Meta-analysis of randomised controlled prostaglandin E1 studies in peripheral arterial occlusive disease stages III and IV.

Background: The relevance of Prostaglandin El (PGE,) in the treatment of peripheral arterial occlusive disease stage III and IV was to be evaluated for the first time by a meta-analysis.

Patients And Methods: Altogether, 643 patients were analyzed from seven randomized, controlled PGE1 studies that were comparable with regard to patient selection, study design and endpoints. Of these, only placebo-controlled studies (n = 254) were included in the formal meta-analysis using the method of DerSimonian and Laird.

Seasonal variation of endothelin-1, angiotensin II, and plasma catecholamines and their relation to outside temperature.

Circannual rhythmicity in plasma catecholamines is well known, but no chronobiologic data are available on endothelin-1 and angiotensin II. This study was designed to investigate in healthy human subjects whether endothelin-1 and angiotensin II exhibit seasonal variations. Furthermore, we assessed the relation of both variables to plasma catecholamines, to environmental temperature, and to relative humidity in northern Germany, a region of a temperate climate.

[Therapy of venous thromboembolism with low-molecular-weight heparins].

Low-molecular-weight heparins, nowadays already widely used for the prevention of thromboembolism, have now also become available for the treatment of deep-vein thrombosis. This article should serve to explain the rationale for this development and to demonstrate the clinically relevant advantages of the use of low-molecular-weight heparins. After briefly describing the characteristic properties of heparins the most relevant studies comparing the use of low-molecular-weight heparin versus unfractionated heparin for the treatment of thromboembolism are discussed.

Randomized reliability study evaluating constant-load and graded-exercise treadmill test for intermittent claudication.

The aim of this randomized study was to compare the reliability of the treadmill test at constant-load (C-test, 3 km/hr; fixed grade of 12%) recommended in Germany with that of the graded-exercise test (G-test, 3 km/hr; increase in grade of 3.5% every 3 minutes) propagated in the United States. In 50 patients with an absolute claudication distance (ACD) in the C-test of between 50 and 400 m, the two treadmill tests were carried out in randomized order on one and the same day, and repeated on 3 days within 1 week.

Standardization of carotid ultrasound: a hemodynamic method to normalize for interindividual and interequipment variability.

Background And Purpose: Accurate carotid Doppler examination is an important issue in the light of large endarterectomy trials, but recommended cutoff values for detection of >70% stenosis vary widely. Standardization of diagnostic criteria should consider patient variation and instrument variability.

Methods: We prospectively analyzed various Doppler parameters in 44 patients undergoing carotid angiography to evaluate whether normalization through individual reference measurements from the common carotid artery or the distal internal carotid artery could improve accuracy.

Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease.

Background: Administration of L-arginine improves nitric oxide (NO) formation and endothelium-dependent vasodilation in atherosclerotic patients.

Objectives: We investigated in this double-blind, controlled study whether prolonged intermittent infusion therapy with L-arginine improves the clinical symptoms of patients with intermittent claudication, as compared with the endothelium-independent vasodilator prostaglandin E1, and control patients.

Methods: Thirty-nine patients with intermittent claudication were randomly assigned to receive 2 x 8 g L-arginine/day, or 2 x 40 microg prostaglandin E1 (PGE1)/day or no hemodynamically active treatment, for 3 weeks.

Intra-arterial and intravenous administration of prostaglandin E1 cause different changes to skin microcirculation in patients with peripheral arterial occlusive disease.

Background: Disturbed skin microcirculation in patients with peripheral arterial occlusive disease (PAOD) might be affected by prostaglandin E1 (PGE1). The purpose of this study was to investigate local skin perfusion at the forefoot and toe of PAOD patients during different modes of administration of PGE1.

Patients And Methods: In 17 patients with severe PAOD local intradermal haemoglobin oxygen saturation (SHB) and dermal vascular reserve capacity, transcutaneous oxygen pressure (tcPO2) and laser Doppler flux (LDF) were determined during intra-arterial (1.

Prostaglandin E1 in peripheral vascular disease: a PET study of muscular blood flow.

Background: Increase of blood flow in the ischaemic leg is believed to represent the main action of prostaglandin E1 (PGE1) in the therapy of peripheral vascular disease (PVD). There is no reliable data in man concerning the amount of increase in muscular blood flow (MBF) of the calf, and the difference between intra-arterial and intravenous application.

Patients And Methods: We conducted a positron emission tomography (PET) study of MBF with 15O-water as flow tracer.

Treadmill testing for evaluation of claudication: comparison of constant-load and graded-exercise tests.

Objectives: To compare the correlation and practicability of single-stage vs. graded treadmill protocols in the assessment of the absolute claudication distance (ACD).

Design: Randomized open study.

[Physiology and pathophysiology of the endothelin system in cardiovascular diseases].

The endothelins are a family of potent vasoconstrictors and mitogenic agents. Since the isolation of ET-1 in 1988 the worldwide scientific research interest has mushroomed, resulting in considerable knowledge about molecular biology, biochemistry and pharmacological actions of these peptides. A body of evidence has parallelly emerged pointing to their role in some physiological phenomena as well as in the pathophysiology of cardiovascular disease.

[Cellular mechanisms of endothelial endothelin synthesis].

Endothelin-1 is a vasoactive peptide produced by endothelial cells. Endothelin-1 exerts potent vasoconstrictory effects upon vascular smooth muscle cells, and it may play a role in the pathogenesis of several cardiovascular disorders such as atherosclerosis and ischemic conditions. Besides the investigation of its biological effects, knowledge about cellular mechanisms of the synthesis, signal transduction pathway(s) and receptor-mediated actions on target cells is mandatory for the development of pharmacological strategies in the treatment of cardiovascular disease.

Nailfold capillaroscopy and laser Doppler fluxmetry for evaluation of Raynaud's phenomenon: how valid is the local cooling test?

Background: Since there is a need for an objective parameter of microcirculation in follow-up of patients with Raynaud's syndrome we evaluated the reproducibility of the reaction to a cold exposure test with nailfold capillaroscopy and laser Doppler fluxmetry during a winter period.

Patients And Methods: 10 healthy subjects and 16 patients with primary Raynaud's syndrome were evaluated with nailfold capillaroscopy and laser Doppler fluxmetry of the finger tips during and after a standardized cold exposure stress test. The measurements were repeated in the controls within 2 weeks, in the patient population twice within 24 weeks.

Changes of dermal haemoglobin oxygenation and concentration in healthy subjects and in patients with peripheral arterial occlusive disease during and after acute ischemia.

Background: Oxygen saturation (SHB) and concentration (CHB) of dermal haemoglobin play an important role in the nutrition of the skin. In patients with severe peripheral arterial occlusive disease (PAOD) they are reduced at the forefoot. We investigated the changes of the named parameters during an acute ischemia and during reactive hyperemia using an occlusion test.

Circadian variation of skin perfusion in arterial occlusive disease.

Background: Many physiological processes are subjected to circadian variation. We tested if circadian changes of skin perfusion can be detected by measuring laser Doppler flux (LDF) in the foot and if such variations are different in patients with peripheral arterial occlusive disease (PAOD).

Patients And Methods: LDF was recorded hourly during a 24-hour period in 10 healthy subjects and in 19 PAOD patients, 9 presenting with claudication (stage II according to Fontaine, ankle artery pressures (AP) 80 +/- 11 mmHg) and 10 with skin necrosis (stage IV, AP 42 +/- 29 mmHg).

Vital capillary microscopy of skin areas at the forefoot of diabetic patients using intraarterial injection of Na-fluorescein.

A modified technique of vital capillary microscopy with intraarterial application of Na-fluorescein has been introduced in the study of nutritional skin microcirculation to assess skin microcirculation of different diabetic patients, comprising one group without neurocutaneous complications (group 2; n = 9), one suffering only from neuropathy (group 3; n = 9) and one with trophic skin lesions in the contralateral foot (group 4; n = 8), all without macroangiopathy, compared to healthy controls (group 1; n = 9). Femoroarterial injection of small boli (10 mg) of Na-fluorescein allowed repeated investigation of the dye appearance times (AT) and capillary-filling times of forefoot skin capillaries within small periods of time before, during and after reactive hyperemia. At rest, AT was significantly shorter in patients of group 4 (16.

Improvement in the quality of life after i.v. PGE1 therapy for intermittent claudication.

Background: Increasingly and justifiably, clinical studies are now being expected to investigate the influence of therapeutic measures also on the quality of life of the patient.

Patients And Methods: Since no data on the variability of changes in the quality of life of the patient following PGE1 treatment are so far available, the initial investigation was designed as an uncontrolled pilot study. 104 patients (median age 64.

Efficacy of a new prostaglandin E1 regimen in outpatients with severe intermittent claudication: results of a multicenter placebo-controlled double-blind trial.

For the first time efficacy and safety of a new prostaglandin E1 (PGE1) regimen in the treatment of intermittent claudication were evaluated in a randomized, double-blind, placebo-controlled multicenter clinical trial. The study involved 213 outpatients with a maximum walking distance of 50 to 200 m measured on the treadmill (3 km/hr, 12% grade). After a 2-week run-in phase they received a 2-hour intravenous infusion of 60 micrograms PGE1 or placebo 5 days a week for 4 weeks.

Treatment of primary Raynaud's syndrome with traditional Chinese acupuncture.

Objective: Evaluation of the effects of a standardized acupuncture treatment in primary Raynaud's syndrome.

Design: A controlled randomized prospective study.

Setting: A winter period of 23 weeks, angiological clinic of Hannover Medical School.