RESUMO
Rapid North Atlantic cooling events during the last deglaciation caused atmospheric reorganizations on global and regional scales. Their impact on Asian climate has been investigated for monsoonal domains, but remains largely unknown in westerly wind-dominated semiarid regions. Here we generate a dust record from southeastern Iran spanning the period 19 to 7 cal. ka B.P. We find a direct link between frequent occurrences of dust plumes originating from the Arabian Peninsula and North Africa and rapid southward shifts of the westerlies associated with changes of the winter stationary waves during Heinrich Stadial 1, the Younger Dryas, the Preboreal Oscillation, and the 8.2-ka event. Dust input rises and falls abruptly at the transitions into and out of these cooling events, which we attribute to changes in the ocean circulation strength that are modulated by the North Atlantic winter sea-ice cover. Our findings reveal that waxing and waning of North American ice sheets have a stronger influence than those of European ice sheets on the winter climate over West Asia.
RESUMO
BACKGROUND: This prospective multicenter study funded by the DEGUM assesses the diagnostic accuracy of standardized contrast-enhanced ultrasound (CEUS) for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients. METHODS: Patients at high risk for HCC with a histologically proven focal liver lesion on B-mode ultrasound were recruited prospectively in a multicenter approach. Clinical and imaging data were entered via online entry forms. The diagnostic accuracies for the noninvasive diagnosis of HCC were compared for the conventional interpretation of standardized CEUS at the time of the examination (=âCEUS on-site) and the two CEUS algorithms ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) and CEUS LI-RADS (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System). RESULTS: 321 patients were recruited in 43 centers; 299 (93.1â%) had liver cirrhosis. The diagnosis according to histology was HCC in 256 cases, and intrahepatic cholangiocarcinoma (iCCA) in 23 cases. In the subgroup of cirrhotic patients (nâ=â299), the highest sensitivity for the diagnosis of HCC was achieved with the CEUS algorithm ESCULAP (94.2â%) and CEUS on-site (90.9â%). The lowest sensitivity was reached with the CEUS LI-RADS algorithm (64â%; pâ<â0.001). However, the specificity of CEUS LI-RADS (78.9â%) was superior to that of ESCULAP (50.9â%) and CEUS on-site (64.9â%; pâ<â0.001). At the same time, the negative predictive value (NPV) of CEUS LI-RADS was significantly inferior to that of ESCULAP (34.1â% vs. 67.4â%; pâ<â0.001) and CEUS on-site (62.7â%; pâ<â0.001). The positive predictive values of all modalities were high (around 90â%), with the best results seen for CEUS LI-RADS and CEUS on-site. CONCLUSION: This is the first multicenter, prospective comparison of standardized CEUS and the recently developed CEUS-based algorithms in histologically proven liver lesions in cirrhotic patients. Our results reaffirm the excellent diagnostic accuracy of CEUS for the noninvasive diagnosis of HCC in high-risk patients. However, on-site diagnosis by an experienced examiner achieves an almost equal diagnostic accuracy compared to CEUS-based diagnostic algorithms.
Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Algoritmos , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Estudos Prospectivos , UltrassonografiaRESUMO
OBJECTIVES: Sedation has been established for GI endoscopic procedures in most countries, but it is also associated with an added risk of complications. Reported complication rates are variable due to different study methodologies and often limited sample size. DESIGNS: Acute sedation-associated complications were prospectively recorded in an electronic endoscopy documentation in 39 study centres between December 2011 and August 2014 (median inclusion period 24 months). The sedation regimen was decided by each study centre. RESULTS: A total of 368 206 endoscopies was recorded; 11% without sedation. Propofol was the dominant drug used (62% only, 22.5% in combination with midazolam). Of the sedated patients, 38 (0.01%) suffered a major complication, and overall mortality was 0.005% (n=15); minor complications occurred in 0.3%. Multivariate analysis showed the following independent risk factors for all complications: American Society of Anesthesiologists class >2 (OR 2.29) and type and duration of endoscopy. Of the sedation regimens, propofol monosedation had the lowest rate (OR 0.75) compared with midazolam (reference) and combinations (OR 1.0-1.5). Compared with primary care hospitals, tertiary referral centres had higher complication rates (OR 1.61). Notably, compared with sedation by a two-person endoscopy team (endoscopist/assistant; 53.5% of all procedures), adding another person for sedation (nurse, physician) was associated with higher complication rates (ORs 1.40-4.46), probably due to higher complexity of procedures not evident in the multivariate analysis. CONCLUSIONS: This large multicentre registry study confirmed that severe acute sedation-related complications are rare during GI endoscopy with a very low mortality. The data are useful for planning risk factor-adapted sedation management to further prevent sedation-associated complications in selected patients. TRIAL REGISTRATION NUMBER: DRKS00007768; Pre-results.
Assuntos
Sedação Consciente/efeitos adversos , Endoscopia Gastrointestinal/efeitos adversos , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Sedação Consciente/mortalidade , Endoscopia Gastrointestinal/métodos , Endoscopia Gastrointestinal/mortalidade , Endoscopia Gastrointestinal/estatística & dados numéricos , Feminino , Alemanha/epidemiologia , Humanos , Hipnóticos e Sedativos/efeitos adversos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Propofol/efeitos adversos , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
Marine silicate alteration plays a key role in the global carbon and cation cycles, although the timeframe of this process in response to extreme weather events is poorly understood. Here we investigate surface sediments across the Peruvian margin before and after extreme rainfall and runoff (coastal El Niño) using Ge/Si ratios and laser-ablated solid and pore fluid Si isotopes (δ30Si). Pore fluids following the rainfall show elevated Ge/Si ratios (2.87 µmol mol-1) and δ30Si values (3.72), which we relate to rapid authigenic clay formation from reactive terrigenous minerals delivered by continental runoff. This study highlights the direct coupling of terrestrial erosion and associated marine sedimentary processes. We show that marine silicate alteration can be rapid and highly dynamic in response to local weather conditions, with a potential impact on marine alkalinity and CO2-cycling on short timescales of weeks to months, and thus element turnover on human time scales.
RESUMO
Aims: The primary goal in the treatment of symptomatic atrial fibrillation/flutter (AF) is to restore sinus rhythm by cardioversion. Electrical shocks are highly effective, but have to be applied under analgo-sedation and can further harm the heart. In order to develop a novel pain-free and less harmful approach, we explored herein the optogenetic cardioversion by light-induced depolarization. Methods and results: Hearts from mice expressing Channelrhodopsin-2 (ChR2) and the AF-promoting loss-of-function Connexin 40 Ala96Ser mutation were explanted and perfused with low K+ Tyrode's solution and an atrial KATP-channel activator. This new protocol shortened atrial refractoriness as well as slowed atrial conduction and thereby enabled the induction of sustained AF. AF episodes could be terminated by epicardial illumination of the atria with focussed blue light (470 nm, 0.4 mW/mm2) with an efficacy of â¼97% (n = 17 hearts). In > 80% of cases, light directly terminated the AF episode with onset of illumination. Because similar illumination intensity was able to locally inhibit atrial activity, we propose that a light-induced block of electrical activity is responsible for reliable AF termination. The success rate was strongly depending on the illuminated area, applied light intensity and duration of illumination. Importantly, we were also able to demonstrate optogenetic termination of AF in vivo, using epicardial illumination through the open chest (n = 3 hearts). To point towards a translational potential, we systemically injected an adeno-associated virus to express ChR2 in wild type hearts. After 6-8 months, we found robust ChR2 expression in the atria, enabling light-mediated AF termination in six of seven mice tested. Conclusion: We provide the first evidence for optogenetic termination of atrial tachyarrhythmia in intact hearts from transgenic as well as wild type mice ex and in vivo. Thus, this report could lay the foundation for the development of implantable devices for pain-free termination of AF.
Assuntos
Fibrilação Atrial/terapia , Função Atrial , Átrios do Coração/fisiopatologia , Frequência Cardíaca , Optogenética , Taquicardia Supraventricular/terapia , Potenciais de Ação , Animais , Fibrilação Atrial/genética , Fibrilação Atrial/metabolismo , Fibrilação Atrial/fisiopatologia , Channelrhodopsins/genética , Channelrhodopsins/metabolismo , Conexinas/genética , Conexinas/metabolismo , Modelos Animais de Doenças , Feminino , Predisposição Genética para Doença , Átrios do Coração/metabolismo , Canais KATP/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Fenótipo , Período Refratário Eletrofisiológico , Taquicardia Supraventricular/genética , Taquicardia Supraventricular/metabolismo , Taquicardia Supraventricular/fisiopatologia , Proteína alfa-5 de Junções ComunicantesRESUMO
In-situ weathered bedrock, saprolite, is locally found in Scandinavia, where it is commonly thought to represent pre-Pleistocene weathering possibly associated with landscape formation. The age of weathering, however, remains loosely constrained, which has an impact on existing geological and landscape evolution models and morphotectonic correlations. Here we provide new geochronological evidence that some of the low-altitude basement landforms on- and offshore southwestern Scandinavia are a rejuvenated geomorphological relic from Mesozoic times. K-Ar dating of authigenic, syn-weathering illite from saprolitic remnants constrains original basement exposure in the Late Triassic (221.3±7.0-206.2±4.2 Ma) through deep weathering in a warm climate and subsequent partial mobilization of the saprolitic mantle into the overlying sediment cascade system. The data support the bulk geomorphological development of west Scandinavia coastal basement rocks during the Mesozoic and later, long-lasting relative tectonic stability. Pleistocene glaciations played an additional geomorphological role, selectively stripping the landscape from the Mesozoic overburden and carving glacial landforms down to Plio-Pleistocene times. Saprolite K-Ar dating offers unprecedented possibilities to study past weathering and landscape evolution processes.
RESUMO
AIM: Prospective analysis of multi-detector CT-colonography (MDCTC) in patients with inflammatory bowel disease (IBD) compared to high-resolution video-endoscopy (HRVC). MATERIALS AND METHODS: Twenty-one patients (mean age 49.6 years) with Crohn's disease or ulcerative colitis underwent MDCTC (Somatom Volume Zoom, Siemens, Erlangen; 1mm collimation, Pitch 8, 100 mAs, 120 kVp). HRVC was performed within 2 h after MDCTC. MDCTC was analyzed by two blinded readers. MDCTC-findings including bowel wall alterations and extraintestinal changes were compared to results of HRVC. RESULTS: Over-all-sensitivity was 100% for endoluminal lesions with correct diagnosis of two cancers. Acute and chronic IBD were correctly identified by MDCTC in 63.6%, and 100%, respectively, with a specificity of 75%, and 100%. Sensitivity, specificity, positive and negative predictive values of MDCTC for diagnosis of acute and chronic disease were best for chronic disease. Sensitivity was worst for acute ulcerative colitis and specificity was worst for acute Crohn's disease. Haustral loss was seen only in ulcerative colitis. Pseudopolyps and fistulae were findings exclusive to Crohn's disease. Particularly extraintestinal findings as increased vascularization and local lymphadenopathy correlated well with endoscopic definition of acute disease. Because of the possibly more vulnerable colonic wall in acute inflammatory bowel disease, the air inflation for MDCTC should be performed most carefully to avoid any risk of colonic perforation. CONCLUSION: MDCTC may help to distinguish between patients with acute and chronic IBD. Especially extraintestinal complications, tumorous as well as pseudo-tumorous lesions can be detected with high sensitivity and specificity.
Assuntos
Colite Ulcerativa/diagnóstico , Colonografia Tomográfica Computadorizada/métodos , Colonoscopia/métodos , Doença de Crohn/diagnóstico , Adulto , Colite Ulcerativa/diagnóstico por imagem , Doença de Crohn/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Gravação em VídeoRESUMO
Ventricular arrhythmias are among the most severe complications of heart disease and can result in sudden cardiac death. Patients at risk currently receive implantable defibrillators that deliver electrical shocks to terminate arrhythmias on demand. However, strong electrical shocks can damage the heart and cause severe pain. Therefore, we have tested optogenetic defibrillation using expression of the light-sensitive channel channelrhodopsin-2 (ChR2) in cardiac tissue. Epicardial illumination effectively terminated ventricular arrhythmias in hearts from transgenic mice and from WT mice after adeno-associated virus-based gene transfer of ChR2. We also explored optogenetic defibrillation for human hearts, taking advantage of a recently developed, clinically validated in silico approach for simulating infarct-related ventricular tachycardia (VT). Our analysis revealed that illumination with red light effectively terminates VT in diseased, ChR2-expressing human hearts. Mechanistically, we determined that the observed VT termination is due to ChR2-mediated transmural depolarization of the myocardium, which causes a block of voltage-dependent Na+ channels throughout the myocardial wall and interrupts wavefront propagation into illuminated tissue. Thus, our results demonstrate that optogenetic defibrillation is highly effective in the mouse heart and could potentially be translated into humans to achieve nondamaging and pain-free termination of ventricular arrhythmia.
Assuntos
Miocárdio/metabolismo , Fibrilação Ventricular/terapia , Animais , Channelrhodopsins , Simulação por Computador , Feminino , Terapia Genética , Humanos , Masculino , Camundongos Transgênicos , Modelos Biológicos , Infarto do Miocárdio , Miocárdio/patologia , Optogenética , Ativação Transcricional/efeitos da radiaçãoRESUMO
AIMS: Optogenetic pacing of the heart has been demonstrated in transgenic animals expressing channelrhodopsin-2 (ChR2). However, for the clinical use of optogenetics to treat cardiac arrhythmias, gene transfer to non-transgenic hearts is required. The aim of this study was to describe a reliable method for gene transfer of ChR2 into a sufficient percentage of cardiomyocytes to overcome the electrical sink of all the coupled non-expressing cardiomyocytes during optical pacing of the whole heart in vivo. METHODS AND RESULTS: Adeno-associated virus (AAV) with cardiac tropism for expression of ChR2 in fusion with mCherry was systemically injected into wild-type mouse hearts. Bright mCherry fluorescence was detected in the whole heart 4-10 weeks later. Single-cell dissociation revealed that on average 58% cardiomyocytes were mCherry-positive. These showed light-induced inward currents, action potentials, and contractions. Pulsed illumination of the left ventricle induced ventricular pacing in vivo in 74% of mice, and higher light intensities were required for reduced pulse duration or size of illumination. Non-responding hearts showed low AAV expression, and the threshold for optical pacing was estimated to be 35-40% ChR2-expressing cardiomyocytes. Optical pacing in vivo was stable over extended periods without negative effects on normal sinus rhythm and ECG parameters after termination of stimulation indicating sufficient cardiac output during pacing. CONCLUSIONS: Gene transfer generates sufficient ChR2 photocurrent for reliable optogenetic pacing in vivo and lays out the basis for future optogenetic pacemaker and pain-free defibrillation therapies.
Assuntos
Dependovirus/genética , Miócitos Cardíacos/metabolismo , Potenciais de Ação/fisiologia , Animais , Arritmias Cardíacas/genética , Arritmias Cardíacas/metabolismo , Feminino , Luz , Camundongos , Optogenética/métodos , Rodopsina/genéticaRESUMO
Optogenetic stimulation allows activation of cells with high spatial and temporal precision. Here we show direct optogenetic stimulation of skeletal muscle from transgenic mice expressing the light-sensitive channel Channelrhodopsin-2 (ChR2). Largest tetanic contractions are observed with 5-ms light pulses at 30 Hz, resulting in 84% of the maximal force induced by electrical stimulation. We demonstrate the utility of this approach by selectively stimulating with a light guide individual intralaryngeal muscles in explanted larynges from ChR2-transgenic mice, which enables selective opening and closing of the vocal cords. Furthermore, systemic injection of adeno-associated virus into wild-type mice provides sufficient ChR2 expression for optogenetic opening of the vocal cords. Thus, direct optogenetic stimulation of skeletal muscle generates large force and provides the distinct advantage of localized and cell-type-specific activation. This technology could be useful for therapeutic purposes, such as restoring the mobility of the vocal cords in patients suffering from laryngeal paralysis.
Assuntos
Músculos Laríngeos/fisiologia , Luz , Contração Muscular , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/fisiologia , Optogenética/métodos , Prega Vocal , Animais , Channelrhodopsins , Dependovirus/genética , Estimulação Elétrica , Músculos Laríngeos/patologia , Potenciais da Membrana , Camundongos , Camundongos Transgênicos , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologiaRESUMO
In a patient with symptomatic liver metastases of a neuroendocrine tumor larger than 10 cm in diameter percutaneous radiofrequency ablation was performed. The ablation resulted in a significant decrease in tumor size and a good long-term improvement of symptoms. Plasma serotonin 48 hours after the ablation was approximately 10-fold lower than before. However, sequential determination of plasma serotonin during the radiofrequency ablation revealed a two-fold increase of plasma serotonin induced by the procedure. There was also an approximately three-fold increase of 5-hydroxyindol acetic acid in urine in the 24 hours following the ablation. The data show that ablation procedures in neuroendocrine tumors may induce hormone release which may be critical in patients with severe clinical symptoms.
Assuntos
Ablação por Cateter , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Tumores Neuroendócrinos/secundário , Tumores Neuroendócrinos/cirurgia , Serotonina/metabolismo , Feminino , Humanos , MasculinoRESUMO
In a 65-year-old female patient, B-mode sonography detected a single focal lesion in the right liver lobe with a diameter < 3 cm. Histopathologic examination revealed a low differentiated hepatocellular carcinoma (HCC; G3). Tumor staging was performed by CT (computed tomography) scan and Resovist MRI (magnetic resonance imaging). Both examinations found a single liver lesion without signs of additional focal hepatic lesions. In addition, phase-inversion sonography in the late phase was performed using the ultrasound contrast agent Levovist. This examination of late-phase Levovist uptake detected more than five additional focal hepatic lesions in the right liver lobe, which were invisible by CT scan and Resovist MRI. This finding of multiloculated HCC was very important to decide on the patient's correct therapy. While liver transplantation is the treatment of choice in single HCC < 3 cm, it is contraindicated in multicentric HCC. In the patient described here, hemihepatectomy of the right liver lobe was performed. The histopathologic examination of the resected liver confirmed the diagnosis of multicentric HCC, which was noninvasively diagnosed only by contrast-enhanced sonography, but not by CT scan or MRI.
Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Polissacarídeos , Idoso , Biópsia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Dextranos , Feminino , Óxido Ferroso-Férrico , Hepatectomia , Humanos , Ferro , Fígado/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita , Óxidos , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
Recent technical developments in computed tomography (CT) and magnetic resonance imaging (MRI) have made a virtual presentation of the colon possible. The results of clinical investigations comparing virtual colonography and conventional colonoscopy up to now are promising. Virtual colonography is a potential tool for colorectal carcinoma screening in the future, but it still has an unsatisfactory sensitivity for the detection of small and flat lesions and exposes the patient to substantial doses of ionizing radiation. Recent investigations using ultra-low-dose (< 2 mSv) multislice CT colonography show promising results. Magnetic resonance (MR) colonography as a radiation-free modality is the technique of the future. Although encouraging results using virtual MR colonography for the detection of colorectal polyps have been reported, the sensitivity of detecting small polyps (= 10 mm) and flat lesions is poor. Main reason is the limited spatial resolution in MRI of the colon. The potential role of virtual colonography in the prevention of colorectal cancer is not yet clear. Larger studies with asymptomatic persons at average risk are needed, and further improvements in the detection of flat and very small (< 5 mm) lesions need to be achieved before advocating the use of virtual colonography for routine colorectal cancer screening.
Assuntos
Adenoma/diagnóstico , Pólipos do Colo/diagnóstico , Colonografia Tomográfica Computadorizada , Colonoscopia , Neoplasias Colorretais/diagnóstico , Imageamento por Ressonância Magnética , Adenoma/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Meios de Contraste , Diagnóstico Diferencial , Humanos , Imageamento Tridimensional , Programas de Rastreamento , Doses de Radiação , Pesquisa , Sensibilidade e Especificidade , Neoplasias do Colo Sigmoide/diagnóstico , Neoplasias do Colo Sigmoide/diagnóstico por imagem , Tomografia Computadorizada EspiralRESUMO
AIM: To evaluate cut-off values and performance of acoustic radiation force impulse imaging (ARFI) using transient elastography [FibroScan© (FS)] as a reference. METHODS: Six hundred and six patients were enrolled in this study. All patients underwent liver stiffness measurement with FS (FS-LS) and ARFI (with shear wave velocity quantification; ARFI-SWV) and the performance of ARFI in comparison to FS was determined. Sixty-eight patients underwent liver biopsy. RESULTS: Significantly higher success rates for the determination of liver stiffness were found using ARFI as compared to FS [604/606 (99.7%) vs. 482/606 (79.5%), P < 0.001]. ARFI-SWV correlated significantly with FS-LS (r = 0.920, P < 0.001). ARFI-SWV increased significantly with the stage of fibrosis (1.09 ± 0.13 m/s for patients with no significant fibrosis (FS-LS < 7.6 kPa); 1.46 ± 0.27 m/s for patients with significant liver fibrosis (7.6 < FS-LS ≤ 13.0 kPa); and 2.55 ± 0.77 m/s for patients with liver cirrhosis (FS-LS > 13.0 kPa)). ARFI-SWV cut-off values were identified for no significant fibrosis (1.29 m/s; sensitivity 91.4% and specificity 92.6%) and for liver cirrhosis (1.60 m/s; sensitivity 92.3% and specificity 96.5%). The optimal cut-off value for predicting liver fibrosis (F ≥ 2) was 1.32 m/s (sensitivity 87.0% and specificity 80.0%) and for liver cirrhosis (F4) 1.62 m/s (sensitivity 100% and specificity 85.7%), for patients who underwent liver biopsy. An excellent inter-and intraobserver reproducibility was observed for ARFI-SWV determinations. CONCLUSION: An ARFI-SWV cut-off value of 1.29 m/s seems to be optimal for patients with no significant liver fibrosis and 1.60 m/s for patients with liver cirrhosis.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Fígado/anatomia & histologia , Fígado/patologia , Adulto , Idoso , Biópsia , Feminino , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The Pliocene is important in the geological evolution of the high northern latitudes. It marks the transition from restricted local- to extensive regional-scale glaciations on the circum-Arctic continents between 3.6 and 2.4Ma. Since the Arctic Ocean is an almost land-locked basin, tectonic activity and sea-level fluctuations controlled the geometry of ocean gateways and continental drainage systems, and exerted a major influence on the formation of continental ice sheets, the distribution of river run-off, and the circulation and water mass characteristics in the Arctic Ocean. The effect of a water mass exchange restricted to the Bering and Fram Straits on the oceanography is unknown, but modelling experiments suggest that this must have influenced the Atlantic meridional overturning circulation. Cold conditions associated with perennial sea-ice cover might have prevailed in the central Arctic Ocean throughout the Pliocene, whereas colder periods alternated with warmer seasonally ice-free periods in the marginal areas. The most pronounced oceanographic change occurred in the Mid-Pliocene when the circulation through the Bering Strait reversed and low-salinity waters increasingly flowed from the North Pacific into the Arctic Ocean. The excess freshwater supply might have facilitated sea-ice formation and contributed to a decrease in the Atlantic overturning circulation.
RESUMO
INTRODUCTION: Intramural dissection of the esophagus is a rare disorder characterized by a lesion between the submucosa and mucosa dividing the esophagus into a false and true lumen. The etiology of esophageal dissection remains uncertain but it affects predominantly women in their seventies and eighties. Symptoms may include uncharacteristic ones such as retrosternal pain, odynophagia or dysphagia. Conservative management is thought to be adequate and surgery should only be performed if complications such as abscess formation or perforation appear. Here we report the case and surgical management of a combined esophageal perforation and dissection. CASE PRESENTATION: We report the case of a combined esophageal perforation and dissection in a 45-year-old Caucasian woman with a history of relapsing periods of dysphagia since her childhood. The clinical course in this patient was complicated by progression to a second perforation, which made a definitive surgical management by esophagectomy necessary. CONCLUSION: To the best of our knowledge, this is the first reported case of a combined esophageal perforation and dissection complicated by progression to a second perforation. This emphasizes that cautious and intensive observation is necessary in patients with esophageal dissection.
RESUMO
Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic disorder that usually develops in the third trimester of pregnancy and persists until delivery. The cause of ICP remains elusive, but there is evidence that mutations in the canalicular ABC transporter phospholipid flippase (MDR3) and in the bile salt export pump (BSEP) can predispose for the development of ICP. MDR3 and BSEP were investigated by gene sequencing and immunofluorescence microscopy in a patient with severe ICP of early onset. ICP was diagnosed in a patient in the first trimester of pregnancy with severe pruritus, elevated levels of bile salts, and 48-fold elevation of transaminase levels. A liver biopsy specimen showed diminished canalicular expression of the bile salt export pump BSEP, while the expression and localization of the phospholipid flippase MDR3 was normal. Gene sequencing revealed a homozygous MDR3 gene mutation (S320F). The patient was also homozygous for the common BSEP polymorphism V444A. Treatment with ursodeoxycholate normalized transaminase levels but could not prevent further elevation of bile salt levels and preterm delivery. The combined homozygous alterations of the canalicular transporters may explain the early onset and severity of ICP in this patient. The common BSEP polymorphism V444A accounts for the reduced canalicular BSEP expression. Reduced bile salt secretion through BSEP may explain the persistence of elevated bile salt levels and incomplete efficacy of ursodeoxycholate treatment.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/genética , Colestase Intra-Hepática/genética , DNA/genética , Mutação , Complicações na Gravidez , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Adulto , Biópsia , Colestase Intra-Hepática/metabolismo , Colestase Intra-Hepática/patologia , Análise Mutacional de DNA , Resistência a Múltiplos Medicamentos , Feminino , Humanos , Polimorfismo Genético , Gravidez , Resultado da Gravidez , Terceiro Trimestre da Gravidez , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Despite the introduction of effective medical treatment of peptic ulcer disease, bleeding is still a frequent complication. The aim of this study was to investigate whether the incidence and the risk profile of peptic ulcer haemorrhage have changed within a 10-year period. MATERIAL AND METHODS: In a prospective epidemiological and observational study the incidence and risk profile of peptic ulcer haemorrhage in Düsseldorf, Germany were compared between two time periods (period A: 1.3.89-28.2.90 and period B: 1.4.99-31.3.2000), involving nine hospitals with both surgical and medical departments. Patients with proven peptic ulcer haemorrhage at endoscopy or operation were included in the study; those with bleeding under defined severe stress conditions were excluded. RESULTS: No differences in bleeding ulcer incidence were observed between periods A and B (51.4 per 100,000 person-years versus 48.7), or for duodenal ulcer (24.9 versus 25.7) or for gastric ulcer bleeding (26.5 versus 23.0). A marked increase in incidence rates was observed with increasing age. In period B, patients with bleeding ulcers were older (56% versus 41% 70 years or older), were usually taking non-steroidal anti-inflammatory drugs (NSAIDs) (45% versus 27%) and were less likely to have a history of ulcer (25% versus 59%) compared with patients in period A. CONCLUSIONS: The persisting high incidence of peptic ulcer disease is a superimposing of two trends: a higher incidence in the growing population of elderly patient with a higher intake of NSAIDs and a lower incidence among younger patients due to a decrease in incidence and improved medical treatment.