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Biomedical subjects

M Riedel

Publications and source records attributed to M Riedel.

At least 91 records · Page 5Linked to original sources

Growth hormone therapy in adults: rationales, results, and perspectives.

This review outlines the present knowledge of the rationales, clinical aspects, and perspectives of a therapy with recombinant human growth hormone (rhGH) in adults. In patients with hypopituitarism the effects of rhGH replacement have been extensively studied. Recent clinical trials show that rhGH treatment improves most alterations of body composition and psychological performance, but many of the metabolic actions of GH remain equivocal. Although side effects after short-term administration are usually mild, the risks of severe long-term adverse effects are still uncertain. A supplementation with rhGH is also suggestive in advanced age and obesity, but the clinical results are controversial so far. The anabolic actions of rhGH were exploited in several recent trials including patients who were severely ill, malnourished, on chronic haemodialysis, or on total parenteral nutrition. Although nitrogen-sparing effects of GH have been demonstrated in most cases, the data do not indicate a clinical benefit in terms of reduced mortality, improved outcome, or accelerated recovery. Therefore, recommendations for the use of rhGH do not have any rationale in these patients yet. The efficacy of rhGH in the treatment of reproductive or immunological disorders remains elusive and needs further investigation. In conclusion, the application of rhGH is still an experimental therapy which should be performed under close observation in well-controlled clinical studies.

Aging↗

Effects of a perfluorocarbon emulsion on regional cerebral blood flow and metabolism after fluid resuscitation from hemorrhage in conscious rats.

Regional cerebral blood flow and metabolism were investigated after addition of a small volume of perfluorocarbon (PFC) emulsion to the resuscitation fluid after hemorrhage. Severe volume-controlled hemorrhage (40 mL/kg body weight (bw) withdrawn over 30 min followed by hypovolemia of 30 min duration) was induced in conscious rats. While breathing 100% oxygen, the intravascular volume was repleted by the infusion of either 6% hydroxyethyl starch (mean mol wt 200,000/0.5; HES) or 6% hydroxyethyl starch plus perflubron (90% wt/vol emulsion of perfluoroctylbromide, 3 mL/kg bw; HES-PFOB). Two hours after fluid resuscitation either iodo[14C]antipyrine or 2[14C]deoxy-D-glucose were infused. Local cerebral blood flow (LCBF) or local cerebral glucose utilization (LCGU) were determined in 34 brain structures using quantitative autoradiography. Local cerebral metabolism was not disturbed in the HES and the HES-PFOB groups after fluid resuscitation, although slight reductions (mean -14%) were measured (HES-PFOB vs HES; P < 0.05). The HES-PFOB group showed LCBF values that were higher in the different brain structures than those of the HES group (mean +30%). A close correlation was found between LCGU and LCBF of the 34 brain structures in both groups (HES: r = 0.96, P < 0.01; HES-PFOB: r = 0.98, P < 0.01), whereas the LCBF-to-LCGU ratio was reset from 2.2 mL/mumol in the HES group to 3.4 mL/mumol in the HES-PFOB group (P < 0.05). The higher blood flows in the HES-PFOB group were sufficient to restore cerebral oxygen delivery to normal levels at a reduced arterial oxygen content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Direct effects of estrogens on vascular tone: characterization and clinical significance].

Estrogen replacement therapy has been found to reduce the incidence of cardio- and cerebrovascular diseases in postmenopausal women. The mechanisms of this vasoprotection are controversial. In recent years, direct vascular actions of estrogens have been proposed in addition to beneficial effects on cardiac risk factors such as hypercholesterolemia. In an attempt to determine the role of direct hormonal influences on human arteries we analyzed the acute vascular responses to 17 beta-estradiol in a series of in vitro and in vivo studies. A dose-dependent estrogen-induced vasorelaxation was found in human coronary arteries in vitro which was more pronounced in women and associated with a significant increase in cyclic AMP and cyclic GMP content. This vascular response could be confirmed in healthy postmenopausal women during a clinical double-blind cross-over study using a quantitative duplex-sonographic approach. Estradiol induced a significant vasodilation and increase of blood flow in femoral arteries, whereas placebo had no effect. As measured by quantitative coronary angiography, high-dose estradiol application was also followed by a significant dilation of epicardial coronary arteries. These direct vascular actions such as vasodilation and increase of blood flow may contribute to the preventive estrogen effects on cardiovascular diseases in postmenopausal women.

Administration, Sublingual↗

Ovarian sex steroids and atherosclerosis.

Estrogens have been found to protect against atherosclerosis in a variety of animal models, and these antiatherogenic properties have been confirmed by epidemiological and clinical studies in women as well. Since the estrogen-induced changes of plasma lipid and lipoprotein levels do not fully account for the prevention of atherosclerosis, additional effects must be assumed. Experimental studies suggest various direct vascular actions. Estrogens enhance the endothelial degradation of low-density lipoprotein cholesterol, and preliminary data indicate antioxidative actions on low-density lipoprotein particles in macrophages. They suppress intimal proliferation and extracellular matrix production in the arterial wall and induce marked vasodilatation in systemic and coronary arteries. Adverse effects on hemostatic factors described with high doses and synthetic compounds are not evident during hormonal replacement in postmenopausal women, in whom an estradiol-induced inhibition of platelet aggregation may even have beneficial clinical effects. The role of progesterone and other progestogens in the progression of atherosclerosis is controversial. Despite a partial antagonism to estrogen-induced changes of plasma lipids, their addition to estrogens does not alter the anti-atherosclerotic properties, at least in animal experiments. The direct vascular actions of progestogens-although not as well documented-seem to be less pronounced than those of estrogens. The experimental data indicate that direct vascular effects play an important role in the antiatherogenic properties of ovarian sex steroids. However, the underlying cellular and molecular mechanisms remain largely unknown.

Animals↗

Quantitative angiographic follow-up studies on the development of coronary artery disease: which coronary segments should be analyzed? Experience from INTACT.

Angiographic follow-up studies on the evolution of coronary artery disease are of increasing relevance. It has still to be evaluated which coronary segments are predominantly involved in the process of atherosclerosis and, thus, should be preferably included in the analysis. Therefore, the correlation of progression and regression of coronary disease with the diameter and location (proximal, mid or distal) of coronary segments was investigated from the data of the INTACT-study, in which 25 different coronary segments were defined including anatomic variants of rather distal segments. In 348 patients with coronary artery disease, standardized coronary angiograms were repeated within 3 years and were quantitatively analyzed (CAAS). In 1063 coronary stenoses (% diameter stenosis > 20%) compared from both angiograms, progression and regression were not influenced by diameter nor location of arterial segments. In the follow-up angiograms, the number of new lesions (stenoses and occlusions) per coronary segment differed with regard to segment diameter (> 3 mm: 64/1125 (6%); 2-3 mm: 139/1967 (7%); < 2 mm: 44/1756 (2%); p < 0.001) and location of segments (proximal: 86/1285 (7%); mid: 84/1193 (7%); distal: 77/2370 (3%); p < 0.001). Out of 77 distal new lesions, only 25 (32%) were found in segments < 2 mm in diameter. Since the absolute number of new lesions was high in distal coronary segments, but low in segments with diameters < 2 mm, angiographic follow-up studies should analyze coronary segments at any location, but may neglect segments with diameters smaller than 2 mm.

Coronary Angiography↗

Quality of life in patients with Addison's disease: effects of different cortisol replacement modes.

This study compares the impact of different modes of cortisol replacement therapy on the health perception and general well-being in patients with primary adrenocortical failure. 14 adults (8 female, 6 male) with Addison's disease on chronic cortisol replacement participated in the study. In a randomized double-blind cross-over design, all patients were treated with 3 modes of cortisol replacement for one week each (mode I: 20 mg hydrocortisone (HC) at 0700 h and 10 mg HC at 1900 h; mode II: 30 mg HC at 0700 h and placebo at 1900 h; mode III: placebo at 0700 h and 30 mg HC at 1900 h). Following the third week, the replacement modes were repeated in a different random order. For quality-of-life assessment the patients completed three different questionnaires (Addison-questionnaire, Basler Befindlichkeits-Skala, Beschwerde-Liste) and were interviewed about their general contentment at the last day of each treatment week. General well-being in terms of subjective contentment was best established during mode I (in 64% of patients) and less often stated with mode II (in 29%) and III (in 14%) (p < 0.05 mode I vs III). With the twice-daily replacement (mode I), sum scores of all questionnaires were changed towards improvement compared to both once-daily regimens (p < 0.05 vs mode II and III), but did not reach normal values of healthy subjects. Differences between mode II and III were insignificant. We conclude that quality of life in Addison patients is mainly influenced by the mode of cortisol replacement therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Addison Disease↗

Endothelium independent relaxation of human coronary arteries by 17 beta-oestradiol in vitro.

OBJECTIVE: There is accumulating evidence that oestrogen replacement therapy protects against the development of coronary atherosclerosis and myocardial infarction in postmenopausal women. The mechanism of this protective effect is uncertain. The aim of this study was to measure the effects of 17 beta-oestradiol on human epicardial coronary artery tone. METHODS: Coronary artery rings were obtained from explanted hearts during cardiac transplantation. The rings were suspended in organ baths for isometric tension measurements. The rings were precontracted with prostaglandin F2 alpha, and were then exposed to either 17 beta-oestradiol (0.3 nM-3 microM) or solvent control (0.2% ethanol v/v). In some rings, cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate content were measured by radioimmunoassay. RESULTS: 17 beta-Oestradiol induced a significant relaxation [maximum effect: 84(SD 18)%]. The onset of the relaxant effect occurred within 5 min, and was maximal within 40 min. The relaxation in response to 3 microM 17 beta-oestradiol was of similar magnitude in rings with and without intact endothelium. The maximum relaxation induced by 3 microM 17 beta-oestradiol was greater in arteries from hearts obtained from women than in those obtained from men [-100.0(3.0)% v -77.5(17.6)%, respectively]. The exposure of rings to 3 microM 17 beta-oestradiol for 30 min resulted in a significant increase in both cyclic AMP and cyclic GMP content, by 88% and 182%, respectively. CONCLUSIONS: 17 beta-Oestradiol produced an endothelium independent relaxation of precontracted human coronary arteries in vitro, and this effect was associated with an increase in both cyclic AMP and the cyclic GMP content. This direct relaxant effect of oestrogens on coronary arteries may contribute to the beneficial effects of oestrogen replacement therapy in postmenopausal women.

Adult↗

Update on cardiac catheterization and coronary arteriography.

Indications for cardiac catheterization--including coronary angiography--have substantially broadened with the advent of nonsurgical therapeutic interventions performed in the catheterization laboratory. Consequently, the increasing number of facilities performing these procedures require clear and unmistakable guidelines regarding the indications for and the safety and ethical aspects of the procedure. Technical developments in image acquisition and evaluation, such as quantitative analysis, allow the exact, reproducible assessment of minute changes in cardiac morphology and function, the evaluation of which becomes increasingly important in prognosis-related clinical trials.

Cardiac Catheterization↗

The pulsatile GH secretion in acromegaly: hypothalamic or pituitary origin?

OBJECTIVE: We studied the effects of different modes of octreotide therapy on the pulsatile pattern of GH release in an attempt to define better its regulation by growth hormone-releasing hormone (GHRH) and somatostatin and its effects on IGF-I plasma levels in acromegaly. DESIGN: In six acromegalic patients not cured by previous treatment we compared the 24-hour GH secretion profiles under basal conditions with subcutaneous (s.c.) bolus injections of 100 micrograms octreotide every 8 hours and with continuous s.c. infusions of the same daily dose. Blood samples were taken every 10 minutes over 24 hours followed by a GHRH test (100 micrograms GHRH i.v.) with blood sampling every 15 minutes for another 2 hours. After a 4-week interval all patients were treated either by the bolus or continuous mode of octreotide application in a randomized cross-over design. On day 4 of treatment blood sampling and GHRH test were repeated. Octreotide treatment was withdrawn for another 4 weeks; all patients then received the alternate application mode and were measured under similar conditions. MEASUREMENTS: Serum GH and plasma IGF-I concentrations were analysed by serial array averaging. IGF-I levels were measured in two different assays with and without previous protein extraction. For GH pulse detection three different algorithms (Cluster, Pulsar, Desade) were applied. RESULTS: With both treatments, the initially elevated basal 24-hour mean serum GH concentrations (58.0 +/- 9.7 mU/l mean +/- SEM) decreased significantly (bolus: 11.5 +/- 4.9 mU/l, P < 0.001 vs basal; continuous infusion: 7.6 +/- 1.9 mU/l, P < 0.001 vs basal) after 4 days. GH suppression was significantly more pronounced following continuous infusion than bolus (P < 0.05). IGF-I plasma concentrations were lowered significantly (P < 0.05) with both forms of treatment which did not differ between themselves. Bolus and continuous infusion treatment significantly inhibited (P < 0.05) the amplitudes of pulsatile GH release, but did not change the pulse frequency. In two of the patients, GHRH stimulation did not increase GH serum levels suggesting a constitutive activation of adenylyl cyclase. CONCLUSION: Continuous subcutaneous octreotide treatment in acromegaly suppresses mean GH levels better than bolus injection. The number of GH pulses remains unaffected by both modes of treatment providing evidence against a somatostatinergic mechanism of pulsatile GH secretion in these patients. The unchanged frequency of pulsatile GH release in the patients unresponsive to exogenous GHRH indicates that this pattern might be independent of hypothalamic GHRH and somatostatin and suggests a pituitary-derived mechanism for GH pulse generation in acromegaly.

Acromegaly↗

HLA and venous thrombosis: a prospective study.

The frequency of venous thrombosis diagnosed by the fibrinogen uptake test and ultrasound in relation to HLA typing was examined in a prospective study of 154 patients undergoing total hip replacement. The results demonstrate an association between venous thrombosis and the presence of HLA Cw4 and B35 (being in a linkage disequilibrium with Cw4) (Cw4 34.4% and B35 27.3%, relative risk 2.531 and 1.935 respectively). These results suggest that the presence of HLA Cw4 can be regarded as one of laboratory risk factors of venous thrombosis.

Adult↗

The role of neuropeptide Y (NPY) in control of gonadotropin and prolactin release in the rat.

Neuropeptide Y is a peptide found in a variety of hypothalamic loci which is frequently colocalized with catecholamines. It is also secreted into hypophyseal portal vessels. We have previously evaluated the effects of this peptide on FSH, LH and prolactin release. In ovariectomized females neuropeptide Y inhibits LH release. It has similarly been reported to inhibit LH release in intact males; however, estrogen priming of ovariectomized animals converts this inhibitory action into a stimulatory effect. In ovariectomized animals the peptide has a direct stimulatory effect on perifused pituitary cells, enhancing the release of both FSH and LH, an effect which is contrary to that obtained with LH release after intraventricular injection of the peptide. In the present experiments the physiological significance of these effects has been evaluated by the intraventricular injection (3V) of highly specific antiserum directed against the peptide. In ovariectomized and in ovariectomized, estrogen-primed rats, the third ventricular injection of antiserum had no effect on gonadotropin release. In male rats intraventricular injection of the antiserum elevated LH, which indicates that the inhibitory action of the peptide seen in intact males is of physiological significance. However, it has been reported by others that the proestrous type discharge of LH-RH is blocked by intraventricular injection of neuropeptide Y antiserum. Neuropeptide Y might therefore play an essential role in the preovulatory release of LH. On the other hand, others have shown that intraventricular injection of neuropeptide Y in male rats can either stimulate, at low doses, or inhibit, at high doses, the release of prolactin. We have confirmed the inhibitory action, which appears to be of physiological significance since antisera directed against the peptide injected intraventricularly resulted in an elevation of prolactin release. The results of these studies indicate that neuropeptide Y plays a very important and often physiologically significant role in the control of LH and prolactin release by hypothalamic action.

Animals↗

Physiological role of neuropeptide Y (NPY) in control of anterior pituitary hormone release in the rat.

Neuropeptide Y (NPY) is a peptide originally isolated from porcine brain and subsequently shown to be widely distributed in the body of several species, including man. Neuropeptide Y is a circulating peptide; however, blood levels were higher in portal than peripheral blood of anesthesized rats. Earlier studies in ovariectomized and intact male rats have shown that intraventricular injection of NPY inhibits release of growth hormone (GH) and luteinizing hormone (LH) without producing significant modification of plasma follicle stimulating hormone (FSH) and thyrotropin stimulating hormone (TSH). In the male low doses of NPY elevate prolactin (PRL) whereas high doses suppress its release. To assess the physiologic significance of these actions, we injected a highly specific anti-NPY serum (aNPY) into the third cerebral ventricle (3V) of unrestrained male, ovariectomized, and ovariectomized, estrogen progesterone blocked rats and measured plasma GH, PRL, LH and TSH by blood sampling via indwelling jugular catheters. Third ventricular injection of aNPY (2 microliters of 1:10 dilution) caused a significant elevation of plasma GH levels after 3 and 4 h compared to the values in NRS (1:10)-injected rats. To determine if these changes were due to alterations in pituitary responsiveness to somatostatin, the rats were injected intravenously with a challenge dose of somatostatin (0.5 microgram) 2 h after previous injection of aNPY or NRS, and blood samples were taken every 10 min for 30 min. The responses did not differ in both groups which indicated that the antiserum was not acting directly on the pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Hemodynamics and gas exchange in acute lung embolism].

The main hemodynamic consequence of pulmonary embolism is the acute mechanical reduction of the pulmonary vascular cross-sectional area. This results in a sudden increase of the pulmonary vascular resistance, and if the cardiac output is to be maintained, in an increase in pulmonary artery pressure and right ventricular work. The extent of hemodynamic changes in pulmonary embolism are determined primarily by the size of the emboli and whether or not the patient has underlying cardiopulmonary disease. Although humoral factors and neural reflexes play a role in determining the severity of hemodynamic responses to pulmonary embolism in experimental animals, their role in patients is uncertain. In patients free of preembolic cardiopulmonary disease, the extent of embolic obstruction can be related directly to the mean pulmonary artery pressure. Accordingly, either the extent of obstruction or the mean pulmonary artery pressure may be used as a measure of right ventricular afterload. Obstruction of 25 to 40% leads to an increase in mean pulmonary artery pressure of 20 to 30 mm Hg, massive obstruction over 75% to a pressure of 40 to 45 mm Hg. Continuous hemodynamic monitoring helps to estimate the speed of the resolution of emboli and to a certain extent the adequacy of treatment. Right arterial pressure is consistently elevated by a mean pulmonary artery pressure over 30 mm Hg and provides also a rough estimate of the degree of pulmonary vascular obstruction. A previously normal right ventricle will dilate at a mean pulmonary artery pressure of 40 to 45 mm Hg. which may result in acute tricuspid insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart Atria↗

[The diagnosis of lung embolism].

An accurate diagnosis of pulmonary embolism is essential to prevent excessive mortality and morbidity from lack of therapy or inappropriate anticoagulation. The clinical diagnosis is highly nonspecific because none of the symptoms or signs of pulmonary embolism is unique and all may be caused by other cardiorespiratory disorders. The diagnosis of pulmonary embolism is unlikely, however, if patients do not have dyspnea, tachypnea, evidence of deep vein thrombosis, or a recognized predisposition to thromboembolic disease. Objective testing is mandatory to either confirm or exclude a diagnosis of pulmonary embolism. The electrocardiogram, chest X-ray and the echocardiogram may assist by excluding other potential diagnoses. Routine laboratory studies and lung function testing including blood gas analysis will not be of much help in the differential diagnosis. The hemodynamic investigation with a floating catheter is of diagnostic value especially in those cases where it is not possible to obtain the definitive diagnosis immediately; this method as well as echocardiography can provide a rough estimate of the degree of pulmonary vascular obstruction and are thus able to guide therapy. Methods such as DSA, CT, MR, SPECT, or radiolabelled thrombus scanning are promising but require more extensive validation before routine use. Lung scanning, with its high sensitivity but low specificity is a very useful procedure but cannot be considered to have diagnostic significance independent of the clinical situation. Pulmonary angiography provides the greatest diagnostic certainty of any test available. Based on current knowledge, a diagnostic approach for the management of clinically suspected pulmonary embolism is proposed. Ventilation-perfusion lung scanning is the appropriate next step after ECG, chest X-ray and echocardiogram. The finding of a normal perfusion scan rules out clinically significant embolism and anticoagulation is withheld. Segmental or lobar perfusion defects with normal ventilation in an appropriate clinical setting is sufficiently indicative of pulmonary embolism to proceed with therapy in patients without contraindications. Ventilation-perfusion scans of low or indeterminate probability for pulmonary embolism neither confirm nor exclude the presence of embolism and pulmonary angiography would then be the definitive procedure. As an alternative approach instrumental examination of the leg veins (with venography, impedance plethysmography, or ultrasound) is proposed (Figure 1). If these tests confirm the presence of deep venous thrombosis, anticoagulation can be commenced without the need to perform pulmonary angiography.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac Catheterization↗