In this study, we used proton-localized spectroscopy ( super(1)H-MRS) for the acquisition of the neurochemical profile longitudinally in a novel rat model of human wild-type alpha-synuclein ( alpha ...-syn) over-expression. Our goal was to find out if the increased alpha -syn load in this model could be linked to changes in metabolites in the frontal cortex. Animals injected with AAV vectors encoding for human alpha -syn formed the experimental group, whereas green fluorescent protein expressing animals were used as the vector-treated control group and a third group of uninjected animals were used as naive controls. Data were acquired at 2, 4, and 8 month time points. Nineteen metabolites were quantified in the MR spectra using LCModel software. On the basis of 92 spectra, we evaluated any potential gender effect and found that lactate (Lac) levels were lower in males compared to females, while the opposite was observed for ascorbate (Asc). Next, we assessed the effect of age and found increased levels of GABA, Tau, and GPC+PCho. Finally, we analyzed the effect of treatment and found that Lac levels (p = 0.005) were specifically lower in the alpha -syn group compared to the green fluorescent protein and control groups. In addition, Asc levels (p = 0.05) were increased in the vector-injected groups, whereas glucose levels remained unchanged. This study indicates that the metabolic switch between glucose-lactate could be detectable in vivo and might be modulated by Asc. No concomitant changes were found in markers of neuronal integrity (e.g., N-acetylaspartate) consistent with the fact that alpha -syn over-expression in cortical neurons did not result in neurodegeneration in this model. We acquired the neurochemical profile longitudinally in a rat model of human wild-type alpha-synuclein ( alpha -syn) over-expression in cortical neurons. We found that Lactate levels were reduced in the alpha -syn group compared to the control groups and Ascorbate levels were increased in the vector-injected groups. No changes were found in markers of neuronal integrity consistent with the fact that alpha -syn over-expression did not result in frank neurodegeneration. We acquired the neurochemical profile longitudinally in a rat model of human wild-type alpha-synuclein ( alpha -syn) over-expression in cortical neurons. We found that Lactate levels were reduced in the alpha -syn group compared to the control groups and Ascorbate levels were increased in the vector-injected groups. No changes were found in markers of neuronal integrity consistent with the fact that alpha -syn over-expression did not result in frank neurodegeneration.
Boosted protease inhibitor monotherapy may offer antiviral efficacy while reducing drug interactions, costs and toxicity. The aim of this study was to assess the efficacy of darunavir/ritonavir ...(DRV/r) and lopinavir/ritonavir (LPV/r) monotherapy in a real life setting.
A retrospective analysis of all HIV infected patients, who had initiated DRV/r or LPV/r monotherapy, was performed. Patients whose HIV viral load had remained undetectable for at least two consecutive follow-up visits and who had no neurocognitive disorder or hepatitis B co-infection, were included.
Sixty patients were included. The median (IQR) time to follow-up was 66 (33-118) weeks. The proportions (CI95%) of patients with virological failure were 6.3% (1.7- 20.2) and 25.0% (12.7-43.4), respectively, in the DRV/r and LPV/r groups (p= 0.0424). The proportions (CI95%) of patients with therapeutic success were 90.6% (80.5-100) in the DRV/r group and 60.7% (42.6-78.8) in the LPV/r group (p=0.0063). No protease inhibitor mutations were detected. During the follow-up, 6 patients with dyslipidemia normalized their lipid values. The median monthly cost was 410 (IQR 242-416) euros per person lower for the monotherapy than for the combined antiretroviral therapy.
Boosted protease inhibitor monotherapy was effective in a real life setting. This study showed differences in favour of DRV/r as compared with LPV/r in terms of therapeutic success; however prospective studies are needed to confirm these results. Finally, although this study was not specifically designed to detect benefits in terms of costs and lipid profile, it shows evidence of a positive impact of monotherapy in these fields.
In this study, we used proton-localized spectroscopy ((1) H-MRS) for the acquisition of the neurochemical profile longitudinally in a novel rat model of human wild type alpha-synuclein (a-syn) ...overexpression. Our goal was to find out if the increased a-syn load in this model could be linked to changes in metabolites in the frontal cortex. Animals injected with AAV vectors encoding for human a-syn formed the experimental group, whereas green fluorescent protein (GFP) expressing animals were used as the vector-treated control group and a third group of uninjected animals were used as naïve controls. Data was acquired at 2, 4 and 8 month time-points. Nineteen metabolites were quantified in the MR spectra using LCModel software. Based on 92 spectra, we evaluated any potential gender effect and found that Lactate levels were lower in males compared to females, while the opposite was observed for Ascorbate. Next, we assessed the effect of age and found increased levels of GABA, Tau and GPC+PCho. Finally, we analyzed the effect of treatment and found that Lactate levels (p=0.005) were specifically lower in the a-syn group compared to the GFP and control groups. Additionally, Ascorbate levels (p=0.05) were increased in the vector-injected groups, while glucose levels remained unchanged. This study indicates that the metabolic switch between Glucose-Lactate could be detectable in-vivo and might be modulated by Ascorbate. No concomitant changes were found in markers of neuronal integrity (e.g. NAA) consistent with the fact that a-syn overexpression in cortical neurons did not result in neurodegeneration in this model. This article is protected by copyright. All rights reserved.
To determine the number of patients with chemotherapy-induced anemia receiving an erythropoiesis-stimulating agent (ESA) in whom iron studies were completed and iron supplementation was provided and ...to document the response rate of ESA therapy without parenteral iron at our medical center.
Retrospective chart review.
Urban (Chicago) academic medical center between January 2004 and December 2005.
Ambulatory patients with a nonmyeloid malignancy receiving chemotherapy during a 2-year period in whom hemoglobin (Hb) was less than 11 grams/dL or ESA therapy was documented.
Review of medical records.
Number of patients reaching target Hb, time to reach target Hb, number of patients receiving a transfusion, number of patients with iron studies, and number of patients receiving iron supplementation.
A total of 174 medical records were reviewed, and 50 patients met study criteria. Of these, 38 patients were treated with darbepoetin alfa, 11 patients were treated with epoetin alfa, and 1 patient was not treated with either agent. 20 patients achieved the target Hb level of 12 grams/dL within a median of 7 weeks (range 1-24 weeks). Only five patients treated with an ESA received iron supplementation, one responder and four nonresponders. Iron indices were measured in 20 patients (40%); 14 patients were candidates for iron therapy based on transferrin saturation, and 3 of these 14 patients received oral iron supplementation. Six responders and six nonresponders received a transfusion (25%).
The overall response rate and time to Hb response were consistent with previous reports. Iron indices were not commonly measured before ESA therapy was started, and only a few patients were provided oral iron supplementation at our medical center.
Background. The Centers for Medicare and Medicaid Services (CMS) issued a national coverage determination (NCD) in July 2007, which imposed restrictions on the reimbursement of ESAs for Medicare and ...Medicaid beneficiaries. Since a majority of our patients are Medicare or Medicaid beneficiaries, we changed our clinical practice regarding the use of erythropoiesis stimulating agents (ESAs) to coincide with the NCD’s reimbursement restriction.
Objective. To evaluate the number of transfusions in patients diagnosed with chemotherapy-induced anemia (CIA) receiving ESAs before and after the clinical practice was changed at the University of Illinois Medical Center (UIMC).
Methods. The medical records of all adult patients diagnosed with a nonmyeloid malignancy and CIA who received an ESA between July 2006 and June 2008 at the UIMC were evaluated. The patients were divided into two groups: patients in receipt of ESAs BEFORE (group 1) and AFTER (group 2). The number of transfusions, the response rates to chemotherapy and ESAs therapy, and overall survival were compared.
Results. Medical records for 110 patients were reviewed. More transfusions were given to patients AFTER we implemented the change in clinical practice (BEFORE 18 transfusions vs. AFTER 52 transfusions, p = 0.004). More patients responded to ESA therapy AFTER we implemented the change (67% vs. 83%, p = NS). The treatment response to chemotherapy and overall survival were similar between the two groups.
Conclusion. The primary goal of reducing the number of transfusions in patients with CIA by administering ESAs cannot be met when clinical practice coincides with the NCD.
Orientador: Gabriela Castellano
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Fisica Gleb Wataghin.
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Previous issue date: 2008
Resumo: Este trabalho visou o estudo e validação de técnicas de pre-processamento e quantificação de dados provenientes da técnica de Espectroscopia por Ressonância Magnética (MRS, do inglês Magnetic Resonance Spectroscopy), obtidos do cérebro humano in vivo, para a extração de informação que fosse clinicamente relevante para o estudo e diagnostico de tumores cerebrais. Para isso, foi feito o estudo da técnica com base na literatura, incluindo a revisão dos aspectos físicos envolvidos, estudando os métodos computacionais utilizados para o pre-processamento e quantificação dos dados, e os aspectos bioquímicos dos metabólicos de interesse presentes no cérebro humano, passiveis de serem quantificados através da técnica. Especificamente, foi estudado um método de quantificação de dados de MRS, o método. AMARES (Advanced Method for Accurate, Robust and Efficient Spectral fitting of MRS data), aplicado na quantificação de dados de MRS adquiridos de sujeitos controles e pacientes portadores de tumores cerebrais, provenientes de uma base de dados do Laboratório de Neuroimagem (LNI - Hospital das Clinicas - UNICAMP). Isso foi feito utilizando o software de domínio público jMRUI (http://sermn02.uab.es/mrui/)1, que possui o método AMARES já implementado. Estes resultados foram comparados com resultados provenientes de uma quantificação manual desses mesmos dados, realizada previamente como parte do projeto de doutorado da Dra. Andréia Vasconcellos (atual docente do Depto. de Radiologia da FCM/UNICAMP)2. Foi verificada a concordância entre os dois métodos de quantificação, e também a viabilidade de usar os resultados da quantificação com o método automático para alem de diferenciar entre os grupos de pacientes e controles, realizar a separação dos Pacientes com tumores em diferentes grupos. Obteve-se que os resultados obtidos com o método automático foram mais precisos e consistentes que os obtidos com o método manual, e permitiram uma melhor classificação dos tipos de tumores. Adicionalmente, foram incluídos neste trabalho os resultados do estudo de perfis metabólicos ex vivo em tumores cerebrais pediátricos através da técnica HR-MAS (do inglês High Resolution Magic Angle Spinning). Este estudo adicional foi realizado no Laboratório de Imagem Molecular da Faculdade de Medicina da Universidade de Valencia (Espanha) através do Programa Santander de Mobilidade Internacional e financiado através de uma bolsa do Banco Santander-Banespa.
Abstract: The aim of this work was to study and validate techniques for pre-processing and quantificating Magnetic Resonance Spectroscopy data, obtained in vivo from the human brain, in order to get information clinically useful for the study and diagnosis of brain tumors. Therefore, a literature-based study of the technique was made, including a review of the Physics concepts involved, the data acquisition process in the scanner and the computational methods used to pre-process and quantificate the spectral data, as well as the biochemical aspects of the metabolites of interest in the human brain that can be detected by this technique. Special attention was given to the AMARES (Advanced Method for Accurate, Robust and Efficient Spectral fitting of MRS data) method for MRS data quantification, which was studied and applied to the quantification of data from control subjects and patients with brain tumors. The data came from a database of the Neuroimaging Laboratory (LNI - Hospital das Clinicas - UNICAMP). The quantification with AMARES was made through the jMRUI software (http://sermn02.uab.es/mrui/) 1, a public domain software for processing and quantification of MRS data. These results were compared to the results obtained with a manual quantification of the same data, previously done as part of the PhD thesis work of Dr. Andreia Vasconcellos (lecturer from the Radiology Department of the School of Medicine, UNICAMP) 2. The agreement between the results from both quantification methods was verified, as well as the feasibility of using the automatic quantification results to differentiate among tumor types, besides differentiating between patients and controls. Results obtained by the automatic method were more accurate and consistent than those obtained by the manual method allowing a better classification. Additionally, in this work were included the results of the study of ex vivo and in vivo metabolic profiling in pediatric brain tumors using the HR-MAS (High Resolution Magic Angle Spinning) technique. This study was carried out in the Molecular Imaging Laboratory, School of Medicine at the University of Val¿encia (Spain), within the Santander-Banespa Bank International Exchange Program.
Mestrado
Física
Mestre em Física
During JADPRO Live 2023, Sandra Cuellar, PharmD, BCOP, FHOPA, FASHP, discussed investigational therapeutic agents in the drug development pipeline. Dr. Cuellar highlighted new drug classes, novel ...mechanisms of action, and safety profiles that advanced practitioners should be aware of.
We investigated multivoxel proton magnetic resonance spectroscopy (
H-MRS) biometrics for preoperative differentiation and prognosis of patients with brain metastases (MET), low-grade glioma (LGG) ...and high-grade glioma (HGG). In total, 33 patients (HGG, 14; LGG, 9; and 10 MET) were included.
H-MRS imaging (MRSI) data were assessed and neurochemical profiles for metabolites N-acetyl aspartate (NAA) + NAAG(NAA), Cr + PCr(total creatine, tCr), Glu + Gln(Glx), lactate (Lac), myo-inositol(Ins), GPC + PCho(total choline, tCho), and total lipids, and macromolecule (tMM) signals were estimated. Metabolites were reported as absolute concentrations or ratios to tCho or tCr levels. Voxels of interest in an MRSI matrix were labeled according to tissue. Logistic regression, receiver operating characteristic, and Kaplan-Meier survival analysis was performed. Across HGG, LGG, and MET, average Ins/tCho was shown to be prognostic for overall survival (OS): low values (≤1.29) in affected hemisphere predicting worse OS than high values (>1.29), (log rank < 0.007). Lip/tCho and Ins/tCho combined showed 100% sensitivity and specificity for both HGG/LGG (
< .001) and LGG/MET (
< .001) measured in nonenhancing/contrast-enhancing lesional tissue. Combining tCr/tCho in perilesional edema with tCho/tCr and NAA/tCho from ipsilateral normal- appearing tissue yielded 100% sensitivity and 81.8% specificity (
< .002) for HGG/MET. Best single biomarker: Ins/tCho for HGG/LGG and total lipid/tCho for LGG/MET showed 100% sensitivity and 75% and 100% specificity, respectively. HGG/MET; NAA/tCho showed 75% sensitivity and 84.6% specificity. Multivoxel 1H-MRSI provides prognostic information for OS for HGG/LGG/MET and a multibiometric approach for differentiation may equal or outperform single biometrics.
Locally advanced tumors in the olfactory area commonly have central nervous system (CNS) involvement and are often incurable.
We report the treatment of a 25-year-old male patient who presented with ...a large, neuroendocrine tumor arising from the ethmoid complex. This locally invasive lesion extended beyond the orbits and into the anterior cranial fossa with associated intracranial involvement. An endoscopic nasal biopsy demonstrated a poorly differentiated neuroendocrine tumor. The patient was treated with 4 cycles of combination induction chemotherapy with irinotecan and cisplatin followed by radiation therapy with concurrent weekly cisplatin. He had a complete response to this therapy confirmed with biopsies that demonstrated no residual disease at 8 weeks after chemoradiotherapy. He remained disease free one and a half years following surgery.
To our knowledge, this combination treatment approach has not been reported in the literature.
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