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1.
EBioMedicine ; 93: 104590, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37300931

RESUMO

BACKGROUND: The phase 2b proof-of-concept Antibody Mediated Prevention (AMP) trials showed that VRC01, an anti-HIV-1 broadly neutralising antibody (bnAb), prevented acquisition of HIV-1 sensitive to VRC01. To inform future study design and dosing regimen selection of candidate bnAbs, we investigated the association of VRC01 serum concentration with HIV-1 acquisition using AMP trial data. METHODS: The case-control sample included 107 VRC01 recipients who acquired HIV-1 and 82 VRC01 recipients who remained without HIV-1 during the study. We measured VRC01 serum concentrations with a qualified pharmacokinetic (PK) Binding Antibody Multiplex Assay. We employed nonlinear mixed effects PK modelling to estimate daily-grid VRC01 concentrations. Cox regression models were used to assess the association of VRC01 concentration at exposure and baseline body weight, with the hazard of HIV-1 acquisition and prevention efficacy as a function of VRC01 concentration. We also compared fixed dosing vs. body weight-based dosing via simulations. FINDINGS: Estimated VRC01 concentrations in VRC01 recipients without HIV-1 were higher than those in VRC01 recipients who acquired HIV-1. Body weight was inversely associated with HIV-1 acquisition among both placebo and VRC01 recipients but did not modify the prevention efficacy of VRC01. VRC01 concentration was inversely correlated with HIV-1 acquisition, and positively correlated with prevention efficacy of VRC01. Simulation studies suggest that fixed dosing may be comparable to weight-based dosing in overall predicted prevention efficacy. INTERPRETATION: These findings suggest that bnAb serum concentration may be a useful marker for dosing regimen selection, and operationally efficient fixed dosing regimens could be considered for future trials of HIV-1 bnAbs. FUNDING: Was provided by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) (UM1 AI068614, to the HIV Vaccine Trials Network [HVTN]; UM1 AI068635, to the HVTN Statistical Data and Management Center [SDMC], Fred Hutchinson Cancer Center [FHCC]; 2R37 054165 to the FHCC; UM1 AI068618, to HVTN Laboratory Center, FHCC; UM1 AI068619, to the HPTN Leadership and Operations Center; UM1 AI068613, to the HIV Prevention Trials Network [HPTN] Laboratory Center; UM1 AI068617, to the HPTN SDMC; and P30 AI027757, to the Center for AIDS Research, Duke University (AI P30 AI064518) and University of Washington (P30 AI027757) Centers for AIDS Research; R37AI054165 from NIAID to the FHCC; and OPP1032144 CA-VIMC Bill & Melinda Gates Foundation.


Assuntos
Vacinas contra a AIDS , Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Anticorpos Amplamente Neutralizantes , Anticorpos Neutralizantes , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Soropositividade para HIV/tratamento farmacológico , Anticorpos Anti-HIV
2.
Rev Iberoam Micol ; 38(3): 138-140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33593708

RESUMO

BACKGROUND: Liver abscesses caused by Candida species are mainly found in immunocompromised hosts, associated with conditions (such as neutropenia and mucositis) that facilitate the spreading of microorganisms from the gastrointestinal tract. CASE REPORT: We present the case of a non-immunocompromised 72-year-old woman with a liver abscess caused by Candida haemulonii var. vulnera, in whom potential associated conditions could be polycystic kidney disease and renal replacement therapy. The patient experienced clinical resolution after percutaneous drainage and treatment with caspofungin. CONCLUSIONS: To our knowledge, this is the first case reported in Peru of a liver abscess due to Candida haemulonii var. vulnera, a clinical presentation that has not been described previously. This finding should prompt us to establish active surveillance of causal agents of systemic candidiasis.


Assuntos
Candidíase , Abscesso Hepático , Idoso , Antifúngicos/uso terapêutico , Candida , Candidíase/tratamento farmacológico , Humanos , Abscesso Hepático/etiologia , Peru
4.
Lancet Infect Dis ; 19(3): 253-264, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30732940

RESUMO

BACKGROUND: Doubts exist regarding optimal second-line treatment options for HIV-1-infected patients in resource-limited settings. We assessed safety and efficacy of dolutegravir compared with ritonavir-boosted lopinavir, plus two nucleoside reverse transcriptase inhibitors (NRTIs) in adults in whom previous first-line antiretroviral therapy with a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two NRTIs has failed. METHODS: DAWNING is a phase 3b, open-label, parallel-group, non-inferiority, active-controlled trial done at 58 sites in 13 countries. Eligible adults were aged at least 18 years and, during at least 6 months of treatment with a first-line treatment containing an NNRTI and two NRTIs, had virological failure (confirmed HIV-1 RNA ≥400 copies per mL). Participants were randomly assigned by a central randomisation system to receive oral dolutegravir (50 mg once daily) or ritonavir-boosted lopinavir (800 mg lopinavir plus 200 mg ritonavir once daily or 400 mg plus 100 mg twice daily), plus two investigator-selected NRTIs (at least one fully active based on resistance testing at screening). The primary outcome was the proportion of participants achieving viral suppression (defined as plasma HIV-1 RNA <50 copies per mL) at week 48 using the snapshot algorithm and a non-inferiority margin of -12%. The primary analysis was done in an intention-to-treat-exposed (ITT-E) population of participants who received at least one dose of study medication, according to original group assignment. Safety was analysed in all participants who received at least one dose of study drug, according to which drug was received. The study was registered at ClinicalTrials.gov, number NCT02227238, and viiv-studyregister.com, number 200304. FINDINGS: Between Dec 11, 2014, and June 27, 2016, 968 adults were screened and 627 were randomly assigned to the dolutegravir group (n=312) or the ritonavir-boosted lopinavir group (n=315). Three patients in the ritonavir-boosted lopinavir group did not receive study medication and so 624 were included in the ITT-E population. At week 48, 261 (84%) of 312 participants in the dolutegravir group achieved viral suppression compared with 219 (70%) of 312 in the ritonavir-boosted lopinavir group (adjusted difference 13·8%; 95% CI 7·3-20·3). Non-inferiority was achieved on the basis of the 95% CI of the adjusted treatment difference having a lower bound greater than -12% (prespecified non-inferiority margin). Because the lower bound of the 95% CI is greater than zero (7·3%), superiority of dolutegravir was also concluded (p<0·0001). The safety profile for dolutegravir was favourable compared with that of ritonavir-boosted lopinavir. More grade 2-4 drug-related adverse events occurred with ritonavir-boosted lopinavir than dolutegravir (44 [14%] of 310 with ritonavir-boosted lopinavir vs 11 [4%] of 314 with dolutegravir), mainly driven by gastrointestinal disorders. INTERPRETATION: When administered with two NRTIs, dolutegravir was superior to ritonavir-boosted lopinavir at 48 weeks and can be considered a suitable option for second-line treatment. FUNDING: ViiV Healthcare.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Terapia de Salvação/métodos , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Terapia de Salvação/efeitos adversos , Resposta Viral Sustentada , Resultado do Tratamento , Carga Viral , Adulto Jovem
5.
Open AIDS J ; 12: 126-135, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30450147

RESUMO

BACKGROUND: There is scarcity of data about the prevalence of non-AIDS defining comorbidities among stable HIV-infected patients in Peru. OBJECTIVE: We aimed to describe the most frequent cardiometabolic comorbidities found among ambulatory adults on ARV in Peru. METHODS: A review of records for patients attending regular visits at 5 clinics in Lima-Callao in January-February 2016 is presented. Patients were adults on ARV for >6 months, with no recent AIDS-defining condition. RESULTS: Three hundred and five medical charts were reviewed. Most patients were male (73.1%, n=223) with a mean age of 46.0 years. Mean time from HIV diagnosis was 9.41 yrs. and mean duration of ARV was 7.78 yrs. Most patients were on an NNRTI-based first line regimen (76.4%, n=233), and 12.1% (n=37) were on rescue regimens. Median CD4 count was 614.2 cells/µL and the proportion of patients with viral load <40 c/mL was 90.8% (n=277). Most frequent metabolic diagnoses were dyslipidemia (51.5%, n=157), obesity (11.1%, n=34), and diabetes mellitus (7.2%, n=22). Hypertension was diagnosed in 8.9% (n=27). Other diagnoses of cardiovascular disease were documented in 3.3% (n=10). Pharmacologic treatment was prescribed in 91.3% of patients with diabetes or hypertension, but in only 29.3% of patients with dyslipidemia. CONCLUSION: A high proportion of metabolic comorbidities was found, with dyslipidemia being the most frequent, followed by obesity and diabetes. In contrast, cardiovascular disease was documented less frequently. Medical treatment was started for only a third of dyslipidemia patients. HIV care policies need to consider proper management of chronic comorbidities to optimize long-term outcomes.

6.
Arch Gerontol Geriatr ; 75: 139-145, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29304508

RESUMO

AIM: CKD-EPIcr (Chronic Kidney Disease Epidemiology Collaboration creatinine) and BIS1 (Berlin Initiative Study) are two serum creatinine-based formulae for the estimation of glomerular filtration rate (GFR). However, their comparative accuracy in older people has not been well established. Our aim was to conduct a systematic comparative study of the accuracy of estimation of GFR in older people with these two formulae. METHODS: We conducted a systematic search in Pubmed, EMBASE and Central databases on the validity of the CKD-EPIcr and BIS1 formulae in people aged 60 or more years. The search ranged from 2009 and 2012 for CKD-EPIcr and BIS1, respectively, until May 2017. The validity criterion for comparing the formulae was to have a P30 accuracy level equal to or greater than 80%. RESULTS: Of 1295 identified studies, 16 met our inclusion criteria. Out of 16 studies reporting the accuracy of the CKD-EPIcr formula, only 5 (31.3%) had P30 scores ≥80% (mean P30 was 77.1 ±â€¯7.711 range 55.5-91.7), and out of 9 studies on accuracy using the BIS1 formula, 6 (66.7%) were ≥80% (mean P30 was 83.88 ±â€¯9.37, range 67.0-95.8). CONCLUSION: Our results suggest that for the estimation of the GFR in older people, BIS1 formula may be more accurate than CKD-EPIcr.


Assuntos
Creatinina/sangue , Taxa de Filtração Glomerular , Biomarcadores/sangue , Humanos , Conceitos Matemáticos , Insuficiência Renal Crônica/sangue
7.
Drug Des Devel Ther ; 10: 2379-86, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27528799

RESUMO

There has been greater interest in developing additional antimicrobial agents due to the increasing health care costs and resistance resulting from bacterial pathogens to currently available treatment options. Gram-negative organisms including Enterobacteriaceae and Pseudomonas aeruginosa are some of the most concerning threats due to their resistance mechanisms: extended-spectrum beta-lactamase production and Klebsiella pneumoniae carbapenemase enzymes. Ceftazidime is a third-generation broad-spectrum cephalosporin with activity against P. aeruginosa and avibactam is a novel nonbeta-lactam beta-lactamase inhibitor. Avycaz(®), the trade name for this new combination antibiotic, restores the activity of ceftazidime against some of the previously resistant pathogens. Avycaz was approved in 2015 for the treatment of complicated urinary tract infections, including pyelonephritis, and complicated intra-abdominal infections with the addition of metronidazole in patients with little to no other treatment options. This review article assesses the clinical trials and data that led to the approval of this antibiotic, in addition to its spectrum of activity and limitations.


Assuntos
Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Ceftazidima/uso terapêutico , Infecções Intra-Abdominais/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico , Inibidores de beta-Lactamases/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Compostos Azabicíclicos/administração & dosagem , Compostos Azabicíclicos/farmacologia , Ceftazidima/administração & dosagem , Ceftazidima/farmacologia , Cefalosporinase/metabolismo , Humanos , Infecções Intra-Abdominais/complicações , Infecções Intra-Abdominais/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Infecções Urinárias/complicações , Infecções Urinárias/microbiologia , Inibidores de beta-Lactamases/administração & dosagem , Inibidores de beta-Lactamases/farmacologia
8.
Acta méd. costarric ; 57(4): 190-194, oct.-dic. 2015. tab, ilus
Artigo em Espanhol | LILACS | ID: lil-778041

RESUMO

Objetivo: Valorar los resultados obtenidos con 38 pacientes intervenidos por tumores del timo.Método:se estudió a todos los pacientes intervenidos por tumores del timo durante el periodo de 1996 a 2013 en el Hospital "Dr. Rafael Ángel Calderón Guardia".Resultados:se intervino a 38 pacientes por tumores del timo en los 17 años evaluados, 20 hombres y 18 mujeres con promedio edad de 50 años. En 26 casos se realizó resección, la cual en 19 fue macroscópicamente completa. Se reportó 20 tumores malignos y 18 benignos. De los 20 casos con tumores malignos, a 9 pacientes se les realizó resección, en 6 la resección fue completa y en 3 incompleta, y a 11 solamente biopsia. 16 de los 20 casos con tumores malignos recibieron quimioterapia. De los casos con tumores malignos 15 tenían más de 5 años de establecido el diagnóstico, y de estos 7 se encontraban vivos, lo que corresponde a una sobrevida a 5 años de un 47%. Los timomas representaron un 17% de todos los tumores del mediastino. Los síntomas manifestados por los pacientes se debieron a la compresión causada por el tumor.Conclusiones:el método de detección más útil fue la radiografía de tórax. La vía más utilizada para tomar biopsia fue mediastinotomía. La quimioterapia desempeño un papel importante en la sobrevida, ya que pacientes con resección incompleta, se encontraron vivos hasta 5 años después del diagnóstico. La conducta que mostró ser más efectiva para los timomas malignos fue, reseccióncompleta complementada con quimioterapia.


Aim: To evaluate the results obtained from 38 patients undergoing surgery for tumors of the thymus at the Hospital Calderon Guardia.Method:All patients undergoing surgery for tumors of the thymus during the period 1996-2013 were studied.Results:38 patients underwent surgery for tumors of the thymus in the 17 years evaluated, 20 men and 18 women, with an average age of 50 years. In 26 cases resection was performed, which was macroscopically complete in 19. Of the 38 tumors, 20 were reports as malignant and 18 as benign. Of the 20 cases with malignant tumors, in 9 patients a resection was performed, in 6 resection was complete and in 3 incomplete, and 11 only had a biopsy; 16 of the 20 patients with malignant tumors received chemotherapy. Of the cases with malignant tumors 15 had over 5 years of the diagnosis, and of these 7 were alive, which corresponds to a 5 year survival of 47%. Thymomas accounted for 17% of all mediastinal tumors. The symptoms manifested by patients were due to compression caused by the tumor.Conclusions:The chest radiography was the most useful screening method. The route most used to take biopsy was mediastinotomy. Chemotherapy played an important role in survival as patients with incomplete resection were found alive five years after diagnosis. The treatment shown to be more effective for malignant thymoma was complete resection complemented with chemotherapy.


Assuntos
Humanos , Masculino , Adulto , Feminino , Costa Rica , Tratamento Farmacológico , Neoplasias do Mediastino , Radiografia Torácica , Timoma , Neoplasias do Timo
9.
J Neuropathol Exp Neurol ; 74(9): 934-42, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26230581

RESUMO

The clinical diagnosis and classification of neurodegenerative diseases based on clinical examination or available biomarkers are currently insufficiently accurate. Although histologic examination is considered the gold standard for diagnosis, brain biopsies have been avoided because of the high risk-benefit ratio. However, brain biopsies have previously been performed with a craniotomy and excision of approximately 1 cm of cerebral cortex tissue, and it is possible that needle core brain biopsies would have a lower morbidity and mortality risk. Here, we compared the ability of simulated needle core biopsy versus simulated open biopsy to detect the frontal cortex histopathology associated with common neurodegenerative diseases in the elderly using 144 autopsy-proven cases. Simulated needle core biopsy, as compared with simulated open biopsy, gave close to 90% sensitivity and specificity for identifying graded densities of ß-amyloid and neuritic plaques, neurofibrillary tangles, phosphorylated α-synuclein, and phosphorylated TDP-43 pathology. This study shows that the presence and densities of the most common molecular pathologies may be histopathologically assessed in simulated frontal cortex needle biopsies, with accuracy very close to that obtained by open cortical biopsy. An accurate estimation of the morbidity and mortality risk associated with cortical needle core biopsy will require specifically designed clinical trials in appropriate subjects.


Assuntos
Lobo Frontal/patologia , Doenças Neurodegenerativas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha/normas , Estudos de Viabilidade , Feminino , Humanos , Masculino
10.
Acta méd. costarric ; 56(3): 121-124, jul.-sep. 2014. tab
Artigo em Espanhol | LILACS | ID: lil-715377

RESUMO

Objetivo: determinar la sensibilidad y especificidad de la mediastinoscopia para diagnóstico y estadiaje de enfermedades del tórax. Métodos: se revisó la información general incluida en la base de datos del servicio de Cirugía de Tórax del Hospital Dr. R. A. Calderón Guardia, de 140 pacientes sometidos a mediastinoscopia durante el periodo comprendido entre 1989 y 2013, la cual se complementó con datos específicos obtenidos de los expedientes clínicos...


Assuntos
Humanos , Masculino , Adolescente , Adulto , Feminino , Pessoa de Meia-Idade , Doenças do Mediastino , Mediastinoscopia , Costa Rica
11.
J Alzheimers Dis ; 42(3): 813-21, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24927705

RESUMO

Abnormal neuronal accumulation and modification of TAR DNA binding protein 43 (TDP-43) have recently been discovered to be defining histopathological features of particular subtypes of frontotemporal dementia and amyotrophic lateral sclerosis, and are also common in aging, particularly coexisting with hippocampal sclerosis and Alzheimer's disease pathology. This case report describes a 72 year old Hispanic male with no family history of neurological disease, who presented at age 59 with obsessive behavior, anxiety, agitation, and dysphasia. Positron emission tomography imaging using the amyloid ligand 18F florbetapir (Amyvid) was positive. Postmortem examination revealed frequent diffuse and neuritic amyloid plaques throughout the cerebral cortex, thalamus, and striatum, Braak stage II neurofibrillary degeneration, and frequent frontal and temporal cortex TDP-43-positive neurites with rare nuclear inclusions. The case is unusual and instructive because of the co-existence of frequent cortical and diencephalic amyloid plaques with extensive TDP-43-positive histopathology in the setting of early-onset dementia and because it demonstrates that a positive cortical amyloid imaging signal in a subject with dementia does not necessarily establish that Alzheimer's disease is the sole cause.


Assuntos
Compostos de Anilina , Proteínas de Ligação a DNA/genética , Etilenoglicóis , Degeneração Lobar Frontotemporal/diagnóstico por imagem , Placa Amiloide/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Idoso , Degeneração Lobar Frontotemporal/complicações , Degeneração Lobar Frontotemporal/genética , Humanos , Corpos de Inclusão/metabolismo , Masculino , Placa Amiloide/complicações , Placa Amiloide/genética , Placa Amiloide/patologia , Tomografia Computadorizada por Raios X
12.
Stud Health Technol Inform ; 200: 124-30, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24851975

RESUMO

This article presents the development process of an acquisition and data storage system managing clinical variables through a cloud storage service and a Personal Health Record (PHR) System. First, the paper explains how a Wireless Body Area Network (WBAN) that captures data from two sensors corresponding to arterial pressure and heart rate is designed. Second, this paper illustrates how data collected by the WBAN are transmitted to a cloud storage service. It is worth mentioning that this cloud service allows the data to be stored in a persistent way on an online database system. Finally, the paper describes, how the data stored in the cloud service are sent to the Indivo PHR System, where they are registered and charted for future revision by health professionals. The research demonstrated the feasibility of implementing WBAN networks for the acquisition of clinical data, and particularly for the use of Web technologies and standards to provide interoperability with PHR Systems at technical and syntactic levels.


Assuntos
Computação em Nuvem , Registros Eletrônicos de Saúde/instrumentação , Registros de Saúde Pessoal , Monitorização Ambulatorial/instrumentação , Monitorização Ambulatorial/métodos , Sinais Vitais/fisiologia , Tecnologia sem Fio , Humanos
13.
Diagnóstico (Perú) ; 52(3): 119-122, jul.-sept. 2013. tab
Artigo em Espanhol | LILACS, LIPECS | ID: lil-713283

RESUMO

El uso de antimicrobianos en la práctica médica contemporánea es generalizado y sometido a complejas circunstancias. Siendo difícil un diagnóstico adecuado de las infecciones, la prescripción de antimicrobianos es mayoritariamente empírica, en especial en los pacientes rnás graves. El empleo de estos fármacos representa costos importantes en la atención de salud con un beneficio no siempre claro y con un riesgo de consecuencias negativas adicionalmente, tanto sobre el paciente, como sobre la generación de resistencia a antimicrobianos. En este contexto, tanto administradores, como clínicos y microbiólogos han venido proponiendo diferentes maneras de mejorar el uso de antimicrobianos. Los objetivos de las estrategias planteadas han variado y en esta revisión queremos discutir brevemente los alcances y limitaciones observados. El tema no está cerrado y se seguirá debatiendo cual es la mejor manera de promover un uso adecuado de antimicrobianos.


Assuntos
Humanos , Anti-Infecciosos
14.
Acta méd. costarric ; 55(3): 128-131, jul.-sep. 2013. tab
Artigo em Espanhol | LILACS | ID: lil-700691

RESUMO

Objetivo: revisar e informar la experiencia adquirida con el manejo de tumores de células germinales del mediastino, en el Hospital Calderón Guardia. Metodología: previa autorización acumulada en la base de datos del Servicio de Cirugía de Tórax y los expedientes clínicos de 29 pacientes con tumores de células germinales del mediastino, operados entre 1986 y 2012. Resultados: se encontró mayor frecuencia en hombres jóvenes con una relación por género de 13.5:1, y edad promedio de 26 años. La localización correspondió en 28 casos al mediastino antero superior y 1 al medio. La presentación en 27 casos fue una radiografía de tórax con ensanchamiento del mediastino, uno con derrame pleural y uno con derrame pleural y mediastino ensanchado. Los síntomas más frecuentes fueron: disnea, dolor retrosternal, fiebre, tos, pérdida de peso, síndrome de vena cava superior, hemoptisis y ginecomastía en un varón con coriocarcinoma. La muestra para diagnóstico se obtuvo por mediastinotomía en 14 casos, toracotomía en 8, videotoracoscopía en 4 esternotomía en 1, mediastinoscopía en 1 y broncoscopía en 1. Conclusión: los tumores germinales del mediastino son infrecuentes; la extirpación quirúrgica es el tratamiento de elección para los técnicamente resecables y se acompaña de curación de los benignos. En los malignos, la aparente resección completa no es garantía de curación, por lo que debe considerarse la quimioterapia adyuvante, que demostró ser de gran utilidad, por cuanto varios tumores parcialmente resecados se curaron con quimioterapia, y algunos con aparente resección completa recidivaron...


Assuntos
Humanos , Masculino , Adolescente , Adulto , Feminino , Neoplasias do Mediastino/cirurgia , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/terapia
15.
J Alzheimers Dis ; 34(2): 529-36, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23246918

RESUMO

Abnormal phosphorylation of the microtubule-associated protein tau develops in selected brain regions in normal aging and becomes widespread throughout the brain in Alzheimer's disease (AD). Braak and others have described the distribution of neurofibrillary tangles and deposition of abnormally phosphorylated tau (p-tau) and correlated this with the progressive cognitive dysfunction in AD. However, to date there have been no comprehensive studies examining abnormally phosphorylated tau deposition in the spinal cord as part of normal aging or AD. We investigated, using immunohistochemical methods, the presence of p-tau in the spinal cord of 46 cases with a clinicopathological diagnosis of AD as well as 37 non-demented aged (ND) individuals lacking any defined central nervous system-related clinicopathological diagnosis. We found the cervical cord segments to be the most frequently affected subdivision (96% AD versus 43% ND), followed by thoracic (69% AD versus 37% ND), lumbar (65% AD versus 27% ND), and sacral (53% AD versus 13% ND). The spinal cord was often affected at early-stage brain disease, with p-tau spinal cord immunoreactivity in 40% of subjects at Braak neurofibrillary stage I; however, there were no cases having spinal cord p-tau that did not have p-tau within the brain. As p-tau immunoreactivity is present within the spinal cords of ND as well as AD subjects, it is likely that the phosphorylation of spinal cord tau occurs in the preclinical stage of AD, prior to dementia. The presence of significant spinal cord p-tau-immunoreactive pathology has important implications for both the pathogenesis and clinical manifestations of AD.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Fosforilação/fisiologia , Medula Espinal/química , Proteínas tau/química
17.
J Alzheimers Dis ; 28(4): 869-76, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22112552

RESUMO

Amyloid imaging may revolutionize Alzheimer's disease (AD) research and clinical practice but is critically limited by an inadequate correlation between cerebral cortex amyloid plaques and dementia. Also, amyloid imaging does not indicate the extent of neurofibrillary tangle (NFT) spread throughout the brain. Currently, the presence of dementia as well as a minimal brain load of both plaques and NFTs is required for the diagnosis of AD. Autopsy studies suggest that striatal amyloid plaques may be mainly restricted to subjects in higher Braak NFT stages that meet clinicopathological diagnostic criteria for AD. Striatal plaques, which are readily identified by amyloid imaging, might therefore be used to predict the presence of a higher Braak NFT stage and clinicopathological AD in living subjects. This study determined the sensitivity and specificity of striatal plaques for predicting a higher Braak NFT stage and clinicopathological AD in a postmortem series of 211 elderly subjects. Subjects included 87 clinicopathologically classified as non-demented elderly controls and 124 with AD. A higher striatal plaque density score (moderate or frequent) had 95.8% sensitivity, 75.7% specificity for Braak NFT stage V or VI and 85.6% sensitivity, 86.2% specificity for the presence of dementia and clinicopathological AD (National Institute on Aging - Reagan Institute "intermediate" or "high"). Amyloid imaging of the striatum may be useful as a predictor, in living subjects, of Braak NFT stage and the presence or absence of dementia and clinicopathological AD. Validation of this hypothesis will require autopsy studies of subjects that had amyloid imaging during life.


Assuntos
Doença de Alzheimer/patologia , Amiloide , Corpo Estriado/patologia , Emaranhados Neurofibrilares/patologia , Placa Amiloide/patologia , Idoso , Idoso de 80 Anos ou mais , Amiloide/análise , Feminino , Humanos , Masculino , Valor Preditivo dos Testes
18.
Acta méd. costarric ; 52(4): 240-245, dic. 2010. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-700613

RESUMO

Analizar las características clínicas, indización para realizar la intervención y los resultados de la cirugía de pacientes con deformidades de la pared torácica. Métodos: Con el fin de obtener la informaci¢ón, se analizaron 32 expedientes clínicos que pudieron ser ubicados y la información incluida en la base de datos del servicio de otros 13 pacientes operados en el servicio de cirugía de tórax del Hospital Rafael Angel Calderón Guardia por Pectus Excavatum o Pectus Carinatum, desde enero de 1998 a enero del 2010. Resultados: Se encontraron 29 pacientes operados por Pectus Excavatum y 16 por Pectus Carinatum, de los cuales 37 fueron varones y 8 mujeres. La edad osciló entre 13 y 24 años con un promedio de 16 años. En 28 pacientes la única indicación para la cirugía fue la afección sicológica causada por la deformidad y en 17 se presentó además algún síntoma como disnea con el ejercicio, dolor torácico o palpitaciones. En 26 de los 29 pacientes operados por Pectus Excavatum se utilizó una barra de metal para manetener el esternón reducido en posición normal mientras se consolidaban retirándola a los seis meses y en los últimos tres las reducción se efectuó con una malla de polipropileno que funcionó igual, pero con la ventaja que no requiere reintervención para retirarla. Los resultados se evaluaron en forma subjetiva de acuerdo a la satisfacción manifestada por el paciente y a la nota del médico; encontrando en un caso de Pectus Excavatum recidiva de la...


Assuntos
Humanos , Masculino , Adolescente , Adulto , Feminino , Anormalidades Congênitas , Tórax em Funil/cirurgia , Tórax/fisiopatologia , Tórax/patologia
19.
Rev Inst Med Trop Sao Paulo ; 51(4): 197-201, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19738999

RESUMO

Limited and contradictory information exists regarding the prognosis of HIV/HTLV-I co-infection. Our goal was to estimate the effect of HTLV-I infection on mortality in HIV-infected patients at a HIV reference center in Peru. We studied a retrospective cohort of HIV-infected patients, who were exposed or unexposed to HTLV-I. Exposed patients were Western Blot (WB) positive for both retroviruses. Unexposed patients were WB positive for HIV, and had least one negative EIA for HTLV-I. These were selected among patients who entered our Program immediately before and after each exposed patient, between January 1990 and June 2004. Survival time was considered between the diagnosis of exposure to HTLV-I and death or censoring. Confounding variables were age, gender, baseline HIV clinical stage, baseline CD4+ T cell count, and antiretroviral therapy. We studied 50 exposed, and 100 unexposed patients. Exposed patients had a shorter survival compared to unexposed patients [median survival: 47 months (95% CI: 17-77) vs. 85 months (95% CI: 70-100), unadjusted p = 0.06]. Exposed patients had a higher rate of mortality compared to unexposed patients (HIV/HTLV-I (24/50 [48%]) vs. HIV only (37/100 [37%]), univariable p = 0.2]. HTLV-I exposure was not associated to a higher risk of death in the adjusted analysis: HR: 1.2 (0.4-3.5). AIDS clinical stage and lack of antiretroviral therapy were associated to a higher risk of dying. In conclusions, HTLV-I infection was not associated with a higher risk of death in Peruvian HIV-infected patients. Advanced HIV infection and lack of antiretroviral therapy may explain the excess of mortality in this population.


Assuntos
Infecções por HIV/mortalidade , Infecções por HTLV-I/mortalidade , Terapia Antirretroviral de Alta Atividade , Linfócitos T CD4-Positivos , Estudos de Coortes , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HTLV-I/complicações , Infecções por HTLV-I/transmissão , Humanos , Peru/epidemiologia , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
20.
Rev. Inst. Med. Trop. Säo Paulo ; 51(4): 197-201, July-Aug. 2009. graf, tab
Artigo em Inglês | LILACS | ID: lil-524374

RESUMO

Limited and contradictory information exists regarding the prognosis of HIV/HTLV-I co-infection. Our goal was to estimate the effect of HTLV-I infection on mortality in HIV-infected patients at a HIV reference center in Peru. We studied a retrospective cohort of HIV-infected patients, who were exposed or unexposed to HTLV-I. Exposed patients were Western Blot (WB) positive for both retroviruses. Unexposed patients were WB positive for HIV, and had least one negative EIA for HTLV-I. These were selected among patients who entered our Program immediately before and after each exposed patient, between January 1990 and June 2004. Survival time was considered between the diagnosis of exposure to HTLV-I and death or censoring. Confounding variables were age, gender, baseline HIV clinical stage, baseline CD4+ T cell count, and antiretroviral therapy. We studied 50 exposed, and 100 unexposed patients. Exposed patients had a shorter survival compared to unexposed patients [median survival: 47 months (95 percent CI: 17-77) vs. 85 months (95 percent CI: 70-100), unadjusted p = 0.06]. Exposed patients had a higher rate of mortality compared to unexposed patients (HIV/HTLV-I (24/50 [48 percent]) vs. HIV only (37/100 [37 percent]), univariable p = 0.2]. HTLV-I exposure was not associated to a higher risk of death in the adjusted analysis: HR: 1.2 (0.4-3.5). AIDS clinical stage and lack of antiretroviral therapy were associated to a higher risk of dying. In conclusions, HTLV-I infection was not associated with a higher risk of death in Peruvian HIV-infected patients. Advanced HIV infection and lack of antiretroviral therapy may explain the excess of mortality in this population.


Existe informação limitada e contraditória sobre o prognóstico da co-infecção pelo Vírus da Imunodeficiência Humana Tipo 1 (HIV-1) e Vírus Linfotrópico de Células T Humanas Tipo I (HTLV-I). Nosso objetivo foi estimar o efeito da infecção pelo HTLV-I na mortalidade de pacientes infectados pelo HIV-1 em Centro de Referência de HIV no Peru. Trata-se de uma coorte retrospectiva de pacientes infectados pelo HIV, expostos ou não expostos ao HTLV-I. Os pacientes expostos tiveram resultados positivos no Western Blot (WB) para ambos retrovírus. Os pacientes não expostos tiveram resultados positivos para o HIV-1 e pelo menos um teste de EIA negativo para o HTLV-I. Esses pacientes foram selecionados entre aqueles que entraram no nosso Programa imediatamente antes ou depois de cada paciente exposto, no período de janeiro de 1990 a junho de 2004. O tempo de sobrevida foi considerado entre o diagnóstico da exposição ao HTLV-I e a morte. As variáveis de confusão foram: idade, gênero, estágio clínico basal da infecção pelo HIV-1, contagem basal de células CD4, e terapia anti-retroviral. Estudamos 50 pacientes expostos e 100 não expostos. Os pacientes expostos tiveram menor sobrevida quando comparados aos não expostos [mediana de sobrevida: 47 meses (95 por cento IC: 17-77) versus 85 meses (70-100), p não ajustado < 0.06]. Os pacientes expostos tiveram maior risco de morte quando comparados aos não expostos (HIV-1/HTLV-I (24/50 [48 por cento]) versus HIV-1 só (37/100 [37 por cento]) p univariado = 0.2). A exposição ao HTLV-I não foi associada a maior risco de morte na análise ajustada: HR: 1.2 (0.4-3.5). O estágio clínico da infecção pelo HIV-1 e a ausência de terapia anti-retroviral foram associados a maior risco de morte. Em conclusão, a infecção pelo HTLV-I não foi associada a maior risco de morte em pacientes peruanos infectados pelo HIV-1. A infecção avançada pelo HIV-1 e a falta de terapia anti-retroviral podem explicar o excesso de mortalidade ...


Assuntos
Humanos , Infecções por HIV/mortalidade , Infecções por HTLV-I/mortalidade , Terapia Antirretroviral de Alta Atividade , Estudos de Coortes , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HTLV-I/complicações , Infecções por HTLV-I/transmissão , Peru/epidemiologia , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
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