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1.
Entropy (Basel) ; 25(9)2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37761597

RESUMO

The literature on the fall of civilizations spans from the archaeology of early state societies to the history of the 20th century. Explanations for the fall of civilizations abound, from general extrinsic causes (drought, warfare) to general intrinsic causes (intergroup competition, socioeconomic inequality, collapse of trade networks) and combinations of these, to case-specific explanations for the specific demise of early state societies. Here, we focus on ancient civilizations, which archaeologists typically define by a set of characteristics including hierarchical organization, standardization of specialized knowledge, occupation and technologies, and hierarchical exchange networks and settlements. We take a general approach, with a model suggesting that state societies arise and dissolve through the same processes of innovation. Drawing on the field of cumulative cultural evolution, we demonstrate a model that replicates the essence of a civilization's rise and fall, in which agents at various scales-individuals, households, specialist communities, polities-copy each other in an unbiased manner but with varying degrees of institutional memory, invention rate, and propensity to copy locally versus globally. The results, which produce an increasingly extreme hierarchy of success among agents, suggest that civilizations become increasingly vulnerable to even small increases in propensity to copy locally.

2.
Scand J Surg ; 112(2): 69-76, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36852550

RESUMO

BACKGROUND AND OBJECTIVE: At present, percutaneous endoscopic gastrostomy (PEG) is the procedure of choice in establishing a permanent feeding tube in patients with chronic severe dysphagia. This is the first prospective randomized study in adults comparing PEG with radiologically inserted gastrostomy (RIG). METHODS: Randomization of 106 patients, eligible for both techniques, to PEG (pull method) or RIG. The groups were comparable in terms of age, body mass index, and underlying diseases. Adverse events were reported 10 and 30 days after the operative procedure, and mortality was up until 6 months. The validated European Quality of life 5 Dimensions 3 level version (EQ-5D) questionnaire was used for health status measurements. RESULTS: The procedures were successfully completed in all patients. The median operative time was 10 min for PEG and 20 min for RIG (p < 0.001). The overall rate of adverse events was lower for PEG (22%) than for RIG (51%, p = 0.002), mostly due to less local self-limiting stoma reactions and tube problems. The 30-day mortality was lower after PEG (2% versus 14%, p = 0.020). Patient-scored health status remained low for the entire cohort, with an EQ-5D utility index of 0.164. Self-rated health was low but improved in the RIG group (52.5 from 41.1, out of 100). CONCLUSION: PEG can be recommended as the primary procedure in patients in need of a feeding gastrostomy, mainly due to a lower frequency of tube complications. However, as the two techniques complement each other, RIG is also a valid alternative method. CLINICAL TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number ISRCTN17642761. https://doi.org/10.1186/ISRCTN17642761.


Assuntos
Gastrostomia , Adulto , Humanos , Nutrição Enteral/métodos , Gastrostomia/efeitos adversos , Gastrostomia/métodos , Intubação Gastrointestinal/efeitos adversos , Intubação Gastrointestinal/métodos , Estudos Prospectivos , Qualidade de Vida
3.
BMJ Open ; 12(11): e065839, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36343995

RESUMO

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance. METHODS AND ANALYSIS: The study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient's first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival. ETHICS AND DISSEMINATION: Participants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden. TRIAL REGISTRATION NUMBER: EudraCT number: 2021-001257-31.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Idarubicina , Neoplasias Hepáticas/tratamento farmacológico , Resultado do Tratamento
4.
Acta Radiol ; 62(9): 1170-1177, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32938223

RESUMO

BACKGROUND: Preoperative portal vein embolization (PVE) is performed to induce hypertrophy of the future liver remnant enabling major liver resection in patients with various types of liver tumors. PURPOSE: To evaluate safety and effectiveness of PVE with n-butyl-cyanoacrylate (NBCA). MATERIAL AND METHODS: All consecutive patients referred to our hospital for PVE between July 2006 and July 2017 were retrospectively reviewed. Volumetry was performed on computed tomography images before and after PVE, segmenting the total liver volume and the future liver remnant (FLR), i.e. liver segments I-III. RESULTS: PVE was performed in 46 patients (18 women, 28 men; mean age = 61 years) using local anesthesia. The ipsilateral technique was used in 45 patients. Adverse events were rare. The mean FLR volume increase was 56%, the degree of hypertrophy was 9.7%, and the kinetic growth rate was 2.1%/week. The median ± SD period between PVE and liver surgery was 7 ± 3 weeks. Forty-two patients (91%) had surgery; liver resection was performed in 37 (80%) patients. Three patients (7%) developed transient liver failure after surgery. There was no 90-day post-PVE or postoperative mortality. CONCLUSION: PVE using NBCA through the ipsilateral approach in local anesthesia is safe and effective in inducing hypertrophy of the future liver remnant enabling surgery, and thereby increasing survival in patients with liver tumors.


Assuntos
Embolização Terapêutica/métodos , Embucrilato/uso terapêutico , Hepatectomia , Neoplasias Hepáticas/terapia , Veia Porta , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
5.
Acta Radiol Open ; 9(10): 2058460120964074, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33110628

RESUMO

BACKGROUND: Portomesenteric vein thrombosis may be life-threatening due to bowel ischemia caused by venous stasis, or variceal bleeding caused by portal hypertension. PURPOSE: To evaluate the effectiveness and safety of recanalization combined with transjugular intrahepatic portosystemic shunt in acute and chronic portomesenteric vein thrombosis in patients with and without liver cirrhosis. MATERIAL AND METHODS: 21 consecutive patients (5 women, 16 men; mean 48 years) with portomesenteric vein thrombosis (8 acute, 13 chronic) treated at the Interventional Radiology department between March 2014 and September 2018 were retrospectively reviewed. The main portal vein was completely obliterated and the portomesenteric vein thrombosis extended into the superior mesenteric vein in all patients. The portomesenteric vein thromboses were recanalized transhepatically, a transjugular intrahepatic portosystemic shunt was inserted, thrombectomy was performed in acute portomesenteric vein thrombosis, and angioplasty with or without additional stenting was performed in chronic portomesenteric vein thrombosis. RESULTS: Recanalization was successful in 8/8 patients (100%) with acute portomesenteric vein thrombosis, and in 11/13 patients (85%) with chronic portomesenteric vein thrombosis. In 12 patients, blood flow was restored in one session. Several sessions were more frequently needed in patients with acute portomesenteric vein thrombosis compared to those with chronic portomesenteric vein thrombosis (p = 0.003). Re-occlusion occurred and was recanalized in 10/19 patients and was more frequent in patients with chronic (n = 8/11) than on those with acute (n = 2/8) portomesenteric vein thrombosis (p = 0.04). Adverse events occurred in five patients. There was no 30-day mortality. CONCLUSION: Recanalization and insertion of a transjugular intrahepatic portosystemic shunt is safe and effective in patients with acute and chronic portomesenteric vein thrombosis with or without cirrhosis. Recanalization was more likely to stay patent in acute compared with chronic portomesenteric vein thrombosis.

7.
Acta Radiol ; 59(8): 953-958, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29202584

RESUMO

Background Acute portomesenteric venous thrombosis (PMVT) is a potentially life-threatening condition and urgent treatment is required. Purpose To retrospectively evaluate the efficacy and safety of treating acute PMVT by the creation of a transjugular intrahepatic portosystemic shunt (TIPS) followed by thrombectomy. Material and Methods Six patients (all men, age range = 39-51 years) presenting with acute PMVT were treated with transjugular thrombectomy (TT) through a TIPS created in the same session. The intervention included iterated venography through the TIPS one to three times within the first week after diagnosis and repeated thrombectomy if needed (n = 5). Results Recanalization was successful with persistent blood flow through the main superior mesenteric vein, portal vein, and TIPS in all six patients. Five patients were treated primarily with thrombectomy through a TIPS with clinical improvement. The final patient was initially treated with surgical thrombectomy and bowel resection. TIPS and TT was performed two days after surgery due to re-thrombosis but the patient deteriorated and died of multi-organ failure. Procedure-related complications were transient hematuria (n = 3) and transient encephalopathy (n = 2). In-hospital time was <14 days in four of the five patients with primary TIPS and TT. No sign of re-thrombosis was noted during follow-up (mean = 18 months, range = 8-28 months). Conclusion Thrombectomy through a TIPS is feasible and can be effective in recanalization and symptom-relief in acute PMVT.


Assuntos
Veias Mesentéricas/cirurgia , Veia Porta/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Trombectomia/métodos , Trombose Venosa/cirurgia , Doença Aguda , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
8.
Mol Pharm ; 14(2): 448-458, 2017 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-27997198

RESUMO

Doxorubicin (DOX) delivered in a lipiodol-based emulsion (LIPDOX) or in drug-eluting beads (DEBDOX) is used as palliative treatment in patients with intermediate-stage hepatocellular carcinoma (HCC). The primary objective of this study was to evaluate the in vivo delivery performance of DOX from LIPDOX or DEBDOX in HCC patients using the local and systemic pharmacokinetics of DOX and its main metabolite doxorubicinol (DOXol). Urinary excretion of DOX and DOXol and their short-term safety and antitumor effects were also evaluated. In this open, prospective, nonrandomized multicenter study, LIPDOX (n = 13) or DEBDOX (n = 12) were injected into the feeding arteries of the tumor. Local (vena cava/hepatic vein orifice) and systemic (peripheral vein) plasma concentrations of DOX and DOXol were determined in samples obtained up to 6 h and 7 days after treatment. Tumor response was assessed using computed tomography or magnetic resonance imaging. The Cmax and AUC0-24 h for DOX were 5.6-fold and 2.4-fold higher in LIPDOX vs DEBDOX recipients, respectively (p < 0.001). After 6 h, the respective mean proportions of the dose remaining in the liver or drug-delivery system (DDS) were 49% for LIPDOX and 88% for DEBDOX. LIPDOX releases DOX faster than DEBDOX in HCC patients and provides more extensive local and systemic exposure (AUC) to DOX and DOXol initially (0-7 days). DEBDOX formulation has a release and distribution of DOX that is more restricted and rate controlled than LIPDOX.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Emulsões/uso terapêutico , Óleo Etiodado/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Fígado/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Eur J Gastroenterol Hepatol ; 28(6): 656-60, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26958788

RESUMO

INTRODUCTION: Treatment of Budd-Chiari syndrome (BCS) has shifted from mainly medical treatment, with surgical shunt and orthotopic liver transplantation (OLT) as rescue, to medical treatment combined with an early endovascular intervention in the past two decades. PURPOSE: To assess the safety and efficiency of endovascular treatment of symptomatic patients with BCS and to compare mortality with symptomatic BCS patients in the same region treated with only sporadic endovascular techniques. METHODS: This was a retrospective review of clinical data, treatment and survival in 14 patients diagnosed with BCS and treated with endovascular methods from 2003 to 2015. A national epidemiology study of BCS from 1986 to 2003 was used for comparison. RESULTS: Thirteen of the 14 patients eventually had transjugular intrahepatic portosystemic shunt (TIPS), four after previous liver vein angioplasty. TIPS were performed with polytetrafluoroethylene-covered stents and technical success was 100%. Calculated preinterventional prognostic indices indicated a high risk of TIPS dysfunction, OLT and death. However, only one patient died and one had an OLT, and the 1- and 2-year primary TIPS-patency was 85 and 67%, respectively. Episodes of de-novo hepatic encephalopathy occurred in three patients. Overall 1- and 5-year transplantation-free survival was 100 and 93% compared with 47 and 28%, respectively, in 1986 to 2003. CONCLUSION: TIPS seems to be a safe and effective treatment for symptomatic BCS and there is an obvious improvement in transplantation-free survival compared with conservatory medical treatment. It should, therefore, be considered early, as first-line intervention, in patients with insufficient response to medical treatment.


Assuntos
Síndrome de Budd-Chiari/cirurgia , Procedimentos Endovasculares/métodos , Hipertensão Portal/cirurgia , Transplante de Fígado/estatística & dados numéricos , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Dor Abdominal/etiologia , Adolescente , Adulto , Angioplastia , Ascite/etiologia , Síndrome de Budd-Chiari/complicações , Síndrome de Budd-Chiari/mortalidade , Intervenção Médica Precoce , Feminino , Veias Hepáticas/cirurgia , Síndrome Hepatorrenal/etiologia , Humanos , Hipertensão Portal/etiologia , Masculino , Pessoa de Meia-Idade , Politetrafluoretileno , Estudos Retrospectivos , Stents , Adulto Jovem
10.
Acta Radiol ; 57(5): 572-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26253926

RESUMO

BACKGROUND: Treatment of patients with portal vein thrombosis (PVT) differs due to different etiology and wide range of symptoms but certain patients seems to benefit from endovascular intervention. PURPOSE: To assess the safety and efficiency of endovascular treatment of acute and chronic PVT in patients with cirrhotic and non-cirrhotic liver. MATERIAL AND METHODS: Twenty-one patients with PVT treated with an endovascular procedure in 2002-2013 were studied retrospectively. Data on etiology, onset and extension of thrombus, presenting symptoms, methods of intervention, portal pressure gradients, complications, recurrence of symptoms, re-interventions, clinical status at latest follow-up, and survival were collected. RESULTS: Four non-cirrhotic patients with acute extensive PVT and bowel ischemia were treated with local thrombolysis, in three combined with placement of a transjugular intrahepatic portosystemic shunt (TIPS) placement. Three recovered and have survived more than 6 years. In six non-cirrhotic patients with chronic PVT and acute or threatening variceal bleeding recanalization and TIPS were successful in three and failed in three. Eleven cirrhotic patients with PVT and variceal bleeding or refractory ascites were successfully treated with recanalization and TIPS. Re-intervention was performed in five of these patients and five patients died, three within 12 months of intervention. Four cirrhotic patients had episodes of shunt-related encephalopathy and three had variceal re-bleeding. CONCLUSION: TIPS was found to be effective in reducing portal hypertension in patients with PVT. In patients with extensive PVT and bowel ischemia treatment with TIPS combined with thrombolysis should be considered.


Assuntos
Procedimentos Endovasculares , Varizes Esofágicas e Gástricas/complicações , Cirrose Hepática/complicações , Veia Porta , Trombose Venosa/etiologia , Trombose Venosa/terapia , Adulto , Idoso , Transfusão de Sangue , Varizes Esofágicas e Gástricas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derivação Portossistêmica Transjugular Intra-Hepática , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Stents , Taxa de Sobrevida , Terapia Trombolítica , Resultado do Tratamento
11.
Eur J Nucl Med Mol Imaging ; 43(8): 1425-31, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26631239

RESUMO

PURPOSE: To evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in patients with unresectable liver metastases from neuroendocrine tumours (NETLMs). METHODS: This retrospective study included 40 patients with progressive NETLMs (22 women, 18 men, mean age 61.6 years) who underwent SIRT with (90)Y-labelled resin microspheres. Tumour response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) on CT or MR images. Medical records were reviewed. RESULTS: In the 40 patients, 54 evaluable SIRT procedures were performed, 33 to the right liver lobe (mean activity 1.31 GBq), 13 to the left lobe (mean activity 0.85 GBq), and 8 to both lobes (mean activity 1.61 GBq). Late follow-up imaging (mean 20 months) was performed after 44 of the treatments. Objective tumour response and disease control rates were 54 % (29 of 54 treatments) and 94 % (51 treatments), respectively, at the early follow-up examination (mean 3 months) and 34 % (15 treatments) and 57 % (25 treatments), respectively at the late follow-up examination. Mean overall survival from the first SIRT was 34,8 months and survival rates at 1, 2, 3 and 5 years were 76 %, 59 %, 52 % and 35 % respectively. Adverse effects were generally mild and easily manageable, except in one patient who died from radiation-induced liver failure. Of the 45 patients, 18 (45 %) had received peptide receptor radionuclide therapy (PRRT) prior to SIRT. CONCLUSION: SIRT with (90)Y-labelled resin microspheres is a safe and effective treatment for patients with progressive NETLM, and also for those who have received prior PRRT.


Assuntos
Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/patologia , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
12.
Cardiovasc Intervent Radiol ; 38(6): 1438-43, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25968476

RESUMO

PURPOSE: To report the experience of a percutaneous closure device used for transfemoral transcatheter aortic valve implantation (TAVI) in an unselected patient and operator population. MATERIALS AND METHODS: Eighty-two consecutive patients (32 women, 50 men) who underwent transfemoral TAVI between September 2009 and February 2014 at our hospital were retrospectively reviewed for percutaneous closure device (PCD) failure, vascular complications, and bleeding. The diameter and calcification of the common femoral artery (CFA) and the thickness of the subcutaneous fat layer in the groin were assessed on computed tomography images. RESULTS: The incidences of PCD failure and minor and major vascular complications were 19.5% (n = 16/82), 19.5% (n = 16/82), and 7% (n = 6/82) respectively. 8.5% (n = 7/82) had a minor perioperative bleeding, 6% (n = 5/82) had a major bleeding, and none had any life-threatening bleeding. When PCD failed, haemostasis was obtained with fascia suturing, covered stent placement, or with surgical cutdown. Thirty-day mortality and 1-year all-cause mortality were 8.5% (n = 7/82) and 19.5% (n = 16/82), respectively. In a multiple regression analysis, the CFA diameter and the presence of severe calcification were independently related to PCD failure (correlation coefficient = -0.24, p = 0.027 and correlation coefficient = 0.23, p = 0.036, respectively). CONCLUSION: PCD failure was related to a small CFA diameter and to a severely calcified CFA. Failure could largely be managed with minimally invasive techniques such as covered stents or fascia suturing.


Assuntos
Valva Aórtica/cirurgia , Artéria Femoral/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Feminino , Artéria Femoral/diagnóstico por imagem , Doenças das Valvas Cardíacas/diagnóstico por imagem , Humanos , Masculino , Sistema de Registros , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Eur J Radiol ; 84(6): 1068-74, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25842009

RESUMO

PURPOSE: To establish the concentrations of iodine contrast media (I-CM) iso-attenuating with 0.5M gadolinium contrast media (Gd-CM), regarded diagnostic in catheter angiography and vascular interventions in azotemic patients, at various X-ray tube potentials with correlation to skin radiation dose. MATERIALS AND METHOD: 20-mL syringes filled with 30, 40, 50, 70 and 90 mgI/mL, 0.5M Gd-CM and air were placed in a water-equivalent phantom and exposed at about 50, 60, 70, 80 and 90 kV in an X-ray angiographic system. Relative contrast between the contrast materials and the background phantom material was measured on a PACS workstation. Radiation entrance dose, measured with a dose meter and estimated from the dose-area-product (DAP), was adjusted for radiation backscatter to simulate absorbed skin dose. RESULT: The iodine concentrations 30, 40, 50, 70 and 90 mg/mL resulted in the same relative contrast as 0.5M gadolinium at 53, 57, 62, 71 and 85 kVp, respectively. Air had lower relative contrast than all iodine concentrations at all kVp-settings except for 30 mgI/mL above 84 kVp. The measured skin radiation dose was less than 1 mGy per exposure at all kVp-settings, and around 25-30% lower than the dose estimations derived from the angiographic system's in-built DAP meter. CONCLUSION: Low-kilovoltage X-ray technique and ultra-low concentrations of I-CM iso-attenuating with 0.5M Gd-CM may be utilizable in peripheral arteriography and endovascular interventions, to minimize the total CM-dose to avoid CIN in azotemic patients.


Assuntos
Meios de Contraste/efeitos adversos , Procedimentos Endovasculares , Gadolínio/efeitos adversos , Iodo , Nefropatias/prevenção & controle , Imagens de Fantasmas , Tomografia Computadorizada por Raios X , Angiografia/métodos , Procedimentos Endovasculares/métodos , Feminino , Fluoroscopia , Gadolínio/administração & dosagem , Humanos , Iodo/administração & dosagem , Nefropatias/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Tomografia Computadorizada por Raios X/métodos
15.
Mol Pharm ; 11(1): 131-44, 2014 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-24171458

RESUMO

Unresectable, intermediate stage hepatocellular carcinoma (HCC) is often treated palliatively in humans by doxorubicin (DOX). The drug is administered either as a drug-emulsified-in-Lipiodol (DLIP) or as drug loaded into drug eluting beads (DEB), and both formulations are administered intrahepatically. However, several aspects of their in vivo performance in the liver are still not well-understood. In this study, DLIP and DEB were investigated regarding the local and systemic pharmacokinetics (PK) of DOX and its primary metabolite doxorubicinol (DOXol). An advanced PK-multisampling site acute in vivo pig model was used for simultaneous sampling in the portal, hepatic, and femoral veins and the bile duct. The study had a randomized, parallel design with four treatment groups (TI-TIV). TI (n = 4) was used as control and received an intravenous (i.v.) infusion of DOX as a solution. TII and TIII were given a local injection in the hepatic artery with DLIP (n = 4) or DEB (n = 4), respectively. TIV (n = 2) received local injections of DLIP in the hepatic artery and bile duct simultaneously. All samples were analyzed for concentrations of DOX and DOXol with UPLC-MS/MS. Compared to DLIP, the systemic exposure for DOX with DEB was reduced (p < 0.05), in agreement with a slower in vivo release. The approximated intracellular bioavailability of DOX during 6 h appeared to be lower for DEB than DLIP. Following i.v. infusion (55 min), DOX had a liver extraction of 41 (28-53)%, and the fraction of the dose eliminated in bile of DOX and DOXol was 20 (15-22)% and 4.2 (3.2-5.2)%, respectively. The AUCbile/AUCVP for DOX and DOXol was 640 (580-660) and 5000 (3900-5400), respectively. In conclusion, DLIP might initially deliver a higher hepatocellular concentration of DOX than DEB as a consequence of its higher in vivo release rate. Thus, DLIP delivery results in higher intracellular peak concentrations that might correlate with better anticancer effects, but also higher systemic drug exposure and safety issues.


Assuntos
Antibióticos Antineoplásicos/farmacocinética , Ductos Biliares/efeitos dos fármacos , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacocinética , Sistemas de Liberação de Medicamentos , Artéria Hepática/efeitos dos fármacos , Infusões Intra-Arteriais , Animais , Antibióticos Antineoplásicos/química , Ductos Biliares/metabolismo , Ductos Biliares/cirurgia , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Óleo Etiodado/química , Artéria Hepática/metabolismo , Artéria Hepática/cirurgia , Masculino , Suínos , Espectrometria de Massas em Tandem , Distribuição Tecidual
16.
J Vasc Interv Radiol ; 24(12): 1826-33, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24144537

RESUMO

PURPOSE: To investigate the long-term morphologic changes of the aorta after thoracic endovascular aortic repair (TEVAR) for acute complicated type B aortic dissection and to analyze whether these changes differed between DeBakey class IIIa and IIIb dissections. MATERIALS AND METHODS: During the period 1999-2009, 58 patients with acute complicated type B aortic dissection were treated with TEVAR. Seven patients lacked follow-up data, leaving 51 patients-17 patients with DeBakey IIIa aortic dissection and 34 patients with DeBakey IIIa aortic dissection IIIb-for inclusion in the study. Computed tomography scans performed before and after TEVAR were evaluated. Maximum thoracic and abdominal aortic diameters and diameters of the true lumen and false lumen at the level of the maximum aortic diameter in the thorax and abdomen were analyzed as well as degree of thrombosis of the false lumen. RESULTS: There was an overall significant reduction of the thoracic aortic diameter, increased true lumen diameter, and reduced false lumen diameter (P < .05). Total thrombosis of the false lumen, with or without reintervention, was seen in 53% of all patients, in 41% primarily and in 12% after reintervention. The IIIa group had a higher degree of total false lumen thrombosis. All patients in the IIIb group had total thrombosis of the false lumen along the stent graft. CONCLUSIONS: Long-term follow-up showed favorable aortic remodeling after TEVAR for acute complicated type B aortic dissection. Total thrombosis of the false lumen occurred more often in patients with DeBakey IIIa aortic dissection compared with patients with DeBakey IIIb aortic dissection.


Assuntos
Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aortografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Trombose/diagnóstico por imagem , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Interact Cardiovasc Thorac Surg ; 17(3): 583-5, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23736660

RESUMO

Internal thoracic artery (ITA) aneurysms are rare, but a rupture is potentially fatal. Most cases of ITA aneurysms are iatrogenic, caused by, for instance, previous sternotomy or pacemaker implantation. Other known aetiologies are vasculopathies, either of inflammatory origin or as part of connective tissue disorders like Marfan's syndrome, Ehler-Dahnlos syndrome or neurofibromatosis Type 1. Idiopathic ITA aneurysms are exceedingly scarce. The present case illustrates an unusual scenario, which posed diagnostic challenges, where spontaneous rupture of an idiopathic or possibly very late post-traumatic aneurysm of the left ITA led to a life-threatening bleeding, successfully treated by endovascular coiling with standby preparation for conversion to open surgery. This case demonstrates the importance of the careful interpretation of radiological findings and the significance of multidisciplinary collaboration between radiologist and clinician.


Assuntos
Aneurisma Roto/etiologia , Hemorragia/etiologia , Artéria Torácica Interna , Aneurisma Roto/diagnóstico , Aneurisma Roto/terapia , Embolização Terapêutica , Hemorragia/diagnóstico , Hemorragia/terapia , Humanos , Masculino , Artéria Torácica Interna/diagnóstico por imagem , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Ruptura Espontânea , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
J Vasc Surg ; 56(4): 973-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22608791

RESUMO

OBJECTIVE: The purpose of this study was to analyze our experience of thoracic endovascular aortic repair (TEVAR) in patients with traumatic aortic transection. METHODS: This was a single-center consecutive case series that was conducted at the Uppsala University Hospital, Tertiary Referral Center. There were a total of 17 consecutive patients undergoing TEVAR for traumatic thoracic aortic transection. All patients undergoing TEVAR for aortic transection were registered prospectively and their medical records were reviewed regarding technical details, mechanism of injury, and concomitant injuries. Long-term outcome was analyzed with respect to need for reintervention and survival. RESULTS: Between 2001 and 2010, 17 patients underwent TEVAR for traumatic aortic injury. Median age was 42 years (range, 18-77 years), and 15 of 17 patients (88%) were men. Fourteen patients had been involved in motor vehicle accidents, two had fallen from heights, and one fell off a bicycle on a slope. In all cases, the aortic injury was located in the proximity of the origin of the left subclavian artery. All patients had concomitant injuries. In all patients, a single stent graft was sufficient to exclude the injured part of the aorta. The median cover length was 120 mm (range, 100-200 mm). In-hospital mortality was 24% (4 of 17 patients). One patient died perioperatively and three postoperatively, two from brain injuries and one from multiorgan failure. After a median follow-up of 36 months (range, 10-98 months), three patients underwent reintervention (18%), each patient only once; one for a type I endoleak, and two for pseudocoarctation secondary to stent graft infolding. Two were treated endovascularly, and one had a stent graft explantation. CONCLUSIONS: Endovascular repair allows rapid and minimally invasive therapy in patients with traumatic aortic injury with good technical results. The outcome is highly dependent on the severity of other concurrent injuries.


Assuntos
Aorta Torácica/lesões , Ruptura Aórtica/terapia , Implante de Prótese Vascular , Procedimentos Endovasculares , Ferimentos não Penetrantes/terapia , Adolescente , Adulto , Idoso , Ruptura Aórtica/diagnóstico , Ruptura Aórtica/mortalidade , Prótese Vascular , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Stents , Resultado do Tratamento , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico , Adulto Jovem
20.
Mov Disord ; 26(2): 331-4, 2011 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20960486

RESUMO

Motor fluctuations in Parkinson's disease (PD) can be reduced by intraduodenal infusion of levodopa-carbidopa (Duodopa®) via percutaneous endoscopic gastrojejunostomy (PEG). We applied the transcutaneous soft-tissue anchored titanium port (T-port) in 15 PD patients with motor fluctuations; 7 Duodopa-naive (non-PEG), and 8 previously receiving Duodopa (former-PEG). Motor scores (UPDRS-III) and quality of life (QOL, PDQ-8) were assessed at baseline and 6 month follow-up. Six patients had local irritation shortly after implantation, persisting in one patient at 6 month follow-up, which led to explantation. After having finished the protocol, four T-ports were explanted in total. UPDRS-III and PDQ-8 scores improved moderately in the non-PEG patients, but remained similar in the former-PEG users. Two former-PEG users developed polyneuropathy. No obstructions, retractions, or leakages occurred. Technical and hygienic properties of the T-port were preferred by most patients. The T-port seems to be suitable for most PD patients qualifying for Duodopa therapy, although local infection may lead to explantation during longer-term follow-up.


Assuntos
Antiparkinsonianos/administração & dosagem , Carbidopa/administração & dosagem , Duodeno , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Antiparkinsonianos/uso terapêutico , Carbidopa/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento
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