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1.
Phys Rev Lett ; 127(27): 279901, 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35061446

RESUMO

This corrects the article DOI: 10.1103/PhysRevLett.127.186803.

2.
Phys Rev Lett ; 127(18): 186803, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34767388

RESUMO

A challenge in plasmonic trapping of small nanoparticles is the heating due to the Joule effect of metallic components. This heating can be avoided with electromagnetic field confinement in high-refractive-index materials, but nanoparticle trapping is difficult because the electromagnetic fields are mostly confined inside the dielectric nanostructures. Herein, we present the design of an all-dielectric platform to capture small dielectric nanoparticles without heating the nanostructure. It consists of a Si nanodisk engineered to exhibit the second-order anapole mode at the infrared regime (λ=980 nm), where Si has negligible losses, with a slot at the center. A strong electromagnetic hot spot is created, thus allowing us to capture nanoparticles as small as 20 nm. The numerical calculations indicate that optical trapping in these all-dielectric nanostructures occurs without heating only in the infrared, since for visible wavelengths the heating levels are similar to those in plasmonic nanostructures.

3.
Pediatr Transplant ; 17(6): 556-60, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23890077

RESUMO

The native spleen is usually removed in patients undergoing MTV. The consequential asplenic state is associated with a high risk of sepsis, especially in immunosuppressed children. In contrast, the inclusion of an allogeneic spleen in multivisceral grafts has been associated with a high incidence of GVHD. We propose an alternative technique for patients undergoing MTV, consisting of the preservation of the native spleen. This approach avoids the additional risk of infection that characterizes the asplenic state without the detrimental side effects of the allogeneic spleen.


Assuntos
Transplante de Órgãos/métodos , Baço/transplante , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus/terapia , Feminino , Doenças da Vesícula Biliar/terapia , Doença Enxerto-Hospedeiro , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Lactente , Atresia Intestinal/terapia , Pseudo-Obstrução Intestinal/terapia , Masculino , Risco , Síndrome do Intestino Curto/terapia , Baço/patologia , Baço/cirurgia , Fatores de Tempo , Fístula Traqueoesofágica/terapia
4.
Arch Esp Urol ; 66(4): 342-9, 2013 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-23676537

RESUMO

OBJECTIVES: Advances in diagnosis of prostate cancer (PCa)have led to an increased detection of these tumors, some of them with low-risk of progression, with the consequent risk of overdiagnosis and overt treatment. In consequence, there is a tendency to offer alternatives to active therapy, like active surveillance (AS)however, some patients under AS need definitive therapy and after surgery it becomes evident that they are not "low-risk" patients. We retrospectively reviewed the data of patients who met criteria for low-risk tumors treated with radical prostatectomy. METHODS: We selected 21 out of 190 patients treated with radical prostatectomy from January 2004 to December 2008 who met Epstein's criteria for low-risk tumors. We analyzed the number of organ-confined tumors,Gleason undergrading and understaging by biopsy, surgical margins and postoperative PSA. RESULTS: Mean age was 58.6 years; mean PSA was 6.6 ng/ml, predominant Gleason score was 6 (3+3), 76%were unilateral tumors and 90%were organ-confined, 10% had extracapsular extension, none had involvement of the seminal % vesicles, 15% of the patients had Gleason score >6 and surgical margins were positive in 30% of the specimens. Eighty five percent had their first postoperative PSA <0.10 ng/ml and 75% remain free of biochemical recurrence. According to the Johns Hopkins criteria for "incurable tumors ", our cohort had 28%. CONCLUSION: Patients with low-risk prostate cancer include cases that may have greater risk than estimated. In our series, we had 10% extracapsular disease, 15% understaging for Gleason score and 25% biochemical recurrence, which demonstrates that current criteria do not warrant good oncological results. Active surveillance offers good quality of life and acceptable oncological results, it can be proposed until definitive therapy, without seriously endangering the patient. Anyway, as a therapeutic tool, it still requires improvements. Technical advances are awaited so as to properly assess each patient's risk and to define the best therapeutic option for every case.


Assuntos
Prostatectomia , Neoplasias da Próstata/cirurgia , Idoso , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Próstata/patologia , Antígeno Prostático Específico/análise , Estudos Retrospectivos , Resultado do Tratamento
5.
Cancer Control ; 19(2): 154-66, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22487978

RESUMO

BACKGROUND: Metastatic bone disease is a common cause of pain in cancer patients. A multidisciplinary approach to treatment is often necessary because simplified analgesic regimens may fail in the face of complex pain generators, especially those involved in the genesis of neuropathic pain. From the origins of formalized guidelines by the World Health Organization (WHO) to recent developments in implantable therapies, great strides have been made to meet the needs of these patients. METHODS: The authors review the existing literature on the pathophysiology and treatment options for pain generated by metastatic bone disease and summarize classic and new approaches. RESULTS: Relatively recent animal models of malignant bone disease have allowed a better understanding of the intimate mechanisms involved in the genesis of pain, resulting in a mechanistic approach to its treatment. Analgesic strategies can be developed with specific targets in mind to complement the classic, opioid-centered WHO analgesic ladder obtaining improved outcomes and quality of life. Unfortunately, high-quality evidence is difficult to produce in pain medicine, and these concepts are evolving slowly. CONCLUSIONS: Treatment options are expanding for the challenging clinical problem of painful metastatic bone disease. Efforts are concentrated on developing alternative nonopioid approaches that appear to increase the success rate and improve patients' quality of life.


Assuntos
Neoplasias Ósseas/complicações , Neoplasias Ósseas/secundário , Dor/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológico , Gerenciamento Clínico , Humanos , Dor/etiologia
6.
J Immunol ; 184(9): 4936-46, 2010 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-20351194

RESUMO

Protective adaptive immune responses rely on TCR-mediated recognition of Ag-derived peptides presented by self-MHC molecules. However, self-Ag (tumor)-specific TCRs are often of too low affinity to achieve best functionality. To precisely assess the relationship between TCR-peptide-MHC binding parameters and T cell function, we tested a panel of sequence-optimized HLA-A(*)0201/NY-ESO-1(157-165)-specific TCR variants with affinities lying within physiological boundaries to preserve antigenic specificity and avoid cross-reactivity, as well as two outliers (i.e., a very high- and a low-affinity TCR). Primary human CD8 T cells transduced with these TCRs demonstrated robust correlations between binding measurements of TCR affinity and avidity and the biological response of the T cells, such as TCR cell-surface clustering, intracellular signaling, proliferation, and target cell lysis. Strikingly, above a defined TCR-peptide-MHC affinity threshold (K(D) < approximately 5 muM), T cell function could not be further enhanced, revealing a plateau of maximal T cell function, compatible with the notion that multiple TCRs with slightly different affinities participate equally (codominantly) in immune responses. We propose that rational design of improved self-specific TCRs may not need to be optimized beyond a given affinity threshold to achieve both optimal T cell function and avoidance of the unpredictable risk of cross-reactivity.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Citotoxicidade Imunológica , Proteínas de Neoplasias/metabolismo , Fragmentos de Peptídeos/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Adesão Celular/genética , Adesão Celular/imunologia , Linhagem Celular , Linhagem Celular Transformada , Linhagem Celular Tumoral , Células Cultivadas , Citotoxicidade Imunológica/genética , Antígenos HLA-A/genética , Antígenos HLA-A/imunologia , Antígenos HLA-A/metabolismo , Antígeno HLA-A2 , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/genética , Fragmentos de Peptídeos/genética , Ligação Proteica/genética , Ligação Proteica/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/genética
7.
Neurologia (Engl Ed) ; 36(8): 597-602, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34654534

RESUMO

INTRODUCTION: Headache is a frequent reason for consultation with primary care (PC) physicians. However, the condition is underdiagnosed and undertreated. One reason for this may be the lack of specific training on headache in PC. METHODS: We conducted a descriptive cross-sectional study of data gathered with a self-administered survey that was completed by PC physicians from our health district. We collected sociodemographic data and information on previous training in neurology and headache, and training needs. RESULTS: The survey was completed by 104 PC physicians, 53% of whom were women; mean age was 49 years. Most respondents worked in urban settings (42.3%) and had been trained via residency (77.9%). Although 65.4% spent more time with patients with headache than with other patients, only 32.7% used the International Classification of Headache Disorders. In our sample, 68.3% of respondents reported a high or very high interest in headache, and 75.9% wished to receive further training on the condition; theoretical and practical courses and update lectures were regarded as the most useful tools. In clinical practice, 90% used triptans and 78% used preventive treatments. The most frequently used drug was amitriptyline; only 22.1% choose topiramate. CONCLUSIONS: PC physicians are in frequent contact with patients with headache and show interest in receiving training on this condition. This could be helpful in designing training programmes aimed at improving quality of care in this area.


Assuntos
Cefaleia , Neurologia , Estudos Transversais , Feminino , Cefaleia/diagnóstico , Humanos , Pessoa de Meia-Idade , Atenção Primária à Saúde , Encaminhamento e Consulta
8.
Cir Pediatr ; 23(3): 177-83, 2010 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-23155666

RESUMO

OBJECTIVE: To analyze the evolution of Small Bowel Transplantation program since the beginning of the program. MATERIAL AND METHODS: [corrected] All children who underwent intestinal transplantation between 1997 and 2009 were retrospectively reviewed: epidemiological data, status before transplant, surgical technique, immunosupression, results, survival and long.term quality of life were analysed. RESULTS: Fifty-two intestinal transplants were performed in 46 children (20 isolated bowel, 20 combined liver and intestine, and 12 multivisceral); median age was 32m (range 7m-19a); weight 12,3 kg (range 3,9-60); 31 had short gut syndrome, 8 dismotility, 5 intractable diarrhea, and two were miscellaneous. Intestinal adaptation was initially attempted in 26 patients, without success, 20 were directly listed for transplant. The modality of transplant was modified in 17 while listed. Baseline immunosupression consisted of tacrolimus and steroids, although 5 required conversion to Sirolimus later. Six died during the first month, due to sepsis/multiorganic failure (poor status at transplant); 13 died during the long-term follow-up. Acute rejection was seen in 20, chronic rejection in 3, PTLD in 8 (6 died) and GVHD in 5 patients (3 died). Overall survival after 5 years of follow-up is 65,2 % (51,7% for the graft). From 2006 to 2008, overall patient/graft survival at 6 m, 1 and 3 years after transplant is 88,7/84,1, 81,2/81,2 and 81,2/71,1%, respectively. After a median follw-up of 39 +/- 29 months, 27 patients are alive (59%), off TPN, (70% had their ostomy taken down), go to school, are scarcely hospitalized and enjoy a good quality of life. CONCLUSIONS: Intestinal transplantation has consolided itself as a good choice for irreversible intestinal failure, being feasible to achieve a normal life. Although overall survival diminishes over time, the center experience has improved the results. These patients need a very close follow-up, once transplant is over, in order to get an early diagnose of immunological complications.


Assuntos
Enteropatias/cirurgia , Intestino Delgado/transplante , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Adulto Jovem
9.
J Cell Biol ; 157(7): 1197-209, 2002 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-12070131

RESUMO

Although correct cycling of neuronal membrane proteins is essential for neurite outgrowth and synaptic plasticity, neuron-specific proteins of the implicated endosomes have not been characterized. Here we show that a previously cloned, developmentally regulated, neuronal protein of unknown function binds to syntaxin 13. We propose to name this protein neuron-enriched endosomal protein of 21 kD (NEEP21), because it is colocalized with transferrin receptors, internalized transferrin (Tf), and Rab4. In PC12 cells, NEEP21 overexpression accelerates Tf internalization and recycling, whereas its down-regulation strongly delays Tf recycling. In primary neurons, NEEP21 is localized to the somatodendritic compartment, and, upon N-methyl-d-aspartate (NMDA) stimulation, the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor subunit GluR2 is internalized into NEEP21-positive endosomes. NEEP21 down-regulation retards recycling of GluR1 to the cell surface after NMDA stimulation of hippocampal neurons. In summary, NEEP21 is a neuronal protein that is localized to the early endosomal pathway and is necessary for correct receptor recycling in neurons.


Assuntos
Endossomos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Receptores da Transferrina/fisiologia , Androstadienos/farmacologia , Animais , Brefeldina A/farmacologia , Compartimento Celular , Dendritos/metabolismo , Regulação para Baixo , Endocitose , Hipocampo/citologia , Complexo Antígeno L1 Leucocitário , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , N-Metilaspartato/farmacologia , Moléculas de Adesão de Célula Nervosa/metabolismo , Neurônios/citologia , Inibidores da Síntese de Proteínas/farmacologia , Proteínas Qa-SNARE , Ratos , Receptores de AMPA/metabolismo , Receptores da Transferrina/metabolismo , Transferrina/metabolismo , Wortmanina , Proteínas rab4 de Ligação ao GTP/metabolismo
10.
Vox Sang ; 95(4): 331-4, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19138264

RESUMO

In the USA, seasonal tickborne transmission of Babesia microti occurs in the Northeast and upper Midwest. A resident of Texas became infected through a red blood cell transfusion from an asymptomatic local donor who had summered in Massachusetts. The patient's infection was diagnosed by blood smear examination in January, 7 weeks post-transfusion. He died 1 week later from variceal haemorrhage complicated by haemolysis. Premortem patient specimens and archived blood from the donor unit tested positive for B. microti antibodies and DNA. Babesiosis should be included in the differential diagnosis of post-transfusion haemolytic anaemia or thrombocytopenia, regardless of the geographical region or season.


Assuntos
Babesiose/transmissão , Transfusão de Eritrócitos/efeitos adversos , Anemia Hemolítica/etiologia , Animais , Babesia microti , Babesiose/complicações , Babesiose/diagnóstico , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Texas , Trombocitopenia/etiologia
11.
Neurologia (Engl Ed) ; 2018 Jul 30.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30072273

RESUMO

INTRODUCTION: Headache is a frequent reason for consultation with primary care (PC) physicians. However, the condition is underdiagnosed and undertreated. One reason for this may be the lack of specific training on headache in PC. METHODS: We conducted a descriptive cross-sectional study of data gathered with a self-administered survey that was completed by PC physicians from our health district. We collected sociodemographic data and information on previous training in neurology and headache, and training needs. RESULTS: The survey was completed by 104 PC physicians, 53% of whom were women; mean age was 49 years. Most respondents worked in urban settings (42.3%) and had been trained via residency (77.9%). Although 65.4% spent more time with patients with headache than with other patients, only 32.7% used the International Classification of Headache Disorders. In our sample, 68.3% of respondents reported a high or very high interest in headache, and 75.9% wished to receive further training on the condition; theoretical and practical courses and update lectures were regarded as the most useful tools. In clinical practice, 90% used triptans and 78% used preventive treatments. The most frequently used drug was amitriptyline; only 22.1% choose topiramate. CONCLUSIONS: PC physicians are in frequent contact with patients with headache and show interest in receiving training on this condition. This could be helpful in designing training programmes aimed at improving quality of care in this area.

12.
Cir Pediatr ; 20(2): 71-4, 2007 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-17650713

RESUMO

OBJECTIVE: [corrected] Our aim was to analyze our results in the management of intestinal failure with a multidisciplinary approach including optimized parenteral nutrition, reconstructive surgery and intestinal transplantation (ITx). MATERIAL AND METHODS: We included all patients evaluated by our team with the diagnosis of IF. We assessed outcome, mortality and complications in children that achieved adaptation and those listed for ITx. RESULTS: Seventy one children (40 boys, 31 girls) were evaluated between 1997 and 2006 because of IF. Forty eight (76%) were referred from other institutions. In 56 cases (80%) IF began in the newborn period. Causes of IF were: short bowel syndrome (52) intestinal motility disorders (16) and intestinal epithelial disorders (3). Median birth weight in the group of SBS was 2.2 Kg and prematurity was an associated condition in 15% of them. Overall, fourteen patients (20%) achieved intestinal adaptation with progressive weaning from PN, the management of these children consisted of optimized parenteral and enteral nutrition and autologous intestinal reconstructive surgery. Nine (13%) are stable under home parenteral nutrition regimen. Eight children (11%), all of them listed for liver and small bowel transplantation, died in the waiting list after a mean waiting time of more than 300 days, with a median of 4 laparotomies and 4 episodes of catheter related sepsis. Four children (5.6%) died in the adaptation process or before their inclusion on the waiting list. Finally, twenty five (35,2%) children underwent 28 intestinal transplantation: 9 isolated small bowel transplantation (SBTx), 16 combined liver and small bowel (CLSB) and 3 multivisceral (MVTx). Among transplanted patients, 9 (36%) died, (3 MVTx, 1 SBTx and 8 CLSB) and four were retransplanted. CONCLUSIONS: Intestinal Transplantation is an established alternative to parenteral nutrition in the treatment of IF, although complications and mortality rates are still considerable, especially MVTx and CLSBTx. Mortality in children listed for intestinal transplantation remains also high. Intestinal adaptation can be achieved with adequate rehabilitation therapy even in some cases with apparently irreversible intestinal transplantation. Early referral before liver failure or other complications arise is crucial is crucial in order to improve the outcome of these patients.


Assuntos
Síndromes de Malabsorção , Feminino , Humanos , Lactente , Recém-Nascido , Síndromes de Malabsorção/complicações , Síndromes de Malabsorção/mortalidade , Síndromes de Malabsorção/terapia , Masculino , Equipe de Assistência ao Paciente
13.
Eur J Pediatr Surg ; 16(6): 399-402, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17211786

RESUMO

AIM: Eosinophilic esophagitis (EoE) is an emergent condition in which a mucosal infiltrate of > 20 eosinophils per high power microscopic field is accompanied by motor disturbances that may cause food impaction in the absence of esophageal stricture. We report a series of such cases to point out the potential involvement of pediatric surgeons in diagnosis and treatment. Furthermore, data on the motor function of the esophagus investigated manometrically is included. MATERIAL AND METHODS: Thirteen patients with EoE were referred to our emergency room for acute food bolus impaction. Their median age at diagnosis was 12 years (range 7.6-14.4). History of allergy, endoscopy with biopsy and esophageal function (24-h combined ambulatory manometry with simultaneous pH-metry) were investigated. RESULTS: In 7 patients emergency endoscopic extraction of the impacted bolus was necessary. Allergic tests were positive in eight patients. The pH probe showed gastroesophageal reflux in two cases. Upon endoscopy, typical features of EoE (esophageal trachealization and whitish papular exudates) were found. Ambulatory 24-h manometry revealed abnormal motility of the distal esophagus with strikingly high amplitudes (> 150 mmHg) and long duration (> 7 sec) of the waves, particularly during the night. Six patients responded rapidly to steroids and/or antiallergic treatment. The remaining patients had a good outcome with dietary treatment alone. CONCLUSIONS: EoE is an emergent condition that may involve the pediatric surgeon in both the diagnosis and treatment. Typical endoscopic findings and biopsy are required for proper diagnosis. Ambulatory manometry reveals a marked propulsive dysfunction that explains impaction. This dysfunction is reversible, since the symptoms usually disappear with steroids or antiallergic treatment.


Assuntos
Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/cirurgia , Eosinofilia/cirurgia , Esofagite/cirurgia , Esofagoscopia , Esôfago/cirurgia , Corpos Estranhos/cirurgia , Adolescente , Criança , Eosinofilia/complicações , Esofagite/complicações , Feminino , Alimentos/efeitos adversos , Humanos , Masculino , Manometria
14.
Eur J Pediatr Surg ; 16(6): 403-6, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17211787

RESUMO

INTRODUCTION: The management of children receiving small bowel grafts involves potentially life-threatening complications that affect their nutritional status. The aim of this paper was to define these factors and their influence on nutritional outcome. PATIENTS AND METHODS: Patients with intestinal failure (IF) who received an isolated small bowel transplantation (SBT) or small bowel/liver transplantation (SBLT) at our hospital during the last 6 years were reviewed for weight Z-score, biochemical nutritional parameters, total parenteral nutrition (TPN) weaning, catheter-related sepsis, rejection and steroid treatment. RESULTS: Twenty patients, 11 females and 9 males, received a SBT or a SBLT and survived the postoperative period; in the present study we only included 11 children with follow-up periods longer than 1 year. Seven males and 4 females with a mean age of 4.5 years (range, 1 to 20 years) received 6 SBLT and 5 SBT. Nine (82%) were weaned from TPN to an amino-acid or peptide enteral formula during the first 6 months after surgery. During the first year there was a significant increase in total protein from 5.11 +/- 1.8 mg/dl to 6.1 +/- 1.5 mg/dl (p < 0.05) and an increase in albumin from 3.8 +/- 0.9 mg/dl to 4.5 +/- 1.1 mg/dl (p < 0.05). There was an increase in weight Z-score in 9 patients (82%) during the first year. Mean Z-score improved from - 2.6 +/- 1 at transplant to - 1.0 +/- 0.6 (p < 0.05) after 1 year. Three patients (27.2%) had at least one rejection period, which was treated with steroids alone or in combination. Mean weight Z-score 1 year after surgery was - 0.9 +/- 0.6 for patients without rejection and - 1.24 +/- 0.8 for those with at least one rejection episode treated with steroids (p > 0.1). Four patients (36%) had at least one catheter-related sepsis episode. Mean weight Z-score 1 year after surgery was - 1.01 +/- 0.6 for patients without catheter-related sepsis and - 1.24 +/- 0.8 for those with at least one catheter-related sepsis episode (p > 0.1). CONCLUSIONS: There was a significant improvement in weight Z-score and biochemical nutritional parameters 1 year after receiving a small bowel graft. No influence of steroids or catheter-related sepsis on children's nutritional status was noted 1 year after surgery, although this point will need further evaluation.


Assuntos
Enteropatias/cirurgia , Intestino Delgado/transplante , Transplante de Fígado , Estado Nutricional , Adolescente , Adulto , Peso Corporal , Criança , Pré-Escolar , Nutrição Enteral , Feminino , Humanos , Lactente , Masculino , Nutrição Parenteral Total , Resultado do Tratamento
15.
Arch Esp Urol ; 69(7): 393-7, 2016 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27617558

RESUMO

OBJECTIVES: Prostate cancer (PCa) is an androgen-dependent disease. In some cases, the tumor progresses despite castration levels of serum testosterone, turning into the lethal phenotype of castration-resistant prostate cancer (CRPC), still driven by androgens and requiring the androgen receptor as a driver and responsible for progression. Enzalutamide, an androgen receptor inhibitor, is indicated for the treatment of metastatic CRPC, asymptomatic or mildly symptomatic, after failure of androgen deprivation. In both clinical trials that led to its approval, Enzalutamide was administered with an LHRH analog, setting the "standard of care" for its use. In this article we evaluate the available evidence and theory on the use of Enzalutamide as monotherapy. METHODS: Androgen deprivation well-known adverse events, together with the fact that its clinical benefit is moderate and the evidence strength is weak, and the direct negative impact on the common chronic conditions affecting this age-group led to investigation of Enzalutamide without LHRH analogs. RESULTS: There are clinical trials on Enzalutamide monotherapy for hormone-sensitive prostate cancer with favourable outcomes, and there are also two ongoing studies in different advanced PCa scenarios, the PROSPER and EMBARK trials. It would be up to now a safe alternative, with less toxicity and lower costs. CONCLUSION: It is mandatory to validate these early results on the use on Enzalutamide monotherapy for advanced prostate cancer, hormone-sensitive or castration resistant, metastatic or not, but in the meantime, we wonder, why not?


Assuntos
Feniltioidantoína/análogos & derivados , Neoplasias da Próstata/tratamento farmacológico , Benzamidas , Humanos , Masculino , Estadiamento de Neoplasias , Nitrilas , Feniltioidantoína/uso terapêutico , Neoplasias da Próstata/patologia
16.
Transplant Proc ; 37(9): 4087-8, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16386633

RESUMO

The results of the isolated intestinal grafts were compared with those of composite grafts (intestinal graft + liver) in a series of 18 transplantations performed in 17 children; 5 isolated intestinal grafts, 12 hepatointestinal grafts, and 1 multivisceral graft. Causes of intestinal failure were short bowel syndrome (n = 13), motility disorders (n = 2) and congenital epithelial disorders (n = 2). Transplantation was indicated due to end-stage liver disease (n = 14), loss of venous access (n = 2), untreatable diarrhea (n = 1) and high morbidity associated with a poor quality of life (n = 1). Six children, all with a composite graft, died after transplantation due to lymphoma (n = 2), sepsis (n = 1); intraabdominal bleeding (n = 1); pneumonia (n = 1); and overwhelming adenoviral infection (n = 1). Digestive autonomy was achieved in 16 of 18 grafts, the 11 surviving children are free of parenteral nutrition with a reasonably good quality of life. In conclusion, intestinal transplantation is a viable therapeutic alternative for children with permanent intestinal failure. The results of transplantation with an isolated intestine are clearly better that those with a composite graft.


Assuntos
Resinas Compostas/uso terapêutico , Enteropatias/cirurgia , Intestinos/transplante , Síndrome do Intestino Curto/cirurgia , Adolescente , Adulto , Pré-Escolar , Feminino , Humanos , Lactente , Enteropatias/mortalidade , Enteropatias/terapia , Masculino , Síndrome do Intestino Curto/mortalidade , Síndrome do Intestino Curto/terapia , Análise de Sobrevida , Resultado do Tratamento
17.
Prensa méd. argent ; 106(1): 29-31, 20200000. ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1370101

RESUMO

Las lesiones traumáticas duodenales son infrecuentes pero producen una tasa de morbi-mortalidad significativa. Se debe tener presente la elevada frecuencia de lesiones asociadas, siendo las de uréter superior las más frecuentes. Masculino de 50 años ingresa por HAF paravertebral derecha. Al ingreso OTE, lucido, vigil, con dolor y defensa abdominal generalizada. En la TC toracobdominal con cte EV y VO se objetiva extravasación de contraste oral a nivel duodenal y en fase excretora renal derecha.Se decide Laparotomía de urgencia objetivando lesión transfixiante de 2da porción de duodeno de < 50% de su circunferencia y sección de uréter derecho proximal. Se realiza rafia en dos planos de duodeno, colocación de pig tail y anastomosis T-T de uréter derecho mas drenaje. Buena evolución postquirúrgica con control tomográfico a las 72 hs sin objetivar fuga. Alta hospitalaria al 6to día. El traumatismo duodenal es una patología rara que se asocia con una tasa considerable de morbimortalidad, su localización retroperitoneal puede hacer que los clásicos signos de peritonismo no estén presentes en el momento de la evaluación, por lo que se recomienda la realización de exámenes clínicos seriados y de estudios complementarios con contraste VO y EV. Las lesiones ureterales asociadas son las más frecuentes. La mayoría tienen una pérdida mínima de tejido, siendo usualmente reparadas mediante desbridación y anastomosis.


Duodenal traumatic injuries are rare but produce a significant morbidity and mortality rate. The high frequency of associated lesions should be kept in mind, with those of the upper ureter being the most frequent. 50-year-old male enters for right paravertebral HAF. At hospital admission, lucid patient and vigil. Thoracoabdominal CT with intravenous and oral contrast show extravasation of oral contrast at the duodenal level and in the right renal excretory phase. Emergency laparotomy is decided by objectifying transfixing lesion of the 2nd portion of the duodenum of <50% of its circumference and proximal right ureter section. Raffia is performed in two planes of the duodenum, placement of pig tail and TT anastomosis of the right ureter plus drainage. Good post-surgical evolution with tomographic control at 72 hours without objectifying leakage. Hospital discharge on the 6th day. Duodenal trauma is a rare pathology that is associated with a considerable morbidity and mortality rate, its retroperitoneal location may make the classic signs of peritonism not present at the time of the evaluation, so clinical exams are recommended series and complementary studies with VO and EV contrast. Associated ureteral lesions are the most frequent, Most have minimal tissue loss, usually repaired by debridement and anastomosis.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Ureter/lesões , Armas de Fogo , Anastomose Cirúrgica/métodos , Serviços Médicos de Emergência , Perfuração Intestinal/cirurgia , Laparotomia/métodos , Traumatismos Abdominais/cirurgia
18.
Neuroscience ; 113(4): 893-905, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12182895

RESUMO

The soluble N-ethylmaleimide-sensitive factor-attached protein receptor (SNARE) proteins syntaxin 1 and synaptosomal-associated protein-25 have been implicated in axonal outgrowth. Neuronal Sec1 (nSec1), also called murine unc18a (Munc18a), is a syntaxin 1-binding protein involved in the regulation of SNARE complex formation in synaptic vesicle membrane fusion. Here we analysed whether nSec1/Munc18a is involved in neurite formation. nSec1/Munc18a expressed under the control of an inducible promoter in differentiated PC12 cells as well as in hippocampal neurons appears first in the cell body, and at later times after induction along neurites and in growth cones. It is localised to distinct tubular and punctated structures. In addition, exogenous nSec1/Munc18a inhibited regulated secretion in PC12 cells. Overexpression in PC12 cells of nSec1/Munc18a or its homologue Munc18b, reduced the total length of neurites. This effect was enhanced with nSec1-T574A, a mutant that lacks a cyclin-dependent kinase 5 phosphorylation site and displays an increased binding to syntaxin 1. In contrast, in hippocampal neurons the total length of all primary neurites and branches was increased upon transfection of nSec1/Munc18a. Detailed morphometric analysis revealed that this was a consequence of an increased number of axonal side branches, while the average lengths in primary neurites and of side branches were not affected. From these results we suggest that nSec1/Munc18a is involved in the regulation of SNARE complex-dependent membrane fusion events implicated in the ramification of axonal processes in neurons.


Assuntos
Axônios/metabolismo , Hipocampo/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Proteínas de Transporte Vesicular/biossíntese , Animais , Axônios/efeitos dos fármacos , Células Cultivadas , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Humanos , Proteínas Munc18 , Proteínas do Tecido Nervoso/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células PC12 , Biossíntese de Proteínas , Proteínas/farmacologia , Ratos , Transfecção/métodos , Proteínas de Transporte Vesicular/farmacologia
19.
Am J Med Sci ; 319(3): 189-90, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10746831

RESUMO

An increasing number of anaerobic bloodstream infections in neutropenic cancer patients have been reported in the last decade. The type of anaerobes isolated from most of these patients suggests an oral source of infection. We describe a case of anaerobic bacteremia in a neutropenic patient with oral mucositis that highlights the importance of considering these organisms when selecting empiric prophylactic or therapeutic antimicrobial regimens, especially in the setting of periodontal disease or oral mucositis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bacteriemia/microbiologia , Bactérias Anaeróbias/isolamento & purificação , Neutropenia/induzido quimicamente , Neutropenia/complicações , Estomatite/microbiologia , Adolescente , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Citarabina/efeitos adversos , Eubacterium/isolamento & purificação , Fusobacterium necrophorum/isolamento & purificação , Humanos , Idarubicina/efeitos adversos , Leucemia Mielomonocítica Aguda/tratamento farmacológico , Masculino , Mucosa Bucal/microbiologia , Estomatite/tratamento farmacológico
20.
Clin Neurol Neurosurg ; 102(4): 236-239, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11154812

RESUMO

Intracranial infections are unusual manifestations of salmonellosis. Even with adequate medical and surgical interventions these infections are often associated with significant morbidity and mortality. We report a case of brain abscess caused by Salmonella enteritidis associated with a brain neoplasm and review previous reports in the literature.


Assuntos
Abscesso Encefálico/patologia , Neoplasias Encefálicas/complicações , Infecções por Salmonella/patologia , Salmonella enteritidis , Abscesso Encefálico/etiologia , Neoplasias Encefálicas/microbiologia , Craniotomia , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Salmonella/etiologia , Salmonella enteritidis/isolamento & purificação
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