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Biomedical subjects

Harald Schmidt

Publications and source records attributed to Harald Schmidt.

At least 19 recordsLinked to original sources
PubMed2006

Activation of soluble guanylate cyclase reverses experimental pulmonary hypertension and vascular remodeling.

BACKGROUND: Severe pulmonary hypertension is a disabling disease with high mortality, characterized by pulmonary vascular remodeling and right heart hypertrophy. Using wild-type and homozygous endothelial nitric oxide synthase (NOS3(-/-)) knockout mice with pulmonary hypertension induced by chronic hypoxia and rats with monocrotaline-induced pulmonary hypertension, we examined whether the soluble guanylate cyclase (sGC) stimulator Bay41-2272 or the sGC activator Bay58-2667 could reverse pulmonary vascular remodeling. METHODS AND RESULTS: Both Bay41-2272 and Bay58-2667 dose-dependently inhibited the pressor response of acute hypoxia in the isolated perfused lung system. When wild-type (NOS3(+/+)) or NOS3(-/-) mice were housed under 10% oxygen conditions for 21 or 35 days, both strains developed pulmonary hypertension, right heart hypertrophy, and pulmonary vascular remodeling, demonstrated by an increase in fully muscularized peripheral pulmonary arteries. Treatment of wild-type mice with the activator of sGC, Bay58-2667 (10 mg/kg per day), or the stimulator of sGC, Bay41-2272 (10 mg/kg per day), after full establishment of pulmonary hypertension from day 21 to day 35 significantly reduced pulmonary hypertension, right ventricular hypertrophy, and structural remodeling of the lung vasculature. In contrast, only minor efficacy of chronic sGC activator therapies was noted in NOS3(-/-) mice. In monocrotaline-injected rats with established severe pulmonary hypertension, both compounds significantly reversed hemodynamic and structural changes. CONCLUSIONS: Activation of sGC reverses hemodynamic and structural changes associated with monocrotaline- and chronic hypoxia-induced experimental pulmonary hypertension. This effect is partially dependent on endogenous nitric oxide generated by NOS3.

Animals↗
PubMed2006

Atrial thrombi-a prospective follow-up study over 3 years with transesophageal echocardiography and cranial magnetic resonance imaging.

BACKGROUND: Patients with atrial fibrillation (AF) and atrial thrombi have an increased risk for cerebral embolism. However, there is little knowledge about the long-term fate of atrial thrombi and the incidence of cerebral embolism in patients under oral anticoagulation. METHODS: Consecutive patients with persistent or permanent AF and left atrial (LA) thrombi were included in the study. We performed serial and prospective transesophageal echocardiography, cranial magnetic resonance imaging, and clinical examinations during a period of 3 years. Oral anticoagulation was continued or initiated in all patients. A target INR of 2.5 was intended in all patients. RESULTS: Forty-three patients with LA thrombi and persistent or permanent AF were included. During the follow-up period 31(72%) of the thrombi disappeared. Patients with disappearance of thrombi had significantly smaller thrombi (P < 0.01), a lower echogenicity of thrombi (P < 0.01), and a lower LA volume (P = 0.02). Twenty-two (51%) patients suffered from cerebral embolism and/or death during the observation period. Five patients died due to embolic events. The only independent predictors of cerebral embolism were an elevated peak emptying velocity of the LA appendage (P < 0.001) and a history of previous thromboembolism (P < 0.01). CONCLUSIONS: Patients with persistent or permanent AF and atrial thrombi have a high long-term risk of cerebral embolism and/or death (51%) even despite the oral anticoagulation therapy. Thrombus size may predict thrombus resolution under continued anticoagulation.

Aged↗
PubMed2006

Diagnosis of ischaemic heart disease by myocardial contrast echocardiography during supine bicycle stress.

INTRODUCTION: Myocardial contrast echocardiography (MCE) is a new imaging modality for diagnosing ischaemic heart disease (IHD). AIM: The aim of this study was to assess 1) the feasibility of MCE during supine bicycle stress and 2) the value of this method in the diagnosis of IHD. METHODS: Supine bicycle stress was performed in 44 consecutive patients (pts) referred for coronary angiography with an intermediate pre-test probability of IHD. MCE was carried out at peak stress and during recovery (once the heart rate returned to the pre-exercise value). During MCE an ultrasound contrast agent (Sonovue) was administered intravenously in a continuous mode using an infusion pump (BR-INF 100, Bracco Research). The acquired images were qualitatively assessed for perfusion and wall motion abnormalities. The 18-segment division of the left ventricle was used in the analysis. Coronary angiography was performed in all pts within 15 days of the exercise test. A quantitative analysis of coronary artery stenoses was carried out using the CAAS system. RESULTS: MCE could not be performed in 2 pts due to technical difficulties. Coronary angiography revealed significant coronary artery stenosis in 25 pts. The sensitivity and specificity of MCE in the diagnosis of IHD were 92.0% and 82.4%, respectively. The positive and negative predictive values were found to be 88.5% and 87.5%, respectively, while the agreement between coronary angiography and MCE was 88.1% (kappa=0.75). CONCLUSIONS: MCE during supine bicycle stress and continuous intravenous administration of an ultrasound contrast agent is a feasible technique and allows accurate diagnosis of IHD in pts in whom the pre-test probability of the disease is intermediate.

Adult↗
PubMed2005

How trimethyl(trifluoromethyl)silane reacts with itself in the presence of naked fluoride--a one-pot synthesis of bis([15]crown-5)cesium 1,1,1,3,5,5,5-heptafluoro-2,4-bis(trifluoromethyl)pentenide.

Reactions of trimethyl(trifluoromethyl)silane in the presence of "naked" fluoride proceed up to a temperature of +5 degrees C mainly with formation of [Me3Si(CF3)2]-. A further rise of temperature up to about 20 degrees C gives evidence for the formation of a salt with the 1,1,1,2,3,6,6,6-octafluoro-2,4,4,5,5-pentakis(trifluoromethyl)hexan-3-ide anion. This intermediate decomposes at room temperature into the 1,1,1,3,5,5,5-heptafluoro-2,4-bis(trifluoromethyl)pentenide anion. The bis([15]crown-5)cesium salt, [Cs([15]crown-5)2][(CF3)2CCFC(CF3)2] has been characterized unambiguously as the stable final product of this reaction sequence. Thermal decomposition of this salt opens a convenient nontoxic route to obtain 1,1,3,3-tetrakis(trifluoromethyl)allene, (F3C)2C=C=C(CF3)2.

Cesium↗
PubMed2005

Patients with atrial fibrillation and dense spontaneous echo contrast at high risk a prospective and serial follow-up over 12 months with transesophageal echocardiography and cerebral magnetic resonance imaging.

OBJECTIVES: We sought to assess the prognosis of patients with atrial fibrillation (AF) and dense spontaneous echo contrast (SEC) and to determine the incidence of cerebral embolism under continued oral anticoagulation. BACKGROUND: Patients with AF and dense SEC have an increased risk of cerebral embolism. However, there is little knowledge about the long-term fate and the rate of clinical silent cerebral embolism under continued oral anticoagulation. METHODS: Between 1998 and 2001, all consecutive patients with AF and dense SEC were included in the study. We performed serial and prospective transesophageal echocardiography, cranial magnetic resonance imaging, and clinical examinations during a period of 12 months. RESULTS: A total of 128 patients with dense SEC and AF were included. The control group consisted of 143 patients with faint SEC and AF. During the follow-up period, three patients (2%) had cerebral embolism with neurologic deficits. A total of eight patients (6%) died due to embolic events, and 19 (15%) patients had silent embolism, as documented on cerebral magnetic resonance imaging. Patients with an event had significantly lower left atrial appendage peak emptying velocities and more commonly had a history of previous thromboembolism and denser SEC, as compared with patients without an event. CONCLUSIONS: Patients with AF and dense SEC have a high likelihood of cerebral embolism (22%) and/or death, despite oral anticoagulation. Low peak emptying velocities of the left atrial appendage and dense SEC are independent predictors of an event.

Anticoagulants↗
PubMed2005

Post mortem analysis of a left atrial appendage occlusion device (PLAATO) in a patient with permanent atrial fibrillation.

Thromboemoblism is the most feared complication of atrial fibrillation. Percutaneous left atrial appendage occlusion is a new interventional procedure for reducing thromboembolic risk in patients with atrial fibrillation. The paper reports of a post mortem analysis of the device demonstrating that one year after implantation the atrial surface of the device is completely covered by neo-endothelium and the device occludes the appendage completely.

Aged↗
PubMed2005

Paradoxical effects of hypoxia-mimicking divalent cobalt ions in human endothelial cells in vitro.

Divalent cobalt ions (Co2+) induce the expression of hypoxia responsive genes and are often used in cell biology to mimic hypoxia. In this in vitro study we compared the effects of hypoxia and Co2+ on human endothelial cells and examined processes that are stimulated in hypoxia in vivo (proliferation and angiogenesis). We analyzed the expression of the hypoxia-inducible factor-1alpha (HIF-1alpha) under different hypoxic conditions (3% and nearly 0% O2) and Co2+ -concentrations (0.01-0.7 mM). As in hypoxia, the amount of HIF-1alpha protein was enhanced by exposure to Co2+ (did not correlate with mRNA amount). however, contrary to the results of hypoxia, in vitro-angiogenesis was inhibited after exposure to even low Co2+-concentrations (> or =0.01 mM). This led to the conclusion that although hypoxia signaling after Co2+ -exposure took place, further yet unknown Co2+ -induced event(s) must have occurred.

Cell Line↗
PubMed2005

Incidence of cerebral embolism after cardioversion of atrial fibrillation: a prospective study with transesophageal echocardiography and cerebral magnetic resonance imaging.

BACKGROUND: After cardioversion of atrial fibrillation the risk for cerebral embolism is increased. There is little knowledge about the incidence of cerebral embolism for patients with transesophageal echocardiography (TEE)-guided cardioversion under oral anticoagulation. METHODS: Consecutive patients with atrial fibrillation and TEE-guided cardioversion were included in the study. We performed serial TEE studies, Holter electrocardiography, cranial magnetic resonance imaging, and clinical examinations during a period of 4 weeks before and after cardioversion. Oral anticoagulation was continued or initiated in all patients. RESULTS: During the observation period 6 of 127 (4.7%) patients had new embolic lesions after cardioversion documented on cerebral magnetic resonance imaging. Patients with an event were significantly older (P = .04) and had a larger left atrium (P = .04) than patients without event. CONCLUSION: Patients with atrial fibrillation and oral anticoagulation have a low rate of clinical apparent cerebral embolism after TEE and anticoagulation-guided cardioversion. The rate of silent cerebral embolism is almost 5%. Age and left atrial size are predictors for an event.

Administration, Oral↗
PubMed2005

Patients at high risk with atrial fibrillation: a prospective and serial follow-up during 12 months with transesophageal echocardiography and cerebral magnetic resonance imaging.

OBJECTIVE: Patients with atrial fibrillation and echocardiographic risk factors have a relevant risk of cerebral embolism. However, there is little knowledge about the long-term fate and the rate of clinical silent cerebral embolism under continued oral anticoagulation. Our aims were to assess the prognosis of patients with atrial fibrillation and determine a high-risk group with an increased risk of cerebral embolism under oral anticoagulation. METHODS: A total of 173 consecutive patients with persistent or permanent atrial fibrillation and left atrial (LA) thrombi, dense spontaneous echocontrast, reduced LA appendage peak emptying velocities, or a combination of these were included in the study. In all, 169 patients with atrial fibrillation and without echocardiographic risk factors served as control patients. We performed serial and prospective transesophageal echocardiography, cranial magnetic resonance imaging, and clinical examinations during a period of 12 months. RESULTS: During the follow-up period 7 (4%) of the patients at high risk had cerebral embolism with neurologic deficits. A total of 4 (2%) patients died because of embolic events and 19 (11%) patients had silent embolism as documented on magnetic resonance imaging. In the control group, 10 (6%) patients had embolic events documented on magnetic resonance imaging; one was clinically apparent. Study patients with an event had more often previous thromboembolism (P < .0001). CONCLUSIONS: Patients with persistent or permanent atrial fibrillation and LA thrombi, dense spontaneous echocontrast, or reduced LA appendage peak emptying velocities have an explicitly increased risk of cerebral embolism (17%) despite oral anticoagulation. Previous thromboembolic event is another important predictor for an event.

Administration, Oral↗
PubMed2005

A prospective two-center study comparing wireless capsule endoscopy with intraoperative enteroscopy in patients with obscure GI bleeding.

BACKGROUND: Capsule endoscopy enables noninvasive diagnostic examination of the entire small intestine. However, sensitivity and specificity of capsule endoscopy have not been adequately defined. We, therefore, compared capsule endoscopy by using intraoperative enteroscopy as a criterion standard in patients with obscure GI bleeding. METHODS: Forty-seven consecutive patients with obscure GI bleeding (11 with ongoing overt bleeding, 24 with previous overt bleeding, and 12 with obscure-occult bleeding) from two German gastroenterologic centers were included. All patients who had a prior nondiagnostic evaluation, including upper endoscopy, colonoscopy with a retrograde examination of the distal ileum, and push enteroscopy, underwent capsule endoscopy followed by intraoperative enteroscopy. RESULTS: Capsule endoscopy identified lesions in 100% of the patients with ongoing overt bleeding, 67% of the patients with previous overt bleeding, and 67% of the patients with obscure-occult bleeding. Angiectasias were the most common source of bleeding (n = 22). Capsule endoscopy showed the source of bleeding in 74.4% of all patients. The method was more effective in patients with ongoing bleeding. Compared with intraoperative enteroscopy sensitivity, specificity, and positive and negative predictive values of capsule endoscopy were 95%, 75%, 95%, and 86%, respectively. CONCLUSIONS: Capsule endoscopy has high sensitivity and specificity to detect a bleeding source in patients with obscure GI bleeding. Thus, wireless capsule endoscopy can be recommended as part of the routine work-up in patients with obscure GI bleeding.

Adolescent↗
PubMed2004

Fate of left atrial thrombi in patients with atrial fibrillation determined by transesophageal echocardiography and cerebral magnetic resonance imaging.

Patients with atrial fibrillation (AF) and atrial thrombi have an increased risk for cerebral embolism. However, there is little knowledge about the long-term fate of atrial thrombi and the incidence of cerebral embolism in patients receiving continued oral anticoagulation. Forty-three consecutive patients with AF and atrial thrombi were enrolled in the study. Serial and prospective transesophageal echocardiographic studies, cranial magnetic resonance imaging (MRI), and clinical examinations were performed during a period of 12 months. Oral anticoagulation was continued or initiated in all patients. An international normalized ratio of 2.0 to 3.0 was regarded as effective. During follow-up, 56% of the thrombi disappeared (7 [16%] at 1 month, 18 [42%] at 3 months, 21 [49%] at 6 months, and 24 [56%] at 12 months). Patients with the disappearance of thrombi had significantly smaller thrombi compared with patients with persistent thrombi (1.5 +/- 0.8 cm in length and 0.8 +/- 0.5 cm in width vs 1.9 +/- 0.6 cm in length and 1.3 +/- 0.4 cm in width, p = 0.04), reduced echogenicity of thrombi (46% vs 89%, p <0.01), and smaller left atrial (LA) volume (83 +/- 27 vs 116 +/- 55 cm(3)). Seven patients (16%) had embolic lesions during follow-up MRI. Six of these patients (86%) had clinically apparent embolisms, and 1 died from stroke. The only independent predictors of cerebral embolism were an elevated peak emptying velocity of the LA appendage (p <0.01) and previous thromboembolic events (p = 0.02). Patients with AF and atrial thrombi have a large likelihood of cerebral embolism (16%) and/or death despite oral anticoagulation therapy. Thrombus size may predict thrombus resolution under continued anticoagulation.

Atrial Fibrillation↗
PubMed2004

Alkynylxenon(II) fluorides.

Alkynylxenon(II) fluorides, RCC(triple bond)XeF, have been prepared from the reactions of the corresponding trimethyl(alkynyl)silanes, Me3(-)SiC(triple bond)CR, and XeF2 in the presence of [NMe4F in common organic solvents at low temperature. The existence of the linear unit C(triple bond)C-Xe-F was proved for PhC(triple bond)CXeF by the 19F-13C NMR correlation method using the HMBC pulse sequence.

Journal Article↗
PubMed2004

Low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis.

BACKGROUND: Studies suggest that heparin has anti-inflammatory effects that could prevent acute post-ERCP pancreatitis. The aim of this investigator-initiated, prospective, randomized, double-blind, multicenter study was to determine whether low-molecular-weight heparin can prevent acute post-ERCP pancreatitis. METHODS: Patients at increased risk for acute post-ERCP pancreatitis based on assessment of known risk factors were randomized to receive low-molecular-weight heparin (Certoparin 3000 IU subcutaneously) or placebo (saline solution 0.3 mL subcutaneously) the day before ERCP. The drug was given 2 hours before and 22 hours after ERCP. Documentation and follow-up included patient history, risk factors for acute post-ERCP pancreatitis, procedure-related data, assessment of pain (visual analogue scale, need for pain medication), laboratory findings before and after ERCP (0, 4, and 24 hours), as well as post-ERCP complications. The two-sided Fisher exact test was used for statistical comparison, and a p value < or =0.05 was considered significant. RESULTS: A total of 458 patients were enrolled in the study. Data from 10 patients could not be evaluated, leaving 221 patients in the low-molecular-weight heparin group and 227 in the placebo group (total 448 patients; 135 men, 313 women; mean age 58 [15] years). Low-molecular-weight heparin and placebo groups were comparable with regard to risk factors for acute post-ERCP pancreatitis (gender distribution, age <65 years, history of pancreatitis, pancreas divisum, disorders of sphincter of Oddi) and procedure-related data (difficult cannulation, diagnostic or therapeutic ERCP, needle-knife papillotomy, endoscopic sphincterotomy, biliary or pancreatic procedure, pancreatic contrast injection, success and final diagnosis of ERCP). Acute post-ERCP pancreatitis occurred in 8.5% (38/448), with one death resulting from severe pancreatitis. Low-molecular-weight heparin offered no benefit compared with placebo based on the frequency of acute post-ERCP pancreatitis (low-molecular-weight heparin, 18/221 vs. placebo, 20/227; p=0.87) and the severity of acute post-ERCP pancreatitis (low-molecular-weight heparin, 14 mild, 3 moderate, one severe; placebo, 18 mild, two moderate, 0 severe). The 24-hour serum amylase values and 24-hour pain scores did not differ significantly between the low-molecular-weight heparin group and the placebo group. Bleeding complications occurred in two patients, both in the low-molecular-weight heparin group (one mild, one moderate). CONCLUSIONS: Prophylactic subcutaneous administration of low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis.

Acute Disease↗
PubMed2004

Induced hyperactivity in boar spermatozoa and its evaluation by computer-assisted sperm analysis.

Hyperactivity, a form of sperm motility characterized by vigorous flagellar movements, has been proposed as essential for fertilization in mammals. The objective of the present study was to establish a method for inducing hyperactivity in vitro in boar spermatozoa and to define threshold values to differentiate between hyperactive and non-hyperactive spermatozoa by computer-assisted sperm analysis (CASA) as a prerequisite for analyzing the energy metabolism during hyperactivity. In TALP-HEPES medium, non-frozen boar spermatozoa were stimulated to hyperactivity by 50 micromol l(-1) Ca2+ within 15 min at 37 degrees C if 5 micromol l(-1) of the Ca2+ ionophore A23187 was present. If 25% seminal plasma was present, boar spermatozoa required higher Ca2+ concentrations (about 700 micromol l(-1)) for hyperactivity. Under both conditions, immobilization and head-to-head agglutination were low so that hyperactive spermatozoa could be analyzed for at least 40 min. The transition from normal to hyperactive movement was characterized by an increase in flagellar beat angle from 49 degrees +/- 12 degrees to 200 degrees +/- 36 degrees (n = 32) and a decrease in flagellar curvature ratio from 0.89 +/- 0.04 to 0.47 +/- 0.11 (n = 32). For quantification of hyperactive boar sperm, kinematic parameters of hyperactive and non-hyperactive spermatozoa were measured by CASA and statistically evaluated (receiver operating characteristic (ROC) curve analysis). The threshold values of the following four parameters were well suited for differentiating between hyperactive and non-hyperactive boar spermatozoa (ROC curve analysis: > 50% specificity at 100% sensitivity). Hyperactive boar spermatozoa showed mean lateral head displacement > 3.5 microm, curvilinear velocity > 97 microm s(-1), linearity < 32% and wobble < 71%. According to this multiparametric definition, induction of hyperactivity increased significantly (P < 0.0001) the fraction of hyperactive spermatozoa in semen samples from 5.1 +/- 4.3% (n = 13) to 48.3 +/- 6.6% (n = 7) in the absence and to 44.2 +/- 7.6% (n = 10) in the presence of 25% seminal plasma, while the overall percentage of motile spermatozoa did not change significantly.

Animals↗
PubMed2003

Silent and apparent cerebral embolism after retrograde catheterisation of the aortic valve in valvular stenosis: a prospective, randomised study.

BACKGROUND: In most patients, severity of valvular aortic stenosis can be accurately assessed non-invasively by echocardiography. However, retrograde catheterisation of the aortic valve is often undertaken. This procedure has a potential risk of neurological complications, with an unknown incidence of clinically silent embolism. We aimed to establish the frequency of clinically apparent and silent cerebral embolism after this procedure. METHODS: We prospectively randomised 152 consecutive patients with valvular aortic stenosis at a German university hospital to receive either cardiac catheterisation with (n=101) or without (n=51) passage through the aortic valve. Patients underwent cranial MRI and neurological assessment within 48 h before and after the procedure to assess cerebral embolism. Controls were 32 patients without valvular aortic stenosis who underwent coronary angiography and laevocardiography. FINDINGS: 22 of 101 patients (22%) who underwent retrograde catheterisation of the aortic valve had focal diffusion-imaging abnormalities in a pattern consistent with acute cerebral embolic events after the procedure; three of these patients (3%) had clinically apparent neurological deficits. By contrast, none of the patients without passage of the valve, or any of the controls, had evidence of cerebral embolism as assessed by MRI. INTERPRETATION: Patients with valvular aortic stenosis who undergo retrograde catheterisation of the aortic valve have a substantial risk of clinically apparent cerebral embolism, and frequently have silent ischaemic brain lesions. Patients should be informed about these risks, and this procedure should be used only in patients with unclear echocardiographical findings when additional information is necessary for clinical management.

Aortic Valve↗
PubMed2003

Radioiodide treatment after sodium iodide symporter gene transfer is a highly effective therapy in neuroendocrine tumor cells.

This study evaluates the possibility of treating Bon1 and QGP pancreatic neuroendocrine tumor cells with radioactive iodide ((131)I) after stable transfection with the thyroid sodium iodide symporter (NIS). NIS expression was driven either by the strong viral cytomegalovirus promoter or by the tissue-specific chromogranin A promoter. Using either approach, NIS expression was confirmed by reverse transcription-PCR and Western blotting. Uptake of radioactive iodide was increased approximately 20-fold by chromogranin A promoter-driven NIS expression and approximately 50-fold by cytomegalovirus promoter-driven NIS expression. Maximal uptake was reached within 15 min in QGP cells and 30 min in Bon1 cells. Effective half-life was 5 min in QGP and 30 min in Bon1 cells. No evidence of organification was detected by high-performance liquid chromatography and gel filtration chromatography. (131)I was a highly effective treatment in NIS-expressing QGP and Bon1 cells, reducing clone formation by 99.83 and 98.75%, respectively, in the in vitro clonogenic assay. In contrast, clone formation was not reduced in QGP and Bon1 cells without NIS expression after incubation with the same activity concentration of (131)I as compared with mock treated cells. Absorbed doses to QGP and Bon1 cells are up to 150 and 30 Gy, respectively. In addition, a direct cytotoxic effect of radioiodide was demonstrated in NIS-expressing Bon1 cells after (131)I incubation. In conclusion, radioiodide treatment after NIS gene transfer appears to be a promising novel approach in the therapy of neuroendocrine tumors if its highly encouraging in vitro effectiveness can be transferred to the in vivo situation.

Carcinoid Tumor↗