RESUMO
BACKGROUND: T1 melanoma substaging was recently modified by the American Joint Committee on Cancer (AJCC). Although sentinel lymph node (SLN) positivity is the most important prognostic factor in melanoma, there is a lack of consensus on whether SLN biopsy should be performed in patients with thin melanoma (≤1 mm). OBJECTIVE: The main aim of this study was to investigate predictors of SLN positivity in patients with thin melanoma, with a special emphasis on mitotic rate. A secondary aim was to evaluate survival in this group of patients. MATERIALS AND METHODS: Retrospective multicenter observational study with analysis of age, sex, tumour location, thickness, mitotic rate, regression and microscopic satellites. Predictive factors were identified using a classification and regression tree (CART) approach. Melanoma-specific survival according to SLN status was estimated using Kaplan-Meier curves. RESULTS: We analysed 203 patients with a melanoma ≤1 mm. Using the new AJCC staging criteria, the CART algorithm identified a 7.5% likelihood of SLN positivity in T1a patients. In the case of T1b melanoma, there was a 14.3% likelihood of SLN positivity in patients with a mitotic rate >1 mitosis/mm2 and a 3.2% likelihood in those with ≤1 mitoses/mm2 . None of the patients with T1b disease who had ≤1 mitoses/mm2 and regression had SLN positivity. In T1b patients, 5-year melanoma-specific survival was 98.7% in the SLN-negative group and 75% in the SLN-positive group (P = 0.05). When stratified by mitotic rate, survival was 100% for patients with a mitotic rate of ≤1 mitoses/mm2 and 91.4% for those with >1 mitosis/mm2 (P = 0.022). There were no deaths in the T1a subgroup. CONCLUSIONS: Sentinel lymph node metastasis was less common in patients with T1b melanoma who had a mitotic rate of ≤1 mitoses/mm2 . Performance of SLN biopsy should be carefully considered in this subgroup of patients, particularly considering the good prognosis.
Assuntos
Melanoma/genética , Índice Mitótico , Neoplasias Cutâneas/genética , Adulto , Feminino , Humanos , Metástase Linfática , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Linfonodo Sentinela , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Post-cesarean hysterectomy is the most extensive procedure used during the postpartum stage. This is an indicator of quality substantially associated with extreme obstetric morbidity. OBJECTIVE: To determine the incidence, indications, and complications associated with obstetric hysterectomy in a hospital, after three years to implement the program of prevention and management of massive obstetric hemorrhage. MATERIALS AND METHODS: Observational, transversal, retrospective and descriptive study conducted from January 2011 to November 2013. We records patients who underwent obstetric hysterectomy, of any age and at any time during pregnancy were reviewed. The results are expressed as frequencies, percentages and central tendency measures. RESULTS: 38 patients were recorded with obstetric hysterectomy. We found prevalence of 18.4 per 10,000, and incidence per year of 1.7, 1.4 and 2.6 per 1,000 births for 2011, 2012 and 2013. The prevalence of post-cesarean hysterectomy was 63.05 per 10,000 while postpartum was 9.05 per 10,000 births. The only difference between scheduled and emergency surgery was operating time. The procedure is associated with anemia in postpartum 13 times and the main indications for the procedures were hypo/atony and placenta accrete. CONCLUSIONS: The prenatal diagnoses of placenta accrete and improvement in the use of blood products and surgical technique has eliminated maternal mortality by massive obstetric hemorrhage in the last three years at the General Hospital "Dr. Aurelio Valdivieso".
Assuntos
Histerectomia/métodos , Placenta Acreta/cirurgia , Complicações Pós-Operatórias/epidemiologia , Hemorragia Pós-Parto/cirurgia , Adulto , Cesárea , Estudos Transversais , Feminino , Hospitais Gerais , Humanos , Histerectomia/efeitos adversos , Incidência , Mortalidade Materna/tendências , México , Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
The cell wall is an essential structure for virtually all bacteria, forming a tough outer shell that protects the cell from damage and osmotic lysis. It is the target of our best antibiotics. L-form strains are wall-deficient derivatives of common bacteria that have been studied for decades. However, they are difficult to generate and typically require growth for many generations on osmotically protective media with antibiotics or enzymes that kill walled forms. Despite their potential importance for understanding antibiotic resistance and pathogenesis, little is known about their basic cell biology or their means of propagation. We have developed a controllable system for generating L-forms in the highly tractable model bacterium Bacillus subtilis. Here, using genome sequencing, we identify a single point mutation that predisposes cells to grow without a wall. We show that propagation of L-forms does not require the normal FtsZ-dependent division machine but occurs by a remarkable extrusion-resolution mechanism. This novel form of propagation provides insights into how early forms of cellular life may have proliferated.
Assuntos
Bacillus subtilis/citologia , Parede Celular/fisiologia , Bacillus subtilis/genética , Proteínas de Bactérias/genética , Divisão Celular/genética , Divisão Celular/fisiologia , Parede Celular/genética , Proteínas do Citoesqueleto/genética , Genes Bacterianos/genética , Mutação/genética , Óperon/genéticaRESUMO
Dystonias are defined as a joint sustained and involuntary contraction of agonist and antagonist muscles, which can cause torsion, repetitive abnormal involuntary movements, and/or abnormal postures. One special group of dystonias are those known as occupational, which include dystonia disorders triggered by a repetitive motor activity associated with a specific professional activity or task. Musicians are a population particularly vulnerable to these types of dystonia, which are presented as a loss of coordination and voluntary motor control movements highly trained in musical interpretation. Our aim is to describe a clinical series of focal dystonias in musicians evaluated and treated in our centre. PATIENTS AND METHODS: Data is presented on a clinical series of 12 musicians with occupational dystonia. Their history and phenomenology are described, as well as well as their outcome after therapy. RESULTS: Demographic details: Mean age 34.8 ± 11.8 years, 10 males (83.3%) and 2 females (16.7%). CLINICAL HISTORY: History of trauma in dystonic segment, 6 patients (50%); family history of neurological diseases in first-degree relatives, 6 patients (50%); occupational history according to music category, 8 patients (66.6%) were classical musicians and 4 patients (33.3%) were popular musicians. PHENOMENOLOGY: The dystonia syndrome was characterised by having a mean age of onset of 28.2 ± 11.3 years (range 18-57 years). The segment affected was the hand (91.7%) in 11 patients. Of all the musicians seen in the clinic, 9 of them (75%) received therapy. The majority of patients appeared to have triggering factors specific to musical execution and linked to the requirement of fine motor control. It should be mentioned that 50% of the musicians treated maintained their professional activity or position in the orchestra to which they belonged. CONCLUSIONS: The majority of our phenomenological findings are consistent with those reported in the current literature. However, it is worth mentioning the presence of triggering factors attributed to the specific requirements of performing music, linked to the participation of fine motor control.
Assuntos
Distúrbios Distônicos/terapia , Música , Doenças Profissionais/terapia , Adulto , Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The main aim of this study was to identify predictors of sentinel lymph node (SN) metastasis in cutaneous melanoma. PATIENTS AND METHODS: This was a retrospective cohort study of 818 patients in 2 tertiary-level hospitals. The primary outcome variable was SN involvement. Independent predictors were identified using multiple logistic regression and a classification and regression tree (CART) analysis. RESULTS: Ulceration, tumor thickness, and a high mitotic rate (≥6 mitoses/mm(2)) were independently associated with SN metastasis in the multiple regression analysis. The most important predictor in the CART analysis was Breslow thickness. Absence of an inflammatory infiltrate, patient age, and tumor location were predictive of SN metastasis in patients with tumors thicker than 2mm. In the case of thinner melanomas, the predictors were mitotic rate (>6 mitoses/mm(2)), presence of ulceration, and tumor thickness. Patient age, mitotic rate, and tumor thickness and location were predictive of survival. CONCLUSIONS: A high mitotic rate predicts a higher risk of SN involvement and worse survival. CART analysis improves the prediction of regional metastasis, resulting in better clinical management of melanoma patients. It may also help select suitable candidates for inclusion in clinical trials.
Assuntos
Metástase Linfática/diagnóstico , Melanoma/secundário , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Fatores Etários , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Linfócitos do Interstício Tumoral/patologia , Masculino , Melanoma/classificação , Pessoa de Meia-Idade , Índice Mitótico , Estudos Retrospectivos , Úlcera Cutânea/etiologia , Centros de Atenção TerciáriaRESUMO
STUDY DESIGN: Single-blind randomized controlled trial of 6 months' duration. OBJECTIVES: To evaluate the efficacy of a novel telehealth intervention, 'CareCall', on reducing pressure ulcers and depression and enhancing the use of appropriate health care. SETTING: General community, Massachusetts and Connecticut, United States METHODS: 'CareCall' is an automated, interactive voice response system that combines patient education, cognitive behavioral interventions, screening and referrals, with alerts to a nurse telerehabilitation coordinator for direct non-emergent phone follow up. Participants consisted of a convenience sample of 142 persons with multiple sclerosis or spinal cord injury using a wheelchair >6 h per day. The intervention group received CareCall (n=71) The control group received usual care (n=71). The main outcome measures were: The pressure ulcer scale for healing tool, Patient Health Questionnaire-9 depression scale, Cornell Services Index and Craig Hospital Inventory of Environmental Factors-Short Form Question 5. RESULTS: CareCall achieved a reduction in presence of pressure ulcers at 6 months in women (P<0.0001). Among those with baseline depression, CareCall reduced 6-month severity of depression, adjusting for age and gender (P<0.047). CareCall did not have a significant impact on health-care utilization (OR=1.8, P=0.07), but did significantly improve participants' report of health-care availability (OR=2.03, P<0.04). CONCLUSION: This is the first study to demonstrate the efficacy of a largely automated telehealth intervention for adults with spinal cord dysfunction. Future research needs to replicate this study in a larger, multisite trial.
Assuntos
Úlcera por Pressão/terapia , Doenças da Medula Espinal/terapia , Telemedicina/organização & administração , Telemedicina/estatística & dados numéricos , Adulto , Idoso , Terapia Cognitivo-Comportamental , Interpretação Estatística de Dados , Depressão/etiologia , Depressão/psicologia , Pessoas com Deficiência , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/terapia , Enfermeiras e Enfermeiros , Educação de Pacientes como Assunto , Projetos Piloto , Úlcera por Pressão/etiologia , Úlcera por Pressão/prevenção & controle , Qualidade de Vida , Fatores Socioeconômicos , Doenças da Medula Espinal/complicações , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/terapia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
The capacity of a tissue to continuously alter its phenotype lies at the heart of how an animal is able to quickly adapt to changes in environmental stimuli. Within tissues, differentiated cells are rigid and play a limited role in adapting to new environments; however, differentiated cells are replenished by stem cells that are defined by their phenotypic plasticity. Here we demonstrate that a Wnt-responsive stem cell niche in the junctional epithelium is responsible for the capability of this tissue to quickly adapt to changes in the physical consistency of a diet. Mechanical input from chewing is required to both establish and maintain this niche. Since the junctional epithelium directly attaches to the tooth surface via hemidesmosomes, a soft diet requires minimal mastication, and consequently, lower distortional strains are produced in the tissue. This reduced strain state is accompanied by reduced mitotic activity in both stem cells and their progeny, leading to tissue atrophy. The atrophied junctional epithelium exhibits suboptimal barrier functions, allowing the ingression of bacteria into the underlying connective tissues, which in turn trigger inflammation and mild alveolar bone loss. These data link the mechanics of chewing to the biology of tooth-supporting tissues, revealing how a stem cell niche is responsible for the remarkable adaptability of the junctional epithelium to different diets.
Assuntos
Inserção Epitelial , Gengiva , Animais , Mastigação , Tecido Conjuntivo , Biologia , EpitélioRESUMO
Tooth extraction triggers alveolar ridge resorption, and when this resorption is extensive, it can complicate subsequent reconstructive procedures that use dental implants. Clinical data demonstrate that the most significant dimensional changes in the ridge occur soon after tooth extraction. Here, we sought to understand whether a correlation existed between the rate at which an extraction socket heals and the extent of alveolar ridge resorption. Maxillary molars were extracted from young and osteoporotic rodents, and quantitative micro-computed tomographic imaging, histology, and immunohistochemistry were used to simultaneously follow socket repair and alveolar ridge resorption. Extraction sockets rapidly filled with new bone via the proliferation and differentiation of Wnt-responsive osteoprogenitor cells and their progeny. At the same time that new bone was being deposited in the socket, tartrate-resistant acid phosphatase-expressing osteoclasts were resorbing the ridge. Significantly faster socket repair in young animals was associated with significantly more Wnt-responsive osteoprogenitor cells and their progeny as compared with osteoporotic animals. Delivery of WNT3A to the extraction sockets of osteoporotic animals restored the number of Wnt-responsive cells and their progeny back to levels seen in young healthy animals and accelerated socket repair in osteoporotic animals back to rates seen in the young. In cases where the extraction socket was treated with WNT3A, alveolar ridge resorption was significantly reduced. These data demonstrate a causal link between enhancing socket repair via WNT3A and preserving alveolar ridge dimensions following tooth extraction.
Assuntos
Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/cirurgia , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/cirurgia , Animais , Dente Molar/diagnóstico por imagem , Dente Molar/cirurgia , Extração Dentária/efeitos adversos , Alvéolo Dental/cirurgiaRESUMO
The roles of Wnt/ß-catenin signaling in regulating the morphology and microstructure of craniomaxillofacial (CMF) bones was explored using mice carrying a constitutively active form of ß-catenin in activating Dmp1-expressing cells (e.g., daßcatOt mice). By postnatal day 24, daßcatOt mice exhibited midfacial truncations coupled with maxillary and mandibular hyperostosis that progressively worsened with age. Mechanistic insights into the basis for the hyperostotic facial phenotype were gained through molecular and cellular analyses, which revealed that constitutively activated ß-catenin in Dmp1-expressing cells resulted in an increase in osteoblast number and an increased rate of mineral apposition. An increase in osteoblasts was accompanied by an increase in osteocytes, but they failed to mature. The resulting CMF bone matrix also had an abundance of osteoid, and in locations where compact lamellar bone typically forms, it was replaced by porous, woven bone. The hyperostotic facial phenotype was progressive. These findings identify for the first time a ligand-independent positive feedback loop whereby unrestrained Wnt/ß-catenin signaling results in a CMF phenotype of progressive hyperostosis combined with architecturally abnormal, poorly mineralized matrix that is reminiscent of craniotubular disorders in humans.
Assuntos
Hiperostose , beta Catenina , Animais , Camundongos , Osteoblastos/metabolismo , Osteócitos/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismoRESUMO
INTRODUCTION: A special group of focal dystonia is that known as occupational, which include dystonic disorders triggered by repetitive motor activity, closely associated with the professional activity of a specific task that the affected person performs. In this sense, musicians are a population particularly vulnerable to this disorder, which is presented during the execution of highly trained movements. OBJECTIVE: This article reviews the pathophysiology of focal dystonia and its therapeutic implications. DEVELOPMENT: The pathophysiological basis of focal dystonia in the musician is still not well established. However, due to the contribution of neurophysiological studies and functional neuroimaging, there is growing evidence of anomalies in the processing of sensory information, sensory-motor integration, cortical and subcortical inhibitory processes, which underline this disease. Clinically, it is characterised by the appearance of involuntary muscle contractions, and is associated with loss of motor control while practicing music. It is a gradual appearance and sometimes there may be a history of musculoskeletal injuries or non-physiological postures preceding the appearance of the symptoms. The neurological examination is usually normal, although subtle dystonic postures can develop spontaneously or with movements that involve the affected segments. The dystonia remains focal and is not generalised. CONCLUSIONS: Treatment is based on using multiple strategies for the management of the dystonia, with variable results. Although a specific therapy has not been defined, there are general principles that are combined in each situation looking for results. This includes, among others, pharmacological interventions, management with botulinum toxin, and sensory re-training techniques.
Assuntos
Distúrbios Distônicos/fisiopatologia , Dedos/fisiopatologia , Música , Doenças Profissionais/fisiopatologia , Antidiscinéticos/uso terapêutico , Toxinas Botulínicas/uso terapêutico , Distúrbios Distônicos/epidemiologia , Distúrbios Distônicos/etiologia , Distúrbios Distônicos/terapia , Ergonomia , Dedos/inervação , Humanos , Rede Nervosa/fisiopatologia , Doenças Profissionais/terapia , Reabilitação , Apoio SocialRESUMO
Upper limb amputations are uncommon but cause severe disability. It is usually of traumatic origin and in young males less than 40 years-old, and active. The frequency of amputation at transradial level is around 35% of cases, with the myoelectric prosthesis achieving greater functionality. Around 25% of the patients give up using of the prosthesis, due to its complexity of use by means of 2 conventional electrodes, one of the most common causes for giving up. The Myo Plus system with an 8-channel electromyograph helps the patient to control the prosthesis using the phantom limb and achieving the closing, opening, and pronation-supination patterns of the hand in a time less than the conventional one and more easily. It also leads to less rehabilitation time, decreasing costs and unnecessary travel, without increasing the time for the manufacture of the socket.
Assuntos
Membros Artificiais , Membro Fantasma , Adulto , Amputação Cirúrgica , Eletromiografia , Mãos , Humanos , MasculinoRESUMO
Acidic and basic fibroblast growth factors (FGFs) are members of a family of proteins that are broad-spectrum mitogens, have diverse hormone-like activities, and function in tumorigenesis. FGF's ability to raise the concentration of intracellular calcium ion suggests that FGF could induce the synthesis of endothelium-derived relaxing factor (EDRF) and consequently vasodilation. Systemic administration of FGF decreased arterial blood pressure. This effect was mediated by EDRF and by adenosine triphosphate-sensitive potassium ion channels. The hypotensive effect of FGF was segregated from its mitogenic activity by protein engineering. These results extend the range of FGF autocrine activities and potential therapeutic applications, emphasize the role of endothelium as an arterial blood pressure--regulating organ, and provide insight on the structural basis of FGF functions.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/farmacologia , Animais , Relação Dose-Resposta a Droga , Fatores de Crescimento de Fibroblastos/química , Glibureto/farmacologia , Óxido Nítrico/fisiologia , Canais de Potássio/efeitos dos fármacos , Coelhos , Ratos , Relação Estrutura-Atividade , Fatores de TempoRESUMO
INTRODUCTION: The treatment of Parkinson's disease (PD) is based on the use of levodopa and/or dopaminergic agonists. This treatment is associated with motor complications in around 50% of the patients over 5 years of treatment. Numerous risk factors have been related to the onset of this motor complications. AIM: To describe the prevalence and risk factors associated with the occurrence of motor complications in our population. PATIENTS AND METHODS: PD patients in control in a movement disorders center were consecutively recruited. Using a multivariate logistic regression model the risk factors associated with the onset of MC were determined. RESULTS: 124 patients were evaluated. Mean age was 66,2 +/- 10,1 years, the years of PD evolution were 8,1 +/- 5,2 years, the on UPDRS score was 27,7 +/- 14,8 points. A 62% of the patients presented at least one motor complication, a 52% with wearing off and a 47,2% dyskinesias. Both motor complications were present in 39%. The multivariate analysis showed that that female sex and the dose of levodopa equivalents were the risk factors for the occurrence of dyskinesias. For the wearing off the main risk factor were the years of evolution of the PD. CONCLUSIONS: This study shows that the time of evolution of the PD is the main risk factor for the wearing off and the female sex and the dose of levodopa equivalents are the risk factor for the development of dyskinesias. These results are in agreement with the previously reported in the literature for other populations.
Assuntos
Transtornos dos Movimentos/etiologia , Doença de Parkinson/complicações , Idoso , Antiparkinsonianos/efeitos adversos , Chile , Progressão da Doença , Agonistas de Dopamina/efeitos adversos , Feminino , Humanos , Levodopa/efeitos adversos , Pessoa de Meia-Idade , Transtornos dos Movimentos/fisiopatologia , Análise Multivariada , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Fatores de RiscoRESUMO
OBJECTIVES: Because fibroblast growth factor (FGF) causes the intracellular accumulation of activated signal transducer and activator of transcription 3 (STAT3), we assessed whether dobesilate, a synthetic FGF inhibitor that has been reported to show antiproliferative and proapoptotic activities in glioma cell cultures, down-regulates the STAT3 signaling pathway in growing cultures of those cells. Because STAT3 signaling pathway plays pleiotropic roles in tumor proliferation, maintenance of STAT3 in its inactive state may prevent glioma growth and spreading. METHODS: Rat glioma C6 cells were treated with dobesilate and cultures were evaluated immunocytochemically for STAT3 activation and enhancement of the expression rate of cyclin D1 and bcl-XL. RESULTS: Dobesilate abrogates the accumulation of activated STAT3 in glioma cells. The decrease in the intracellular levels of activated STAT3 by the dobesilate treatment runs parallel with a significant attenuation of cyclin D1 and bcl-XL expression. CONCLUSION: Treatment with inhibitors of FGF down-regulates the STAT3 signaling pathway. These alterations could be correlated to the already observed inhibition of cell proliferation and promotion of apoptosis in glioma cell cultures by dobesilate. The reported results may open new avenues for developing new treatments against these tumors.
Assuntos
Neoplasias Encefálicas/metabolismo , Dobesilato de Cálcio/farmacologia , Ciclina D1/metabolismo , Glioma/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteína bcl-X/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Ciclina D1/efeitos dos fármacos , Ciclina D1/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Fatores de Crescimento de Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Glioma/tratamento farmacológico , Glioma/genética , Inibidores do Crescimento/farmacologia , Hemostáticos/farmacologia , Ratos , Fator de Transcrição STAT3/efeitos dos fármacos , Fator de Transcrição STAT3/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/genética , Proteína bcl-X/efeitos dos fármacos , Proteína bcl-X/genéticaRESUMO
INTRODUCTION: Depression is a frequently occurring problem in Parkinson's disease (PD). The purpose of this study is to describe the characteristics of episodes of major depression (EMD) in a population of outpatients with PD and the risk factors linked to their appearance. PATIENTS AND METHODS: We conducted an open study involving 85 patients with PD; their mean age was 65.8 +/- 12.3 years and the mean length of time since disease onset was 7.2 +/- 5 years. Data that was collected included information from the patient record, evaluation with the Motor Examination section of the Unified PD Rating Scale (UPDRS-III), the Parkinson Mini-Mental test, the Neuropsychiatric Inventory (NPI) and the short version of Beck's Depression Inventory (BDI). EMD were diagnosed clinically by means of a semi-structured interview that allowed us to examine the symptoms that are included in the DSM-IV criteria for diagnosis of EMD. RESULTS: In 21 cases (24.7%) DSM-IV criteria for EMD were satisfied, with a BDI score (mean +/- standard deviation) of 17.5 +/- 6.2. In 64 cases (75.3%) who did not fulfil the criteria for EMD, the BDI score was 6.4 +/- 4.7 (p < 0.001). The items on the UPDRS-III related to the dopaminergic response in patients with EMD were 24.9 +/- 11.9 and in patients without EMD the values were 21.2 +/- 10.9 (NS). Those not related to the dopaminergic response in patients with EMD were 9.9 +/- 5.3 and in those without EMD the values were 6.2 +/- 4.6 (p < 0.001). CONCLUSION: In our sample, the presence of motor symptoms that do not respond to levodopa in patients with PD is a risk factor for the appearance of EMD.
Assuntos
Transtorno Depressivo Maior , Pacientes Ambulatoriais , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Idoso , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/fisiopatologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Escalas de Graduação Psiquiátrica , Fatores de Risco , Estatística como AssuntoRESUMO
We undertook a series of systematic studies to address the role of fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) activity in tumor growth and angiogenesis. We expressed dominant-negative FGFR2 (FGFR2-DN) or FGFR1 (FGFR1-DN) in glioma C6 cells by using constitutive or tetracycline-regulated expression systems. Anchorage-dependent or independent growth was inhibited in FGFR-DN-expressing cells. Tumor development after xenografting FGFR-DN-expressing cells in immunodeficient mice or after transplantation in rat brain was strongly inhibited. Quantification of microvessels demonstrated a significant decrease in vessel density in tumors derived from FGFR-DN-expressing cells. Furthermore, in a rabbit corneal assay, the angiogenic response after implantation of FGFR-DN-expressing cells was decreased. In tumors expressing FGFR-DN, vascular endothelial growth factor expression was strongly inhibited as compared with control tumor. These results indicate that inhibition of FGF activity may constitute a dominant therapeutic strategy in the treatment of FGF-producing cerebral malignancies and may disrupt both angiogenesis-dependent and -independent signals required for glioma growth and invasion.
Assuntos
Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/patologia , Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Glioma/irrigação sanguínea , Glioma/patologia , Neovascularização Patológica/patologia , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Divisão Celular/fisiologia , Fatores de Crescimento Endotelial/biossíntese , Fatores de Crescimento Endotelial/genética , Fator 2 de Crescimento de Fibroblastos/biossíntese , Fator 2 de Crescimento de Fibroblastos/genética , Fator 4 de Crescimento de Fibroblastos , Fatores de Crescimento de Fibroblastos/biossíntese , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/fisiologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/genética , Glioma/metabolismo , Linfocinas/biossíntese , Linfocinas/genética , Masculino , Camundongos , Neovascularização Patológica/metabolismo , Fenótipo , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , Coelhos , Ratos , Ratos Sprague-Dawley , Receptores Proteína Tirosina Quinases/biossíntese , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/fisiologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Receptores de Fatores de Crescimento de Fibroblastos/biossíntese , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/fisiologia , Tetraciclina/farmacologia , Transfecção , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
The free-living amebas Naegleria and Acanthamoeba are recognized as causal agents of central nervous system infections. Recently a third free-living ameba, Balamuthia mandrillaris, was identified as the causal agent of granulomatous encephalitis in humans. We report a case of Balamuthia encephalitis in an immunocompetent school-age girl who presented cutaneous lesions that compromised the central portion of the face. The skin biopsy revealed granulomatous lesion with positive PCR for non-tuberculous Mycobacterium. We started treatment for atypical extrapulmonary mycobacteriosis. Nevertheless, the child was readmitted six months later, with progressive neurological involvement, dying about one year after the onset of cutaneous symptoms. The brain necropsy showed the presence of B. mandrillaris cysts and trophozoites. Balamuthia mandrillaris infection should be considered in the differential diagnosis of a patient with chronic granulomatous disease with neurologic symptoms.
Assuntos
Amebíase/parasitologia , Amoeba/isolamento & purificação , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Granuloma/parasitologia , Meningoencefalite/parasitologia , Dermatopatias Parasitárias/parasitologia , Amebíase/patologia , Amoeba/classificação , Animais , Infecções Protozoárias do Sistema Nervoso Central/patologia , Pré-Escolar , Evolução Fatal , Feminino , Granuloma/patologia , Humanos , Hospedeiro Imunocomprometido , Meningoencefalite/patologia , Dermatopatias Parasitárias/patologiaRESUMO
OBJECTIVES: Dihydroxy-2,5 benzenesulphonate (dobesilate) is used as an oral agent for treatment of vascular complications of diabetic retinopathy. We previously showed that blockade of fibroblast growth factor (FGF) driving angiogenesis with dobesilate inhibited new blood vessel formation in a mouse gelatine plug assay. In the present study we assessed the effects of dobesilate in rat glioma cells. METHODS: Rat C6 cells line were grown as adherent cells in Dulbecco modified Eagle medium supplemented with 1% (v/v) fetal bovine serum and antibiotics. Calcium dobesilate was added in independent experiments at the following concentrations: 10, 25, 50, 75 and 100 microM, and cells were incubated for 24 hours. Effects of dobesilate in glioma cell proliferation and survival were assessed using crystal violet staining and TUNEL assay, respectively. RESULTS: Incubation of glioma cells with dobesilate for 24 hours concentration-dependently decreased cell proliferation with an apparent IC50 of 25 microM, and this antiproliferative effect was related to a significant increase in glioma cell apoptosis. CONCLUSIONS: The results suggest that dobesilate is a promising candidate leading to the development of a new adjuvant therapeutic strategy for gliomas.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Dobesilato de Cálcio/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Glioma/patologia , Animais , Antineoplásicos/administração & dosagem , Dobesilato de Cálcio/administração & dosagem , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Concentração Inibidora 50 , RatosRESUMO
OBJECTIVES: The goals of the present study are to obtain, expand and characterize a stem cell population from human omentum and to evaluate its in vivo angiogenic capacities. METHODS: Human omental CD34+ cells were obtained from samples of human omentum by density gradient centrifugation in Ficoll. Proliferative pattern, marker expression (by flow cytometry) and angiogenic growth factor synthesis by omental cell cultures were determined. In vivo angiogenic capacity of the cells was evaluated in rats. RESULTS: Omental stem cells showed a high rate of proliferation (Ki67 staining), expressed CD34 marker and synthesized bFGF and VEGF. When implanted in rats, omental cells promoted neovascularization. Human omental cells were localized in rat tissue, mainly forming the endothelium of neo-vessels. Implantation of omental cells also facilitated angiogenesis of rat origin. CONCLUSION: CD34+ cell population of human omentum could be responsible for the clinical benefit of omental transplantation by promoting angiogenesis and synthesizing angiogenic growth factors to facilitate revascularization of injured tissue.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Neovascularização Fisiológica/fisiologia , Omento/citologia , Animais , Antígenos CD34/análise , Diferenciação Celular , Divisão Celular , Separação Celular , Endotélio Vascular/citologia , Feminino , Fator 2 de Crescimento de Fibroblastos/biossíntese , Humanos , Próteses e Implantes , Ratos , Ratos Sprague-Dawley , Tampões de Gaze Cirúrgicos , Transplante Heterólogo , Fator A de Crescimento do Endotélio Vascular/biossínteseRESUMO
Basal cell carcinoma (BCC) is the most common skin cancer, occurring more frequently than malignancies of any other tissue or organ, either individually or in total. Medical treatment modalities of BCC offer cost reduction and clinical advantages in selected cases. Neomycin has been reported to have an important role on proliferation of endothelial cells and neoplastic cells. This finding may lead to new strategies for the therapeutic use of agents which block FGF activities in disease states associated with enhanced keratinocyte proliferation. We report here a case of BCC treated with neomycin 5% cream that induced a regression of BCC.