RESUMEN
BACKGROUND: Body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin (UFH) for the treatment of patients with venous thromboembolism. However, body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing. Therefore a fixed LMWH dose, independent of body-weight, might rationalize initial treatment for venous thromboembolism. METHODS: Patients with proven proximal deep-vein thrombosis were randomly assigned to fixed dose subcutaneous LMWH Certoparin (8,000 anti-factor Xa U b.i.d.; 265 patients) or to adjusted dose i.v. UFH (273 patients) for 12 days. Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months. The primary outcome measure was a 30 percent or greater improvement in the Marder Score, as revealed by repeated venography on day 12 (end of the initial treatment). The secondary composite outcome measure included death, recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee. RESULTS: The Marder score improved by 30% or more in 30.3% and 25.0% of patients assigned to LMWH (198 paired venograms) and UFH (192 paired venograms), respectively (2p = 0.26). At the end of the initial treatment, the composite outcome was observed in 4 of the 265 patients (1.5%) randomized to LMWH, as compared with 14 of the 273 patients (5.1%) randomized to UFH (2p = 0.03). At 6 months these figures were 6.8% and 12.8%, respectively (risk reduction 0.53, confidence interval 0.31-0.90, 2p = 0.02). CONCLUSION: Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis.
Asunto(s)
Anticoagulantes/administración & dosificación , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina/administración & dosificación , Trombosis de la Vena/tratamiento farmacológico , Enfermedad Aguda , Adulto , Anciano , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Peso Corporal , Estudios de Cohortes , Femenino , Hemorragia/inducido químicamente , Heparina/efectos adversos , Heparina/uso terapéutico , Heparina de Bajo-Peso-Molecular/efectos adversos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Humanos , Inyecciones Intravenosas , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Flebografía , Vena Poplítea , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/mortalidad , Recurrencia , Resultado del Tratamiento , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/mortalidad , Vitamina K/antagonistas & inhibidoresRESUMEN
BACKGROUND: The aim of this randomized, double-blind and prospective clinical trial was to investigate whether an increase of the conventional daily dosage (3,000 IU aXa) of the low molecular weight heparin certoparin up to 5,000 IU aXa/day might lower the incidence of deep vein thrombosis (DVT) in patients undergoing elective hip surgery. METHODS: The main criterium of this trial was the incidence of DVT diagnosed by bilateral ascending venography, which was performed either if DVT was clinically suspected or in each remaining patient between the 12th and the 14th postoperative day. A total number of 172 patients were enrolled to receive the conventional dosage of 3,000 IU aXa (Mono-Embolex NM) and 169 patients to receive the high dosage form (5,000 IU aXa) once daily. The mean age (+/-SD) was 69.6+/-9.5 and 67+/-11.7 years. RESULTS: No relevant differences were found concerning predisposing risk factors. The duration of surgery was 93+/-25.2 and 88+/-21.4 min (mean+/-SD). Surgical type and approach were not different between the groups. Deep vein thrombosis was detected in 17 patients (9.9%) in the conventional dose group and in 16 patients (9.5%) in the high dose group (intent-to-treat analysis; n.s.). The rate of bleeding complications was not significantly different except the cell saver volumes (770+/-136 vs 475+/-186 ml; p<0.001). No significant difference was found in the serious adverse event reporting along the lines of EC-GCP (10 vs 8 events; p=0.65). CONCLUSIONS: This clinical trial confirmed that the conventional dosage (3,000 IU aXa/day) of certoparin ensures maximal antithrombotic activity.
Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Heparina de Bajo-Peso-Molecular/uso terapéutico , Trombosis de la Vena/etiología , Trombosis de la Vena/prevención & control , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Hematoma/etiología , Hemorragia/etiología , Heparina de Bajo-Peso-Molecular/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Edema Pulmonar/etiología , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiologíaRESUMEN
Polycystic kidney disease (PKD) is characterized by interstitial fibrosis and formation of renal cysts. Interestingly, interstitial fibrosis and renal cyst formation were also seen in human endothelin-1 (ET-1) transgenic mice. This study, therefore, analyzes the tissue distribution of ET-1, the tissue concentrations of ET-1, as well as the expression of ET receptor subtypes in the kidneys of a rat model of PKD: Han:SPRD rats. Six-week-old heterozygous (cy/+) and homozygous (cy/cy), as well as 6-mo-old heterozygous (cy/+) Han:SPRD rats and the corresponding age-matched Sprague Dawley littermates (SD) (+/+) were analyzed. Furthermore, the acute effects of the mixed (A/B) endothelin receptor antagonist bosentan on hemodynamic and renal function were investigated in 6-mo-old, conscious, chronically instrumented (cy/+) rats. The kidneys of affected rats showed significantly elevated tissue levels of ET-1 compared with age-matched controls (3.5 +/- 0.3-fold in young cy/cy rats, P < 0.01; 1.4 +/- 0.2-fold in young cy/+ rats, P < 0.01; 6.2 +/- 0.4-fold in old cy/+ rats, P < 0.001) due to a highly increased ET-1 synthesis within the epithelial cells of the cysts. Analyzing tissue sections from patients with typical autosomal dominant PKD demonstrated a high ET-1 expression within the epithelial cells of the cysts as well. Scatchard analysis revealed a markedly decreased ETA and ETB receptor density in all groups of affected rats. The acute blockade of both endothelin receptor subtypes using bosentan in 6-mo-old heterozygous PKD rats led to a significant decrease in mean arterial BP (MAP) (-19.7 +/- 2.1 mmHg, P < 0.05) and GFR (-41 +/- 5%, P < 0.005). Renal blood flow (RBF) was significantly increased (+2.1 +/- 0.5 ml/min, P < 0.05) after bosentan, whereas bosentan had no effect on MAP, GFR, and RBF in age-matched controls. These data show that the paracrine renal endothelin system is activated in PKD and participates in the regulation of MAP, GFR, RBF, and possibly contributes to renal cyst formation and fibrosis.
Asunto(s)
Endotelina-1/metabolismo , Enfermedades Renales Poliquísticas/metabolismo , Receptores de Endotelina/metabolismo , Análisis de Varianza , Animales , Antihipertensivos/farmacología , Unión Competitiva , Bosentán , Técnicas de Cultivo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Endotelina-1/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Inmunohistoquímica , Masculino , Enfermedades Renales Poliquísticas/patología , Radioinmunoensayo , Ratas , Ratas Sprague-Dawley , Receptores de Endotelina/efectos de los fármacos , Valores de Referencia , Circulación Renal/efectos de los fármacos , Sulfonamidas/farmacologíaRESUMEN
Polycystic kidney disease (PKD) is characterized by structural alterations such as thickening of the tubule basement membrane, interstitial fibrosis, and formation of cysts. Han:SPRD rats are a well-known rat model of human PKD. Interestingly, interstitial fibrosis, glomerulosclerosis, and cyst formation were also seen in human endothelin-1 (ET-1) transgenic mice. We therefore analyzed the tissue concentrations of ET-1 and the expression of ET receptor subtypes in the kidneys of young homozygous (cy/cy), heterozygous (cy/+) 6 week-old male Han:SPRD, and corresponding control rats. The kidneys of affected rats showed significantly elevated tissue levels of ET-1 compared to age-matched controls. Scatchard analysis, on the other hand, revealed markedly decreased ETA and ETB receptor density in all groups of affected rats. The binding affinity of both ET receptor subtypes was slightly decreased in Han:SPRD rats. These data show that the renal paracrine ET system is activated in PKD and might contribute to renal cyst formation and development of end-stage kidney disease.
Asunto(s)
Endotelinas/fisiología , Enfermedades Renales Poliquísticas/genética , Enfermedades Renales Poliquísticas/fisiopatología , Animales , Endotelina-1/metabolismo , Humanos , Riñón/metabolismo , Cinética , Masculino , Ratones , Enfermedades Renales Poliquísticas/metabolismo , Ratas , Ratas Endogámicas , Ratas Sprague-Dawley , Receptor de Endotelina A , Receptor de Endotelina B , Receptores de Endotelina/metabolismoRESUMEN
UNLABELLED: The efficacy and safety of low molecular weight heparin (LMWH), unfractionated heparin (UFH) and warfarin for prophylaxis of thrombo-embolism in orthopaedic surgery were compared using meta-analysis techniques. Twenty-two studies were included, 2 of which compared LMWH to warfarin. The mean probabilities to develop deep-vein thrombosis (DVT), pulmonary embolism and major and minor bleeding using UFH were: 0.21 (95% confidence interval, CI: 0.18-0.24); 0.01 (95% CI: 0.01-0.02); 0.05 (95% CI: 0.03-0.07), and 0.19 (95% CI: 0.17-0.22), respectively. The relative risk (RR) of DVT for LMWH vs. UFH was 0.76 (95% CI: 0.60-0.91), p < 0.05 and for LMWH vs. warfarin 0.78 (95% CI: 0.69-0.87), p < 0.05. The RR of minor bleeding for LMWH vs. UFH was 0.76 (95% CI: 0.64-0.92), p < 0.05. The RR of minor bleeding for LMWH vs. warfarin was 3.28 (95% CI: 2.21-4.70), p < 0.05. CONCLUSION: in orthopaedic surgery, LMWH is significantly superior to both UFH and warfarin in the prevention of DVT and results in significantly less minor bleeding complications when compared to UFH, but significantly more minor bleeding when compared to warfarin.
Asunto(s)
Anticoagulantes/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina/uso terapéutico , Ortopedia , Complicaciones Posoperatorias/prevención & control , Tromboembolia/prevención & control , Warfarina/uso terapéutico , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Heparina/efectos adversos , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Warfarina/efectos adversosRESUMEN
A randomized, double-blind multicenter trial was performed to compare the safety and efficacy of a new low-molecular-weight heparin (LMWH) (LU 47311, Clivarine) and standard unfractionated heparin for the prophylaxis of postoperative venous thromboembolism. Altogether 1351 patients scheduled to undergo abdominal surgery were included. Main outcome measures included the incidence of thromboembolic events (deep vein thrombosis, pulmonary embolism, or both) and bleeding complications, including wound hematoma. A total of 655 patients received 1750 anti-Xa IU of LMWH plus a placebo injection daily; 677 patients received 5000 IU of unfractionated heparin (UFH) twice a day. Both drugs were found to be equally effective, as 4.7% of patients in the LMWH group and 4.3% in the UFH group developed postoperative thromboembolic complications. However, the incidence of bleeding complications was significantly reduced in the LMWH group: 55 (8.3%) patients in the LMWH group and 80 (11.8%) in the UFH group developed bleeding complications, a relative risk (RR) of 0.70 (95% CI 0.51-0.97;p = 0.03); wound hematoma occurred in 29 (4.4%) of the LMWH group compared with 55 (7.7%) in those in the UFH group for an RR of 0.57 (95% CI 0.37-0.88;p = 0.01). This study confirmed that a very low dose of 1750 anti-Xa IU daily of this new LMWH is as effective as 10,000 IU of UFH for preventing postoperative deep vein thrombosis. At this dose its administration is associated with a significant reduction in the risk of bleeding including wound hematoma.
Asunto(s)
Anticoagulantes/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Heparina/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Tromboembolia/prevención & control , Adulto , Anciano , Método Doble Ciego , Femenino , Hemorragia/inducido químicamente , Heparina/efectos adversos , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Embolia Pulmonar/mortalidad , Embolia Pulmonar/prevención & control , Factores de Riesgo , Tromboflebitis/epidemiología , Tromboflebitis/prevención & control , Resultado del TratamientoRESUMEN
BACKGROUND: Endoscopic ultrasonography (EUS) and somatostatin receptor scintigraphy (SRS) can detect a high percentage of gastroenteropancreatic neuroendocrine tumours especially in the upper gastrointestinal tract. The ability of these procedures to localise primary tumour lesions and metastases of gastrinomas and insulinomas was evaluated in comparison with transabdominal ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). PATIENTS AND METHODS: In a prospective trial, patients with gastrinomas (n = 10) and insulinomas (n = 10) diagnosed by clinical signs and laboratory tests were assessed by EUS, SRS, US, CT and MRI. RESULTS: In 10 patients with gastrinoma and 10 patients with insulinoma, a total of 14 separate primary tumour lesions were histologically confirmed for each of the tumour entities. The mean diameter was 2.1 cm for gastrinomas and 1.5 cm for insulinomas. All insulinomas and nine gastrinoma lesions were located in the pancreas. Three gastrinomas were found in the duodenal wall, one in a periduodenal lymph node, and one in the liver, For gastrinomas, sensitivities were 79% with EUS, 86% with SRS and 29% with CT, US, and MRI. For insulinomas, sensitivities were 93% with EUS, 14% with SRS, 21% with CT and 7% with US and MRI. CONCLUSIONS: EUS is of high value for localising primary lesions of both tumour entities. SRS is a very sensitive procedure for diagnosing of gastrinomas but not insulinomas. CT, US and MRI are primarily useful for visualising metastases.
Asunto(s)
Endosonografía , Gastrinoma/diagnóstico , Insulinoma/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Receptores de Somatostatina , Tomografía Computarizada de Emisión de Fotón Único , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Gastrinoma/diagnóstico por imagen , Humanos , Insulinoma/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico por imagen , Estudios Prospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: The renal endothelin system has been implicated in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). However, little is known about the function and cellular distribution of endothelin receptor subtypes in the kidneys of SHR. METHODS: We analyzed the expression of endothelin receptor subtypes in the kidneys of 16-week-old SHR using Scatchard analysis, receptor autoradiography, Northern blot analysis and in situ hybridization. Wistar-Kyoto rats (WKY) served as controls. Furthermore, we investigated the effects of the mixed (A/B) endothelin receptor antagonist bosentan and the ETA receptor antagonist BQ 123 on mean arterial blood pressure (MAP), renal blood flow (RBF) and glomerular filtration rate (GFR) in conscious chronically instrumented rats. RESULTS: In SHR, we found by receptor autoradiography an overexpression of the endothelin A receptor (ETA) in the glomeruli (2.2 +/- 0.4-fold; P < 0.05) and smooth muscle cells of intrarenal arteries (1.9 +/- 0.2-fold; P < 0.05) compared to age-matched WKY. In addition, our study revealed a pronounced upregulation of endothelin B receptor (ETB) in the glomeruli of SHR (5.6 +/- 0.8-fold; P < 0.01). Blockade of endothelin receptors in SHR with bosentan (A and B receptor blockade) as well as with BQ 123 (A receptor blockade) led to a significant decrease in MAP (-18.6 +/- 2.1 and -19 +/- 1.3 mmHg, respectively; P < 0.05 in both cases) and a significant increase in RBF (+2.8 +/- 0.5 and +3.1 +/- 0.37 ml/min, respectively; P < 0.05 in both cases). The blockade of both ETA and ETB by bosentan had no further effect on MAP reduction or RBF increase in SHR compared to the ETA blockade by BQ 123. The ETA antagonist BQ 123 had no effect on GFR either in SHR or in WKY, whereas the combined blockade of ETA and ETB by bosentan significantly decreased GFR in SHR by about 50% but not in WKY. CONCLUSIONS: Our data demonstrated a correlation between the overexpression of vascular ETA receptors and the pronounced upregulation of glomerular ETB receptors in the kidneys of SHR and their impact on the regulation of renal blood flow, glomerular filtration rate and blood pressure in these animals.
Asunto(s)
Hipertensión/metabolismo , Riñón/metabolismo , Receptores de Endotelina/metabolismo , Regulación hacia Arriba , Animales , Autorradiografía , Presión Sanguínea/efectos de los fármacos , Northern Blotting , Bosentán , Antagonistas de los Receptores de Endotelina , Tasa de Filtración Glomerular/efectos de los fármacos , Hibridación in Situ , Riñón/química , Glomérulos Renales/química , Masculino , Músculo Liso Vascular/química , Péptidos Cíclicos/farmacología , Unión Proteica , ARN Mensajero/análisis , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptores de Endotelina/genética , Circulación Renal/efectos de los fármacos , Sulfonamidas/farmacologíaRESUMEN
Somatostatin receptor scintigraphy is a new, very sensitive procedure for detecting receptor-positive neuroendocrine tumors. Radiolabeled somatostatin analogues are selectively taken up after intravenous administration by tissue carrying somatostatin receptors and, as with the skeletal scintiscan, permit a whole-body visualization of receptor-positive tumors and metastases. Somatostatin receptor scintigraphy shows an overall sensitivity of about 84% for neuroendocrine gastroenteropancreatic tumors. This kind of scintigraphy should be applied in primary tumor localization, staging, and course control in a confirmed or highly probable neuroendocrine gastroenteropancreatic tumor. Furthermore, the use of a gamma probe for intraoperative tumor localization is demonstrated. Therapy with radioactively marked somatostatin analogues should be possible because of the highly selective tumor uptake. The development of an optimal tracer is the subject of current research.
Asunto(s)
Neoplasias Gastrointestinales/diagnóstico , Tumores Neuroendocrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Receptores de Somatostatina/análisis , Neoplasias Gastrointestinales/radioterapia , Humanos , Radioisótopos de Indio , Tumores Neuroendocrinos/radioterapia , Neoplasias Pancreáticas/radioterapia , Receptores de Somatostatina/clasificación , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
The paracrine renal endothelin system has been implicated in acute and chronic kidney diseases. However, there are only few data about the expression of endothelin receptor subtypes and their impact on renal function in the normal rat kidney. Therefore, we analyzed the age-dependent expression of endothelin receptors (endothelin receptor A and B) using Scatchard analysis, in vitro and in vivo receptor autoradiography. Furthermore, we investigated the effects of the mixed (A/B) endothelin receptor antagonist bosentan on haemodynamic and renal function in conscious chronically instrumented rats. The renal endothelin receptor A and endothelin receptor B expression is age-dependent. The relative amount of endothelin receptor A significantly decreased with age, whereas the endothelin receptor B significantly increased with age. Compared to the other renal structures, a high endothelin receptor density (endothelin receptor B >> endothelin receptor A) was seen in the renal tubules and even more in the glomeruli. Bosentan blocks both the pressor and depressor response of endothelin. Blocking of both endothelin receptor subtypes using bosentan without application of endothelin, on the other hand, did not alter blood pressure, heart rate, renal blood flow, water excretion or glomerular filtration rate, but significantly decreased sodium excretion.
Asunto(s)
Hemodinámica/efectos de los fármacos , Riñón/metabolismo , Receptores de Endotelina/metabolismo , Sulfonamidas/farmacología , Envejecimiento , Animales , Autorradiografía , Presión Sanguínea/efectos de los fármacos , Bosentán , Antagonistas de los Receptores de Endotelina , Endotelinas/antagonistas & inhibidores , Endotelinas/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Riñón/citología , Riñón/efectos de los fármacos , Riñón/fisiología , Masculino , Fragmentos de Péptidos/farmacología , Péptidos Cíclicos/farmacología , Unión Proteica , Ratas , Ratas Endogámicas WKY , Receptores de Endotelina/clasificación , Circulación Renal/efectos de los fármacos , Sodio/metabolismo , Sodio/orina , Micción/efectos de los fármacos , Resistencia Vascular/efectos de los fármacosRESUMEN
The renal endothelin (ET) system has been implicated in the maintenance of hypertension in spontaneously hypertensive rats (SHRs). However, little is known about the expression and cellular distribution of the ET receptor subtypes in the kidney of SHRs. We therefore analyzed the expression of ET receptor subtypes in the kidneys of 16-week-old SHRs. Wistar-Kyoto (WKY) rats served as controls. Furthermore, we investigate the effects of the ETA receptor antagonist BQ 123 and the mixed (ETA/ETB) receptor antagonist bosentan on mean arterial blood pressure (MAP), renal blood flow (RBF), and glomerular filtration rate (GFR) in conscious, chronically instrumented rats. In SHRs we found overexpression of the ETA in the glomeruli and smooth muscle cells of intrarenal arteries compared to age-matched WKY rats. Furthermore, our study revealed a pronounced upregulation of the ETB in the glomeruli of SHRs. Blockade of ETA and ETB receptors in SHR with bosentan as well as with BQ 123 led to a significant decrease in MAP and a significant increase in RBF, indicating that the ETA receptor plays a major role in the maintenance of high blood pressure and the regulation of RBF in SHRs. The blockade of both ETA and ETB receptors by bosentan has no further effect on MAP reduction or increase in RBF in SHRs compared to ETA blockade by BQ 123. In contrast, combined blockade of ETA and ETB receptors by bosentan significantly decreased GFR in SHRs, whereas no effect on GFR was observed in WKY rats, suggesting that the glomerular ETB overexpression in SHRs is of pathophysiologic relevance.
Asunto(s)
Antagonistas de los Receptores de Endotelina , Hemodinámica/efectos de los fármacos , Hipertensión/fisiopatología , Riñón/efectos de los fármacos , Animales , Tasa de Filtración Glomerular/efectos de los fármacos , Riñón/fisiología , Masculino , Péptidos Cíclicos/farmacología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptores de Endotelina/análisisAsunto(s)
Neoplasias Gastrointestinales/diagnóstico por imagen , Radioisótopos de Indio , Tumores Neuroendocrinos/diagnóstico por imagen , Octreótido/análogos & derivados , Neoplasias Pancreáticas/diagnóstico por imagen , Ácido Pentético/análogos & derivados , Receptores de Somatostatina/metabolismo , Tumor Carcinoide/diagnóstico por imagen , Tumor Carcinoide/secundario , Humanos , Tumores Neuroendocrinos/secundario , Octreótido/metabolismo , Ácido Pentético/metabolismo , Cintigrafía , Sensibilidad y EspecificidadRESUMEN
Localization of gastroenteropancreatic neuroendocrine tumors with conventional imaging techniques can be difficult. With the advent of the somatostatin-receptor scintigraphy the diagnosis of these could be improved. In this study 76 patients with immunohistologically proven neuroendocrine tumors were analysed by comparing somatostatin-receptor scintigraphy with conventional imaging techniques. Somatostatin-receptor-positive lesions were observed in 61 of all patients. Conventional imaging techniques (transabdominal ultrasonography, computerized tomographic scanning of the abdomen, magnetic resonance imaging of the abdomen) revealed neuroendocrine tumors in 42 patients (69%). A follow up of 19 patients with initially false positive somatostatin-receptor scintigrams showed that at least 6 patients had escaped the initial diagnosis by conventional techniques. All in all, our data support previous findings and demonstrate that somatostatin-receptor scintigraphy is a safe and sensitive procedure for in vivo imaging of gastroenteropancreatic neuroendocrine tumors. In addition, in certain cases, somatostatin-receptor scintigraphy is able to detect tumors that had escaped conventional imaging techniques.
Asunto(s)
Neoplasias Gastrointestinales/diagnóstico por imagen , Tumores Neuroendocrinos/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Receptores de Somatostatina/análisis , Terapia Combinada , Reacciones Falso Positivas , Femenino , Estudios de Seguimiento , Neoplasias Gastrointestinales/terapia , Humanos , Radioisótopos de Indio , Metástasis Linfática , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/terapia , Neoplasias Pancreáticas/terapia , Cintigrafía , Somatostatina/análogos & derivadosRESUMEN
BACKGROUND: Gastroenteropancreatic neuroendocrine tumors are often difficult to localize. This study was conducted to examine the value of somatostatin-receptor scintigraphy for visualization of gastroenteropancreatic neuroendocrine tumors. METHODS: Applying the recently developed indium-labeled somatostatin analogue 111In-pentetreotide to 40 patients with gastroenteropancreatic neuroendocrine tumors, the diagnostic power of pentreotide-receptor scintigraphy was evaluated in comparison with conventional imaging techniques. RESULTS: Expression of somatostatin receptors was observed in the majority of patients (11 of 17 in the foregut, 14 of 16 in the midgut, and 7 of 7 in metastatic neuroendocrine tumors with unknown primary). Comparative imaging by computerized tomography, magnetic resonance imaging, and transabdominal ultrasonography yielded false-negative results for somatostatin-receptor scintigraphy in 8 of 40 patients; however, in 16 patients, tumor tissue that had escaped conventional imaging techniques was detected by 111In-pentetreotide scintigraphy. CONCLUSIONS: 111In-pentetreotide scintigraphy is a practical, safe, and sensitive procedure for in vivo imaging of gastroenteropancreatic neuroendocrine tumors.
Asunto(s)
Neoplasias Gastrointestinales/diagnóstico por imagen , Radioisótopos de Indio , Tumores Neuroendocrinos/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Receptores de Somatostatina/análisis , Somatostatina/análogos & derivados , Adolescente , Adulto , Anciano , Niño , Femenino , Neoplasias Gastrointestinales/química , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/química , Neoplasias Pancreáticas/química , CintigrafíaRESUMEN
Cardiac function is determined by preload, afterload, heart rate and contractility. During orthostatic stress, the footward blood shift is compensated for by an increase of afterload. LBNP is widely used to analyze effects of volume displacement during orthostatic stress. Comparisons of invasive (right heart catheterization) and non-invasive approach (echocardiography) yielded similar changes. Preload and afterload change with graded LBNP, heart rate increases, and stroke volume and cardiac output decrease. Thus, the working point on the left ventricular function curve is shifted to the left and downward, similar to hypovolemia. However, position on the Frank-Starling curve, the unchanged ejection fraction, and the constant Vcf indicate a normal contractile state during LBNP. A decrease of arterial oxygen partial pressure during LBNP shows impaired ventilation/ perfusion ratio. Finally, LBNP induced cardiac and hemodynamic changes can be effectively countermeasured by dihydroergotamine, a potent venoconstrictor. Comparison of floating catheter data with that of echocardiography resulted in close correlation for cardiac output and stroke volume. In addition, cardiac dimensions changed in a similar way during LBNP. From our findings, echocardiography as a non-invasive procedure can reliably used in LBNP and orthostatic stress tests. Some information can be obtained on borderline values indicating collapse or orthostatic syncope. Early fainters can be differentiated from late fainters by stroke volume changes.
Asunto(s)
Hemodinámica/fisiología , Hipotensión Ortostática/fisiopatología , Presión Negativa de la Región Corporal Inferior/efectos adversos , Cateterismo Cardíaco/métodos , Dihidroergotamina/farmacología , Ecocardiografía/métodos , Corazón/fisiología , Hemodinámica/efectos de los fármacos , Humanos , Hipotensión Ortostática/etiología , Hipotensión Ortostática/prevención & control , Volumen Sistólico/fisiología , Síncope Vasovagal/etiología , Síncope Vasovagal/fisiopatología , Vasoconstrictores/farmacología , Función Ventricular Izquierda/fisiología , Medidas contra la IngravidezRESUMEN
In a prospective, double-blind, randomized multicenter trial the efficacy and safety of low molecular weight heparin and unfractionated heparin were compared for the prevention of postoperative deep vein thrombosis in patients undergoing abdominal surgery. Six hundred and seventy-three patients were randomly allocated to the two prophylaxis groups; 20 of these, however, did not undergo surgery and did not receive any prophylaxis. Of the remaining 653 patients 323 received one subcutaneous injection of 3,000 anti-Xa units of low molecular weight heparin and 330 received subcutaneously 5,000 U heparin three times a day. Treatment was initiated 2 h preoperatively and continued for 7 to 10 days. The occurrence of DVT was determined by the 125I-labelled fibrinogen uptake test and phlebography. Venous thrombosis was diagnosed in 24 of 323 patients (7.4%) treated with low molecular weight heparin and in 26 of 330 patients (7.9%) treated with low-dose heparin. DVT of proximal veins was detected in four patients of the low molecular weight heparin group and in three patients of the low-dose heparin group. During the observation period three pulmonary emboli - one fatal and two non-fatal - occurred in patients receiving prophylaxis with low-dose heparin. No pulmonary embolism was found in patients treated with low molecular weight heparin. Both prophylactic schemes were well tolerated. Intra- and postoperative blood loss, incidence of wound hematoma, frequency and volume of intra- and postoperative blood transfusion were similar in both groups with a slight advantage for the low molecular weight heparin group.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Abdomen/cirugía , Heparina de Bajo-Peso-Molecular/uso terapéutico , Laparotomía , Complicaciones Posoperatorias/prevención & control , Tromboembolia/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Heparina/administración & dosificación , Heparina/efectos adversos , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
As isradipine is known to be less cardiodepressant than nifedipine, myocardial wall stress--an important determinant of cardiac oxygen demand--may also be more favorably influenced by isradipine. Therefore, the acute effects of an intravenous (i.v.) infusion of isradipine (0.4 mg) vs. nifedipine (2.0 mg) on cardiac hemodynamics and systolic wall stress were investigated in a crossover study of 12 hypertensive patients. Vasodilation-induced reflex activation was limited by pretreatment with i.v. propranolol at 0.1 mg/kg of body weight. The hemodynamic parameters measured were statistically comparable at baseline and after propranolol with both calcium antagonists, as was blood pressure reduction. However, the end-systolic volume decreased with isradipine, but not with nifedipine [before: 69 +/- 7.0 ml (mean +/- SEM); after: 61 +/- 6.1 ml; 2p less than 0.01 vs. before: 62 +/- 6.1 ml; after: 64 +/- 7.0 ml; NS, (difference between changes in response to treatments: 2p less than 0.05)]. The ejection fraction increased only with isradipine vs. nifedipine [before: 48 +/- 2.3%; after: 54 +/- 2.3%; 2p less than 0.001 vs. before: 52 +/- 2.0%; after: 52 +/- 2.3%; NS (difference between changes in response to treatments: 2p less than 0.05)]. Systolic wall stress decreased significantly more with isradipine than with nifedipine [before: 2,767 +/- 231; after: 2,153 +/- 162 relative units; 2p less than 0.001 vs. before: 2,636 +/- 212; after: 2,310 +/- 199 relative units; 2p less than 0.05 (difference between changes in response to treatments: 2p less than 0.05)]. These results suggest that isradipine, given acutely, unloads the heart more than does nifedipine.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Dihidropiridinas/farmacología , Hemodinámica/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Nifedipino/farmacología , Anciano , Bloqueadores de los Canales de Calcio/administración & dosificación , Dihidropiridinas/administración & dosificación , Humanos , Infusiones Intravenosas , Isradipino , Persona de Mediana Edad , Nifedipino/administración & dosificaciónRESUMEN
Hemodynamic Effects of Isradipine and Nifedipine in Hypertension Myocardial wall tension is an important determinant of the oxygen demand, the function and the degree of hypertrophy of the left ventricle. Myocardial wall tension should be influenced more favourably by a non-cardiodepressive antihypertensive than by a potentially cardiodepressive one. Therefore, we investigated the effects of an intravenous infusion of the calcium antagonists isradipine (I; 0.4 mg; 3,5-pyridinecarboxylic acid, 4-[benzofurazanyl]-1,4-dihydro-2,6-dimethyl-,methyl-ethylester+ ++ [9CI]; CAS75695-93-1) and nifedipine (N; 2.0 mg) resp., on hemodynamics and myocardial wall tension in 12 hypertensives by an intraindividual comparison. The adrenergic reflex activation induced by vasodilation was limited by pre-medication with 0.1 mg propranolol/kg body weight (i.v.) before application of I and N. Baseline blood pressure of the patients and its changes in response to both calcium antagonists were statistically comparable, as were the left ventricular end-diastolic volumes. The end-systolic volumes, however, decreased significantly on I but not on N: before I: 69 +/- 7.0 (mean +/- standard error), after I: 61 +/- 6.1 ml, 2p less than 0,001; before N: 62 +/- 6.1, after N: 64 +/- 7.0 ml, n.s. (difference to I: 2 p less than 0.05). Stroke volume increased only on I (before I: 62 +/- 4.1, after I: 69 +/- 4.1 ml, 2p less than 0.001; before N: 64 +/- 3.5, after N: 65 +/- 3.8 ml, n.s. (difference to I: 2p less than 0.05)).(ABSTRACT TRUNCATED AT 250 WORDS)