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Biomedical subjects

J Meyer

Publications and source records attributed to J Meyer.

At least 595 records · Page 33Linked to original sources

Increase in endogenous fibrinolysis and platelet activity during exercise in young volunteers.

The influence of physical exercise and intake of oral contraceptives on endogenous fibrinolytic activity and platelet aggregation behaviour was studied in young healthy women and compared to an age matched group of male volunteers. Physical exercise beyond the anaerobic threshold significantly increased the activity of tissue-plasminogen activator (t-PA) in male and female volunteers from initial values of 1.6 +/- 0.1 and 1.8 +/- 0.2 IU/ml to 5.5 +/- 1.0 and 5.3 +/- 0.9 IU/ml (P less than 0.01), respectively. In women taking low-dose estrogen oral contraceptives t-PA increased from 1.5 +/- 0.2 to 3.8 +/- 0.5 (P less than 0.01). There were no major alterations in plasminogen activator inhibitor - I (PAI-I) plasma activities. Platelet activity during exercise was significantly enhanced in male test persons indicated by a significant decrease in the ED50 values for ADP. In contrast, in women ED50 values were basically unaltered, irrespective of the intake of oral contraceptives.

Adolescent↗

Effects of ciprostene on restenosis rate during therapeutic transluminal coronary angioplasty.

Ciprostene, a chemically stable prostacyclin analog was studied for its effects on restenosis in patients with coronary artery disease undergoing therapeutic percutaneous transluminal coronary angioplasty (PTCA). In a double-blind, randomized trial 32 patients were randomized to receive either ciprostene or the respective placebo. The infusion started intracoronarily at a rate of 40 ng/kg/min 20 min before introduction of the balloon catheter into the coronary artery. Thereafter infusion was continued intravenously for 36 hours at a rate of 120 ng/kg/min and a tapering off period until 48 hours. The quantitative analyses of the degree of coronary artery stenoses on the angiographic films before PTCA, after PTCA and after 6 month of follow-up was performed in 24 patients available. In patients receiving placebo (n = 12) coronary artery stenoses was 81 +/- 3% before PTCA and was reduced to 34 +/- 3% by angioplasty. At the 6 month follow up angiography stenoses diameter was measured as 63 +/- 8%, being not significantly different from the % stenoses before PTCA. In contrast, coronary artery stenoses in patients receiving ciprostene (n = 12) measured 83 +/- 3% before PTCA, 31 +/- 4% after PTCA and 55 +/- 9% at 6 month, being still significantly different from pre-PTCA value (P less than 0.05). When patients were characterized according to their clinical status, these differences were accounted for by patients with unstable angina receiving ciprostene. Ciprostene seems to reduce restenosis 6 month after coronary angioplasty in patients with unstable angina. The infusion rate of 40 ng/kg/min i.c. followed by 120 ng/kg/min i.v. was tolerated well, although the incidence of catheter associated bleeding was increased.

Adult↗

Image-guided 1H NMR spectroscopical and histological characterization of a human brain tumor model in the nude rat; a new approach to monitor changes in tumor metabolism.

In this study a human glioma-derived intracerebral tumor model was analyzed histologically and examined by image-guided 1H NMR spectroscopy. It was shown that histological characteristics such as cellular subpopulation and necrosis of the primary tumor were preserved in the implants. Usually circumscript tumor growth was present with tumor cells invading the surrounding brain parenchyma. It was demonstrated that tumor growth and tumor metabolism could be monitored by image-guided 1H NMR spectroscopy in a longitudinal study. One of the initial changes noticed was the rise of the lactate signal in the tumor region followed by an increase of the choline and a decrease of N-acetyl-aspartate and phosphocreatine signals. Even before tumor invasion in brain adjacent to the central tumor area could be demonstrated by NMR imaging increased lactate and moderately increased choline signals were measured in these regions. By histopathological examination these areas were shown to be infiltrated by single tumor cells. These observations indicate that image-guided 1H NMR spectroscopy could play an important role in the study of brain tumor biology, especially in the case of changing tumor metabolism during growth.

Animals↗

Spontaneous echo contrast imaging in infective endocarditis: a predictor of complications?

Infective endocarditis is associated with significant morbidity and mortality. Valvular destruction and congestive heart failure are more common in patients with echocardiographically detectable vegetations. In addition, spontaneous platelet aggregation is increased when vegetations are present on cardiac valves. The aim of the study was to assess the prognostic value of spontaneous echo contrast (SEC) imaging, as SEC is supposed to reflect red blood cell aggregates stimulated by platelet activity. We studied 293 patients with clinical signs of infective endocarditis. Vegetations, attached to the aortic or mitral valve, were found in 130 patients (44.4%) who were followed for a mean period of 12 months. In 34 of these 130 patients (26.2%) SEC was imaged during the initial transesophageal echocardiographic examination. In these patients SEC indicated a prolonged healing of infective endocarditis with a specificity of 91.2%, a sensitivity of 77.3%, a positive accuracy of 77.3%, a negative accuracy of 74.3%. Multivariate analysis revealed that SEC is a risk factor for valve replacement (p less than 0.001) and for embolic events (p less than 0.001), less for mortality (p less than 0.01), and lowest for abscess formation (p less than 0.05). The dose of ADP to induce half-maximal platelet aggregation was significantly lower in patients with SEC (0.71 +/- 0.15 microliters) than without SEC (1.05 +/- 0.12 microliters; p less than 0.05), implying an increased spontaneous platelet aggregation in the presence of SEC. Our data provide evidence that systemically activated coagulation plays an important role in infective endocarditis. SEC, the echocardiographic implication of an increased platelet aggregation, predicts complications such as thromboembolic events and the need for surgery and is closely related to the prolonged healing period of infective endocarditis. In addition to demonstrating vegetations, transesophageal echocardiography provides information helpful in assigning patients to a high-risk subgroup. Transesophageal echocardiography may play an important role in assessing the clinical outcome of these patients.

Adult↗

Monitoring prothrombin fragment 1 + 2 during initiation of oral anticoagulant therapy after intracoronary stenting.

Patients with intracoronary stent implantation are treated with aggressive anticoagulant and antiplatelet therapy consisting of high-dose heparin, phenprocoumon, acetylsalicylic acid, dipyridamole, and the infusion of dextran to prevent a subacute thrombotic occlusion of the stented segment. In an effort to optimize this treatment by reducing both imminent bleeding complications and subacute thrombotic occlusion, the concentrations of prothrombin fragment 1 + 2 (F 1 + 2) were determined after intracoronary Palmaz-Schatz stent implantation in 19 consecutive patients. The F 1 + 2 concentrations after stent implantation and before the initiation of oral anticoagulant therapy (OAT) were 0.35 nm/l and 0.25-0.53 nm/l (median and 25th-75th percentile), versus 0.74 nm/l and 0.52-0.78 nm/l, in healthy subjects and 0.61 nm/l and 0.30-1.02 nm/l in 15 patients with ongoing proximal DVT. Nine days after initiation of OAT, F 1 + 2 concentrations in both patient groups had not yet reached levels observed in patients with OAT in the stable state (0.16 nm/l, 0.12-0.26 nm/l; n = 76; P less than 0.0001 compared with healthy subjects; INR 2.0-4.5). Despite an INR greater than 2.0, accompanying heparinization was terminated on day 9. In two stented patients a minor bleeding complication arose after the removal of the arterial catheter. Subacute thrombotic occlusions were not observed. Since F 1 + 2 concentrations did not exceed the upper limit of normal range (1.11 nm/l) in any of the 19 patients, the therapeutic regimen was not changed. Monitoring F 1 + 2 may thus be helpful in introducing a more individual treatment if aggressive anticoagulation has to be performed.

Administration, Oral↗

The effects of the nitric oxide donors molsidomine and SIN-I on human polymorphonuclear leucocyte function in vitro and ex vivo.

The nitrovasodilator and nitric oxide donor molsidomine and its metabolite SIN-I dilate vascular smooth muscle and inhibit platelet activation by increasing intracellular concentrations of cyclic GMP. We have therefore studied the effects of molsidomine and SIN-I on isolated human polymorphonuclear leucocytes (PMN) in vitro and ex vivo. In vitro molsidomine dose-dependently reduced beta-glucuronidase release and the generation of superoxide anions from non-activated and from FMLP- or PAF-stimulated human PMNs. SIN-I was equally effective in reducing beta-glucuronidase release and totally inhibited oxygen radical generation at a concentration of 580 mumol.l-1. In a double-blind, placebo-controlled, randomized trial we also studied beta-glucuronidase release and the generation of superoxide anions from isolated PMNs. Blood was drawn from 12 healthy volunteers before and 3 h after oral molsidomine (16 mg) or placebo. There was no statistically significant difference in beta-glucuronidase release and superoxide anion formation when the PMNs were isolated before or after molsidomine or placebo. This was the case for non-activated, as well as FMLP- or PAF-stimulated PMNs. Thus, the nitric oxide donors molsidomine and its metabolite SIN-I caused a dose-dependent inhibition of PMN functions in vitro, but no significant inhibition when the PMNs were isolated after oral molsidomine.

Adult↗

Development of an in vitro cell culture system to mimic the blood-brain barrier.

Primary cultures of brain capillary endothelial cells (BCECs) cocultured together with astroglia cells were used to investigate the induction of blood-brain barrier (BBB) characteristics in vitro. By immunofluorescence, histochemical staining, two-dimensional gel electrophoresis and enzyme activity tests we are able to show that BCECs in vitro loose typical blood-brain barrier properties but not their common endothelial phenotype. Astrocytes induce the expression of the blood-brain barrier characteristic enzymes gamma-glutamyltranspeptidase and alkaline phosphatase but only in a coculture system with direct cell to cell contact between BCECs and astroglia cells. C6-glioma cells also re-establish the BBB phenotype but were less effective compared to astrocytes. The susceptibility of the BCECs to an astroglial stimulus depends on the proliferative state of the BCECs.

Alkaline Phosphatase↗

Gene order and genetic distance of 13 loci spanning murine chromosome 15.

Thirteen genetic loci spanning murine chromosome 15 from 15A2 (Mlvi-2) to 15F2-3 (Gdc-1) have been mapped. The genetic distance extends to 55.4 cM. Among 151 animals, only 1 animal with a double cross-over was found. The linear order is unambiguous, with the exception of the distal end on 15F1-3. Our analysis favors the order cen-Ela-1/Hox-3-Wnt-1-Gdc-1-ter. This ordering makes necessary the introduction of three tightly spaced double recombination events around and within the Hox-3 locus. Alternatively, Hox-3 may be most distal, and several double recombinations at the telomere lead to map expansion. Despite the unequal distribution along chromosome 15 of G-versus R-bands, a comparison of distances determined by physical and genetic mapping does not indicate an overt difference in distance between both mapping techniques.

Animals↗

Relative sensitivity of four noninvasive methods in assessing systolic cardiovascular effects of isoproterenol in healthy volunteers.

STUDY OBJECTIVE: The study was performed to evaluate the relative sensitivity of various noninvasive methods to detect and describe the systolic cardiovascular effects of stepwise increasing doses of isoproterenol: two-dimensional left ventricular echocardiography (main variable, ejection fraction), ACVF (attenuation compensated volume flow)--dual-beam Doppler echoaortography (time-averaged mean velocity), electrical impedance cardiography [(dZ/dtmax)/RZ index], and systolic time intervals from mechanocardiography (PEP and QS2c). METHODS: Isoproterenol was administered by constant rate intravenous infusion in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 minutes). Saline control infusions were given in analog fashion. The treatments (isoproterenol and saline solution) were administered in a period-balanced two-way crossover design with randomly allocated sequences. The subjects, observers, and analysts were blinded to the treatment protocol. Study subjects were 10 healthy male volunteers (age range, 23 to 31 years; mean age, 26.6 years). RESULTS: Compared with saline solution, isoproterenol caused a dose-related increase in ejection fraction, (dz/dt)/RZ index, and time-averaged mean velocity and a dose-related shortening of PEP and QS2c. The responses are congruent with an enhancement of cardiac systolic performance caused by a positive inotropic stimulation and an afterload reduction ("inodilatory" response). The effects on systolic time intervals reached statistical significance (alpha = 0.05) at the first isoproterenol dose step, the effects on the impedance cardiography and the Doppler echoaortography variables reached statistical significance at the second dose step, and the effects on the two-dimensional echocardiography reached statistical significance at the third dose step. CONCLUSIONS: All methods allowed to detect isoproterenol-related changes. Systolic time intervals were the most sensitive, followed by impedance cardiography, ACVF--dual-beam Doppler echoaortography, and two-dimensional echocardiography. The practical convenience and high sensitivity of the systolic time intervals makes them suitable to evaluate investigational systolic inodilatory changes in humans.

Adult↗

[Tubal malpositioning as a cause of tubal cuff hernia].

Airway obstruction of endotracheal tubes may occur during general anaesthesia. A case is reported where endobronchial intubation and inflation of the cuff caused herniation into the left bronchus before the malpositioning had been corrected. This led to a cuff herniation that caused airway obstruction at the end of anaesthesia. The regional overinflation of the tubes cuff could be reproduced by a model by other tubes of the same type. Malpositioning of endotracheal tubes may cause cuff herniation that potentially leads to acute airway obstruction.

Aged↗

Arrhythmia profile in acromegaly.

In a controlled study, the cardiac involvement and arrhythmia profile of 32 patients with acromegaly were correlated with endocrine parameters (somatomedine C, growth hormone), clinical score and duration of the disease. Data were compared with those of 50 controls free of cardiac disease. Stress ECG, 24 h Holter monitoring and echocardiography were performed. Supraventricular premature complexes occurred no more often in acromegalics than in controls. Both prevalence and severity of ventricular arrhythmia, however, were significantly higher in patients compared to controls (P less than 0.01). 15/32 (48%) acromegalic patients had complex ventricular arrhythmias (Lown III-IV) as compared with 6/50 (12%) normal subjects (P less than 0.01). Repetitive ventricular arrhythmias (Lown IV a/b) occurred in 10/32 (31%) patients, but only in 4/50 (8%) controls (P less than 0.01). Furthermore, the frequency of ventricular premature complexes increased with duration of acromegaly (P less than 0.01). No correlation was found between the severity of ventricular arrhythmia and hormone levels. Left ventricular muscle mass was significantly increased (285 +/- 139 g, P less than 0.02) due to concentric hypertrophy. Severity of ventricular arrhythmias correlated with left ventricular mass and with clinical activity score (P less than 0.01). Thus, compared to controls, acromegalic patients show more frequent and complex ventricular arrhythmias and left ventricular hypertrophy. Duration of the disease rather than hormone levels seems to be relevant for these pathological changes.

Acromegaly↗

Clinical relevance of vegetation localization by transoesophageal echocardiography in infective endocarditis.

Infective endocarditis is associated with significant morbidity and mortality, with valvular destruction and congestive heart failure being more common in patients with echocardiographically discernible vegetations. The transoesophageal approach affords consistently high quality images with excellent structural resolution. Two-hundred and eighty-one patients with clinically suspected infective endocarditis were studied, to evaluate the prognostic value of ascertaining the site of vegetations. Among them were 118 patients with vegetations attached to the aortic or mitral valve. These patients were followed for a mean period of 14 months. Mitral valve vegetations were associated with a significantly higher incidence of embolic events than vegetations on aortic valves (25% vs 9.7%). The incidence of abscess formation was higher in aortic than in mitral valve endocarditis (6% vs 0%), as were the need for surgical intervention (11% vs 5.5%) and mortality (1.6% vs 0%) respectively). Bivalvular endocarditis was associated with an increased rate of complications: embolism (50%), abscess formation (15%), surgery (35%) and mortality (10%). By multivariate analysis, echocardiographically accessible risk factors for subsequent embolism were a vegetation size of more than 10 mm and mitral valve involvement. Risk factors associated with in-hospital fatality were embolism, a vegetation size of more than 10 mm, and Staphylococcus aureus infection. Our data suggest that the site influences both the rate and the type of complications. Precise echocardiographic visualization of vegetations helps to stratify patients into a high-risk sub-group, perhaps warranting early prophylactic surgical intervention. Transoesophageal echocardiography may play an important role in assessing the clinical outcome for these patients.

Abscess↗

Rate of fibrinogen breakdown related to coronary patency and bleeding complications in patients with thrombolysis in acute myocardial infarction--results from the PRIMI trial.

Four hundred and one patients with acute myocardial infarction of less than 4 h duration were randomized to receive intravenous thrombolytic treatment with either 80 mg of full length unglycosylated single-chain-urokinase plasminogen activator (INN saruplase) or 1.5 million IU of streptokinase delivered over a 60 min period. Angiographic patency rates were higher at 60 min in saruplase treated patients (71.8% vs 48%; P less than 0.001), but did not differ significantly at 90 min (71.2% vs 63.9%; P = 0.15). Fibrinogen levels dropped markedly in both groups, the decrease being delayed and less pronounced with saruplase. Total fibrin and fibrinogen degradation products and D-dimer values rose earlier and to higher peak values in streptokinase treated patients. In both groups marked plasminogen and alpha 2-antiplasmin consumption was observed. Lower fibrinogen levels, and in particular the faster rate of fibrinogen breakdown, were associated with higher patency rates at 90 min (P less than 0.05). Patients with bleeding complications had lower 'lowest points' and a more rapid decrease in fibrinogen (P less than 0.05). These findings were not related to the drug used. Increased heparin levels at 6 to 12 h were correlated to bleeding complications in streptokinase treated patients. It is concluded that the rate of fibrinogen breakdown during and following thrombolytic treatment for acute myocardial infarction is related to early vessel patency and bleeding complications.

Blood Coagulation Tests↗

Acute hemodynamic effects of nicorandil in coronary artery disease.

Nicorandil is a potent vasodilator with antianginal and anti-ischemic properties that acts on both the coronary and the peripheral vascular bed. Because of its dual vasodilatory mechanisms mediated by an increase in cyclic GMP similar to that of nitrates and by a selective increase in the K+ conductance of the smooth muscle cell membrane, nicorandil unloads the right and left ventricles at rest and during exercise. Thus, compared with the classic nitrates, nicorandil is a more balanced vasodilator, i.e., it affects not only the venous capacitance vessels (as predominantly affected by nitrates) but also the arterial resistance vessels. In clinical pharmacologic trials, nicorandil has been administered intravenously (2 to approximately 14 mg) as well as sublingually and orally in single doses of 10-60 mg. In patients with coronary artery disease and impaired left ventricular function, the decrease in preload resulted in a significant improvement of cardiac output. Depending on the doses applied and the patient populations studied, observed decreases in systemic blood pressure were consistent with decreases in peripheral vascular resistance. The effect on heart rate was small, and no influence on atrioventricular conduction could be detected. Nicorandil enhanced exercise capacity in patients with ischemic heart disease. This benefit can be attributed to the reduction in loading of the right and left ventricle as well as to an improvement of regional wall motion abnormalities secondary to the coronary dilatory properties of the drug. Nicorandil appears to be a valuable additive to the antianginal and anti-ischemic management of coronary artery disease.

Animals↗

Intravascular ultrasound imaging of arterial wall architecture.

Intravascular ultrasound (IVUS) is a promising new technique for assessing vascular morphology and structure. Controversy exists whether the three-layer appearance of the arterial wall correctly reflects the histologic structures of the intima, media, and adventitia. We performed an experimental study to clarify the three-layer appearance. The vessel wall architecture was analyzed by IVUS on eight different kinds of plastic cylinders, 24 normal blood vessels from pigs, and 59 human arterial segments. A distinct three-layer appearance was observed on all the plastic cylinders when the ultrasound beam was perpendicular to the wall. A three-layer appearance was also seen in the arterial wall, in the muscular (iliac, femoral artery) and elastic types (aorta), when the echo beam was perpendicular to the vessel wall. The three-layer pattern was even observed on the arterial wall when the intima was removed. Furthermore, the removed intima itself provided a three-layer image. Histologic examination showed that there was no correspondence between the IVUS three-layer appearance and the intima, media, and adventitia. Moreover, we also performed IVUS on nine patients who suffered from aortic dissection. Intravascular ultrasonic visualization of the dissected intima showed a distinct three-layer pattern. The pattern disappeared when: (1) the echo beam was not perpendicular to the vessel wall; (2) there was connective tissue around the vessel wall; (3) there was arterial wall calcification; or (4) the vessel wall was too thick or the distance between the ultrasound transducer and the vessel wall was too large.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dissection following balloon angioplasty of aortic coarctation: review of the literature.

Balloon angioplasty of the coarctation of the aorta can result in intimal or medial or even adventitial dissections as demonstrated by in vitro studies and animal experiments. As a typical sign of stretching of the aortic wall, patients complain of pain during the angioplasty procedure. In the literature, aortic wall rupture and ventricular fibrillation during the procedure are reported. Additional sudden deaths can occur within 40 hours after the procedure. Mortality ranges from 0.1% to 2.5%. By transesophageal echocardiography, monitoring of balloon angioplasty, control of the positioning of the balloon, and control of the results and detection of complications are possible. Intimal as well as medial dissections can be detected with observed healing for intimal but also medial dissections. In order to avoid the patient's discomfort, intraaortic ultrasound will be used in the future, when major methodological improvements are done. Computed tomography demonstrates medial dissections but is not able to visualize intimal dissections. Using computed tomography and magnetic resonance after angioplasty of the coarctation of the aorta, irregularities are described in up to 17% of the patients. For angiography, a low detection rate of medial dissections has to be expected, when not biplane angiographies of the whole thoracic aorta are performed. Medial dissections can be seen, but intimal dissections are missed. In conclusion, a review of the literature demonstrates a high incidence of intimal and medial dissections after angioplasty of the coarctation of the aorta with spontaneous healing in most patients. As is the way with coronary angioplasty, aortic wall ruptures are rare, but stand-by surgery is necessary.

Aortic Dissection↗

Gingival crevicular fluid of patients with gingivitis or periodontal disease: evaluation of elastase-alpha 1 proteinase inhibitor complex.

Elastase-alpha 1 proteinase inhibitor (E alpha 1PI) concentrations were assessed in gingival crevicular fluids and evaluated in relation to the clinical signs of periodontal disease. 7 gingivitis patients (group G), 38 patients with adult periodontitis and clinically stable lesions (group AP), 21 patients with rapidly progressive periodontitis and clinically stable lesions (group RPP) and 11 patients with either adult periodontitis or rapidly progressive periodontitis and clinically progressive lesions (group Pr) were studied. 6 healthy subjects served as the control group (group H). Significantly differences were observed in the E alpha 1PI concentration between the healthy, gingivitis, clinically stable periodontitis and clinically progressive periodontitis group. In the control group, no E alpha 1PI was detected. Groups G, AP and RPP showed mean E alpha 1PI concentrations of 10.95 +/- 4.96 micrograms/ml, 35.55 +/- 18.64 micrograms/ml and 38.56 +/- 20.89 micrograms/ml, respectively. In these groups, high enzyme levels were correlated with clinical signs of inflammation. The highest E alpha 1PI levels were observed in the clinically progressive lesions. However, they were not necessarily associated with bleeding on probing or clinical evidence of inflammation. These data suggest that a significant increase in crevicular E alpha 1PI levels may be an early manifestation of a progressive or potentially progressive periodontal lesion.

Adult↗