamiento , GemcitabinaRESUMEN
Influenza virus (InfV) infection during pregnancy is a known risk factor for neurodevelopment abnormalities in the offspring, including the risk of schizophrenia, and has been shown to result in an abnormal behavioral phenotype in mice. However, previous reports have concentrated on neuroadapted influenza strains, whereas increased schizophrenia risk is associated with common respiratory InfV. In addition, no specific mechanism has been proposed for the actions of maternal infection on the developing brain that could account for schizophrenia risk. We identified two common isolates from the community with antigenic configurations H3N2 and H1N1 and compared their effects on developing brain with a mouse modified-strain A/WSN/33 specifically on the developing of dopaminergic neurons. We found that H1N1 InfV have high affinity for dopaminergic neurons in vitro, leading to nuclear factor kappa B activation and apoptosis. Furthermore, prenatal infection of mothers with the same strains results in loss of dopaminergic neurons in the offspring, and in an abnormal behavioral phenotype. We propose that the well-known contribution of InfV to risk of schizophrenia during development may involve a similar specific mechanism and discuss evidence from the literature in relation to this hypothesis.
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Encéfalo/virología , Neuronas Dopaminérgicas/virología , Subtipo H1N1 del Virus de la Influenza A , Subtipo H3N2 del Virus de la Influenza A , Infecciones por Orthomyxoviridae/virología , Efectos Tardíos de la Exposición Prenatal/virología , Esquizofrenia/virología , Animales , Conducta Animal/fisiología , Encéfalo/inmunología , Encéfalo/fisiopatología , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Aprendizaje por Laberinto/fisiología , Ratones , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/fisiopatología , Embarazo , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Reconocimiento en Psicología/fisiologíaRESUMEN
PURPOSE: To design, implement, and examine the psychoneuroendocrine responses of three different types of stress management programs. DESIGN: Randomly assigned. A pre/post experimental design comparing variables between three different programs and a control group. The first program included training in deep breathing, relaxation response, meditation, and guided imagery techniques (RRGI). The second program included training in cognitive behavioral techniques (CB). The third program included both RRGI and CB (RRGICB). SETTING: The study was conducted at Buenos Aires University. SUBJECTS: Participants (N â= 52) were undergraduate students. MEASURES: Anxiety, anger, hopelessness, neuroticism, respiration rate, and salivary cortisol levels were assessed. ANALYSIS: Wilcoxon signed rank test was used to investigate differences in pre and post variables. RESULTS: Subjects in the RRGI group showed significantly lower levels of anxiety (p < .011), anger (p < .012), neuroticism (p < .01), respiratory rate (p < .002), hopelessness (p < .01), and salivary cortisol (p < .002) after the treatment. Subjects in the CB group showed significantly lower levels of anxiety (p < .018), anger (p < .037), and neuroticism (p < .03) after the treatment. Subjects in the RRGICB group showed significantly lower levels of anxiety (p < .001), anger (p < .001), neuroticism (p < .008), hopelessness (p < .01), respiratory rate (p < .001), and salivary cortisol (p < .002) after the treatment. Subjects in the control group showed only one variable modification, a significant increase in cortisol levels (p < .004). CONCLUSIONS: The combination of deep breathing, relaxation response, meditation, and guided imagery techniques with CB seems to be effective at helping people to deal with stress.
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Adaptación Psicológica , Estrés Psicológico/prevención & control , Estudiantes/psicología , Adolescente , Ira , Ansiedad , Argentina , Femenino , Humanos , Hidrocortisona/análisis , Imágenes en Psicoterapia , Masculino , Trastornos Neuróticos/psicología , Psicometría , Estadísticas no Paramétricas , Estrés Psicológico/psicología , Adulto JovenAsunto(s)
Cuerpos Extraños/etiología , Aspiración Respiratoria/etiología , Convulsiones/complicaciones , Tráquea , Adulto , Broncoscopía , Dentaduras , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/terapia , Humanos , Masculino , Radiografía , Aspiración Respiratoria/diagnóstico por imagen , Aspiración Respiratoria/terapiaRESUMEN
PURPOSE: Although concurrent chemotherapy and radiation is the standard approach for good risk unresectable stage III non-small cell lung cancer (NSCLC) patients, there is no optimal concurrent chemotherapy regimen. Administration of chemotherapy at full dose with maximal activity against local and micrometastatic disease is highly desirable. This study tested the feasibility of 3 cycles of full dose cisplatin and pemetrexed concurrent with definitive thoracic radiotherapy followed by consolidation pemetrexed, without the dose-limiting toxicity (DLT) exceeding 33% of the patients. METHODS: Patients with unresectable stage III NSCLC, good performance status and no serious comorbidity were eligible. Patients received thoracic radiation to a dose of 66 Gy concurrently with three 21-day cycles of pemetrexed 500 mg/m(2), and cisplatin at escalating doses from 60 to 75 mg/m(2). Consolidation chemotherapy of pemetrexed 500 mg/m(2) was provided for 3 more 21-day cycles. Cisplatin doses were escalated as far as no more than 1/3 of the patients in a level developing dose limiting toxicities (DLT). RESULTS: Fifteen eligible patients were enrolled: nine in the first dose level and 3 in the second and third dose levels respectively. Two out of 9 patients in the first dose level experienced DLT (grade 3 esophagitis resulting in delay in treatment administration). The major serious acute toxicities were esophagitis (40%) and febrile neutropenia (20%). With a median follow up time of 22 months, median time to progression and overall survival has not been reached. The rate of survival at 24 months was 57.5% (95% CI: 27.5-87.4%) of the patients. CONCLUSIONS: Three systemic dose levels of pemetrexed and cisplatin could be administered concurrently with radiotherapy. The rate of survival at 24 months was encouraging.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Quimioterapia de Consolidación , Neoplasias Pulmonares/terapia , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Progresión de la Enfermedad , Esofagitis/etiología , Femenino , Estudios de Seguimiento , Glutamatos/administración & dosificación , Glutamatos/efectos adversos , Guanina/administración & dosificación , Guanina/efectos adversos , Guanina/análogos & derivados , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neutropenia/etiología , Pemetrexed , Análisis de SupervivenciaRESUMEN
Despite the strong immune responses elicited after natural infection with Trypanosoma cruzi or vaccination against it, parasite survival suggests that these responses are insufficient or inherently inadequate. T. cruzi contains a major cystein proteinase, cruzipain, which has a catalytic N-terminal domain and a C-terminal extension. Immunizations that employed recombinant cruzipain or its N- and C-terminal domains allowed evaluation of the ability of cruzipain to circumvent responses against the catalytic domain. This phenomenon is not a property of the parasite but of cruzipain itself, because recombinant cruzipain triggers a response similar to that of cruzipain during natural or experimental infection. Cruzipain is not the only antigen with a highly immunogenic region of unknown function that somehow protects an essential domain for parasite survival. However, our studies show that this can be reverted by using the N-terminal domain as a tailored immunogen able to redirect host responses to provide enhanced protection.
Asunto(s)
Enfermedad de Chagas/prevención & control , Cisteína Endopeptidasas/inmunología , Vacunas Antiprotozoos/inmunología , Trypanosoma cruzi/genética , Animales , Anticuerpos Antiprotozoarios/sangre , Femenino , Ratones , Ratones Endogámicos C3H , Músculo Esquelético/patología , Miocardio/patología , Proteínas Protozoarias/inmunología , Proteínas Recombinantes/inmunología , Trypanosoma cruzi/enzimología , Trypanosoma cruzi/inmunologíaRESUMEN
Trypanosoma cruzi, the agent of Chagas disease contains a major cysteine proteinase, cruzipain (Cz), with an unusual carboxyl-terminal extension (C-T). We have previously reported the presence of sulfate groups in the N-linked oligosaccharide chains of this domain. In order to evaluate the immune responses to sulfated moieties on Cz, BALB/c mice were immunized with purified Cz and C-T prior and after desulfation treatment. The humoral immune response to sulfates on Cz or C-T was mainly IgG2b. Interestingly, the abolishment of IgG2b reactivity when desulfated antigens were used as immunogens demonstrates that esterified sulfate groups are absolutely required for eliciting IgG2b response to Cz. Sera from chronically T. cruzi-infected subjects with mild disease displayed higher levels of total IgG and IgG2 antibodies specific for sulfated epitopes compared with those in more severe forms of the disease. A significant reduction of C-T-specific delayed-type hypersensitivity reaction in C-T-immunized mice was observed when desulfated C-T was challenged, suggesting the involvement of sulfate groups in the generation of memory T-cell responses. Moreover, immunization with C-T in the absence of infection elicited ultrastructural abnormalities in heart tissue. Surprisingly, hearts from sulfate-depleted C-T-immunized mice did not present pathological alterations. This is the first report showing that sulfate-bearing glycoproteins from trypanosomatids are able to elicit specific humoral and cellular immune responses and appeared to be involved in the generation of heart tissue damage. These results represent a further step in the understanding of the role of Cz in the course of T. cruzi infection.
Asunto(s)
Enfermedad de Chagas/inmunología , Cisteína Endopeptidasas/inmunología , Cardiopatías/inmunología , Inmunoglobulina G/sangre , Sulfatos/inmunología , Trypanosoma cruzi/inmunología , Animales , Enfermedad de Chagas/sangre , Enfermedad Crónica , Cisteína Endopeptidasas/química , Cisteína Endopeptidasas/aislamiento & purificación , Modelos Animales de Enfermedad , Femenino , Cardiopatías/patología , Humanos , Hipersensibilidad Tardía/inmunología , Inyecciones Subcutáneas , Ratones , Ratones Endogámicos BALB C , Miocardio/inmunología , Miocardio/patología , Miocardio/ultraestructura , Fragmentos de Péptidos/inmunología , Estructura Terciaria de Proteína , Proteínas Protozoarias , Reproducibilidad de los Resultados , Pruebas Serológicas , Trypanosoma cruzi/enzimologíaRESUMEN
BACKGROUND: Radiation therapy (RT) alone is frequently used in elderly patients with medically inoperable early stage (I/II) non-small cell lung cancer (NSCLC). We retrospectively investigated the effectiveness of RT alone in this patient population treated in our institution. MATERIAL AND METHODS: Between 1995 and 1999, a total of 33 patients were treated with RT alone in our institution, all being males. RT doses ranged 66-78 Gy (median, 70 Gy) using standard fractionation (2.0 Gy per fraction). The age range was 71-97 years (median, 75 years) with 11 patients being >or=80 years old. Twenty-two (67%) patients had a squamous cell carcinoma. There were 24 (73%) stage I and nine (27%) stage II patients. RESULTS: Radiographic objective response rate was observed in 23 (70%) patients. The median survival time was 37.4 months and 3-year survival time was 50%, while the median cause-specific survival time was 48.1 months and a 3-year cause-specific survival rate was 55.3%. The median time to local recurrence was 36.8 months and a 3-year local recurrence-free survival rate was 50.2%, while the median time to distant metastasis was not achieved yet, the 3-year distant metastasis-free survival rate being 71.4%. One (3%) patient died of RT-induced acute lung toxicity, while only two (6%) patients experienced late grade 3 lung toxicity. No other high-grade toxicity was observed during this study. CONCLUSIONS: RT alone was effective and low toxic in elderly with early stage (I/II) NSCLC and could be considered as treatment of choice in this patient population.