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1.
Exp Eye Res ; 150: 149-65, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27020758

RESUMO

Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.


Assuntos
Células Fotorreceptoras de Vertebrados/metabolismo , Retina/fisiopatologia , Retinose Pigmentar/metabolismo , Humanos , Neuroglia/metabolismo , Neuroglia/patologia , Células Fotorreceptoras de Vertebrados/patologia , Retina/metabolismo , Retina/patologia , Retinose Pigmentar/patologia
2.
Ophthalmic Genet ; 42(4): 402-404, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33781147

RESUMO

Renowned French painter Edgar Degas suffered of progressive light sensitivity and blurred central vision in both eyes, which affected his life and art in many ways. A first cousin from his mother's side, Estelle Musson of New Orleans also lost vision in a similar fashion at a comparable age. We postulated that Edgar and Estelle shared the same retinal pathology that possibly developed in a hereditary fashion, and we were interested whether any of their living family descendants might carry ABCA4 mutations to test the possibility that Edgar Degas may have had Stargardt disease.Edgar was never married and had no children, but Estelle had five children, four of whom from her marriage to Edgar's younger brother, and there are several descendants still living in New Orleans area. Genetic testing on five of Estelle's great grandchildren (Edgar's great grandnieces) were performed searching for ABCA4 mutations.We could not document any disease-causing variations in the ABCA4 gene in any of the descendants and therefore concluded that Edgar Degas most likely did not have Stargardt disease. Estelle and Edgar may have shared a different hereditary disease or have had two different retinal dystrophies or had another eye disease, including the unlikely possibility of inflammatory disease.


Assuntos
Pessoas Famosas , Medicina nas Artes , Pinturas/história , Doença de Stargardt/história , Transportadores de Cassetes de Ligação de ATP/genética , França , História do Século XIX , História do Século XX , Humanos , Linhagem , Doença de Stargardt/genética
3.
J Exp Med ; 177(3): 647-56, 1993 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-8382253

RESUMO

Exposure of normal juvenile chicken bone marrow cells to the replication defective avian reticuloendotheliosis virus strain T (REV-T) (chicken syncytial virus [CSV]) in vitro resulted in the generation of transformed cell lines containing T cells. The transformed T cells derived from bone marrow included cells expressing either alpha/beta or gamma/delta T cell receptors (TCRs) in proportions roughly equivalent to the proportions of TCR-alpha/beta and TCR-gamma/delta T cells found in the normal bone marrow in vivo. Essentially all TCR-alpha/beta-expressing transformed bone marrow-derived T cells expressed CD8, whereas few, if any, expressed CD4. In contrast, among TCR-gamma/delta T cells, both CD8+ and CD8- cells were derived, all of which were CD4-. Exposure of ex vivo spleen cells to REV-T(CSV) yielded transformed polyclonal cell lines containing > 99% B cells. However, REV-T(CSV) infection of mitogen-activated spleen cells in vitro resulted in transformed populations containing predominantly T cells. This may be explained at least in part by in vitro activation resulting in dramatically increased levels of T cell REV-T(CSV) receptor expression. In contrast to REV-T(CSV)-transformed lines derived from normal bone marrow, transformed lines derived from activated spleen cells contained substantial numbers of CD4+ cells, all of which expressed TCR-alpha/beta. While transformed T cells derived from bone marrow were stable for extended periods of in vitro culture and were cloned from single cells, transformed T cells from activated spleen were not stable and could not be cloned. We have therefore dissociated the initial transformation of T cells with REV-T(CSV) from the requirements for long-term growth. These results provide the first demonstration of efficient in vitro transformation of chicken T lineage cells by REV-T(CSV). Since productive infection with REV-T(CSV) is not sufficient to promote long-term growth of transformed cells, these results further suggest that immortalization depends not only upon expression of the v-rel oncogene but also on intracellular factor(s) whose expression varies according to the state of T cell physiology and/or activation.


Assuntos
Transformação Celular Viral/fisiologia , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Receptores de Antígenos de Linfócitos T gama-delta/análise , Vírus da Reticuloendoteliose/fisiologia , Linfócitos T/ultraestrutura , Animais , Medula Óssea/química , Medula Óssea/ultraestrutura , Células da Medula Óssea , Antígenos CD4/análise , Antígenos CD8/análise , Galinhas , Fluorescência , Baço/química , Baço/citologia , Baço/ultraestrutura , Linfócitos T/microbiologia , Linfócitos T/fisiologia
4.
Br J Dermatol ; 162(3): 647-54, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20374604

RESUMO

BACKGROUND: Tretinoin is considered the benchmark prescription topical therapy for improving fine facial wrinkles, but skin tolerance issues can affect patient compliance. In contrast, cosmetic antiwrinkle products are well tolerated but are generally presumed to be less efficacious than tretinoin. OBJECTIVES: To compare the efficacy of a cosmetic moisturizer regimen vs. a prescription regimen with 0.02% tretinoin for improving the appearance of facial wrinkles. METHODS: An 8-week, randomized, parallel-group study was conducted in 196 women with moderate to moderately severe periorbital wrinkles. Following 2 weeks washout, subjects on the cosmetic regimen (n = 99) used a sun protection factor (SPF) 30 moisturizing lotion containing 5% niacinamide, peptides and antioxidants, a moisturizing cream containing niacinamide and peptides, and a targeted wrinkle product containing niacinamide, peptides and 0.3% retinyl propionate. Subjects on the prescription regimen (n = 97) used 0.02% tretinoin plus moisturizing SPF 30 sunscreen. Subject cohorts (n = 25) continued treatment for an additional 16 weeks. Changes in facial wrinkling were assessed by both expert grading and image analysis of digital images of subjects' faces and by self-assessment questionnaire. Product tolerance was assessed via clinical erythema and dryness grading, subject self-assessment, and determinations of skin barrier integrity (transepidermal water loss) and stratum corneum protein changes. RESULTS: The cosmetic regimen significantly improved wrinkle appearance after 8 weeks relative to tretinoin, with comparable benefits after 24 weeks. The cosmetic regimen was significantly better tolerated than tretinoin through 8 weeks by all measures. CONCLUSIONS: An appropriately designed cosmetic regimen can improve facial wrinkle appearance comparably with the benchmark prescription treatment, with improved tolerability.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Emolientes/administração & dosagem , Niacinamida/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Tretinoína/administração & dosagem , Vitamina A/análogos & derivados , Administração Tópica , Adulto , Idoso , Cosméticos/administração & dosagem , Diterpenos , Face , Feminino , Humanos , Pessoa de Meia-Idade , Peptídeos/administração & dosagem , Ésteres de Retinil , Higiene da Pele/métodos , Resultado do Tratamento , Vitamina A/administração & dosagem
5.
J Hosp Infect ; 105(4): 710-716, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32553893

RESUMO

The rapid growth of the coronavirus disease 2019 (COVID-19) pandemic, limited availability of personal protective equipment, and uncertainties regarding transmission modes of severe acute respiratory syndrome coronavirus-2 have heightened concerns for the safety of healthcare workers (HCWs). Systematic studies of occupational risks for COVID-19 in the context of community risks are difficult and have only recently started to be reported. Ongoing quality improvement studies in various locales and within many affected healthcare institutions are needed. A template design for small-scale quality improvement surveys is proposed. Such surveys have the potential for rapid implementation and completion, are cost-effective, impose little administrative or workforce burden, can reveal occupational risks while taking community risks into account, and can be repeated easily with short time intervals between repetitions. This article describes a template design and proposes a survey instrument that is easily modifiable to fit the particular needs of various healthcare institutions in the hope of beginning a collaborative effort to refine the design and instrument. These methods, along with data management and analytic techniques, can be widely useful and shared globally. The authors' goal is to facilitate quality improvement surveys aimed at reducing the risk of occupational infection of HCWs during the COVID-19 pandemic.


Assuntos
Infecções por Coronavirus/diagnóstico , Diagnóstico Precoce , Guias como Assunto , Pessoal de Saúde/estatística & dados numéricos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Equipamento de Proteção Individual/normas , Pneumonia Viral/diagnóstico , Melhoria de Qualidade/normas , Adulto , Betacoronavirus , COVID-19 , Feminino , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pandemias , Equipamento de Proteção Individual/estatística & dados numéricos , Melhoria de Qualidade/estatística & dados numéricos , Fatores de Risco , SARS-CoV-2 , Inquéritos e Questionários , Estados Unidos
6.
Exp Eye Res ; 88(1): 22-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18955050

RESUMO

Retinal stimulation with high spatial resolution requires close proximity of electrodes to target cells. This study examines the effects of material coatings and 3-dimensional geometries of subretinal prostheses on their integration with the retina. A trans-scleral implantation technique was developed to place microfabricated structures in the subretinal space of RCS rats. The effect of three coatings (silicon oxide, iridium oxide and parylene) and three geometries (flat, pillars and chambers) on the retinal integration was compared using passive implants. Retinal morphology was evaluated histologically 6 weeks after implantation. For 3-dimensional implants the retinal cell phenotype was also evaluated using Computational Molecular Phenotyping. Flat implants coated with parylene and iridium oxide were generally well tolerated in the subretinal space, inducing only a mild gliotic response. However, silicon-oxide coatings induced the formation of a significant fibrotic seal around the implants. Glial proliferation was observed at the base of the pillar electrode arrays and inside the chambers. The non-traumatic penetration of pillar tips into the retina provided uniform and stable proximity to the inner nuclear layer. Retinal cells migrated into chambers with apertures larger than 10 mum. Both pillars and chambers achieved better proximity to the inner retinal cells than flat implants. However, isolation of retinal cells inside the chamber arrays is likely to affect their long-term viability. Pillars demonstrated minimal alteration of the inner retinal architecture, and thus appear to be the most promising approach for maintaining close proximity between the retinal prosthetic electrodes and target neurons.


Assuntos
Materiais Revestidos Biocompatíveis , Próteses e Implantes , Retina/patologia , Degeneração Retiniana/terapia , Animais , Materiais Revestidos Biocompatíveis/efeitos adversos , Compostos de Epóxi , Fibrose/etiologia , Gliose/etiologia , Irídio/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Óxidos/farmacologia , Polímeros/farmacologia , Próteses e Implantes/efeitos adversos , Desenho de Prótese , Implantação de Prótese/métodos , Ratos , Retina/efeitos dos fármacos , Degeneração Retiniana/patologia , Vasos Retinianos/patologia , Compostos de Silício/farmacologia , Xilenos/farmacologia
7.
Science ; 167(3914): 65-7, 1970 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-5409480

RESUMO

The resting potential of a molluscan neuron can be separated experimentally into two components: one which depends on ionic gradients and permeabilities in accordance with the Goldman equation, and a second which depends on the electrogenicity of active sodium transport.


Assuntos
Transporte Biológico Ativo , Permeabilidade da Membrana Celular , Potenciais da Membrana , Neurônios , Animais , Modelos Neurológicos , Moluscos , Sódio/metabolismo
8.
Science ; 242(4880): 916-9, 1988 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-3187532

RESUMO

Increasing mortality in intravenous (IV) drug users not reported to surveillance as acquired immunodeficiency syndrome (AIDS) has occurred in New York City coincident with the AIDS epidemic. From 1981 to 1986, narcotics-related deaths increased on average 32% per year from 492 in 1981 to 1996 in 1986. This increase included deaths from AIDS increasing from 0 to 905 and deaths from other causes, many of which were infectious diseases, increasing from 492 to 1091. Investigations of these deaths suggest a causal association with human immunodeficiency virus (HIV) infection. These deaths may represent a spectrum of HIV-related disease that has not been identified through AIDS surveillance and has resulted in a large underestimation of the impact of AIDS on IV drug users and blacks and Hispanics.


Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/microbiologia , Causas de Morte , Endocardite/complicações , HIV , Soropositividade para HIV , Homossexualidade , Humanos , Masculino , Cidade de Nova Iorque , Pneumonia/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Tuberculose/complicações
9.
Doc Ophthalmol ; 118(1): 69-77, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19030905

RESUMO

This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV Standard for clinical electroretinography (ERG). The parameters for flash stimulation and background adaptation have been tightened, and responses renamed to indicate the flash strength (in cd x s x m(-2)). The ISCEV Standard specifies five responses: (1) Dark-adapted 0.01 ERG (rod response); (2) Dark-adapted 3.0 ERG (combined rod-cone response); (3) Dark-adapted 3.0 oscillatory potentials; (4) Light-adapted 3.0 ERG (cone response); (5) Light-adapted 3.0 flicker (30 Hz flicker). An additional Dark-adapted 10.0 ERG or Dark-adapted 30.0 ERG response is recommended.


Assuntos
Eletrorretinografia/instrumentação , Eletrorretinografia/normas , Adaptação Ocular , Adulto , Idoso , Idoso de 80 Anos ou mais , Calibragem , Criança , Pré-Escolar , Protocolos Clínicos/normas , Eletrodos , Humanos , Lactente , Estimulação Luminosa/métodos , Projetos de Pesquisa/normas , Estatística como Assunto/métodos , Terminologia como Assunto
10.
Prog Neurobiol ; 5(2): 167-95, 1975.
Artigo em Inglês | MEDLINE | ID: mdl-830083

RESUMO

The molluscan neuron, because of its large size and accessibility, has been an important model for studying the electrophysiology of nerve cells. This review catalogs data about specific molluscan neurons, but the greater importance of this material is in the broad picture of how a neuronal membrane maintains internal potential and is responsive to changes in the environment. Electrical properties of the membrane. The mechanisms which contribute to the resting potential in molluscan neurons can be separated into ionic and metabolic components. When the electrogenic sodium pump is eliminated experimentally, the ionic component of the potential follows the constant field equation quite closely. Many of the "constants" and "parameters" which characterize the membrane of molluscan neurons are actually variables which depend upon temperature, ionic environment, and membrane potential. The evaluation of the electrical parameters is complicated by extensive infoldings of the somatic membrane, and by large axons which drain current from the soma. Most molluscan neurons have a very high specific membrane resistance and a correspondingly low potassium permeability. Membrane capacitance is close to the 1 microF/cm2 value which characterizes biological membranes. The current-voltage relation of molluscan neurons may be complicated by inward-going rectification, but if that is inhibited the I-V curve follows the prediction of either the constant field equation or a simple electrical model. Factors which modify membrane behavior. The resting potential of molluscan neurons is very sensitive to changes in temperature and Ko, through a combination of effects upon the electrogenic sodium pump, inward-going rectification, and the membrane "parameters". Inward-going rectification depends upon a rectifying K conductance, and can be eliminated by cold or the removal of Ko. Strong or prolonged currents have time-dependent effects upon the membrane, and excessive polarization leads to a "high conductance state". The underlying (non-rectifying) K permeability of the membrane is relatively insensitive to temperature and ionic changes, whereas the Na permeability increases with warming. Membrane resistance varies with both temperature and ions (because the I-V curve is sensitive to these conditions) but membrane capacitance is relatively insensitive to external factors. Electrogenic sodium transport. Sodium transport is electrogenic in molluscan neurons. It can be stimulated by warm temperatures and an excess of substrate (e.g. high Nai); it can be inhibited by cold, by an absence of substrate (e.g. low Ko), or by pharmacologic agents such as cyanide or ouabain.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Moluscos/fisiologia , Neurônios/fisiologia , Animais , Eletrofisiologia/métodos , Potenciais da Membrana , Sódio/metabolismo
11.
Cancer Res ; 54(9): 2347-58, 1994 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-8162580

RESUMO

Endometrial carcinoma is associated with antecedent simple and complex hyperplasia, and the endometrium is a target tissue for the action of cytokines and growth factors. Transforming growth factor (TGF)-beta s are potent cellular growth and differentiation regulatory factors. Therefore, we investigated the potential role for TGF-beta s in the normal proliferative endometrium and its possible involvement in the transition to complex hyperplasia and progression to endometrial carcinoma. The angiogenic and mitogenic growth factor, basic fibroblast growth factor, was used for comparison. Differential TGF-beta isoform-specific immunoreactivity was observed in the normal endometrium, which is composed of glandular and stromal cells. There was an increase in TGF-beta 3 but not TGF-beta 1 or TGF-beta 2 in the glandular epithelium from the proliferative to the secretory phase of the menstrual cycle. Immunostaining for TGF-beta 2 was more intense in the stroma than the glands. In contrast, TGF-beta 1 and TGF-beta 3 were near equal intensity in these two endometrial compartments, TGF-beta 3 being the most intense. The glandular epithelium demonstrated a statistically significant stepwise increase in the expression of all three TGF-beta s progressing from the normal proliferative endometrium to simple hyperplasia and on to complex hyperplasia. However, the stromal cells maintained approximately the same level of immunoreactivity for TGF-beta in all these samples. In comparing proliferative endometrium with complex hyperplasia, there was a 5.1-, 3.4-, and 2.6-fold increase in immunostaining in the glands for TGF-beta 1, TGF-beta 2, and TGF-beta 3, respectively (P < or = 0.001). There was no further increase in immunoreactivity with progression from preneoplastic complex hyperplasia to carcinoma. Immunoreactive basic fibroblast growth factor was slight in normal endometrium and simple hyperplasia. There was a 4.6- and 4.2-fold increase in immunostaining observed in complex hyperplasia compared with proliferative endometrium in the glandular (P < or = 0.0054) and stromal (P < or = 0.0053) cells, respectively, with no further increase in carcinoma. By in situ hybridization, an increase in mRNA for all TGF-beta isoforms paralleled TGF-beta immunoreactivity. However, in contrast to the increased immunostaining in the glands in complex hyperplasia, there was remarkably more mRNA in the stromal cell compartment. The discordant expression of mRNA and protein was only observed in the pathological endometrium since both were more highly expressed in the stromal cells in normal proliferative endometrium.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Adenocarcinoma/química , Hiperplasia Endometrial , Neoplasias do Endométrio/química , Endométrio/química , Fator 2 de Crescimento de Fibroblastos/análise , Fator de Crescimento Transformador beta/análise , Feminino , Humanos , Pós-Menopausa , RNA Mensageiro/análise
12.
Eye (Lond) ; 30(2): 287-303, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26563659

RESUMO

The purpose of this study was to examine normal vision and eye disease in relation to art. Ophthalmology cannot explain art, but vision is a tool for artists and its normal and abnormal characteristics may influence what an artist can do. The retina codes for contrast, and the impact of this is evident throughout art history from Asian brush painting, to Renaissance chiaroscuro, to Op Art. Art exists, and can portray day or night, only because of the way retina adjusts to light. Color processing is complex, but artists have exploited it to create shimmer (Seurat, Op Art), or to disconnect color from form (fauvists, expressionists, Andy Warhol). It is hazardous to diagnose eye disease from an artist's work, because artists have license to create as they wish. El Greco was not astigmatic; Monet was not myopic; Turner did not have cataracts. But when eye disease is documented, the effects can be analyzed. Color-blind artists limit their palette to ambers and blues, and avoid greens. Dense brown cataracts destroy color distinctions, and Monet's late canvases (before surgery) showed strange and intense uses of color. Degas had failing vision for 40 years, and his pastels grew coarser and coarser. He may have continued working because his blurred vision smoothed over the rough work. This paper can barely touch upon the complexity of either vision or art. However, it demonstrates some ways in which understanding vision and eye disease give insight into art, and thereby an appreciation of both art and ophthalmology.


Assuntos
Oftalmopatias/fisiopatologia , Pinturas , Visão Ocular/fisiologia , Percepção de Cores/fisiologia , Sensibilidades de Contraste/fisiologia , Humanos , Retina/fisiologia
13.
AIDS ; 7(3): 409-14, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8471204

RESUMO

OBJECTIVE: To investigate the relationship between heterosexual behaviors associated with HIV infection and ethnicity, sex, and intravenous drug use. METHODS: Subjects were recruited from Bellevue Hospital Center, New York City between 1986 and 1989, and interviewed about sexual behaviors and intravenous drug use. Analyses were based on 1561 black, white, or Hispanic individuals who reported having sexual contact with a member of the opposite sex. RESULTS: Twenty-seven per cent of the study population were black, 43% Hispanic, and 31% white. Blacks were more likely than whites or Hispanics to have initiated sexual intercourse at an early age, and to have had a sexually transmitted disease. Sex with a female drug user was more common among white men, and contact with a prostitute more frequent among Hispanic men. Among the women, Hispanics had fewer sexual risk factors overall than whites or blacks. Use of barrier contraceptives was uniformly low across all ethnic groups. Intravenous drug use was significantly associated with sexual risk-taking. Women were more likely than men to have an intravenous drug-using (IVDU) sexual partner. CONCLUSIONS: The large prevalence of high-risk sexual practices observed in this study emphasizes the continuing need to target AIDS prevention programs at those at highest risk of heterosexually transmitted HIV: racial minorities, IVDU, and their sexual partners.


Assuntos
Infecções por HIV/transmissão , Comportamento Sexual , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adolescente , Adulto , Fatores Etários , Comorbidade , Etnicidade , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cidade de Nova Iorque , Fatores de Risco , Fatores Sexuais , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/epidemiologia , Abuso de Substâncias por Via Intravenosa/epidemiologia
14.
AIDS ; 5(4): 365-72, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1676279

RESUMO

To determine the relationships between individuals' baseline T-cell subsets, their rates of change with time, and AIDS-free survival time, data were collected at 6-monthly intervals from 379 HIV-seropositive homosexual Sydney men, of whom 31 developed AIDS during the 3-year observation period. Both CD4% and rate of change of CD4% in an individual had significant prognostic value in determining AIDS-free survival time. Compared with subjects whose CD4% remained stable, subjects whose CD4% dropped by 7% or more in a year had a relative hazard of 35.1 (95% confidence interval = 11.7-105.6, P less than 0.001) of developing AIDS. Increasing CD4% had a significant protective effect, reducing the risk of developing AIDS. CD4%, CD4 cell count and CD4: CD8 ratios showed steeper declines in subjects who were later diagnosed with AIDS than in those who remained AIDS-free. The rates of immunological change in AIDS-free seroconverters and seropositives were similar, despite indeterminate differences in durations of infections. In the multivariate Cox regression analysis, baseline CD4%, the rate of change of CD4%, and baseline lymphocyte count were associated with AIDS-free survival time. Baseline CD4% had greater prognostic value than baseline CD4 cell count. Baseline CD8%, baseline CD8 count, their rates of change and their mean square errors were not independently significant in this analysis. These findings are important for clinicians monitoring HIV infection in an individual and for entry criteria and monitoring procedures in clinical trials. They also have implications for resource-poor settings; prognosis based on CD4% can be made with a flow cytometer without a full blood count.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Síndrome da Imunodeficiência Adquirida/diagnóstico , Linfócitos T CD4-Positivos , Soropositividade para HIV/sangue , Linfócitos T Reguladores , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/mortalidade , Austrália/epidemiologia , Estudos de Coortes , Soropositividade para HIV/imunologia , Homossexualidade , Humanos , Contagem de Leucócitos , Masculino , Análise Multivariada , Estudos Prospectivos , Taxa de Sobrevida , Subpopulações de Linfócitos T
15.
AIDS ; 11(11): 1389-93, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9302450

RESUMO

OBJECTIVES: To investigate whether serum thiol levels are altered by HIV disease, and whether low serum thiols predict time to death among HIV-infected injecting drug users (IDU). DESIGN: A cross-sectional study of serum thiol levels among 13 HIV-seronegative IDU, 116 HIV-seropositive IDU, and 17 HIV-seropositive IDU with a history of AIDS, and a cohort study of the 133 HIV-infected IDU who took part in the cross-sectional study. METHODS: Subjects were recruited from a methadone-maintenance treatment program during 1990-1991. Total serum thiols were determined spectrophotometrically at enrolment; low serum thiols were defined as those with an absorbance at 412 nm < or = 0.46. Deaths through 31 December 1993 were determined from the National Death Index (NDI). Twenty-six HIV-seropositive subjects died during follow up; death certificates, which were obtained for 23 subjects, indicated AIDS or HIV infection for 20. Product-limit estimation was used to calculate survival. Multivariate analyses employed Cox proportional-hazards regression. RESULTS: Analysis of cross-sectional data showed that serum thiols did not differ significantly among HIV-free subjects, HIV-infected subjects, and HIV-infected subjects with a history of AIDS. Cohort analysis, adjusted for age, revealed that persons with those with high serum thiols (relative hazard = 2.83; 95% confidence interval (CI), 1.15, 6.97); a significant interaction between low serum thiols and a history of AIDS was associated with a relative hazard of 5.65 (95% CI, 1.22-2.61). CONCLUSIONS: Among HIV-infected persons, low serum thiols, especially in concert with a history of AIDS, predict mortality risk. These findings support the hypothesis that oxidative stress is critical to the pathogenesis of HIV infection.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/metabolismo , Compostos de Sulfidrila/análise , Compostos de Sulfidrila/metabolismo , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Infecções por HIV/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Estresse Oxidativo , Valor Preditivo dos Testes , Abuso de Substâncias por Via Intravenosa/epidemiologia , Abuso de Substâncias por Via Intravenosa/mortalidade , Abuso de Substâncias por Via Intravenosa/virologia , Compostos de Sulfidrila/sangue , Análise de Sobrevida
16.
AIDS ; 1(1): 39-44, 1987 May.
Artigo em Inglês | MEDLINE | ID: mdl-3122788

RESUMO

We report here the results of a survey of 308 intravenous drug abusers recruited from hospital-based methadone maintenance or drug detoxification programmes located in Manhattan, New York City. Complete interviews and serological analyses for antibodies to human immunodeficiency virus (HIV) using both enzyme-linked immunosorbent and Western blot assays were obtained from 290 (94%) of the subjects. HIV antibodies were found by both assays in 147 (50.7%) of the tested subjects; conflicting results were found in three (1%) of the subjects; and negative results on both tests were found in 140 (48.3%) of the subjects. Logistic regression analysis identified significant relative risks for HIV infection associated with the frequency of drug injection and the proportion of injections in 'shooting galleries'. Additional risk among men was associated with a history of homosexual relations. Traditional efforts taken by subjects to clean syringes between uses, such as washing with water or alcohol, showed no evidence of being protective. Programmes aimed at prevention of HIV infection should focus on reducing use of shooting galleries and sharing of needles and syringes as well as reducing intravenous drug abuse generally.


Assuntos
Soropositividade para HIV/transmissão , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Feminino , Humanos , Injeções Intravenosas , Masculino , Cidade de Nova Iorque , Fatores de Risco
17.
AIDS ; 1(2): 105-11, 1987 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2896511

RESUMO

A cohort of 334 intravenous (IV) drug users from New York City drug treatment programs were followed over a mean 9-month period. Among the 165 who were seropositive at enlistment, four developed clinical AIDS, for an annual rate of 3%. Elevated IgA was a significant predictor of developing AIDS. Among 72 subjects who were initially seronegative and who were re-interviewed, four were seropositive at follow-up, for a seroconversion rate of 7% per year among seronegatives. Among seropositive subjects who did not develop AIDS or fatal AIDS related complex (ARC), continued drug injection was associated with rate of T4 cell loss, and there was a non-significant trend for males to lose T4 cells more rapidly than females. While it was not possible to distinguish the mechanism underlying the relationship between continued drug injection and T4 cell loss, seropositive IV drug users should be warned that continued injection may lead to increased HIV-related immunosuppression as well as, if injection equipment is shared, risking viral transmission to others.


Assuntos
Síndrome da Imunodeficiência Adquirida/etiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/imunologia , Anticorpos Antivirais/biossíntese , Métodos Epidemiológicos , Feminino , HIV/imunologia , Anticorpos Anti-HIV , Humanos , Tolerância Imunológica , Injeções Intravenosas/efeitos adversos , Masculino , Cidade de Nova Iorque , Transtornos Relacionados ao Uso de Substâncias/imunologia , Linfócitos T/imunologia
18.
AIDS ; 12(7): 785-93, 1998 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-9619811

RESUMO

OBJECTIVE: To determine the willingness of populations at high risk of HIV-1 infection to participate in HIV vaccine efficacy trials, determine factors influencing decision-making, and evaluate knowledge levels of vaccine trial concepts. DESIGN: Cross-sectional study. METHODS: HIV-1-negative homosexual men, male and female injecting drug users and non-injecting women at heterosexual risk were recruited in eight cities in the United States (n=4892). RESULTS: A substantial proportion of the study population (77%) would definitely (27%) or probably (50%) be willing to participate in a randomized vaccine efficacy trial. Increased willingness was associated with high-risk behaviors, lower education level, being uninsured or covered by public insurance, and not having been in a previous vaccine preparedness study. Altruism and a desire for protection from the vaccine were major motivators for participation. Major concerns included positive HIV-1 antibody test due to vaccine, safety of the vaccine, and possible problems with insurance or foreign travel. Baseline knowledge of vaccine trial concepts was low. CONCLUSIONS: It is likely that high-risk volunteers will be willing to enroll in HIV vaccine efficacy trials. A variety of participant and community educational strategies are needed to address participant concerns, and to ensure understanding of key concepts prior to giving consent for participation.


Assuntos
Vacinas contra a AIDS , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Ensaios Clínicos como Assunto , Estudos Transversais , Feminino , Educação em Saúde , Humanos , Masculino , Fatores de Risco , Estados Unidos
19.
Artigo em Inglês | MEDLINE | ID: mdl-2656989

RESUMO

The literature is briefly summarized as to how several nutrients affect immune function, susceptibility to infection, and cancer susceptibility or progression. Nutritional deficiencies can impair immunity and so influence susceptibility to infectious agents, including ones that are common and relatively virulent in acquired immune deficiency syndrome (AIDS) patients. A variety of nutrients affect several of the immune functions that are defective in human immunodeficiency virus (HIV)-infected individuals. For example, beta-carotene increased the number of CD4+ cells; vitamin E decreased the number of CD8+ cells and increased the CD4+/CD8+ ratio; vitamin D decreased the CD4+/CD8+ ratio; and iron increased the number of peripheral lymphocytes in humans receiving supplementation. Furthermore, nutritional deficiencies can influence gastrointestinal function, while infectious diseases can influence nutrient requirements by altering the efficiency of absorption and the rate of tissue metabolism. Malnutrition, depressed serum zinc levels, and intestinal nutrient malabsorption have been found in AIDS patients. The above findings suggest that dietary manipulations might diminish the immune defects in HIV infection and enhance resistance to opportunistic infections. However, dietary alterations in immune defects are generally not well quantified and may be small relative to the magnitude of the defects observed in AIDS patients. Because conflicting or adverse effects have been reported for some nutrients, recommendations for dietary supplementation in HIV-infected individuals are premature and possibly hazardous. Further studies are much needed to relate dietary nutrient intakes to clinical outcomes.


Assuntos
Soropositividade para HIV/imunologia , Distúrbios Nutricionais/imunologia , Humanos , Enteropatias Parasitárias/imunologia , Masculino , Neoplasias/imunologia , Fenômenos Fisiológicos da Nutrição
20.
J Acquir Immune Defic Syndr (1988) ; 7(7): 700-4, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8207647

RESUMO

We employed a nested case-control study design to evaluate the efficacy of bleach-cleaning of needles and syringes among injecting drug users (IDUs) as a means of preventing human immunodeficiency virus (HIV) infection. Sixteen HIV-seroconverters who responded to bleach use questions and who reported injecting with shared or used equipment in the 6 months prior to their first positive visit were compared with 89 controls. Controls had remained HIV-seronegative at two or more visits, reported injecting with shared or used equipment, responded to bleach-cleaning questions, and were seen at recall visits +/- 6 months from the date of seroconversion of the index case. Risk factors associated with HIV seroconversion in univariate analyses were a history of sexual intercourse with an HIV-infected partner and the frequency of speedball (mixed heroin and cocaine) injections. After adjusting for confounders, we found no evidence that bleach use protected against HIV infection.


Assuntos
Desinfecção , Infecções por HIV/etiologia , Hipoclorito de Sódio , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Estudos de Casos e Controles , Cocaína , Estudos de Coortes , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Heroína , Humanos , Masculino , Agulhas , Cidade de Nova Iorque/epidemiologia , Razão de Chances , Análise de Regressão , Fatores de Risco , Parceiros Sexuais , Seringas
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