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1.
Biol Cell ; 112(3): 92-101, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31922615

RESUMO

BACKGROUND: Non-typhoidal Salmonella (NTS) causes a severe invasive syndrome (iNTS disease) described in HIV-positive adults. The impact of HIV-1 on Salmonella pathogenesis and the molecular basis for the differences between these bacteria and classical diarrhoeal S. Typhimurium remains unclear. RESULTS: Here, we show that iNTS-associated S. Typhimurium Sequence Type 313 (ST313) bacteria show greater intracellular survival in primary human macrophages, compared with a 'classical' diarrhoeal S. Typhimurium ST19 isolate. The increased intracellular survival phenotype of ST313 is more pronounced in HIV-infected macrophages. We explored the possibility that the bacteria take advantage of the HIV-associated viral-containing compartments created in human macrophages that have low pH. Confocal fluorescence microscopy and focussed ion beam-scanning electron microscopy tomography showed that Salmonella did not co-localise extensively with HIV-positive compartments. CONCLUSION: The capacity of ST313 bacteria to survive better than ST19 bacteria within primary human macrophages is enhanced in cells pre-infected with HIV-1. Our results indicate that the ST313 bacteria do not directly benefit from the niche created by the virus in HIV-1-infected macrophages, and that they might take advantage from a more globally modified host cell. SIGNIFICANCE: A better understanding of the interplay between HIV-1 and Salmonella is important not only for these bacteria but also for other opportunistic pathogens.


Assuntos
Interações entre Hospedeiro e Microrganismos/fisiologia , Interações Microbianas , Salmonella typhimurium/crescimento & desenvolvimento , Coinfecção/microbiologia , Citoplasma/microbiologia , Citoplasma/virologia , Tomografia com Microscopia Eletrônica/métodos , Infecções por HIV/complicações , HIV-1/crescimento & desenvolvimento , Humanos , Macrófagos/microbiologia , Macrófagos/fisiologia , Macrófagos/virologia , Interações Microbianas/fisiologia , Microscopia Confocal , Cultura Primária de Células , Infecções por Salmonella/etiologia
2.
BMC Genomics ; 16: 546, 2015 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-26223308

RESUMO

BACKGROUND: Silene latifolia represents one of the best-studied plant sex chromosome systems. A new approach using RNA-seq data has recently identified hundreds of new sex-linked genes in this species. However, this approach is expected to miss genes that are either not expressed or are expressed at low levels in the tissue(s) used for RNA-seq. Therefore other independent approaches are needed to discover such sex-linked genes. RESULTS: Here we used 10 well-characterized S. latifolia sex-linked genes and their homologs in Silene vulgaris, a species without sex chromosomes, to screen BAC libraries of both species. We isolated and sequenced 4 Mb of BAC clones of S. latifolia X and Y and S. vulgaris genomic regions, which yielded 59 new sex-linked genes (with S. vulgaris homologs for some of them). We assembled sequences that we believe represent the tip of the Xq arm. These sequences are clearly not pseudoautosomal, so we infer that the S. latifolia X has a single pseudoautosomal region (PAR) on the Xp arm. The estimated mean gene density in X BACs is 2.2 times lower than that in S. vulgaris BACs, agreeing with the genome size difference between these species. Gene density was estimated to be extremely low in the Y BAC clones. We compared our BAC-located genes with the sex-linked genes identified in previous RNA-seq studies, and found that about half of them (those with low expression in flower buds) were not identified as sex-linked in previous RNA-seq studies. We compiled a set of ~70 validated X/Y genes and X-hemizygous genes (without Y copies) from the literature, and used these genes to show that X-hemizygous genes have a higher probability of being undetected by the RNA-seq approach, compared with X/Y genes; we used this to estimate that about 30% of our BAC-located genes must be X-hemizygous. The estimate is similar when we use BAC-located genes that have S. vulgaris homologs, which excludes genes that were gained by the X chromosome. CONCLUSIONS: Our BAC sequencing identified 59 new sex-linked genes, and our analysis of these BAC-located genes, in combination with RNA-seq data suggests that gene losses from the S. latifolia Y chromosome could be as high as 30 %, higher than previous estimates of 10-20%.


Assuntos
Cromossomos de Plantas/genética , Evolução Molecular , Processos de Determinação Sexual , Silene/genética , Sequência de Bases , Regulação da Expressão Gênica de Plantas , Dados de Sequência Molecular , Cromossomos Sexuais/genética , Silene/crescimento & desenvolvimento
3.
Support Care Cancer ; 21(2): 511-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22842921

RESUMO

PURPOSE: A prospective cohort study was conducted to analyze whether self-reported fatigue predicts overall survival in patients with esophageal cancer. METHODS: Patients enrolled in the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry between September 2001 and January 2009 who completed a baseline quality of life instrument were eligible for evaluation. The fatigue component was scored on a 0-10 scale, with 0 as extreme fatigue. Patients were categorized as having a decreased energy level if they reported a score of ≤ 5. Fatigue scores ≥ 6 reflect normal levels of energy. RESULTS: Data from a total of 659 enrolled patients were analyzed. A total of 392 (59 %) and 267 (41 %) patients reported decreased and normal energy, respectively. Univariate analysis indicates patients with normal energy had improved 5-year survival compared to patients with decreased energy (37 vs 28 %, hazard ratio (HR) 0.74, p = 0.006). Among the patients with locally advanced disease, the same relationship was seen (28 vs 17 %, HR = 0.67, p = 0.003); this remained significant on multivariate analysis (HR = 0.71, p = 0.015). CONCLUSIONS: A decreased energy level is associated with poor survival in patients with esophageal cancer. Thus, patients with high levels of fatigue should be referred for psychological support and be considered for therapy aimed at amelioration of fatigue symptoms.


Assuntos
Esôfago de Barrett/complicações , Neoplasias Esofágicas/complicações , Fadiga/etiologia , Qualidade de Vida , Adenocarcinoma/complicações , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/mortalidade , Esôfago de Barrett/patologia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sistema de Registros , Perfil de Impacto da Doença , Análise de Sobrevida , Adulto Jovem
4.
Dis Esophagus ; 25(4): 356-66, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21518102

RESUMO

Barrett's esophageal (BE) metaplasia is a premalignant condition of the distal esophagus that develops as a consequence of gastroesophageal reflux disease. The progression to carcinogenesis results from progressive dysplastic changes of the metaplastic epithelium through low-grade and then high-grade dysplasia (HGD) to eventually adenocarcinoma of the esophagus. The management of HGD is controversial with proponents for each of the three major management strategies: endoscopic surveillance, endoscopic ablative therapies, and esophagectomy. The aim of the study was to define and discuss the various management strategies of HGD arising from BE metaplasia. There is a paucity of randomized controlled data from which to draw definitive conclusions. All strategies for the management of HGD are reasonable options and are complimentary. BE with HGD is a malignant lesion. A multidisciplinary approach individualizing therapy should be undertaken when possible. Esophageal resection should be reserved for otherwise healthy patients. Endoscopic techniques are viable alternatives to surgery.


Assuntos
Esôfago de Barrett/terapia , Esofagectomia , Fotoquimioterapia , Vigilância da População , Lesões Pré-Cancerosas/terapia , Esôfago de Barrett/patologia , Ablação por Cateter , Eletrocoagulação , Esofagectomia/efeitos adversos , Esofagoscopia , Humanos , Mucosa/cirurgia , Lesões Pré-Cancerosas/patologia
5.
Dis Esophagus ; 25(7): 645-51, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22243561

RESUMO

Esophagectomy has one of the highest mortality rates among all surgical procedures. We investigated the type and frequency of complications associated with perioperative mortality after esophagectomy. We performed a retrospective review of all perioperative deaths following esophagectomy for esophageal cancer at the Mayo Clinic, Rochester from 1993 through 2009. Of 1522 esophagectomies, perioperative mortality occurred in 45 (3.0%). The majority who died were male (82%); median age was 72 years (range 46-92). The median age-adjusted Charlson comorbidity score was 6. Twenty-three (51%) underwent neoadjuvant chemoradiotherapy. The type of esophagectomy was transthoracic in 27 patients (60%), transhiatal in eight (18%), tri-incisional in seven (16%), left thoracoabdominal in one (2%), and transabdominal in one (2%). A mean of 3.2 major complications occurred prior to death (median 2.5, range 1-8), with the most common being pulmonary complications occurring in 30 patients (67%) and anastomotic complications in 20 (44%). The primary underlying cause of death was pulmonary complications and anastomotic complications in 18 patients (40%) each, respectively, abdominal sepsis in three (7%), fatal hemorrhage in three (7%), and pulmonary embolism, stroke and multisystem organ failure in one each (2%), respectively. Patients died a median of 19 days (range 3-98) following esophagectomy. Most patients who died following esophagectomy experienced multiple serious complications rather than a single causative event. Major pulmonary and anastomotic complications were implicated in the vast majority of perioperative mortality, and should remain the focus of efforts to improve clinical outcomes.


Assuntos
Fístula Anastomótica/mortalidade , Neoplasias Esofágicas/cirurgia , Esofagectomia/mortalidade , Complicações Pós-Operatórias/mortalidade , Hemorragia Pós-Operatória/mortalidade , Síndrome do Desconforto Respiratório/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Esofagectomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais
6.
Pathol Biol (Paris) ; 57(3): e37-42, 2009 May.
Artigo em Francês | MEDLINE | ID: mdl-18456428

RESUMO

MRSA-carrier screening is recommended to prevent MRSA dissemination in hospitals. Rapid and specific detection of MRSA in the laboratory is a key element in enabling control measures. Our objective was to evaluate the impact of different lengths of pre-incubation in a nutritive broth and prolonged incubation of MRSA-ID, a chromogenic agar medium, on its performances for identifying MRSA in screening samples. According to our results, short-length pre-enrichments only provided a weak increase of sensitivity as compared to the absence of pre-enrichment. On the contrary, the sensitivity increase provided by an overnight pre-enrichment was significant. The prolongation of incubation in the chromogenic agar medium (48 hours instead of 24 hours) did not provide any significant increase of sensitivity but was associated with a strong and significant loss of specificity. Therefore, it seems relevant to reject prolonged incubation of selective agar media and to make a choice between the absence of pre-enrichment (faster results) and an overnight pre-enrichment (higher sensitivity), according to local epidemiology and local practices implemented for prevention.


Assuntos
Programas de Rastreamento/métodos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Infecções Estafilocócicas/microbiologia , Ágar , Portador Sadio/microbiologia , Meios de Cultura , Hospitais/normas , Humanos , Pacientes Internados , Cinética , Programas de Rastreamento/normas , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Sensibilidade e Especificidade , Infecções Estafilocócicas/transmissão , Fatores de Tempo
7.
Dis Esophagus ; 21(4): 328-33, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18477255

RESUMO

Lymph node involvement may impact postoperative therapeutic decision-making and prognosis in patients undergoing esophagectomy. This study evaluates which surgical approach yields the most lymph nodes. We undertook a retrospective chart review of esophagectomies performed by six surgeons from April 1994 to February 2004 using a prospective general thoracic surgery database at Mayo Clinic, Rochester, Minnesota, US. Lymph nodes were categorized into one of 17 regions per the American Joint Committee on Cancer, with the total number of lymph nodes, summed over each region, used as the primary outcome. A total of 517 esophagectomies were performed: 68 transhiatal, 392 Ivor Lewis, and 57 extended Ivor Lewis. A mean of 18.7 (SD 8.5) lymph nodes were retrieved with the Ivor Lewis approach as compared to 17.4 (SD 9.2) with the extended Ivor Lewis approach (P = 0.30). Since there was no statistical difference between the number of nodes collected in either Ivor Lewis approach, they were collapsed into one group for comparison with the transhiatal cases. Significantly more lymph nodes were collected with an Ivor Lewis approach (mean 18.5, SD 8.6) than with a transhiatal approach (mean 9.0, SD 5.0, P < 0.001). As expected, more thoracic lymph nodes were retrieved with the Ivor Lewis approach [mean 12.4 (SD 7.0) vs. 4.7 (SD 5.3), P < 0.001]. The Ivor Lewis approach was also superior for retrieval of abdominal nodes [mean 6.1 (SD 5.6) versus 4.3 (SD 4.4), P = 0.01]. More lymph nodes are obtained at esophagectomy with an Ivor Lewis than a transhiatal approach.


Assuntos
Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Linfonodos/patologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Esôfago de Barrett/patologia , Esôfago de Barrett/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Dis Esophagus ; 21(3): 241-50, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18430106

RESUMO

While endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) are the most accurate techniques for locoregional staging of esophageal cancer, little evidence exists that these innovations impact on clinical care. The objective on this study was to determine the frequency with which EUS and EUS-FNA alter the management of patients with localized esophageal cancer, and assess practice variation among specialists at a tertiary care center. Three gastroenterologists, three medical oncologists, three radiation oncologists and four thoracic surgeons were asked to independently report their management recommendations as the anonymized staging information of 50 prospectively enrolled patients from another study were sequentially disclosed on-line. Compared to initial management recommendations, that were based upon history, physical examination, upper endoscopy and CT scan results, EUS prompted a change in management 24% (95% CI: 12-36%) of the time; usually to a more resource-intensive approach (71%), for example from recommending palliation to recommending neoadjuvant chemoradiation therapy. EUS-FNA plus cytology results altered management an additional 8% (95% CI: 6-15%) of the time. Agreement between specialists ranged from fair (intraclass correlation [ICC=0.32) to substantial (ICC=0.65); improving with additional information. Among specialists, agreement was greatest for patients with stage I disease. EUS and EUS-FNA changed patient management the most for patients with stages IIA, IIB or III disease. EUS, with or without FNA, significantly impacts the management of patients with localized esophageal cancer. With respect to the optimal treatment for each patient, agreement among physicians incrementally increases with endoscopic ultrasound results. Specialty training appears to influence therapeutic decision-making behavior.


Assuntos
Biópsia por Agulha Fina/métodos , Endossonografia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Esofagoscopia , Padrões de Prática Médica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastroenterologia , Humanos , Masculino , Oncologia , Pessoa de Meia-Idade , Estudos Prospectivos , Radiologia , Cirurgia Torácica
9.
Ann Biol Clin (Paris) ; 63(6): 573-9, 2005.
Artigo em Francês | MEDLINE | ID: mdl-16330375

RESUMO

The theoretical bases of medical knowledge exert a strong influence on both clinical practice and representations of living and health. In this perspective, reduction and emergence notions play a major role. Microreduction is the predominant analytical strategy used today in biology, as it is usually considered that essential life mechanisms can be reduced to molecular processes. Likewise, macroreduction proposes that parts can be defined in terms of their belonging to wholes, as it is usually assumed, for instance, in genetic epidemiology. With regard to emergence, this notion, which focuses on properties of a whole that cannot be deduced from properties of its parts, is consistent with both nature of living and evolution theory. The apparent success of reduction like analytical modality has generated in scientific community and public opinion an ideological reductionism, which corresponds, ontologically, to both physicalism (things can be entirely understood in terms of their parts), and atomism (things go their own way, independently of other things). Genetic reductionism has generated new cosmological representations of living, where past, present and future of living beings could potentially be deduced from fallacious, simple views of genome sequences. These views may lead to quantitative or qualitative definitions of standard patterns and hierarchies. In practical terms, research activity should integrate limits, strains as well as reductionism advantages. Biologists should also consider risks associated with an ideological, unrestricted reductionism, applied to any existence aspect, a notion with questionable legitimacy and with potential ethical, philosophical, and political involvements that go beyond the simple selection of a research strategy.


Assuntos
Pesquisa Biomédica/normas , Filosofia
10.
Ars vet ; 36(4): 253-270, 2020. tab, graf
Artigo em Português | VETINDEX | ID: biblio-1463552

RESUMO

Essa revisão apresenta considerações acerca da relevância das infecções de parasitos gastrintestinais (PGI) em ruminantes, abordando a importância de fármacos antiparasitários no controle das helmintoses e demais alternativas. Foi realizada uma abordagem conceitual e histórica sobre o controle de PGI e o processo de desenvolvimento da resistência parasitária. Como alternativa da baixa eficácia de medicamentos, foi feita uma descrição detalhada sobre o uso de óleos essenciais (OE) e de componentes bioativos no controle das PGI em ruminantes. A produção de OE de plantas, passa pela composição química, técnicas de extração dos componentes, mecanismo de ação e ensaios para validação da sua atividade terapêutica, incluindo sua ação anti-helmíntica. Este artigo traz, na sua segunda parte, uma descrição detalhada de duas espécies do gênero Mentha, com foco em sua biologia, composição química e mecanismos de ação de seus OE. Dentro desse tópico, as espécies Mentha vilosa e M. piperita são as mais estudadas, bem como os seus componentes majoritários e bioativos; carvone e limoneno. Ao final do documento, discutimos sobre a técnica de cromatografia gasosa e espectrometria de massas, que se faz obrigatória para a identificação de compostos presentes em OE. Incluímos ainda, o detalhamento sobre tecnologias de nanoemulsão e suas vantagens na confecção de formulações mais estáveis, menos tóxicas aos hospedeiros e com potencial de aumentar a eficácia de fármacos contra as PGI, para o desenvolvimento de novos compostos fitoterápicos ecosustentáveis.


This review presents considerations about the relevance of gastrointestinal parasite (GIP) infections in ruminants, covering also the importance of antiparasitic drugs in the control of helminth infections and some other alternatives. This document describes a conceptual and historical view of the development of routine GIP control and the process of development of drug resistance. As an alternative to the low efficacy of some products, a detailed description was made of the use of essential oils (EO) and their bioactive compounds in the control of GIP in ruminants. The production of EO from plants, goes through the chemical composition, techniques of extraction of components, mechanism of action and assays for the validation of their activity, including the anthelmintic activity. The present document brings, in its second part, a more detailed description of two species of the genus Mentha, focusing on their biology, chemical composition and the mechanism of action of their EO. Within this topic, the species of Mentha vilosa and M. piperita are better studied, as well as their chemical composition and bioactive components carvone and limonene. At the end, it is discussed the gas chromatography and mass spectrometry techniques that are useful to identify compounds present in EO. It was also included the details about nanoemulsion technologies and their advantages in obtaining a more stable formulation, less toxic to the host, with a great potential to increase anthelmintic efficacy against GIP, for the development of new herbal bioactive and ecofriendly compounds.


Assuntos
Animais , Fitoterapia/veterinária , Gastroenteropatias/parasitologia , Gastroenteropatias/veterinária , Mentha , Plantas Medicinais , Ruminantes
11.
Ars Vet. ; 36(4): 253-270, 2020. tab, graf
Artigo em Português | VETINDEX | ID: vti-29928

RESUMO

Essa revisão apresenta considerações acerca da relevância das infecções de parasitos gastrintestinais (PGI) em ruminantes, abordando a importância de fármacos antiparasitários no controle das helmintoses e demais alternativas. Foi realizada uma abordagem conceitual e histórica sobre o controle de PGI e o processo de desenvolvimento da resistência parasitária. Como alternativa da baixa eficácia de medicamentos, foi feita uma descrição detalhada sobre o uso de óleos essenciais (OE) e de componentes bioativos no controle das PGI em ruminantes. A produção de OE de plantas, passa pela composição química, técnicas de extração dos componentes, mecanismo de ação e ensaios para validação da sua atividade terapêutica, incluindo sua ação anti-helmíntica. Este artigo traz, na sua segunda parte, uma descrição detalhada de duas espécies do gênero Mentha, com foco em sua biologia, composição química e mecanismos de ação de seus OE. Dentro desse tópico, as espécies Mentha vilosa e M. piperita são as mais estudadas, bem como os seus componentes majoritários e bioativos; carvone e limoneno. Ao final do documento, discutimos sobre a técnica de cromatografia gasosa e espectrometria de massas, que se faz obrigatória para a identificação de compostos presentes em OE. Incluímos ainda, o detalhamento sobre tecnologias de nanoemulsão e suas vantagens na confecção de formulações mais estáveis, menos tóxicas aos hospedeiros e com potencial de aumentar a eficácia de fármacos contra as PGI, para o desenvolvimento de novos compostos fitoterápicos ecosustentáveis.(AU)


This review presents considerations about the relevance of gastrointestinal parasite (GIP) infections in ruminants, covering also the importance of antiparasitic drugs in the control of helminth infections and some other alternatives. This document describes a conceptual and historical view of the development of routine GIP control and the process of development of drug resistance. As an alternative to the low efficacy of some products, a detailed description was made of the use of essential oils (EO) and their bioactive compounds in the control of GIP in ruminants. The production of EO from plants, goes through the chemical composition, techniques of extraction of components, mechanism of action and assays for the validation of their activity, including the anthelmintic activity. The present document brings, in its second part, a more detailed description of two species of the genus Mentha, focusing on their biology, chemical composition and the mechanism of action of their EO. Within this topic, the species of Mentha vilosa and M. piperita are better studied, as well as their chemical composition and bioactive components carvone and limonene. At the end, it is discussed the gas chromatography and mass spectrometry techniques that are useful to identify compounds present in EO. It was also included the details about nanoemulsion technologies and their advantages in obtaining a more stable formulation, less toxic to the host, with a great potential to increase anthelmintic efficacy against GIP, for the development of new herbal bioactive and ecofriendly compounds.(AU)


Assuntos
Animais , Fitoterapia/veterinária , Gastroenteropatias/parasitologia , Gastroenteropatias/veterinária , Mentha , Plantas Medicinais , Ruminantes
12.
Clin Pharmacol Ther ; 68(6): 647-57, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11180025

RESUMO

OBJECTIVE: The aim of this work was to model the pharmacokinetic and pharmacodynamic relationship of mizolastine, a new H1-receptor antagonist obtained from histamine-induced wheal and flare inhibition test. METHODS: Fifteen healthy volunteers participated in this double-blind crossover study and randomly received single doses of 5, 10, 15, and 20 mg of mizolastine and placebo at 1 week intervals. Simultaneous histamine tests and blood samples were performed before and at 9 different times up to 24 hours after each dosing. Pharmacokinetic and pharmacodynamic modeling were performed subject by subject for the 4 doses altogether by nonlinear regression. First, plasma concentrations were fit according to a two-compartment open model with zero order absorption and first order elimination. Then an indirect response model with inhibition of the formation rate was developed to describe the pharmacodynamic relationships between flare or wheal raw areas and plasma concentrations with the use of the pharmacokinetic parameters that were previously estimated. RESULTS: Mizolastine dose dependently inhibited the histamine-induced wheal and flare formation with a submaximum effect attained after 10 mg. The mean values of the pharmacodynamic parameters of apparent zero-order rate constant for the flare or wheal spontaneous appearance (k(in)), the first-order rate constant for the flare or wheal disappearance, the mizolastine concentration that produced 50% suppression of the maximum attainable inhibition of k(in), and the maximum attainable inhibition of the effect production were 14.1 cm2/h (coefficient of variation [CV], 32%), 0.68 h(-1) (CV, 24%), 21.1 ng/mL (CV, 77%), and 0.92 (CV, 8%), respectively, for the flare and 1.9 cm2/h (CV, 64%), 0.63 h-1 (CV, 39%), 43.9 ng/mL (CV, 68%), and 0.87 (CV, 12%), respectively, for the wheal inhibition. CONCLUSION: Pharmacokinetic and pharmacodynamic relationships of mizolastine were reliably described with the use of an indirect pharmacodynamic model; this led to an accurate prediction of the pharmacodynamic activity of mizolastine.


Assuntos
Benzimidazóis/farmacologia , Benzimidazóis/farmacocinética , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores Histamínicos H1/farmacocinética , Modelos Biológicos , Administração Oral , Adulto , Benzimidazóis/efeitos adversos , Compartimentos de Líquidos Corporais , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Histamina , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Humanos , Masculino , Placebos , Valor Preditivo dos Testes , Testes Cutâneos , Urticária/induzido quimicamente , Urticária/prevenção & controle
13.
Int J Radiat Oncol Biol Phys ; 45(2): 315-21, 1999 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-10487551

RESUMO

PURPOSE: Patients with pathologically staged American Joint Committee on Cancer stage I (T1 N0 or T2 N0) non-small cell lung cancer have a favorable prognosis after complete surgical resection compared with patients with more advanced stages. Benefits of adjuvant therapy in this setting are unproved. However, there may be subgroups of patients with stage I disease at high enough risk for local recurrence to prompt consideration of adjuvant or neoadjuvant radiation therapy. Likewise, there may be subgroups of patients at high enough risk for distant metastasis to justify the evaluation of chemotherapy. METHODS AND MATERIALS: From 1987 through 1990, 370 patients undergoing gross total resection of non-small cell lung cancer had stage I disease and received no chemotherapy or radiation therapy as part of their primary treatment. These patients were the subject of a retrospective review to separate patients into high-, intermediate-, and low-risk groups with respect to freedom from local recurrence (FFLR), freedom from distant metastasis (FFDM), and overall survival by using a regression tree analysis. RESULTS: The 5-year rates of FFLR, FFDM, and survival were 85%, 83%, and 66%, respectively. Regression analyses revealed that the factors independently predicting for a poorer FFLR rate included fewer than 15 lymph nodes dissected and pathologically evaluated (p = 0.002) and the presence of a T2 tumor (p = 0.04). Factors independently predicting for a poorer FFDM rate included a maximal dimension greater than 5 cm (p = 0.02) and nonsquamous histology (p = 0.03). Factors independently predicting for a poorer survival rate included fewer than 15 lymph nodes dissected and pathologically evaluated p = 0.001) and a maximal dimension greater than 3 cm (p = 0.003). Regression tree analyses were used to separate patients into risk groups. CONCLUSION: Incorporating the aforementioned factors into regression tree analyses, three risk groups were identified with respect to FFLR. Two each were identified for FFDM and for survival. For each of these three end-points, the differences in outcomes for each risk group were found to be both statistically and clinically significant. These risk groups may be useful in the future design of phase III trials evaluating the use of adjuvant chemotherapy and radiation therapy in the stage I setting.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Regressão , Projetos de Pesquisa , Estudos Retrospectivos , Risco , Taxa de Sobrevida
14.
Int J Radiat Oncol Biol Phys ; 45(1): 91-5, 1999 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-10477011

RESUMO

BACKGROUND: Previous studies of patients with surgically resected non-small cell lung cancer and chest wall invasion have shown conflicting results with respect to prognosis. Whether high-risk subsets of the T3 N0 M0 population exist with respect to patterns of failure and overall survival has been difficult to ascertain, owing to small numbers of patients in most series. METHODS AND MATERIALS: A retrospective review was performed to determine patterns of failure and overall survival for patients with completely resected T3 N0 M0 non-small cell lung cancer. From 1979 to 1993, 92 evaluable patients underwent complete resection for T3 N0 M0 non-small cell lung cancer. The following potential prognostic factors were recorded from the history: tumor size, location, grade, histology, patient age, use of adjuvant radiation therapy (18 of 92 patients), and type of surgical procedure (chest wall or extrapleural resection). RESULTS: The actuarial 2- and 4-year overall survival rates for the entire cohort were 48% and 35%, respectively. The actuarial local control at 4 years was 94%. Neither the type of surgical procedure performed nor the addition of thoracic radiation therapy impacted local control or overall survival. CONCLUSION: Patients with completely resected T3 N0 M0 non-small cell lung cancer have similar local control and overall survival irrespective of primary location, type of surgery performed, or use of adjuvant radiation therapy. Additionally, the tumor recurrence rate and overall survival found in this study support the placement of this group of patients in Stage IIB of the 1997 AJCC lung staging classification.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Neoplasias Pulmonares/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Falha de Tratamento
15.
Mayo Clin Proc ; 73(6): 552-66, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9621865

RESUMO

Lung volume reduction surgery (LVRS) has recently been rediscovered and offers the potential of improving the quality of life of patients with advanced emphysema. In this article, we discuss the historical and contemporary versions of LVRS. Although initial enthusiasm has been substantial, existing data seem insufficient to demonstrate the safety and efficacy of the procedure in comparison with conventional medical therapy. Fundamental questions remain regarding the long-term effects of an operation versus medical therapy, the optimal selection criteria, the best measures of efficacy, the mechanisms of improvement, the cost-effectiveness of the procedure, and the optimal surgical technique. Until such questions are answered, advising patients about the best management their emphysema will be difficult. The National Emphysema Treatment Trial will address many of these issues and should be embraced by both health-care providers and patients.


Assuntos
Pneumonectomia/métodos , Enfisema Pulmonar/cirurgia , Volume Expiratório Forçado , Humanos , Transplante de Pulmão , Enfisema Pulmonar/mortalidade , Taxa de Sobrevida , Resultado do Tratamento
16.
Mayo Clin Proc ; 66(6): 565-71, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2046394

RESUMO

A case of cerebral air embolism sustained during replacement of the mitral valve resulted in postoperative coma and seizures. Hyperbaric treatment, begun 30 hours after the occurrence of the air embolism, resulted in good immediate and long-term recovery. Mild deficits of the left hemisphere were present at follow-up 53 days after the embolus was sustained, and lesser, minimal residua were present at 14-month follow-up. Hyperbaric treatment is the definitive therapy for cerebral air embolism. Although it is most effective when administered early, the outcome may be excellent even with late treatment.


Assuntos
Embolia Aérea/terapia , Oxigenoterapia Hiperbárica , Embolia e Trombose Intracraniana/terapia , Valva Mitral/cirurgia , Ponte Cardiopulmonar , Embolia Aérea/complicações , Embolia Aérea/etiologia , Feminino , Humanos , Embolia e Trombose Intracraniana/complicações , Embolia e Trombose Intracraniana/etiologia , Complicações Intraoperatórias , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Fatores de Tempo
17.
Mayo Clin Proc ; 67(5): 462-4, 1992 May.
Artigo em Inglês | MEDLINE | ID: mdl-1405772

RESUMO

Solitary pulmonary nodules continue to challenge all diagnostic skills. Herein we describe video-assisted thoracic surgical intervention, a new, minimally invasive technique that aids physicians in obtaining a definitive histologic diagnosis in a select group of patients with an indeterminate solitary pulmonary nodule.


Assuntos
Granuloma/patologia , Pneumopatias/patologia , Nódulo Pulmonar Solitário/patologia , Toracoscopia/métodos , Gravação de Videoteipe/métodos , Granuloma/diagnóstico por imagem , Granuloma/cirurgia , Humanos , Pneumopatias/diagnóstico por imagem , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgia , Tomografia Computadorizada por Raios X
18.
Mayo Clin Proc ; 70(10): 946-50, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7564546

RESUMO

OBJECTIVE: To present our experience with mediastinal parathyroid cysts and summarize previously reported cases. DESIGN: We retrospectively reviewed medical records and reviewed the pertinent literature. MATERIAL AND METHODS: The clinical, operative, and pathologic findings in 7 cases of mediastinal parathyroid cysts encountered at one institution and 31 cases previously reported in the literature are described. RESULTS: Rarely, cysts may arise from an aberrant mediastinal parathyroid gland. Such cysts may manifest as a symptomatic mass, as an asymptomatic finding on roentgenography, or during the assessment of a patient with hyperparathyroidism. The diagnosis may be made by fine-needle aspiration or by excision and pathologic examination. CONCLUSION: Functioning parathyroid cysts represent degeneration of a hyperfunctioning gland, such as an adenoma, and are usually removed through a cervical approach. Nonfunctioning cysts in asymptomatic patients with normal serum calcium levels are considered indeterminate and should be managed accordingly. Excision is usually recommended.


Assuntos
Cisto Mediastínico , Doenças das Paratireoides , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Cisto Mediastínico/diagnóstico , Cisto Mediastínico/cirurgia , Pessoa de Meia-Idade , Doenças das Paratireoides/diagnóstico , Doenças das Paratireoides/cirurgia , Estudos Retrospectivos
19.
Mayo Clin Proc ; 71(4): 351-9, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8637257

RESUMO

OBJECTIVE: To describe an initial 3-year experience with video-assisted thoracic surgical procedures (VATS) at Mayo Clinic Rochester. DESIGN: We review the cumulative data on 771 VATS performed between June 1, 1991, and May 31, 1994, and assess the applications for this technique. MATERIAL AND METHODS: The indications for VATS, our techniques used, and the associated mortality and morbidity are summarized. In addition, the frequency of conversion of VATS to open procedures and the reasons for choosing this strategy are discussed. RESULTS: The 771 study patients (401 male and 370 female patients) had a median age of 62 years (range, 7 to 96). For all VATS. we used one-lung general anesthesia, without carbon dioxide insufflation. Indications for performing VATS were a pulmonary nodule in 333 patients, pleural effusion in 208, pulmonary infiltrate in 117, pneumothorax in 51, mediastinal mass in 22, pleural mass in 17, air leak in 13, and other in 10. The procedure was a wedge excision in 352 patients, examination of the pleural cavity in 128, pleural biopsy in 86, talc pleurodesis in 85, wedge excision and mechanical pleurodesis in 46, decortication in 27, excision of a mediastinal mass in 12, sympathectomy in 4, and other in 16. The rate of conversion of VATS to thoracotomy was 33.1% and did not change throughout the period of the study. The most common reasons for conversion were to complete a resection of a malignant lesion or to remove a deep nodule. The overall operative mortality was 1.9%. Complications occurred in 43 patients (8.3%) who underwent VATS without conversion to an open procedure and included prolonged air leak in 14, respiratory failure in 8, pneumothorax in 6, and atrial fibrillation in 5. The median hospitalization was 5 days (range, 1 to 104). CONCLUSION: VATS is safe and useful for selected thoracic conditions. We favor conversion to thoracotomy when curative resection of a malignant lesion is intended.


Assuntos
Cirurgia Torácica/métodos , Gravação em Vídeo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Toracotomia/efeitos adversos
20.
Mayo Clin Proc ; 68(6): 593-602, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8388525

RESUMO

Most patients who have lung cancer will receive radiation therapy at some point during the course of their disease. For patients with non-small-cell lung cancer, radiation therapy is sometimes used after complete resection, particularly in patients with lymph node involvement. In addition, irradiation is commonly used after incomplete resection. In patients with unresectable non-small-cell lung cancer, radiation therapy alone is typically used, although recent studies of a combination of chemotherapy and radiation therapy, or radiation therapy given in twice-daily fractions, have yielded promising results. For patients with small-cell lung cancer who have limited (that is, nonmetastatic) disease, the addition of thoracic radiation therapy to chemotherapy has improved survival over that with chemotherapy only. The role of prophylactic cranial irradiation in small-cell lung cancer remains controversial. Radiation therapy has a major role in the management of locally recurrent and metastatic lung cancer. Both the bones and the brain are common metastatic sites in patients with lung cancer. Radiation therapy provides effective palliation of symptoms from these and other metastatic lesions.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Humanos
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