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H Vetter

Publications and source records attributed to H Vetter.

At least 37 records · Page 2Linked to original sources

17 Beta-estradiol regulates nNOS and eNOS activity in the hippocampus.

Estrogen treatment in symptomatic postmenopausal women appears to improve cognitive performance including memory, an effect which may involve enhanced nitric oxide formation in hippocampal neurons. To study whether 17beta-estradiol (E2) affects NO synthase activity in the hippocampus, we investigated the influence of E2 on hippocampal NO synthase expression and activity in female rats. Ovariectomy, which significantly decreased E2 serum levels, reduced neuronal (nNOS) and endothelial NO synthase (eNOS) expression and Ca(2+)-dependent NOS activity. E2 substitution reversed these effects. It is concluded that E2 increases nNOS and eNOS expression and activity in female hippocampus and thus improves hippocampal function.

Animals↗

[Effects of angiotensin II on inflammation mediators in healthy subjects].

BACKGROUND AND OBJECTIVE: Inflammatory reactions mediated by cytokines play a central role in the development of atherosclerotic vascular changes. Numerous experimental studies have suggested a connection between the renin-angiotensin-aldosterone system and cytokine liberation from endothelium. This study investigated the effect of exogenous angiotensin II on cytokine liberation in healthy subjects. METHODS: Nine healthy men, aged 25-28 years, having given informed consent, were given angiotensin II infusions of 1, 3 and 10 ng/kg/min, each time over 45 min, once with and once without preceding oral intake of an AT (1)-receptor antagonist (160 mg valsartan). Arterial blood pressures were measured oscillometrically every 5 min. Blood was taken at the end of each perfusion period and one each after its end, measurements being made of plasma activity of angiotensin II, aldosterone, and the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and the vascular cell adhesion molecule (VCAM)-1. RESULTS: Plasma angiotensin II concentrations during perfusion rose from 14.7 +/- 16.5 pg/ml to 200.1 +/- 127.2 pg/ml (p< 0.001). The plasma concentrations of angiotensin II were again within the basal range (16.3 +/- 24.8 pg/ml) one hour after the end of perfusion. Angiotensin II raised the systolic and diastolic blood pressure from 121 +/- 9/70 +/- 6 mmHg to a maximum of 146 +/- 6/97 +/- 3 mmHg (p<0.001). This blood pressure rise was prevented by prior administration of the AT (1)-receptor antagonist. Neither the angiotensin II infusion nor the simultaneous administration of AT (1)-antagonist altered the circulating plasma level of TNF-alpha, IL-6 or VCAM-1. CONCLUSION: Increased circulating plasma levels of angiotensin II induce a significant rise in arterial pressure of healthy male subjects, but do not in the short therm produce a change in the plasma levels of the cytokines TNF-alpha, IL-6 and VCAM-1. These results in healthy subjects throw doubt on the hypothesis that, at least in the short term, the effect of angiotensin II on changes in those cytokines measured in this study are independent of the blood pressure.

Adult↗

[Hypertensive female patients often undertreated or treated too late. Therapy of hypertension needs women's initiative].

Both the cardiovascular risk profile and the incidence of arterial hypertension are known to show gender-specific differences. In postmenopausal women, the cardiovascular risk is clearly elevated. At particular risk are women with diabetes mellitus, overweight and hypertriglyceridemia. In numerous clinical studies on the treatment of arterial hypertension, however, the percentage of women involved is small, and not representative. Furthermore, studies on the confirmation of the diagnosis and treatment show that treatment of hypertension in female patients has often been less effective and less rigorously applied than in men. At the same time, it is known that the success of rigorous risk reduction is independent of gender.

Adult↗

[Circadian rhythm of silent myocardial ischemia. Why morning is so risky for hypertensive patients].

The circadian pattern of numerous cardiovascular events (myocardial infarction, sudden cardiac death, stroke) reveals a peak in the early hours of the morning. A circadian rhythm peaking in the morning is also found for so-called silent myocardial ischaemia, which occurs in more than 20% of patients with arterial hypertension, and can be regularly detected in combined 24-h-ABPM/EKG examinations. Comparative studies have shown that hypertensives with SMI suffer more cardiac events than those with no SMI. It has further been demonstrated that an elevated blood pressure amplitude, with is considered an independent risk factor for cardiac events, is associated with an increased incidence of SMI in patients with micro- or macro-angiopathy. Accordingly, consideration should be given to SMI when deciding on treatment, also in hypertensives with no angina pectoris symptoms.

Circadian Rhythm↗

[Lowering of blood pressure, blood pressure amplitude and heart rate by treatment with valsartan or valsartan/hydrochlorothiazide. Results of an open observation study of 11,447 hypertensives].

OBJECTIVE: This trial investigated the decrease of blood pressure, safety and tolerability of valsartan, an angiotensin-receptor blocker, alone or combined with the diuretic hydrochlorothiazide. In addition, the effect on pulse pressure, heart rate and mean blood pressure were recorded as independent markers of cardiovascular risk. PATIENTS AND METHODS: 12278 hypertensive patients were treated for 12 weeks with valsartan alone or combined with hydrochlorothiazide in a multi-centre open trial. Previously established antihypertensive treatment was continued. Systolic and diastolic pressure, pulse pressure and resting heart rate were recorded at the start of the trial and at 1, 4 and 12 weeks thereafter. RESULTS: Data on 11447 were complete enough to be evaluated (54% males, 46% females; mean age 60.8 years). 44% of the patients were at the same time receiving other antihypertensive drugs at the start of the trial, but the numbers so treated decreased during the trial period. Systolic pressure was reduced by 27.8 mmHg. diastolic pressure by 14.7 mmHg, with a calculated reduction of pulse pressure from 71.5 to 58.7 mmHg. Heart rate was reduced by 3.4 beats. The treatment had to be stopped prematurely in 2.3% of patients because of side effects. There were no severe or life-threatening side effects. CONCLUSION: Treatment with valsartan alone or combined with hydrochlorothiazide provides effective blood pressure reduction and is well tolerated. This trial suggests that, in addition to the fall in blood pressure, the independent risk factors of cardiovascular disease, pulse pressure and resting heart rate, were also reduced during administration of valsartan.

Angiotensin Receptor Antagonists↗

Anti-inflammatory activity of 1.8-cineol (eucalyptol) in bronchial asthma: a double-blind placebo-controlled trial.

Airway hypersecretion is mediated by increased release of inflammatory mediators and can be improved by inhibition of mediator production. We have recently reported that 1.8-cineol (eucalyptol) which is known as the major monoterpene of eucalyptus oil suppressed arachidonic acid metabolism and cytokine production in human monocytes. Therefore, the aim of this study was to evaluate the anti-inflammatory efficacy of 1.8-cineol by determining its prednisolone equivalent potency in patients with severe asthma. Thirty-two patients with steroid-dependent bronchial asthma were enrolled in a double-blind, placebo-controlled trial. After determining the effective oral steroid dosage during a 2 month run-in phase, subjects were randomly allocated to receive either 200 mg 1.8-cineol t. i.d. or placebo in small gut soluble capsules for 12 weeks. Oral glucocorticosteroids were reduced by 2.5 mg increments every 3 weeks. The primary end point of this investigation was to establish the oral glucocorticosteroid-sparing capacity of 1.8-cineol in severe asthma. Reductions in daily prednisolone dosage of 36% with active treatment (range 2.5-10 mg, mean: 3.75 mg) vs. a decrease of only 7% (2.5-5 mg, mean: 0.91 mg) in the placebo group (P = 0.006) were tolerated. Twelve of 16 cineol vs. four out of 16 placebo patients achieved a reduction of oral steroids (P = 0.012). Long-term systemic therapy with 1.8-cineol has asignificant steroid-saving effect in steroid-depending asthma. This is the first evidence suggesting an anti-inflammatory activity of the monoterpene 1.8-cineol in asthma and a new rational for its use as mucolytic agent in upper and lower airway diseases.

Adult↗

[Atrial lead placement in cases of intraoperative atrial fibrillation].

AIM: Evaluating the efficiency of a prescribed concept for atrial lead placement in cases of intraoperative atrial fibrillation (AF). METHODS: Over the period from 11/1998 to 5/2000, we carried out a prospective study on 40 patients with AF. After implantation of the screw electrode into the lateral wall of the atrium, an amplitude of the intracardial ECG of > or = 1.4 mV was arbitrarily defined as tolerable. At amplitudes of < 1.4 mV, atrial overdrive-stimulation occurred at 400 to 800 ppm in order to convert the AF to sinus rhythm (SR). Following successful overdrive-stimulation, the atrial electrode was positioned according to standard values (P-wave > 3 mV, pacing threshold < 0.5 V at 0.5 ms). In the case of unsuccessful intraoperative atrial stimulation, the electrode was repositioned until an amplitude of > or = 1.4 mV was reached. In all cases bipolar atrial screw electrodes (Model 4068, Medtronic Inc., Minneapolis, MN, USA) were implanted. The intraoperative measurements were carried out via the atrial channel of a 5311 PSA (Medtronic Inc., Minneapolis, MN, USA). In follow-up after 6 weeks, the atrial stimulation threshold was measured in [V] at 0.5 ms and the signal amplitude of the P-wave in [mV], or in the case of AF detection with successful mode switch activation. RESULTS: In 31/40 patients (77.5 %) with intraoperative persistent AF, fibrillation amplitudes of 1.4 to 3.1 mV (mean value 1.9 +/- 0.4 mV) were measured. In 9/40 patients (22.5 %) with intraoperative AF, 4 cases of conversion to SR using burst stimulation were documented. Atrial lead placement was performed using standard values. After 6 weeks, 33/40 patients (82.5 %) had SR, while intermittent AF episodes with successful mode switch activation were documented in 21 patients (52.5 %). The P-wave amplitude was 3.63 +/- 0.69 mV (range 1.8 to 4.9 mV), the atrial stimulation threshold was 1.3 +/- 0.4 mV (range 0.4 to 1.9 mV). Atrial lead adjustment due to sensing defects was not required for any patients. CONCLUSION: The results show that all atrial leads implanted in accordance with this concept demonstrate proper sensing at SR as well as under AF, with successful mode switch episodes and acceptable stimulation thresholds.

Aged↗

[Therapy resistant hypertension--significance of electronic compliance monitoring].

HISTORY AND CLINICAL FINDINGS: A 71-year-old woman was admitted with arterial hypertension resistant to drug therapy (office readings 197/82 mmHg) under medication with beta-blocker, AT 1 -antagonist and a diuretic. The only physical pathologic finding was an adipositas. DIAGNOSIS, TREATMENT AND COURSE: The patient was suffering from isolated systolic hypertension, grade 3 corresponding to WHO-guidelines. Despite antihypertensive triple therapy office as well as self-measured blood pressure values (mean 170/82 mmHg) remained elevated. Thus, the patient fulfilled the criteria of a resistant hypertension. The degree of compliance was only 50 %, detected by using a Medication-Event-Monitoring-System (correct dosing interval 17.1 %). We discussed the results of compliance- and blood pressure self-measurement with the patient. In the following period of compliance- and blood pressure self-measurement (with unchanged antihypertensive therapy) the compliance increased dramatically with a degree of 90,9 % and self-measured blood pressure values almost normalized (mean 137/71 mmHg). CONCLUSION: The control of compliance by using electronic compliance-monitoring may help to discover non-compliance as a frequent cause of resistant hypertension and to avoid unnecessary cost-extensive procedures.

Aged↗

[Recurrent spontaneous hemorrhage in a patient with light chain immunocytoma].

The 48-year-old female patient was sent to our clinic for further evaluation of a spontaneous decrease of prothrombin- and prolongation of the bleeding-time. She presented in good conditions with an enlargement of cervical lymphnodes and the history of a monoclonal plasmacyte dyscrasia. The laboratory results revealed a pronounced decrease of prothrombin-time, a prolonged activated partial thromboplastin-time, a decrease of factor VII and X activity and a light chain paraprotein. The histological examination of the bone marrow led to the diagnosis of an immunocytoma and a medullar amyloidosis. For the aim of influencing the coagulopathy the patient was treated with chemotherapy. However, she developed severe bleedings. Further haemostaseological tests presented an amyloidosis-associated decrease of factor VII and X, an acquired von Willebrands disease, an acquired thrombozytopathy and a lupus-like anticoagulans. Under substitution of factor VIII-von Willebrand-factor-complex and chemotherapeutic treatment a stabilisation over several years was achieved till the patient died due to an amyloid-associated acute pancreatitis.

Amyloidosis↗

A method for the rapid construction of cRNA standard curves in quantitative real-time reverse transcription polymerase chain reaction.

Quantification of nucleic acids, especially of mRNA, is increasingly important in biomedical research. The recently developed quantitative real-time polymerase chain reaction (PCR) - a highly sensitive technology for the rapid, accurate and reproducible quantification of gene expression - offers major advantages over conventional quantitative PCR. Transcript quantification is performed in the exponential phase of the PCR reaction through extrapolation of fluorescence signals from a standard calibration curve which represents the initial copy number for a given fluorescence signal. We have developed a method for gene transcript quantification which is based on a LightCycler - assisted real-time PCR in combination with a simple and rapid approach for the construction of external cRNA standards with identical gene sequences as the target gene. Synthesis of cRNAs was performed by in vitro transcription with T7 RNA polymerase followed by reverse transcription and real-time PCR. We applied this approach for transcript quantification of eukaryotic initiation factor 3 p110 (EIF3S8) mRNA in normal testicular tissue. We also present a rapid and simple strategy for the construction of cRNA standards for use in real-time PCR.

Adult↗

The fibrinolytic system in chronic renal failure.

BACKGROUND: Patients with chronic renal failure (CRF) face a high risk of cardiovascular morbidity and mortality. Impaired fibrinolysis has recently been acknowledged to function as a risk factor for cardiovascular ischemic complications. Whether changes in fibrinolytic function contribute to the increased cardiovascular risk in CRF, however, remains unclear. METHODS: In the present study, tissue-plasminogen activator (t-PA) and its main antagonist plasminogen activator inhibitor-1 (PAI- 1) were determined in 12 subjects with normal renal function (group A) [serum creatinine (Cr) <1.3 mg/dl], 24 patients with impaired renal function (Cr 1.3-6.5 mg/dl) (group B) and 22 patients with endstage renal disease (ESRD) on hemodialysis (Cr>6.5 mg/dl) (group C). RESULTS: Plasma concentrations of PAI-1 and t-PA antigen as well as the PAI-1:t-PA molar ratio were unchanged in group B as compared to group A. However, in ESRD patients (group C), t-PA concentrations markedly decreased [13.7 +/- 2.9 ng/ml vs. 32.8 +/- 4.7 ng/ml (group B, p <0.01) and 35.4 +/- 8.4 ng/ml (group A, p <0.01)] while PAI-1 antigen concentrations remained in the control range. Thus, the PAI-1:t-PA molar ratio significantly increased in group C patients [12.4 +/- 4. 0 vs. 6.0 +/- 2.5 (group B; p<0.01) and 4.5 +/- 1.7 (group A; p<0.01]. CONCLUSIONS: From our data it may be suggested that fibrinolysis is markedly disturbed in ESRD due to a decreased availability of t-PA. Thus, it may be speculated that the development of atherothrombotic events in hemodialysis patients is, at least in part, due to an impaired fibrinolysis.

Adult↗

Activation of estrogen receptor beta is a prerequisite for estrogen-dependent upregulation of nitric oxide synthases in neonatal rat cardiac myocytes.

Physiological effects of estrogen on myocardium are mediated by two intracellular estrogen receptors, ERalpha and ERbeta, that regulate transcription of target genes through binding to specific DNA target sequences. To define the role of ERbeta in the transcriptional activation of both endothelial (eNOS) and inducible nitric oxide synthase (iNOS) in cardiac myocytes, we used the complete ER-specific antagonist R,R-tetrahydrochrysene (R,R-THC). R,R-THC inhibited activation of iNOS/eNOS promoter-luciferase reporter constructs (iNOS/eNOS-Luc) in a dose-dependent fashion in COS7 cells selectively transfected with ERbeta, but failed to influence ERalpha-mediated increase of iNOS/ eNOS-Luc. In neonatal rat cardiomyocytes transfected with eNOS-Luc or iNOS-Luc, incubation with 17betaestradiol (E2, 10(-8) M) for 24 h stimulated expression of eNOS and iNOS. R,R-THC (10(-5) M) completely inhibited this effect. Furthermore, eNOS and iNOS protein expression in cardiac myocytes induced by E2 was completely blocked by R,R-THC as shown by immunoblot analysis. Taken together, these results show that ERbeta mediates transcriptional activation of eNOS and iNOS by E2.

Animals↗

[An uncommon cause of severe soft tissue bleeding during phenprocoumon treatment].

HISTORY AND ADMISSION FINDINGS: A 66-year-old patient presented to our clinic with extensive left arm and left flank haematomas, anaemia, a prolonged activated partial thromboplastin time (aPTT), and reduced factor IX activity 6 weeks after prosthetic mechanical aortic valve implantation. INVESTIGATION: Treatment with both vitamin K and a single injection of factor IX concentrate led to normalization of the activated partial thromboplastin time and factor IX activity, which remained constant for several days. No acquired factor IX inhibitor was detectable. Analysis of exon 2 of the factor IX gene revealed a C-->T mutation in codon 10 of the propeptide region, resulting in the substitution of alanine by valine. Echocardiography revealed a significant paravalvular leak. TREATMENT AND COURSE: The substitution of valine for alanine in the factor IX propeptide leads to an impaired affinity of factor IX to the vitamin K-carboxylase complex. In this situation, treatment with coumarin derivatives can profoundly reduce factor IX activity and result in severe bleeding episodes. This patient was re-exposed to warfarin under close hematological monitoring. After 4 days factor IX activity had decreased to 15%, which was associated with an increase of the aPTT and a mild decrease of the prothrombin time. Due to rapid progression of the paravalvular leak and almost impossible long-term orale anticoagulation with coumarin derivatives, we recommended replacement of the prosthetic mechanical valve with a biological device. CONCLUSION: The development of severe bleeding in the context of initiating warfarin therapy raises the suspicion of a factor IX propeptide mutation. The initial screening test is the activated partial thromboplastin time, which is elevated in the presence of the mutation. If concomitantly diminished factor IX activity is found the factor IX propeptide mutation should be excluded. Use of lifelong coumarin derivatives is contraindicated in patients with this mutation. However, a general screening of the activated partial thromboplastin time after coumarin initiation is not justified by cost/benefit analysis.

Aged↗