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1.
Osteoarthritis Cartilage ; 30(12): 1658-1669, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36108937

RESUMO

OBJECTIVE: Intra-articular corticosteroid injections (IACIs) provide temporary symptom relief in osteoarthritis (OA). This meta-analysis investigated the effects of recurrent IACIs at 3 months and beyond. DESIGN: We searched Medline, Embase and Cochrane from inception to January 2021 for randomised controlled trials (RCTs) of patients with OA who received recurrent IACIs compared with other injectables, placebo or no treatment (primary outcomes: pain, function). Mean differences (MDs) with 95% confidence intervals were reported. RESULTS: Ten RCTs were included (eight knee OA (n = 763), two trapeziometacarpal OA (n = 121)). Patients received between 2 and 8 injections, varying by trial. Trials compared recurrent IACIs with hyaluronic acid (HA), platelet-rich plasma (PRP), saline or orgotein (follow-up 3-24 months). Greater improvements in pain, function and QoL at 3-24 months were noted for the comparators than with IACIs, with comparators demonstrating an equal or superior effect, or the intervention effect attenuated during follow-up. Recurrent IACIs demonstrated no benefits in pain or function over placebo at 12-24 months. No serious adverse events were recorded. No studies reported on time-to-future interventions, risk of future prosthetic joint infection or other adverse events associated with subsequent joint replacement. CONCLUSIONS: Recurrent IACIs often provide inferior (or non-superior) symptom relief compared with other injectables (including placebo) at 3 months and beyond. Other injectables (HA, PRP) often yielded greater improvements in pain and function up to 24 months post-injection. Existing RCTs on recurrent IACIs lack sufficient follow-up data to assess disease progression and time-to-future interventions.


Assuntos
Osteoartrite do Joelho , Plasma Rico em Plaquetas , Humanos , Injeções Intra-Articulares , Osteoartrite do Joelho/terapia , Ácido Hialurônico , Corticosteroides/uso terapêutico , Dor/tratamento farmacológico , Resultado do Tratamento
2.
J Transl Med ; 18(1): 1, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900168

RESUMO

The present review aimed to discuss contemporary scientific literature involving differences between the tumor microenvironment (TME) in melanoma, lung cancer, and breast cancer in their primary site and TME in brain metastases (BM). TME plays a fundamental role in the behavior of cancer. In the process of carcinogenesis, cells such as fibroblasts, macrophages, endothelial cells, natural killer cells, and other cells can perpetuate and progress carcinogenesis via the secretion of molecules. Oxygen concentration, growth factors, and receptors in TME initiate angiogenesis and are examples of the importance of microenvironmental conditions in the performance of neoplastic cells. The most frequent malignant brain tumors are metastatic in origin and primarily originate from lung cancer, breast cancer, and melanoma. Metastatic cancer cells have to adhere to and penetrate the blood-brain barrier (BBB). After traversing BBB, these cells have to survive by producing various cytokines, chemokines, and mediators to modify their new TME. The microenvironment of these metastases is currently being studied owing to the discovery of new therapeutic targets. In these three types of tumors, treatment is more effective in the primary tumor than in BM due to several factors, including BBB. Understanding the differences in the characteristics of the microenvironment surrounding the primary tumor and their respective metastasis might help improve strategies to comprehend cancer.


Assuntos
Neoplasias Encefálicas , Microambiente Tumoral , Carcinogênese , Células Endoteliais , Humanos , Neovascularização Patológica
3.
Scand J Med Sci Sports ; 25(6): e655-63, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25441263

RESUMO

This study was a preliminarily investigation into the prevention of unintentional doping on the basis of self-determination theory (SDT). Specifically, we examined the relationship between athletes' motives for doping avoidance and their behavior when offered an unfamiliar food product. Participants were young Australian athletes (n = 410) that were offered a free lollipop prior to completing a questionnaire. It was noted whether participants refused to take or eat the lollipop and whether they read the ingredients of the lollipop. The questionnaire assessed autonomous and controlled forms of motivation, amotivation, doping intentions, and adherence regarding doping avoidance behaviors. The results showed that young athletes who adopted controlled reasons to avoid doping in sport (e.g., not getting caught) tended to report higher adherence to behaviors related to avoiding and monitoring banned substances, whereas those who adopted autonomous reasons (e.g., anti-doping being consistent with life goals) appeared to be more willing to read the ingredients of the provided food. The significant interaction effect between autonomous and controlled motivation indicated that autonomous motivation was more predictive to doping intention for athletes with low controlled motivation. It is concluded that SDT may help understand the motivational processes of the prevention of unintentional doping in sport.


Assuntos
Atletas/psicologia , Dopagem Esportivo/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Motivação , Autonomia Pessoal , Adolescente , Doces , Dopagem Esportivo/prevenção & controle , Comportamento Alimentar , Feminino , Rotulagem de Alimentos , Humanos , Intenção , Masculino , Teoria Psicológica , Inquéritos e Questionários , Adulto Jovem
4.
Environ Technol ; : 1-10, 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37441776

RESUMO

The present study evaluated the effect of the Fenton process as pretreatment for metronidazole (MNZ) removal coupled with a phytoremediation system using Scirpus lacustris as macrophyte. Initial concentrations of 0.5, 5, 10, 15, and 20 mg MNZ/L were studied in batch cultures. Results obtained in the MNZ removal by phytoremediation showed efficiencies of 93 ± 2%, 81 ± 4%, 85 ± 1%, 84 ± 2%, and 87 ± 6%, respectively. The metronidazole pretreated by the Fenton process and subsequently fed to the phytoremediation system increased the removal efficiencies up to 93 ± 3%, 99 ± 1%, 99 ± 4%, 94 ± 2%, and 94 ± 3%, respectively. Individual studies with Scirpus lacustris in touch with metronidazole displayed relative growth rates of 0.02-0.04 d-1, showing the not toxic effect of the antibiotic on the macrophyte growth. On the other hand, the BMG kinetic model best describes the removal of MNZ by phytoremediation. Finally, applying the Fenton process as a pretreatment makes the MNZ more assimilable for the phytoremediation system, converting the integration of Fenton with the phytoremediation like other attractive technology to be considered in removing emerging compounds.

5.
Nat Commun ; 14(1): 2146, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-37081049

RESUMO

Animal tolerance towards humans can be a key factor facilitating wildlife-human coexistence, yet traits predicting its direction and magnitude across tropical animals are poorly known. Using 10,249 observations for 842 bird species inhabiting open tropical ecosystems in Africa, South America, and Australia, we find that avian tolerance towards humans was lower (i.e., escape distance was longer) in rural rather than urban populations and in populations exposed to lower human disturbance (measured as human footprint index). In addition, larger species and species with larger clutches and enhanced flight ability are less tolerant to human approaches and escape distances increase when birds were approached during the wet season compared to the dry season and from longer starting distances. Identification of key factors affecting animal tolerance towards humans across large spatial and taxonomic scales may help us to better understand and predict the patterns of species distributions in the Anthropocene.


Assuntos
Animais Selvagens , Comportamento Animal , Aves , Ecossistema , Interação Humano-Animal , Animais , Humanos , Animais Selvagens/fisiologia , Animais Selvagens/psicologia , Austrália , Aves/fisiologia , População Urbana , África , América do Sul , População Rural , Clima Tropical
6.
Cell Rep ; 32(7): 108047, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32814050

RESUMO

Oligodendrogenesis occurs during early postnatal development, coincident with neurogenesis and synaptogenesis, raising the possibility that microglia-dependent pruning mechanisms that modulate neurons regulate myelin sheath formation. Here we show a population of ameboid microglia migrating from the ventricular zone into the corpus callosum during early postnatal development, termed "the fountain of microglia," phagocytosing viable oligodendrocyte progenitor cells (OPCs) before onset of myelination. Fractalkine receptor-deficient mice exhibit a reduction in microglial engulfment of viable OPCs, increased numbers of oligodendrocytes, and reduced myelin thickness but no change in axon number. These data provide evidence that microglia phagocytose OPCs as a homeostatic mechanism for proper myelination. A hallmark of hypomyelinating developmental disorders such as periventricular leukomalacia and of adult demyelinating diseases such as multiple sclerosis is increased numbers of oligodendrocytes but failure to myelinate, suggesting that microglial pruning of OPCs may be impaired in pathological states and hinder myelination.


Assuntos
Microglia/metabolismo , Bainha de Mielina/metabolismo , Células Precursoras de Oligodendrócitos/metabolismo , Animais , Diferenciação Celular , Masculino , Camundongos , Células-Tronco
7.
Tob Control ; 18(3): 218-21, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19264731

RESUMO

OBJECTIVE: To assess the influence of point-of-sale (POS) cigarette displays on unplanned purchases. METHODS: Intercept interviews were conducted with customers observed purchasing cigarettes from retail outlets featuring POS cigarette displays. Measures included intention to purchase cigarettes prior to entering the store, unprompted and prompted salience of POS tobacco displays, urge to buy cigarettes as a result of seeing the POS display, brand switching and support for a ban on POS cigarette displays. RESULTS: In total, 206 daily smokers aged 18-76 years (90 male, 116 female) were interviewed. Unplanned cigarette purchases were made by 22% of participants. POS displays influenced nearly four times as many unplanned purchases as planned purchases (47% vs 12%, p<0.01). Brand switching was reported among 5% of participants, half of whom were influenced by POS displays. Four times as many smokers were supportive of a ban on POS tobacco displays than unsupportive (49% vs 12%), and 28% agreed that such a ban would make it easier to quit. CONCLUSIONS: POS tobacco displays act as a form of advertising even in the absence of advertising materials. They stimulate unplanned cigarette purchases, play an important role in brand selection and tempt smokers trying to quit. This justifies removing POS tobacco displays from line of sight-something that very few smokers in our sample would object to.


Assuntos
Comércio/economia , Comportamento Impulsivo/economia , Fumar/economia , Adolescente , Adulto , Idoso , Sinais (Psicologia) , Feminino , Humanos , Comportamento Impulsivo/psicologia , Masculino , Pessoa de Meia-Idade , Fumar/psicologia , Responsabilidade Social , Adulto Jovem
8.
Int J STD AIDS ; 19(11): 780-1, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18931274

RESUMO

In hepatitis B virus (HBV) monoinfection, alanine aminotransferase (ALT) levels are linearly correlated with HBV DNA levels and lamivudine resistance. In human immunodeficiency virus (HIV)/HBV co-infection, little is known about the association between ALT, HBV DNA, and lamivudine resistance. We assessed HBV DNA, lamivudine resistance and ALT levels in 45 time points in 11 patients with HIV/HBV co-infection during lamivudine-containing antiretroviral therapy. High HBV DNA levels (>10(6) copies/mL) and lamivudine resistance developed in 45% and 91% of patients, respectively. However, ALT levels were not elevated in the setting of high HBV DNA levels (mean ALT, 48 IU/mL) or lamivudine resistance (mean ALT, 44 IU/mL). HBV viraemia and lamivudine resistance during extended lamivudine-containing antiretroviral therapy are common in HIV/HBV co-infection, occurring in the absence of significant ALT elevations. In HIV/HBV co-infection, measurement of HBV DNA and HBV resistance mutations may identify HBV virological failure before biochemical changes and should be routinely used in the management of HIV/HBV co-infection.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/sangue , Alanina Transaminase/sangue , DNA Viral/sangue , Infecções por HIV/sangue , Hepatite B/sangue , Adulto , Fármacos Anti-HIV/farmacologia , Terapia Antirretroviral de Alta Atividade , Auditoria Clínica , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Hepatite B/tratamento farmacológico , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Lamivudina/farmacologia , Masculino , Pessoa de Meia-Idade
9.
Scott Med J ; 53(4): 7-10, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19051656

RESUMO

OBJECTIVE: Young children may develop renal scarring following a urinary tract infection (UTI) especially after pyelonephritis which is difficult to diagnose. Permanent renal scars are diagnosed by dimercapto-succinic acid (DMSA) scan several months later. To decrease unnecessary exposure to radiation, we investigate the role of renal power Doppler (RPD) in predicting those who may not require a late DMSA scan. METHODS: Children under four years of age with a first UTI underwent an RPD study soon after diagnosis, and a DMSA scintigraphy six months later. The predictive values of the early RPD to detect DMSA renal scarring were calculated. RESULTS: Twenty three children (median age 30 months) were enrolled: 13 had a febrile presentation, two with bacteraemia. Permanent scarring occurred in three children (13%). In the 46 kidney units studied, initial RPD was abnormal in two and late DMSA abnormal in three units. Overall concordance between RPD and DMSA was 93.5%. The sensitivity of RPD for renal scar as per DMSA was 33.3%, specificity 97.7%; positive predictive value 50% and a negative predictive value of 95.4%. CONCLUSIONS: RPD offered no advantage over ultrasound to predict renal scarring and cannot be recommended to predict renal scarring following UTI.


Assuntos
Cicatriz/diagnóstico por imagem , Rim/diagnóstico por imagem , Ultrassonografia Doppler , Infecções Urinárias/complicações , Pré-Escolar , Cicatriz/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Cintilografia , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Ácido Dimercaptossuccínico Tecnécio Tc 99m
10.
J Perinatol ; 37(1): 42-48, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27711042

RESUMO

OBJECTIVE: To investigate the effects of fortification and storage on nutrients and properties of various human milk (HM) types. STUDY DESIGN: Mother's own milk (MOM) and pasteurized donor human milk (DHM; n=118) were analyzed pre- and post fortification with Enfamil and Similac human milk fortifier (EHMF and SHMF) before and after 24 h of refrigerated storage. RESULTS: Milk fortified with SHMF had significantly greater osmolality, pH and lipase activity than EHMF. Changes in protein, pH and osmolality following refrigerated storage differed between fortifiers. When milk type was factored into the analysis, protein and lipase activity changes in fresh MOM differed significantly from DHM and frozen MOM. Analysis of UNF HM found higher protein levels in preterm vs term samples and in MOM vs DHM. CONCLUSION: Nutrient composition of HM varies significantly by milk type. Although fortifiers enhance select nutrients, each has the potential to affect HM properties in a unique way and these affects may vary by milk type.


Assuntos
Alimentos Fortificados/análise , Recém-Nascido Prematuro/crescimento & desenvolvimento , Proteínas do Leite/análise , Leite Humano/química , Valor Nutritivo , Feminino , Armazenamento de Alimentos/métodos , Humanos , Concentração de Íons de Hidrogênio , Lactente , Recém-Nascido , Refrigeração
11.
J Leukoc Biol ; 40(1): 21-8, 1986 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3458862

RESUMO

Previous studies have demonstrated that one of the most salient features of tumor necrosis factor (TNF) is its ability to induce tumor necrosis in vivo, and the specificity of its cytotoxic/cytostatic activity for tumor cells has been demonstrated in in vitro studies in which this lymphokine has been shown to kill cultured cells of malignant lines and to have no effect on cells of normal diploid lines. Studies described herein defined the effect of highly purified human recombinant TNF on cells of 34 different human and murine hematopoietic cell lines, particularly human leukemic T and B cells of long-term lymphoblastoid cultures. Results of these studies demonstrated that TNF at concentrations of 3,600 U/ml had no significant effect on the growth of these cells as defined by cytotoxicity, measured with the use of the trypan blue dye-exclusion assay and as defined by cytostasis, assayed by the enumeration of cells and the uptake of [3H]-thymidine and -uridine. In contrast, positive control cultures of TNF-sensitive cells from a murine tumor (L-M/clone L-929, connective tissue) displayed at 50% (LD50) reduction in growth by TNF at approximately 5 U/ml. Likewise, human tumors (MCF-7, breast, and HT-29, colon) were also highly sensitive (LD50 less than 100 U/ml). These studies demonstrate that T and B cells of lymphoblastoid lines as well as cells of other hematopoietic lines display little or no sensitivity to TNF.


Assuntos
Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glicoproteínas/farmacologia , Proteínas Recombinantes/farmacologia , Animais , Linhagem Celular , Células-Tronco Hematopoéticas/citologia , Humanos , Camundongos , Fator de Necrose Tumoral alfa
12.
J Leukoc Biol ; 41(6): 481-91, 1987 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3474331

RESUMO

A computer-assisted approach has been designed to analyze and quantitate polymorphonuclear leukocyte (PMN) chemotaxis. This approach involves a rapid, objective, and semiautomated (user-directed) image-analysis system that is video- and microscope-based. The entire system consists of a microvideo set-up that is put on line with a Digital DEC-LSI-11/73 microcomputer, interfaced with a Datacube analog-digital/digital-analog converter. Video signals of PMN movement are digitized by the system at a resolution of 240 pixels vertically by 320 pixels horizontally (at 256 gray levels) and stored in a 76,800-byte frame buffer. The digitized data are stored for later use or utilized immediately for image segmentation, image display, movement, and morphometric computations for each PMN in a maximum phase field (at 645 X high dry) of 50 PMNs at 10-second intervals. The digitized data are used for computation of cell perimeter, surface area, optical density, contour-ratio, position, speed, and direction of locomotion with the utilization of micro-image-analysis programs written in FORTRAN and MACRO assembly language, with the computer operating under RT-11/TSX+. The reliability, objectivity, and reproducibility of measurements made with this quantitative approach have been tested by comparing with manual-tracing measurements of PMN movement. A correlation factor of 0.99 has been obtained. However, the quantitative-microscopic approach is much faster, more objective, less tedious, and much easier to operate than the conventional manual-tracing method.


Assuntos
Quimiotaxia de Leucócito , Processamento de Imagem Assistida por Computador , Neutrófilos/fisiologia , Humanos , Técnicas In Vitro , Neutrófilos/ultraestrutura , Software , Gravação de Videoteipe
13.
J Leukoc Biol ; 38(2): 203-11, 1985 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3861744

RESUMO

The orientation (chemotaxis) and locomotion (chemokinesis) of human polymorphonuclear leukocytes (PMNs) are generated by an internal movement mechanism that involves active cytoplasmic movement; they are influenced by external environmental and ionic conditions. We have studied the degree to which the orientation and movement mechanisms of PMNs are self-contained within the cell and the degree to which they are under membrane control. PMNs were partially and selectively demembranated by treatment with the non-ionic detergent, octyl-phenoxyl-polyethoxyethanol (commercially known as Triton X-100) under controlled conditions. The tritonated PMNs (referred to in the literature as models) were non-motile and non-locomotory. Addition of ATP/Mg++ with a trace amount of Ca++ to the medium was followed by reactivation of the tritonated PMN models to move again as motile cells. Although these reactivated PMN models actively locomoted, they could no longer orient to chemoattractants. Thus, the reactivation process restored the physical self-contained movement parameters but could not reestablish the orientation capacity (chemotactic responsiveness) that was characteristic of live PMNs. The demembranation process apparently destroyed the chemotactic receptors and/or eradicated the coordination function of the membrane. Videotapes of normal (control) as well as reactivated PMN movement were analyzed for movement characteristics. These characteristics were objectively analyzed with a newly designed computer-assisted micro-image-processing technique whereby the videotapes were digitized and quantified and the actual PMN movement printed out in computer-graphics and tracings (Freeman codes) for confirmation of orientation and movement arising as a result of reactivation.


Assuntos
Quimiotaxia de Leucócito , Neutrófilos/fisiologia , Trifosfato de Adenosina/farmacologia , Membrana Celular/fisiologia , Movimento Celular , Computadores , Humanos , Modelos Biológicos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Polietilenoglicóis
14.
J Sci Med Sport ; 18(3): 315-22, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24793786

RESUMO

OBJECTIVES: Motivation in sport has been frequently identified as a key factor of young athletes' intention of doping in sport, but there has not been any attempt in scrutinizing the motivational mechanism involved. The present study applied the trans-contextual model of motivation to explain the relationship between motivation in a sport context and motivation and the social-cognitive factors (attitude, subjective norm, perceived behavioral control, and intention) from the theory of planned behavior (TPB) in an anti-doping context. DESIGN: A cross-sectional survey was conducted. METHODS: Questionnaire data was collected from 410 elite and sub-elite young athletes in Australia (Mean age [17.7±3.9 yr], 55.4% male, Years in sport [9.1±3.2]). We measured the key model variables of study in relation to sport motivation (Behavioral Regulation in Sport Questionnaire), and the motivation (adapted version of the Treatment Self-Regulation Questionnaire) and social cognitive patterns (the theory of planned behavior questionnaire) of doping avoidance. The data was analyzed by variance-based structural equation modeling with bootstrapping of 999 replications. RESULTS: The goodness-of-fit of the hypothesized model was acceptable. The bootstrapped parameter estimates revealed that autonomous motivation and amotivation in sport were positively associated with the corresponding types of motivation for the avoidance of doping. Autonomous motivation, subjective norm, and perceived behavioral control in doping avoidance fully mediated the relationship between autonomous motivation in sport and intention for doping avoidance. CONCLUSIONS: The findings support the tenets of the trans-contextual model, and explain how motivation in sport is related to athletes' motivation and intention with respect to anti-doping behaviors.


Assuntos
Desempenho Atlético/psicologia , Dopagem Esportivo/psicologia , Motivação , Autonomia Pessoal , Esportes/psicologia , Adolescente , Atitude , Aprendizagem da Esquiva , Comportamento de Escolha , Estudos Transversais , Feminino , Humanos , Intenção , Masculino , Modelos Psicológicos , Adulto Jovem
15.
J Acquir Immune Defic Syndr (1988) ; 7(12): 1237-41, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7965634

RESUMO

Good markers for monitoring the efficacy of antiretroviral therapy in children do not currently exist. This study examined the effect of antiretroviral therapy on human immunodeficiency virus (HIV-1) unintegrated DNA (uDNA), integrated DNA (iDNA), percent uDNA, immune complex dissociated (ICD) p24 antigenemia, and plasma viral titer. Seven children were followed at therapy initiation and at approximately 3- and 10-month intervals. HIV-1 uDNA was detected in all children prior to start of therapy (average percent uDNA, 43%). At 3 months, the percent HIV uDNA decreased in all patients to an average of 18% (p = 0.01) and at 10 months decreased to an average of 1%. In contrast, the amount of HIV iDNA was relatively constant after initiation of therapy. ICD HIV p24 antigen was detected in all patients prior to therapy (average, 538 pg/ml). Over the study period, the ICD p24 antigen level decreased in three patients and remained relatively unchanged in four patients. Plasma cultures of HIV-1 were positive in only one of the seven patients prior to therapy. Among the methods evaluated, measurement of uDNA was the only parameter which reliable decreased after initiation of nucleoside therapy.


Assuntos
DNA Viral/sangue , Didanosina/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Zidovudina/uso terapêutico , Contagem de Linfócito CD4 , Pré-Escolar , Quimioterapia Combinada , Feminino , Proteína do Núcleo p24 do HIV/sangue , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/imunologia , Humanos , Lactente , Leucócitos Mononucleares/virologia , Masculino , Reação em Cadeia da Polimerase , Viremia/virologia , Zidovudina/farmacologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-1856789

RESUMO

The effect of treatment with 400-1,200 mg/day of zidovudine (ZDV) on HIV DNA concentrations in patient peripheral blood mononuclear cells (PBMCs) was studied in six patients during a 5- to 14-month period of therapy. HIV DNA was measured in PBMCs at intervals using a recently developed quantitative polymerase chain reaction assay. The amount of HIV DNA ranged from 2,000 to 40,000 copies of provirus per microgram of cellular DNA. The HIV provirus copy number showed little change with time in five patients, and increased and then remained constant in one patient. Thus, prolonged treatment with ZDV does not decrease the levels of HIV DNA in PBMCs.


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , DNA Viral/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Leucócitos Mononucleares/microbiologia , Provírus/genética , Zidovudina/uso terapêutico , Adulto , DNA Viral/análise , Esquema de Medicação , Feminino , HIV-1/genética , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Estudos Prospectivos , Provírus/efeitos dos fármacos , Zidovudina/administração & dosagem
17.
Artigo em Inglês | MEDLINE | ID: mdl-1310734

RESUMO

Better markers are needed to monitor the efficacy of antiretroviral drugs in persons infected with human immunodeficiency virus (HIV). We investigated the effects of zidovudine (ZDV) and dideoxycytidine (ddC) on the presence of unintegrated HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) from AIDS patients. DNA was extracted from PBMCs and separated into low molecular weight (unintegrated) and high molecular weight (integrated) chromosomal fractions. These DNA fractions were then amplified by a quantitative polymerase chain reaction (PCR) and the amount and percentage of unintegrated HIV DNA were determined. Very high levels of unintegrated HIV DNA were found in AIDS patients not receiving treatment with ZDV or ddC (median = 95% unintegrated HIV DNA). In contrast, most patients who had received 4 or more weeks of antiretroviral therapy had lower levels of unintegrated HIV DNA (median = 30% unintegrated HIV DNA for patients receiving ZDV). Paired samples taken from five patients before and after therapy showed a striking reduction in the percentage of unintegrated HIV DNA. The decrease in the proportion of unintegrated HIV DNA in AIDS patients was due to both a reduction in the copy number of unintegrated HIV DNA and an increase in the copy number of integrated HIV DNA. Thus, measurements of unintegrated and integrated HIV DNA may be useful in providing objective assessments of the effectiveness of antiretroviral therapies.


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , DNA Viral/sangue , HIV-1/genética , Zalcitabina/uso terapêutico , Zidovudina/uso terapêutico , Síndrome da Imunodeficiência Adquirida/microbiologia , DNA Viral/química , DNA Viral/genética , Resistência Microbiana a Medicamentos , HIV-1/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/microbiologia , Peso Molecular , Reação em Cadeia da Polimerase , Integração Viral , Zalcitabina/farmacologia , Zidovudina/farmacologia
18.
Int J Radiat Oncol Biol Phys ; 50(1): 133-8, 2001 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-11316556

RESUMO

PURPOSE: To evaluate the role of stereotactic radiosurgery in the treatment of angiographically occult vascular malformations (AOVMs). METHODS AND MATERIALS: From 1987 to 1996, 21 patients, 10 males and 11 females, median age of 41 years (range: 7-75 years), with an intracerebral AOVM underwent stereotactic radiosurgery at our institution. All were considered at high risk for surgical intervention. The vascular lesions were located in the brainstem (17 patients), basal ganglia (2), occipital lobe (1), and cerebellum (1). Diagnosis was based on high-resolution magnetic resonance imaging (MRI). Clinical presentation at onset included previous intracerebral hemorrhage (20 patients) and epilepsy (1). All patients were treated with a linac-based radiosurgical technique. The median dose delivered was 25 Gy (range 13-50 Gy), typically prescribed to the 80-90% isodose surface (range 50-90%), which corresponded to the periphery of the vascular malformation. Patients were followed by clinical neurologic assessment and by MRI on a regular interval basis. RESULTS: Follow-up was obtained in 20 patients; clinical or MRI information was not available for 1 patient, and this patient was excluded from our analysis. At a median follow-up of 77 months (range: 4-141 months), follow-up MRIs postradiosurgery do not demonstrate any changes in the appearance of the AOVM. Four patients developed an intracranial bleed at 4, 8, 35, and 57 months postradiosurgery. Annual hemorrhage rates were considerably higher in the observation period preradiosurgery than postradiosurgery (30% vs. 3.2%, p < 0.001). Complications postradiosurgery were observed in 4 patients. Three patients developed mild to moderate edema surrounding the radiosurgical target, expressed at 5, 8, and 24 months, respectively. In all cases, the edema was transient and resolved completely on subsequent MRIs. One of the 4 patients developed radiation necrosis 8 months after radiosurgery. CONCLUSION: The use of stereotactic radiosurgery in the treatment of AOVM continues to be controversial. Our results appear to show a reduction in the risk of symptomatic hemorrhage post treatment. Patients with previous history of hemorrhage or progressive neurologic deficit and small, well circumscribed lesions may benefit from a trial of stereotactic radiosurgery.


Assuntos
Malformações Arteriovenosas Intracranianas/cirurgia , Radiocirurgia/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversos , Resultado do Tratamento
19.
Transplantation ; 60(12): 1401-6, 1995 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-8545864

RESUMO

Black kidney transplant recipients have worse graft survival than white recipients. Speculation regarding etiology has focused on differences in human lymphocyte antigens (HLA). Some suggest that improvements in graft survival would be obtained if donor and recipient race were matched. We reviewed 236 cadaver transplants performed over 9 years at a single center using an HLA-match-driven allocation system and a uniform immunosuppressive protocol to determine the impact of donor race on graft survival. A multivariate analysis of graft survival using patient race, sex, age, transplant number, current and maximum plasma renin activity, donor race, cold ischemia time and HLA mismatch, the need for dialysis, and the presence of rejection as independent variables. Sixty percent of recipients were black, and 82% were primary transplants; 28 kidneys (12%) were from black donors. The 112 patients with the same race donor had identical 5-year graft survival as the 124 who had a different race donor (40%; P = 0.1726). The 5-year survival of the 88 white recipients of white donor organs was better than that of the 120 black recipients of white donor organs (54% vs. 42%, respectively; P = 0.0398). Black recipients (t1/2 = 37 months) did worse than white recipients (t1/2 = 60 months) regardless of organ source (P = 0.023). In the multivariate analysis, neither donor nor recipient race were an independent variable in predicting graft survival. Rejection (RR = 2.9) and the need for dialysis on the transplant admission (RR = 4.1) were the only factors that predicted poor survival. Black recipients had more rejection (P = 0.04) but not more need for dialysis posttransplant regardless of donor race. Donor race did not affect graft survival in this series. The effect of recipient race on graft survival was due to an increased incidence of rejection episodes in black recipients, which was independent of HLA mismatch. These data suggest that improvements in immunosuppression, not changes in allocation, are needed to improve graft survival.


Assuntos
Sobrevivência de Enxerto , Transplante de Rim , Adulto , Fatores Etários , População Negra , Seguimentos , Sobrevivência de Enxerto/genética , Sobrevivência de Enxerto/imunologia , Teste de Histocompatibilidade , Humanos , Análise de Regressão , Fatores de Risco , Fatores Sexuais , População Branca
20.
J Histochem Cytochem ; 33(6): 551-6, 1985 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3839005

RESUMO

A rapid, semiautomated cytophotometry system for quantitative histochemistry and cytochemistry was constructed. The system consists of a Fairchild charge coupled device (CCD) image camera, a Zeiss Universal microscope, a Datacube analog to digital converter, and a digital Equipment Corporation LSI 11/23 computer operating under RT-11. Computer programs were written in FORTRAN and the MACRO assembly language for the acquisition of data from the CCD device. These data were then used for image segmentation, image display, and calculation of total optical density, perimeter, cell area, and several shape features. The reproducibility of measurement made with the CCD-based cytophotometry system was tested by repeated measurements. The coefficient of variation was estimated to be 1.7% for total optical density and 0.9% for cell area. The CCD-based cytophotometry system was further evaluated by comparing results with measurements made on the same cells with a scanning stage cytophotometer using the HIDACSYS computer programs. Correlation coefficients of 0.96 for total optical density and 0.91 for cell area were obtained between the two systems. We conclude that the high-speed, dimensional stability, small size, and linearity of the CCD-based cytophotometry system will make it useful for quantitative histochemistry and cytochemistry.


Assuntos
Computadores , Citometria de Fluxo/instrumentação , Histocitoquímica/métodos , Macrófagos/análise , Software , Animais , Apresentação de Dados , Citometria de Fluxo/métodos , Histocitoquímica/instrumentação , Microcomputadores , Ratos , Ratos Endogâmicos
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