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Projetos de Pesquisa
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Departamento de Cirurgia, Faculdade de Medicina - Docente
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 10 de 116
  • article 3 Citação(ões) na Scopus
    Effects of diazoxide in experimental acute necrotizing pancreatitis
    (2017) ANDRADE, Roberta de Oliveira; KUNITAKE, Tiago; KOIKE, Marcia Kiyomi; MACHADO, Marcel C. C.; SOUZA, Heraldo Possolo
    OBJECTIVE: We aimed to assess the effects of diazoxide on the mortality, pancreatic injury, and inflammatory response in an experimental model of acute pancreatitis. METHODS: Male Wistar rats (200-400 g) were divided randomly into two groups. Fifteen minutes before surgery, animals received physiological (0.9%) saline (3 mL/kg) (control group) or 45 mg/kg diazoxide (treatment group) via the intravenous route. Acute pancreatitis was induced by injection of 2.5% sodium taurocholate via the biliopancreatic duct. Mortality (n= 38) was observed for 72 h and analyzed by the Mantel-Cox Log-rank test. To study pancreatic lesions and systemic inflammation, rats (10 from each group) were killed 3 h after acute pancreatitis induction; ascites volume was measured and blood as well as pancreases were collected. Pancreatic injury was assessed according to Schmidt's scale. Cytokine expression in plasma was evaluated by the multiplex method. RESULTS: Mortality at 72 h was 33% in the control group and 60% in the treatment group (p = 0.07). Ascites volumes and plasma levels of cytokines between groups were similar. No difference was observed in edema or infiltration of inflammatory cells in pancreatic tissues from either group. However, necrosis of acinar cells was lower in the treatment group compared to the control group (3.5 vs. 3.75, p = 0.015). CONCLUSIONS: Treatment with diazoxide can reduce necrosis of acinar cells in an experimental model of acute pancreatitis, but does not affect the inflammatory response or mortality after 72 h.
  • article 17 Citação(ões) na Scopus
    Cathelicidin-deficient mice exhibit increased survival and upregulation of key inflammatory response genes following cecal ligation and puncture
    (2017) SEVERINO, Patricia; ARIGA, Suely Kubo; BARBEIRO, Hermes Vieira; LIMA, Thais Martins de; SILVA, Elisangela de Paula; BARBEIRO, Denise Frediani; MACHADO, Marcel Cerqueira Cesar; NIZET, Victor; SILVA, Fabiano Pinheiro da
    Antimicrobial peptides possess a myriad of molecular properties including bacterial killing and the regulation of many aspects of innate immunity. Cathelicidins are a group of antimicrobial peptides widely investigated by the scientific community. Many studies have focused on the bactericidal and pro-inflammatory roles of cathelicidins. Because the role of endogenous cathelicidin expression remains obscure in deep-seated systemic infections, we induced sepsis in cathelicidin knockout and wild-type (WT) mice by cecal ligation and puncture, performing transcriptome screening by DNA micro-array in conjunction with other immunologic assays. Cathelicidin-deficient mice showed increased survival compared to WT mice in this established experimental model of polymicrobial sepsis, in association with upregulation of certain key inflammatory response genes. Therefore, cathelicidins can exert both pro- and anti-inflammatory activities depending on the disease and cellular context.
  • article 16 Citação(ões) na Scopus
    Systematic use of isolated pancreatic anastomosis after pancreatoduodenectomy: Five years of experience with zero mortality
    (2016) MACHADO, M. C. C.; MACHADO, M. A. C.
    Objective: The aim of this study is to perform a comprehensive evaluation of 5 years of experience with the technique of isolated pancreatic anastomosis reconstruction after pancreatoduodenectomy from the perspective of safety and surgical efficacy using a prospective database. Methods: The study included all consecutive patients undergoing pancreatoduodenectomy from April 2009 to April 2014 at a single referral center for hepato-pancreato-biliary diseases. The primary endpoint was the safety of the procedures, which was assessed as the occurrence of complications during hospitalization. Ninety-day mortality was also assessed. Postoperative pancreatic fistulas were classified as grade A, B, or C according to the International Study Group of Pancreatic Fistula classification. Results: The study group included 214 consecutive patients with a median age of 60 years who underwent pancreatoduodenectomy. Portal vein resection was performed on 41 patients. Indications for resection were 165 pancreatic head tumors, 33 ampullary tumors, 7 chronic pancreatitis, 3 distal bile duct tumors, and 6 duodenal tumors. There was no perioperative or 90-day mortality in this series. Complications occurred in 68 patients (32%), and 42 patients presented with pancreatic fistulas (19.6%). Grade A fistulas were present in 38 patients. Three patients presented persistent pancreatic fistula and were treated with percutaneous drainage. One patient developed combined pancreatic and biliary fistulas and was reoperated on for pancreatic abscess drainage. Conclusions: The technique of isolated pancreatic anastomosis by diverting the pancreatic from biliary secretion may contribute to reducing the severity of pancreatic fistulas and therefore the severity of this complication. (C) 2016 The Author(s).
  • article 13 Citação(ões) na Scopus
    Laparoscopic Pylorus-Preserving Pancreatoduodenectomy with Double Jejunal Loop Reconstruction: An Old Trick for a New Dog
    (2013) MACHADO, Marcel Autran C.; MAKDISSI, Fabio F.; SURJAN, Rodrigo C. T.; MACHADO, Marcel C. C.
    Background: Pancreatoduodenectomy is an established procedure for the treatment of benign and malignant diseases located at the pancreatic head and periampullary region. In order to decrease morbidity and mortality, we devised a unique technique using two different jejunal loops to avoid activation of pancreatic juice by biliary secretion and therefore reduce the severity of pancreatic fistula. This technique has been used for open pancreatoduodenectomy worldwide but to date has never been described for laparoscopic pancreatoduodenectomy. This article reports the technique of laparoscopic pylorus-preserving pancreatoduodenectomy with two jejunal loops for reconstruction of the alimentary tract. Materials and Methods: After pancreatic head resection, retrocolic end-to-side pancreaticojejunostomy with duct-to-mucosa anastomosis is performed. The jejunal loop is divided with a stapler, and side-to-side jejunojejunostomy is performed with the stapler, leaving a 40-cm jejunal loop for retrocolic hepaticojejunostomy. Finally, end-to-side duodenojejunostomy is performed in an antecolic fashion. Results: This technique has been successfully used in 3 consecutive patients with pancreatic head tumors: 2 patients underwent hand-assisted laparoscopic pylorus-preserving pancreatoduodenectomy, and 1 patient underwent totally laparoscopic pylorus-preserving pancreatoduodenectomy. One patient presented a Grade A pancreatic fistula that was managed conservatively. One patient received blood transfusion. Mean operative time was 9 hours. Mean hospital stay was 7 days. No postoperative mortality was observed. Conclusions: Laparoscopic pylorus-preserving pancreatoduodenectomy with double jejunal loop reconstruction is feasible and may be useful to decrease morbidity and mortality after pancreatoduodenectomy. This operation is challenging and may be reserved for highly skilled laparoscopic surgeons.
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    Superiority of prothrombin complex concentrate versus frozen fresh plasma in cardiologic patients with coumarin intoxication
    (2016) SOEIRO, A.; CESAR, M. C.; BISELLI, B.; BOSSA, A. S.; ARAUJO, V. A.; HAJJAR, L. A.; LEAL, T. C. A. T.; SOEIRO, M. C. F. A.; VELLA, J. P.; SERRANO JR., C. V.; OLIVEIRA JR., M. T.
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    Intestinal Barrier Dysfunction in Ageing Animals With Acute Pancreatitis: Increased Intestinal Inflammation?
    (2015) MACHADO, Marcel C.; SILVA, Fabiano Pinheiro da; CUNHA, Debora G.; BARBEIRO, Denise F.; COELHO, Ana Maria M.; SOUZA, Heraldo P.
  • conferenceObject
    LL-37 upregulates genes related to stemness in breast cancer cells
    (2016) SILVA, F. Pinheiro da; LIMA, T. Martins de; COELHO NETO, G. Tude; MACHADO, M. Cesar
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  • article 11 Citação(ões) na Scopus
    Diazoxide reduces local and remote organ damage in a rat model of intestinal ischemia reperfusion
    (2018) DOURADO, Saulo Fernandes de Mattos; BARBEIRO, Denise Frediani; KOIKE, Marcia Kiyomi; BARBEIRO, Hermes Vieira; SILVA, Fabiano Pinheiro da; MACHADO, Marcel Cerqueira Cesar
    Background: Intestinal ischemia reperfusion is a common clinical condition that causes functional impairment. Once tight junctions are damaged, barrier function is compromised, and the intestines become a source for entry of bacterial and inflammatory mediators into the circulation, leading to systemic inflammatory response syndrome, multiple organ failure, and death. It is possible that diazoxide could protect the intestines against ischemia reperfusion. The aim of this study is to determine whether diazoxide can provide protection in a rat model of intestinal ischemia reperfusion. Methods: A total of 32 adult male specific pathogen-free Wistar rats were randomized into three groups: a control group, n = 6; a saline group, n = 13; and a diazoxide group, n = 13. The saline and diazoxide groups underwent clamping of the superior mesenteric artery for 1 h, with samples in all the groups being collected 12 h later. Results: Intestinal histology showed greater damage in the intestinal ischemia reperfusion groups. mRNA expression of zonula occludens-1 and occludin (tight junction proteins) and interleukin-6 and cyclooxygenase-2 was the highest in the Saline group. The Diazoxide group showed a reduction in aspartate aminotransferase serum levels compared with the other groups. Conclusions: Increased expression of zonula occludens-1, occludin, and cyclooxygenase-2 suggested a greater regenerative effort because ofmore severe lesions in the saline group. In addition, increased expression of interleukin-6 in the saline group was suggestive of inflammation, indicating that diazoxide had protective effects in the diazoxide group. Reduced aspartate aminotransferase in the diazoxide group suggested liver protection. Diazoxide protects the intestines and liver fromintestinal ischemia reperfusion lesions in rats.
  • article 50 Citação(ões) na Scopus
    Penetrance of Functioning and Nonfunctioning Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 in the Second Decade of Life
    (2014) GONCALVES, Tatiana D.; TOLEDO, Rodrigo A.; SEKIYA, Tomoko; MATUGUMA, Sergio E.; MALUF FILHO, Fauze; ROCHA, Manoel S.; SIQUEIRA, Sheila A. C.; GLEZER, Andrea; BRONSTEIN, Marcelo D.; PEREIRA, Maria A. A.; JUREIDINI, Ricardo; BACCHELLA, Telesforo; MACHADO, Marcel C. C.; TOLEDO, Sergio P. A.; LOURENCO JR., Delmar M.
    Context: Data are scarce on the penetrance of multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-PETs) and insulinomas in young MEN1 patients. Apotential positive correlation between tumor size and malignancy (2-3 cm, 18%; >3 cm, 43%) has greatly influenced the management of MEN1 adults with NF-PETs. Objective: The aim of the study was to estimate the penetrance of NF-PETs, insulinomas, and gastrinomas in young MEN1 carriers. Design: The data were obtained from a screening program (1996-2012) involving 113 MEN1 patients in a tertiary academic reference center. Patients: Nineteen MEN1 patients (aged 12-20 y; 16 patients aged 15-20 y and 3 patients aged 12-14 y) were screened for NF-PETs, insulinomas, and gastrinomas. Methods: Magnetic resonance imaging/computed tomography and endoscopic ultrasound (EUS) were performed on 10 MEN1 carriers, magnetic resonance imaging/computed tomography was performed on five patients, and four other patients underwent an EUS. Results: The overall penetrance of PETs during the second decade of life was42%(8 of 19). All eight PET patients had NF-PETs, and half of those tumors were multicentric. One-fifth of the screened patients (21%; 4 of 19) harbored at least one large tumor (>2.0 cm). Insulinoma was detected in two NF-PET patients (11%) at the initial screening; gastrinoma was not present in any cases. Six of the 11 (54%) screened patients aged 15-20 years who underwent an EUS had NF-PETs. Potential false-positive EUS results were excluded based on EUS-guided biopsy results, the reproducibility of the NF-PET findings, or the observation of increased tumor size during follow-up. Distal pancreatectomy and the nodule enucleation of pancreatic head tumors were conducted on three patients with large tumors (>2.0 cm; T2N0M0) that were classified as grade 1 neuroendocrine tumors (Ki-67 < 2%). Conclusions: Our data demonstrated high penetrance of NF-PETs in 15- to 20-year-old MEN1 patients. The high percentage of the patients presenting consensus criteria for surgery for NF-PET alone or NF-PET/insulinoma suggests a potential benefit for the periodic surveillance of these tumors in this age group.