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2.
J Clin Gastroenterol ; 49(5): 413-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-24921209

RESUMEN

GOALS AND BACKGROUND: Screening colonoscopy for colorectal cancer has proven to reduce mortality rates. Recently the Endocuff (EC), an attachment to the distal tip of the colonoscope, was introduced. The aim of our study was to compare EC-assisted colonoscopies with standard colonoscopies for the detection of colonic polyps. STUDY: This study is a randomized prospective 2-center trial. The study was conducted at 2 tertiary care centers. PARTICIPANTS: A total of 498 patients [249 males; median age 67 y; interquartile range (IQR), 56-75 y] for colon adenoma screening purposes were included. All patients underwent standard colonoscopy with or without the use of EC. Overall polyp detection rate, the number of colonic polyps, and the polyp distribution in the colon were measured. Difference in recognition of polyps with or without the use of EC was assessed. Statistical analysis was applied. RESULTS: In the EC group, the number of polyps detected per patient was 63% higher [2.00 (IQR, 1.00-4.00) vs. 1.00 (IQR, 1.00-2.25), P<0.0001]. The polyp detection rate in patients increased by 14% with the use of EC (56% vs. 42%, P=0.001). For polyp detection, superiority by use of EC could be observed in the sigmoid (P=0.001) and cecum (P=0.002) for polyps <1 cm in diameter. In the EC group, the number of adenomas detected per patient significantly increased by 86% (P=0.002). No major complications occurred in both groups. CONCLUSIONS: The use of the EC is feasible and safe with significantly higher polyp detection rates, especially for those located in the sigmoid region. The cuff system has the potential to improve the accuracy of screening colonoscopies.


Asunto(s)
Adenoma/diagnóstico , Carcinoma/diagnóstico , Neoplasias del Colon/diagnóstico , Pólipos del Colon/diagnóstico , Colonoscopía/instrumentación , Detección Precoz del Cáncer/instrumentación , Adenoma/patología , Anciano , Carcinoma/patología , Ciego , Colon Sigmoide , Neoplasias del Colon/patología , Pólipos del Colon/patología , Colonoscopía/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
5.
Digestion ; 83(1-2): 24-31, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-20847560

RESUMEN

BACKGROUND: Overt hepatic encephalopathy (HE) following insertion of a transjugular intrahepatic portosystemic shunt (TIPS) is a problem in some patients. In contrast to overt HE, minimal HE (MHE) following TIPS is studied to a limited degree only. We therefore evaluated the incidence of MHE in patients following TIPS insertion by determination of the critical flicker frequency (CFF). METHODS: 45 cirrhotic patients (Child A/B/C: 7/24/14; Child-Pugh score 8.5 ± 2.0) underwent TIPS because of recurrent esophageal bleeding (n = 15), refractory ascites (n = 25) or a combination of bleeding and refractory ascites (n = 5). Hemodynamic parameters were recorded during TIPS insertion. CFF was determined using a portable analyzer 2 days before and 3, 28 and 84 days after TIPS. At these time points the number connection test and biochemical markers were recorded as well. RESULTS: TIPS led to a reduction of the portal pressure gradient from 19.1 ± 5.9 to 9.3 ± 6.1 mm Hg together with a slight but significant increase in bilirubin from 1.5 ± 0.9 to 2.2 ± 1.9 mg/dl and in the international normalized ratio from 1.2 ± 0.3 to 1.4 ± 0.5. Creatinine decreased from 1.3 ± 0.6 to 1.1 ± 0.5 mg/dl. Pre-TIPS, 27 patients had normal CFF (>38 Hz, CFF 41.1 ± 2.4 Hz) and 18 patients had altered CFF (≤38 Hz, CFF 34.4 ± 3.0 Hz): 3 had grade I and 15 MHE. Three days post-TIPS, 3 of the 27 patients (11.1%) with normal CFF deteriorated to MHE, 1 of the patients with grade I HE deteriorated to grade II HE, 1 maintained grade I HE and the other improved. No patient with MHE deteriorated to overt HE. CONCLUSIONS: Using the determination of the CFF, we were able to show that elective TIPS insertion in patients with preserved liver function causes a MHE in only the minority of patients. In addition, patients with preexisting MHE did not deteriorate to overt HE.


Asunto(s)
Fusión de Flicker , Encefalopatía Hepática/diagnóstico , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Adulto , Anciano , Biomarcadores , Progresión de la Enfermedad , Femenino , Encefalopatía Hepática/etiología , Encefalopatía Hepática/psicología , Humanos , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios Prospectivos , Psicometría
6.
Int J Infect Dis ; 106: 265-268, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33848675

RESUMEN

INTRODUCTION: Use of hydroxychloroquine in patients with coronavirus disease 2019 (COVID-19) was widespread and uncontrolled until recently. Patients vulnerable to severe COVID-19 are at risk of hydroxychloroquine interactions with co-morbidities and co-medications contributing to detrimental, including fatal, adverse treatment effects. METHODS: A retrospective survey was undertaken of health conditions and co-medications of patients with COVID-19 who were pre-screened for enrolment in a randomized, double-blind, placebo-controlled hydroxychloroquine multi-centre trial. RESULTS: The survey involved 305 patients [median age 71 (interquartile range 59-81) years]. The majority of patients (n = 279, 92%) considered for inclusion in the clinical trial were not eligible, mainly due to safety concerns caused by health conditions or co-medications. The most common were QT-prolonging drugs (n = 188, 62%) and haematologic/haemato-oncologic diseases (n = 39, 13%) which prohibited the administration of hydroxychloroquine. In addition, 165 (54%) patients had health conditions and 167 (55%) patients were on co-medications that did not prohibit the use of hydroxychloroquine but had a risk of adverse interactions with hydroxychloroquine. The most common were diabetes (n = 86, 28%), renal insufficiency (n = 69, 23%) and heart failure (n = 58, 19%). CONCLUSION: The majority of hospitalized patients with COVID-19 had health conditions or took co-medications precluding safe treatment with hydroxychloroquine. Therefore, hydroxychloroquine should be administered with extreme caution in elderly patients with COVID-19, and only in clinical trials.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Hidroxicloroquina/efectos adversos , SARS-CoV-2 , Anciano , Anciano de 80 o más Años , Comorbilidad , Contraindicaciones de los Medicamentos , Interacciones Farmacológicas , Femenino , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
7.
Sci Rep ; 11(1): 14471, 2021 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-34262116

RESUMEN

Early detection of severe forms of COVID-19 is absolutely essential for timely triage of patients. We longitudinally followed-up two well-characterized patient groups, hospitalized moderate to severe (n = 26), and ambulatory mild COVID-19 patients (n = 16) at home quarantine. Human D-dimer, C-reactive protein (CRP), ferritin, cardiac troponin I, interleukin-6 (IL-6) levels were measured on day 1, day 7, day 14 and day 28. All hospitalized patients were SARS-CoV-2 positive on admission, while all ambulatory patients were SARS-CoV-2 positive at recruitment. Hospitalized patients had higher D-dimer, CRP and ferritin, cardiac troponin I and IL-6 levels than ambulatory patients (p < 0.001, p < 0.001, p = 0.016, p = 0.035, p = 0.002 respectively). Hospitalized patients experienced significant decreases in CRP, ferritin and IL-6 levels from admission to recovery (p < 0.001, p = 0.025, and p = 0.001 respectively). Cardiac troponin I levels were high during the acute phase in both hospitalized and ambulatory patients, indicating a potential myocardial injury. In summary, D-dimer, CRP, ferritin, cardiac troponin I, IL-6 are predictive laboratory markers and can largely determine the clinical course of COVID-19, in particular the prognosis of critically ill COVID-19 patients.


Asunto(s)
COVID-19/sangre , COVID-19/diagnóstico , Atención Ambulatoria , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Diagnóstico Precoz , Ferritinas/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Estudios de Seguimiento , Hospitalización , Humanos , Interleucina-6/sangre , Estudios Longitudinales , Neumonía Viral/sangre , Neumonía Viral/diagnóstico , Medicina de Precisión , Pronóstico , Cuarentena , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Troponina I/sangre
8.
Hepatology ; 47(4): 1264-76, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18318439

RESUMEN

UNLABELLED: In cirrhosis, splanchnic vasodilation contributes to portal hypertension, subsequent renal sodium retention, and formation of ascites. Urotensin II(U-II) is a constrictor of large conductive vessels. Conversely, it relaxes mesenteric vessels, decreases glomerular filtration, and increases renal sodium retention. In patients with cirrhosis, U-II plasma levels are increased. Thus, we investigated hemodynamic and renal effects of U-II and its receptor antagonist, palosuran, in cirrhotic bile duct-ligated rats (BDL). In BDL and sham-operated rats, we studied acute effects of U-II (3 nmol/kg; intravenously) and palosuran (10 mg/kg; intravenously) and effects of oral administration of palosuran (30 mg/kg/day; 3 days) on hemodynamics and renal function. We localized U-II and U-II-receptor (UTR) in livers and portal veins by immunostaining. We determined U-II-plasma levels by enzyme-linked immunosorbent assay (ELISA), and mesenteric nitrite/nitrate-levels by Griess-reaction. RhoA/Rho-kinase and endothelial nitric oxide synthase (eNOS) pathways were determined by western blot analysis and reverse transcription polymerase chain reaction (RT-PCR) in mesenteric arteries. U-II plasma levels, as well as U-II and UTR-receptor expression in livers and portal veins of cirrhotic rats were significantly increased. U-II administration further augmented the increased portal pressure (PP) and decreased mean arterial pressure (MAP), whereas palosuran decreased PP without affecting MAP. The decrease in PP was associated with an increase in splanchnic vascular resistance. In mesenteric vessels, palosuran treatment up-regulated expression of RhoA and Rho-kinase, increased Rho-kinase-activity, and diminished nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) signaling. Moreover, palosuran increased renal blood flow, sodium, and water excretion in BDL rats. CONCLUSION: In BDL rats, U-II is a mediator of splanchnic vasodilation, portal hypertension and renal sodium retention. The U-II-receptor antagonist palosuran might represent a new therapeutic option in liver cirrhosis with portal hypertension.


Asunto(s)
Hemodinámica/efectos de los fármacos , Riñón/efectos de los fármacos , Cirrosis Hepática Biliar/tratamiento farmacológico , Quinolinas/uso terapéutico , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Urea/análogos & derivados , Urotensinas/uso terapéutico , Administración Oral , Animales , GMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Pruebas de Función Renal , Hígado/metabolismo , Cirrosis Hepática Biliar/metabolismo , Masculino , Arterias Mesentéricas/metabolismo , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Nitritos/metabolismo , Vena Porta/metabolismo , Quinolinas/administración & dosificación , Quinolinas/farmacología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Urea/administración & dosificación , Urea/farmacología , Urea/uso terapéutico , Urotensinas/sangre , Urotensinas/metabolismo , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/metabolismo
9.
Digestion ; 80(3): 165-9, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19776579

RESUMEN

BACKGROUND/AIMS: Coexisting gastric varices at baseline or the risk of their formation during treatment could alter the approach for primary bleeding prophylaxis in patients with large esophageal varices. METHODS: Data analysis of 152 patients with cirrhosis and large esophageal varices included in the German multicenter trial on primary prevention of variceal bleeding. RESULTS: 20 patients (13.6%) had coexisting gastric varices at baseline (GOV+). 10 of those each received either band ligation or propranolol, respectively. During follow-up (34.4 +/- 18.9 months) new gastric varices occurred in 2/75 (2.7%, ligation) and 4/77 (5.2%, propranolol) patients, respectively. One patient with newly developed gastric varices bled (propranolol group). GOV+ patients had a better baseline liver function and overall survival. Bleeding incidence did not differ significantly between GOV+ and GOV- patients (3-year actuarial risk: 20.0 +/- 10.6% (GOV+), 38.1 +/- 4.4% (GOV-), p = 0.195). Among GOV+ patients, bleeding occurred in 3/10 patients of the propranolol group and in 0/10 in the ligation group (p = 0.038). CONCLUSION: Prophylactic band ligation of large esophageal varices is safe and effective also in patients with coexisting gastric varices. Band ligation did not increase the risk of secondary gastric varices compared to propranolol.


Asunto(s)
Várices Esofágicas y Gástricas/cirugía , Hemorragia Gastrointestinal/prevención & control , Cirrosis Hepática/complicaciones , Adolescente , Adulto , Anciano , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/patología , Femenino , Hemorragia Gastrointestinal/etiología , Humanos , Estimación de Kaplan-Meier , Ligadura , Masculino , Persona de Mediana Edad , Adulto Joven
10.
Liver Int ; 28(3): 331-8, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18290775

RESUMEN

AIM: Nitric oxide levels are decreased in the cirrhotic liver and increased in the systemic vasculature. We investigated whether the nitric oxide synthase (NOS) transcription enhancer AVE 9488 ameliorates portal hypertension in cirrhotic rats. METHODS: Rats with secondary biliary cirrhosis [bile duct ligation (BDL)] were treated with AVE 9488. BDL animals without treatment served as controls. Blood flow was determined with the microsphere technique. Intrahepatic resistance was measured by in situ perfusion. NOS-3 mRNA and protein levels in the liver, aorta and superior mesenteric artery (SMA) were measured. RESULTS: Arterial pressure did not differ between treated and non-treated animals. Portal pressure, hepatic portal-vascular resistance and perfusion pressure of the in situ perfused liver were lower in the AVE 9488-treated animals. Arterial splanchnic resistance, portal venous inflow and shunt volume were increased by AVE 9488. N (G)-nitro-l-arginine methyl ester abolished the effect of AVE 9488. AVE 9488-treated rats had higher liver NOS-3 mRNA and protein levels, whereas NOS-3 mRNA and protein in the aorta and the SMA did not vary between groups. Phosphorylation of liver vasodilator-stimulated phosphoprotein (VASP) and NOS-3 as well as hepatic nitrite/nitrate was increased by AVE 9488. CONCLUSIONS: Treatment of BDL rats with the NOS transcription enhancer AVE 9488 induces an increase in NOS-3 mRNA and protein in the liver. This is associated with an amelioration of portal hypertension.


Asunto(s)
Benzamidas/uso terapéutico , Colestasis Extrahepática , Hipertensión Portal/tratamiento farmacológico , Hipertensión Portal/etiología , Cirrosis Hepática Biliar/complicaciones , Hígado/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Factores de Transcripción/uso terapéutico , Animales , Benzamidas/administración & dosificación , Benzamidas/farmacología , Presión Sanguínea/efectos de los fármacos , Hígado/irrigación sanguínea , Cirrosis Hepática Biliar/tratamiento farmacológico , Masculino , Óxido Nítrico/metabolismo , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
11.
Eur J Gastroenterol Hepatol ; 20(4): 353-5, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18334881

RESUMEN

Megacystis-microcolon intestinal hypoperistalsis syndrome (MMHIS or Berdon syndrome) is an autosomal-recessive disorder characterized by chronic intestinal obstruction. Although the disease is often diagnosed in female infants we describe a man with late diagnosis in adulthood. Our patient presented soon after birth with intestinal obstruction and developed short bowel syndrome after multiple intestinal resections. Of note, the connective tissue net within the muscle layers of the intestinal wall was absent ('aplastic desmosis'). This case illustrates the variable clinical features of MMHIS and aplastic desmosis, which might delay the correct diagnosis of a severe disorder.


Asunto(s)
Anomalías Múltiples , Enfermedades del Colon/etiología , Tejido Conectivo/anomalías , Obstrucción Intestinal/etiología , Peristaltismo , Síndrome del Intestino Corto/etiología , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/cirugía , Anomalías Múltiples/terapia , Adulto , Enfermedades del Colon/diagnóstico por imagen , Enfermedades del Colon/cirugía , Nutrición Enteral , Humanos , Obstrucción Intestinal/diagnóstico por imagen , Obstrucción Intestinal/cirugía , Masculino , Síndrome , Resultado del Tratamiento , Ultrasonografía
12.
Eur J Gastroenterol Hepatol ; 19(10): 846-52, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17873607

RESUMEN

BACKGROUND: The aim of this study was to determine the prognostic relevance of the portal pressure gradient (PPG) before and after transjugular intrahepatic portosystemic stent shunt (TIPS) insertion in patients with liver cirrhosis and recurrent oesophageal variceal bleeding. METHODS: 118 cirrhotic patients (Child A/B/C, 41/56/21; Child score, 7.7+/-2.0; baseline PPG, 21.8+/-4.7 mmHg) underwent TIPS for the prevention of variceal rebleeding. A multivariate logistic regression analysis was applied to identify the independent determinants of rebleeding and survival. The estimated rebleeding rate and the estimated survival were compared by log-rank testing. RESULTS: TIPS insertion reduced the PPG by 53.2+/-17.7%. During follow-up 21 patients suffered significant rebleeding (17.8%); bleeding-related mortality was 3.4% (four patients). The median survival [95% confidence intervals (CI)] was 48.2 (39.8; 60.8) months. The multivariate Cox model identified creatinine as the only independent predictor of survival, and the initial decrease of the PPG after TIPS as the only independent predictor of rebleeding. PPG before TIPS (21.8+/-4.7 mmHg) and the gradient at the time of rebleeding (22.0+/-2.9 mmHg) did not differ significantly. Patients with an initial decrease of the PPG after TIPS <30% were at the highest risk for rebleeding. Patients with an initial decrease of the PPG >60% rarely suffered from rebleeding. CONCLUSIONS: The initial decrease in the PPG after TIPS is a predictor for the risk of rebleeding but not for survival after TIPS. For that reason, in patients undergoing TIPS placement for the prevention of recurrent bleeding from oesophageal varices, an initial reduction of the PPG of 30-50% should be attempted.


Asunto(s)
Várices Esofágicas y Gástricas/cirugía , Hemorragia Gastrointestinal/prevención & control , Cirrosis Hepática/complicaciones , Presión Portal , Derivación Portosistémica Intrahepática Transyugular , Anciano , Métodos Epidemiológicos , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/fisiopatología , Femenino , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/fisiopatología , Humanos , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Pronóstico , Recurrencia , Resultado del Tratamiento
13.
Rofo ; 189(2): 146-151, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28002852

RESUMEN

Purpose Q fever is a worldwide zoonosis that causes clinical symptoms ranging from mild flu-like symptoms to severe pneumonia and/or hepatitis. This retrospective study was conducted to describe the radiographic and clinical signs in patients with acute Q fever pneumonia in Southwest Germany. Patients and Methods 40 patients with IgM-positive Q fever-related pneumonia who were treated in the years 2006 to 2016 in our hospital were retrospectively identified. Clinical and laboratory data were analyzed. Chest radiographs were reviewed by two radiologists and interpreted using a standardized protocol. Results Females and males were equally affected. The mean age was 44.9 ±â€Š15.7 years. About half of the patients (45 %) acquired their infection in the second quarter of the year. The main complaints were fever, cough and dyspnea. While the white cell blood count was in the normal range in most of the patients, the CRP value was markedly elevated. Q fever-related hepatitis was found in 63 % of the patients. Air space opacification was the predominant radiographic sign and was found in 27 of the patients (82 %). The typical chest radiographic pattern was a single segmental opacity. However, multiple segmental opacities and patchy opacities were also found. Lobar opacities were found in only 2 (6 %) of the patients. Conclusion Unilobar, unilateral, segmental opacities are the key feature of Q fever pneumonia chest radiographs. Definitive radiographic differentiation from other community-acquired pneumonias is not possible, but Q fever pneumonia should be considered in middle-aged patients with segmental opacities living in an endemic area. Key points · Unilobar, unilateral, segmental opacities are the key feature of Q fever pneumonia.. · Lobar and patchy as well as multisegmental opacities are also found.. · Chest radiography does not allow the differentiation of Q fever from other pneumonias.. Citation Format · Biecker A, Bitzer M, Biecker E. Q Fever Pneumonia in Southwest Germany: Radiographic and Clinical Findings. Fortschr Röntgenstr 2017; 189: 146 - 151.


Asunto(s)
Enfermedades Endémicas/estadística & datos numéricos , Neumonía Bacteriana/diagnóstico por imagen , Neumonía Bacteriana/epidemiología , Fiebre Q/diagnóstico , Fiebre Q/epidemiología , Radiografía Torácica/estadística & datos numéricos , Adulto , Distribución por Edad , Femenino , Alemania/epidemiología , Humanos , Masculino , Neumonía Bacteriana/patología , Prevalencia , Fiebre Q/patología , Factores de Riesgo , Distribución por Sexo
14.
Comp Hepatol ; 5: 9, 2006 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-17147823

RESUMEN

BACKGROUND: Hepatic sinusoidal resistance is regulated by vasoactive factors including endothelin-1 (ET-1) and nitric oxide (NO). In the absence of NO, vasoconstrictor response to endothelin is expected to predominate. Therefore, we hypothesized sensitivity to endothelin to be increased in mice lacking the endothelial cell NO synthase gene. Response of vascular resistance to endothelin was assessed in the in situ perfused liver of endothelial constitutive nitric oxide synthase (ecNOS) knockout and wild type mice. Livers were also harvested for RNA and protein isolation for quantitative PCR and Western blotting, respectively. The expression of endothelin receptors, isoenzymes of NO synthase, heme-oxygenase and adrenomedullin was quantified. RESULTS: Endothelin increased hepatic vascular resistance in a dose-dependent manner in both strains; however, this increase was significantly less in ecNOS knockout mice at physiologic concentrations. Expression of heme-oxygenases and adrenomedullin was similar in both groups, whereas inducible nitric oxide synthase (iNOS) protein was not detectable in either strain. mRNA levels of pre-pro-endothelin-1 and ETB receptor were comparable in both strains, while mRNA for ETA receptor was decreased in ecNOS knockouts. CONCLUSION: Livers of ecNOS knockout mice have a decreased sensitivity to endothelin at physiologic concentrations; this is associated with a decreased expression of ETA receptors, but not with other factors, such as iNOS, ETB receptors, adrenomedullin or heme-oxygenase. Further studies targeting adaptive changes in ETA receptor distribution and/or intracellular signaling downstream of the receptor are indicated.

15.
Exp Biol Med (Maywood) ; 231(6): 1101-5, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16741057

RESUMEN

Altered activity of retinal endothelin-1 (ET-1) and nitric oxide may play a causal role in the hemodynamic and histopathological changes of diabetic retinopathy. This study evaluated the therapeutic potential of long-term selective blockade of the ET-1(A) receptor (ETRA) to prevent the development of retinopathy in a genetic mouse model of nonobese type 1 diabetes (NOD). Mice with NOD that received subcutaneous implantation of insulin pellets and wild-type control mice were treated for 4 months with the selective ETRA antagonist LU208075 (30 mg/kg/day) via drinking water. At the end of the study, blood glucose levels were evaluated, and animals were anesthetized and perfused intracardially with FITC-labeled dextran. Retinas were removed and either fixed in formalin for confocal microscope evaluation of retinal vascular filling or transferred to RNALater for quantitative reverse transcriptase-polymerase chain reaction to evaluate expression of NOS-3, NOS-1, ET-1, ETRA, ETRB, and the angiogenic factor adrenomedullin. Compared with wild-type controls, expression of ET-1, ETRA, ETRB, and adrenomedullin in mice with NOD were markedly upregulated in the retinas of nontreated mice (cycle time values relative to GAPDH [deltaCt], 14.8 vs. 13.7, 18.57 vs. 17.5, 10.76 vs. 9.9, and 11.7 vs. 9.1, respectively). Mean integral fluorescence intensity (MIFI) of retinal vascular filling was reduced from normal values of 24 to 12.5 in nontreated animals. LU208075 treatment normalized the upregulated expression of ET-1 and adrenomedullin, as well as the deficit in MIFI, but did not affect the increased ETRA and ETRB expression or the elevated plasma glucose levels found in nontreated animals. NOS isoform expression was essentially unchanged. ETRA antagonists may provide a novel therapeutic strategy to slow or prevent progression of retinal microvascular damage and proliferation in patients for whom there is clear evidence of activation of the ET-1 system.


Asunto(s)
Retinopatía Diabética/prevención & control , Antagonistas de los Receptores de la Endotelina A , Endotelina-1/antagonistas & inhibidores , Péptidos/farmacología , Vasodilatadores/farmacología , Adrenomedulina , Animales , Glucemia/análisis , Femenino , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Inyecciones Subcutáneas , Insulina/administración & dosificación , Insulina/farmacología , Ratones , Ratones Endogámicos NOD , Fenilpropionatos/farmacología , Piridazinas , Factores de Tiempo
16.
World J Gastrointest Pharmacol Ther ; 6(4): 172-82, 2015 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-26558151

RESUMEN

Non-variceal upper gastrointestinal bleeding (UGIB) is defined as bleeding proximal to the ligament of Treitz in the absence of oesophageal, gastric or duodenal varices. The clinical presentation varies according to the intensity of bleeding from occult bleeding to melena or haematemesis and haemorrhagic shock. Causes of UGIB are peptic ulcers, Mallory-Weiss lesions, erosive gastritis, reflux oesophagitis, Dieulafoy lesions or angiodysplasia. After admission to the hospital a structured approach to the patient with acute UGIB that includes haemodynamic resuscitation and stabilization as well as pre-endoscopic risk stratification has to be done. Endoscopy offers not only the localisation of the bleeding site but also a variety of therapeutic measures like injection therapy, thermocoagulation or endoclips. Endoscopic therapy is facilitated by acid suppression with proton pump inhibitor (PPI) therapy. These drugs are highly effective but the best route of application (oral vs intravenous) and the adequate dosage are still subjects of discussion. Patients with ulcer disease are tested for Helicobacter pylori and eradication therapy should be given if it is present. Non-steroidal anti-inflammatory drugs have to be discontinued if possible. If discontinuation is not possible, cyclooxygenase-2 inhibitors in combination with PPI have the lowest bleeding risk but the incidence of cardiovascular events is increased.

17.
Eur J Gastroenterol Hepatol ; 15(4): 423-7, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12655265

RESUMEN

The clinical presentation of adult coeliac disease is often uncharacteristic, with extraintestinal symptoms being the main findings. We report a 48-year-old woman who presented with type II, hepatitis-C-negative cryoglobulinaemia, elevated liver enzymes, and iron deficiency. Antinuclear antibodies were positive, and immunoglobulin G (IgG) levels were elevated. On liver biopsy, a diagnosis of type I autoimmune hepatitis with a possible autoimmune cholangitis overlap syndrome was made. Immunosuppressive treatment led to a normalization of transaminase levels and resolved the cryoglobulinaemic vasculitis. In addition, the patient exhibited low ferritin and iron levels, which led to the diagnosis of coeliac disease. Long-standing, untreated coeliac disease is recognized to be a trigger for autoimmune disorders and is known to be associated with other autoimmune diseases, but the association with autoimmune hepatitis or autoimmune cholangitis is reported rarely. We conclude that in patients with autoimmune liver disease and unspecific clinical signs, such as iron deficiency, coeliac disease must be ruled out.


Asunto(s)
Enfermedad Celíaca/complicaciones , Crioglobulinemia/complicaciones , Hepatitis Autoinmune/complicaciones , Antiinflamatorios/uso terapéutico , Azatioprina/uso terapéutico , Enfermedad Celíaca/tratamiento farmacológico , Crioglobulinemia/tratamiento farmacológico , Femenino , Hepatitis Autoinmune/tratamiento farmacológico , Humanos , Inmunosupresores/uso terapéutico , Persona de Mediana Edad , Prednisona/uso terapéutico
18.
PLoS One ; 9(12): e114267, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25470133

RESUMEN

OBJECTIVES: The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC). METHODS: This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany. PARTICIPANTS: 500 patients (235 males, median age 64[IQR 54-73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR). RESULTS: The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29-41%] vs. 20.7%[95%CI 15-26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01-1.05), male sex (OR 1.74; 95%CI 1.10-2.73), withdrawal time (OR 1.16; 95%CI 1.05-1.30), procedure time (OR 1.07; 95%CI 1.04-1.10), colon cleanliness (OR 0.60; 95%CI 0.39-0.94) and use of Endocuff (OR 2.09; 95%CI 1.34-3.27) were independent predictors of adenoma detection rates. CONCLUSIONS: EC increases the adenoma detection rate by 14.7%(95%CI 6.9-22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas. TRIAL REGISTRATION: ClinicalTrials.gov NCT02034929.


Asunto(s)
Adenoma/diagnóstico , Neoplasias del Colon/diagnóstico , Colonoscopios , Anciano , Colonoscopía , Reacciones Falso Negativas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
19.
World J Gastroenterol ; 19(31): 5035-50, 2013 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-23964137

RESUMEN

Bleeding from esophageal varices is a life threatening complication of portal hypertension. Primary prevention of bleeding in patients at risk for a first bleeding episode is therefore a major goal. Medical prophylaxis consists of non-selective beta-blockers like propranolol or carvedilol. Variceal endoscopic band ligation is equally effective but procedure related morbidity is a drawback of the method. Therapy of acute bleeding is based on three strategies: vasopressor drugs like terlipressin, antibiotics and endoscopic therapy. In refractory bleeding, self-expandable stents offer an option for bridging to definite treatments like transjugular intrahepatic portosystemic shunt (TIPS). Treatment of bleeding from gastric varices depends on vasopressor drugs and on injection of varices with cyanoacrylate. Strategies for primary or secondary prevention are based on non-selective beta-blockers but data from large clinical trials is lacking. Therapy of refractory bleeding relies on shunt-procedures like TIPS. Bleeding from ectopic varices, portal hypertensive gastropathy and gastric antral vascular ectasia-syndrome is less common. Possible medical and endoscopic treatment options are discussed.


Asunto(s)
Várices Esofágicas y Gástricas/terapia , Hemorragia Gastrointestinal/terapia , Hipertensión Portal/terapia , Antagonistas Adrenérgicos beta/uso terapéutico , Antibacterianos/uso terapéutico , Endoscopía , Várices Esofágicas y Gástricas/diagnóstico , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/prevención & control , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Hemostasis Endoscópica , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Ligadura , Derivación Portosistémica Intrahepática Transyugular , Stents , Resultado del Tratamiento , Vasoconstrictores/uso terapéutico
20.
ISRN Hepatol ; 2013: 541836, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-27335828

RESUMEN

Gastrointestinal bleeding related to portal hypertension is a serious complication in patients with liver cirrhosis. Most patients bleed from esophageal or gastric varices, but bleeding from ectopic varices or portal hypertensive gastropathy is also possible. The management of acute bleeding has changed over the last years. Patients are managed with a combination of endoscopic and pharmacologic treatment. The endoscopic treatment of choice for esophageal variceal bleeding is variceal band ligation. Bleeding from gastric varices is treated by injection with cyanoacrylate. Treatment with vasoactive drugs as well as antibiotic treatment is started before or at the time point of endoscopy. The first-line treatment for primary prophylaxis of esophageal variceal bleeding is nonselective beta blockers. Pharmacologic therapy is recommended for most patients; band ligation is an alternative in patients with contraindications for or intolerability of beta blockers. Treatment options for secondary prophylaxis include variceal band ligation, beta blockers, a combination of nitrates and beta blockers, and combination of band ligation and pharmacologic treatment. A clear superiority of one treatment over the other has not been shown. Bleeding from portal hypertensive gastropathy or ectopic varices is less common. Treatment options include beta blocker therapy, injection therapy, and interventional radiology.

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