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Biomedical subjects

C Diehm

Publications and source records attributed to C Diehm.

At least 19 recordsLinked to original sources
PubMed2001

Anticoagulation: the present and future.

Thrombin is a central bioregulator of coagulation and is therefore a key target in the therapeutic prevention and treatment of thromboembolic disorders, including deep vein thrombosis and pulmonary embolism. The current mainstays of anticoagulation treatment are heparins, which are indirect thrombin inhibitors, and coumarins, such as warfarin, which modulate the synthesis of vitamin K-dependent proteins. Although efficacious and widely used, heparins and coumarins have limitations because their pharmacokinetics and anticoagulant effects are unpredictable, with the risk of bleeding and other complications resulting in the need for close monitoring with their use. Low-molecular-weight heparins (LMWHs) provide a more predictable anticoagulant response, but their use is limited by the need for subcutaneous administration. In addition, discontinuation of heparin treatment can result in a thrombotic rebound due to the inability of these compounds to inhibit clot-bound thrombin. Direct thrombin inhibitors (DTI) are able to target both free and clot-bound thrombin. The first to be used was hirudin, but DTIs with lower molecular weights, such as DuP 714, PPACK, and efegatran, have subsequently been developed, and these agents are better able to inhibit clot-bound thrombin and the thrombotic processes that take place at sites of arterial damage. Such compounds inhibit thrombin by covalently binding to it, but this can result in toxicity and nonspecific binding. The development of reversible noncovalent DTIs, such as inogatran and melagatran, has resulted in safer, more specific and predictable anticoagulant treatment. Oral DTIs, such as ximelagatran, are set to provide a further breakthrough in the prophylaxis and treatment of thrombosis.

Administration, Oral↗
PubMed1999

European multicenter study on propionyl-L-carnitine in intermittent claudication.

OBJECTIVES: This study was performed to identify a target population of claudicants for propionyl-L-carnitine treatment. BACKGROUND: Previous studies suggest that the efficacy of propionyl-L-carnitine in intermittent claudication is greater in patients with severe functional impairment than in those with mild walking disability. METHODS: After run-in, 485 claudicant patients were randomized to placebo or propionyl-L-carnitine (1 g bid, p.o.) and then stratified on the basis of maximal walking distance (cutoff point 250 m) and maximal walking distance variability (cutoff point 25%). Treatment lasted 12 months. Walking capacity was assessed by treadmill and quality of life by a questionnaire exploring various aspects of daily life. RESULTS: In the target population, that is, patients who at baseline walked < or = 250 m and showed a maximal walking distance variability < or = 25%, per-protocol analysis showed that the effect of propinyl-L-carnitine was significantly greater than that with placebo for both maximal walking distance and initial claudication distance (ICD). In the intention-to-treat population, maximal walking distance increased by 62 +/- 14% on propionyl-L-carnitine and by 46 +/- 9% (p < 0.05) on placebo, while no difference between treatments was observed for ICD. The beneficial effect of propionyl-L-carnitine was confirmed when data of the target population were pooled with those of patients who at baseline walked < or = 250 m and showed a > 25% maximal walking distance < 50% variability. Actually, maximal walking distance increased by 98 +/- 16% in the propionyl-L-carnitine group and by only 54 +/- 10% in the placebo group (p < 0.01). The corresponding values for ICD were 99 +/- 21% and 51 +/- 8% (p < 0.05). For patients with baseline maximal walking distance > 250 m, no difference between treatments was observed. CONCLUSIONS: Claudicants with maximal walking distance < or = 250 m benefited from the use of propionyl-L-carnitine, with improvement in walking distance and quality of life. However, patients with mild functional impairment (i.e., walking distance > 250 m) showed no response to propionyl-L-carnitine.

Cardiotonic Agents↗
PubMed1999

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↗
PubMed1998

Neutrophil function in peripheral arterial occlusive disease: the effects of prostaglandin E1.

The role of polymorph nuclear neutrophils (PMN) in limb ischemia and reperfusion has been recognized only in recent years. The present study aimed to investigate the systemic and local (in femoral venous blood) effects of intra-arterially or intravenously applied prostaglandin E1 (PGE1) on systemic and ischemia-induced local changes in neutrophil function. Thirty patients with intermittent claudication were randomly assigned to intra-arterial or intravenous infusion of prostaglandin E1 (10 microg i.a. or 15 microg i.v. over 30 min). Prior to infusion femoral arterial and venous blood samples were obtained from the predominantly affected leg under resting conditions and immediately after a 3-min period of ischemia induced by suprasystolic thigh compression. After 24 h additional blood samples were obtained at baseline, following infusion of prostaglandin E1, and again after another 3-min period of ischemia following the prostaglandin E1 infusion. Intra-arterially administered prostaglandin E1 caused an increase in the PMN count by 3.5 +/- 2% (p<0.05) and a decrease in free oxygen radical production by 13 +/- 8% (p<0.05) measured by whole blood chemiluminescence. Additionally, a trend for lower PMN filterabilities (9 +/- 12%, NS) was observed. Intra-arterially infused prostaglandin E1 significantly reduced the ischemia-induced decrease in neutrophil filterability (arterial and venous blood difference after ischemia -- control: 22 +/- 17% (p<0.05); IA PGE1: 8 +/- 11% (NS), each compared to baseline). Intravenously administered prostaglandin E1 showed similar systemic effects as the intra-arterial application, but did not affect the ischemia-induced changes in neutrophil filterability. In conclusion, prostaglandin E1 reduces PMN activation in patients with peripheral arterial occlusive disease.

Aged↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

[The prevalence of hyperhomocysteinemia in thromboangiitis obliterans. Does homocysteine play a role pathogenetically?].

OBJECTIVE: As hyperhomocysteinaemia is known to be an important risk factor in the early onset of arteriosclerotic occlusive disease and leg-vein thrombosis, we investigated the prevalence of hyperhomocysteinaemia in patients with thromboangiitis obliterans (TAO), a condition predominantly affecting peripheral arteries and veins. PATIENTS AND METHODS: Plasma homocysteine (HC), before and after administration of methionine (0.1 g/kg) as well as serum folic acid, vitamins B6 and B12 were measured in 15 patients with TAO (12 men, 3 women; mean age 33.3 years: group 1), in 15 non-smokers without peripheral vascular disease (group 2) and 15 smokers without peripheral vascular disease (group 3). At the time of the study, of those in group 1 seven were active smokers, seven were ex-smokers and one was a non-smoker. RESULTS: Before methionine administration four patients (27%), none of the healthy non-smokers and one smoker without vascular disease (7%) had increased HC levels (> 13.9 nmol/ml). The difference between groups 1 and 2 was statistically significant (P < 0.05), but not that between groups 1 and 3 and between 2 and 3. 4 hours after methionine increased HC levels (> or = 31 nmol/ml) were measured in nine patients but in none of the healthy controls. The difference between patients and the two control groups without vascular disease was clearly significant (P = 0.0107). There was a difference in folic acid levels between the patients and the smokers without vascular disease: in eight patients (53%) the levels were in the lower third of normal, in six (40%) they were in the middle and in one (7%) in the upper third. Corresponding levels in group 3 were: four (27%), three (20%) and eight (53%). CONCLUSION: Hyperhomocysteinaemia occurs frequently in patients with TAO. It may play an important and nicotine-independent role in its pathogenesis.

Adult↗
PubMed1996

Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency.

BACKGROUND: Diseases of the venous system are widespread disorders sometimes associated with modern civilisation and are among the major concerns of social and occupational medicine. This study was carried out to compare the efficacy (oedema reduction) and safety of compression stockings class II and dried horse chestnut seed extract (HCSE, 50 mg aescin, twice daily). METHODS: Equivalence of both therapies was examined in a novel hierarchical statistical design in 240 patients with chronic venous insufficiency. Patients were treated over a period of 12 weeks in a randomised, partially blinded, placebo-controlled, parallel study design. FINDINGS: Lower leg volume of the more severely affected limb decreased on average by 43.8 mL (n = 95) with HCSE and 46.7 mL (n = 99) with compression therapy, while it increased by 9.8 mL with placebo (n = 46) after 12 weeks therapy for the intention-to-treat group (95% CI: HCSE: 21.1-66.4; compression: 30.4-63.0; placebo: 40.0-20.4). Significant oedema reductions were achieved by HCSE (p = 0.005) and compression (p = 0.002) compared to placebo, and the two therapies were shown to be equivalent (p = 0.001); in this design, however, compression could not be proven as standard with regard to oedema reduction in the statistical test procedure. Both HCSE and compression therapy were well tolerated and no serious treatment-related events were reported. INTERPRETATION: These results indicate that compression stocking therapy and HCSE therapy are alternative therapies for the effective treatment of patients with oedema resulting from chronic venous insufficiency.

Bandages↗