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1.
AIDS Behav ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014029

RESUMO

We examined past-year intimate partner violence (IPV), including psychological violence without physical/sexual violence, and health outcomes among people with HIV (PWH) in care in a multi-site U.S. cohort. Between 2016 and 2022, PWH reported 12-month psychological, physical, and sexual IPV in a routine assessment. We used linear and logistic regression models adjusted for age, race/ethnicity, and site to examine relationships with health outcomes. Among 9748 PWH (median age 50 years, 81% cisgender male/16% cisgender female/1% transgender female; 44% non-Hispanic white/36% non-Hispanic Black/15% Hispanic), 9.3% (n = 905) reported any IPV in the past 12 months; half reported psychological IPV without physical/sexual IPV (n = 453). PWH reporting any type of IPV were on average younger than those who did not experience IPV. In adjusted models, any IPV was associated with increased likelihood of unstable housing, HIV viral load detection (HIV viral load ≥ 75 copies/mL), moderate-to-severe depressive symptoms, anxiety with panic symptoms, substance use (methamphetamines, cocaine/crack, illicit opioids, marijuana, heavy episodic/hazardous drinking), and concern about exposure to sexually transmitted infection. PWH reporting any IPV in the past 12 months had 4.2% lower adherence to antiretroviral therapy, 2.4 more HIV-related symptoms, a 1.9 point higher HIV stigma score, and a 9.5% lower quality of life score than those without IPV. We found similar associations among PWH reporting only psychological IPV, without physical/sexual IPV. IPV was common among PWH. Half reporting IPV reported only psychological IPV and had similarly poor outcomes as those reporting physical/sexual IPV, demonstrating the need to assess psychological as well as physical and sexual IPV.


RESUMEN: Examinamos la violencia de la pareja íntima (intimate partner violence, IPV) del año anterior, incluida la violencia psicológica sin violencia física y sexual, así como los resultados sanitarios entre las personas con VIH (people with HIV, PWH) que reciben atención en una cohorte multicéntrica de los Estados Unidos. Entre 2016 y 2022, las PWH informaron situaciones de IPV psicológica, física y sexual durante los 12 meses en una evaluación de rutina. Se utilizaron modelos de regresión lineal y logística ajustados por edad, raza/etnia y centro para examinar las relaciones con los resultados sanitarios. Entre 9748 PWH (mediana de edad de 50 años, 81% de hombres cisgénero/16% de mujeres cisgénero/1% de mujeres transgénero; 44% de blancos no hispanos/36% de negros no hispanos/15% de hispanos), el 9,3% (n = 905) informaron haber sufrido algún tipo de IPV en los últimos 12 meses; la mitad informó situaciones de IPV psicológica sin IPV física y sexual (n = 453). Las PWH que informaron de cualquier tipo de IPV fueron, en promedio, más jóvenes que las que no sufrieron IPV. En los modelos ajustados, cualquier IPV se asoció con una mayor probabilidad de vivienda inestable, detección de carga viral del VIH (carga viral del VIH ≥ 75 copias/ml), síntomas depresivos de moderados a graves, ansiedad con síntomas de pánico, consumo de sustancias (metanfetaminas, cocaína/crack, opioides ilícitos, marihuana, consumo excesivo episódico/peligroso de alcohol) y preocupación por la exposición a infecciones de transmisión sexual. Las PWH que informaron alguna situación de IPV en los últimos 12 meses tuvieron un 4,2% menos de cumplimiento de la terapia antirretrovírica, un 2,4% más de síntomas relacionados con el VIH, una puntuación de estigma del VIH 1,9 puntos más alta y una puntuación de calidad de vida un 9,5% más baja que las que no sufrieron IPV. Se encontraron asociaciones similares entre las PWH que informaron solo IPV psicológica, sin IPV física y sexual. La IPV fue común entre las PWH. La mitad de las personas que informaron IPV solo informaron IPV psicológica y tuvieron resultados igualmente deficientes que los que informaron IPV física y sexual, lo que demuestra la necesidad de evaluar la IPV psicológica, al igual que la IPV física y sexual.

2.
AIDS Care ; 36(5): 618-630, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37419138

RESUMO

Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence (p < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) (p < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized.


Assuntos
Infecções por HIV , Drogas Ilícitas , Metanfetamina , Transtornos Relacionados ao Uso de Substâncias , Adulto , Masculino , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Transtornos Relacionados ao Uso de Substâncias/complicações , Antirretrovirais/uso terapêutico , Etanol/uso terapêutico , Metanfetamina/uso terapêutico , Adesão à Medicação
3.
medRxiv ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34909782

RESUMO

OBJECTIVES: To define the incidence of clinically-detected COVID-19 in people with HIV (PWH) in the US and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19. DESIGN: Observational study within the CFAR Network of Integrated Clinical Systems cohort in 7 cities during 2020. METHODS: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4 count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores. RESULTS: Among 16,056 PWH in care, of whom 44.5% were Black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4 count < 350, including 7% < 200; 95.5% were on antiretroviral therapy, and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and Black PWH respectively, than non-Hispanic White PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or Black identity, lowest historical CD4 count <350 (proxy for CD4 nadir), current low CD4/CD8 ratio, diabetes, and obesity. CONCLUSIONS: Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWHPWH with immune exhaustion as evidenced by lowest historical CD4 or current low CD4:CD8 ratio had greater risk of COVID-19.

4.
AIDS Care ; 31(5): 554-562, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30558446

RESUMO

People aging with HIV face social stressors which may negatively affect their overall nutrition. Here, we assess relationships between self-reported measures of depression, perceived stress, social support, and food insecurity with diet quality in older adults with HIV. A retrospective analysis of self-reported data from parent study at The University of Alabama at Birmingham 1917 HIV Clinic was performed. The study sample consisted of sixty people living with HIV (PLWH) with controlled HIV infection (<50 copies/mL), aged 50 years or older who participated in a cross-sectional microbiome study. Dietary intake was measured using the NHANES 12-month Food Frequency Questionnaire (FFQ) and three Automated Self-Administered (ASA) 24-hr diet recalls to calculate diet quality scores using the Mediterranean Diet Score (MDS); alternative Healthy Eating Index (aHEI); and the Recommended Food Score (RFS) indices. Food insecurity was measured with the Food Security Questionnaire (FSQ). Participants completed the following psychosocial scales: (1) depression - Patient Health Questionnaire-8 (PHQ8); (2) perceived stress - Perceived Stress Scale (PSS-10); (3) social support - Multidimensional Scale of Perceived Social Support (MSPSS). Linear regression models were used to investigate relationships among variables controlling for gender and income. The cohort was characterized as follows: Mean age 56 ± 4.6 years, 80% African-American, and 32% women. Mean body mass index (BMI) was 28.4 ± 7.2 with 55% reporting food insecurity. Most participants reported having post-secondary education (53%), although 77% reported annual incomes <$20,000. Food insecurity was independently associated with measures of poor dietary intake: aHEI (ß = -0.08, p = .02) and MDS (ß = -0.23, p < 0.01) and with low dietary intake of fibre (ß = -0.27, p = .04), vitamin E (ß = -0.35, p = .01), folate (ß = -0.31, p = .02), magnesium (ß = -0.34, p = .01) and copper (ß = -0.36, p = .01). These data indicate food insecurity is associated with poor diet quality among PLWH. Clinical interventions are needed to improve food access for PLWH of low SES.


Assuntos
Dieta , Comportamento Alimentar , Abastecimento de Alimentos/estatística & dados numéricos , Infecções por HIV/psicologia , Estresse Psicológico , Idoso , Alabama , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Depressão , Fibras na Dieta , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Inquéritos Nutricionais , Estado Nutricional , Estudos Retrospectivos , Apoio Social , Inquéritos e Questionários
5.
HIV Med ; 16(9): 572-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25960080

RESUMO

OBJECTIVES: Adipose tissue affects several aspects of the cellular immune system, but prior epidemiological studies have differed on whether a higher body mass index (BMI) promotes CD4 T-cell recovery on antiretroviral therapy (ART). The objective of this analysis was to assess the relationship between BMI at ART initiation and early changes in CD4 T-cell count. METHODS: We used the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data set to analyse the relationship between pre-treatment BMI and 12-month CD4 T-cell recovery among adults who started ART between 1998 and 2010 and maintained HIV-1 RNA levels < 400 copies/mL for at least 6 months. Multivariable regression models were adjusted for age, race, sex, baseline CD4 count and HIV RNA level, year of ART initiation, ART regimen and clinical site. RESULTS: A total of 8381 participants from 13 cohorts contributed data; 85% were male, 52% were nonwhite, 32% were overweight (BMI 25-29.9 kg/m(2) ) and 15% were obese (BMI > 30 kg/m(2) ). Pretreatment BMI was associated with 12-month CD4 T-cell change (P < 0.001), but the relationship was nonlinear (P < 0.001). Compared with a reference of 22 kg/m(2) , a BMI of 30 kg/m(2) was associated with a 36 cells/µL [95% confidence interval (CI) 14, 59 cells/µL] greater CD4 T-cell count recovery among women and a 19 cells/µL (95% CI 9, 30 cells/µL) greater recovery among men at 12 months. At a BMI > 30 kg/m(2) , the observed benefit was attenuated among men to a greater degree than among women, although this difference was not statistically significant. CONCLUSIONS: A BMI of approximately 30 kg/m(2) at ART initiation was associated with greater CD4 T-cell recovery at 12 months compared with higher or lower BMI values, suggesting that body composition may affect peripheral CD4 T-cell recovery.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Índice de Massa Corporal , Linfócitos T CD4-Positivos/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Conjuntos de Dados como Assunto , Feminino , Infecções por HIV/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte , Análise de Regressão , Resultado do Tratamento
6.
Diagn Interv Imaging ; 94(6): 601-8, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23680452

RESUMO

PURPOSE: Screening for cardiac iron overload is generally done by magnetic resonance imaging (MRI) and demonstrated by a shortening of the myocardial T2* below 20 ms at 1.5 Tesla. This measurement was validated with a specific sequence and the CMRTools(®) calculation software (reference technique). The objective of this study was to validate the use of sequences and software programs that are available in routine clinical practice to screen for iron overload. MATERIAL AND METHODS: First, a phantom of 11 tubes with a T2* between 4 and 33 ms was tested at three sites that had MRI machines of different brands. Second, the myocardial T2* values of 75 patients were measured in routine clinical practice using two methods. The first method used the reference sequence specially installed in the machines associated with the CMRTool software. The second method used the standard acquisition sequences available in the machines followed by calculation on a computer spreadsheet. RESULTS: In the phantom, the mean of the differences in T2* between each machine was 0.6 ms. Thirteen patients had a lowered T2* value with the reference technique. Three cases were poorly classified using the routine technique and corresponded with false positives of low overload (T2* between 18 and 20 ms). CONCLUSION: Screening for myocardial iron overload can be done by MRI by using sequences and calculation software available in routine clinical practice during the same examination as the one for the evaluation of hepatic iron overload.


Assuntos
Transfusão de Sangue , Cardiomiopatias/diagnóstico , Insuficiência Cardíaca/diagnóstico , Hemocromatose/diagnóstico , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Sobrecarga de Ferro/diagnóstico , Imageamento por Ressonância Magnética/métodos , Programas de Rastreamento/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatias/patologia , Criança , Feminino , Ferritinas/sangue , Septos Cardíacos/patologia , Humanos , Aumento da Imagem/instrumentação , Fígado/patologia , Imageamento por Ressonância Magnética/instrumentação , Masculino , Programas de Rastreamento/instrumentação , Computação Matemática , Pessoa de Meia-Idade , Miocárdio/patologia , Imagens de Fantasmas , Valores de Referência , Software , Adulto Jovem
7.
Technol Cancer Res Treat ; 11(6): 561-70, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22712607

RESUMO

In vivo cell electropermeabilization can be used alone or in combination with a hydrophilic, nonpermeant cytotoxic drug such as bleomycin (electrochemotherapy) to efficiently treat tumors. We used magnetic resonance imaging to detect rapid structural modifications in tumors treated by electroporation-based methods. Water diffusion coefficient (ADC), transverse relaxation time (T(2)) and tumor volume of fibrosarcomas xenografted on syngenic mice were measured upon 3 groups of 6 treated mice within the 48 hrs following ECT done with a normal (BE) or a high dose of bleomycin (HBE), and after irreversible electroporation (IRE), and in three control groups. As expected, the tumor volume increased in the control groups at 48 hrs (p < 0.05) and the values of ADC and T2 did not varied significantly in the control groups except for ADC decrease and T2 increase observed between 3 hrs and 24 hrs (p < 0.03) in the group that received bleomycin only. Tumor volumes decreased significantly at 24 hrs in the IRE and HBE groups. The mean tumor ADC increased significantly at 24 hrs (117.6%, p < 0.03) in the BE group, probably reflecting apoptosis, while in the HBE group the mean tumor ADC increased earlier, at 10 hrs (119%, p < 0.03) because of the speed of the pseudoapopototic process. In the IRE group, the mean tumor ADC decreased significantly at 1 hrs (p < 0.05) and 3 hrs (p < 0.03), and T(2) decreased (p < 0.03), both probably reflecting cell swelling induced by the vascular lock. Thus ADC and T(2) changes in the treated tumors correlated with previous histological observations on the same tumor models. Noteworthy, ADC allowed the visualization of early and rapid changes in the treated tumors, when tumor volume monitoring was not yet able to detect any effect of the treatments.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias Experimentais/diagnóstico , Animais , Linhagem Celular Tumoral , Eletroquimioterapia , Eletroporação , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Resultado do Tratamento , Carga Tumoral
8.
J Hum Hypertens ; 26(2): 98-107, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21248781

RESUMO

Cardiovascular disease has a progressively earlier age of onset, and disproportionately affects African Americans (AAs) in the United States. It has been difficult to establish the extent to which group differences are due to physiological, genetic, social or behavioural factors. In this study, we examined the association between blood pressure and these factors among a sample of 294 children, identified as AA, European American or Hispanic American. We use body composition, behavioural (diet and physical activity) and survey-based measures (socio-economic status and perceived racial discrimination), as well as genetic admixture based on 142 ancestry informative markers (AIMs) to examine associations with systolic and diastolic blood pressure. We find that associations differ by ethnic/racial group. Notably, among AAs, physical activity and perceived racial discrimination, but not African genetic admixture, are associated with blood pressure, while the association between blood pressure and body fat is nearly absent. We find an association between blood pressure and an AIM near a marker identified by a recent genome-wide association study. Our findings shed light on the differences in risk factors for elevated blood pressure among ethnic/racial groups, and the importance of including social and behavioural measures to grasp the full genetic/environmental aetiology of disparities in blood pressure.


Assuntos
Negro ou Afro-Americano , Pressão Sanguínea , Composição Corporal/genética , Comportamentos Relacionados com a Saúde/etnologia , Disparidades nos Níveis de Saúde , Hispânico ou Latino , Hipertensão/etnologia , Fatores Socioeconômicos , População Branca , Negro ou Afro-Americano/genética , Negro ou Afro-Americano/psicologia , Alabama/epidemiologia , Pressão Sanguínea/genética , Criança , Estudos Transversais , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Hispânico ou Latino/genética , Hispânico ou Latino/psicologia , Humanos , Hipertensão/genética , Hipertensão/fisiopatologia , Hipertensão/psicologia , Modelos Lineares , Masculino , Cadeias de Markov , Método de Monte Carlo , Medição de Risco , Fatores de Risco , População Branca/genética , População Branca/psicologia
9.
Int J Obes (Lond) ; 35(1): 60-5, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20877287

RESUMO

OBJECTIVE: Although differences in body composition parameters among African American (AA), Hispanic American (HA) and European American (EA) children are well documented, the factors underlying these differences are not completely understood. Environmental and genetic contributors have been evaluated as contributors to observed differences. This study evaluated the extent to which African or European ancestral genetic background influenced body composition and fat distribution in 301 peripubertal AA (n = 107), HA (n = 79) and EA (n = 115) children aged 7-12. DESIGN: Estimates of African admixture (AFADM) and European admixture (EUADM) were obtained for every subject using 142 ancestry informative DNA markers. Dual energy X-ray absorptiometry and computed tomography scanning were used to determine body composition and abdominal fat distribution, respectively. Multiple regression models were conducted to evaluate the contribution of admixture estimates to body composition and fat distribution. RESULTS: Greater AFADM was associated with lower fat mass (P = 0.0163), lower total abdominal adipose tissue (P = 0.0006), lower intra-abdominal adipose tissue (P = 0.0035), lower subcutaneous abdominal adipose tissue (P = 0.0115) and higher bone mineral content (BMC) (P = 0.0253), after adjusting for socio-economic status, sex, age, height, race/ethnicity and pubertal status. Greater EUADM was associated with lower lean mass (LM) (P = 0.0056). CONCLUSION: These results demonstrate that ancestral genetic background contributes to racial/ethnic differences in body composition above and beyond the effects of racial/ethnic classification and suggest a genetic contribution to total body fat accumulation, abdominal adiposity, LM and BMC.


Assuntos
Negro ou Afro-Americano/genética , Composição Corporal/genética , Distribuição da Gordura Corporal , Densidade Óssea , Hispânico ou Latino/genética , Gordura Subcutânea Abdominal , População Branca/genética , Absorciometria de Fóton , Negro ou Afro-Americano/estatística & dados numéricos , Alabama/epidemiologia , Densidade Óssea/genética , Criança , Estudos Transversais , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Masculino , Tomografia Computadorizada por Raios X , População Branca/estatística & dados numéricos
10.
Magn Reson Med ; 55(2): 450-4, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16342333

RESUMO

Mechanisms generating BOLD contrast are complex and depend on parameters that are prone to large variations, in particular in skeletal muscle. Here, we simultaneously measured perfusion by ASL, and BOLD response in the calf muscle of 6 healthy volunteers during post-ischemic reactive hyperemia. We tested whether the relation between the two was altered for varying degrees of leg vascular replenishment induced by prior positioning of the leg at different heights relative to the heart. We found that the BOLD response depended on perfusion, but also on the degree of repletion of leg blood vessels. We conclude that simultaneous determination of perfusion by ASL is important to identify the mechanisms underlying BOLD contrast in the skeletal muscle.


Assuntos
Hiperemia/fisiopatologia , Perna (Membro)/irrigação sanguínea , Espectroscopia de Ressonância Magnética/métodos , Músculo Esquelético/irrigação sanguínea , Análise de Variância , Humanos , Isquemia/fisiopatologia , Modelos Lineares , Oxigênio/sangue , Postura , Marcadores de Spin
12.
Gene Ther ; 12(19): 1434-43, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15877048

RESUMO

In vivo gene electrotransfer (ET) is a simple method of gene delivery in various tissues relying on the injection of plasmid DNA followed by application of electric pulses. Noninvasive tools are needed to evaluate the ET efficiency and the resulting tissue damages. In this study, we performed ET of rat tibialis muscle after injection of either a plasmid coding for luciferase or a contrast agent (CA) detected by using magnetic resonance imaging (MRI). Plasmid expression and CA intracellular trapped quantity were compared throughout the electric field intensity range 0-300 V/cm. Although the CA trapped quantity reflects only the electropermeabilization step, both measurements were correlated. MRI measurements gave easy access to tridimensional visualization of the labelled zones where the CA has been injected and the applied electric field had a value allowing permeabilization. We also performed MRI measurements of the water transverse relaxation time T2 as an indicator of tissue modification, and tested whether another CA specific for necrosis could be used to detect muscle necrosis at high electric field intensity. In conclusion, MRI measurements may bring multiparametric information upon the efficiency and tissue toxicity of an ET protocol by using a simple and safe CA.


Assuntos
Eletroporação/métodos , Terapia Genética/métodos , Luciferases/genética , Imageamento por Ressonância Magnética , Músculo Esquelético/enzimologia , Animais , Meios de Contraste/análise , Expressão Gênica , Terapia Genética/efeitos adversos , Compostos Heterocíclicos/análise , Injeções Intramusculares , Luciferases/análise , Masculino , Compostos Organometálicos/análise , Plasmídeos/administração & dosagem , Ratos , Ratos Wistar
13.
Am J Physiol Regul Integr Comp Physiol ; 287(6): R1441-9, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15528402

RESUMO

In human muscle the role of myoglobin (Mb) and its relationship to factors such as muscle perfusion and metabolic capacity are not well understood. We utilized nuclear magnetic resonance (NMR) to simultaneously study the Mb concentration ([Mb]), perfusion, and metabolic characteristics in calf muscles of athletes trained long term for either sprint or endurance running after plantar flexion exercise and cuff ischemia. The acquisitions for (1)H assessment of Mb desaturation and concentration, arterial spin labeling measurement of muscle perfusion, and (31)P spectroscopy to monitor high-energy phosphate metabolites were interleaved in a 4-T magnet. The endurance-trained runners had a significantly elevated [Mb] (0.28 +/- 0.06 vs. 0.20 +/- 0.03 mmol/kg). The time constant of creatine rephosphorylation (tauPCr), an indicator of oxidative capacity, was both shorter in the endurance-trained group (34 +/- 6 vs. 64 +/- 20 s) and negatively correlated with [Mb] across all subjects (r = 0.58). The time to reach maximal perfusion after cuff release was also both shorter in the endurance-trained group (306 +/- 74 vs. 560 +/- 240 s) and negatively correlated with [Mb] (r = 0.56). Finally, Mb reoxygenation rate tended to be higher in the endurance-trained group and was positively correlated with tauPCr (r = 0.75). In summary, these NMR data reveal that [Mb] is increased in human muscle with a high oxidative capacity and a highly responsive vasculature, and the rate at which Mb resaturates is well correlated with the rephosphorylation rate of Cr, each of which support a teleological role for Mb in O(2) transport within highly oxidative human skeletal muscle.


Assuntos
Exercício Físico/fisiologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Mioglobina/fisiologia , Esportes/fisiologia , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Consumo de Oxigênio , Corrida/fisiologia
14.
Neuromuscul Disord ; 13(5): 397-407, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12798795

RESUMO

Gene and cell therapies convey high hopes for treatment of skeletal and heart muscle diseases. In the experimental protocols under development as well as in the first clinical trials, longitudinal control by an atraumatic procedure is needed. Nuclear magnetic resonance (NMR), via its two modalities, imaging or spectroscopy, should play a major role both for in vivo animal and human studies, because of the great number of parameters that can be measured, sequentially or simultaneously, and because of its aptitude to monitor several steps of protocols, in particular to detect physiological modifications induced by therapies. We review here the many possible applications of nuclear magnetic resonance in gene/cell therapies where muscle is the target organ, with emphasis on the application of nuclear magnetic resonance to functional studies.


Assuntos
Transplante de Células , Terapia Genética , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Músculo Esquelético , Doenças Musculares/terapia , Miocárdio , Animais , Transplante de Células/tendências , Expressão Gênica , Terapia Genética/tendências , Humanos , Imageamento por Ressonância Magnética/tendências , Músculo Esquelético/fisiopatologia , Miocárdio/patologia
15.
Rev Neurol (Paris) ; 159(1): 56-67, 2003 Jan.
Artigo em Francês | MEDLINE | ID: mdl-12618654

RESUMO

One hundred patients presenting with exercise intolerance or rhabdomyolysis episodes have been examined successively by 31P Nuclear Magnetic Resonance Spectroscopy (MRS) of leg plantar flexor muscles with exercise test. In all cases a muscle biopsy was performed. At the end of investigations, diagnosis of a metabolic myopathy was made in 33 patients: glycogenolysis or glycolysis deficiency in 8 cases, mitochondrial myopathy in 24 cases and CPT II deficiency in one case. Muscular dystrophy or congenital myopathy were diagnosed in 6 cases. No precise etiology could be found in 30 patients with either high CK levels or muscle biopsy abnormalities. Seven patients had rhabdomyolysis related to excessive physical activities. Twenty-four patients had functional symptoms. The principal MRS parameters used for diagnosis were the values of intracellular pH at the end of exercise and the time constant of phosphocreatine resynthesis during recovery. Lack of acidosis after exercise was observed in all patients with blockade of glycogenolysis or glycolysis. A slowing in phosphocreatine resynthesis was found in 66 p.cent of patients with definite mitochondrial myopathy. The specificity of these parameters were respectively 92.4 p.cent and 85.5 p.cent for the two groups. In conclusion (31)P MRS allows the detection of muscular glycogenoses with a sensitivity close to 100 p.cent. However, its sensitivity was lower for the detection of mitochondrial myopathies, as is also known for the other in vivo metabolic investigations, reflecting the heterogeneity of expression of mitochondrial abnormalities in a given muscle. The integration of imaging in the examination protocol may help to orientate towards the diagnostic of a dystrophy in some patients.


Assuntos
Tolerância ao Exercício/fisiologia , Músculo Esquelético/patologia , Rabdomiólise/patologia , Adolescente , Adulto , Idoso , Exercício Físico , Teste de Esforço , Feminino , Glicogênio/metabolismo , Glicólise , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/enzimologia , Músculo Esquelético/fisiopatologia , Fosfocreatina/metabolismo , Rabdomiólise/enzimologia , Rabdomiólise/fisiopatologia
16.
J Appl Physiol (1985) ; 94(3): 1012-24, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12571132

RESUMO

Skeletal muscle voluntary contractions (VC) and electrical stimulations (ES) were compared in eight healthy men. High-energy phosphates and myoglobin oxygenation were simultaneously monitored in the quadriceps by interleaved (1)H- and (31)P-NMR spectroscopy. For the VC protocol, subjects performed five or six bouts of 5 min with a workload increment of 10% of maximal voluntary torque (MVT) at each step. The ES protocol consisted of a 13-min exercise with a load corresponding to 10% MVT. For both protocols, exercise consisted of 6-s isometric contractions and 6-s rest cycles. For an identical mechanical level (10% MVT), ES induced larger changes than VC in the P(i)-to-phosphocreatine ratio [1.38 +/- 1.14 (ES) vs. 0.13 +/- 0.04 (VC)], pH [6.69 +/- 0.11 (ES) vs. 7.04 +/- 0.07 (VC)] and myoglobin desaturation [43 +/- 15.9 (ES) vs. 6.1 +/- 4.6% (VC)]. ES activated the muscle facing the NMR coil to a greater extent than did VCs when evaluated under identical technical conditions. This metabolic pattern can be interpreted in terms of specific temporal and spatial muscle cell recruitment. Furthermore, at identical levels of energy charge, the muscle was more acidotic and cytoplasm appeared more oxygenated during ES than during VC. These results are in accordance with a preferential recruitment of type II fibers and a relative muscle hyperperfusion during ES.


Assuntos
Músculo Esquelético/fisiologia , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Adulto , Estimulação Elétrica , Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Glicólise/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Isquemia/metabolismo , Isquemia/fisiopatologia , Contração Isométrica/fisiologia , Espectroscopia de Ressonância Magnética , Masculino , Contração Muscular/fisiologia , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/química , Músculo Esquelético/citologia , Mioglobina/metabolismo , Consumo de Oxigênio/fisiologia , Fosfocreatina/metabolismo , Recrutamento Neurofisiológico/fisiologia
18.
Magn Reson Med ; 46(2): 305-11, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11477634

RESUMO

T(1)-based determination of perfusion was performed with the high temporal and spatial resolution that monitoring of exercise physiology requires. As no data were available on the validation of this approach in human muscles, T(1)-based NMRI of perfusion was compared to standard strain-gauge venous occlusion plethysmography performed simultaneously within a 4 T magnet. Two different situations were investigated in 21 healthy young volunteers: 1) a 5-min ischemia of the leg, or 2) a 2-3 min ischemic exercise consisting of a plantar flexion on an amagnetic ergometer. Leg perfusion was monitored over 5-15 min of the recovery phase, after the air-cuff arterial occlusion had been released. The interesting features of the sequence were the use of a saturation-recovery module for the introduction of a T(1) modulation and of single-shot spin echo for imaging. Spatial resolution was 1.7 x 2.0 mm and temporal resolution was 2 s. For data analysis, ROIs were traced on different muscles and perfusion was calculated from the differences in muscle signal intensity in successive images. To allow comparison with the global measurement of perfusion by plethysmography, the T(1)-based NMR measurements in exercising muscles were rescaled to the leg cross-section. The perfusion measurements obtained by plethysmography and NMRI were in close agreement with a correlation coefficient between 0.87 and 0.92. This indicates that pulsed arterial techniques provide determination of muscle perfusion not only with superior spatial and temporal resolution but also with exactitude.


Assuntos
Perna (Membro)/irrigação sanguínea , Espectroscopia de Ressonância Magnética/métodos , Músculo Esquelético/irrigação sanguínea , Pletismografia/métodos , Adulto , Exercício Físico/fisiologia , Feminino , Humanos , Isquemia/fisiopatologia , Modelos Lineares , Masculino , Variações Dependentes do Observador , Marcadores de Spin
19.
Artigo em Inglês | MEDLINE | ID: mdl-11223385

RESUMO

The goal of this study was to evaluate morphofunctional changes in mitochondrial ultrastructure after platelet-derived growth factor application in fibroblasts as an indicator of mitochondrial activation in processes like wound healing. NRK-49F fibroblasts were synchronized, incubated with PDGF (platelet-derived growth factor) and studied by electron microscopy. Volume density (Vv), numerical density (Nv) and surface density (Sv) were measured by stereological analysis. Application of PDGF on NRK-49F caused an increase in mitochondrial volume density by 57% and surface area of cristae per mitochondrion by 65%. The numerical density of the mitochondria was decreased in the PDGF-treated cells by 23%, but at the same time their mean volume was increased. Furthermore, the mitochondria had a complex and highly variable shape both in control and PDGF-treated cells, possibly indicating the existence of a mitochondrial reticulum. The results demonstrated that biochemically active membrane systems in fibroblast mitochondria are enlarged as a direct effect of small doses of platelet-derived growth factor and support the concept that this factor and related peptides serve as mitogens for connective tissue forming cells. Thus, in mitogenic processes like wound healing, the high energy demand of fibroblasts is provided by the increase of the inner surface of mitochondria.


Assuntos
Mitocôndrias/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/farmacologia , Animais , Linhagem Celular , Fibroblastos/efeitos dos fármacos , Fibroblastos/ultraestrutura , Microscopia Eletrônica , Mitocôndrias/ultraestrutura
20.
Neuromuscul Disord ; 11(1): 50-5, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11166166

RESUMO

A magnetic resonance imaging protocol was tested in a cardiotoxin-induced myonecrosis of hindlimb muscles of three normal mice to assess the usefulness of data provided by longitudinal follow-up of a few individuals. Magnetic resonance imaging examinations were performed sequentially at 4 T between days 1 and 11 post-injury. Axial T1-weighted images after injection of a paramagnetic contrast agent were used to determine the volume of lesions from regions of increased signal intensity. T2 measurements were performed from a single-slice ten-echo acquisition centered upon the largest section of lesion. Early after injury, a very large T2 increase was observed. As recovery proceeded, T2 values progressively decreased toward normal values. Similarly, the volumes of lesions decreased to virtually zero by days 10-11. The evolution of these indices followed the same time scheme observed in histological studies. The use of a volume probe allowed accurate measurement of T2 values, and the acquisition of volumetric data. Such magnetic resonance imaging follow-up should help gather valuable information using few animals.


Assuntos
Modelos Animais de Doenças , Músculo Esquelético/patologia , Distrofias Musculares/patologia , Recuperação de Função Fisiológica/fisiologia , Animais , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/lesões , Músculo Esquelético/fisiopatologia , Distrofias Musculares/fisiopatologia , Necrose
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