[Raynaud's phenomenon--current diagnosis and therapy].
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Diagnosis, Differential↗
Biomedical subjects
A Creutzig
Publications and source records attributed to A Creutzig.
[Prevention and treatment of deep vein thrombosis with ximelagatran].
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Anticoagulants↗
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. Additionally, the response rate and the rate of adverse events were determined for the pooled groups of all studies. RESULTS: At the end of treatment, PGE1 showed a significantly better response (ulcer healing and/or pain reduction) as compared to placebo (47.8% for PGE1, vs. 25.2% for placebo, p = 0.0294). A significant difference in favor of PGE1 was also seen for the combined endpoint "major amputation or death" after 6-month follow-up (22.6% for PGE1 vs. 36.2% for placebo, p = 0.0150). The response rate (ulcer healing and/or pain relief) of the pooled treatment groups was 60.2% for PGE1, 25.2% for placebo, and 53.6% for iloprost. The adverse events rate of the pooled treatment groups showed good tolerability for PGE, with a rate of 39.6% in comparison to 73.9% for iloprost and 15.4% for placebo. CONCLUSION: For patients with peripheral arterial occlusive disease stage III or IV not eligible for arterial reconstruction, PGE1 therapy not only has significant beneficial effects over placebo on ulcer healing and pain relief but also increases the rate of patients surviving with both legs after 6-months follow-up.
Alprostadil↗
[Clinical evidence].
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Evidence-Based Medicine↗
[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. In conclusion, clinical trials suggest that low-molecular-weight heparins given subcutaneously can replace the hitherto standard intravenous application of unfractionated heparin in the initial treatment of deep-vein thrombosis, granting equal or even better efficacy and potentially lower rates of adverse side effects. Furthermore, the simplicity of this therapeutic regime allows for treatment of patients at home, thus offering patients mobility and also reducing the cost of treatment.
Anticoagulants↗
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. For assessment of interindividual and interequipment variability, we performed repeated measurements of 40 carotid arteries in 21 patients. Two color-coded duplex ultrasound systems were compared for machine variability estimation: Hewlett Packard SONOS 2500 and ATL Ultramark 9 HDI. RESULTS: Intrastenotic divided by distally recorded mean blood flow velocity (mean velocity ratio) showed the closest correlation with angiography: R2=0.93. Mean velocity ratio >5 was 97% sensitive and 98% specific for detection of >70% carotid stenosis. Intrastenotic blood flow velocities were significantly different between the 2 duplex systems (0.22+/-0.16 versus 0.17+/-0. 11 m/s; P<0.001), whereas mean velocity ratio values did not differ significantly. Interobserver variation expressed as 95% CI for predicted stenosis between 2 observers was 13.6% (peak systolic velocity) and 15.4% (mean velocity ratio). CONCLUSIONS: A mean velocity ratio using distal reference measurement in the internal carotid artery can normalize for interindividual and interequipment variability.
Aged↗
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. For the initial claudication distance (ICD), the intraclass correlation was 0.88 in the C-test and 0.87 in the G-test. For the ACD the coefficients were identical at 0.91. The within-subject variation (CVwithin) in the C-test and G-test was 25% and 27% for the ICD and for the ACD 24% and 21%, respectively. The between-subject variation was very similar with 72% and 73% (ICD) and with 78% and 68% (ACD). However, in ACDs below 100 m and between 100 to 150 m, the C-test showed significantly smaller coefficients of variation than the G-test: 13% vs 81% and 14% vs 50%, respectively. In conclusion, the results showed that both C-test and G-test are equally well reproducible.
Analysis of Variance↗
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. The pain-free and absolute walking distances were assessed on a walking treadmill at 3 km/h, 12% slope, and NO-mediated, flow-induced vasodilation of the femoral artery was assessed by ultrasonography at baseline, at 1, 2 and 3 weeks of therapy and 6 weeks after the end of treatment. Urinary nitrate and cyclic guanosine-3', 5'-monophosphate (GMP) were assessed as indices of endogenous NO production. RESULTS: L-Arginine improved the pain-free walking distance by 230+/-63% and the absolute walking distance by 155+/-48% (each p < 0.05). Prostaglandin E1 improved both parameters by 209+/-63% and 144+/-28%, respectively (each p < 0.05), whereas control patients experienced no significant change. L-Arginine therapy also improved endothelium-dependent vasodilation in the femoral artery, whereas PGE1 had no such effect. There was a significant linear correlation between the L-arginine/asymmetric dimethylarginine (ADMA) ratio and the pain-free walking distance at baseline (r=0.359, p < 0.03). L-Arginine treatment elevated the plasma L-arginine/ADMA ratio and increased urinary nitrate and cyclic GMP excretion rates, indicating normalized endogenous NO formation. Prostaglandin E1 therapy had no significant effect on any of these parameters. Symptom scores assessed on a visual analog scale increased from 3.51+/-0.18 to 83+/-0.4 (L-arginine) and 7.0+/-0.5 (PGE1; each p < 0.05), but did not significantly change in the control group (4.3+/-0.4). CONCLUSIONS: Restoring NO formation and endothelium-dependent vasodilation by L-arginine improves the clinical symptoms of intermittent claudication in patients with peripheral arterial occlusive disease.
Aged↗
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. Fifteen patients with PVD and three healthy volunteers were given 5 micrograms PGE1 intra-arterially over 50 min; PET scans were taken at 0, 25 and 50 min. Additionally, eight of the patients were investigated during an intravenous infusion of 40 micrograms PGE1 over 120 min; PET scans were taken at 0, 30, 60 and 120 min. RESULTS: Increase of muscular blood flow by intra-arterial PGE1 averaged 80%. A steal phenomenon was not observed. The amount of flow enhancement depended on whether or not the femoral artery was patent. During intravenous PGE1, muscular blood flow remained unchanged. CONCLUSIONS: In man, the pharmacodynamic profile of intra-arterial PGE1 differs clearly from intravenous PGE1. The flow-enhancing property is lost during metabolization in the lung. Since no difference exists between the therapeutic efficacy of intraarterial and intravenous PGE1, the impact on muscular blood flow is not as important as suggested previously.
Adult↗
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 (1.5 ng/kg body weight/min) and intravenous (6 ng/kg body weight/min) infusion of PGE1. RESULTS: SHB significantly increased at both locations during intravenous PGE1; intra-arterial administration significantly increased SHB in the skin of the forefoot only. Reserve capacity increased during intravenous administration and was markedly reduced during intra-arterial infusion. No significant changes were found regarding tcPO2 and LDF. CONCLUSIONS: These data suggest different therapeutic mechanisms for intra-arterial and intravenous administered of PGE1.
Aged↗
[Low-dose acetylsalicylic acid].
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Aspirin↗
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. It was followed by a 4-week interval treatment with the same medication administered only twice a week. Patients were monitored for 3 months when they received no study medication. In the PGE1 group the intention-to-treat analysis (n = 208) revealed an increase in walking distance after 4 weeks of 75% (placebo, 43%). At the end of the interval treatment the walking distance had improved to 101% (placebo, 60%). The results remained virtually constant during follow-up (PGE1, 104%, placebo, 63%). Between-group comparisons showed significant differences in favor of PGE1 for all three time points of measurement (p < 0.05, p < 0.01, and p < 0.05). PGE1 was well tolerated; the rate of adverse reactions related to the treatment was 12.8% (placebo, 7.7%). In summary, these results show that the new PGE1 regimen is effective and safe in the treatment of outpatients with intermittent claudication.
Aged↗
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. MATERIAL AND METHODS: In 52 patients with peripheral arterial occlusive disease, the ACD on treadmill at 3 km/h and 12% grade (constant-load test = C-test) ranged form 50 to 400 m. The C-test and the graded-exercise test (walking on the treadmill at 3 km/h and 0% gradient for 3 min, with subsequent increase in gradient of 3.5% every 3 min = G-test) were carried out at random on the same day under standardized conditions. RESULTS: The ACD was higher in the G-test than in the C-test (360.4 +/- 208.8m vs. 166.5 +/- 93.6m; p < 0.001). The coefficients of variation were very similar (57.9% and 56.2%, respectively). In the subgroup of patients with an ACD of between 100 m and 150 m, a large difference was found both for the coefficient of variation (58.6% G-test, 9.6% C-test) and for the standard deviation (339.8 +/- 199.0m and 133.1 +/- 12.8m, respectively). CONCLUSIONS: For the assessment of the ACD in patients with severe claudication the C-test would seem to be more suitable than the G-test.
Exercise Test↗
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. SUBJECTS: Thirty-three patients with primary Raynaud's syndrome (16 control, 17 treatment). INTERVENTIONS: The patients of the treatment group were given seven acupuncture treatments during the weeks 10 and 11 of the observation period. MAIN OUTCOME MEASURES: All patients kept a diary throughout the entire observation period noting daily frequency, duration and severity of their vasospastic attacks. A local cooling test combined with nailfold capillaroscopy was performed for all patients at baseline (week 1) and in weeks 12 and 23, recording flowstop reactions of the nailfold capillaries. RESULTS: The treated patients showed a significant decrease in the frequency of attacks from 1.4 day-1 to 0.6 day-1, P < 0.01 (control 1.6 to 1.2, P = 0.08). The overall reduction of attacks was 63% (control 27%, P = 0.03). The mean duration of the capillary flowstop reaction decreased from 71 to 24 s (week 1 vs. week 12, P = 0.001) and 38 s (week 1 vs. week 23, P = 0.02) respectively. In the control group the changes were not significant. CONCLUSIONS: These findings suggest that traditional Chinese acupuncture is a reasonable alternative in treating patients with primary Raynaud's syndrome.
Acupuncture Therapy↗
Non-invasive determination of dermal hemoglobin oxygenation and concentration in patients with peripheral arterial occlusive disease.
BACKGROUND: Oxygen saturation (SHB) and concentration (CHB) of dermal hemoglobin are important parameters for the supply of the skin. They may be non-invasively assessed by means of reflection photometry as hemoglobin is predominantly contributing to the skin reflection spectrum. METHODS AND RESULTS: Dermal reflection spectra from the middle of the forefoot and from the tip of the toe of 20 healthy subjects and 61 patients suffering from peripheral arterial occlusive disease (PAOD) were recorded and compared to transcutaneous oxygen pressure (tcPO2). SHB, and tcPO2 were significantly higher in controls: compared to patients (ankle pressure (AP) > 50 mmHg) SHB in the skin of the forefoot was 63.8 vs. 54.5% (p < 0.05), CHB was 0.89 vs. 0.62 aU (p < 0.01). In the great toe SHB was 92.9 vs. 59.9% (p < 0.001), CHB was 2.21 vs. 0.92 aU (p < 0.001). Heating the skin of the forefoot to 44 degrees C yields local dermal vascular reserve capacity: SHB and CHB increased in all healthy subjects (96.4%; 1.44 aU, respectively). SHB decreased at the forefoot in 14 and at the toe in 18 of 21 patients with AP < 50 mmHg. At the toe decrease was found in 50 of 61 patients (sensitivity 82%, specificity 100%). CONCLUSIONS: Local vascular reserve capacity of dermal perfusion is reduced in patients with PAOD, depending on AP. It should be determined preferably in patients with severe PAOD.
Adult↗
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 64.5 years) with a maximum of walking distance on the treadmill (3 km/12%) of 50-250 m were included and given a daily intravenous infusion of 60 micrograms PGE1 (Prostavasin) over a period of 4 weeks excluding weekends. This was followed by a treatment-free follow-up period of 3 months. Changes in the quality of life were recorded with both the newly developed disease-specific questionnaire PAVK-86, and the generic questionnaire SF 36; in addition, the pain-free and maximum walking distances on the treadmill were also established prior to and immediately following treatment, as also at the end of the follow-up period. RESULTS: The quality of life was significantly improved in all dimensions (functional status, complaints, pain, mood, anxiety, social life, treatment expectations) in addition to a marked increase in the median pain-free walking distance from 77 to 108 m (p < 0.001) and the maximum walking distance from 118 to 171 m (p < 0.001). At the end of the 3-month observation period, the improvement was essentially still demonstrable. CONCLUSION: The study has shown for the first time that treatment with intravenous PGE1 brings about not only the already known increase in the walking distance, but also a clinically relevant and significant improvement in the patient's quality of life.
Adult↗
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). RESULTS: Circadian variability of LDF was significantly reduced in stage IV patients compared both with stage II patients and controls (p < 0.01). An increase in LDF could be observed early in the afternoon and, more pronounced, during the night, occurring to the same extent in healthy and PAOD patients in stage II (p < 0.001). In stage IV the increase in LDF was not significant and a decrease was observed in two patients. LDF and local skin temperature were correlated in controls and stage II patients (mean r = 0.69 +/- 0.12 and 0.7 +/- 0.14, respectively), but not in stage IV (mean r = 0.23 +/- 0.18). A further limitation of LDF variability and nocturnal increase was seen in the presence of diabetes. CONCLUSION: Circadian variations of skin blood flow are comparable in controls and patients with claudication but markedly reduced in patients with severe PAOD presenting with ulcers, in whom skin perfusion seems uncoupled from temperature regulation, possibly due to local factors causing continuous arteriolar vasodilation.
Aged↗