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BACKGROUND: Children from low-socioeconomic backgrounds exhibit more behavioural difficulties than those from more affluent families. Influential theoretical models specify family stress and child characteristics as mediating this effect. These accounts, however, have often been based on cross-sectional data or longitudinal analyses that do not capture all potential pathways, and therefore may not provide good policy guidance. METHODS: In a UK representative sample of 2399 children aged 5-15, we tested mediation of the effect of household income on parent and teacher reports of conduct problems (CP) via unhealthy family functioning, poor parental mental health, stressful life events, child physical health and reading ability. We applied cross-lagged longitudinal mediation models which allowed for testing of reciprocal effects whereby the hypothesised mediators were modelled as outcomes as well as predictors of CP. RESULTS: We found the predicted significant longitudinal effect of income on CP, but no evidence that it was mediated by the child and family factors included in the study. Instead, we found significant indirect paths from income to parental mental health, child physical health and stressful life events that were transmitted via child CP. CONCLUSION: The results confirm that income is associated with change in CP but do not support models that suggest this effect is transmitted via unhealthy family functioning, parental mental health, child physical health, stressful life events or reading difficulties. Instead, the results highlight that child CP may be a mediator of social inequalities in family psychosocial functioning.
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Renda , Saúde Mental , Criança , Humanos , Adolescente , Estudos Transversais , Fatores Socioeconômicos , Inquéritos e Questionários , Pais/psicologiaRESUMO
Over the past decade, the increasing availability of the World Wide Web has held out the possibility that the efficiency of scientific measurements could be enhanced in cases where experiments were being conducted at distant facilities. Examples of early successes have included X-ray diffraction (XRD) experimental measurements of protein crystal structures at synchrotrons and access to scanning electron microscopy (SEM) and NMR facilities by users from institutions that do not possess such advanced capabilities. Experimental control, visual contact, and receipt of results has used some form of X forwarding and/or VNC (virtual network computing) software that transfers the screen image of a server at the experimental site to that of the users' home site. A more recent development is a web services platform called Science Studio that provides teams of scientists with secure links to experiments at one or more advanced research facilities. The software provides a widely distributed team with a set of controls and screens to operate, observe, and record essential parts of the experiment. As well, Science Studio provides high speed network access to computing resources to process the large data sets that are often involved in complex experiments. The simple web browser and the rapid transfer of experimental data to a processing site allow efficient use of the facility and assist decision making during the acquisition of the experimental results. The software provides users with a comprehensive overview and record of all parts of the experimental process. A prototype network is described involving X-ray beamlines at two different synchrotrons and an SEM facility. An online parallel processing facility has been developed that analyzes the data in near-real time using stream processing. Science Studio and can be expanded to include many other analytical applications, providing teams of users with rapid access to processed results along with the means for detailed discussion of their significance.
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BACKGROUND: Patients with advanced biliary tract cancer who progress on first-line therapy have limited treatment options. The TreeTopp study assessed varlitinib, a reversible small molecule pan-human epidermal growth factor receptor inhibitor, plus capecitabine in previously treated advanced biliary tract cancer. PATIENTS AND METHODS: This global, double-blind, randomized, placebo-controlled phase II study enrolled patients with confirmed unresectable or metastatic biliary tract cancer and disease progression after one prior line of gemcitabine-containing chemotherapy. Patients received oral varlitinib 300 mg or placebo twice daily (b.i.d.) for 21 days, plus oral capecitabine 1000 mg/m2 b.i.d. on days 1-14, in 21-day treatment cycles. Co-primary endpoints were objective response rate and progression-free survival (PFS) according to RECIST v1.1 by Independent Central Review. RESULTS: In total, 127 patients received varlitinib plus capecitabine (n = 64) or placebo plus capecitabine (n = 63). The objective response rate was 9.4% with varlitinib plus capecitabine versus 4.8% with capecitabine alone (odds ratio 2.28; P = 0.42). Median PFS was 2.83 versus 2.79 months [hazard ratio (HR), 0.90; 95% confidence interval (CI), 0.60-1.37; P = 0.63] and overall survival was 7.8 versus 7.5 months (HR, 1.11; 95% CI, 0.69-1.79; P = 0.66), respectively. In a subgroup analysis, the addition of varlitinib appeared to provide a PFS benefit in female patients (median, 4.1 versus 2.8 months; HR, 0.59; 95% CI, 0.28-1.23) and those with gallbladder cancer (median, 2.9 versus 1.6 months; HR, 0.55; 95% CI, 0.26-1.19). Grade ≥3 treatment-emergent adverse events were reported in 65.6% of patients receiving varlitinib plus capecitabine versus 58.7% of those receiving capecitabine alone. CONCLUSIONS: In patients with advanced biliary tract cancer, second-line treatment with varlitinib plus capecitabine was well tolerated but did not improve efficacy versus capecitabine alone. A PFS benefit was suggested in female patients and those with gallbladder cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/patologia , Capecitabina/farmacologia , Capecitabina/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Intervalo Livre de ProgressãoRESUMO
Numerical and computational modelling of flow and pollutant dynamics in urban drainage systems is becoming more and more integral to planning and design. The main aim of integrated flow and pollutant models is to quantify the efficiency of different measures at reducing the amount of pollutants discharged into receiving water bodies and minimise the consequent negative water quality impact. The open source toolbox CITY DRAIN developed in the Matlab/Simulink environment, which was designed for integrated modelling of urban drainage systems, is used in this work. The goal in this study was to implement and test computational routines for representing sediment and pollutant loads in order to evaluate catchment surface pollution. Tested models estimate the accumulation, erosion and transport of pollutants--aggregately--on urban surfaces and in sewers. The toolbox now includes mathematical formulations for accumulation of pollutants during dry weather period and their wash-off during rainfall events. The experimental data acquired in a previous research project carried out by the Environmental Engineering Research Centre (CIIA) at the Universidad de los Andes in Bogotá (Colombia) was used for the calibration of the models. Different numerical approaches were tested for their ability to calibrate to the sediment transport conditions. Initial results indicate, when there is more than one peak during the rainfall event duration, wash-off processes probably can be better represented using a model based on the flow instead of the rainfall intensity. Additionally, it was observed that using more detailed models (compared with an instantaneous approach) for representing pollutant accumulation do not necessarily lead to better results.
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Simulação por Computador , Sedimentos Geológicos , Modelos Teóricos , Movimentos da Água , Poluentes Químicos da Água , Cidades , Colômbia , Rios , Engenharia Sanitária , Fatores de Tempo , Incerteza , Poluentes da Água , Poluição da Água/prevenção & controleRESUMO
Current climate projections for the Great Plains of North America indicate markedly increased air temperatures by the end of the current century. Because the Great Plains contains >80,000 intermittent wetlands that serve as irreplaceable wildlife habitat, this projected warming may have profound effects throughout a continental-scale trophic network. However, little research has been done to determine how projected warming may affect the growth, development, or survival of even common species in this region. We conducted laboratory warming experiments, using an abundant amphibious predatory insect, Enallagma civile (Hagen, 1861), as a model organism, to determine whether projected warming may affect development or survival. Eggs were collected and reared under four water temperature regimes representing current (26°C) and projected future conditions (32, 38, and 41°C). Nymph body size after each molt, development rate, and deaths were recorded. Elevated water temperatures were found to significantly affect the survivorship of E. civile eggs and nymphs as well as adult body size at emergence: an increase in temperature incurred a decrease in survival and size. Nymphs in the two hotter treatments were smaller and had low survivorship whereas individuals in the cooler temperatures generally survived to adulthood and were larger. Nymphs reared at 32°C experienced accelerated ontogenetic development compared with the other temperatures, going from egg to adult in 26 d. Projected elevated temperatures may, thus, be both advantageous and detrimental, causing concern for aquatic invertebrates in this region in the future.
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Mudança Climática , Odonatos , Animais , América do Norte , Óvulo , Temperatura , ÁguaRESUMO
We used a dual-isotope method (oral [1-14C]glucose and intravenous [6-3H]glucose) to examine whether the oral glucose intolerance of cirrhosis is due to (a) a greater input of glucose into the systemic circulation (owing to a lower first-pass hepatic uptake of ingested glucose, or to impaired inhibition of hepatic glucose output), (b) a lower rate of glucose removal, or (c) a combination of these mechanisms. Indirect calorimetry was used to measure oxidative and nonoxidative metabolism. Basal plasma glucose levels (cirrhotics, 5.6 +/- 0.4[SE], controls, 5.1 +/- 0.2 mmol/liter), and rates of glucose appearance (Ra) and disappearance (Rd) were similar in the two groups. After 75 g of oral glucose, plasma glucose levels were higher in cirrhotics than controls, the curves diverging for 80 min despite markedly higher insulin levels in cirrhotics. During the first 20 min, there was very little change in glucose Rd and the greater initial increase in plasma glucose in cirrhotics resulted from a higher Ra of ingested [1-14C]glucose into the systemic circulation, suggesting a reduced first-pass hepatic uptake of portal venous glucose. The continuing divergence of the plasma glucose curves was due to a lower glucose Rd between 30 and 80 min (cirrhotics 236 +/- 17 mg/kg in 50 min, controls 280 +/- 17 mg/kg in 50 min, P < 0.05, one-tailed test). Glucose metabolic clearance rate rose more slowly in cirrhotics and was significantly lower than in controls during the first 2 h after glucose ingestion (2.24 +/- 0.17 vs 3.30 +/- 0.23 ml/kg per min, P < 0.005), in keeping with their known insulin insensitivity. Despite the higher initial glucose Ra in cirrhotics, during the entire 4-h period the quantity of total glucose and of ingested glucose (cirrhotics 54 +/- 2 g [72% of oral load], controls 54 +/- 3 g) appearing in the systemic circulation were similar. Overall glucose Rd (cirrhotics 72.5 +/- 3.8 g/4 h, controls 77.2 +/- 2.2 g/4h) and percent suppression of hepatic glucose output over 4 h (cirrhotics, 53 +/- 10%, controls 49 +/- 8%) were also similar. After glucose ingestion much of the extra glucose utilized was oxidized to provide energy that in the basal state was derived from lipid fuels. Glucose oxidation after glucose ingestion was similar in both groups and accounted for approximately two-thirds of glucose Rd. The reduction in overall nonoxidative glucose disposal did not reach significance (21 +/- 5 vs. 29 +/- 3 g/4 h, 0.05 < P < 0.1). Although our data would be compatible with an impairment of tissue glycogen deposition after oral glucose, glucose storage as glycogen probably plays a small part part in overall glucose disposal. Our results suggest that the higher glucose levels seen in cirrhotics after oral glucose are due initially to an increase in the amount of ingested glucose appearing in the systemic circulation, and subsequently to an impairment in glucose uptake by tissues due to insulin insensitivity. Impaired suppression of hepatic glucose output does not contribute to oral glucose intolerance.
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Glicemia/metabolismo , Glucose/metabolismo , Cirrose Hepática Alcoólica/metabolismo , Administração Oral , Radioisótopos de Carbono , Glucose/administração & dosagem , Glicólise , Humanos , Insulina/sangue , Cinética , Cirrose Hepática Alcoólica/sangue , Pessoa de Meia-Idade , Técnica de Diluição de Radioisótopos , Valores de Referência , Fatores de Tempo , TrítioRESUMO
Echinocytes were frequently found in patients with liver disease when their blood was examined in wet films, but rarely detected in dried, stained smears. When normal erythrocytes (discocytes) were incubated with physiologic concentrations of the abnormal high density lipoproteins (HDL) from some jaundiced patients, echinocytosis developed within seconds. Other plasma fractions were not echinocytogenic. There was a close correlation between the number of echinocytes found in vivo and the ability of the corresponding HDL to induce discocyte-echinocyte transformation. On incubation with normal HDL, echinocytes generated in vitro rapidly reverted to a normal shape, and echinocytes from patients showed a similar trend. Echinocytosis occurred without change in membrane cholesterol content, as did its reversal, and was not caused by membrane uptake of lysolecithin or bile acids. Abnormal, echinocytogenic HDL showed saturable binding to approximately 5,000 sites per normal erythrocyte with an association constant of 10(8) M-1. Nonechinocytogenic patient HDL and normal HDL showed only nonsaturable binding. Several minor components of electrophoretically separated erythrocyte membrane proteins bound the abnormal HDL; pretreatment of the cells with trypsin or pronase reduced or eliminated binding. Echinocytosis by abnormal HDL required receptor occupancy, rather than transfer of constituents to or from the membrane, because cells reversibly prefixed in the discoid shape by wheat germ agglutinin, and then exposed to abnormal HDL, did not become echinocytes when the HDL and lectin were successively removed. Binding did not cause dephosphorylation of spectrin. We conclude that the echinocytes of liver disease are generated from discocytes by abnormal HDL, and we infer that the shape change is mediated by cell-surface receptors for abnormal HDL molecules.
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Eritrócitos Anormais/patologia , Lipoproteínas HDL/sangue , Hepatopatias/sangue , Carcinoma/sangue , Membrana Eritrocítica/ultraestrutura , Eritrócitos Anormais/ultraestrutura , Feminino , Hepatite/sangue , Hepatite Alcoólica/sangue , Hepatite Crônica/sangue , Doença de Hodgkin/sangue , Humanos , Cirrose Hepática/sangue , Cirrose Hepática Biliar/sangue , Masculino , Neoplasias Pancreáticas/sangueRESUMO
Liquid 1-decanethiol was confined on an atomic force microscope (AFM) tip apex and the effect was investigated by measuring amplitude-distance curves in dynamic force mode. Within the working distance in the dynamic force mode AFM, the thiol showed strong interactions bridging between a gold-coated probe tip and a gold-coated Si substrate, resulting in unstable amplitude and noisy AFM images. We show that under such a situation, the amplitude change is dominated by the extra forces induced by the active material loaded on the tip apex, overwhelming the amplitude change caused by the geometry of the sample surface, thus resulting in noise in the image the tip collects. We also show that such a contaminant may be removed from the apex by pushing the tip into a material soft enough to avoid damage to the tip.
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We describe a simple experimental approach for delivering self-assembled monolayers (SAMs) of octadecylphosphonic acid (OPA) on many oxide surfaces using a nonpolar medium with a dielectric constant around 4 (e.g., trichloroethylene). This approach readily results in the formation of full-coverage OPA SAMs on a wide variety of oxide surfaces including cleaved mica, Si wafer, quartz, and aluminum. Especially, the availability of delivering full-coverage OPA SAM on a Si wafer is unique, as no OPA SAMs at all could be formed on a Si wafer when using a polar OPA solution. The reason a nonpolar solvent is superior lies in the very fact that the hydrophilic OPA headgroup tends to escape from the nonpolar solution and is thus enriched at the medium-air interface. It is these OPA headgroups seeking a hydrophilic surface that make possible the well-controlled OPA monolayer on an oxide surface.
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In patients with liver disease there are usually increases in erythrocyte cholesterol and phosphatidylcholine concentrations. This increase in membrane lipid changes the shape of the erythrocyte and "spur" or "target" cells may be present. Sodium fluxes were measured in erythrocytes from 17 patients with a variety of liver diseases and from 17 normal subjects and the values related to the lipid content of the membrane. Ouabain-insensitive and ouabain-sensitive effluxes were lower in patients than in normal subjects and the reduction in ouabain-insensitive efflux was more marked. Sodium influx was also significantly lower in erythrocytes from patients than controls. Ouabain-sensitive and ouabain-insensitive effluxes and sodium influx did not correlate with the cholesterol content of erythrocytes from patients. Significant negative correlations were noted between ouabain-insensitive sodium efflux (r=--0.63, P less than 0.01), sodium influx (r=--0.61, P less than 0.01) and intracellular sodium concentration (r=--0.66, P less than 0.01) and the cholesterol : phospholipid molar ratio of the cell but there was no significant correlation between this ratio and the ouabain-sensitive sodium efflux (r=0.41, P less than 0.05). These results support the hypothesis that an altered lipid composition may affect the permeability of the erythrocyte membrane in patients with liver disease.
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Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Hepatopatias/sangue , Lipídeos de Membrana/sangue , Sódio/sangue , Transporte Biológico , Transporte Biológico Ativo/efeitos dos fármacos , Colesterol/sangue , Membrana Eritrocítica/efeitos dos fármacos , Humanos , Ouabaína/farmacologia , Fosfatidilcolinas/sangueRESUMO
Lipid molecules in lipoprotein surfaces exchange with their counterparts in cell plasma membranes. In human or experimental liver disease, plasma lipoprotein surfaces are enriched in cholesterol and deficient in arachidonate; corresponding alterations occur in membrane lipids of erythrocytes. To determine whether similar changes take place in membranes of nucleated cells, the lipid content of plasma and of erythrocyte, liver and kidney membranes was measured in rats with acute (3-day) galactosamine-induced hepatitis or chronic (3-week) biliary obstruction. In both models of liver injury the cholesterol:phospholipid ratio in plasma and in erythrocytes was significantly increased (P less than 0.001). Although this ratio was also elevated in liver and kidney microsomes, only in liver microsomes of obstructed rats was the increase significant (P less than 0.001). However, the cholesterol:phospholipid ratio of kidney brush-border membranes, was significantly higher in bile-duct-ligated rats; presumably, compensating mechanisms limit cholesterol accumulation in intracellular membranes. Kidney brush-border membranes from obstructed rats were deficient in arachidonate as were plasma and erythrocytes. However, arachidonate levels were unchanged in kidney microsomes; renal delta 6-desaturase, the rate-limiting enzyme in the conversion of linoleic acid to arachidonic acid, was increased by 50% (P less than 0.001) and may have counteracted a reduced supply of exogenous lipoprotein arachidonate. We conclude that in experimental liver disease lipoprotein-induced lipid abnormalities can occur in renal membranes, although compensatory mechanisms may operate; the alterations seen, cholesterol accumulation and arachidonate depletion, would be expected to interfere with sodium transport and prostaglandin production, respectively. Our findings support the hypothesis that lipid abnormalities in kidney membranes contribute to the renal dysfunction which is a frequent complication of human liver disease.
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Membrana Eritrocítica/análise , Hepatite/metabolismo , Córtex Renal/análise , Hepatopatias/metabolismo , Fígado/análise , Lipídeos de Membrana/análise , Doença Aguda , Animais , Ductos Biliares/fisiologia , Membrana Celular/análise , Doença Hepática Induzida por Substâncias e Drogas , Colesterol/análise , Doença Crônica , Galactosamina , Masculino , Lipídeos de Membrana/sangue , Microssomos/análise , Microssomos Hepáticos/análise , Microvilosidades/análise , Microvilosidades/ultraestrutura , Fosfolipídeos/análise , Ratos , Ratos Endogâmicos , Triglicerídeos/análiseRESUMO
The protein sequencing of tryptic peptides from purified human lecithin: cholesterol acyltransferase (LCAT) identified sufficient amino-acid sequence to construct a corresponding mixed oligonucleotide probe. This was used to screen an adult human cDNA liver library, from which incomplete cDNA clones were isolated. The DNA sequence of these clones allows the prediction of the entire amino-acid sequence of the mature LCAT enzyme. The mature protein consists of 416 amino acids and contains several marked stretches of hydrophobic residues and four potential glycosylation sites. The cDNA probe detects LCAT mRNA sequences approx. 1500 bases long in human liver, but not intestine, RNA. The cDNA probe was used to isolate LCAT genomic recombinants from a human genomic library. Southern blotting data, and restriction site mapping, suggest that there is a single human LCAT structural gene between 4.3 and 5.5 kb in size.
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Clonagem Molecular , DNA/isolamento & purificação , Genes , Fosfatidilcolina-Esterol O-Aciltransferase/genética , Sequência de Aminoácidos , Sequência de Bases , Enzimas de Restrição do DNA , Humanos , Dados de Sequência Molecular , Fragmentos de Peptídeos/análise , Fosfatidilcolina-Esterol O-Aciltransferase/sangue , PlasmídeosRESUMO
BACKGROUND/OBJECTIVES: An increased risk of mortality and cardiovascular disease (CVD) is observed in people with chronic kidney disease (CKD) even in early stages. Dietary sodium intake has been associated with important CVD and CKD progression risk factors such as hypertension and proteinuria in this population. We aimed to investigate the relationship between sodium intake and CVD or CKD progression risk factors in a large cohort of patients with CKD stage 3 recruited from primary care. SUBJECTS/METHODS: A total of 1733 patients with previous estimated glomerular filtration rate (eGFR) of 30-59 ml/min/1.73m(2), with a mean age 72.9±9.0 years, were recruited from 32 general practices in primary care in England. Medical history was obtained and participants underwent clinical assessment, urine and serum biochemistry testing. Sodium intake was estimated from three early-morning urine specimens using an equation validated for this study population. RESULTS: Sixty percent of participants who had estimated sodium intake above recommendation (>100 mmol/day or 6 g salt/day) also had higher diastolic blood pressure, mean arterial pressure (MAP), urinary albumin-to-creatinine ratio, high-sensitive C-reactive protein and uric acid and used a greater number of anti-hypertensive drugs. In multivariable regression analysis, excessive sodium intake was an independent predictor of MAP (B=1.57, 95% confidence interval (CI) 0.41-2.72; P=0.008) and albuminuria (B=1.35, 95% CI 1.02-1.79; P=0.03). CONCLUSIONS: High sodium intake was associated with CVD and CKD progression risk factors in patients with predominantly early stages of CKD followed up in primary care. This suggests that dietary sodium intake could afffect CVD risk even in early or mild CKD. Intervention studies are warranted to investigate the potential benefit of dietary advice to reduce sodium intake in this population.
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Doenças Cardiovasculares/etiologia , Falência Renal Crônica/etiologia , Sódio na Dieta/intoxicação , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Estudos Transversais , Progressão da Doença , Inglaterra/epidemiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/etiologia , Incidência , Mediadores da Inflamação/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/urina , Masculino , Atenção Primária à Saúde , Estudos Prospectivos , Proteinúria/epidemiologia , Proteinúria/etiologia , Fatores de Risco , Índice de Gravidade de Doença , Sódio/urinaRESUMO
Thirty-six patients with primary biliary cirrhosis (PBC) receiving calcium and calciferol supplements (100,000 IU monthly by im injection) were investigated for their calcium, vitamin D, PTH, and osteocalcin status. The corrected plasma calcium concentrations in PBC patients were significantly greater than those in normal subjects. While the mean serum 25-hydroxycholecalciferol and 1,25-dihydroxyvitamin D concentrations in these patients were similar to those in normal subjects, the mean serum PTH concentration was significantly greater, and it was supranormal in 11 patients. Three patients had elevated corrected calcium concentrations; 1 of them had a concomitant increase in ionized calcium and a supranormal PTH level, and another had a high normal PTH. Ionized calcium concentrations were normal in the rest. Serum osteocalcin concentrations were significantly lower in the patients compared with those in normal subjects. These results indicate that PTH concentrations are frequently elevated in PBC patients despite adequate vitamin D supplementation and normal or even supranormal plasma calcium concentrations. Nonsuppression of PTH concentrations and autonomy of PTH secretion suggest that vitamin D deficiency and secondary hyperparathyroidism in such patients probably occur much earlier in the natural history of this disease than is currently realized. Persistent nonsuppressible hypersecretion of PTH probably contributes to the bone disease of primary biliary cirrhosis. The low osteocalcin concentrations probably reflect diminished osteoblastic activity, which may also contribute to osteopenia in these patients.
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Proteínas de Ligação ao Cálcio/sangue , Ergocalciferóis/uso terapêutico , Hiperparatireoidismo/etiologia , Cirrose Hepática Biliar/complicações , Adulto , Idoso , Calcifediol/sangue , Calcitriol/sangue , Cálcio/sangue , Cálcio/uso terapêutico , Feminino , Humanos , Hiperparatireoidismo/sangue , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Osteocalcina , Hormônio Paratireóideo/sangueRESUMO
OBJECTIVE: The purpose of this paper is to provide a comprehensive review of information accumulated over the past 26 years regarding the psychometric properties and utility of the Mini-Mental State Examination (MMSE). PARTICIPANTS: The reviewed studies assessed a wide variety of subjects, ranging from cognitively intact community residents to those with severe cognitive impairment associated with various types of dementing illnesses. MAIN OUTCOME MEASURES: The validity of the MMSE was compared against a variety of gold standards, including DSM-III-R and NINCDS-ADRDA criteria, clinical diagnoses, Activities of Daily Living measures, and other tests that putatively identify and measure cognitive impairment. RESULTS: Reliability and construct validity were judged to be satisfactory. Measures of criterion validity showed high levels of sensitivity for moderate-to-severe cognitive impairment and lower levels for mild degrees of impairment. Content analyses revealed the MMSE was highly verbal, and not all items were equally sensitive to cognitive impairment. Items measuring language were judged to be relatively easy and lacked utility for identifying mild language deficits. Overall, MMSE scores were affected by age, education, and cultural background, but not gender. CONCLUSIONS: In general, the MMSE fulfilled its original goal of providing a brief screening test that quantitatively assesses the severity of cognitive impairment and documents cognitive changes occurring over time. The MMSE should not, by itself, be used as a diagnostic tool to identify dementia. Suggestions for the clinical use of the MMSE are made.
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Transtornos Cognitivos/diagnóstico , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Atividades Cotidianas , Fatores Etários , Idoso , Transtornos Cognitivos/psicologia , Demência/diagnóstico , Demência/psicologia , Feminino , Humanos , Probabilidade , Escalas de Graduação Psiquiátrica/normas , Testes Psicológicos/normas , Testes Psicológicos/estatística & dados numéricos , Psicometria , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Fatores SexuaisRESUMO
Immunoreactive trypsin concentration and pancreatic lipase activity were measured in the sera of 33 patients with primary biliary cirrhosis. Immunoreactive trypsin was increased (above the normal range) in 16 (48%) and pancreatic lipase activity in 18 (55%) patients. Both enzymes were increased in 10 (30%) patients. Twenty four patients (73%) had an increase of either one or both enzymes. There was a significant correlation between immunoreactive trypsin and pancreatic lipase activity. This abnormality was not related to treatment with D-penicillamine, the age of the patients, the stage of the disease, or the severity of cholestasis. Thus most patients with primary biliary cirrhosis have increased pancreatic enzyme activity and immunoreactive trypsin concentration in their sera. These data are indicative of damage to the exocrine pancreas. The cause of this damage is as yet unknown.
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Isoenzimas/sangue , Lipase/sangue , Cirrose Hepática Biliar/enzimologia , Tripsina/sangue , Fatores Etários , Idoso , Feminino , Humanos , Cirrose Hepática Biliar/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pâncreas/enzimologia , Penicilamina/uso terapêuticoRESUMO
We used isotope dilution techniques (constant intravenous [IV] infusion of 2-3H-glycerol and 1-14C-palmitate) and indirect calorimetry to measure lipid kinetics and substrate oxidation rates during IV fructose administration at 200 and then 500 mg/kg/h in eight cirrhotic patients and seven normal control subjects. Fasting plasma glucose, glycerol, and glycerol appearance rate (Ra) were similar in both groups, but insulin levels were fourfold higher in cirrhotics (P < .01). Fasting serum nonesterified fatty acid (NEFA) levels (cirrhotics, 869 +/- 124, controls, 717 +/- 90 mumol/L) and NEFA Ra (7.1 +/- 0.8 v 5.5 +/- 0.9 mumol/min/kg) were higher in cirrhotics, but the differences were not significant. Plasma fructose was similar in both groups at both fructose infusion rates. Fructose appeared to stimulate insulin secretion. With i.v. fructose, serum NEFA levels decreased, reaching similar low levels when 500 mg/kg/h was infused, due to a reduction in NEFA Ra and an increase in the NEFA metabolic clearance rate (MCR). Glycerol levels showed little change. As glycerol Ra decreased by less than 20% in both groups, the decrease in serum NEFA was primarily due to enhanced reesterification of fatty acids both within adipose tissue (preventing their release) and in other tissues (enhancing their removal from plasma). Although total fructose utilization was normal in cirrhotics, they oxidized more of the infused fructose; nonoxidative disposal was reduced (first step, 242 +/- 12 v 318 +/- 16 mg/kg in 2 hours, P < .002; second step, 657 +/- 32 v 786 +/- 21 mg/kg in 2 hours, P < .005). Although tissue fructose uptake is insulin-independent, insulin resistance in cirrhosis may influence the intracellular metabolism of fructose.
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Frutose/farmacologia , Metabolismo dos Lipídeos , Cirrose Hepática/metabolismo , Adulto , Metabolismo Energético , Ácidos Graxos não Esterificados/sangue , Feminino , Glicerol/sangue , Humanos , Infusões Intravenosas , Insulina/sangue , Cinética , Masculino , Pessoa de Meia-Idade , Oxirredução , Valores de ReferênciaRESUMO
We used specific, monoclonal antibody-based, two-site immunoradiometric assays to test the hypothesis that serum levels of proinsulin and des-31,32 proinsulin would be increased in cirrhosis, particularly in those with overt diabetes. A 75-g oral glucose tolerance test was performed after an overnight fast in eight cirrhotic patients with diabetes (fasting blood glucose, 7.8 +/- 2.2 [SE] mmol/L), seven nondiabetic cirrhotic patients, and eight normal control subjects. Fasting serum immunoreactive insulin levels were approximately six times higher in cirrhotics than in controls, but were not different between diabetic and nondiabetic cirrhotic patients. After oral glucose, the incremental area under the serum insulin concentration curve was 3,475 +/- 1,009 pmol.L-1.h in nondiabetic cirrhotic patients, significantly higher than in controls (761 +/- 48, P < .001) or diabetic cirrhotic patients (881 +/- 186, P < .05). Fasting serum proinsulin levels in diabetic cirrhotic patients (24.0 +/- 5.7 pmol/L) were higher than in controls (2.3 +/- .05, P < .001) or nondiabetic cirrhotic patients (4.4 +/- 0.8, P < .005). Fasting serum levels of des-31,32 proinsulin were also much higher in diabetic cirrhotic patients than in nondiabetic cirrhotic patients or controls (P < .02 and P < .005, respectively). Fasting proinsulin plus des-31,32 proinsulin constituted 12.5% +/- 1.4% of serum immunoreactive insulin in diabetic cirrhotics, higher than in nondiabetic cirrhotics (3.7% +/- 0.5%, P < .001) and normal controls (7.8% +/- 1.5%, P = .035).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Diabetes Mellitus/metabolismo , Insulina/metabolismo , Cirrose Hepática Alcoólica/metabolismo , Proinsulina/sangue , Precursores de Proteínas/sangue , Adulto , Anticorpos Monoclonais , Complicações do Diabetes , Jejum , Teste de Tolerância a Glucose , Humanos , Imunoensaio , Cirrose Hepática Alcoólica/complicações , Pessoa de Meia-IdadeRESUMO
Platelet function was assessed in 28 patients with primary biliary cirrhosis (PBC), of whom 10 were receiving D-penicillamine. Patients not on D-penicillamine treatment had platelet aggregation similar to that in the healthy control group; the group treated with D-penicillamine showed significantly enhanced platelet aggregation in response to threshold doses of adrenaline and collagen but not ADP. Median thromboxane B2 production was also higher in D-penicillamine treated patients than in controls or untreated patients; this difference did not reach statistical significance. The addition of D-penicillamine in vitro to platelet rich plasma from normal subjects was shown to enhance adrenaline- and collagen-induced platelet aggregation. Abnormalities of platelet function in PBC patients did not correlate with serum cholesterol concentration or with liver function tests but were related to the stage of disease. The present study emphasises the need to consider the aetiology, disease stage and type of treatment when assessing platelet function and prostanoid release in liver disease.
Assuntos
Cirrose Hepática Biliar/tratamento farmacológico , Penicilamina/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Tromboxano A2/metabolismo , Idoso , Colesterol/sangue , Feminino , Humanos , Cirrose Hepática Biliar/metabolismo , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/efeitos dos fármacos , Tromboxano B2/metabolismoRESUMO
This study investigated the bonding mechanisms of glass-ionomer cement to dentin. The approaches included mechanical determination of bond strengths, analysis of surface morphology by means of scanning electron microscopy (SEM) and confocal microscopy, and measurement of chemical changes of fracture bond sites by means of x-ray photoelectron spectroscopy (XPS) and secondary ion mass spectrometry (SIMS). The highest bond strengths were obtained with light-cured glass-ionomer cement. SEM and confocal images showed evidence of mechanical interlocking of cement in dentinal tubules. SIMS depth profiles confirmed the ion-exchange process between the light-cured glass-ionomer cement and the dentin surface. From corresponding XPS results, it was clear that the adhesion characteristics were significantly affected by light-curing and the chemical structure of the polymer.