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1.
Soc Sci Med ; 339: 116406, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37979491

RESUMO

Increasingly, applied social scientists and clinicians recognize the value of engaging transgender and gender-diverse (TGD) people, particularly TGD individuals with lived experience as care recipients (peers), to inform the provision of gender-affirming care. Despite this trend, few researchers have systematically examined how this group can contribute to and enhance the development and delivery of interventions intended to affirm gender diversity. In this article, we address limitations in the literature by drawing on a secondary analysis of qualitative data - originally collected to examine the peer support experiences of TGD individuals - to explore the potential that TGD peers hold for elevating gender-affirming care. The study was informed methodologically by an abductive approach to grounded theory, and conceptually by critical resilience and intersectional scholarship. Data collection involved virtual, semi-structured interviews with 35 TGD individuals in two Canadian cities who indicated having experiences of seeking, receiving, and/or providing peer support. Data analysis comprised an iterative, abductive process of cross-referencing participant accounts with relevant scholarship to arrive at an account of how TGD peers may contribute to the growth of gender-affirming care. Our findings suggest, broadly, that TGD peers may enhance gender-affirming care by: (1) validating a growing diversity of embodiments and experiences in healthcare decision-making, (2) nurturing and diversifying relevant networks of safety, community support, and advocacy outside formal systems of care, and (3) strengthening possibilities for resisting and transforming existing healthcare systems. After outlining these findings, we briefly consider the implications of our analysis and leverage our inferences to substantiate the notion of community-driven gender-affirming care, meaning care that is intentional in its incorporation of relevant community stakeholders to shape governance and service provision. We conclude with reflections on the promise of community-driven care at a time of heightened volatility across systems serving TGD populations.


Assuntos
Pessoas Transgênero , Humanos , Canadá , Cidades , Confiabilidade dos Dados , Análise de Dados
2.
Sci Rep ; 13(1): 18155, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875514

RESUMO

The development of high intensity petawatt lasers has created new possibilities for ion acceleration and nuclear fusion using solid targets. In such laser-matter interaction, multiple ion species are accelerated with broad spectra up to hundreds of MeV. To measure ion yields and for species identification, CR-39 solid-state nuclear track detectors are frequently used. However, these detectors are limited in their applicability for multi-ion spectra differentiation as standard image recognition algorithms can lead to a misinterpretation of data, there is no unique relation between track diameter and particle energy, and there are overlapping pit diameter relationships for multiple particle species. In this report, we address these issues by first developing an algorithm to overcome user bias during image processing. Second, we use calibration of the detector response for protons, carbon and helium ions (alpha particles) from 0.1 to above 10 MeV and measurements of statistical energy loss fluctuations in a forward-fitting procedure utilizing multiple, differently filtered CR-39, altogether enabling high-sensitivity, multi-species particle spectroscopy. To validate this capability, we show that inferred CR-39 spectra match Thomson parabola ion spectrometer data from the same experiment. Filtered CR-39 spectrometers were used to detect, within a background of ~ 2 × 1011 sr-1 J-1 protons and carbons, (1.3 ± 0.7) × 108 sr-1 J-1 alpha particles from laser-driven proton-boron fusion reactions.

3.
J Orthop Res ; 41(12): 2694-2702, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37203456

RESUMO

Since idiopathic scoliosis is a multifactorial disorder, the proprioceptive defect is considered one of its etiological factors. Genetic studies have separately revealed this relationship, yet it remains indeterminate which specific genes that related to proprioception contributed to the initiation, progression, pathology, and treatment outcomes of the curvature. A systematic search was conducted on four online databases, including PubMed, Web of Science, Embase, and Academic search complete. Studies were included if they involved human or animal subjects with idiopathic scoliosis and evaluated with proprioceptive genes. The search period was the inception of the database to February 21, 2023. Four genes (i.e., Ladybird homeobox 1 [LBX1], Piezo type mechanosensitive ion channel component 2 [PIEZO2], Runx family transcription factor 3 [RUNX3], and neurotrophin 3 [NTF3]) investigated in 19 studies were included. LBX1 has confirmed the correlation with the development of idiopathic scoliosis in 10 ethnicities, whereas PIEZO2 has shown a connection with clinical proprioceptive tests in subjects with idiopathic scoliosis. However, curve severity was less likely to be related to the proprioceptive genes. The potential pathology took place at the proprioceptive neurons. Evidence of proprioception-related gene mutations in association with idiopathic scoliosis was established. Nevertheless, the causation between the initiation, progression, and treatment outcomes with proprioceptive defect requires further investigation.


Assuntos
Escoliose , Animais , Humanos , Escoliose/genética , Propriocepção/fisiologia , Mutação
4.
Eur Spine J ; 31(12): 3347-3364, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36069938

RESUMO

PURPOSE: This review aimed to identify effective physical performance tests (PPT) as clinical outcome indicators for detecting and monitoring degenerative cervical myelopathy (DCM). METHODS: A comprehensive literature search was performed on seven electronic databases on the effectiveness in detection and monitoring of DCM by PPT. All included studies were reviewed and undergone quality assessments on the risk-of-bias by Newcastle-Ottawa Scale and were pooled by random-effect analysis with level of significance at 0.05. Homogeneity among studies was assessed by I2-statistics and effect of PPT was confirmed by Cohen's d effect size and confidence intervals. RESULTS: Totally, 3111 articles were retrieved, and 19 studies were included for review and meta-analysis. There were 13 studies investigating PPT regarding the upper limbs and 12 studies regarding the lower limbs. Performance in 10-second-Grip-and-Release Test (G&R) and 9-Hole-Peg Test (9HPT) was studied in 10 and 3 articles, respectively, while 10-second-Stepping Test (SST), 30-meter-Walking Test (30MWT) and Foot-Tapping Test (FTT) for lower limbs were studied in 5, 4, and 3 articles correspondingly. Only 1 study utilized the Triangle-Stepping Test. High-quality study with fair risk-of-bias was revealed from Newcastle-Ottawa scale. Large effect size facilitated detection and monitoring in DCM was unveiling for G&R, 9HPT, SST, and 30MWT. FTT, while also effective, was hindered by a high-degree heterogeneity in the meta-analysis. CONCLUSION: Effective PPT including G&R, 9HPT, SST, 30MWT, and FTT was identified for disease detection and monitoring in DCM.


Assuntos
Vértebras Cervicais , Doenças da Medula Espinal , Humanos , Doenças da Medula Espinal/diagnóstico , Pescoço , Extremidade Inferior , Desempenho Físico Funcional
5.
Brain Inj ; 36(5): 607-619, 2022 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-35507697

RESUMO

PRIMARY OBJECTIVES: Determine if an abnormal preliminary neuroendocrine disorder (NED) blood test screen is associated with mild TBI (mTBI) history or post-concussiveclinical features. RESEARCH DESIGN: Observational. METHODS: Among 1,520 participants with military combatexposure, we measured randomly timed serum levels of insulin-likegrowth factor-1, thyroid stimulating hormone (TSH), and total testosterone as a preliminary NED screen. Using multivariable models, we analyzed relation of screen results in mTBI group membership and post-concussiveclinical features (fatigue, depression, cognitive symptoms, executive function, processing speed). RESULTS: None of the mTBI positive groups, including repetitive (≥3 mTBI) and blast-related,differed from the non-TBIcontrols on rates of abnormal lab screen or rates of growth hormone deficiency (GHD), hypothyroidism or male hypogonadism in treatment records. Lab screen findings were also not associated with any clinical feature. CONCLUSIONS: This study shows no evidence that remote mTBI(s) or implicated post-concussiveclinical features are linked to GHD, hypothyroidism or male hypogonadism. Large case-controlstudies incorporating more definitive neuroendocrine disorder NED testing (TSH plus thyroxine, early morning testosterone, LH, FSH, prolactin and GH provocative testing) are needed to determine whether mTBI(s) alone elevate one's risk for chronic NED and how best to select patients for comprehensive testing.


Assuntos
Concussão Encefálica , Lesões Encefálicas Traumáticas , Hipogonadismo , Hipotireoidismo , Militares , Transtornos de Estresse Pós-Traumáticos , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Humanos , Hipogonadismo/complicações , Hipogonadismo/etiologia , Hipotireoidismo/complicações , Hipotireoidismo/diagnóstico , Masculino , Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/complicações , Testosterona , Tireotropina
6.
J Dance Med Sci ; 26(1): 41-49, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34865681

RESUMO

Some studies suggested that adolescent scoliotic dancers were more likely to sustain dance injuries than non-scoliotic dancers. This study aimed to investigate the association between scoliosis and dance injury among children and adolescent recreational dancers. Identical web-based and paper-based questionnaires were distributed to children and adolescent recreational dancers to collect demographic information, dance experiences, history and location of dance injuries, as well as the frequency of dance injury in the last 12 months. The prevalence rates of the top three dance injury sites (lower back, knee, and ankles) were estimated. Associations between the presence of scoliosis and various dance injuries in the last 12 months were evaluated by multivariate logistic regression. Data from 704 respondents (644 females, 13.3 ± 2.4 years) was analyzed. Ninety-one respondents (12.9%) reported scoliosis and 11 respondents (1.6%) were wearing scoliosis braces. The 12-month prevalence rates of lumbar, knee, and ankle injuries in scoliotic dancers (24.2%, 22.2%, and 28.5%, respectively) were significantly higher than those of non-scoliotic dancers (10.4%, 14.9%, and 14.8%, respectively). Scoliosis was an independent risk factor for lumbar spine injury (Odds ratio, OR = 2.7), knee injury (OR = 2.6), and multi-site dance-related injury (OR = 1.9). Given the observed strong associations between scoliosis and lumbar or knee dance injuries in the current study, future studies are warranted to investigate the underlying causes.


Assuntos
Dança , Traumatismos do Joelho , Escoliose , Adolescente , Articulação do Tornozelo , Criança , Estudos Transversais , Dança/lesões , Feminino , Humanos , Traumatismos do Joelho/epidemiologia , Escoliose/epidemiologia
7.
Global Spine J ; 12(8): 1852-1861, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34911378

RESUMO

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: The present review aimed to summarize the evidence regarding differences in proprioception between children with and without adolescent idiopathic scoliosis (AIS). METHODS: Seven electronic databases were searched from their inception to April 10, 2021. Articles were included if they involved: (1) AIS patients aged between 10 and 18 years, (2) measurements of proprioceptive abilities, and (3) comparisons with non-AIS controls. Animal studies, case reports, commentaries, conference proceedings, research protocols, and reviews were excluded. Two reviewers independently conducted literature screening, data extraction, risks of bias assessments, and quality of evidence evaluations. Relevant information was pooled for meta-analyses. RESULTS: From 432 identified citations, 11 case-control studies comprising 1121 participants were included. The meta-analyses showed that AIS participants displayed proprioceptive deficits as compared to non-AIS controls. Moderate evidence supported that AIS participants showed significantly larger repositioning errors than healthy controls (pooled mean difference = 1.27 degrees, P < .01). Low evidence substantiated that AIS participants had significantly greater motion detection threshold (pooled mean difference = 1.60 degrees, P < .01) and abnormal somatosensory evoked potentials (pooled mean difference = .36 milliseconds, P = .01) than non-AIS counterparts. CONCLUSIONS: Consistent findings revealed that proprioceptive deficits occurred in AIS patients. Further investigations on the causal relationship between AIS and proprioception, and the identification of the subgroup of AIS patients with proprioceptive deficit are needed.

8.
Prev Med ; 151: 106559, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34217410

RESUMO

Women from racial and ethnic minority groups face a disproportionate burden of cervical and breast cancers in the United States. The Coronavirus Disease 2019 (COVID-19) pandemic might exacerbate these disparities as supply and demand for screening services are reduced. The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides cancer screening services to women with low income and inadequate health insurance. We examined COVID-19's impact on NBCCEDP screening services during January-June 2020. We found the total number of NBCCEDP-funded breast and cervical cancer screening tests declined by 87% and 84%, respectively, during April 2020 compared with the previous 5-year averages for that month. The extent of declines varied by geography, race/ethnicity, and rurality. In April 2020, screening test volume declined most severely in Health and Human Services Region 2 - New York (96% for breast, 95% for cervical cancer screening) compared to the previous 5-year averages. The greatest declines were among American Indian/Alaskan Native women for breast cancer screening (98%) and Asian Pacific Islander women for cervical cancer screening (92%). Test volume began to recover in May and, by June 2020, NBCCEDP breast and cervical cancer screening test volume was 39% and 40% below the 5-year average for that month, respectively. However, breast cancer screening remained over 50% below the 5-year average among women in rural areas. NBCCEDP programs reported assisting health care providers resume screening.


Assuntos
Neoplasias da Mama , COVID-19 , Neoplasias do Colo do Útero , Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer , Etnicidade , Feminino , Humanos , Programas de Rastreamento , Pessoas sem Cobertura de Seguro de Saúde , Grupos Minoritários , New York , SARS-CoV-2 , Estados Unidos , Neoplasias do Colo do Útero/diagnóstico
9.
J Bone Joint Surg Am ; 103(15): 1438-1450, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34166276

RESUMO

BACKGROUND: Although multiple studies have investigated risk factors for symptomatic adjacent segment disease (ASD) after lumbar fusion, their findings were diverse and inconsistent. This review aimed to summarize risk factors for ASD in order to guide the management of ASD and future research. METHODS: Six electronic databases were systematically searched from inception to December 2019. Two reviewers independently screened titles, abstracts, and full-text articles to identify studies investigating risk factors for ASD after lumbar fusion in humans. The methodological quality of the included studies and the strength of evidence regarding risk factors were evaluated. RESULTS: Sixteen studies involving 3,553 patients were included. Meta-analyses revealed that high body mass index, facet joint violation, anterior shift of the preoperative and postoperative lumbosacral sagittal plumb line, decreased preoperative and postoperative lumbar lordosis, preoperative adjacent disc degeneration, decreased preoperative adjacent disc height, increased postoperative lumbopelvic mismatch, postoperative pelvic incidence, and postoperative pelvic tilt were significantly related to ASD. CONCLUSIONS: This meta-analysis addressed the limitations of prior reviews and summarized evidence with regard to risk factors for ASD following lumbar fusion. Future prospective studies should investigate whether modification of these risk factors can reduce the ASD development. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Complicações Pós-Operatórias/epidemiologia , Fusão Vertebral/efeitos adversos , Índice de Massa Corporal , Humanos , Incidência , Degeneração do Disco Intervertebral/epidemiologia , Degeneração do Disco Intervertebral/etiologia , Degeneração do Disco Intervertebral/patologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Complicações Pós-Operatórias/etiologia , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Articulação Zigapofisária/diagnóstico por imagem , Articulação Zigapofisária/patologia
10.
BMJ Mil Health ; 166(E): e21-e24, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31123090

RESUMO

BACKGROUND: Open-book pelvic fractures are associated with significant mortality. Emergency management may require a commercial pelvic circumferential compression device to reduce the fracture and compress haemorrhaging pelvic vasculature. Standard, commercial, twin-sized bedsheets are acceptable should commercial devices be unavailable. However, obese victims or personnel with insufficient body strength may impede successful reduction. OBJECTIVE: To demonstrate the value of an improvisational windlass (intravenous pole) in improving the ability to reduce an open-book pelvic fracture. METHODS: The Institutional Review Board-approved study involved 28 diverse healthcare students and emergency medicine residents. Each participant's demographic information and physical characteristics were recorded. A METIman was prepared with knee and ankle binding and a sphygmomanometer set at 40 mm Hg placed over the symphysis pubis. Two-person teams were randomly selected to place a bedsheet at greater trochanter level and atop the sphygmomanometer. The bedsheet was secured with maximum effort by the pairs and the pressure recorded. Following this, the pairs inserted an intravenous pole in the knot and torqued the pole to maximum effort and a repeat pressure recorded. RESULTS: The mean increase in pressure using only the bedsheet was 106.43 mm Hg per team. With bedsheet and intravenous pole, the mean pressure increase was 351.79 mm Hg per team. The difference was statistically significant (independent samples t-test: t = 17.177, p < 0.001, 95% CI (216.65 to 274.07 mm Hg). There was no correlation between pressure increases and the individual physical characteristics of the subjects (r = - 0.183, p = 0.352). CONCLUSIONS: Regardless of personnel's physical attributes, the addition of an improvisational windlass to a pelvic circumferential compression bedsheet can improve the ability to reduce an open-book fracture, especially in obese victims.


Assuntos
Fraturas Ósseas/cirurgia , Procedimentos Ortopédicos/métodos , Ossos Pélvicos/lesões , Treinamento por Simulação/normas , Fenômenos Biomecânicos , Bandagens Compressivas/efeitos adversos , Bandagens Compressivas/normas , Humanos , Manequins , Procedimentos Ortopédicos/normas , Procedimentos Ortopédicos/estatística & dados numéricos , Ossos Pélvicos/cirurgia , Treinamento por Simulação/métodos , Treinamento por Simulação/estatística & dados numéricos , Esfigmomanômetros/efeitos adversos , Esfigmomanômetros/normas
11.
Proteomics ; 6(7): 2101-7, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16518871

RESUMO

Here we describe the use of SELDI-MS to detect dose-dependent peptide changes in plasma from mice treated with vehicle or rosiglitazone at one of two doses (10 and 30 mg/kg). SELDI features differentiating spectra from the three conditions were found and used to train classifiers. Samples treated with vehicle could be reliably distinguished from samples treated with either dose, but samples treated with the different doses could not be reliably distinguished from one another. We conclude that while SELDI-TOF mass spectra can be used to distinguish treated from untreated samples, the reproducibility and information content of SELDI-TOF are currently not sufficient as a pharmacodynamic readout to distinguish between mice treated with 10 or 30 mg/kg of rosiglitazone. This raises more general questions about whether SELDI's sensitivity is sufficient for detecting dose-dependent changes in plasma.


Assuntos
Peptídeos/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Tiazolidinedionas/administração & dosagem , Animais , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Masculino , Camundongos , Modelos Biológicos , Peptídeos/análise , Peptídeos/química , Reprodutibilidade dos Testes , Rosiglitazona , Tiazolidinedionas/farmacologia
12.
Sex Transm Dis ; 32(10 Suppl): S43-7, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16205292

RESUMO

BACKGROUND: Eight US cities experienced large outbreaks of syphilis among men having sex with men (MSM), beginning during 2000-2001. Provider-assisted partner notification via disease intervention specialists has traditionally composed a large part of syphilis control efforts. OBJECTIVES: Report current effectiveness of syphilis partner notification for MSM and identify related problems and solutions. RESULTS: One thousand five hundred seventeen MSM diagnosed with syphilis claimed 10,254 sex partners. Many claimed anonymous partners (median = 65%), or provided insufficient locating information (median = 42%). Median cases found per index case were 0.09 (total = 116), although an additional 197 partners had been previously treated. Principal impediments to partner notification fell into 3 areas: (1) diagnosis outside health department settings delayed interviews, (2) partners were often anonymous, and (3) mistrust among MSM, public health professionals, and health care providers in private settings. CONCLUSIONS: Characteristics of the current outbreaks among MSM make traditional partner notification more difficult than in the past. Some modifications, complements, and even alternatives to partner notification are either planned or in operation.


Assuntos
Busca de Comunicante , Homossexualidade Masculina , Parceiros Sexuais , Sífilis , Cidades , Surtos de Doenças , Humanos , Masculino , Sífilis/diagnóstico , Sífilis/epidemiologia , Sífilis/prevenção & controle , Estados Unidos
13.
J Pediatr Health Care ; 15(6): 291-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11717685

RESUMO

INTRODUCTION: The purpose of this study was to describe the characteristics of employment, the characteristics of children served, and the role functions of recent graduates of pediatric nurse practitioner (PNP) programs and to compare these characteristics across programs. METHOD: A 60-item multiple-choice survey tool was sent to graduates from 1996-1998 of 6 universities across the United States. RESULTS: A total of 137 surveys were received for a return rate of 52%. Less than half of the respondents (44%) indicated that they were employed in a primary care practice. Seventy percent indicated they "often" or "sometimes" provided care to children with acute/critical conditions, and 77% reported caring for children with chronic conditions. Role functions of case management, staff development, consultation, administration, and implementation of research were performed "often" or "sometimes" by more than 50% of respondents. Findings were fairly consistent in 5 out of 6 programs surveyed. DISCUSSION: Graduates of PNP programs are increasingly called on to provide care to children with complex health care needs in non-primary care settings. Role functions beyond the traditional areas required for pediatric primary care are now common practice. Educational programs should address these dynamic changes by assessing the adequacy of their curricula and clinical residencies in preparing graduates.


Assuntos
Educação de Pós-Graduação em Enfermagem/organização & administração , Emprego/estatística & dados numéricos , Profissionais de Enfermagem/educação , Profissionais de Enfermagem/estatística & dados numéricos , Prática Profissional/estatística & dados numéricos , Administração de Caso/estatística & dados numéricos , Criança , Coleta de Dados , Humanos , Enfermeiros Administradores/estatística & dados numéricos , Profissionais de Enfermagem/organização & administração , Pediatria/educação
14.
Ann Neurol ; 48(3): 395-8, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10976650

RESUMO

The detection of 14-3-3 protein by Western immunoblot is a sensitive and specific cerebrospinal fluid marker of Creutzfeldt-Jakob disease (CJD). We developed a quantitative enzyme-linked immunosorbent assay (ELISA) that reliably detects 14-3-3 in cerebrospinal fluid. In a prospective study of 147 cerebrospinal fluid samples, the mean 14-3-3 concentration among pathologically confirmed CJD patients (28.0+/-20.6 ng/ml, n = 41) is significantly higher than the mean in the cerebrospinal fluid of those with other neurological disorders (3.1+/-2.9 ng/ ml, n = 84). At a cutoff value of 8.3 ng/ml, the ELISA has a sensitivity of 92.7% and a specificity of 97.6%. The 14-3-3 ELISA supports a diagnosis of CJD in patients who fulfill clinical criteria for possible CJD.


Assuntos
Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Inibidores Enzimáticos/análise , Ensaio de Imunoadsorção Enzimática/métodos , Proteínas/análise , Tirosina 3-Mono-Oxigenase , Proteínas 14-3-3 , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
15.
J Chromatogr B Biomed Sci Appl ; 742(1): 173-83, 2000 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-10892596

RESUMO

A HPLC-MS-MS method was developed and validated to measure lamivudine and zidovudine simultaneously in small volumes of human seminal plasma. Sample preparation was simple and rapid, requiring 25 microl of sample, the use of isotopically labeled lamivudine and zidovudine as internal standards and ultrafiltration through a molecular mass cut-off membrane. Lamivudine and its internal standard were separated from zidovudine and its internal standard with isocratic HPLC. Detection was carried out using tandem mass spectrometry. This validated method was used to analyze seminal samples obtained from six HIV-positive patients prescribed lamivudine and zidovudine.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Lamivudina/análise , Espectrometria de Massas/métodos , Inibidores da Transcriptase Reversa/análise , Sêmen/química , Zidovudina/análise , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/análise , Fármacos Anti-HIV/uso terapêutico , Calibragem , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Humanos , Lamivudina/administração & dosagem , Lamivudina/uso terapêutico , Masculino , Padrões de Referência , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/uso terapêutico , Zidovudina/administração & dosagem , Zidovudina/uso terapêutico
16.
J Pharm Biomed Anal ; 22(6): 967-83, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10857566

RESUMO

A method employing high performance liquid chromatography (HPLC) with tandem mass spectrometry (MS) has been developed and validated for the simultaneous determination of clinically relevant levels of zidovudine (AZT) and lamivudine (3TC) in human serum. The method incorporates a fully automated ultrafiltration sample preparation step that replaces the solid-phase extraction step typically used for HPLC with UV detection. The calibration range of the dual-analyte LC-MS/MS method is 2.5-2,500 and 2.5-5,000 ng ml-1 for AZT and 3TC, respectively, using 0.25 ml of human serum. The lower limit of quantification was 2.5 ng ml-1 for each analyte, with a chromatographic run time of approximately 6 min. Overall accuracy, expressed as bias, and inter- and intra-assay precision are < +/- 7 and < 10% for AZT, and < +/- 5 and < 12.1% for 3TC over the full concentration ranges. A cross-validation study demonstrated that the LC-MS/MS method afforded equivalent results to established methods consisting of a radioimmuno-assay for AZT and an HPLC-UV method for 3TC. Moreover, the LC-MS/MS was more sensitive, allowed markedly higher-throughput, and required smaller sample volumes (for 3TC only). The validated method has been used to support post-marketing clinical studies for Combivir a combination tablet containing AZT and 3TC.


Assuntos
Fármacos Anti-HIV/sangue , Lamivudina/sangue , Zidovudina/sangue , Especificidade de Anticorpos , Calibragem , Cromatografia Líquida de Alta Pressão , Humanos , Indicadores e Reagentes , Marcação por Isótopo , Espectrometria de Massas , Radioimunoensaio , Padrões de Referência , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta
18.
Clin Diagn Lab Immunol ; 6(6): 983-5, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10548598

RESUMO

We established four hybridoma cell lines producing monoclonal antibodies (MAbs) against 14-3-3 proteins. Immunoblot analysis revealed that epsilon and gamma isoforms were specifically increased in premortem cerebrospinal fluid samples from patients with sporadic Creutzfeldt-Jakob disease. Furthermore, dot immunoblot analysis showed that MAbs were more specific for native antigen than polyclonal antibodies were.


Assuntos
Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Proteínas , Tirosina 3-Mono-Oxigenase , Proteínas 14-3-3 , Anticorpos Monoclonais , Especificidade de Anticorpos , Humanos , Hibridomas , Immunoblotting , Isomerismo , Proteínas/química , Proteínas/imunologia , Proteínas/metabolismo
20.
Ann Neurol ; 41(4): 463-9, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9124803

RESUMO

Charcot-Marie-Tooth type 1B is an uncommon form of hereditary motor and sensory neuropathy caused by mutations in the P(0) myelin protein gene on chromosome 1. We report here a 20-year observation of 13 members of the first family with Charcot-Marie-Tooth disease to demonstrate linkage to chromosome 1 and now known to have a C270A mutation in the P(0) gene altering the extracellular domain of the protein. Affected individuals generally show an early age at onset, often indicated by delayed ability to walk. Proximal muscle weakness of the lower extremities is common and often marked, but the individuals remain ambulatory and there is no decrease in life span. Motor nerve conduction velocities of the fastest fibers are severely slowed (mean, 9-11 m/sec), even when compared with 3 families having Charcot-Marie Tooth type 1A (mean, 19-21 m/sec). Variability of disability between family members suggests that genetic and environmental factors in addition to the P(0) mutation play a role in the final phenotype. Nerve biopsy specimens demonstrate hypertrophy, onion bulb formation, loss of myelinated fibers, and occasional myelin thickening similar to that described in P(0) myelin knockout mice. Autopsy of the 92-year-old great-grandmother in this family demonstrated diffuse involvement of sensory and motor nerves, with loss of myelin in the posterior columns of the spinal cord and loss of anterior horn neurons but without other involvement of the central nervous system. This family demonstrates the long-term phenotypic consequences on the peripheral nervous system of a specific point mutation in the P(0) myelin gene.


Assuntos
Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Axônios/ultraestrutura , Biópsia , Doença de Charcot-Marie-Tooth/fisiopatologia , Criança , Pré-Escolar , Cromossomos Humanos Par 1 , Feminino , Fibrose , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Proteínas da Mielina/ultraestrutura , Condução Nervosa/fisiologia , Linhagem , Fenótipo , Raízes Nervosas Espinhais/ultraestrutura , Nervo Sural/ultraestrutura
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