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1.
Colorectal Dis ; 26(6): 1223-1230, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38702908

RESUMO

AIM: The aim of this work was to determine racial disparities in access to minimally invasive proctectomy using a national database. METHOD: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program evaluated for surgical approach (robotic, laparoscopic or open), demographics and comorbidity, and then compared by race. RESULTS: A total of 3511 patients (325 Asian, 2925 White, 261 African American/Black) with cancer who underwent a proctectomy between 2016 and 2020 were included. Both Asians and Whites had significantly higher rates of laparoscopic proctectomy relative to African Americans (38.5%, 33.8% and 28.7%, respectively; p = 0.0001). Asians had the highest rate of robotic proctectomy (38.2%, p = 0.0001). Conversely, Black patients had significantly higher rates of open proctectomy followed by Whites and then Asians (42.1%, 35.4% and 23.4%, respectively; p = 0.0001). In multivariable logistic regression with backward elimination, African Americans were 0.7 times as likely to undergo laparoscopic proctectomy and 1.4 times more likely to undergo open proctectomy than Whites (p = 0.043). Compared with Whites, Asians were 1.8, 1.7 and 1.9 times more likely to undergo minimally invasive, laparoscopic proctectomy and robotic proctectomy, respectively (p = 0.0001, p = 0.001, p = 0.0001). CONCLUSION: Asians had the highest rate of laparoscopic and robotic proctectomy, while Blacks had the highest rate of open proctectomy. African Americans were least likely to undergo laparoscopic proctectomy compared with all races. Race is an independent risk factor for access to minimally invasive proctectomy.


Assuntos
Negro ou Afro-Americano , Disparidades em Assistência à Saúde , Laparoscopia , Protectomia , Melhoria de Qualidade , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , População Branca , Humanos , Masculino , Feminino , Neoplasias Retais/cirurgia , Neoplasias Retais/etnologia , Protectomia/estatística & dados numéricos , Protectomia/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Idoso , Laparoscopia/estatística & dados numéricos , Laparoscopia/métodos , Negro ou Afro-Americano/estatística & dados numéricos , População Branca/estatística & dados numéricos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Estados Unidos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Asiático/estatística & dados numéricos , Modelos Logísticos , Bases de Dados Factuais
2.
Curr Opin Obstet Gynecol ; 36(4): 239-246, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38743685

RESUMO

PURPOSE OF REVIEW: This review aims to summarize recent literature on the surgical treatment of colorectal endometriosis. RECENT FINDINGS: The last decade has seen a surge in the number of studies on bowel endometriosis, with a focus on preoperative evaluation, perioperative management, surgical approach, and surgical outcomes. Many of these studies have originated from large-volume referral centers with varying surgical approaches and philosophies. Colorectal surgery for endometriosis seems to have a positive impact on patient symptoms, quality of life, and fertility. However, these benefits must be weighed against a significant risk of postoperative complications and the potential for long-term bowel or bladder dysfunction, especially for more radical procedures involving the lower rectum. Importantly, most studies regarding surgical technique and outcomes have been limited by their observational design. SUMMARY: The surgical management of bowel endometriosis is complex and should be approached by a multidisciplinary team. Methodical preoperative evaluation, including appropriate imaging, is vital for surgical planning and patient counseling. The decision to perform a more conservative or radical excision is nuanced and remains an area of controversy. High quality studies in the form of multicenter randomized controlled trials are needed before clear recommendations can be made.


Assuntos
Endometriose , Qualidade de Vida , Doenças Retais , Humanos , Endometriose/cirurgia , Feminino , Doenças Retais/cirurgia , Complicações Pós-Operatórias/etiologia , Doenças do Colo/cirurgia , Resultado do Tratamento , Laparoscopia/métodos
3.
Int J Colorectal Dis ; 39(1): 1, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38055072

RESUMO

PURPOSE: We aimed to describe the incidence and identify risk factors for the occurrence of short-term major posto-perative complications following colorectal resection for endometriosis. METHODS: A cohort study using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database from 2012-2020. We included patients with a primary diagnosis of endometriosis who underwent colon or rectal resections for endometriosis. RESULTS: Of 755 women who underwent colorectal resection, 495 (65.6%) had laparoscopic surgery and 260 (34.4%) had open surgery. The major complication rate was 13.5% (n = 102). Women who underwent open surgery had a higher proportion of major complications (n = 53, 20.4% vs. n = 49, 9.9%, p < 0.001). In a multivariable regression analysis, Black race (aOR 95%CI 2.81 (1.60-4.92), p < 0.001), Hispanic ethnicity (aOR 95%CI 3.02 (1.42-6.43), p = 0.004), hypertension (aOR 95%CI 1.89 (1.08-3.30), p = 0.025), laparotomy (aOR 95%CI 1.64 (1.03-3.30), p = 0.025), concomitant enterotomy (aOR 95%CI 3.02 (1.26-7.21), p = 0.013), and hysterectomy (aOR 95%CI 2.59 (1.62-4.15), p < 0.001) were independently associated with major post-operative complications. In a subanalysis of laparoscopies only, Hispanic ethnicity, chronic hypertension, lysis of bowel adhesions, and hysterectomy were independently associated with major complications. In a subanalysis of laparotomies only, Black race and hysterectomy were independently positively associated with the occurrence of major complications. CONCLUSION: This study provides a current population-based estimate of short-term complications after surgery for colorectal endometriosis in the USA. The identified risk factors for complications can assist during preoperative shared decision-making and informed consent process.


Assuntos
Neoplasias Colorretais , Endometriose , Hipertensão , Humanos , Feminino , Estados Unidos/epidemiologia , Endometriose/cirurgia , Estudos de Coortes , Fatores de Risco
4.
Int J Mol Sci ; 24(24)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38139086

RESUMO

Given the need to improve the sensitivity of non-invasive methods to detect colorectal neoplasia, particularly adenomas, we compared a fecal test using a monoclonal antibody (Mab) raised against constituents of colonic adenomas designated Adnab-9 (Adenoma Antibody 9), recognizing an N-linked 87 kDa glycoprotein, to gFOBT, which is shown to reduce CRC mortality. p87 immunohistochemistry testing is significantly more sensitive (OR 3.64[CI 2.37-5.58]) than gFOBT (guaiac-based fecal occult blood test) for adenomas (<3 in number), advanced adenomas (OR 4.21[CI 2.47-7.15]), or a combination of the two (OR 3.35[CI 2.47-4.53]). p87 immunohistochemistry shows regional Paneth cell (PC) expression mainly in the right-sided colon and is significantly reduced in the ceca of African Americans (p < 0.0001). In a subset of patients, we obtained other body fluids such as urine, colonic effluent, and saliva. Urine tests (organ-specific neoantigen) showed a significant difference for advanced adenomas (p < 0.047). We conclude that fecal p87 testing is more sensitive than gFOBT and Adnab-9 and could be used to better direct the colonoscopy screening effort.


Assuntos
Adenoma , Neoplasias Colorretais , Humanos , Guaiaco , Sangue Oculto , Programas de Rastreamento/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Colonoscopia/métodos , Adenoma/diagnóstico , Sensibilidade e Especificidade , Detecção Precoce de Câncer/métodos
5.
Bioengineering (Basel) ; 10(10)2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37892886

RESUMO

This research study is the preliminary phase of an effort to develop a generic data transfer method via human haptic thermal sensation (i.e., a coded language such as Morse or Braille). For the method to be effective, it must include a large variety of short, recognizable cues. Hence, we propose the concept of cues based on sequences of thermal pulses: combinations of warm and cool pulses with several levels of intensity. The objective of this study was to determine the feasibility of basing a generic data transfer method on haptic thermal cues using sequences of short pulses. The research included defining the basic characteristics of the stimuli parameters and developing practical methods for generating and measuring them. Several patterns of different sequences were designed considering the relevant data known to date and improved by implementing new insights acquired throughout the tests that were conducted. The final thermal cues presented to the participants were sensed by touch and clearly recognized. The results of this study indicate that developing this new method is feasible and that it could be applicable in various scenarios. In addition, the low impact measured on the user's skin temperature represents an inherent advantage for future implementation. This report presents promising findings and offers insights for further investigations.

6.
Int J Mol Sci ; 24(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37108697

RESUMO

SARS-CoV-2 severity predictions are feasible, though individual susceptibility is not. The latter prediction allows for planning vaccination strategies and the quarantine of vulnerable targets. Ironically, the innate immune response (InImS) is both an antiviral defense and the potential cause of adverse immune outcomes. The competition for iron has been recognized between both the immune system and invading pathogens and expressed in a ratio of ferritin divided by p87 (as defined by the Adnab-9 ELISA stool-binding optical density, minus the background), known as the FERAD ratio. Associations with the FERAD ratio may allow predictive modeling for the susceptibility and severity of disease. We evaluated other potential COVID-19 biomarkers prospectively. Patients with PCR+ COVID-19 tests (Group 1; n = 28) were compared to three other groups. In Group 2 (n = 36), and 13 patients displayed COVID-19-like symptoms but had negative PCR or negative antibody tests. Group 3 (n = 90) had no symptoms and were negative when routinely PCR-tested before medical procedures. Group 4 (n = 2129) comprised a pool of patients who had stool tests and symptoms, but their COVID-19 diagnoses were unknown; therefore, they were chosen to represent the general population. Twenty percent of the Group 4 patients (n = 432) had sufficient data to calculate their FERAD ratios, which were inversely correlated with the risk of COVID-19 in the future. In a case report of a neonate, we studied three biomarkers implicated in COVID-19, including p87, Src (cellular-p60-sarcoma antigen), and Abl (ABL-proto-oncogene 2). The InImS of the first two were positively correlated. An inverse correlation was found between ferritin and lysozyme in serum (p < 0.05), suggesting that iron could have impaired an important innate immune system anti-viral effector and could partially explain future COVID-19 susceptibility.


Assuntos
COVID-19 , Humanos , Recém-Nascido , Biomarcadores Tumorais , COVID-19/epidemiologia , Ferritinas , Sistema Imunitário , Ferro , Pandemias , Estudos Prospectivos , SARS-CoV-2
7.
Circulation ; 146(8): 587-596, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35880530

RESUMO

BACKGROUND: Understanding the predictive utility of previously derived polygenic risk scores (PRSs) for long-term risk of coronary heart disease (CHD) and its additive value beyond traditional risk factors can inform prevention strategies. METHODS: Data from adults 20 to 59 years of age who were free of CHD from the FOS (Framingham Offspring Study) and the ARIC (Atherosclerosis Risk in Communities) study were analyzed. Because the PRS was derived from samples of predominantly European ancestry, individuals who self-reported White race were included. The sample was stratified by age and cohort: young (FOS, 20-39 years [median, 30 years] of age), early midlife (FOS, 40-59 years [median, 43] years of age), and late midlife (ARIC, 45-59 years [median, 52 years] of age). Two previously derived and validated prediction tools were applied: (1) a 30-year traditional risk factor score and (2) a genome-wide PRS comprising >6 million genetic variants. Hazard ratios for the association between each risk estimate and incident CHD were calculated. Predicted and observed rates of CHD were compared to assess discrimination for each model individually and together with the optimism-corrected C index (95% CI). RESULTS: Among 9757 participants, both the traditional risk factor score (hazard ratio per 1 SD, 2.60 [95% CI, 2.08-3.27], 2.09 [95% CI, 1.83-2.40], and 2.11 [95% CI, 1.96-2.28]) and the PRS (hazard ratio, 1.98 [95% CI, 1.70-2.30], 1.64 [95% CI, 1.47-1.84], and 1.22 [95% CI, 1.15-1.30]) were significantly associated with incident CHD in young, early midlife, and late midlife, respectively. Discrimination was similar or better for the traditional risk factor score (C index, 0.74 [95% CI, 0.70-0.78], 0.70 [95% CI, 0.67-0.72], and 0.72 [95% CI, 0.70-0.73]) compared with an age- and sex-adjusted PRS (0.73 [95% CI, 0.69-0.78], 0.66 [95% CI, 0.62-0.69], and 0.66 [95% CI, 0.64-0.67]) in young, early-midlife, and late-midlife participants, respectively. The ΔC index when PRS was added to the traditional risk factor score was 0.03 (95% CI, 0.001-0.05), 0.02 (95% CI, -0.002 to 0.037), and 0.002 (95% CI, -0.002 to 0.006) in young, early-midlife, and late-midlife participants, respectively. CONCLUSIONS: Despite a statistically significant association between PRS and 30-year risk of CHD, the C statistic improved only marginally with the addition of PRS to the traditional risk factor model among young adults and did not improve among midlife adults. PRS, an immutable factor that cannot be directly intervened on, has minimal clinical utility for long-term CHD prediction when added to a traditional risk factor model.


Assuntos
Doença das Coronárias , Predisposição Genética para Doença , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Doença das Coronárias/genética , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Adulto Jovem
8.
Artigo em Inglês | MEDLINE | ID: mdl-34250398

RESUMO

Patients with EGFR-mutant lung cancer have no approved targeted therapies after disease progression on first-line osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Preclinical studies suggest that tumors with both EGFR-sensitizing alteration and acquired second-site EGFR resistance alterations after treatment with osimertinib retain sensitivity to second-generation EGFR TKIs. We hypothesized that dacomitinib, a pan-human epidermal growth factor receptor TKI, may be effective in this setting. METHODS: In this phase II study, patients who had progressed on first-line osimertinib were treated with dacomitinib 45 mg orally daily until disease progression or intolerability. The primary end point was objective response rate. RESULTS: We enrolled 12 patients. Two partial responses were documented (17% objective response rate; 95% CI, 5 to 45). The median progression-free survival was 1.8 months (95% CI, 1.6 to not reached). One patient with an original sensitizing EGFR G719A mutation and one patient without molecular testing available had partial responses, whereas 0 of the 3 patients with second-site acquired EGFR resistance mutations (two C797S and one G724S) met the response criteria. The patient with EGFR G719A has an ongoing response at 17 months, which exceeds prior time on osimertinib (11 months). CONCLUSION: In the first trial evaluating a second-generation EGFR TKI after first-line third-generation osimertinib, we found that dacomitinib after disease progression on osimertinib has limited benefit.


Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Quinazolinonas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Projetos Piloto , Estudos Prospectivos , Retratamento
10.
Am J Surg ; 218(6): 1239-1243, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31399196

RESUMO

BACKGROUND: There is little consensus with regards to the most appropriate surgical management for low-grade appendiceal mucinous adenocarcinomas (LAMA), though right hemicolectomy is usually recommended. METHODS: The SEER database was queried for all patients with non-metastatic LAMA. Disease specific and overall survival was compared by surgery type: 1) appendectomy, 2) formal right hemicolectomy 3) non-formal colectomy (including ileocecectomy). RESULTS: A total of 579 patients with non-metastatic LAMA were identified. 133 (23%), 404 (70%), and 42 (7%) of patients had stage I, II, and III disease, respectively. 99 (17.1%) had appendectomy, 87 (15%) had non-formal colectomy, and 302 (52.2%) had formal right hemicolectomy. We observed no significant differences in disease specific or overall survival by surgery type. Controlling for age and stage, surgery type was not a significant predictor of disease specific or overall survival. CONCLUSION: In patients with localized LAMA, right hemicolectomy did not increase disease specific or overall survival. Right hemicolectomy should be reserved for LAMA patients with positive margins post appendectomy.


Assuntos
Adenocarcinoma Mucinoso/cirurgia , Neoplasias do Apêndice/cirurgia , Colectomia/métodos , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apendicectomia , Neoplasias do Apêndice/patologia , Feminino , Humanos , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Seleção de Pacientes , Programa de SEER , Taxa de Sobrevida
11.
J Pediatr Urol ; 15(1): 69.e1-69.e3, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30449678

RESUMO

OBJECTIVE: To report very rarely encountered scrotal injuries during neonatal circumcision. Hospitals and physicians in the authors' country are mandated to report circumcision complications to the Ministry of Health. Those reports include the discharge summary from the emergency room or the admitting department. This is believed to be the first case series describing scrotal injuries during ritual circumcision. PATIENTS AND METHODS: Reports of all circumcision complications between 2007 and 2014 were evaluated. Retrieved data on cases of scrotal injuries included patient's age, time between injury and hospital admission, nature of the injury, and administered treatment. RESULTS: Twelve of a total of 489 reports of circumcision injuries involved the scrotum (2.5%). All circumcisions were performed during the neonatal period, and the infants were admitted on the day of injury. The only related genital injury was significant shortage of penile skin reported in six patients. Scrotal exploration and skin closure in the operating room was undertaken in six cases, five under general anesthesia. Suture closure in the emergency department was performed in three patients, and the scrotal skin was left to heal with secondary intention in three other patients. Scrotal content injury that extended to the tunica vaginalis of the testis was noted in one exploration. DISCUSSION: The injuries sustained by the 12 study infants were mostly superficial and are not expected to cause long-term damage, although half of the patients required treatment under general anesthesia in the operating room or under sedation in the emergency department. While all reported patients emerged unscathed from the anesthetic procedures, the possible immediate complications of anesthesia as well as its long-term effects are not to be taken lightly, especially when treating a newborn. Further education of medical providers as well as performers of ritual circumcisions may help lower the risk of this rare injury as well as other more severe complications. CONCLUSION: Scrotal injury during neonatal circumcision is rare. While half of the 12 reported patients required exploration in the operating room, the injuries were mostly superficial and did not involve scrotal content, although they often involved extensive resection of penile skin.


Assuntos
Circuncisão Masculina/efeitos adversos , Complicações Intraoperatórias/etiologia , Escroto/lesões , Comportamento Ritualístico , Humanos , Recém-Nascido , Masculino
12.
Proteins ; 86(2): 229-236, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29178591

RESUMO

A rational design of protein complexes with defined functionalities and of drugs aimed at disrupting protein-protein interactions requires fundamental understanding of the mechanisms underlying the formation of specific protein complexes. Efforts to develop efficient small-molecule or protein-based binders often exploit energetic hot spots on protein surfaces, namely, the interfacial residues that provide most of the binding free energy in the complex. The molecular basis underlying the unusually high energy contribution of the hot spots remains obscure, and its elucidation would facilitate the design of interface-targeted drugs. To study the nature of the energetic hot spots, we analyzed the backbone dynamic properties of contact surfaces in several protein complexes. We demonstrate that, in most complexes, the backbone dynamic landscapes of interacting surfaces form complementary "stability patches," in which static areas from the opposing surfaces superimpose, and that these areas are predominantly located near the geometric center of the interface. We propose that a diminished enthalpy-entropy compensation effect augments the degree to which residues positioned within the complementary stability patches contribute to complex affinity, thereby giving rise to the energetic hot spots. These findings offer new insights into the nature of energetic hot spots and the role that backbone dynamics play in facilitating intermolecular recognition. Mapping the interfacial stability patches may provide guidance for protein engineering approaches aimed at improving the stability of protein complexes and could facilitate the design of ligands that target complex interfaces.


Assuntos
Proteínas/química , Animais , Bases de Dados de Proteínas , Humanos , Simulação de Dinâmica Molecular , Ligação Proteica , Mapas de Interação de Proteínas , Estabilidade Proteica , Proteínas/metabolismo , Termodinâmica
13.
Gene Ther ; 23(3): 237-46, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26588709

RESUMO

Small caliber synthetic vascular grafts are commonly used for bypass surgery and dialysis access sites but have high failure rates because of neointima formation and thrombosis. Seeding synthetic grafts with endothelial cells (ECs) provides a biocompatible surface that may prevent graft failure. However, EC detachment following exposure to blood flow still remains a major obstacle in the development of biosynthetic grafts. We tested the hypothesis that induced expression by the seeded EC, of vascular endothelial growth factor165 (VEGF165) and of fibulin-5, an extracellular matrix glycoprotein that has a crucial role in elastin fiber organization and increase EC adherence to surfaces, may improve long-term graft patency. Autologous ECs were isolated from venous segments, and were transduced with retroviral vectors expressing fibulin-5 and VEGF165. The modified cells were seeded on expanded polytetrafluoroethylene (ePTFE) grafts and implanted in a large animal model. Three months after transplantation, all grafts seeded with modified EC were patent on a selective angiography, whereas only a third of the control grafts were patent. Similar results were shown at 6 months. Thus, seeding ePTFE vascular grafts with genetically modified EC improved long-term small caliber graft patency. The biosynthetic grafts may provide a novel therapeutic modality for patients with peripheral vascular disease and patients requiring vascular access for hemodialysis.


Assuntos
Células Endoteliais/transplante , Proteínas da Matriz Extracelular/uso terapêutico , Doenças Vasculares Periféricas/terapia , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Enxerto Vascular/métodos , Animais , Células Endoteliais/fisiologia , Proteínas da Matriz Extracelular/genética , Humanos , Modelos Animais , Ratos , Ovinos , Fator A de Crescimento do Endotélio Vascular/genética , Grau de Desobstrução Vascular
14.
Gastroenterol Clin North Am ; 42(4): 801-13, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24280401

RESUMO

Pruritus ani is a common condition with multiple causes. Primary causes are thought to be fecal soiling or food irritants. Secondary causes include malignancy, infections including sexually transmitted diseases, benign anorectal diseases, systemic diseases, and inflammatory conditions. A broad differential diagnosis must be considered. A reassessment of the diagnosis is required if symptoms or findings are not responsive to therapy. The pathophysiology of itching, an overview of primary and secondary causes, and various treatment options are reviewed.


Assuntos
Prurido Anal/diagnóstico , Neoplasias do Ânus/complicações , Neoplasias do Ânus/diagnóstico , Candidíase/complicações , Candidíase/diagnóstico , Carcinoma in Situ/complicações , Carcinoma in Situ/diagnóstico , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Dermatite Seborreica/complicações , Dermatite Seborreica/diagnóstico , Herpes Zoster/complicações , Herpes Zoster/diagnóstico , Humanos , Líquen Plano/complicações , Líquen Plano/diagnóstico , Líquen Escleroso e Atrófico/complicações , Líquen Escleroso e Atrófico/diagnóstico , Doença de Paget Extramamária/complicações , Doença de Paget Extramamária/diagnóstico , Prurido Anal/etiologia , Prurido Anal/terapia , Psoríase/complicações , Psoríase/diagnóstico , Uremia/complicações , Uremia/diagnóstico
15.
Ann Thorac Surg ; 96(4): 1480-1481, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24088469

RESUMO

This report documents a case of completely spontaneous ascending aortic disruption. A 54-year-old African American male day laborer presented with severe retro-sternal chest and back pain and shortness of breath. He had no history of hypertension, smoking, or trauma and was taking no medications. The computed tomographic angiography scan performed to exclude pulmonary embolism instead demonstrated a hemorrhagic pericardial effusion and an ascending aortic pseudoaneurysm. He was taken emergently to the operating room for repair of his ascending aorta. The histopathology report was normal.


Assuntos
Ruptura Aórtica , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Ruptura Espontânea
16.
PLoS Comput Biol ; 9(4): e1003028, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23592972

RESUMO

Knowledge of the structural basis of protein-protein interactions (PPI) is of fundamental importance for understanding the organization and functioning of biological networks and advancing the design of therapeutics which target PPI. Allosteric modulators play an important role in regulating such interactions by binding at site(s) orthogonal to the complex interface and altering the protein's propensity for complex formation. In this work, we apply an approach recently developed by us for analyzing protein surfaces based on steered molecular dynamics simulation (SMD) to the study of the dynamic properties of functionally distinct conformations of a model protein, calmodulin (CaM), whose ability to interact with target proteins is regulated by the presence of the allosteric modulator Ca(2+). Calmodulin is a regulatory protein that acts as an intracellular Ca(2+) sensor to control a wide variety of cellular processes. We demonstrate that SMD analysis is capable of pinpointing CaM surfaces implicated in the recognition of both the allosteric modulator Ca(2+) and target proteins. Our analysis of changes in the dynamic properties of the CaM backbone elicited by Ca(2+) binding yielded new insights into the molecular mechanism of allosteric regulation of CaM-target interactions.


Assuntos
Cálcio/química , Calmodulina/química , Mapeamento de Interação de Proteínas/métodos , Sítio Alostérico , Sítios de Ligação , Biologia Computacional/métodos , Proteínas Fúngicas/química , Íons , Modelos Moleculares , Simulação de Dinâmica Molecular , Probabilidade , Ligação Proteica , Estrutura Terciária de Proteína , Saccharomyces cerevisiae , Propriedades de Superfície
17.
Front Cell Neurosci ; 6: 37, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22973194

RESUMO

Professional deep-water divers exposed to high pressure (HP) above 1.1 MPa suffer from High Pressure Neurological Syndrome (HPNS), which is associated with CNS hyperexcitability. We have previously reported that HP augments N-methyl-D-aspartate receptor (NMDAR) synaptic responses, increases neuronal excitability, and potentially causes irreversible neuronal damage. We now report that HP (10.1 MPa) differentially affects eight specific NMDAR subtypes. GluN1(1a or 1b) was co-expressed with one of the four GluN2(A-D) subunits in Xenopus laevis oocytes. HP increased ionic currents (measured by two electrode voltage clamps) of one subtype, reduced the current in four others, and did not affect the current in the remaining three. 3D theoretical modeling was aimed at revealing specific receptor domains involved with HP selectivity. In light of the information on the CNS spatial distribution of the different NMDAR subtypes, we conclude that the NMDAR's diverse responses to HP may lead to selective HP effects on different brain regions. These discoveries call for further and more specific investigation of deleterious HP effects and suggest the need for a re-evaluation of deep-diving safety guidelines.

18.
J Mol Biol ; 415(2): 419-28, 2012 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-22100447

RESUMO

Understanding the structural basis of protein-protein interactions (PPIs) may shed light on the organization and functioning of signal transduction and metabolic networks and may assist in structure-based design of ligands (drugs) targeting protein-protein interfaces. The residues at the bimolecular interface, designated as the hot spots, contribute most of the free binding energy of PPI. To date, there is no conclusive atomistic explanation for the unique functional properties of the hot spots. We hypothesized that backbone compliance may play a role in protein-protein recognition and in the mechanism of binding of small-molecule compounds to protein surfaces. We used a steered molecular dynamics simulation to explore the compliance properties of the backbone of surface-exposed residues in several model proteins: interleukin-2, mouse double minute protein 2 and proliferating cell nuclear antigen. We demonstrated that protein surfaces exhibit distinct patterns in which highly immobile residues form defined clusters ("stability patches") alternating with areas of moderate to high mobility. These "stability patches" tend to localize in functionally important regions involved in protein-protein recognition. We propose a mechanism by which the distinct structural organization of the hot spots may contribute to their role in mediating PPI and facilitating binding of structurally diverse small-molecule compounds to protein surfaces.


Assuntos
Interleucina-2/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Domínios e Motivos de Interação entre Proteínas , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Animais , Humanos , Interleucina-2/química , Camundongos , Modelos Moleculares , Simulação de Dinâmica Molecular , Antígeno Nuclear de Célula em Proliferação/química , Ligação Proteica , Conformação Proteica , Proteínas Proto-Oncogênicas c-mdm2/química
19.
Biochem Biophys Res Commun ; 348(3): 1024-33, 2006 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-16904068

RESUMO

BACKGROUND: Fibulin-5 is a novel extracellular protein that is thought to act as a bridging peptide between elastin fibers and cell surface integrins in blood vessel wall. Fibulin-5 binding to endothelial cell (EC) surface integrins may effect cell proliferation and cell attachment to extracellular matrix (ECM) or to artificial surfaces. In this paper, we describe the effects of fibulin-5 on attachment, adhesion, and proliferation of primary human EC. After demonstrating that fibulin-5 over-expression inhibited EC proliferation, we tested the hypothesis that co-expression of fibulin-5 and VEGF165 will lead to unique EC phenotype that will exhibit increased adherence properties and retain its proliferation capacity. METHODS AND RESULTS: Fibulin-5 and VEGF165 gene transfer to primary human saphenous vein endothelial cells was accomplished using retroviral vectors encoding the two genes. Transgene expression was verified using immunohistochemistry, Western blotting, and ELISA. Fibulin 5 over-expression tended to improve immediate EC attachment (30 min after seeding) and improved significantly adhesion (>40%) under shear stress tested 24h after EC seeding. The effects of fibulin-5 and VEGF165 on EC proliferation in the presence or absence of basic FGF were also tested. EC expressing fibulin-5 had reduced proliferation while VEGF165 co-expression ameliorated this effect. CONCLUSION: Fibulin-5 improved EC attachment to artificial surfaces. Dual transfer of fibulin-5 and VEGF165 resulted in EC phenotype with increased adhesion and improved proliferation. This unique EC phenotype can be useful for tissue engineering on endovascular prostheses.


Assuntos
Proliferação de Células , Células Endoteliais/citologia , Células Endoteliais/fisiologia , Proteínas da Matriz Extracelular/fisiologia , Inibidores do Crescimento/fisiologia , Adesão Celular/fisiologia , Separação Celular , Células Cultivadas , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Proteínas da Matriz Extracelular/genética , Técnicas de Transferência de Genes , Inibidores do Crescimento/genética , Humanos
20.
Lancet ; 367(9515): 987-91, 2006 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-16564360

RESUMO

BACKGROUND: The Bedouin Arab population of southern Israel is in transition from a semi-nomadic lifestyle to permanent settlement, with many characteristics of a third-world population. A major outbreak of measles in the winter of 1990-91, with an incidence of 415.6 per 100,000 and a case fatality rate of 2.2 % among the Bedouin, led to the establishment of a national committee, which recommended an intervention programme. We report on the effect of the programme implementation on the reduction of vaccine-preventable communicable diseases in a Bedouin Arab population. METHODS: We compared immunisation coverage and incidence of reportable vaccine-preventable communicable diseases before and after implementation of the intervention programme. FINDINGS: Implementation of the intervention programme was associated with a marked increase in immunisation coverage, from 53% for first measles immunisation among those born in 1988, and reaching 2 years of age in 1990 at the start of the outbreak, to 90% at age 2 years among those born in 2001. We noted a decrease in all vaccine-preventable communicable diseases, except for pertussis, during this period. INTERPRETATION: The implementation of a targeted programme to improve immunisation coverage, and other concomitant changes in health-care delivery, was temporally associated with reduction of vaccine-preventable communicable diseases in a population of Bedouin Arabs in Israel who are living in semi-nomadic conditions. The success of the programme could be applicable to semi-nomadic populations living in other areas of the middle east.


Assuntos
Árabes , Surtos de Doenças/prevenção & controle , Programas de Imunização/organização & administração , Sarampo/epidemiologia , Serviços Preventivos de Saúde/organização & administração , Adolescente , Adulto , Criança , Pré-Escolar , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Feminino , Humanos , Programas de Imunização/estatística & dados numéricos , Incidência , Lactente , Israel/epidemiologia , Masculino , Sarampo/mortalidade , Sarampo/prevenção & controle , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Serviços Preventivos de Saúde/estatística & dados numéricos , Sistema de Registros
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