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2.
Actas urol. esp ; 47(3): 172-178, abr. 2023. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-218407

RESUMO

Introducción Las opciones de tratamiento quirúrgico del cáncer de próstata han experimentado cambios significativos gracias a la expansión de la robótica. Sin embargo, la prostatectomía radical retropúbica abierta (PRA) seguirá realizándose en aquellos entornos con limitaciones económicas o con escaso acceso a la robótica. El objetivo de este estudio fue determinar los resultados oncológicos a largo plazo, clasificar las tasas de complicaciones y examinar las tasas de recuperación temprana de la continencia en pacientes tratados con PRA. Métodos Identificamos a todos los pacientes sometidos a PRA en nuestra institución entre 2000 y 2020. Se utilizó un pad test (prueba de la compresa) estandarizado para determinar las tasas de continencia precoz tras la retirada del catéter; la continencia tardía, alrededor de un año después de la cirugía, se determinó mediante el número de compresas por día. Se utilizó la clasificación de Clavien-Dindo para informar las tasas de complicaciones. Las tasas de supervivencia libre de recidiva bioquímica (RB) y de supervivencia global (SG) se definieron mediante el método de Kaplan-Meier y el análisis log-rank. Se utilizaron modelos multivariantes de regresión de Cox para comprobar el efecto de los distintos factores sobre la recidiva bioquímica. Resultados Se analizaron los datos de 1.095 pacientes. La mediana de seguimiento fue de 93,4 meses. Se encontró una supervivencia global libre de RB a 10años y una SG del 73% y del 82%, respectivamente. Se observó una tasa de complicaciones de Clavien Dindo ≥3 en el 4,8% de los pacientes. La tasa de continencia precoz fue del 81,4% y la tasa de continencia tardía fue del 89,1%. El nivel de PSA preoperatorio, la suma de la puntuación de Gleason, el estadio pT, el estado de los ganglios linfáticos y el estado de los márgenes quirúrgicos fueron predictores independientes de RB (p<0,001). Entre las limitaciones del estudio están su diseño retrospectivo y unicéntrico (AU)


Introduction The surgical treatment options for prostate cancer have changed rapidly, given the expansion of robotics. However, open retropubic radical prostatectomy (ORP) will continue to be performed in areas with financial limitations or with limited access to robotics. The purpose of this study was to determine the long-term oncological outcomes, to categorize complication rates and to examine the early continence rates in patients treated with ORP. Methods We identified all patients who underwent ORP at our institution between 2000 and 2020. A standardized pad test was used to determine the early continence rates upon catheter removal, the late continence around a year after surgery was determined by the number of pads per day. The Clavien-Dindo classification was used to report the complication rates. The biochemical recurrence (BCR)-free survival and overall survival (OS) rates were defined using the Kaplan-Meier method and log-rank analysis. Multivariable Cox-regression models were used to test the effect of different factors on biochemical recurrence. Results We analyzed 1095 patients. The median follow-up was 93.4months. An overall 10-year BCR-free survival and OS of 73% and 82% respectively was found. A complication rate for Clavien Dindo ≥3 was seen in 4.8% of patients. The early continence rate was 81.4% and the late continence 89.1%. Preoperative PSA level, Gleason score sum, pT stage, lymph node status, and surgical margin status were independent predictors of BCR (P<.001). Limitations include retrospective and single centre study design. Conclusions ORP is a surgical procedure that provides excellent oncological- and early continence-rates (AU)


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Recidiva Local de Neoplasia , Resultado do Tratamento , Análise de Sobrevida , Seguimentos , Estadiamento de Neoplasias
3.
Actas Urol Esp (Engl Ed) ; 47(3): 172-178, 2023 04.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36372360

RESUMO

INTRODUCTION: The surgical treatment options for prostate cancer have changed rapidly, given the expansion of robotics. However, open retropubic radical prostatectomy (ORP) will continue to be performed in areas with financial limitations or with limited access to robotics. The purpose of this study was to determine the long-term oncological outcomes, to categorize complication rates and to examine the early continence rates in patients treated with ORP. METHODS: We identified all patients who underwent ORP at our institution between 2000 and 2020. A standardized pad test was used to determine the early continence rates upon catheter removal, the late continence around a year after surgery was determined by the number of pads per day. The Clavien-Dindo classification was used to report the complication rates. The biochemical recurrence (BCR)-free survival and overall survival (OS) rates were defined using the Kaplan-Meier method and log-rank analysis. Multivariable Cox-regression models were used to test the effect of different factors on biochemical recurrence. RESULTS: We analyzed 1095 patients. The median follow-up was 93.4 months. An overall 10-year BCR-free survival and OS of 73% and 82% respectively was found. A complication rate for Clavien Dindo≥3 was seen in 4.8% of patients. The early continence rate was 81.4% and the late continence 89,1%. Preoperative PSA level, Gleason score sum, pT stage, lymph node status, and surgical margin status were independent predictors of BCR (p<0.001, 95% CI). Limitations include retrospective and single center study design. CONCLUSIONS: ORP is a surgical procedure that provides excellent oncological- and early continence-rates.


Assuntos
Neoplasias da Próstata , Robótica , Masculino , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Neoplasias da Próstata/patologia , Prostatectomia/métodos
5.
Aerosol Sci Technol ; 56(1): 63-74, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-35602286

RESUMO

A sampling system for measuring emissions of nonvolatile particulate matter (nvPM) from aircraft gas turbine engines has been developed to replace the use of smoke number and is used for international regulatory purposes. This sampling system can be up to 35 m in length. The sampling system length in addition to the volatile particle remover (VPR) and other sampling system components lead to substantial particle losses, which are a function of the particle size distribution, ranging from 50 to 90% for particle number concentrations and 10-50% for particle mass concentrations. The particle size distribution is dependent on engine technology, operating point, and fuel composition. Any nvPM emissions measurement bias caused by the sampling system will lead to unrepresentative emissions measurements which limit the method as a universal metric. Hence, a method to estimate size dependent sampling system losses using the system parameters and the measured mass and number concentrations was also developed (SAE 2017; SAE 2019). An assessment of the particle losses in two principal components used in ARP6481 (SAE 2019) was conducted during the VAriable Response In Aircraft nvPM Testing (VARIAnT) 2 campaign. Measurements were made on the 25-meter sample line portion of the system using multiple, well characterized particle sizing instruments to obtain the penetration efficiencies. An agreement of ± 15% was obtained between the measured and the ARP6481 method penetrations for the 25-meter sample line portion of the system. Measurements of VPR penetration efficiency were also made to verify its performance for aviation nvPM number. The research also demonstrated the difficulty of making system loss measurements and substantiates the E-31 decision to predict rather than measure system losses.

6.
Rev Gastroenterol Mex (Engl Ed) ; 86(1): 13-20, 2021.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32173132

RESUMO

INTRODUCTION AND AIMS: Neoadjuvant therapy in rectal cancer is associated with a decrease in tumor size and is the therapeutic indication for patients with T3 or T4 tumors or lymph node involvement. Our aim was to describe the frequency of pathologic response and the survival rate in patients that underwent neoadjuvant therapy for rectal cancer. MATERIALS AND METHODS: A retrospective follow-up study with a survival analysis was conducted. Patients with locally advanced rectal cancer that received neoadjuvant treatment and were operated on at the Instituto de Cancerología Las Américas (Medellín, Colombia) were analyzed. Survival was calculated using the Kaplan-Meier method. RESULTS: A total of 152 patients were included. Mean patient age was 59 years (12.8 SD), 53.9% were men, and 58.6% of the patients were diagnosed with stage IIIB disease. The pathologic complete response (pCR) was achieved in 17% of the patients. A total of 146 (96.1%) patients received the chemoradiotherapy protocol. Fifty-two (34.2%) patients developed metastasis and/or relapse, and one (3.8%) of those patients had presented with pCR. The median follow-up period was 33 months (Q1-Q3: 20-45), with an overall survival rate of 79.5% (95% CI 70.9-85.8). The 5-year survival rate for the patients that had pCR was 80% (95% CI 20.3-96.9). CONCLUSIONS: The frequency of pCR was similar to that in other published studies and disease recurrence was lower, compared with patients with no response. The 5-year survival rate in patients with pCR was high, albeit lower than that reported in other studies.

7.
Neth J Med ; 78(6): 385-388, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33380537

RESUMO

We describe a patient with an orthohantavirus infection in the north of the Netherlands. Orthohantavirus cases in the Netherlands are rare and most cases occur in the east of the Netherlands. Orthohantavirus infections should be included in the differential diagnosis in travellers and non-travellers, and patients from areas other than the east of the Netherlands if flu-like symptoms and acute renal insufficiency are present.


Assuntos
Insuficiência Renal , Humanos , Países Baixos/epidemiologia , Insuficiência Renal/etiologia
8.
Pharmazie ; 74(11): 648-657, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31739830

RESUMO

Two series of 2-imino-coumarin based hybrids: 3-(benzoxazol-2-yl)-2H-chromen-2-imines 3-9 (series A-I) and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 10-16 (series A-II), as well as their coumarin analogues: 3-(benzoxazol-2-yl)-2H-chromen-2-ones 17-21 (series B-I) and 3-(benzothiazol-2-yl)-2H-chromen-2-ones 22-28 (series B-II) were prepared as potential antitumor agents. The in vitro cytotoxic potency of the synthesized compounds was evaluated against five human cancer cell lines: DAN-G, A-427, LCLC-103H, RT-4 and SISO, and relationships between structure and anticancer activity are discussed. Among the compounds tested, 3-(benzo[d] oxazol-2-yl)-N,N-diethyl-2-imino-2H-chromen-7-amine (6, series A-I) and 3-(benzo[d]thiazol-2-yl)-6-fluoro-2H-chromen-2-one (26, series B-II) exhibited the most potent cytotoxic activity with IC50 values ranging from <0.01 µM to 1.1 µM. In particular, compound 6 demonstrated remarkable cytotoxicity against the A-427 ovarian cancer, the lung cancer LCLC-103H, urinary bladder cancer RT-4 and cervical cancer SISO cell lines with IC50 <0.01-0.30µM, inducing apoptosis in two representative cell lines.


Assuntos
Antineoplásicos/farmacologia , Benzotiazóis/farmacologia , Benzoxazóis/farmacologia , Cumarínicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Benzotiazóis/síntese química , Benzotiazóis/química , Benzoxazóis/síntese química , Benzoxazóis/química , Linhagem Celular Tumoral , Cumarínicos/síntese química , Cumarínicos/química , Humanos , Concentração Inibidora 50 , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Relação Estrutura-Atividade
9.
Rev Gastroenterol Mex (Engl Ed) ; 84(2): 174-184, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29884570

RESUMO

INTRODUCTION AND AIMS: In Colombia, cancer of the colon is the third most frequent cancer in relation to incidence and mortality. Five-year survival depends on stage at diagnosis, albeit that rate is not known for the country. The aim of the present study was to characterize the overall survival and disease-free survival rates in an adult population with colorectal cancer treated at an oncology center in Medellín, Colombia. MATERIALS AND METHODS: A retrospective cohort study was conducted. The case records of patients with a histologic diagnosis of colorectal cancer, seen within the time frame of 2011 and 2015, were reviewed. The overall survival and disease-free survival curves were calculated using the Kaplan-Meier method. RESULTS: A total of 824 (54.9%) patients with cancer of the colon and 676 (45.1%) with cancer of the rectum were treated. Mean patient age was 63.3 years, female sex predominated (56.3%), and 98.1% of the tumors were adenocarcinomas. The majority of the lesions were stage iii (31.9% in the colon and 35.5% in the rectum) at the time of diagnosis. Surgery was the most frequent treatment in the colon (85.2%) and radiotherapy was the most frequent in the rectum (75.4%). Overall survival at the median follow-up (27.3 months) was 66.7% for cancer of the colon and 63.9% for cancer of the rectum. Disease-free survival at the median follow-up (18.6 months in colon and 14.9 in rectum) was 72.5 and 68.9%, respectively. CONCLUSIONS: The clinical characteristics and treatment of patients were similar to those found in other studies. Two-year survival was higher than in other Colombian reports and 5-year survival was lower than that observed in developed countries.


Assuntos
Neoplasias Colorretais/mortalidade , Serviço Hospitalar de Oncologia , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Colômbia/epidemiologia , Neoplasias Colorretais/terapia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Análise de Sobrevida , Adulto Jovem
10.
J Appl Physiol (1985) ; 124(1): 118-130, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28860177

RESUMO

Estrogen deficiency and aging are associated with osteoporosis, impaired bone healing, and lower cognitive performance. Close functional and physical connections occur between bone and the central nervous system. An anti-inflammatory drug, zileuton (which is an inhibitor of arachidonate 5-lipoxygenase), is known to have a positive effect on bone tissue repair and brain ischemia. We studied the effect of zileuton on osteopenic bone and its healing and on the genes considered to be crucial for the cross talks between bone and brain. Three-month-old Sprague-Dawley rats were ovariectomized or left untreated. After 8 wk, bilateral metaphyseal tibia osteotomy with plate osteosynthesis was performed in all rats. Ovariectomized rats were fed with food containing zileuton (1, 10, or 100 mg/kg body wt) for 5 wk. In tibiae, bone volume, callus and cortical volume, and gene expression of osteocalcin and alkaline phosphatase were enhanced by zileuton (10 or 100 mg); biomechanical properties and bone density were not changed. In femur, zileuton enlarged cortical volume distal and trabecular volume proximal, decreasing their density. The expression level of brain Sema3a, known to regulate bone mass positively, was downregulated after ovariectomy. In contrast, bone Sema4d, a negative regulator of bone mass, was upregulated in the tibia callus after ovariectomy, whereas zileuton treatment (10 or 100 mg) resulted in reverse effects. Here, we describe for the first time the expression of Rbbp4 mRNA and its increase in tibia after ovariectomy. Zileuton caused downregulation of Rbbp4 in the hippocampus and had an effect on bone healing, changed the expression of genes involved in cross talk between bones and brain, and may be a potent drug for further examination in estrogen deficiency-related dysfunction(s). NEW & NOTEWORTHY Zileuton, a 5-lipoxygenase inhibitor, increased bone volume, callus and cortical volume in osteotomized tibia, and trabecular and cortical volume in femur. Although the expression of Sema3a (positively regulating bone mass) in brain was downregulated and Sema4d (negatively regulating bone mass) was upregulated in tibia callus after ovariectomy, zileuton could counteract these effects. Rbbp4 (involved in age-related memory loss) was increased in tibia callus after ovariectomy.


Assuntos
Encéfalo/efeitos dos fármacos , Hidroxiureia/análogos & derivados , Inibidores de Lipoxigenase/uso terapêutico , Osteoporose/tratamento farmacológico , Tíbia/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Avaliação Pré-Clínica de Medicamentos , Feminino , Hidroxiureia/farmacologia , Hidroxiureia/uso terapêutico , Inibidores de Lipoxigenase/farmacologia , Ovariectomia , Ratos Sprague-Dawley , Tíbia/metabolismo , Microtomografia por Raio-X
11.
Hautarzt ; 68(3): 217-223, 2017 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-27981385

RESUMO

BACKGROUND: Psoriasis is known today as a T­cell-mediated autoimmunological systemic disease. The chronic inflammatory processes involve neuroimmunological factors that are held responsible not only for various aspects of psychiatric-neurological comorbidities but also for neurosensory problems, primarily itching. Amongst other things, the significance of GABAA receptors are often discussed in this context. The topical use of chloral hydrate in semisolid preparations for antipruritic therapy goes back to Neisser and is currently experiencing a revival in individually manufactured formulations. However, it is currently unknown whether the unwanted side effects that are described for systemic use of chloral hydrate are also relevant for topical application. OBJECTIVES: For lack of clinical safety data, preclinical tests for cutaneous cytotoxicity and calculations for systemic bioavailability after topical application have been performed. CONCLUSION: The present data cannot fully remove safety concerns for topical application of chloral hydrate in the formulation favoured by the NRF (Neues Rezepturformularium)-the so-called 1­2-3-cream. A twice daily use of the 1­2-3-cream on a maximum of 10% of the body surface can be regarded as safe. For a better assessment of harmlessness, tests for cutaneous bioavailability (concentration-time profile) on human skin and clinical studies would be necessary.


Assuntos
Hidrato de Cloral/administração & dosagem , Toxidermias/diagnóstico , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Modelos Biológicos , Prurido/tratamento farmacológico , Psoríase/tratamento farmacológico , Administração Cutânea , Administração Tópica , Linhagem Celular , Hidrato de Cloral/efeitos adversos , Simulação por Computador , Relação Dose-Resposta a Droga , Toxidermias/etiologia , Toxidermias/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Queratinócitos/patologia , Taxa de Depuração Metabólica , Prurido/metabolismo , Prurido/patologia , Psoríase/metabolismo , Psoríase/patologia
12.
J Dairy Sci ; 99(4): 3183-3192, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26830734

RESUMO

The objective of this study was to describe and compare husbandry practices on organic and conventional dairy farms of similar sizes in Minnesota. Organic (ORG, n=35), same-sized conventional (SC, n=15, <200 cows) and medium-sized conventional (MC, n=13, ≥200 cows) dairy herds were visited in 2012, and farmers were interviewed once about their farm, herd demographics, and herd management practices concerning nutrition, housing, and reproductive programs. Organic farms had been established as long as conventional farms, and ORG producers had most commonly selected ORG farming because of a negative perception of pesticides for human health. The distribution of cattle breeds and ages differed across farm types. Organic farms had more crossbred cows and a greater number of older cows than conventional farms, who had mainly Holstein cattle. Organic farms did not dock tails, were more likely to use breeding bulls, and were less likely to conduct pregnancy diagnoses in cattle. All conventional farmers fed corn, corn silage, and hay, but no forage or feed supplement was fed by all ORG farms with the exception of pasture. Kelp was supplemented on most ORG farms but on none of the conventional farms. In summary, although there were differences across farm types regarding the use of pasture, feeds, and feed additives, breed and age distribution, reproductive management, and the use of tail docking, observations in other management areas showed large overlap across herd types.


Assuntos
Bovinos , Indústria de Laticínios/métodos , Agricultura Orgânica , Animais , Cruzamento , Doenças dos Bovinos , Dieta/veterinária , Feminino , Abrigo para Animais , Masculino , Minnesota , Gravidez , Reprodução , Silagem , Zea mays
13.
Hautarzt ; 67(2): 107-11, 2016 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-26636143

RESUMO

Epithelial senescence is a complex process depending on intrinsic as well as extrinsic factors (e.g., UV or IR light, tobacco smoke) and must be seen in the context of the aging process especially of the corium and the subcutis. Morphological alterations become apparent in the form of epithelial atrophy, structural changes within the basal membrane, and a decrease in cell count of melanocytes and Langerhans cells. Signs of cellular senescence are reduced proliferation of keratinocytes, cumulation of dysplastic keratinocytes, various mutations (e.g., c-Fos/c-Jun, STAT3, FoxO1), as well as multiple lipid or amino acid metabolic aberrations (e.g., production of advanced glycation endproducts). This causes functional changes within the physical (lipid deficiency, water distribution dysfunction, lack of hygroscopic substances), chemical (pH conditions, oxygen radicals), and immunological barrier. Prophylactically, barrier-protective care products, antioxidant substances (e.g., vitamin C, B3, E, polyphenols, flavonoids), sunscreen products/measurements, and retinoids are used. For correcting alterations in aged epidermis, chemical peelings (fruit acids, ß-hydroxy acid, trichloroacetic acid, phenolic compounds), non-ablative (IPL, PDL, Nd:YAG) as well as ablative (CO2, Erbium-YAG) light-assisted methods are used.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Epiderme/efeitos dos fármacos , Epiderme/fisiologia , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/fisiologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Envelhecimento/fisiologia , Epiderme/patologia , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Absorção Cutânea/efeitos dos fármacos , Absorção Cutânea/fisiologia , Envelhecimento da Pele/patologia
14.
J Dairy Sci ; 98(5): 3143-51, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25726119

RESUMO

The objective of this study was to describe the prevalence and practices used to manage internal helminth parasites and external arthropod parasites on organic and conventional dairy herds in Minnesota. All organic (ORG) dairy herds in Minnesota (n=114) and a convenience sample of conventional herds were invited to participate in the study. Thirty-five ORG herds and 28 conventional herds were visited once in summer and fall of 2012. Conventional dairy herds were split into small conventional (SC,<200 cows) and medium-sized conventional herds (MC, ≥200 cows) so that SC herds were comparable in size to the ORG herds. Dairy managers were surveyed to assess their farm management practices and perceptions about parasites, hygiene scores were recorded for adult stock, and fecal samples were collected from a nominal 20 breeding-age heifers to characterize abundance of internal parasites. Nonparametric tests were used to compare fecal egg counts per gram (FEC) among farms grouped by management systems and practices. Organic farms had more designated pasture and were more likely to use rotational grazing compared with conventional farms, but the stocking densities of animals on pasture were similar among farm types. The overall FEC were very low, and only a few individual ORG heifers had FEC >500 eggs/gram. Samples from heifers on ORG farms had significantly more strongyle-type eggs than those on SC and MC farms (ORG: 6.6±2.1; SC: 0.5±0.3; MC: 0.8±0.7), but egg counts of other types of gastrointestinal parasites did not differ significantly among the 3 herd groups. Fly control measures were applied mainly to milking cows and preweaned calves and were used on 88.6% of ORG herds, 60.0% of SC herds, and 91.7% of MC herds. Approximately half of the producers reported having seen skin conditions suggestive of lice or tail mange in their cattle during the previous winter (ORG: 48.6%, SC: 57.1%, MC: 53.9%). Although most conventional producers reported treating these skin conditions, most organic producers stated they had not treated them. In conclusion, gastrointestinal parasite egg counts were low overall at the time of the survey, and most surveyed producers did not perceive gastrointestinal parasites to be a problem for their animals' health. Independent of the herd type, fly control was mostly targeted at the lactating herd and preweaned calves.


Assuntos
Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/parasitologia , Indústria de Laticínios/métodos , Agricultura Orgânica/métodos , Animais , Artrópodes , Bovinos , Doenças dos Bovinos/epidemiologia , Ectoparasitoses/epidemiologia , Ectoparasitoses/prevenção & controle , Ectoparasitoses/veterinária , Fezes/parasitologia , Feminino , Trato Gastrointestinal/parasitologia , Helmintos , Abrigo para Animais , Lactação , Leite , Minnesota , Contagem de Ovos de Parasitas/veterinária , Dermatopatias/parasitologia , Dermatopatias/veterinária
15.
Blood Cancer J ; 3(1): e99, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23359317

RESUMO

Epigenetic silencing of the tumor suppressor gene p15Ink4b (CDKN2B) is a frequent event in blood disorders like acute myeloid leukemia and myelodysplastic syndromes. The molecular function of p15Ink4b in hematopoietic differentiation still remains to be elucidated. Our previous study demonstrated that loss of p15Ink4b in mice results in skewing of the differentiation pattern of the common myeloid progenitor towards the myeloid lineage. Here, we investigated a function of p15Ink4b tumor suppressor gene in driving erythroid lineage commitment in hematopoietic progenitors. It was found that p15Ink4b is expressed more highly in committed megakaryocyte-erythroid progenitors than granulocyte-macrophage progenitors. More importantly, mice lacking p15Ink4b have lower numbers of primitive red cell progenitors and a severely impaired response to 5-fluorouracil- and phenylhydrazine-induced hematopoietic stress. Introduction of p15Ink4b into multipotential progenitors produced changes at the molecular level, including activation of mitogen-activated protein kinase\extracellular signal-regulated kinase (MEK/ERK) signaling, increase GATA-1, erythropoietin receptor (EpoR) and decrease Pu1, GATA-2 expression. These changes rendered cells more permissive to erythroid commitment and less permissive to myeloid commitment, as demonstrated by an increase in early burst-forming unit-erythroid formation with concomitant decrease in myeloid colonies. Our results indicate that p15Ink4b functions in hematopoiesis, by maintaining proper lineage commitment of progenitors and assisting in rapid red blood cells replenishment following stress.

16.
J Eur Acad Dermatol Venereol ; 24(10): 1176-82, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20236198

RESUMO

BACKGROUND: Reports on controlled trials on the efficacy and tolerability of sulfonated shale oils in atopic eczema are not available so far. The aim of this study was to investigate whether topically applied, specially prepared pale sulfonated shale oil (PSSO) cream is capable of improving symptoms/signs of mild to moderate atopic eczema in children more efficaciously than a corresponding vehicle cream. PATIENTS AND METHODS: A total of 99 children suffering from mild to moderate atopic eczema were enrolled in this multicentre, randomized, vehicle-controlled study. Verum or vehicle cream was applied to the affected skin area three times a day over 4 weeks. As the primary outcome parameter served the reduction of the total score after 4 weeks of treatment, compared with the initial examination. Secondary outcome parameters were addressed as well. Tolerability was judged by investigators and patients/parents, and adverse events were documented. RESULTS: After 4 weeks of treatment, the total score declined from 13.4 ± 3.7 to 4.5 ± 7.4 score points in the verum group and from 13.0 ± 3.1 to 11.7 ± 8.6 score points in the vehicle group (P < 0.0001). The superiority of verum regarding total score was already apparent after a treatment period of 1 week (reduction by 5.6 ± 4.3 vs. 1.3 ± 5.9 score points; P < 0.0001). Tolerability was found superior at the end of the treatment in the verum when compared with the control group--both by investigators (P < 0.0001) and patients/parents (P = 0.0051). CONCLUSION: Pale sulfonated shale oil cream 4% is capable to treat mild to moderate atopic eczema in children more efficaciously than vehicle and is well tolerated. PSSO thus represents a valuable addition to our therapeutic armamentarium. PSSO should be considered in particular when valid alternatives for topical glucocorticoids are sought for.


Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Emolientes/uso terapêutico , Compostos de Amônio Quaternário/uso terapêutico , Administração Tópica , Criança , Pré-Escolar , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Emolientes/administração & dosagem , Emolientes/efeitos adversos , Feminino , Humanos , Lactente , Masculino , Compostos de Amônio Quaternário/administração & dosagem , Compostos de Amônio Quaternário/efeitos adversos , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Rev Chilena Infectol ; 27(1): 65-74, 2010 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-20140318

RESUMO

Depression is one of the main psychiatric co-morbidities in HIV infection, presenting with a significantly higher prevalence than in the general population (around 35%). Its presence has been associated with poor quality of life, HIV disease progression and poor adherence to antiretroviral therapy. Although antidepressive treatment has demonstrated effectiveness on the management of depressive symptoms, improvement of clinical and laboratory parameters, and enhancement of antiretroviral adherence, depression is frequently under diagnosed and under treated in these patients. We analyzed the main international findings on depression prevalence, risk factors, con-sequences and management in people with HIV disease.


Assuntos
Depressão/etiologia , Infecções por HIV/psicologia , Antidepressivos/uso terapêutico , Depressão/terapia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Prevalência , Psicoterapia , Fatores de Risco
18.
Rev. chil. infectol ; 27(1): 65-74, feb. 2010. tab
Artigo em Espanhol | LILACS | ID: lil-537169

RESUMO

Depression is one of the main psychiatric co-morbidities in HIV infection, presenting with a significantly higher prevalence than in the general population (around 35 percent). Its presence has been associated with poor quality of life, HIV disease progression and poor adherence to antiretroviral therapy. Although antidepressive treatment has demonstrated effectiveness on the management of depressive symptoms, improvement of clinical and laboratory parameters, and enhancement of antiretroviral adherence, depression is frequently under diagnosed and under treated in these patients. We analyzed the main international findings on depression prevalence, risk factors, con-sequences and management in people with HIV disease.


La depresión es una de las principales co-morbilidades psiquiátricas en el curso de la infección por VIH, presentándose con una prevalencia significativamente mayor que en población general (alrededor de 35 por ciento). Su presencia se ha asociado a deterioro de la calidad de vida, progresión de la enfermedad por VIH y disminución en la adherencia a la terapia anti-retroviral. El adecuado tratamiento antidepresivo ha demostrado ser efectivo en el manejo de la sintomatología depresiva, en la mejoría de parámetros clínicos y de laboratorio, y en reforzar la adherencia a la terapia anti-retroviral. A pesar de su importancia, la depresión suele ser sub-diagnosticada y sub-tratada en estos pacientes. En este trabajo se revisan los principales hallazgos internacionales sobre prevalencia, factores de riesgo, consecuencias y abordaje de la depresión en personas infectadas por VIH.


Assuntos
Humanos , Depressão/etiologia , Infecções por HIV/psicologia , Antidepressivos/uso terapêutico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Depressão/terapia , Prevalência , Psicoterapia , Fatores de Risco
19.
Oncogene ; 29(13): 1963-75, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-20062079

RESUMO

E2A-hepatic leukemia factor (HLF) is a chimeric protein found in B-lineage acute lymphoblastic leukemia (ALL) with t(17;19). To analyze the leukemogenic process and to create model mice for t(17;19)-positive leukemia, we generated inducible knock-in (iKI) mice for E2A-HLF. Despite the induced expression of E2A-HLF in the hematopoietic tissues, no disease was developed during the long observation period, indicating that additional gene alterations are required to develop leukemia. To elucidate this process, E2A-HLF iKI and control littermates were subjected to retroviral insertional mutagenesis. Virus infection induced acute leukemias in E2A-HLF iKI mice with higher morbidity and mortality than in control mice. Inverse PCR detected three common integration sites specific for E2A-HLF iKI leukemic mice, which induced overexpression of zinc-finger transcription factors: growth factor independent 1 (Gfi1), zinc-finger protein subfamily 1A1 isoform a (Zfp1a1, also known as Ikaros) and zinc-finger protein 521 (Zfp521). Interestingly, tumors with Zfp521 integration exclusively showed B-lineage ALL, which corresponds to the phenotype of human t(17;19)-positive leukemia. In addition, ZNF521 (human counterpart of Zfp521) was found to be overexpressed in human leukemic cell lines harboring t(17;19). Moreover, both iKI for E2A-HLF and transgenic for Zfp521 mice frequently developed B-lineage ALL. These results indicate that a set of transcription factors promote leukemic transformation of E2A-HLF-expressing hematopoietic progenitors and suggest that aberrant expression of Zfp521/ZNF521 may be clinically relevant to t(17;19)-positive B-lineage ALL.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Proteínas de Ligação a DNA/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Animais , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Transformação Celular Neoplásica , Humanos , Camundongos , Mutação , Proteínas Nucleares , Ativação Transcricional/genética
20.
Inform Prim Care ; 17(2): 103-12, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19807952

RESUMO

PURPOSE: To examine integration of electronic medical records (EMRs) by primary care providers (PCPs) in a diabetes telemedicine project (IDEATel) in medically underserved rural areas and assess if access to digital records is associated with diabetes intermediate outcomes. METHOD: PCPs (n=61) with patients in IDEATel participated in structured interviews to determine current (2006 to 2007) and projected (2007 to 2008) use of paper and/or electronic medical data. T-tests examined group differences. RESULTS: 28% (17/61) of PCPs had comprehensive EMRs, but most electronic data were non-interoperative between offices; 6% of PCPs solely used paper; 92% of PCPs used mixed paper/electronic records. Half of 61 PCPs anticipated no migration within one year to an electronic record for common patient data, while one third anticipated that function would become greatly more electronic. Among 31 PCPs interviewed in depth in person, 70% (7/10) in private practice and 69% (9/13) in networks anticipated greater electronic media migration through system change, whereas 100% of responding academic PCPs (n=6) expected only system modifications. PCPs were most interested in data exchange for chronic disease management (94%), regional benchmarking (84%) and quality improvement (87%). Patient personal electronic health records were rarely mentioned. IDEATel patients of PCPs with or without access to comprehensive EMRs achieved similar haemoglobin A1c, blood pressure, LDL-cholesterol, and body mass index, but the small number invokes cautious interpretation. CONCLUSIONS: Our findings suggest an effective and complementary element of national health information technology (HIT) strategy, telemedicine, can be implemented by PCPs with success despite the lack of a concurrent EMR for efficient data exchange.


Assuntos
Diabetes Mellitus/terapia , Registros de Saúde Pessoal , Educação de Pacientes como Assunto/métodos , Atenção Primária à Saúde/métodos , Telemedicina , Adulto , Idoso , Idoso de 80 Anos ou mais , Atitude do Pessoal de Saúde , Feminino , Humanos , Masculino , Registro Médico Coordenado/métodos , Área Carente de Assistência Médica , Pessoa de Meia-Idade , New York
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