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BACKGROUND AND AIMS: To assess safety of the Exilis™ gastric electrical stimulation (GES) system and to investigate whether the settings can be adjusted for comfortable chronic use in subjects with morbid obesity. Gastric emptying and motility and meal intake were evaluated. METHOD: In a multicenter, phase 1, open prospective cohort study, 20 morbidly obese subjects (17 female, mean BMI of 40.8 ± 0.7 kg/m2) were implanted with the Exilis™ system. Amplitude of the Exilis™ system was individually set during titration visits. Subjects underwent two blinded baseline test days (GES ON vs. OFF), after which long-term, monthly follow-up continued for up to 52 weeks. RESULTS: The procedure was safe, and electrical stimulation was well tolerated and comfortable in all subjects. No significant differences in gastric emptying halftime (203 ± 16 vs. 212 ± 14 min, p > 0.05), food intake (713 ± 68 vs. 799 ± 69 kcal, p > 0.05), insulin AUC (2448 ± 347 vs. 2186 ± 204, p > 0.05), and glucose AUC (41 ± 2 vs.41 ± 2, p > 0.05) were found between GES ON and OFF. At week 4, 13, and 26, a significant (p < 0.01) reduction in weight loss was observed but not at week 52. At this time point, the mean excess weight loss (EWL) was 14.2 ± 4.5%. CONCLUSION: Gastric electrical stimulation with the Exilis™ system can be considered as safe. No significant effect on food intake, gastric emptying, or gastric motility was observed. The reduction in weight loss with Exilis™ GES was significant but short lasting. Further electrophysiological research is needed to gain more insight in optimal stimulation parameters and lead localization.
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Terapia por Estimulação Elétrica , Obesidade Mórbida , Estimulação Elétrica , Eletrodos Implantados , Feminino , Esvaziamento Gástrico , Humanos , Masculino , Obesidade Mórbida/cirurgia , Estudos ProspectivosRESUMO
Screening for pancreatic cancer (PC) in high-risk groups aimed to detect early cancers is currently done only in the research setting, and data on psychological outcomes of screening in these populations is scarce. To determine the psychological impact of a national Australian pancreatic screening program, a prospective study was conducted using validated psychological measures: impact of events scale (IES), psychological consequences questionnaire (PCQ) and the cancer worry scale. Measures were administered at baseline, 1-month and at 1-year post-enrolment and correlations with abnormal endoscopic ultrasound (EUS) results were calculated. Over a 6-year period, 102 participants were recruited to the screening program. Thirty-nine patients (38.2%) had an abnormal endoscopic ultrasound, and two patients (2.0%) were diagnosed with PC and two with other malignancies. Those with a personal history of cancer or a positive BRCA2 mutation demonstrated significantly increased worry about developing other types of cancer at baseline (p < 0.01). Irrespective of EUS result, there was a significant decrease of total IES score at 1 year (Z = - 2.0, p = 0.041). In patients with abnormal EUS results, there was a decrease in the total IES score at 1 year (Z = - 2.5, p = 0.011). In participants deemed to be most distressed at baseline based on their negative PCQ score, there was a significant decrease of the total PCQ (Z = - 3.2, p = 0.001), emotional (Z = - 3.0, p = 0.001), social (Z = 3.0, p = 0.001) and physical (Z = - 2.8, p = 0.002) subscale at 1-year post-intervention. This study provides evidence of the long-term psychological benefits of PC screening in high-risk patients. There was no negative impact of screening in the short-term and the positive benefits appeared at 1-year post-intervention irrespective of screening result.
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Detecção Precoce de Câncer/psicologia , Neoplasias Pancreáticas/psicologia , Angústia Psicológica , Adulto , Idoso , Feminino , Genes BRCA2 , Humanos , Masculino , Pessoa de Meia-Idade , New South Wales , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/genética , Estudos Prospectivos , Inquéritos e Questionários/estatística & dados numéricos , Fatores de Tempo , UltrassonografiaRESUMO
There is a growing interest in cylindrical structures of hard and soft particles. A promising new method to assemble such structures has recently been introduced by Lee et al. [Lee, Gizynski, and Grzybowski, Adv. Mater. 29, 1704274 (2017)ADVMEW0935-964810.1002/adma.201704274]. They used rapid rotations around a central axis to drive spheres of lower density than the surrounding fluid towards the axis. This resulted in different structures as the number of spheres is varied. Here, we present comprehensive analytic energy calculations for such self-assembled structures, based on a generic soft sphere model, from which we obtain a phase diagram. It displays interesting features, including peritectoid points. These analytic calculations are complemented by preliminary numerical simulations for finite sample sizes with soft spheres. A similar analytic approach could be used to study packings of spheres inside cylinders of fixed dimensions, but with a variation in the number of spheres.
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Chronic morphine therapy has been associated with paradoxically increased pain. Codeine is a widely used opioid, which is metabolized to morphine to elicit analgesia. Prolonged morphine exposure exacerbates pain by activating the innate immune toll-like receptor-4 (TLR4) in the central nervous system. In silico docking simulations indicate codeine also docks to MD2, an accessory protein for TLR4, suggesting potential to induce TLR4-dependent pain facilitation. We hypothesized codeine would cause TLR4-dependent hyperalgesia/allodynia that is disparate from its opioid receptor-dependent analgesic rank potency. Hyperalgesia and allodynia were assessed using hotplate and von Frey tests at days 0, 3 and 5 in mice receiving intraperitoneal equimolar codeine (21 mg kg(-1)), morphine (20 mg kg(-1)) or saline, twice daily. This experiment was repeated in animals with prior partial nerve injury and in TLR4 null mutant mice. Interventions with interleukin-1 receptor antagonist (IL-1RA) and glial-attenuating drug ibudilast were assessed. Analyses of glial activation markers (glial fibrillary acid protein and CD11b) in neuronal tissue were conducted at the completion of behavioural testing. Despite providing less acute analgesia (P=0.006), codeine induced similar hotplate hyperalgesia to equimolar morphine vs saline (-9.5 s, P<0.01 and -7.3 s, P<0.01, respectively), suggesting codeine does not rely upon conversion to morphine to increase pain sensitivity. This highlights the potential non-opioid receptor-dependent nature of codeine-enhanced pain sensitivity-although the involvement of other codeine metabolites cannot be ruled out. IL-1RA reversed codeine-induced hyperalgesia (P<0.001) and allodynia (P<0.001), and TLR4 knock-out protected against codeine-induced changes in pain sensitivity. Glial attenuation with ibudilast reversed codeine-induced allodynia (P<0.001), and thus could be investigated further as potential treatment for codeine-induced pain enhancement.
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Analgésicos Opioides/farmacologia , Codeína/farmacologia , Hiperalgesia/induzido quimicamente , Morfina/farmacologia , Neuroglia/metabolismo , Limiar da Dor/efeitos dos fármacos , Analgésicos Opioides/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Codeína/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Morfina/administração & dosagem , Neuroglia/efeitos dos fármacos , Distribuição Aleatória , Nervo Isquiático/lesões , Receptor 4 Toll-LikeRESUMO
Inconsistent evidence exists regarding the association between work-related factors and risk of multiple sclerosis (MS). We examined the association between occupational exposures and risk of a first clinical diagnosis of central nervous system demyelination (FCD), which is strongly associated with progression to MS, in a matched case-control study of 276 FCD cases and 538 controls conducted in Australia (2003-2006). Using a personal residence and work calendar, information on occupational history and exposure to chemicals and animals was collected through face-to-face interviews. Few case-control differences were noted. Fewer cases had worked as professionals (≥6 years) than controls (adjusted odds ratio (AOR) = 0.60, 95% confidence interval (CI): 0.37, 0.96). After further adjustment for number of children, cases were more likely to have ever been exposed to livestock than controls (AOR = 1.54, 95% CI: 1.03, 2.29). Among women, there was an increase in FCD risk associated with 10 or more years of exposure to livestock (AOR = 2.78, 95% CI: 1.22, 6.33) or 6 or more years of farming (AOR = 2.00, 95% CI: 1.23, 3.25; also adjusted for number of children). Similar findings were not evident among men. Thus, farming and exposure to livestock may be important factors in the development of FCD among women, with this finding further revealed after the confounding effect of parity or number of children is considered.
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Agricultura/estatística & dados numéricos , Doenças Desmielinizantes/etiologia , Exposição Ocupacional/efeitos adversos , Adolescente , Adulto , Animais , Austrália , Estudos de Casos e Controles , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/diagnóstico , Feminino , Humanos , Entrevistas como Assunto , Gado , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Esclerose Múltipla/etiologia , Exposição Ocupacional/estatística & dados numéricos , Ocupações/classificação , Ocupações/estatística & dados numéricos , Fatores de Risco , Distribuição por Sexo , Inquéritos e Questionários , Fatores de Tempo , Adulto JovemRESUMO
The development and evaluation of a prototype cardiac gating system for double-shot dual-energy (DE) imaging is described. By acquiring both low- and high-kVp images during the resting phase of the cardiac cycle (diastole), heart misalignment between images can be reduced, thereby decreasing the magnitude of cardiac motion artifacts. For this initial implementation, a fingertip pulse oximeter was employed to measure the peripheral pulse waveform ('plethysmogram'), offering potential logistic, cost and workflow advantages compared to an electrocardiogram. A gating method was developed that accommodates temporal delays due to physiological pulse propagation, oximeter waveform processing and the imaging system (software, filter-wheel, anti-scatter Bucky-grid and flat-panel detector). Modeling the diastolic period allowed the calculation of an implemented delay, t(imp), required to trigger correctly during diastole at any patient heart rate (HR). The model suggests a triggering scheme characterized by two HR regimes, separated by a threshold, HR(thresh). For rates at or below HR(thresh), sufficient time exists to expose on the same heartbeat as the plethysmogram pulse [t(imp)(HR) = 0]. Above HR(thresh), a characteristic t(imp)(HR) delays exposure to the subsequent heartbeat, accounting for all fixed and variable system delays. Performance was evaluated in terms of accuracy and precision of diastole-trigger coincidence and quantitative evaluation of artifact severity in gated and ungated DE images. Initial implementation indicated 85% accuracy in diastole-trigger coincidence. Through the identification of an improved HR estimation method (modified temporal smoothing of the oximeter waveform), trigger accuracy of 100% could be achieved with improved precision. To quantify the effect of the gating system on DE image quality, human observer tests were conducted to measure the magnitude of cardiac artifact under conditions of successful and unsuccessful diastolic gating. Six observers independently measured the artifact in 111 patient DE images. The data indicate that successful diastolic gating results in a statistically significant reduction (p < 0.001) in the magnitude of cardiac motion artifact, with residual artifact attributed primarily to gross patient motion.
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Coração/fisiologia , Oximetria/métodos , Artefatos , Frequência Cardíaca , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de TempoRESUMO
Experimental and theoretical studies were conducted to determine optimal acquisition techniques for a prototype dual-energy (DE) chest imaging system. Technique factors investigated included the selection of added x-ray filtration, kVp pair, and the allocation of dose between low- and high-energy projections, with total dose equal to or less than that of a conventional chest radiograph. Optima were computed to maximize lung nodule detectability as characterized by the signal-difference-to-noise ratio (SDNR) in DE chest images. Optimal beam filtration was determined by cascaded systems analysis of DE image SDNR for filter selections across the periodic table (Z(filter) = 1-92), demonstrating the importance of differential filtration between low- and high-kVp projections and suggesting optimal high-kVp filters in the range Z(filter) = 25-50. For example, added filtration of approximately 2.1 mm Cu, approximately 1.2 mm Zr, approximately 0.7 mm Mo, and approximately 0.6 mm Ag to the high-kVp beam provided optimal (and nearly equivalent) soft-tissue SDNR. Optimal kVp pair and dose allocation were investigated using a chest phantom presenting simulated lung nodules and ribs for thin, average, and thick body habitus. Low- and high-energy techniques ranged from 60-90 kVp and 120-150 kVp, respectively, with peak soft-tissue SDNR achieved at [60/120] kVp for all patient thicknesses and all levels of imaging dose. A strong dependence on the kVp of the low-energy projection was observed. Optimal allocation of dose between low- and high-energy projections was such that approximately 30% of the total dose was delivered by the low-kVp projection, exhibiting a fairly weak dependence on kVp pair and dose. The results have guided the implementation of a prototype DE imaging system for imaging trials in early-stage lung nodule detection and diagnosis.
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Neoplasias Pulmonares/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Radiografia Torácica/instrumentação , Radiografia Torácica/métodos , Cobre/química , Desenho de Equipamento , Humanos , Neoplasias Pulmonares/diagnóstico , Modelos Teóricos , Molibdênio/química , Imagens de Fantasmas , Radiografia/métodos , Radiometria , Prata/química , Técnica de Subtração , Zircônio/químicaRESUMO
Human observer performance tests were conducted to identify optimal imaging techniques in dual-energy (DE) imaging of the chest with respect to a variety of visualization tasks for soft and bony tissue. Specifically, the effect of kVp selection in low- and high-energy projection pairs was investigated. DE images of an anthropomorphic chest phantom formed the basis for observer studies, decomposed from low-energy and high-energy projections in the range 60-90 kVp and 120-150 kVp, respectively, with total dose for the DE image equivalent to that of a single chest radiograph. Five expert radiologists participated in observer preference tests to evaluate differences in image quality among the DE images. For visualization of soft-tissue structures in the lung, the [60/130] kVp pair provided optimal image quality, whereas [60/140] kVp proved optimal for delineation of the descending aorta in the retrocardiac region. Such soft-tissue detectability tasks exhibited a strong dependence on the low-kVp selection (with 60 kVp providing maximum soft-tissue conspicuity) and a weaker dependence on the high-kVp selection (typically highest at 130-140 kVp). Qualitative examination of DE bone-only images suggests optimal bony visualization at a similar technique, viz., [60/140] kVp. Observer preference was largely consistent with quantitative analysis of contrast, noise, and contrast-to-noise ratio, with subtle differences likely related to the imaging task and spatial-frequency characteristics of the noise. Observer preference tests offered practical, semiquantitative identification of optimal, task-specific imaging techniques and will provide useful guidance toward clinical implementation of high-performance DE imaging systems.
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Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/instrumentação , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Radiografia Torácica/instrumentação , Radiografia Torácica/métodos , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Desenho de Equipamento , Humanos , Processamento de Imagem Assistida por Computador , Variações Dependentes do Observador , Imagens de Fantasmas , Doses de Radiação , Reprodutibilidade dos Testes , Tórax/patologiaRESUMO
AIM: The feasibility of coronary artery bypass grafting (CABG) concomitant with aortic valve replacement (AVR) is well established. However, its impact on long-term patient-perceived quality of life (QoL) in the elderly remains undefined. METHODS: Retrospective analysis was conducted on 866 patients 65 years of age and over who underwent AVR between October 1976 and December 1999 with a Carpentier-Edwards porcine bioprosthesis. This cohort was divided between those who underwent isolated AVR (n=438) and those with AVR and concomitant CABG (AVR+CABG; n=428). Mean age was 77.0+/-6.1 years (range, 65 to 91) in the AVR group and 78.2+/-5.5 years (range, 65 to 93) in the AVR+CABG group. QoL was assessed with the Short Form-36 health survey for survivors at follow-up, which was 97% complete. RESULTS: Operative mortality (OM) was 6.2% (27/438) for the AVR group and 8.9% (38/428) for the AVR+CABG group (P=0.130). The occurrence of hospital complications (P=0.162) and postoperative length of stay (P=0.980) was similar for the 2 groups. Actuarial survival at 10 years was 37.1+/-3.4% for AVR and 38.7+/-4% for AVR+CABG patients (P=0.088). On multivariate analyses, CABG was not a predictor of either OM or long-term survival. QoL was similar for the 2 groups on the summary components: physical health (39.4+/-11.4 versus 40.2+/-12.1; P=0.461) and mental health (50.2+/-10.8 versus 51.9+/-10.1; P=0.103). CONCLUSIONS: Despite the presence of severe coronary artery disease, CABG preserved the long-term QoL in elderly patients undergoing AVR.
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Estenose da Valva Aórtica/psicologia , Estenose da Valva Aórtica/cirurgia , Doença da Artéria Coronariana , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/patologia , Estudos de Coortes , Ponte de Artéria Coronária , Feminino , Florida/epidemiologia , Serviços de Saúde para Idosos , Implante de Prótese de Valva Cardíaca , Humanos , Tempo de Internação , Masculino , Prontuários Médicos , Complicações Pós-Operatórias , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Análise de SobrevidaRESUMO
Long-term survival and progression of disability in multiple sclerosis have not been studied previously in Australia. We report the findings in a cohort of 159 patients from Newcastle. Median survival time from onset of symptoms to death was 42 years. When expected survival rates are compared with those of the Australian population, there is approximately a 10% reduction in survival time in multiple sclerosis patients, after 20 years or more from disease onset. The expected time to reach DSS 3 and DSS 6 was 7 years and 27 years respectively. Survival time of multiple sclerosis patients and rate of progression of the disease are similar in the Northern and Southern Hemispheres.
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Esclerose Múltipla , Adulto , Austrália/epidemiologia , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/mortalidade , Esclerose Múltipla/fisiopatologia , Prognóstico , Análise de SobrevidaRESUMO
A new quantitative thin-film X-ray analysis procedure termed the zeta-factor method is proposed. This new zeta-factor method overcomes the two major limitations of the conventional Cliff-Lorimer method for quantification: (1) use of pure-element rather than multielement, thin-specimen standards and (2) built-in X-ray absorption correction with simultaneous thickness determination. Combined with a universal, standard, thin specimen, a series of zeta-factors covering a significant fraction of the periodic table can be estimated. This zeta-factor estimation can also provide information about both the detector efficiency and the microscope-detector interface system. Light-element analysis can also be performed more easily because of the built-in absorption correction. Additionally, the new zeta-factor method has several advantages over the Cliff-Lorimer ratio method because information on the specimen thickness at the individual analysis points is produced simultaneously with compositions, thus permitting concurrent determination of the spatial resolution and the analytical sensitivity. In this work, details of the zeta-factor method and how it improves on the Cliff-Lorimer approach are demonstrated, along with several applications.
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A Nion spherical-aberration (Cs) corrector was recently installed on Lehigh University's 300-keV cold field-emission gun (FEG) Vacuum Generators HB 603 dedicated scanning transmission electron microscope (STEM), optimized for X-ray analysis of thin specimens. In this article, the impact of the Cs-corrector on X-ray analysis is theoretically evaluated, in terms of expected improvements in spatial resolution and analytical sensitivity, and the calculations are compared with initial experimental results. Finally, the possibilities of atomic-column X-ray analysis in a Cs-corrected STEM are discussed.
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The Australian EEG Database is a web-based de-identified searchable database of 18,500 EEG records recorded at a regional public hospital over an 11-year period. Patients range in age from a premature infant born at 24 weeks gestation, through to people aged over 90 years. This paper will describe the history of the database, the range of patients represented in the database, and the nature of the text-based and digital data contained in the database. Preliminary results of the first two studies undertaken using the database are presented. Plans for sharing data from the Australian EEG database with researchers are discussed. We anticipate that such data will be useful in not only helping to answer clinical questions but also in the field of mathematical modeling of the EEG.
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Sistemas de Gerenciamento de Base de Dados , Bases de Dados Factuais , Eletroencefalografia/métodos , Disseminação de Informação/métodos , Armazenamento e Recuperação da Informação/métodos , Sistemas Computadorizados de Registros Médicos , Interface Usuário-Computador , Adolescente , Adulto , Idoso , Animais , Austrália , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Eletroencefalografia/normas , Humanos , Lactente , Recém-Nascido , Armazenamento e Recuperação da Informação/normas , Internet , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS FNA) is a relatively new imaging modality that has been reported to be useful for mediastinal nodal staging of lung cancer and for the evaluation of mediastinal adenopathy of unknown cause. However, the technique is not commonly used in Australia. METHODS: A retrospective review of all patients who had mediastinal EUS FNA was undertaken. Of a total of 787 patients who had undergone endoscopic ultrasound (EUS) studies from November 1999 to March 2004, 27 patients were identified to have had mediastinal EUS FNA. Details were recorded including study indication, history of malignancy, source of referral, prior attempts for tissue diagnosis, EUS and EUS FNA findings, complications, surgical pathology if available and clinical outcome after diagnosis. RESULTS: Mediastinal EUS FNA was performed on an outpatient basis and no complications were recorded. Diagnostic material was obtained from all patients with a mean number of three passes. Nodal stations sampled included left paratracheal, subcarinal, aortopulmonary window and inferior mediastinum. Indications for the studies included mediastinal adenopathy of uncertain cause (17), lung cancer staging (7) and gastrointestinal cancer staging (3). EUS FNA confirmed malignancy in 16/27 patients, sarcoidosis in three patients, tuberculosis in one patient and seven patients were deemed to have reactive adenopathy. Primary cytopathological diagnosis of malignancy was determined by EUS FNA in nine patients. CONCLUSIONS: EUS FNA is a safe, efficient and effective modality for mediastinal staging of lung cancer and for the diagnosis of mediastinal adenopathy of uncertain origin. EUS FNA has the potential to significantly impact on patient management, avoiding more invasive procedures as well as unnecessary operations.
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Biópsia por Agulha Fina/métodos , Endossonografia , Linfonodos/patologia , Doenças Linfáticas/diagnóstico , Mediastino , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Endossonografia/instrumentação , Desenho de Equipamento , Seguimentos , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
AIMS: Previous isobolographic analysis revealed that coadministration of morphine and oxycodone produces synergistic antinociception in laboratory rodents. As both opioids can produce ventilatory depression, this study was designed to determine whether their ventilatory effects were synergistic when coadministered to healthy human subjects. METHODS: A placebo-controlled, randomized, crossover study was performed in 12 male volunteers. Ventilatory responses to hypoxaemia and hypercapnia were determined from 1-h intravenous infusions of saline ('placebo'), 15 mg morphine sulphate (M), 15 mg oxycodone hydrochloride (O), and their combination in the dose ratios of 1:2, 1:1, 2:1. Drug and metabolite concentrations in serial peripheral venous blood samples were measured by high-performance liquid chromatography-MS/MS. RESULTS: 'Placebo' treatment was without significant ventilatory effects. There were no systematic differences between active drug treatments on either the slopes or intercepts of the hypoxaemic and hypercapnia ventilation responses. During drug treatment, the mean minute ventilation at PetCO(2) = 55 mmHg (V(E55)) decreased to 74% of the subjects' before treatment values (95% confidence interval 62, 87), 68% (57, 80), 69% (59, 79), 68% (63, 73), and 61% (52, 69) for M15, M10/O5, M7.5/O7.5, M5/O10 and O15, respectively. Recovery was more prolonged with increasing oxycodone doses, corresponding to its greater potency and lower clearance compared with morphine. CONCLUSIONS: Although adverse ventilatory effects of these drugs were found as expected, no unexpected or disproportionate effects of any of the morphine and oxycodone treatments were found that might impede their use in combination for pain management.
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Analgésicos Opioides/farmacologia , Dióxido de Carbono/sangue , Morfina/farmacologia , Oxicodona/farmacologia , Oxigênio/sangue , Respiração/efeitos dos fármacos , Adolescente , Adulto , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/sangue , Estudos Cross-Over , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Morfina/sangue , Oxicodona/administração & dosagem , Oxicodona/sangueRESUMO
The prevalence of multiple sclerosis (MS) in Newcastle, Australia increased significantly between 1961 and 1981 and the incidence of the disease also increased between the decades 1950-1959 and 1971-1981. The present study sought to determine whether there has been a further increase in the frequency of MS in the subsequent 15 years, and to examine the potential factors underlying this change. The incidence, prevalence and clinical profile of multiple sclerosis were therefore re-examined in Newcastle, Australia in 1996 using comparable diagnostic criteria and methods to those employed in studies in the same region in 1961 and 1981. There has been a significant progressive increase in prevalence from 19.6 to 59.1 per 100,000 population and a significant increase in incidence from 1.2 to 2.4 per 100,000 population from 1961 to 1996. The most pronounced increase in prevalence was in females and in the age-group over 60 years, and there was also an increased incidence in females aged 20-29 years. There was little change in the age of disease onset, but duration of disease in females had increased substantially. The significant increase in prevalence is attributed to increased incidence, particularly in females; and to increased survival. Although such trends in prevalence have been observed in the Northern Hemisphere, this is the first such study in the Southern Hemisphere to show a longitudinal increase in prevalence and incidence over a period of this duration.
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Esclerose Múltipla/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Envelhecimento , Austrália/epidemiologia , Criança , Progressão da Doença , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Prevalência , Caracteres SexuaisRESUMO
OBJECTIVE: To report a successful IVF pregnancy in an infertile couple after conservative treatment of endometrial cancer. DESIGN: Case report and literature review. SETTING: University teaching hospital. PATIENT(S): A 29-year-old infertile white woman. MAIN OUTCOME MEASURE(S): Successful pregnancy after conservative management of endometrial cancer. INTERVENTION(S): Grade 1 endometrial adenocarcinoma diagnosed at hysteroscopy, followed by dilatation and curettage (D&C). On follow-up D&C, pathologic examination was normal after high-dose progesterone therapy. The patient subsequently underwent an IVF cycle with transfer of three blastocysts. RESULT(S): The patient delivered triplets by cesarean section. Laparoscopic-assisted vaginal hysterectomy and bilateral salpingo-oophorectomy was then done. No residual endometrial cancer was evident in the hysterectomy specimen, but a 1.1-cm cystic mixed endometrioid and clear cell-type adenocarcinoma was discovered in the left ovary. The patient is doing well after 3 cycles of chemotherapy; her CA-125 level is normal. The triplets are also doing well. CONCLUSION(S): In carefully chosen situations, deferring surgery in infertile patients with endometrial cancer may be a viable option permitting subsequent successful pregnancy.
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Adenocarcinoma/terapia , Neoplasias do Endométrio/terapia , Fertilização in vitro , Gravidez , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia Vaginal , Segunda Neoplasia Primária/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Fatores de Tempo , Resultado do TratamentoRESUMO
Benzodiazepines allosterically modulate GABA(A) receptors to increase currents induced by submaximal GABA concentrations. Benzodiazepine-induced conformational changes in the transmembrane domain increase the reactivity of cysteines substituted for a subset of residues in the alpha(1) subunit M3 membrane-spanning segment. With the cysteine-substitution mutant alpha(1)F296Cbeta(1)gamma(2) we previously noted that p-chloromercuribenzenesulfonate (pCMBS(-)) modification in the presence of diazepam potentiated subsequent GABA-induced currents. In contrast, pCMBS(-) modification in the presence of GABA caused inhibition of subsequent responses. We now show that in the presence of diazepam, pCMBS(-) only reacts with the engineered cysteine in one of the two alpha subunits; whereas, in the presence of GABA, pCMBS(-) reacts with the cysteine in the other alpha subunit, or with both cysteines. This implies that the two alpha subunits have distinct conformations in the diazepam-bound state. Based on analysis of single channel kinetic data, others have hypothesized that diazepam only alters the GABA affinity of one of the two GABA binding sites. The results presented here provide structural evidence to support the hypothesis that diazepam binding only alters the conformation of one of the two alpha subunits in a GABA(A) receptor and provides new insights into the mechanism of allosteric potentiation by benzodiazepines.
Assuntos
Anticonvulsivantes/metabolismo , Diazepam/metabolismo , Receptores de GABA-A/química , Receptores de GABA-A/metabolismo , Regulação Alostérica/fisiologia , Animais , Feminino , Ratos , Xenopus laevis , Ácido gama-Aminobutírico/metabolismoRESUMO
A fundamental limitation of X-ray energy-dispersive (EDS) spectrometry is the detection and quantitative analysis of characteristic X-rays from one element, in the presence of an overlapping peak from another element. This problem is particularly acute when the unambiguous detection of one element is crucial to ensuring the mechanical performance of the material, such as the presence of an embrittling species. This paper addresses the specific problem of defining the conditions of specimen composition and thickness under which phosphorus can be detected in the presence of molybdenum, since the Mo L1 and the P Kalpha elemental peaks are separated by 2eV. This separation is significantly below the resolution limit of X-ray spectrometry in the electron microscope. Simulations of the X-ray spectra from low-alloy steels have been performed via Desk-Top Spectrum Analyzer and compared with experimental measurements on a field-emission gun VG HB 603 dedicated scanning transmission electron microscope.