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1.
Neurotrauma Rep ; 5(1): 574-583, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39036427

RESUMO

Early evidence-based medical interventions to improve patient outcomes after traumatic brain injury (TBI) are lacking. In patients admitted to the ICU after TBI, optimization of nutrition is an emerging field of interest. Specialized enteral nutrition (EN) formulas that include immunonutrition containing omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been developed and are used for their proposed anti-inflammatory and proimmune properties; however, their use has not been rigorously studied in human TBI populations. A single-center, retrospective, descriptive observational study was conducted at the LAC + USC Medical Center. Patients with severe TBI (sTBI, Glasgow Coma Scale score ≤ 8) who remained in the ICU for ≥2 weeks and received EN were identified between 2017 and 2022 using the institutional trauma registry. Those who received immunonutrition formulas containing n-3 PUFAs were compared with those who received standard, polymeric EN with regard to baseline characteristics, clinical markers of inflammation and immune function, and short-term clinical outcomes. A total of 151 patients with sTBI were analyzed. Those who received immunonutrition with n-3 PUFA supplementation were more likely to be male, younger, Hispanic/Latinx, and have polytrauma needing non-central nervous system surgery. No differences in clinical markers of inflammation or infection rate were found. In multivariate regression analysis, immunonutrition was associated with reduced hospital length of stay (LOS). ICU LOS was also reduced in the subgroup of patients with polytrauma and TBI. This study identifies important differences in patient characteristics and outcomes associated with the EN formula prescribed. Study results can directly inform a prospective pragmatic study of immunonutrition with n-3 PUFA supplementation aimed to confirm the biomechanistic and clinical benefits of the intervention.

2.
Res Sq ; 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37986931

RESUMO

Background: Early evidence-based medical interventions to improve patient outcomes after traumatic brain injury (TBI) are lacking. In patients admitted to the ICU after TBI, optimization of nutrition is an emerging field of interest. Specialized enteral nutrition (EN) formulas that include immunonutrition containing omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been developed and are used for their proposed anti-inflammatory and pro-immune properties; however, their use has not been rigorously studied in human TBI populations. Methods: A single-center, retrospective, descriptive observational study was conducted at LAC + USC Medical Center. Patients with severe TBI (sTBI, Glasgow Coma Scale score ≤ 8) who remained in the ICU for ≥ 2 weeks and received EN were identified between 2017 and 2022 using the institutional trauma registry. Those who received immunonutrition formulas containing n-3 PUFAs were compared to those who received standard, polymeric EN in regard to baseline characteristics, clinical markers of inflammation and immune function, and short-term clinical outcomes. Results: A total of 151 patients with sTBI were analyzed. Those who received immunonutrition with n-3 PUFA supplementation were more likely to be male, younger, Hispanic/Latinx, and have polytrauma needing non-central nervous system surgery. No differences in clinical markers of inflammation or infection rate were found. In multivariate regression analysis, immunonutrition was associated with reduced hospital length of stay (LOS). ICU LOS was also reduced in the subgroup of patients with polytrauma and TBI. Conclusion: This study identifies important differences in patient characteristics and outcomes associated with the EN formula prescribed. Study results can directly inform a prospective pragmatic study of immunonutrition with n-3 PUFA supplementation aimed to confirm the biomechanistic and clinical benefits of the intervention.

3.
Clin Transl Oncol ; 25(12): 3519-3526, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37329429

RESUMO

BACKGROUND: Soft tissue sarcomas (STSs) are an uncommon and heterogeneous group of tumours. Several drugs and combinations have been used in clinical practice as second-line (2L) and third-line (3L) treatment. The growth modulation index (GMI) has previously been used as an exploratory efficacy endpoint of drug activity and represents an intra-patient comparison. METHODS: We performed a real-world retrospective study including all patients with advanced STS who had received at least 2 different lines of treatment for advanced disease between 2010 and 2020 at a single institution. The objective was to study the efficacy of both 2L and 3L treatments, analysing the time to progression (TTP) and the GMI (defined as the ratio of TTP between 2 consecutive lines of therapy). RESULTS: Eighty-one patients were included. The median TTP after 2L and 3L treatment was 3.16 and 3.06 months, and the median GMI was 0.81 and 0.74, respectively. The regimens most frequently used in both treatments were trabectedin, gemcitabine-dacarbazine, gemcitabine-docetaxel, pazopanib and ifosfamide. The median TTP by each of these regimens was 2.80, 2.23, 2.83, 4.10, and 5.00 months, and the median GMI was 0.78, 0.73, 0.67, 1.08, and 0.94, respectively. In terms of histotype, we highlight the activity (GMI > 1.33) of gemcitabine-dacarbazine in undifferentiated pleomorphic sarcoma (UPS) and in leiomyosarcoma, pazopanib in UPS, and ifosfamide in synovial sarcoma. CONCLUSIONS: In our cohort, regimens commonly used after first-line STS treatment showed only slight differences in efficacy, although we found significant activity of specific regimens by histotype.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Ifosfamida/uso terapêutico , Estudos Retrospectivos , Desoxicitidina/uso terapêutico , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Gencitabina , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/patologia , Dacarbazina/uso terapêutico
4.
Bioorg Chem ; 133: 106410, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36822000

RESUMO

Most of the currently available cytotoxic agents for tackling cancer are devoid of selectivity, thus causing severe side-effects. This situation stimulated us to develop new antiproliferative agents with enhanced affinity towards tumour cells. We focused our attention on novel chalcogen-containing compounds (thiosemicarbazones, disulfides, selenoureas, thio- and selenocyanates), and particularly on selenium derivatives, as it has been documented that this kind of compounds might act as prodrugs releasing selenium-based reactive species on tumour cells. Particularly interesting in terms of potency and selectivity was a pharmacophore comprised by a selenocyanato-alkyl fragment connected to a p-phenylenediamine residue, where the nature of the second amino moiety (free, Boc-protected, enamine-protected) provided a wide variety of antiproliferative activities, ranging from the low micromolar to the nanomolar values. The optimized structure was in turn conjugated through a peptide linkage with biotin (vitamin B7), a cellular growth promoter, whose receptor is overexpressed in numerous cancer cells; the purpose was to develop a selective vector towards malignant cells. Such biotinylated derivative behaved as a very strong antiproliferative agent, achieving GI50 values in the low nM range for most of the tested cancer cells; moreover, it was featured with an outstanding selectivity, with GI50 > 100 µM against human fibroblasts. Mechanistic studies on the mode of inhibition of the biotinylated selenocyanate revealed (Annexin-V assay) a remarkable increase in the number of apoptotic cells compared to the control experiment; moreover, depolarization of the mitochondrial membrane was detected by flow cytometry analysis, and with fluorescent microscopy, what supports the apoptotic cell death. Prior to the apoptotic events, cytostatic effects were observed against SW1573 cells using label-free cell-living imaging; therefore, tumour cell division was prevented. Multidrug resistant cell lines exhibited a reduced sensitivity towards the biotinylated selenocyanate, probably due to its P-gp-mediated efflux. Remarkably, antiproliferative levels could be restored by co-administration with tariquidar, a P-gp inhibitor; this approach can, therefore, overcome multidrug resistance mediated by the P-gp efflux system.


Assuntos
Antineoplásicos , Citostáticos , Selênio , Humanos , Citostáticos/farmacologia , Linhagem Celular Tumoral , Selênio/farmacologia , Cianatos/farmacologia , Apoptose , Proliferação de Células , Antineoplásicos/farmacologia , Antineoplásicos/química , Relação Estrutura-Atividade
5.
Clin Genitourin Cancer ; 20(4): 363-370, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35317987

RESUMO

INTRODUCTION: Docetaxel 75 mg/m2 every 3 weeks is the standard schedule for metastatic prostate cancer (mPC). Alternative dosing of 50 mg/m2 every 2 weeks may be an option for frail patients. Our aim is to define which factors influence the choice of schedule and to compare the outcomes of both schedules in daily clinical practice. PATIENTS AND METHODS: We retrospectively included patients with mPC treated with docetaxel in our institution. We compared data from patients treated with 3-weekly, 75 mg/m2 docetaxel or 2-weekly, 50 mg/m2 docetaxel, including basal characteristics, predefined prognostic factors, treatment received, toxicity and survival data. RESULTS: We included 200 patients, 86% of whom presented castration resistant mPC. A total of 158 patients (79%) were treated with 3-weekly scheme. Compared with these patients, patients treated with 2-weekly scheme were significantly older, had higher Eastern Cooperative Oncology Group performance status (ECOG PS) and Charlson Comorbidity Index, presented more visceral metastases and needed opioid treatment more frequently. Patients treated with 2-weekly scheme presented shorter median overall survival; however, these differences were not shown after multivariate analysis with significant prognostic factors. Patients treated with 2-weekly scheme had more treatment delays and suspensions, but less clinically impairing toxicities such as febrile neutropenia, neuropathy and diarrhea; toxic deaths were 5 in the 3-weekly group while none in the 2-weekly group. CONCLUSION: Compared to docetaxel 75 mg/m2 every 3 weeks, dosing of 50 mg/m2 every 2 weeks may be an alternative for older, frailer and more comorbid patients. Two-weekly dosing may be used more frequently in selected patients.


Assuntos
Neoplasias da Próstata , Taxoides , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/uso terapêutico , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/etiologia , Estudos Retrospectivos , Taxoides/uso terapêutico
6.
Rev. latinoam. cienc. soc. niñez juv ; 17(2): 240-261, jul.-dic. 2019. graf
Artigo em Espanhol | LILACS | ID: biblio-1043051

RESUMO

Resumen (analítico) Analizamos los factores que promueven la incursión de menores de edad a mercados laborales ilícitos en la frontera norte de México. Se analiza el caso de los niños, niñas y adolescentes de circuito. Llevamos a cabo una revisión bibliográfica, hemerográfica, así como desarrollamos y aplicamos indicadores de desarrollo social en una de las regiones de mayor incidencia del fenómeno y realizamos entrevistas a actores clave en la atención institucional a esta población. Concluimos que este fenómeno tiene un origen multifactorial, pero con un trasfondo geográfico y de deficiencias en desarrollo social con una visión incluyente de la niñez y la adolescencia.


Abstract (analytical) In this study the authors explore the factors that promote the involvement of children and adolescences in illicit labor markets in Mexico's northern border region. The study analyses cases from the population known as circuit children and adolescents. The research includes bibliographic, hemerographic, and statistical analyses, as well as the application of social development indicators in one of the regions that has the highest concentration of cases. The study also included interviews with key informants who provide institutional assistance to this population. The authors conclude that there are multiple factors that contribute to the insertion of minors in illicit labor markets. These can be traced to geographic conditions and a lack of social development that has an inclusive vision for children and adolescents.


Resumo (analítico) Este artigo analisa a relação entre as condições de desenvolvimento social e a incursão de menores de idade em mercados de trabalho ilícitos na fronteira norte do México. Analisa-se o caso de meninos, meninas e adolescentes de circuito. Realizou-se uma revisão bibliográfica, hemerográfica, desenvolveram-se e aplicaram-se indicadores de desenvolvimento social em uma das regiões com maior incidência do fenômeno, e realizaram-se entrevistas com atores-chave no atendimento institucional dessa população. Concluiu-se que esse fenômeno tem origem geográfica e multifatorial, mas com um pano de fundo de deficiências no desenvolvimento social com visão inclusiva da infância e adolescência.


Assuntos
Humanos , Mudança Social , Adolescente , Emigração e Imigração
7.
Eur J Med Chem ; 181: 111550, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31376562

RESUMO

Concerned by the devastating effects of Alzheimer's disease, and the lack of effective drugs, we have carried out the design of a series of tacrine-phenolic heterodimers in order to tackle the multifactorial nature of the disease. Hybridization of both pharmacophores involved the modification of the nature (imino, amino, ether) and the length of the tether, together with the type (hydroxy, methoxy, benzyloxy), number and position of the substituents on the aromatic residue. Title compounds were found to be strong and selective inhibitors of human BuChE (from low nanomolar to subnanomolar range), an enzyme that becomes crucial in the more advanced stages of the disease. The lead compound, bearing an ether-type tether, had an IC50 value of 0.52 nM against human BuChE, and a selectivity index of 323, with an 85-fold increase of activity compared to parent tacrine; key interactions were analysed using molecular modelling. Moreover, it also inhibited the self-aggregation of Aß42, lacking neurotoxicity up to 5 µM concentration, and showed neuroprotective activity in primary rat neurons in a serum and K+ deprivation model, widely employed for reproducing neuronal injury and senescence. Moreover, low hepatoxicity effects and complete stability under physiological conditions were found for that compound. So, overall, our lead compound can be considered as a promising multitarget-directed ligand against Alzheimer's disease, and a good candidate for developing new drugs.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antineoplásicos/farmacologia , Inibidores da Colinesterase/farmacologia , Fármacos Neuroprotetores/farmacologia , Fenóis/farmacologia , Tacrina/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Butirilcolinesterase/metabolismo , Proliferação de Células/efeitos dos fármacos , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Dimerização , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Electrophorus , Cavalos , Humanos , Ligantes , Modelos Moleculares , Estrutura Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Fenóis/síntese química , Fenóis/química , Relação Estrutura-Atividade , Tacrina/síntese química , Tacrina/química , Células Tumorais Cultivadas
8.
J Immunol Res ; 2019: 2974753, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019980

RESUMO

BACKGROUND AND AIM: The presumed role of the inhibitory receptor LAIR-1 (CD305) in the inflammatory response suggests that it might contribute to the pathophysiology of chronic inflammatory diseases such as liver cirrhosis. We studied the LAIR-1 expression on liver macrophages and blood monocytes related to the progression of liver cirrhosis. METHODS: The expression of LAIR-1 was analyzed by immunohistochemistry, flow cytometry, and Western blot. RESULTS: We found a decreased number of macrophages expressing LAIR-1 in cirrhotic liver that could be due to a high presence of collagen, ligand of LAIR-1, in the fibrotic tissue which could downregulate its expression or interfere with the immunostaining. The expression of LAIR-1 decreased after cell differentiation, and the total content, but not the cell surface expression, increased after activation in the HL-60 human macrophage in vitro model. Blood monocytes exhibited higher LAIR-1 expression levels in cirrhotic patients, which were evident even in early clinical stages in all monocyte subsets, and greater in the "intermediate" inflammatory monocyte subpopulation. The in vitro activation of human blood monocytes did not increase its expression on the cell surface suggesting that the in vivo increase of LAIR-1 must be the result of a specific combination of stimuli present in cirrhotic patients. This represents an exclusive feature of liver cirrhosis, since blood monocytes from other chronic inflammatory pathologies showed similar or lower LAIR-1 levels compared with those of healthy controls. CONCLUSIONS: These results may indicate that monocyte LAIR-1 expression is a new biomarker to early detect liver damage caused by chronic inflammation in liver cirrhosis.


Assuntos
Progressão da Doença , Cirrose Hepática/diagnóstico , Monócitos/imunologia , Receptores Imunológicos/genética , Adulto , Idoso , Biomarcadores/análise , Diferenciação Celular , Feminino , Citometria de Fluxo , Células HL-60 , Humanos , Inflamação/diagnóstico , Inflamação/etiologia , Lipopolissacarídeos , Fígado/imunologia , Cirrose Hepática/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade
9.
Ann Transl Med ; 7(22): 691, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31930092

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors. Preoperative portal vein embolization (PVE) is currently the most accepted treatment before major hepatic resection for HCC in patients with liver fibrosis or cirrhosis and associated insufficient future liver remnant (FLR). In the last decade, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique has been described to obtain an increase of volume regarding PVE and a decrease of drop out. The initial excessive morbidity and mortality of this technique have decreased drastically due to a better selection of patients, the learning curve and the use of less aggressive variations of the original technique in the first stage. For both techniques a complete preoperative assessment of the FLR is the most important issue and only patients with and adequate FLR should be resected. ALPPS could be a feasible technique in very selected patients with HCC and cirrhosis. As long as it is performed in an experienced center could be used as a first choice technique versus PVE or could be used as a rescue technique in case of PVE failure.

10.
Eur J Med Chem ; 138: 761-773, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-28728108

RESUMO

We have designed a series of tacrine-based homo- and heterodimers that incorporate an antioxidant tether (selenoureido, chalcogenide) as new dual compounds: for the treatment of Alzheimer's disease and as antiproliferative agents. Symmetrical homodimers bearing a dichalcogenide or selenide-based tether, the best compounds in the series, were found to be strong and highly selective electric eel AChE inhibitors, with inhibition constants within the low nanomolar range. This high inhibitory activity was confirmed on recombinant human AChE for the most interesting derivatives. The three most promising homodimers also showed a good inhibitory activity towards amyloid-ß self aggregation. The symmetric disulfide derivative bis[5-(1',2',3',4'-tetrahydroacridin-9'-ylamino)pentyl]disulfide (19) showed the best multipotent profile and was not neurotoxic on immortalized mouse cortical neurons even at 50 µM concentration. These results represent an improvement in activity and selectivity compared to parent tacrine, the first marketed drug against Alzheimer's disease. Title compounds also exhibited excellent in vitro antiproliferative activities against a panel of 6 human tumor cell lines, with GI50 values within the submicromolar range for the most potent derivatives (0.12-0.95 µM); such values represent a spectacular increase compared to currently-used chemotherapeutic agents, such as 5-FU (up to 306-fold) and cisplatin (up to 162-fold). Cell cycle experiments indicated the accumulation of cells in the G1 phase of the cycle, a different mechanism than the reported for cisplatin. The breast cancer cell lines turned out to be the most sensitive one of the panel tested.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Calcogênios/farmacologia , Inibidores da Colinesterase/farmacologia , Compostos Organosselênicos/farmacologia , Tacrina/farmacologia , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Calcogênios/química , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Dimerização , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Estrutura Molecular , Compostos Organosselênicos/química , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/metabolismo , Agregados Proteicos/efeitos dos fármacos , Relação Estrutura-Atividade , Tacrina/química
11.
Int J Occup Environ Health ; 22(3): 249-258, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27670588

RESUMO

BACKGROUND: Occupational exposure to manufactured nanomaterials (MNMs) and its potential health impacts are of scientific and practical interest, as previous epidemiological studies associate exposure to nanoparticles with health effects, including increased morbidity of the respiratory and the circulatory system. OBJECTIVES: To estimate the occupational exposure and effective internal doses in a real production facility of TiO2 MNMs during hypothetical scenarios of accidental release. METHODS: Commercial software for geometry and mesh generation, as well as fluid flow and particle dispersion calculation, were used to estimate occupational exposure to MNMs. The results were introduced to in-house software to calculate internal doses in the human respiratory tract by inhalation. RESULTS: Depending on the accidental scenario, different areas of the production facility were affected by the released MNMs, with a higher dose exposure among individuals closer to the particles source. CONCLUSIONS: Granted that the study of the accidental release of particles can only be performed by chance, this numerical approach provides valuable information regarding occupational exposure and contributes to better protection of personnel. The methodology can be used to identify occupational settings where the exposure to MNMs would be high during accidents, providing insight to health and safety officials.


Assuntos
Poluentes Ocupacionais do Ar/análise , Vazamento de Resíduos Químicos , Exposição por Inalação/análise , Modelos Teóricos , Nanoestruturas/análise , Exposição Ocupacional/análise , Monitoramento Ambiental , Humanos , Pulmão/metabolismo
12.
Immunobiology ; 221(5): 595-603, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26850323

RESUMO

The mayor goal still outstanding into the solid organ transplantation field involves the search of surrogate biomarkers able to predict several clinical events, such as acute rejection (AR) or opportunistic infection. In the present multicenter study, a series of interesting surface antigens with important activator or inhibitory immune functions on cultured peripheral T cells were monitored in liver transplant recipients drawn at baseline and up to one year after transplantation. Sixty-four patients were included in the multicenter study during 3 years. Pre- and post-transplantation surface antigens levels displayed significant differences between AR and non acute rejection (NAR) groups, and also this differential expression was used to construct a risk predictive model based on a composite panel of outcome biomarkers (CD38, CD69, CD95 and CD154). The model was able to stratify these patients at high risk of AR. These preliminary results could provide basic information to improve the immunosuppressive treatment and it might better help to predict AR episodes.


Assuntos
Aloenxertos/imunologia , Antígenos CD/metabolismo , Rejeição de Enxerto/imunologia , Transplante de Fígado , Linfócitos T/imunologia , Linfócitos T/metabolismo , ADP-Ribosil Ciclase 1 , Adulto , Idoso , Aloenxertos/metabolismo , Antígenos CD/genética , Antígenos de Diferenciação de Linfócitos T , Biomarcadores , Ligante de CD40 , Células Cultivadas , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/metabolismo , Humanos , Imunofenotipagem , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Lectinas Tipo C , Transplante de Fígado/efeitos adversos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Prognóstico , Curva ROC , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Adulto Jovem , Receptor fas
13.
Transplantation ; 95(8): 1037-44, 2013 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-23478359

RESUMO

BACKGROUND: Killer immunoglobulin-like receptors (KIRs) bind human leukocyte antigen (HLA) class-I (HLA-I) ligands and regulate functions of natural killer cells and subsets of T cells. KIR/HLA-I interactions allow predicting natural killer cell alloreactivity in hematopoietic stem cell transplantation and in HLA-compatible kidney transplants, but its meaning in liver transplantation remains controversial. METHODS: KIR and HLA genotypes were studied in 402 liver transplants, using sequence-specific oligonucleotides and primer methods. Recipients and donor KIRs, HLA-C genotypes, KIR gene mismatches (MMs) between recipient-donor pairs, and KIR/HLA-ligand combinations were analyzed in overall transplantations, in the acute rejection (AR; n=110) and non-AR (n=292) groups. RESULTS: KIR gene MMs between recipients and donors, mainly in activating KIRs, and KIR2DL3 and KIR2DS1 of recipients in the presence of donor C2 ligands, significantly enhanced early AR rate (P<0.05), with KIR2DL3 and KIR2DS1 exhibiting a synergic effect in dependence of the donor C2 ligand number (χ2=7.662, P=0.022). KIR2DL3, KIR2DS1, and also KIR2DS4 significantly influenced short-term graft survival, with a benefit for transplantations combining KIR2DL3 recipients and donors having C1 ligands (log rank, P<0.019 at 1 year; hazards ratio [HR], 0.321; 95% confidence interval [CI], 0.107-0.962; P=0.042), whereas KIR2DS1 and KIR2DS4 recipients combined with donors lacking C1 ligands (C2/C2) exhibited a worse graft survival (log rank, P=0.035 at 6 months; HR, 7.713; 95% CI, 2.156-27.369; P=0.002 for KIR2DS1; and log rank, P=0.006 at 1 year; HR, 3.794; 95% CI, 1.267-11.365; P=0.017 for KIR2DS4). CONCLUSIONS: This study shows that KIR gene-gene MMs increase AR and that KIRs/C ligands associated to AR and KIR2DS4/C ligands also influence short-term graft survival.


Assuntos
Transplante de Fígado/imunologia , Receptores KIR/genética , Estudos de Coortes , Feminino , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/genética , Sobrevivência de Enxerto/imunologia , Antígenos HLA-C/metabolismo , Hepatite C/etiologia , Hepatite C/imunologia , Teste de Histocompatibilidade , Humanos , Células Matadoras Naturais/imunologia , Ligantes , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Receptores KIR2DL3/genética , Recidiva , Subpopulações de Linfócitos T/imunologia , Fatores de Tempo
14.
Salus ; 15(3): 13-18, dic. 2011. tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: lil-701589

RESUMO

En el ámbito mundial los estudios sobre la eficacia del ultrasonido en la predicción del peso al nacer del recién nacido son controversiales; especialmente relacionado con la validez de la técnica del cálculo del peso fetal por ultrasonido. Se planteo calcular el peso al nacer en las embarazadas de alto riesgo por ultrasonido que acudieron a la Unidad de Perinatología de la Universidad de Carabobo entre enero y septiembre 2009, muestra no probabilística circunstancial de 305 pacientes cuyos criterios de inclusión fueron embarazos mayores de 22 semanas de gestación con ausencia de malformaciones fetales y ecografía previa al parto o cesárea menor o igual a 15 días. La patología obstétrica más frecuente fue la amenaza de parto pre término 7,9 % y las patologías medicas, la obesidad 43,6 %, encontrando asociación estadísticamente significativa (P< 0,0001) entre la restricción del crecimiento intrauterino y obesidad materna, hipertensión arterial durante el embarazo y oligohidramnios, así como asociación entre el feto grande para la edad gestacional con la diabetes gestacional. La diferencia de peso obtenida entre el calculado por ultrasonido y el obtenido al nacer fue 108,76 gr con asociación estadística entre ambas variables de carácter lineal positiva y coeficiente de correlación R² = 0,710 (P < 0,0001), el error típico de estimación de 387,76042. La ecuación de regresión lineal para la variable del peso al nacer: PN = 217,134 + Peso ecográfico x 0,096 días, error porcentual 3,63%. Concluyendo que a través del ultrasonido se puede calcular el peso al nacer cuando este, se estima en los 15 días antes de la finalización del embarazo.


Globally there are studies on the effectiveness of ultrasound in predicting birth weight infant, but some authors question the validity of the technique of calculation of fetal weight by ultrasound. Coupled with our patients are high risk. (4), based on this arises: Assessing the Effectiveness of Ultrasound in Predicting Birth Weight in High-Risk Pregnant Women attending Perinatology CHET in the period January to September 2009 of which A sample circumstantial and not random volunteer subjects comprising 305 patients whose inclusion criteria were pregnancies after 22 weeks of gestation with no fetal malformations and had an ultrasound prior to delivery or caesarean section less than or equal to 15 days. The pathology score was the most common obstetric preterm labor 7.9% and medical diseases with obesity 43.6%, finding statistically significant P <0.0001 between the restriction intrauterine growth with obesity, hypertension during pregnancy and oligohydramnios, and the big fetus for gestational age with gestational diabetes. The weight difference was obtained between the calculated and obtained by ultrasound at birth 108.76 grams with statistical association between two variables which was a positive linear with a correlation coefficient R2 = 0.710, P <0.0001 and a standard error of estimate of 387.76042. The linear regression equation for the variable of birth weight was: PN was ECOG Weight = 217.134 + x 0.096 days, error rate of 3.63%, explaining the ultrasound weight, 70.8% of the weight variation at birth.

15.
Arch Esp Urol ; 60(4): 430-8, 2007 May.
Artigo em Espanhol | MEDLINE | ID: mdl-17626535

RESUMO

OBJECTIVES: laparoscopic surgery has demonstrated that it is a good alternative to conventional surgery for the treatment of localized prostate cancer. Robotic surgery could be a therapeutic option. We try to evaluate both techniques, analyzing a series of parameters that allow us to describe the advantages and disadvantages of both techniques. METHODS: We performed a MEDLINE search and reviewed the main series of laparoscopic radical prostatectomy (LRP) and robotic radical prostatectomy (RRP). The parameters analyzed for each techniques were: oncological results, functional results, blood loss, transfusion rates, surgical times, complications rates, learning curve and cost. RESULTS: Both techniques have the advantage of being minimally invasive, which results in better recovery and aesthetic results. The learning curve of the robotic prostatectomy is shorter, 10 to 20 cases in comparison with 50 to 60 for the LRP. Cost analysis is more favourable for LRP, with a single-use instrument expenditure of 533 dollars per patient in comparison with 1.705 dollars with the robot. The cost of the robot is 1.200.000 dollars plus 100.000 dollars of annual maintenance (1). Operative time was 182 minutes [ 14 1-250] for robotic surgery and 234 min. [151-453] for LRP. Within the same institution, like Montsouris, times are very similar: 155 min. for the RRP and 18 1 min. for the (LRP). Mean operative blood loss was 234 ml [75-500] for the robot and 482 ml [185-859] for the LRP depending on the technique employed and the institution. Complication rate is similar for both techniques. The percentage of positive surgical margins is 20.6% for LRP and 19.24% for RRP Long term results on the biochemical PSA recurrence cannot be given due to the short life of both techniques. Continence rates are 56-100% for LRP and 70-98% for RRP Potency rates are 25-82% for LRP and 79-100% for RRP It is difficult to evaluate hospital stay because it depends on the politics of the medical institutions; nevertheless, it seems there are not significant differences between techniques. CONCLUSIONS: Introoperative and postoperative advantages are comparable with both techniques. Robotic prostatectomy has a shorter learning curve. Prospective studies with longer follow-up are necessary to compare oncological and functional results. The cost of LRP is lower than RRP.


Assuntos
Laparoscopia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Robótica , Humanos , Masculino
16.
Acta bioquím. clín. latinoam ; 41(2): 229-236, abr.-jun. 2007. graf, tab
Artigo em Espanhol | LILACS | ID: lil-633008

RESUMO

En este trabajo se ha determinado el contenido de plomo (Pb) en sangre en operarios de estaciones de servicio de la ciudad de Mérida (Venezuela) y en un grupo de personas no expuestas ocupacionalmente. Las muestras de sangre provenientes de sujetos de ambos sexos n=21 (controles) y n=65 (personal expuesto) fueron procesadas por absorción atómica con atomización electrotérmica (ETAAS). Las concentraciones obtenidas de 15,27±9,62 y 83,74±28,95 µg/L para los grupos denominados como control y expuesto respectivamente, muestran diferencias altamente significativas que evidencian una exposición directa al Pb, por cuanto los valores del grupo expuesto ocupacional son más de 5 veces superiores a los del grupo control. Los resultados obtenidos también muestran que valores iguales o superiores a 54,79 µg/L son indicadores de exposición directa al Pb, permitiendo establecer valores de tolerancia entre los intervalos de 24,89 y 112,69 µg/L. Estos valores de referencia se encuentran por debajo de lo descripto por Burguera y cols. (1997), lo cual podría atribuirse al reemplazo gradual de la gasolina con plomo, en los últimos años, que ha llevado a una disminución de un 27% en los niveles de plomo en sangre, en comparación con un estudio similar realizado en esta misma ciudad en el año 1997.


In this work the lead (Pb) content in blood was determined in petrol station workers in the city of Merida-Venezuela and in a group of people not occupationally exposed. The blood samples coming from subjects of both sexes n=21 controls and n=65 exposed workers were processed by atomic absorption with electrothermal atomization (ETAAS). The 15.27±9.62 and 83.74±28.95 µg/L concentrations obtained for the group referred to as control and exposed respectively show highly significant differences that evidence a direct exposure to Pb, since the values of the occupationally exposed group are more than 5 times higher than those of the control group. The results obtained also show that values equal to or higher than 54.79 µg/L are indicative of direct exposure to Pb, making it possible to establish tolerance values between the 24.89 and 112.69 µg/L intervals. These reference values are below what was reported by Burguera et al (1997) which could be attributed to the gradual substitution of gasoline for lead that has originated a 27% decrease in lead levels in blood, if compared with a similar study carried out in the same city in 1997.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Chumbo/normas , Chumbo/sangue , Chumbo/toxicidade , Intoxicação por Chumbo/sangue , Doenças Profissionais/sangue , Espectrofotometria Atômica , Posto de Combustível/efeitos adversos , Chumbo/efeitos adversos , Doenças Profissionais/complicações
17.
Braz. j. oral sci ; 4(12): 670-675, Jan.-Mar. 2005. ilus, tab, graf
Artigo em Inglês | LILACS, BBO - Odontologia | ID: lil-412435

RESUMO

Odontogenic cysts are lesions that deserve every attention, mainly because of all complications they can cause. To study their characteristics, the authors did a retrospective clinicopathological analysis of 124 oral biopsies that were diagnosed as odontogenic cysts, in Hospital Geral de Santo António - Porto. Clinical variables such as age, sex, location, clinical diagnosis and histological diagnosis were studied. Inflammatory radicular cysts were the most commons (48.4%) followed by dentigerous cysts (21.0%), residual cysts (17.7%)and keratocysts (12.1%). The most frequent clinical manifestation was swelling (62.9%). Age appears to be related to the type of cyst, expressing the etiopathologic characteristics of each one. It is concluded that a definitive diagnosis is based on a triad of radiology, clinics and histology, which presupposes a tight cooperation between the clinician and the histopathologist


Assuntos
Cistos Odontogênicos/patologia , Doenças Mandibulares , Patologia Bucal , Síndrome do Nevo Basocelular
18.
Rev. Fac. Farm. (Merida) ; 46(1): 22-26, ene.-jun. 2004. tab, graf
Artigo em Espanhol | LILACS | ID: lil-433241

RESUMO

La carbamazepina es un fármaco antiepiléptico sobre el cual se han publicado trabajos en donde se indican alteraciones hematológicas. Además, estas alteraciones pueden estar asociadas a factores de idiosincrasia; debido a esto, en este trabajo se estudiaron 48 pacientes que acuden a realizarse los niveles terapéuticos de la carbamazepina, en el Laboratorio de Toxicología del Instituto Autónomo Hospital Universitario de Los Andes (IAHULA) de la Ciudad de Mérida, Venezuela. A los pacientes, se les determinaron diferentes parámetros hematológicos los cuales se asociaron con la dosis, tiempo de tratamiento, sexo, peso y estatura. Como resultado se observaron cambios hematológicos entre los cuales se destacan una alteración en los índices hematimétricos, y, una leucopenia tardía en pacientes con 108 a 312 meses de tratamiento. Sin embargo, se sugiere realizar estudios similares utilizando pacientes controles que permitan determinar mediante análisis epidemiológicos, la fuerza de asociación epidemiológica entre las variables estudiadas


Assuntos
Masculino , Humanos , Feminino , Carbamazepina , Distúrbios do Sono por Sonolência Excessiva , Hematologia , Farmácia , Venezuela
19.
Rev. Fac. Farm. (Merida) ; 46(1): 51-56, ene.-jun. 2004. tab
Artigo em Espanhol | LILACS | ID: lil-433247

RESUMO

En Venezuela, los niveles cnsiderados como referencia de la colinesterasa plasmática en el ganado vacuno generalmente son de distintas poblaciones; esta distinción se debe a variaciones que incluyen factores como raza, edad, sexo, condiciones clímaticas y geográficas, entre otras. Debido a esto, es recomendable establecer niveles de referencia propios de las poblaciones consideradas con riesgo de exposición a sustancias inhibidras de la colinesterasa, y obtener de esta manera los niveles basales más cercanos a la población ganadera de una región determinada. Con base a lo anterior, en este trabajo, se determinaron los niveles de referencia de la colinesterasa plasmática en dos fincas ubicadas en la Zona Sur del Lago de Maracaibo. Los resultados obtenidos, muestran un valor comprendido entre 251.77 y 459.57 U/1. Estos resultados, permitirán no solo establecer controles periódicos de los animales de esa región, sino también utilizarlos como herramienta de diagnóstico en caso de intoxicación por inhbidores de la colinesterasa


Assuntos
Bovinos , Animais , Bovinos , Inibidores da Colinesterase , Compostos Organofosforados , Praguicidas , Farmácia , Venezuela
20.
Can J Anaesth ; 49(1): 25-31, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11782325

RESUMO

PURPOSE: To compare two protocols of epidural administration of racemic methadone for postoperative analgesia (continuous infusion and intermittent bolus), focussing on plasma concentration, analgesic efficacy and side effects. METHODS: Ninety patients undergoing abdominal or lower-limb surgery were randomly assigned to two groups in a prospective double-blind design. The continuous infusion patients (n=60) received initial doses of 3 to 6 mg followed by 6 to 12 mg by continuous infusion over 24 hr. The bolus administration patients (n=30) received repeated boluses of 3 to 6 mg of racemic methadone every eight hours. Pain intensity was assessed on a visual analog scale. Amount of supplementary analgesia was recorded, as was the incidence of side effects. Plasma methadone concentrations were determined by high performance liquid chromatography. Treatment was continued for 72 hr. RESULTS: Pain relief was good and comparable in both groups throughout the three days of treatment. No accumulation of plasma racemic methadone was observed in either group, although the concentrations were significantly higher in the bolus group. Miosis was significantly more frequent in the bolus group. CONCLUSION: Plasma methadone concentrations were significantly lower with continuous infusion. Plasma methadone accumulation, which is considered the main disadvantage for its purported influence on the incidence of side effects, did not occur at the doses used over the three days of treatment that we report.


Assuntos
Analgesia Epidural , Analgésicos Opioides/farmacocinética , Analgésicos Opioides/uso terapêutico , Metadona/farmacocinética , Metadona/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Adulto , Idoso , Analgésicos Opioides/efeitos adversos , Gasometria , Método Duplo-Cego , Feminino , Humanos , Masculino , Metadona/efeitos adversos , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Estereoisomerismo
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