American Journal of Physiology-regulatory Integrative and Comparative Physiology, Apr 1, 1992
In contrast to mammalian brain, which exhibits rapid degeneration during anoxia, the brains of ce... more In contrast to mammalian brain, which exhibits rapid degeneration during anoxia, the brains of certain species of turtles show an extraordinary capacity to survive prolonged anoxia. The decrease in energy expenditure shown by the anoxic turtle brain is likely to be a key factor for anoxic survival. The "channel arrest" hypothesis proposes that ion channels, which regulate brain electrical activity in normoxia, may be altered during anoxia in the turtle brain as a mechanism to spare energy. Goals of present research were to test this hypothesis and to determine whether down-regulation of sodium channels is a possible explanation for spike threshold shifts seen during anoxia in isolated turtle cerebellum. We report here that anoxia induced a significant (42%) decline in voltage-gated sodium channel density as determined by studies of the binding of a sodium channel ligand, [3H]brevetoxin. This study demonstrates that sodium channel densities in brain may be regulated by tissue oxygenation or by physiological events associated with anoxia. Moreover, it also suggests that downregulation of sodium channels may be a basis for changes in action potential thresholds, the electrical depression and energy conservation that provide the unique anoxic tolerance of turtle brain.
Alpha synuclein is increased in dopamine neurons of cocaine abusers and in rats whose alcohol pre... more Alpha synuclein is increased in dopamine neurons of cocaine abusers and in rats whose alcohol preference is inbred. Recent studies have shown increased alpha-synuclein protein expression in serum of alcoholic patients that is linked with severity of alcohol craving. The aim of this study was to analyze the serum levels of alpha synuclein in healthy subjects and in recently abstinent cocaine abusers. Alpha synuclein protein expression was measured by enzyme-linked immunosorbent assay in serum specimens obtained from 38 recently abstinent cocaine dependent patients and 14 control subjects. The presence of cocaine dependence disorder was based on the Structured Clinical Interview (DSM-IV). Drug severity was assessed by the Addiction Severity Index ratings and composite measures. Scores of the intensity and frequency of cocaine craving episodes were obtained from the Minnesota Cocaine Craving Questionnaire. The serum concentrations of alpha synuclein in cocaine dependent patients were significantly higher as compared with age-matched drug-free controls (p < 0.001). Alpha synuclein levels in blood were significantly correlated with the intensity (r = 0.60, p < 0.001) and frequency (r = 0.64. p < 0.001) of cocaine craving and with thirty days of cocaine use in the prior month before entry to treatment (r = 0.56, p < 0.005). However, there was no correlation between the serum protein levels of alpha synuclein and age in either group. This report is the first demonstration of altered alpha synuclein levels in peripheral blood from cocaine abusers. These data agree with previous reports in postmortem brain of cocaine abusers and provide support for an association between alpha synuclein and cocaine dependence.
International Journal of Radiation Oncology Biology Physics, Sep 1, 2014
lymphedema rates were higher with SNB + ALND than with SNB. However, there was no significant imp... more lymphedema rates were higher with SNB + ALND than with SNB. However, there was no significant impact of RT on long-term (6-36 months) lymphedema (p > 0.8). There were no significant differences at the individual time points (TABLE). As evidenced by kappa coefficient ranging between 0.02 and 0.21, little agreement was noted between subjective and objective lymphedema measures. Conclusions: In this large cohort of patients with prospectively collected data, RAVD > 10% was detected in 13% of women undergoing ALND and in 7% of women undergoing SNB at 36 months. There is no evidence to suggest a detrimental impact of RT on risk of lymphedema beyond surgery. Subjective lymphedema, defined as bothersome to patients, was endorsed less frequently (8% ALND and 3.5% SNB at 36 months) and had a poor agreement with objectively measured RAVD > 10%. Additional analyses of objective data are in progress to evaluate quantification methods that may better correlate with subjective assessments.
Background: The purpose of this study was to evaluate treatment patterns and outcomes of stereota... more Background: The purpose of this study was to evaluate treatment patterns and outcomes of stereotactic body radiotherapy (SBRT) for centrally located primary non-small cell lung cancer (NSCLC) or lung metastases from the RSSearch ® Patient Registry, an international, multi-center patient registry dedicated to radiosurgery and SBRT. Methods: Eligible patients included those with centrally located lung tumors clinically staged T1-T2 N0, M0, biopsy-confirmed NSCLC or lung metastases treated with SBRT between November 2004 and January 2014. Descriptive analysis was used to report patient demographics and treatment patterns. Overall survival (OS) and local control (LC) were determined using Kaplan-Meier method. Toxicity was reported using the Common Terminology Criteria for Adverse Events version 3.0. Results: In total, 111 patients with 114 centrally located lung tumors (48 T1-T2,N0,M0 NSCLC and 66 lung metastases) were treated with SBRT at 19 academic and community-based radiotherapy centers in the US and Germany. Median follow-up was 17 months (range, 1-72). Median age was 74 years for primary NSCLC patients and 65 years for lung metastases patients (p < 0.001). SBRT dose varied from 16-60 Gy (median 48 Gy) delivered in 1-5 fractions (median 4 fractions). Median dose to centrally located primary NSCLC was 48 Gy compared to 37.5 Gy for lung metastases (p = 0.0001) and median BED 10 was 105.6 Gy for primary NSCLC and 93.6 Gy for lung metastases (p = 0.0005). Two-year OS for T1N0M0 and T2N0M0 NSCLC was 79 and 32.1 %, respectively (p = 0.009) and 2-year OS for lung metastases was 49.6 %. Two-year LC was 76.4 and 69.8 % for primary NSCLC and lung metastases, respectively. Toxicity was low with no Grade 3 or higher acute or late toxicities. Conclusion: Overall, patients with centrally located primary NSCLC were older and received higher doses of SBRT than those with lung metastases. Despite these differences, LC and OS was favorable for patients with central lung tumors treated with SBRT. Reported toxicity was low, although low grade toxicities were observed in patients where dose tolerances approached or exceeded published guidelines. Prospective studies are needed to further define the optimal SBRT dose for this cohort of patients. Trial registration: Clinicaltrials.gov Identifier: NCT01885299
Objectives Stereotactic body radiotherapy (SBRT) is a definitive local treatment option for patie... more Objectives Stereotactic body radiotherapy (SBRT) is a definitive local treatment option for patients with stage I non-small cell lung cancer (NSCLC) who are not surgical candidates and patients who refuse surgery. The purpose of this study was to assess the impact of SBRT on T1-T2 NSCLC from a national registry, reflecting practices and outcomes in a real-world setting. Methods The RSSearch® Patient Registry was screened for T1-T2N0M0 NSCLC patients treated from May 2004 to May 2013 with SBRT. Descriptive analyses were used for patient, tumor, and treatment characteristics. Overall survival (OS) and local control (LC) were calculated using the Kaplan-Meier method. Results In total, 723 patients with 517 T1 and 224 T2 lesions were treated with SBRT. Median follow-up was 12 months (1-87 months) with a median age of 76 years. Median SBRT dose was 54 Gy (range 10-80 Gy) delivered in a median of 3 fractions (range 1-5), and median biological equivalent dose (BED 10) was 151.2 Gy (range 20-240 Gy). Median OS was 30 and 26 months for T1 and T2 tumors, respectively (p= 0.019). LC was associated with higher BED 10 for T2 tumors, but not in T1 tumors at a median follow-up of 17 months. Seventeen-month LC for T2 tumors treated with BED 10 < 105 Gy, BED 10 105-149, and BED 10 ≥150 Gy was 43, 74, and 95 %, respectively (p=0.011). Local failure rates for T2 tumors treated with BED 10 < 105 Gy, 105-149 Gy, and ≥150 Gy were 32, 21, and 8 % (p=0.029), respectively.
Hoy en día las empresas que solicitan los servicios de auditoría, saben que es primordial una eva... more Hoy en día las empresas que solicitan los servicios de auditoría, saben que es primordial una evaluación al sistema de control interno, ya que el fin es evitar riesgos que puedan perjudicar directamente con el cumplimiento del sistema de cada departamento evaluando la eficiencia de las mismas, es por esos que la investigación está realizada a la evaluación del control interno del departamento de riesgos de la empresa Novacredit S.A, basado en el coso II, utilizando los métodos de evaluación más conocidos como son el del cuestionario y flujogramas o diagramas de flujo de los sub procesos del mismo departamento con el objetivo de llegar a conclusiones y dar recomendaciones a los administradores para que cumplan con los objetivos de la misma empresa. Palabras claves.
The regulation of neuronal iron is necessary for the synthesis of iron containing cytochromes and... more The regulation of neuronal iron is necessary for the synthesis of iron containing cytochromes and to prevent damage from free radicals by iron-oxygen interactions. We have shown that transferrin receptors are elevated over the substantia nigra in the human and rat brain (Mash et al., 1990) and are depleted concomitantly with dopaminergic terminals in the MPTP-treated mouse striatum (Mash et al., 1991). Given the iron dependency for both synthetic and degradative enzyme activities, dopaminergic neurons may express transferrin receptors on their cell surface to facilitate the uptake of iron bound to transferrin. If the intracellular iron pool is regulated by receptor-mediated transferrin uptake, then an up-regulation of transferrin receptor number may play a role in the pathogenesis of nigral cell damage in Parkinson’s disease. Early in the disease process, surviving dopaminergic neurons may increase the number of transferrin receptors in order to meet the increased metabolic demand associated with compensatory changes in dopamine synthesis and turnover. The uptake of ferrotransferrin by dopaminergic neurons may result in a progressive elevation in the cellular iron load that exceeds the regulatory capacity for increased ferritin expression in the aging brain.
San Lorenzo de Vinces, canton de la provincia de Los Rios, posee una ubicacion geografica privile... more San Lorenzo de Vinces, canton de la provincia de Los Rios, posee una ubicacion geografica privilegiada, ya que sus llanuras y el sistema hidrografico contribuyen a la presencia de una gran diversidad de flora y fauna. Entre los recursos culturales y turisticos mas visitados se encuentran: el antiguo Palacio Municipal, el Malecon Eloy Alfaro, el Muelle Nautico, Paseo Paris, Parque Central, Puente Peatonal, Templeta a los Heroes del Cenepa, Obelisco a Isidoro Weinza, Humedal de Abras de Mantequilla, Playas de Vinces, entre otros. Dentro de estos recursos, el de mayor importancia es el Humedal de Abras de Mantequilla, uno de los mas extensos del pais y un sitio de categoria RAMSAR (The Ramsar Convention for Wetlands, 2012) 1, situado a 10 Km. de la ciudad cuenta con una extension de 65.000 has. aproximadamente, y es el habitat de mas de 100 especies de aves en peligro de extincion (Vida de los Pajaros, 2012). Hermosas playas de agua dulce, rica gastronomia nacional, artesanias, belleza...
The norepinephrine transporter (NET) is a membrane protein responsible for transporting extracell... more The norepinephrine transporter (NET) is a membrane protein responsible for transporting extracellular norepinephrine. The cocaine and tricyclic antidepressant-sensitive NET belongs to a family of sodium and chloride coupled transporters that include the monoamines dopamine and serotonin and the amino acids GABA and glycine. The regional distribution of the NET has been defined by synaptosomal uptake of norepinephrine and by autoradiographic approaches in rodent and primate brain. However, the NET has not been well characterized in the human brain due to the overall low abundance of protein expressed in axon terminals. Recently, immunolocalization studies have been used to identify the regional distribution of the cytoplasmic NET epitope in rodent brain. We report here on the characteristics of drug interactions with the native NET protein in human postmortem brain. Antisera raised against a 17-amino acid peptide from the N-terminus of the hNET recognized an 80 kDa species in human cerebral cortex. Chronic exposure to cocaine upregulated NET protein expression and [3H]nisoxetine binding sites in the insular cortex from brains of cocaine addicts. These results demonstrate that immunologic and radioligand binding approaches afford specific labeling of the native transport protein in postmortem human brain.
α-Synuclein is a presynaptic protein that has been implicated as a possible causative agent in th... more α-Synuclein is a presynaptic protein that has been implicated as a possible causative agent in the pathogenesis of Parkinson's disease. The native protein is a major component of nigral Lewy bodies in Parkinson's disease, and full-length α-synuclein accumulates in Lewy neurites. Here we present evidence that α-synuclein levels are elevated in midbrain dopamine (DA) neurons of chronic cocaine abusers. Western blot and immunoautoradiographic studies were conducted on postmortem neuropathological specimens from cocaine users and age-matched drug-free control subjects. The results demonstrated that α-synuclein levels in the DA cell groups of the substantia nigra/ventral tegmental complex were elevated threefold in chronic cocaine users compared with normal age-matched subjects. The increased protein levels in chronic cocaine users were accompanied by changes in the expression of α-synuclein mRNA in the substantia nigra and ventral tegmental area. Although α-synuclein expression ...
La investigación que se presenta tiene como propósito establecer la relación de las estrategias d... more La investigación que se presenta tiene como propósito establecer la relación de las estrategias de metacomprensión lectora con los estilos de aprendizaje en estudiantes universitarios. Los participantes fueron 809 estudiantes de ambos sexos a quienes se aplicó el Inventario de Estrategias de Metacomprensión de Schimitt y el Inventario de Estrategias de Aprendizaje de Kolb. Los resultados mostraron que los participantes poseen un bajo nivel de desarrollo de las estrategias metacomprensivas y no se evidencia un estilo de aprendizaje predominante. Finalmente, no se halló relación entre las estrategias de metacomprensión lectora y los estilos de aprendizaje.
International journal of radiation oncology, biology, physics, Mar 15, 2017
Randomized trials have shown that honey is effective for the prevention of radiation-induced muco... more Randomized trials have shown that honey is effective for the prevention of radiation-induced mucositis in head and neck cancer patients. Because there is no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis. The patients were stratified by percentage of esophagus receiving specific radiation dose (V60 Gy esophagus <30% or ≥30%) and were then randomized between supportive care, 10 mL of liquid manuka honey 4 times a day, and 2 lozenges (10 mL of dehydrated manuka honey) 4 times a day during concurrent chemotherapy and radiation therapy. The primary endpoint was patient-reported pain on swallowing, with the use of an 11-point (0-10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). The study was designed to detect a 15% relative reduction of change in NRPS score. The secondary endpoints were trend of pain over time, opioid use, clinically graded and...
To report overall survival and local control for patients identified in the RSSearch® Patient Reg... more To report overall survival and local control for patients identified in the RSSearch® Patient Registry with metastatic cancer to the lung treated with SBRT. Seven hundred two patients were identified with lung metastases in the RSSearch® Registry. Of these patients, 577 patients had SBRT dose and fractionation information available. Patients were excluded if they received prior surgery, radiation, or radiofrequency ablation to the SBRT treated area. Between April 2004-July 2015, 447 patients treated with SBRT at 30 academic and community-based centers were evaluable for overall survival (OS). Three hundred four patients with 327 lesions were evaluable for local control (LC). All doses were converted to Monte Carlo equivalents and subsequent BED Gy10 for dose response analysis. Median age was 69 years (range, 18-93 years). Median Karnofsky performance status (KPS) was 90 (range 25/75% 80-100). 49.2% of patients had prior systemic therapy. Median metastasis volume was 10.58 cc (range ...
The consequences of drug abuse (e.g. overdoses, and violent crime) continues to increase the burd... more The consequences of drug abuse (e.g. overdoses, and violent crime) continues to increase the burden on an already over-burdened health care system. A non-addicting pharmacological agent in combination with psychotherapy may prove a viable alternative to interdiction of supply and incarceration. Anecdotal reports from addict self-help groups suggest that ibogaine may block opiate withdrawal and reduce drug craving for cocaine
Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al], 2015
The purpose of this work is to analyze patterns of care and outcome after stereotactic body radio... more The purpose of this work is to analyze patterns of care and outcome after stereotactic body radiotherapy (SBRT) for centrally located, early-stage, non-small cell lung cancer (NSCLC) and to address the question of potential risk for increased toxicity in this entity. A total of 90 patients with centrally located NSCLC were identified among 613 cases in a database of 13 German and Austrian academic radiotherapy centers. The outcome of centrally located NSCLC was compared to that of cases with peripheral tumor location from the same database. Patients with central tumors most commonly presented with UICC stage IB (50 %), while the majority of peripheral lesions were stage IA (56 %). Average tumor diameters were 3.3 cm (central) and 2.8 cm (peripheral). Staging PET/CT was available for 73 and 74 % of peripheral and central tumors, respectively. Biopsy was performed in 84 % (peripheral) and 88 % (central) of cases. Doses varied significantly between central and peripheral lesions with a...
The Journal of pharmacology and experimental therapeutics, 2001
Ibogaine is a naturally occurring compound with purported antiaddictive properties. When administ... more Ibogaine is a naturally occurring compound with purported antiaddictive properties. When administered to primates, ibogaine is rapidly o-demethylated to form the metabolite 12-hydroxyibogamine (noribogaine). Peak blood levels of noribogaine exceed those of ibogaine, and noribogaine persists in the bloodstream for at least 1 day. Very few studies have systematically evaluated the neurobiological effects of noribogaine in vivo. In the present series of experiments, we compared the effects of i.v. administration of ibogaine and noribogaine (1 and 10 mg/kg) on motor behaviors, stress hormones, and extracellular levels of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of male rats. Ibogaine caused dose-related increases in tremors, whereas noribogaine did not. Both ibogaine and noribogaine produced significant elevations in plasma corticosterone and prolactin, but ibogaine was a more potent stimulator of corticosterone secretion. Neither drug altered extracellular DA levels ...
Drug metabolism and disposition: the biological fate of chemicals, 1998
Ibogaine is a psychoactive alkaloid that possesses potential as an agent to treat opiate and coca... more Ibogaine is a psychoactive alkaloid that possesses potential as an agent to treat opiate and cocaine addiction. The primary metabolite arises via O-demethylation at the 12-position to yield 12-hydroxyibogamine. In this report, evidence is presented that the O-demethylation of ibogaine observed in human hepatic microsomes is catalyzed primarily by the polymorphically expressed cytochrome P-4502D6 (CYP2D6). An enzyme kinetic examination of ibogaine O-demethylase activity in pooled human liver microsomes suggested that two (or more) enzymes are involved in this reaction: one with a low KMapp (1.1 microM) and the other with a high KMapp (>200 microM). The low KMapp activity comprised >95% of total intrinsic clearance. Human liver microsomes from three individual donors demonstrated similar enzyme kinetic parameters (mean KMapp = 0.55 +/- 0.09 microM and 310 +/- 10 microM for low and high KM activities, respectively). However, a fourth human microsome sample that appeared to be a p...
American Journal of Physiology-regulatory Integrative and Comparative Physiology, Apr 1, 1992
In contrast to mammalian brain, which exhibits rapid degeneration during anoxia, the brains of ce... more In contrast to mammalian brain, which exhibits rapid degeneration during anoxia, the brains of certain species of turtles show an extraordinary capacity to survive prolonged anoxia. The decrease in energy expenditure shown by the anoxic turtle brain is likely to be a key factor for anoxic survival. The &quot;channel arrest&quot; hypothesis proposes that ion channels, which regulate brain electrical activity in normoxia, may be altered during anoxia in the turtle brain as a mechanism to spare energy. Goals of present research were to test this hypothesis and to determine whether down-regulation of sodium channels is a possible explanation for spike threshold shifts seen during anoxia in isolated turtle cerebellum. We report here that anoxia induced a significant (42%) decline in voltage-gated sodium channel density as determined by studies of the binding of a sodium channel ligand, [3H]brevetoxin. This study demonstrates that sodium channel densities in brain may be regulated by tissue oxygenation or by physiological events associated with anoxia. Moreover, it also suggests that downregulation of sodium channels may be a basis for changes in action potential thresholds, the electrical depression and energy conservation that provide the unique anoxic tolerance of turtle brain.
Alpha synuclein is increased in dopamine neurons of cocaine abusers and in rats whose alcohol pre... more Alpha synuclein is increased in dopamine neurons of cocaine abusers and in rats whose alcohol preference is inbred. Recent studies have shown increased alpha-synuclein protein expression in serum of alcoholic patients that is linked with severity of alcohol craving. The aim of this study was to analyze the serum levels of alpha synuclein in healthy subjects and in recently abstinent cocaine abusers. Alpha synuclein protein expression was measured by enzyme-linked immunosorbent assay in serum specimens obtained from 38 recently abstinent cocaine dependent patients and 14 control subjects. The presence of cocaine dependence disorder was based on the Structured Clinical Interview (DSM-IV). Drug severity was assessed by the Addiction Severity Index ratings and composite measures. Scores of the intensity and frequency of cocaine craving episodes were obtained from the Minnesota Cocaine Craving Questionnaire. The serum concentrations of alpha synuclein in cocaine dependent patients were significantly higher as compared with age-matched drug-free controls (p < 0.001). Alpha synuclein levels in blood were significantly correlated with the intensity (r = 0.60, p < 0.001) and frequency (r = 0.64. p < 0.001) of cocaine craving and with thirty days of cocaine use in the prior month before entry to treatment (r = 0.56, p < 0.005). However, there was no correlation between the serum protein levels of alpha synuclein and age in either group. This report is the first demonstration of altered alpha synuclein levels in peripheral blood from cocaine abusers. These data agree with previous reports in postmortem brain of cocaine abusers and provide support for an association between alpha synuclein and cocaine dependence.
International Journal of Radiation Oncology Biology Physics, Sep 1, 2014
lymphedema rates were higher with SNB + ALND than with SNB. However, there was no significant imp... more lymphedema rates were higher with SNB + ALND than with SNB. However, there was no significant impact of RT on long-term (6-36 months) lymphedema (p > 0.8). There were no significant differences at the individual time points (TABLE). As evidenced by kappa coefficient ranging between 0.02 and 0.21, little agreement was noted between subjective and objective lymphedema measures. Conclusions: In this large cohort of patients with prospectively collected data, RAVD > 10% was detected in 13% of women undergoing ALND and in 7% of women undergoing SNB at 36 months. There is no evidence to suggest a detrimental impact of RT on risk of lymphedema beyond surgery. Subjective lymphedema, defined as bothersome to patients, was endorsed less frequently (8% ALND and 3.5% SNB at 36 months) and had a poor agreement with objectively measured RAVD > 10%. Additional analyses of objective data are in progress to evaluate quantification methods that may better correlate with subjective assessments.
Background: The purpose of this study was to evaluate treatment patterns and outcomes of stereota... more Background: The purpose of this study was to evaluate treatment patterns and outcomes of stereotactic body radiotherapy (SBRT) for centrally located primary non-small cell lung cancer (NSCLC) or lung metastases from the RSSearch ® Patient Registry, an international, multi-center patient registry dedicated to radiosurgery and SBRT. Methods: Eligible patients included those with centrally located lung tumors clinically staged T1-T2 N0, M0, biopsy-confirmed NSCLC or lung metastases treated with SBRT between November 2004 and January 2014. Descriptive analysis was used to report patient demographics and treatment patterns. Overall survival (OS) and local control (LC) were determined using Kaplan-Meier method. Toxicity was reported using the Common Terminology Criteria for Adverse Events version 3.0. Results: In total, 111 patients with 114 centrally located lung tumors (48 T1-T2,N0,M0 NSCLC and 66 lung metastases) were treated with SBRT at 19 academic and community-based radiotherapy centers in the US and Germany. Median follow-up was 17 months (range, 1-72). Median age was 74 years for primary NSCLC patients and 65 years for lung metastases patients (p < 0.001). SBRT dose varied from 16-60 Gy (median 48 Gy) delivered in 1-5 fractions (median 4 fractions). Median dose to centrally located primary NSCLC was 48 Gy compared to 37.5 Gy for lung metastases (p = 0.0001) and median BED 10 was 105.6 Gy for primary NSCLC and 93.6 Gy for lung metastases (p = 0.0005). Two-year OS for T1N0M0 and T2N0M0 NSCLC was 79 and 32.1 %, respectively (p = 0.009) and 2-year OS for lung metastases was 49.6 %. Two-year LC was 76.4 and 69.8 % for primary NSCLC and lung metastases, respectively. Toxicity was low with no Grade 3 or higher acute or late toxicities. Conclusion: Overall, patients with centrally located primary NSCLC were older and received higher doses of SBRT than those with lung metastases. Despite these differences, LC and OS was favorable for patients with central lung tumors treated with SBRT. Reported toxicity was low, although low grade toxicities were observed in patients where dose tolerances approached or exceeded published guidelines. Prospective studies are needed to further define the optimal SBRT dose for this cohort of patients. Trial registration: Clinicaltrials.gov Identifier: NCT01885299
Objectives Stereotactic body radiotherapy (SBRT) is a definitive local treatment option for patie... more Objectives Stereotactic body radiotherapy (SBRT) is a definitive local treatment option for patients with stage I non-small cell lung cancer (NSCLC) who are not surgical candidates and patients who refuse surgery. The purpose of this study was to assess the impact of SBRT on T1-T2 NSCLC from a national registry, reflecting practices and outcomes in a real-world setting. Methods The RSSearch® Patient Registry was screened for T1-T2N0M0 NSCLC patients treated from May 2004 to May 2013 with SBRT. Descriptive analyses were used for patient, tumor, and treatment characteristics. Overall survival (OS) and local control (LC) were calculated using the Kaplan-Meier method. Results In total, 723 patients with 517 T1 and 224 T2 lesions were treated with SBRT. Median follow-up was 12 months (1-87 months) with a median age of 76 years. Median SBRT dose was 54 Gy (range 10-80 Gy) delivered in a median of 3 fractions (range 1-5), and median biological equivalent dose (BED 10) was 151.2 Gy (range 20-240 Gy). Median OS was 30 and 26 months for T1 and T2 tumors, respectively (p= 0.019). LC was associated with higher BED 10 for T2 tumors, but not in T1 tumors at a median follow-up of 17 months. Seventeen-month LC for T2 tumors treated with BED 10 < 105 Gy, BED 10 105-149, and BED 10 ≥150 Gy was 43, 74, and 95 %, respectively (p=0.011). Local failure rates for T2 tumors treated with BED 10 < 105 Gy, 105-149 Gy, and ≥150 Gy were 32, 21, and 8 % (p=0.029), respectively.
Hoy en día las empresas que solicitan los servicios de auditoría, saben que es primordial una eva... more Hoy en día las empresas que solicitan los servicios de auditoría, saben que es primordial una evaluación al sistema de control interno, ya que el fin es evitar riesgos que puedan perjudicar directamente con el cumplimiento del sistema de cada departamento evaluando la eficiencia de las mismas, es por esos que la investigación está realizada a la evaluación del control interno del departamento de riesgos de la empresa Novacredit S.A, basado en el coso II, utilizando los métodos de evaluación más conocidos como son el del cuestionario y flujogramas o diagramas de flujo de los sub procesos del mismo departamento con el objetivo de llegar a conclusiones y dar recomendaciones a los administradores para que cumplan con los objetivos de la misma empresa. Palabras claves.
The regulation of neuronal iron is necessary for the synthesis of iron containing cytochromes and... more The regulation of neuronal iron is necessary for the synthesis of iron containing cytochromes and to prevent damage from free radicals by iron-oxygen interactions. We have shown that transferrin receptors are elevated over the substantia nigra in the human and rat brain (Mash et al., 1990) and are depleted concomitantly with dopaminergic terminals in the MPTP-treated mouse striatum (Mash et al., 1991). Given the iron dependency for both synthetic and degradative enzyme activities, dopaminergic neurons may express transferrin receptors on their cell surface to facilitate the uptake of iron bound to transferrin. If the intracellular iron pool is regulated by receptor-mediated transferrin uptake, then an up-regulation of transferrin receptor number may play a role in the pathogenesis of nigral cell damage in Parkinson’s disease. Early in the disease process, surviving dopaminergic neurons may increase the number of transferrin receptors in order to meet the increased metabolic demand associated with compensatory changes in dopamine synthesis and turnover. The uptake of ferrotransferrin by dopaminergic neurons may result in a progressive elevation in the cellular iron load that exceeds the regulatory capacity for increased ferritin expression in the aging brain.
San Lorenzo de Vinces, canton de la provincia de Los Rios, posee una ubicacion geografica privile... more San Lorenzo de Vinces, canton de la provincia de Los Rios, posee una ubicacion geografica privilegiada, ya que sus llanuras y el sistema hidrografico contribuyen a la presencia de una gran diversidad de flora y fauna. Entre los recursos culturales y turisticos mas visitados se encuentran: el antiguo Palacio Municipal, el Malecon Eloy Alfaro, el Muelle Nautico, Paseo Paris, Parque Central, Puente Peatonal, Templeta a los Heroes del Cenepa, Obelisco a Isidoro Weinza, Humedal de Abras de Mantequilla, Playas de Vinces, entre otros. Dentro de estos recursos, el de mayor importancia es el Humedal de Abras de Mantequilla, uno de los mas extensos del pais y un sitio de categoria RAMSAR (The Ramsar Convention for Wetlands, 2012) 1, situado a 10 Km. de la ciudad cuenta con una extension de 65.000 has. aproximadamente, y es el habitat de mas de 100 especies de aves en peligro de extincion (Vida de los Pajaros, 2012). Hermosas playas de agua dulce, rica gastronomia nacional, artesanias, belleza...
The norepinephrine transporter (NET) is a membrane protein responsible for transporting extracell... more The norepinephrine transporter (NET) is a membrane protein responsible for transporting extracellular norepinephrine. The cocaine and tricyclic antidepressant-sensitive NET belongs to a family of sodium and chloride coupled transporters that include the monoamines dopamine and serotonin and the amino acids GABA and glycine. The regional distribution of the NET has been defined by synaptosomal uptake of norepinephrine and by autoradiographic approaches in rodent and primate brain. However, the NET has not been well characterized in the human brain due to the overall low abundance of protein expressed in axon terminals. Recently, immunolocalization studies have been used to identify the regional distribution of the cytoplasmic NET epitope in rodent brain. We report here on the characteristics of drug interactions with the native NET protein in human postmortem brain. Antisera raised against a 17-amino acid peptide from the N-terminus of the hNET recognized an 80 kDa species in human cerebral cortex. Chronic exposure to cocaine upregulated NET protein expression and [3H]nisoxetine binding sites in the insular cortex from brains of cocaine addicts. These results demonstrate that immunologic and radioligand binding approaches afford specific labeling of the native transport protein in postmortem human brain.
α-Synuclein is a presynaptic protein that has been implicated as a possible causative agent in th... more α-Synuclein is a presynaptic protein that has been implicated as a possible causative agent in the pathogenesis of Parkinson's disease. The native protein is a major component of nigral Lewy bodies in Parkinson's disease, and full-length α-synuclein accumulates in Lewy neurites. Here we present evidence that α-synuclein levels are elevated in midbrain dopamine (DA) neurons of chronic cocaine abusers. Western blot and immunoautoradiographic studies were conducted on postmortem neuropathological specimens from cocaine users and age-matched drug-free control subjects. The results demonstrated that α-synuclein levels in the DA cell groups of the substantia nigra/ventral tegmental complex were elevated threefold in chronic cocaine users compared with normal age-matched subjects. The increased protein levels in chronic cocaine users were accompanied by changes in the expression of α-synuclein mRNA in the substantia nigra and ventral tegmental area. Although α-synuclein expression ...
La investigación que se presenta tiene como propósito establecer la relación de las estrategias d... more La investigación que se presenta tiene como propósito establecer la relación de las estrategias de metacomprensión lectora con los estilos de aprendizaje en estudiantes universitarios. Los participantes fueron 809 estudiantes de ambos sexos a quienes se aplicó el Inventario de Estrategias de Metacomprensión de Schimitt y el Inventario de Estrategias de Aprendizaje de Kolb. Los resultados mostraron que los participantes poseen un bajo nivel de desarrollo de las estrategias metacomprensivas y no se evidencia un estilo de aprendizaje predominante. Finalmente, no se halló relación entre las estrategias de metacomprensión lectora y los estilos de aprendizaje.
International journal of radiation oncology, biology, physics, Mar 15, 2017
Randomized trials have shown that honey is effective for the prevention of radiation-induced muco... more Randomized trials have shown that honey is effective for the prevention of radiation-induced mucositis in head and neck cancer patients. Because there is no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis. The patients were stratified by percentage of esophagus receiving specific radiation dose (V60 Gy esophagus <30% or ≥30%) and were then randomized between supportive care, 10 mL of liquid manuka honey 4 times a day, and 2 lozenges (10 mL of dehydrated manuka honey) 4 times a day during concurrent chemotherapy and radiation therapy. The primary endpoint was patient-reported pain on swallowing, with the use of an 11-point (0-10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). The study was designed to detect a 15% relative reduction of change in NRPS score. The secondary endpoints were trend of pain over time, opioid use, clinically graded and...
To report overall survival and local control for patients identified in the RSSearch® Patient Reg... more To report overall survival and local control for patients identified in the RSSearch® Patient Registry with metastatic cancer to the lung treated with SBRT. Seven hundred two patients were identified with lung metastases in the RSSearch® Registry. Of these patients, 577 patients had SBRT dose and fractionation information available. Patients were excluded if they received prior surgery, radiation, or radiofrequency ablation to the SBRT treated area. Between April 2004-July 2015, 447 patients treated with SBRT at 30 academic and community-based centers were evaluable for overall survival (OS). Three hundred four patients with 327 lesions were evaluable for local control (LC). All doses were converted to Monte Carlo equivalents and subsequent BED Gy10 for dose response analysis. Median age was 69 years (range, 18-93 years). Median Karnofsky performance status (KPS) was 90 (range 25/75% 80-100). 49.2% of patients had prior systemic therapy. Median metastasis volume was 10.58 cc (range ...
The consequences of drug abuse (e.g. overdoses, and violent crime) continues to increase the burd... more The consequences of drug abuse (e.g. overdoses, and violent crime) continues to increase the burden on an already over-burdened health care system. A non-addicting pharmacological agent in combination with psychotherapy may prove a viable alternative to interdiction of supply and incarceration. Anecdotal reports from addict self-help groups suggest that ibogaine may block opiate withdrawal and reduce drug craving for cocaine
Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al], 2015
The purpose of this work is to analyze patterns of care and outcome after stereotactic body radio... more The purpose of this work is to analyze patterns of care and outcome after stereotactic body radiotherapy (SBRT) for centrally located, early-stage, non-small cell lung cancer (NSCLC) and to address the question of potential risk for increased toxicity in this entity. A total of 90 patients with centrally located NSCLC were identified among 613 cases in a database of 13 German and Austrian academic radiotherapy centers. The outcome of centrally located NSCLC was compared to that of cases with peripheral tumor location from the same database. Patients with central tumors most commonly presented with UICC stage IB (50 %), while the majority of peripheral lesions were stage IA (56 %). Average tumor diameters were 3.3 cm (central) and 2.8 cm (peripheral). Staging PET/CT was available for 73 and 74 % of peripheral and central tumors, respectively. Biopsy was performed in 84 % (peripheral) and 88 % (central) of cases. Doses varied significantly between central and peripheral lesions with a...
The Journal of pharmacology and experimental therapeutics, 2001
Ibogaine is a naturally occurring compound with purported antiaddictive properties. When administ... more Ibogaine is a naturally occurring compound with purported antiaddictive properties. When administered to primates, ibogaine is rapidly o-demethylated to form the metabolite 12-hydroxyibogamine (noribogaine). Peak blood levels of noribogaine exceed those of ibogaine, and noribogaine persists in the bloodstream for at least 1 day. Very few studies have systematically evaluated the neurobiological effects of noribogaine in vivo. In the present series of experiments, we compared the effects of i.v. administration of ibogaine and noribogaine (1 and 10 mg/kg) on motor behaviors, stress hormones, and extracellular levels of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of male rats. Ibogaine caused dose-related increases in tremors, whereas noribogaine did not. Both ibogaine and noribogaine produced significant elevations in plasma corticosterone and prolactin, but ibogaine was a more potent stimulator of corticosterone secretion. Neither drug altered extracellular DA levels ...
Drug metabolism and disposition: the biological fate of chemicals, 1998
Ibogaine is a psychoactive alkaloid that possesses potential as an agent to treat opiate and coca... more Ibogaine is a psychoactive alkaloid that possesses potential as an agent to treat opiate and cocaine addiction. The primary metabolite arises via O-demethylation at the 12-position to yield 12-hydroxyibogamine. In this report, evidence is presented that the O-demethylation of ibogaine observed in human hepatic microsomes is catalyzed primarily by the polymorphically expressed cytochrome P-4502D6 (CYP2D6). An enzyme kinetic examination of ibogaine O-demethylase activity in pooled human liver microsomes suggested that two (or more) enzymes are involved in this reaction: one with a low KMapp (1.1 microM) and the other with a high KMapp (>200 microM). The low KMapp activity comprised >95% of total intrinsic clearance. Human liver microsomes from three individual donors demonstrated similar enzyme kinetic parameters (mean KMapp = 0.55 +/- 0.09 microM and 310 +/- 10 microM for low and high KM activities, respectively). However, a fourth human microsome sample that appeared to be a p...
Uploads
Papers by John Lie Pablo