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1.
Nature ; 606(7913): 276-280, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35676430

RESUMO

Interpreting high-energy, astrophysical phenomena, such as supernova explosions or neutron-star collisions, requires a robust understanding of matter at supranuclear densities. However, our knowledge about dense matter explored in the cores of neutron stars remains limited. Fortunately, dense matter is not probed only in astrophysical observations, but also in terrestrial heavy-ion collision experiments. Here we use Bayesian inference to combine data from astrophysical multi-messenger observations of neutron stars1-9 and from heavy-ion collisions of gold nuclei at relativistic energies10,11 with microscopic nuclear theory calculations12-17 to improve our understanding of dense matter. We find that the inclusion of heavy-ion collision data indicates an increase in the pressure in dense matter relative to previous analyses, shifting neutron-star radii towards larger values, consistent with recent observations by the Neutron Star Interior Composition Explorer mission5-8,18. Our findings show that constraints from heavy-ion collision experiments show a remarkable consistency with multi-messenger observations and provide complementary information on nuclear matter at intermediate densities. This work combines nuclear theory, nuclear experiment and astrophysical observations, and shows how joint analyses can shed light on the properties of neutron-rich supranuclear matter over the density range probed in neutron stars.

2.
HIV Med ; 24(11): 1115-1125, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37641541

RESUMO

BACKGROUND: Understanding the health care activity and associated hospital costs of caring for people living with HIV is an important component of assessing the cost effectiveness of new technologies and for budget planning. METHODS: Data collected between 2010 and 2017 from an English HIV treatment centre were combined with national reference costs to estimate the rate of hospital attendances and costs per quarter year, according to demographic and clinical factors. The final dataset included records for 1763 people living with HIV, which was analysed using negative binomial regression models and general estimating equations. RESULTS: People living with HIV experienced an unadjusted average of 0.028 (standard deviation [SD] 0.20) inpatient episodes per quarter, equivalent to one every 9 years, and 1.85 (SD 2.30) outpatient visits per quarter. The unadjusted mean quarterly cost per person with HIV (excluding antiretroviral drug costs) was £439 (SD 604). Outpatient appointments and inpatient episodes accounted for 88% and 6% of total costs, respectively. In adjusted models, low CD4 count was the strongest predictor of inpatient stays and outpatient visits. Low CD4 count and new patient status (having a first visit at the Trust in the last 6 months) were the factors that most increased estimated costs. Associations were weaker or less consistent for demographic factors (age, sex/sexual orientation/ethnicity). Sensitivity analyses suggest that the findings were generally robust to alternative parameter and modelling assumptions. CONCLUSION: A number of factors predicted hospital activity and costs, but CD4 cell count and new patient status were the strongest. The study results can be incorporated into future economic evaluations and budget impact assessments of HIV-related technologies.


Assuntos
Infecções por HIV , Humanos , Masculino , Feminino , Infecções por HIV/tratamento farmacológico , Custos Hospitalares , Dados de Saúde Coletados Rotineiramente , Inglaterra/epidemiologia , Hospitais , Custos de Cuidados de Saúde
3.
Phys Rev Lett ; 129(13): 132501, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36206412

RESUMO

Nuclear charge radii of ^{55,56}Ni were measured by collinear laser spectroscopy. The obtained information completes the behavior of the charge radii at the shell closure of the doubly magic nucleus ^{56}Ni. The trend of charge radii across the shell closures in calcium and nickel is surprisingly similar despite the fact that the ^{56}Ni core is supposed to be much softer than the ^{48}Ca core. The very low magnetic moment µ(^{55}Ni)=-1.108(20) µ_{N} indicates the impact of M1 excitations between spin-orbit partners across the N,Z=28 shell gaps. Our charge-radii results are compared to ab initio and nuclear density functional theory calculations, showing good agreement within theoretical uncertainties.

4.
Phys Rev Lett ; 127(19): 192701, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34797158

RESUMO

The symmetry energy and its density dependence are crucial inputs for many nuclear physics and astrophysics applications, as they determine properties ranging from the neutron-skin thickness of nuclei to the crust thickness and the radius of neutron stars. Recently, PREX-II reported a value of 0.283±0.071 fm for the neutron-skin thickness of ^{208}Pb, implying a slope parameter L=106±37 MeV, larger than most ranges obtained from microscopic calculations and other nuclear experiments. We use a nonparametric equation of state representation based on Gaussian processes to constrain the symmetry energy S_{0}, L, and R_{skin}^{^{208}Pb} directly from observations of neutron stars with minimal modeling assumptions. The resulting astrophysical constraints from heavy pulsar masses, LIGO/Virgo, and NICER clearly favor smaller values of the neutron skin and L, as well as negative symmetry incompressibilities. Combining astrophysical data with PREX-II and chiral effective field theory constraints yields S_{0}=33.0_{-1.8}^{+2.0} MeV, L=53_{-15}^{+14} MeV, and R_{skin}^{^{208}Pb}=0.17_{-0.04}^{+0.04} fm.

5.
Phys Rev Lett ; 119(26): 262502, 2017 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-29328704

RESUMO

We show that the empirical linear relation between the magnitude of the EMC effect in deep inelastic scattering on nuclei and the short-range correlation scaling factor a_{2} extracted from high-energy quasielastic scattering at x≥1 is a natural consequence of scale separation and derive the relationship using effective field theory. While the scaling factor a_{2} is a ratio of nuclear matrix elements that individually depend on the calculational scheme, we show that the ratio is independent of this choice. We perform Green's function Monte Carlo calculations with both chiral and Argonne-Urbana potentials to verify this and determine the scaling factors for light nuclei. The resulting values for ^{3}He and ^{4}He are in good agreement with experimental values. We also present results for ^{9}Be and ^{12}C extracted from variational Monte Carlo calculations.

6.
Phys Rev Lett ; 119(18): 181803, 2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-29219546

RESUMO

Searches for invisible Higgs decays at the Large Hadron Collider constrain dark matter Higgs-portal models, where dark matter interacts with the standard model fields via the Higgs boson. While these searches complement dark matter direct-detection experiments, a comparison of the two limits depends on the coupling of the Higgs boson to the nucleons forming the direct-detection nuclear target, typically parametrized in a single quantity f_{N}. We evaluate f_{N} using recent phenomenological and lattice-QCD calculations, and include for the first time the coupling of the Higgs boson to two nucleons via pion-exchange currents. We observe a partial cancellation for Higgs-portal models that makes the two-nucleon contribution anomalously small. Our results, summarized as f_{N}=0.308(18), show that the uncertainty of the Higgs-nucleon coupling has been vastly overestimated in the past. The improved limits highlight that state-of-the-art nuclear physics input is key to fully exploiting experimental searches.

7.
J Antimicrob Chemother ; 68(6): 1354-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23435690

RESUMO

OBJECTIVES: The pharmacokinetic and pharmacodynamic effects of antiretroviral therapy may differ in older compared with younger subjects with HIV infection. We aimed to assess factors associated with plasma antiretroviral drug exposure, including age, within a large HIV-infected cohort undergoing therapeutic drug monitoring (TDM). METHODS: Data from the Liverpool TDM Registry were linked with the UK Collaborative HIV Cohort (CHIC) Study. All TDM of protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) was included and in order to account for different antiretroviral drugs the plasma concentrations were standardized by group measurements according to drug, dosing and timing of TDM. Regression modelling was used to evaluate associations of drug exposure with age and clinical parameters, including hepatic transaminase results and time to antiretroviral treatment modification. RESULTS: Data from 3589 TDM samples were available from 2447 subjects. The greatest numbers of plasma concentrations were assessed for lopinavir (22.4%), efavirenz (18.5%), atazanavir (17.0%) and saquinavir (11.6%). As age increased, median standardized NNRTI concentrations remained constant, whereas PI concentrations increased (correlation coefficient 0.04, P = 0.033). In a regression analysis stratified by antiretroviral drug class, standardized plasma concentrations were significantly associated with age for PIs (0.05 increase in standard deviation of drug concentration with each 10 year increase in age, P = 0.044), but not for NNRTIs or other clinical parameters, including hepatic transaminase results or time to antiretroviral treatment modification. CONCLUSIONS: With increasing age, statistically significant rises in plasma PI exposure, but not NNRTI exposure, were observed. The clinical relevance of this observation merits further investigation.


Assuntos
Envelhecimento/metabolismo , Fármacos Anti-HIV/sangue , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/sangue , Adulto , Idoso , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Monitoramento de Medicamentos , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C/complicações , Humanos , Testes de Função Hepática , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/sangue , Inibidores da Transcriptase Reversa/farmacocinética , Reino Unido , Carga Viral
8.
Int J STD AIDS ; 32(12): 1165-1173, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34156330

RESUMO

OBJECTIVES: The objective of this study was to describe the real-world use and effectiveness of dolutegravir-based regimens (DBRs) in routine clinical practice in the United Kingdom. METHODS: Retrospective analysis was conducted using data from four National Health Service trusts using Climate-HIV, an electronic case record system. Eligible patients were aged ≥18 years with HIV-1 infection who were prescribed a DBR from December 2012 to March 2018. Outcome measurements were accessed at DBR initiation and at weeks 24, 48 and 96 and the last recorded visit up to the extraction date (last measurement). The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at Week 48. RESULTS: The study cohort included 934 patients; 337 (36%) were female, 414 (47%) were white and 717 (77%) were treatment experienced (TE). The Kaplan-Meier estimated probability of achieving HIV-1 RNA <50 copies/mL at 48 weeks was 96% for treatment-naive (TN) patients and 86% for TE patients. Median times to viral suppression (<50 copies/mL) were 49 and 57 days for TN and TE patients with detectable baseline viral load, respectively, according to Kaplan-Meier analysis. Median follow-up time was 377 days (interquartile range: 131-683). At last measurement, 87% (809/934) of patients remained on a DBR; among those patients, 681 (84%) had HIV-1 RNA <50 copies/mL. CONCLUSIONS: High levels of virologic suppression and low rates of discontinuation of DBRs were seen in a large, diverse, UK-based population with HIV-1 infection. These findings are broadly consistent with efficacy data from phase III studies.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis , Humanos , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Piridonas/uso terapêutico , Estudos Retrospectivos , Medicina Estatal , Resultado do Tratamento , Carga Viral
9.
Phys Rev Lett ; 105(3): 032501, 2010 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-20867759

RESUMO

The limit of neutron-rich nuclei, the neutron drip line, evolves regularly from light to medium-mass nuclei except for a striking anomaly in the oxygen isotopes. This anomaly is not reproduced in shell-model calculations derived from microscopic two-nucleon forces. Here, we present the first microscopic explanation of the oxygen anomaly based on three-nucleon forces that have been established in few-body systems. This leads to repulsive contributions to the interactions among excess neutrons that change the location of the neutron drip line from (28)O to the experimentally observed (24)O. Since the mechanism is robust and general, our findings impact the prediction of the most neutron-rich nuclei and the synthesis of heavy elements in neutron-rich environments.

10.
Haematologica ; 94(6): 875-80, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19336735

RESUMO

Since the introduction of highly active antiretroviral therapy, there has been a decline in the incidence of non-Hodgkin's lymphoma among HIV-infected individuals. We described trends in the incidence of systemic non-Hodgkin's lymphoma in the UK CHIC Study from 1996-2006 and evaluated the association between immunosuppression and development of systemic non-Hodgkin's lymphoma: 286/23,155 (1.2%) individuals developed an AIDS-defining lymphoma (258 systemic). Younger age, receipt of highly active antiretroviral therapy and later calendar year were all independently associated with a reduced risk of systemic non-Hodgkin's lymphoma. A lower latest CD4 count was strongly associated with systemic non-Hodgkin's lymphoma, in patients who had (RR per log(2)(cells/mm(3)) higher: 0.62) and had not (0.70) received highly active antiretroviral therapy. Associations with other measures of immunosuppression, including nadir CD4 count, experience and duration of severe immunosuppression, were generally weaker. Earlier highly active anti-retroviral therapy initiation and wider access to HIV testing is advocated to reduce the risk of systemic non-Hodgkin's lymphoma.


Assuntos
Infecções por HIV/imunologia , Linfoma Relacionado a AIDS/imunologia , Linfoma não Hodgkin/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/etiologia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/etiologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , Reino Unido/epidemiologia , Adulto Jovem
11.
Lancet ; 370(9603): 1923-8, 2007 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-18068516

RESUMO

BACKGROUND: The long-term durability of viral-load suppression provided by the three original antiretroviral drugs is not well characterised. We estimated the proportion of patients who had extensive triple-class failure during long-term follow-up and examined characteristics associated with an increased rate of failure. METHODS: 7916 patients who started antiretroviral therapy with three or more drugs were followed up from the time that therapy started until the last viral-load measure. Extensive triple-class virological failure was defined by failure of three subclasses of nucleoside reverse transcriptase inhibitors, a non-nucleoside reverse transcriptase inhibitor, and a ritonavir-boosted protease inhibitor. FINDINGS: 167 patients developed extensive triple-class failure during 27 441 person-years of follow-up. The Kaplan-Meier estimate for the cumulative risk of extensive triple-class failure was 9.2% by 10 years (95% CI 5.0-13.4). There was evidence that this rate has decreased over time (adjusted hazard ratio 0.86 [0.77-0.96] per year more recent; p=0.006). Of the 167 patients with extensive triple-class failure, 101 (60%) subsequently had at least one viral load less than 50 copies per mL. The risk of death by 5 years from the time of extensive triple-class failure was 10.6% (2.4-18.8, nine deaths). INTERPRETATION: We have shown that extensive virological failure of the three main classes of drugs occurs slowly in routine clinical practice. This finding has implications for the planning of treatment programmes in developing countries, where additional drugs outside these classes are unlikely to be available for some time.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Antirretrovirais/classificação , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Humanos , Masculino , Falha de Tratamento , Reino Unido , Carga Viral
12.
AIDS ; 21(13): 1717-21, 2007 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-17690569

RESUMO

OBJECTIVE: To assess the absolute rate of AIDS and death in antiretroviral therapy (ART)-naive patients with a high CD4 cell count. Such information would be helpful in the design of a trial investigating early initiation of ART. DESIGN: Analysis of data from an ongoing HIV cohort study. METHODS: The rate of (severe) AIDS or death and death alone was evaluated in ART-naive patients according to the current CD4 cell count, focusing on CD4 cell counts > or = 350 cells/microl among patients in the UK CHIC Study. RESULTS: In a total of 30 313 person-years of follow-up, there were 1557 AIDS or death events. The rate of AIDS or death in persons with most recent CD4 cell count 350-499, 500-649 and > 650 cells/microl was 2.49, 1.54 and 0.96 per 100 person-years, respectively. The rate ratio for those with CD4 cell count 500-649 cells/microl compared with those with CD4 cell count > or = 650 cells/microl was 1.55 [95% confidence interval (CI), 1.11-2.17; P = 0.01]. In a Poisson regression model based on person years with CD4 cell count > or = 350 cells/microl , there was a strong effect of CD4 cell count on rate of AIDS or death (rate ratio, 0.84; 95% CI, 0.76-0.93; P = 0.001), independent of viral load and age. CONCLUSIONS: The trend of decreasing rate of AIDS and death with higher CD4 cell count is present throughout the CD4 cell count > or = 350 cells/microl range in ART-naive people.


Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/transmissão , Síndrome da Imunodeficiência Adquirida/virologia , Adulto , Fatores Etários , Contagem de Linfócito CD4 , Estudos de Coortes , Progressão da Doença , Feminino , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Reino Unido/epidemiologia , Carga Viral
13.
Lancet ; 368(9540): 1012-21, 2006 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-16980117

RESUMO

BACKGROUND: We investigated the potential of proteomic fingerprinting with mass spectrometric serum profiling, coupled with pattern recognition methods, to identify biomarkers that could improve diagnosis of tuberculosis. METHODS: We obtained serum proteomic profiles from patients with active tuberculosis and controls by surface-enhanced laser desorption ionisation time of flight mass spectrometry. A supervised machine-learning approach based on the support vector machine (SVM) was used to obtain a classifier that distinguished between the groups in two independent test sets. We used k-fold cross validation and random sampling of the SVM classifier to assess the classifier further. Relevant mass peaks were selected by correlational analysis and assessed with SVM. We tested the diagnostic potential of candidate biomarkers, identified by peptide mass fingerprinting, by conventional immunoassays and SVM classifiers trained on these data. FINDINGS: Our SVM classifier discriminated the proteomic profile of patients with active tuberculosis from that of controls with overlapping clinical features. Diagnostic accuracy was 94% (sensitivity 93.5%, specificity 94.9%) for patients with tuberculosis and was unaffected by HIV status. A classifier trained on the 20 most informative peaks achieved diagnostic accuracy of 90%. From these peaks, two peptides (serum amyloid A protein and transthyretin) were identified and quantitated by immunoassay. Because these peptides reflect inflammatory states, we also quantitated neopterin and C reactive protein. Application of an SVM classifier using combinations of these values gave diagnostic accuracies of up to 84% for tuberculosis. Validation on a second, prospectively collected testing set gave similar accuracies using the whole proteomic signature and the 20 selected peaks. Using combinations of the four biomarkers, we achieved diagnostic accuracies of up to 78%. INTERPRETATION: The potential biomarkers for tuberculosis that we identified through proteomic fingerprinting and pattern recognition have a plausible biological connection with the disease and could be used to develop new diagnostic tests.


Assuntos
Biomarcadores/sangue , Mapeamento de Peptídeos/métodos , Proteômica , Tuberculose/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose/diagnóstico
14.
AIDS ; 31(18): 2525-2532, 2017 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-28926400

RESUMO

OBJECTIVES: To compare rates of all-cause, liver-related, and AIDS-related mortality among individuals who are HIV-monoinfected with those coinfected with HIV and hepatitis B (HBV) and/or hepatitis C (HCV) viruses. DESIGN: An ongoing observational cohort study collating routinely collected clinical data on HIV-positive individuals attending for care at HIV treatment centres throughout the United Kingdom. METHODS: Individuals were included if they had been seen for care from 2004 onwards and had tested for HBV and HCV. Crude mortality rates (all cause, liver related, and AIDS related) were calculated among HIV-monoinfected individuals and those coinfected with HIV, HBV, and/or HCV. Poisson regression was used to adjust for confounding factors, identify independent predictors of mortality, and estimate the impact of hepatitis coinfection on mortality in this cohort. RESULTS: Among 25 486 HIV-positive individuals, with a median follow-up 4.5 years, HBV coinfection was significantly associated with increased all-cause and liver-related mortality in multivariable analyses: adjusted rate ratios (ARR) [95% confidence intervals (95% CI)] were 1.60 (1.28-2.00) and 10.42 (5.78-18.80), respectively. HCV coinfection was significantly associated with increased all-cause (ARR 1.43, 95% CI 1.15-1.76) and liver-related mortality (ARR 6.20, 95% CI 3.31-11.60). Neither HBV nor HCV coinfection were associated with increased AIDS-related mortality: ARRs (95% CI) 1.07 (0.63-1.83) and 0.40 (0.20-0.81), respectively. CONCLUSION: The increased rate of all-cause and liver-related mortality among hepatitis-coinfected individuals in this HIV-positive cohort highlights the need for primary prevention and access to effective hepatitis treatment for HIV-positive individuals.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/mortalidade , Hepatite B/epidemiologia , Hepatite B/mortalidade , Hepatite C/epidemiologia , Hepatite C/mortalidade , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Reino Unido/epidemiologia
16.
PLoS Med ; 1(1): e18, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15526044

RESUMO

BACKGROUND: The degree of volume depletion in severe malaria is currently unknown, although knowledge of fluid compartment volumes can guide therapy. To assist management of severely ill children, and to test the hypothesis that volume changes in fluid compartments reflect disease severity, we measured body compartment volumes in Gabonese children with malaria. METHODS AND FINDINGS: Total body water volume (TBW) and extracellular water volume (ECW) were estimated in children with severe or moderate malaria and in convalescence by tracer dilution with heavy water and bromide, respectively. Intracellular water volume (ICW) was derived from these parameters. Bioelectrical impedance analysis estimates of TBW and ECW were calibrated against dilution methods, and bioelectrical impedance analysis measurements were taken daily until discharge. Sixteen children had severe and 19 moderate malaria. Severe childhood malaria was associated with depletion of TBW (mean [SD] of 37 [33] ml/kg, or 6.7% [6.0%]) relative to measurement at discharge. This is defined as mild dehydration in other conditions. ECW measurements were normal on admission in children with severe malaria and did not rise in the first few days of admission. Volumes in different compartments (TBW, ECW, and ICW) were not related to hyperlactataemia or other clinical and laboratory markers of disease severity. Moderate malaria was not associated with a depletion of TBW. CONCLUSIONS: Significant hypovolaemia does not exacerbate complications of severe or moderate malaria. As rapid rehydration of children with malaria may have risks, we suggest that fluid replacement regimens should aim to correct fluid losses over 12-24 h.


Assuntos
Hidratação , Hipovolemia/etiologia , Hipovolemia/terapia , Malária Falciparum/complicações , Equilíbrio Hidroeletrolítico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Valores de Referência , Índice de Gravidade de Doença
17.
Am J Clin Nutr ; 77(2): 392-8, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12540399

RESUMO

BACKGROUND: Pulmonary tuberculosis is the classic cause of "consumption," but the pathogenesis of such wasting is largely unknown. Animal studies in other conditions suggest that leptin may be a mediator between proinflammatory cytokine activity and wasting. OBJECTIVE: We tested whether the leptin concentration, after control for body fat mass, is higher during active pulmonary tuberculosis than after recovery and whether it correlates with energy metabolism and proinflammatory cytokine activity. DESIGN: Nondiabetic adults with pulmonary tuberculosis (n = 32) were recruited into a prospective observational study. Patients found to be antibody positive for human immunodeficiency virus were excluded from the study. Dual-energy X-ray absorptiometry, indirect calorimetry, and food intake protocols were performed at baseline and after 1 and 6 mo of tuberculosis treatment. Fasting plasma leptin, tumor necrosis factor alpha and its soluble receptor, and interleukin 6 were measured by enzyme-linked immunosorbent assay. RESULTS: Resting energy expenditure was close to Harris-Benedict predictions and did not change significantly during treatment, but energy intake increased. Leptin concentration was correlated in a log-linear fashion with percentage body fat but was independent of cytokines and energy intake. There was no significant difference in leptin, corrected for energy balance and fat mass, at baseline and after 1 and 6 mo of treatment. CONCLUSIONS: These data are compatible with recovery from anorexia or starvation without discernible hyper- or hypometabolism. The close correlation of leptin with body fat mass is similar to observations in healthy subjects. No additional influence of disease state or proinflammatory cytokine activity was found. Leptin does not appear to be a component of the immune response to human pulmonary tuberculosis, and thus it cannot account for the weight loss and anorexia associated with tuberculosis.


Assuntos
Metabolismo Energético/fisiologia , Leptina/sangue , Tuberculose Pulmonar/metabolismo , Absorciometria de Fóton/métodos , Tecido Adiposo/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Água Corporal/metabolismo , Calorimetria Indireta/métodos , Doença Crônica , Citocinas/sangue , Ingestão de Energia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/fisiopatologia , Redução de Peso
18.
Am J Clin Nutr ; 79(6): 1006-12, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15159230

RESUMO

BACKGROUND: Tuberculosis is an important cause of wasting. The functional consequences of wasting and recovery may depend on the distribution of lost and gained nutrient stores between protein and fat masses. OBJECTIVE: The goal was to study nutrient partitioning, ie, the proportion of weight change attributable to changes in fat mass (FM) versus protein mass (PM), during antimycobacterial treatment. DESIGN: Body-composition measures were made of 21 men and 9 women with pulmonary tuberculosis at baseline and after 1 and 6 mo of treatment. All subjects underwent dual-energy X-ray absorptiometry and deuterium bromide dilution tests, and a four-compartment model of FM, total body water (TBW), bone minerals (BM), and PM was derived. The ratio of PM to FM at any time was expressed as the energy content (p-ratio). Changes in the p-ratio were related to disease severity as measured by radiologic criteria. RESULTS: Patients gained 10% in body weight (P < 0.001) from baseline to month 6. This was mainly due to a 44% gain in FM (P < 0.001); PM, BM, and TBW did not change significantly. Results were similar in men and women. The p-ratio decreased from baseline to month 1 and then fell further by month 6. Radiologic disease severity was not correlated with changes in the p-ratio. CONCLUSIONS: Microbiological cure of tuberculosis does not restore PM within 6 mo, despite a strong anabolic response. Change in the p-ratio is a suitable parameter for use in studying the effect of disease on body composition because it allows transformation of such effects into a normal distribution across a wide range of baseline proportion between fat and protein mass.


Assuntos
Tecido Adiposo , Composição Corporal , Estado Nutricional , Tuberculose Pulmonar/metabolismo , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Peso Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/tratamento farmacológico , Síndrome de Emaciação/etiologia , Síndrome de Emaciação/metabolismo
19.
Clin Nutr ; 21(5): 385-8, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12381335

RESUMO

BACKGROUND: Measurement of resting energy expenditure in patients with active respiratory infection is hampered by the risk of contamination of indirect calorimeters and connecting tubes that cannot be sterilized. This validation study tested whether the use of disposable standard-bore air tubes and an antibacterial filter, by reducing air flow, introduces an error due to recirculation of expired air in the canopy. METHODS: Eleven healthy volunteers underwent indirect calorimetry twice in random order, using a Deltatrac calorimeter either with standard wide-bore tubing or with a disposable standard-bore air tube and filter. Methods were compared by Bland-Altman plots and by calculating trends over time. RESULTS: The new tube and filter reduced air flow by 40%. Measured resting energy expenditure did not differ significantly between methods, with limits of agreement -135 to +188 kcal/d. Carbon dioxide flow (VCO(2)) and respiratory quotient (RQ), but not oxygen flow decreased slowly over time with both methods. CONCLUSIONS: The use of an air filter and standard-bore tubes do not introduce a systematic error into indirect calorimetry. Although trends in VCO(2) and RQ are consistent with minor recirculation of exhaled air, this modified Deltatrac system can be safely and reliably used to measure resting energy expenditures in patients with active tuberculosis and other airborne infection.


Assuntos
Calorimetria Indireta , Infecção Hospitalar/prevenção & controle , Infecções Respiratórias/fisiopatologia , Adulto , Análise de Variância , Dióxido de Carbono/fisiologia , Equipamentos Descartáveis , Metabolismo Energético/fisiologia , Feminino , Humanos , Masculino , Valores de Referência , Respiração
20.
Nutrition ; 20(3): 249-54, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14990264

RESUMO

OBJECTIVE: Glutamine has stimulatory effects on lymphocytes and mucosa cells in vitro and, when given with parenteral nutrition, has been shown to improve the clinical course of patients after bone marrow transplantation and in the critically ill. This study investigated the clinical and immunologic effects of parenteral glycyl-glutamine supplementation in patients with acute leukemia receiving intensive conventional chemotherapy without bone marrow transplantation. METHODS: A randomized, double-blind, controlled study compared a standard glutamine-free parenteral nutrition with a glycyl-glutamine-supplemented parenteral nutrition (Glamin, Baxter, Erlangen, Germany) containing 20 g of glutamine in adult patients with acute myeloid leukemia undergoing myelosuppressive chemotherapy. Clinical end points included the duration of neutropenia and the incidence and duration of neutropenic fever. To analyze the effects of glutamine on immunocompetent cells, CD4+ and CD8+ T cells and HLA-DR expression on monocytes were assessed by flow cytometry throughout the treatment course. RESULTS: Fifty-four adult patients entered the study and were randomized. In 45 of 127 chemotherapy cycles, parenteral nutrition was given, and 40 cycles (20 with and 20 without glutamine) were evaluated for comparison. The median durations of neutropenia were 18 d (range, 9-29 d) in the glutamine group and 22.5 d (range, 13-48 d) in the control group (P = 0.052), whereas the median durations of neutropenic fever were 5.5 d (range, 0-13 d) and 5 d (range, 0-31 d), respectively (P = 0.74). Using Kaplan-Meier analysis and controlling for the type of chemotherapy, we found a significantly faster neutrophil recovery in patients receiving glutamine than in the control group (P = 0.040) in patients receiving a high-dose cytarabine regimen. There was no significant difference in the recovery of CD4+ or CD8+ lymphocytes or monocyte activation between groups. CONCLUSION: In patients with acute myeloid leukemia requiring parenteral nutrition, glycyl-glutamine supplementation could hasten neutrophil recovery after intensive myelosuppressive chemotherapy. However, no impact of glutamine on neutropenic fever or other criteria of immunologic recovery was detected.


Assuntos
Antineoplásicos/uso terapêutico , Dipeptídeos/administração & dosagem , Leucemia Mieloide Aguda/terapia , Nutrição Parenteral Total , Adolescente , Adulto , Idoso , Antineoplásicos/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Dipeptídeos/imunologia , Método Duplo-Cego , Feminino , Citometria de Fluxo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Neutropenia/tratamento farmacológico , Neutropenia/imunologia , Neutropenia/terapia , Estudos Prospectivos
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