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Da der Diabetes mellitus Typ 2 immer haufiger wird und die Behandlungskosten in die Hohe schnellen, kommt der Diabetespravention eine ubergeordnete Bedeutung zu. Bei der Wahl der moglichen Praventionsmethoden scheint allein die bariatrische Chirurgie ein Erfolg versprechender, kosteneffizienter Ansatz. Mittels derartiger Eingriffe konnen nicht nur bestehende Erkrankungen in Remission gebracht, sondern auch ein Neuauftreten des Diabetes verhindert bzw. dieses verzogert und Spatschaden sowie die Mortalitat reduziert werden. Die bariatrische Chirurgie ist rein nichtchirurgischen oder medikamentosen Praventionsstrategien bezuglich der Stoffwechselerkrankung Diabetes uberlegen.

BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide-1 (GLP-1) receptor agonist developed for the treatment of type 2 diabetes. We aimed to compare the efficacy and safety of flexible dose adjustments of oral semaglutide with sitagliptin 100 mg. METHODS: In this 52-week, multicentre, randomised, open-label, phase 3a trial, we recruited patients with type 2 diabetes from 81 sites in ten countries. Patients were eligible if they were aged 18 years or older (19 years or older in South Korea), had type 2 diabetes (diagnosed ≥90 days before screening), HbA1c of 7·5-9·5% (58-80 mmol/mol), and were inadequately controlled on stable daily doses of one or two oral glucose-lowering drugs (for 90 days or more before screening). Participants were randomly assigned (1:1) by use of an interactive web-response system, stratified by background glucose-lowering medication at screening, to oral semaglutide with flexible dose adjustments to 3, 7, or 14 mg once daily or sitagliptin 100 mg once daily. To approximate treatment individualisation in clinical practice, oral semaglutide dose could be adjusted on the basis of prespecified HbA1c and tolerability criteria. Two efficacy-related estimands were prespecified: treatment policy (regardless of treatment discontinuation or use of rescue medication) and trial product (on treatment and without use of rescue medication) for participants randomly assigned to treatment. The primary endpoint was achievement of HbA1c of less than 7% (53 mmol/mol) at week 52 and the confirmatory secondary efficacy endpoint was change in bodyweight from baseline to week 52. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02849080, and European Clinical Trials Database, EudraCT number 2015-005593-38, and an open-label extension is ongoing. FINDINGS: Between Sept 20, 2016, and Feb 7, 2017, of 804 patients assessed for eligibility, 504 were eligible and randomly assigned to oral semaglutide (n=253) or sitagliptin (n=251). Most participants were male (285 [57%] of 504) with a mean age of 57·4 years (SD 9·9). All participants were given at least one dose of their allocated study drug except for one participant in the sitagliptin group. From a mean baseline HbA1c of 8·3% (SD 0·6%; 67 mmol/mol [SD 6·4]), a greater proportion of participants achieved an HbA1c of less than 7% with oral semaglutide than did with sitagliptin (treatment policy estimand: 58% [134 of 230] vs 25% [60 of 238]; and trial product estimand: 63% [123 of 196] vs 28% [52 of 184]). The odds of achieving an HbA1c of less than 7% was significantly better with oral semaglutide than sitagliptin (treatment policy estimand: odds ratio [OR] 4·40, 95% CI 2·89-6·70, p

Seit Ende 2012 steht in Deutschland eine neue Substanzklasse zur Therapie des Typ 2 Diabetes zur Verfugung. Das Wirkprinzip ist neu und beruht auf einer Modulation der Glukoseruckresorption im Harn durch Inhibition so genannter Sodium Glucose Linked Transporter (SGLT). Dadurch wird eine therapeutische Glukosurie induziert. Dies ist ein fur den Arzt ungewohnter Behandlungsansatz, der die Niere als Ort der Glukoseregulation in den therapeutischen Mittelpunkt stellt. Daher sind eine nahere Betrachtung der hierfur verantwortlichen renalen Mechanismen sowie eine Darstellung der Vor- und Nachteile dieser Medikamentengruppe sinnvoll.

During pregnancy one should largely avoid invasive and radiological diagnostic methods. However, real-time sonography and venous occlusion plethysmography yield non-hazardous information on venous morphology and venous function. It became possible to demonstrate by means of these examination methods that the diameters of the veins are enlarged in pregnancy compared to the situation post partum. The difference in significant. Venous occlusion plethysmography points to a deterioration of venous function post partum, since the difference to the values in the third trimenon is not significant. Venous function measurement often pointed to the existence of an obstacle to flow during pregnancy, whereas sonographically a dilatation of the veins was revealed the existence of an obstacle to flow represented by the pregnant uterus. Hence, it appears meaningful to combine both investigation methods to confirm the occurrence of venous changes during pregnancy.

There is a high risk of venous thromboembolism when patients are immobilised following trauma. The combination of low-molecular-weight heparin (LMWH) with graduated compression stockings is frequently used in orthopaedic surgery to try and prevent this, but a relatively high incidence of thromboembolic events remains. Mechanical devices which perform continuous passive motion imitate contractions and increase the volume and velocity of venous flow.In this study 227 trauma patients were randomised to receive either treatment with the Arthroflow device and LMWH or only with the latter. The Arthroflow device passively extends and plantarflexes the feet. Patients were assessed initially by venous-occlusion plethysmography, compression ultrasonography and continuous wave Doppler, which were repeated weekly without knowledge of the category of randomisation. Those who showed evidence of deep-vein thrombosis underwent venography for confirmation. The incidence of deep-vein thrombosis was 25% in the LMWH group compared with 3.6% in those who had additional treatment with the Arthroflow device (p < 0.001). There were no substantial complications or problems of non-compliance with the Arthroflow device. Logistic regression analysis of the risk factors of deep-vein thrombosis showed high odds ratios for operation (4.1), immobilisation (4.3), older than 40 years of age (2.8) and obesity (2.2).

In a randomized cross-over study, the effect of PGE 1 and iloprost on microcirculation as well as the tolerability was investigated in 36 patients with peripheral arterial occlusive disease stage III and IV according to Fontaine. Patients received PGE 1 and iloprost by single 3-h i.v. infusions on two different days at doses recommended by the manufacturers or in previous studies (PGE 1 : first hour 20 μg, next 2 h 30 μg each. Iloprost: first hour 0.5 ng/kg/min, next 2 h 1.0 ng/kg/min). Transcutaneous oxygen pressure (tc P O 2 ) values increased much more with PGE 1 . Median tc P O 2 increase over baseline 30 min after the end of infusion was 9 and 2 mmHg for PGE 1 and iloprost, respectively, corresponding to median AUC differences from baseline of 1050 and 210 min mmHg. Because of its exploratory character, the study was not powered to test for significance. Adverse effects occurred in 19.4% (PGE 1 ) and 30.6% (iloprost) of patients. Dose reduction was required in 3 patients receiving iloprost (hypotension, nausea, irritation of the infused vein), and in none receiving PGE 1 .

Objectives: Due to an increase in the percentage of older people in industrialized countries there is an increasing demand for medical care for the elderly. With advancing age, a series of structural, architectural and compositional modifications take place in the vasculature. Therefore, we analyzed the influence of patient age on the reocclusion rate of recanalized peripheral arteries. Patients and Methods: 471 patients (mean age ± SD: 62 ± 12 years, range: 28–90 years) successfully treated by interventional recanalization were followed up (mean ± SD: 18 ± 17 months, range:6–48 months). Reocclusion of the recanalized arterial segment could be proven in 175 patients (37%), whereas octogenarians had the highest patency rate i.e. 68%. Univariate analysis, multivariate logistic regression analysis, and ROC analysis were performed. Results: The univariate analysis showed a significant relation between reocclusion and PAOD stage, hyperlipoproteinemia, and total cholesterol level and erythrocyte sedimentation rate (ESR), respectively. Excluding age-related risk factors, the multivariate logistic regression analysis with backward selection reached a significant level for PAOD stage with p = 0.0012 and an odds ratio of 1.63, and for ESR with a p = 0.0013 and an odds ratio of only 1.02. Age did not reach a significant level with a p value of 0.13 and an odds ratio of 0.98. In the ROC analysis, prognostic relevance could be shown for the combination of PAOD stage and ESR adjusted for age and hyperlipidemia, and for PAOD stage and ESR value as a single prognostic factor, but not for patient age. Conclusion: Thus, despite proven and hypothetical differences in the vascular biology of older people compared to younger people, age is not related to middle term patency rates after interventional recanalization of peripheral arterial occlusions.

Die sichere rein klinische Diagnose der Venenthrombose ist nur bei eindeutiger Symptomatik moglich. Bei gering ausgepragten Beschwerden, unklarem Befund oder auch schon bei hohem Risiko fur Venenthrombosen muss die klinische Untersuchung durch apparative Verfahren erganzt werden, da sich Thrombosen uber lange Zeit ohne nennenswerte Symptomatik entwickeln konnen. Neben funktionsdiagnostischen Methoden standen als Goldstandard der Diagnostik lange Jahre allein die Phlebographie und Phleboskopie zur Verfugung. Durch die Entwicklung der Ultraschalldiagnostik bietet sich heute eine nichtinvasive Alternative in der Thrombosediagnostik. Im vorliegenden Beitrag werden die Indikationen, Moglichkeiten und Grenzen der einzelnen Verfahren der bildgebenden Diagnostik der Venenthrombose dargestellt.

Physical methods became recently more important as an alternative to anticoagulation for prophylaxis of thromboembolism and were studied for their efficacy. The AV-impulse-system proved efficient in reducing thromboembolic complications in patients undergoing hip surgery by increasing the return of venous blood in the deep veins of the leg. In a preclinical trial we studied the influence of the AV-impulse-system and of active forefoot movement on venous blood return in 12 lower extremities of 6 healthy individuals immobilized in below the knee plaster casts. Our results show a significant increase in venous blood flow caused by the AV-impulse-system (p < 0.05) and by active forefoot movements (p < 0.05). Prevention of thromboembolic complications in trauma and orthopaedic patients immobilized in plaster cast seems possible by using the AV-impulse-system which significantly increases the venous blood flow independent from patient compliance.

Background: To prove whether the aortoiliac, femoropopliteal or crural segments of the peripheral arteries might have a different sensitivity to a risk profile we did a statistical analysis of segmental peripheral atherosclerosis and risk factors. Patients and methods: In 132 patients (mean age 61 ± 13 years) with peripheral arterial occlusions the arterial segments with occlusion or stenosis were angiographically documented: 17 had occluded or stenosed aortoiliac, 45 femoropopliteal and 25 crural arteries and 45 patients had multiple manifestations. Analysis of total cholesterol, HDL- and LDL-cholesterol, triglyceride, lipoprotein a, fibrinogen, uric acid, homocystein, hematocrit, erythrocyte sedimentation rate, HBA1, IgG- and IgM-antibodies versus Cytomegalovirus, Herpes simplex-virus, Chlamydia pneumoniae and Helicobacter pylori were done and nicotine abuse, arterial hypertension and obesity were evaluated. Results: Age of the patients had the strongest correlation with isolated segmental manifestation (p < 0.0001). Patients with isolated aortoiliac manifestation were younger than patients without this manifestation (54 ± 9 years versus 62 ± 13 years). Patients with isolated femoropopliteal manifestation were older than patients without this manifestation (66 ± 11 years versus 58 ± 13 years). None of the investigated risk factors showed a correlation with these age related differences. Independent from the age related differences for the nicotine abuse a p-value of 0.08 was estimated, but in smokers a diffuse manifestation was most frequent. Conclusion: There are age dependent differences of the prevalence of isolated aortoiliac or femoropopliteal atherosclerotic occlusions or stenosis. An association of these differences to a specific risk profile was not found.

ZusammenfassungAn zehn venengesunden Probanden (5 Männern und 5 Frauen; Durchschnitts-alter: 25,5 ± 3 Jahre) wurde die Bedeutung der Beweglichkeit im Sprung- und Kniegelenk für den Blutrücktransport aus den Beinvenen beim Gehen phlebodynamometrisch untersucht. Die Probanden gingen auf einem Laufbandergometer (Geschwindigkeit: 1,5 km/h; keine Steigung; Gehzeit: 1 Minute) zunächst ohne Bewegungseinschränkung (Versuch I), dann mit Bewegungseinschränkung im Kniegelenk (Versuch II) und schließlich mit Bewegungseinschränkung im oberen Sprunggelenk (Versuch III). Primäre Zielvariable war der maximale venöse Druckabfall (ΔPmax) unter Belastung, sekundäre Zielvariablen die venöse Druckausgleichszeit (T0) bzw. die halbmaximale Druckausgleichszeit (Tmax1/2) nach Belastung. Der maximale Druckabfall im Beinvenensystem wurde durch die Aufhebung der Beweglichkeit im Knie- (p = 0,0323) bzw. im oberen Sprung-gelenk (p = 0,0051) signifikant reduziert. Die Verminderung von ΔPmax durch die Bewegungseinschränkung betrug für das Kniegelenk 12,0% und für das obere Sprunggelenk 21,5% (p = 0,0469). Demgegenüber wurden die venösen Auffüllzeiten (T0 und Tmax1/2) durch die Bewegungseinschränkung nicht beeinflußt (p >0,05; jeweils Vorzeichen-Rang-Test nach Wilcoxon). Diese Ergebnisse zeigen, daß Bewegungseinschränkungen im Knie- und insbesondere im oberen Sprunggelenk selbst bei venengesunden Probanden zu einer ambulatorischen venösen Hypertonie führen. Da diese ein gleichzeitig bestehendes Venenleiden aggravieren oder für sich selbst den venösen Blutabtransport stören können, sollten zur Gesamtbeurteilung der funktionellen Auswirkungen von Beinvenenerkrankungen stets die Gelenkfunktionen mitberücksichtigt werden. Dies gilt für die klinische Praxis ebenso wie für gutachterliche Fragestellungen.

Manifestation of atherosclerosis is one of the alterations in venous bypass grafts. Its progression and morphology usually cannot be described by sonography. The venous part of a hemodialysis fistula can be compared to a venous bypass graft. The authors investigated the venous part of hemodialysis fistula in 16 patients. They found athero sclerosis in 7 patients. The morphologic findings were similar to arterial atherosclerosis. Looking at the venous part of hemodialysis fistulas may be an adequate model to inves tigate the initiation and progression of atherosclerotic lesions in venous bypass grafts.

Plaster cast immobilisation following trauma is a major risk factor for the development of deep vein thrombosis. In our controlled, randomized and prospective study in patients with minor injuries the incidence of deep vein thrombosis was 4.3% in conservatively treated outpatients with plaster cast immobilisation of the leg (n = 163 control group without prophylaxis). By application of low molecular weight heparin once daily the number of deep vein thrombosis in the prophylaxis group (n = 176) was reduced to 0% (p = 0.006). No severe side effects of low molecular weight heparin were observed. Subcutaneous injections were self-applicated by 89% of males and 72% of females. We conclude that thromboprophylaxis with low molecular weight heparin once daily is effective to reduce the risk of deep vein thrombosis in outpatients with plaster cast immobilisation of the leg.

Significant increases in the costs of the health system in all Western countries indicate the importance of both economic and efficacy studies in evaluating the various treatments for peripheral arterial occlusive disease (PAOD). On the basis of this background, an attempt was made to compare the efficacy and the costs of different treatment regimens for PAOD using data from the literature. In severe PAOD, the therapeutic approaches are supplementary methods that must be applied according to the patient's situation; the treatment cannot be chosen on the basis of its costs. In patients with claudication, different treatment alternatives such as physical exercise, oral or intravenous medical treatment, and percutaneous transluminal angioplasty (PTA) exist, and cost-efficacy comparisons can be made among these. Oral treatment with vasoactive compounds results in efficacy costs ranging from DM 37.31 ($22.61 U.S.) to DM 146.16 ($88.58 U.S.) per patient for a drug-induced 10% increase of pain-free walking distance (PFWD) using the cheapest therapeutic alternative. Long-term physical exercise (twice for 2 h/week for 24 months) leads to efficacy costs of DM 189.09 ($114.60 U.S.) per patient for a 10% increase of PFWD. Intensive therapeutic regimens using intravenous infusions produce efficacy costs of DM 116.61 ($98.27 U.S.) to DM 2,529.81 ($1,533.22 U.S.) per patient, but result in an average improvement in PFWD of 21% to 62% within 2 to 4 weeks. PTA with a cost of DM 6,000 ($3,636.40 U.S.) per intervention is the most expensive method of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

ZusammenfassungIn einer prospektiven, randomisierten Untersuchung zur Thromboseinzidenz bei gipsimmobilisierten Patienten ohne besondere Risikofaktoren ergab sich ein Thromboserisiko in Abhängigkeit von der Verletzungslokalisation zwischen 2,9% (Unterschenkelgips) und 9,5% (Oberschenkelgipstutoren). Die Thromboseprophylaxe mit niedermolekularem Heparin führte zu einer signifikanten Senkung des Thromboserisikos (p

ZusammenfassungIn den fortgeschrittenen Stadien der chronischen arteriellen Verschlußkrankheit gehören die Prostanoide, hier insbesondere Prostaglandin E1 (PGE1), zum festen Therapiekonzept, wenn lumeneröffnende Verfahren nicht durchführbar oder bereits erfolglos gewesen sind.Wie zahlreiche Studien an mehr als 1000 Patienten zeigen, kommt es nach i. a. oder i.v. PGE1 lnfusion zu deutlichen Verbesserungen trophischer Läsionen, zur vollständigen oder zumindest erheblichen Reduktion des Ruheschmerzes mit gleichzeitiger Verminderung des Analgetikabedarfs sowie zur Senkung der Amputationsrate. Bei schwerer Claudicatio mit extrem kurzen Gehstrecken konnte sowohl die schmerzfreie als auch die maximale Gehstrecke signifikant und klinisch relevant gesteigert werden. Darüber hinaus wurde der Nachweis erbracht, daß das positive Behandlungsergebnis bei den meisten Patienten sogar noch nach Monaten vorgefunden werden kann. Ein erhöhtes Risiko für unerwünschte schwerwiegende Arzneimittelwirkungen konnte weder unter i.a. noch i.v. PGE1 lnfusion aufgedeckt werden.

Purpose: To determine if ultrasound angioplasty in a percutaneous approach was capable of recanalizing occluded arteries in acute and subacute peripheral arterial occlusions. Material and Methods: We applied an ultrasound angioplasty device in a percutaneous approach in 9 patients with peripheral arterial occlusions. All patients suffered from severe leg ischemia due to subacute thrombotic occlusions. Results: The ultrasound transmitter easily created a channel within the occlusive material. To further reduce the mass of the occlusive material, an aspiration thrombectomy was performed in all cases, leading to a complete recanalization in 7 cases. In 2 cases, a remaining stenosis was successfully dilated. Conclusion: Intravascular ultrasonic devices can be useful for recanalization of occluded peripheral arteries. In particular, if thrombolytic therapy of longer peripheral arterial occlusions fails or is contraindicated, ultrasound angioplasty may be a new approach for recanalization.

Case report. The tumor necrosis factor (TNF) receptor–associated periodic syndrome (TRAPS) is an autosomally dominant inherited disorder resulting from mutations within the TNF super family 1A gene ( TNFRSF1A ), which impair cleavage of p55 TNF receptors (TNFR1), decrease soluble TNFR1 serum levels, and affect intracellular trafficking of mutant proteins.1 The associated unopposed TNFα signaling confers self-limited auto-inflammation and may promote amyloidosis. Here, we provide clinical and histologic evidence that TRAPS may affect the CNS and has to be included in the spectrum of autoimmune inflammatory CNS disorders. Our patient was diagnosed with a C55A mutation in exon 3 of the TNFRSF1A gene and had experienced recurrent attacks of fever, myalgias, arthralgias, and painful migratory rashes since childhood. At age 38 he developed brainstem and cerebellar symptoms from an extensively contrast-enhancing lesion in the left cerebellar peduncle; acute disseminated encephalomyelitis (ADEM) or lymphoma was considered.2 However, …

Several polymorphisms have been identified in the RAGE-promoter region that might modulate the outcome of disease. Here we analyse the association of a 63bp deletion (delta63) spanning from bp - 407 to bp - 345 with diabetic nephropathy. The deletion was determined using the polymerase chain reaction (PCR) in a cross-sectional study with 1087 patients with type 1 diabetes (n = 559) and type 2 diabetes (n = 528). 475 patients with osteoporosis served as disease independent control. The prevalence of the heterozygous genotype did not significantly differ between the three groups (type 1: 2.15 %, type 2: 2.27 %, controls: 1.47 %), indicating that heterozygous delta63 is not related to the manifestation of diabetes. Homozygous carriers were not identified in this study. The heterozygous delta63 genotype, was associated with a reduced prevalence of diabetic nephropathy in patients with type 2 diabetes (OR = 0.06; 95 % CI: [0.05, 0.07]), but not in patients with type 1 (OR = 1.49; 95 % CI: [1.14, 1.94]). We conclude, that patients with type 2 diabetes and the 63bp deletion in the promoter of RAGE seem to be protected from diabetic nephropathy. The observed difference between type 1 and type 2 diabetes might point to diverse pathomechanisms of nephropathy in both types of diabetes.

The major reasons for venous thrombosis are inflammation, increased blood coagula bility, and blood stasis. Investigation of these processes in vivo in a particular vein is difficult. Blood stasis in the peripheral veins is assumed to increase the risk of thrombosis during immobilization. By duplex sonography the authors were able to demonstrate different echogenicity in single veins of the lower limb in healthy subjects in a sitting position. Of 25 subjects, 7 presented a high echogenicity of the venous blood similar to that of the surrounding tissue. An additional 5 subjects presented this phenomenon after venous blood flow was stopped by a pressure cuff. The remaining 13 subjects still presented a dark lumen of the veins. Duplex sonography can discriminate different compositions of resting venous blood associated with venous stasis. Whether these findings correlate with an increased risk of thrombosis is not known.

Deep-vein thrombosis is common after plaster-cast immobilisation for traumatic injury. We did a randomised prospective study of the effect of low-molecular-weight heparin on the incidence of deep-vein thrombosis in patients with minor injuries treated with plaster-cast immobilisation of the leg. A control group (n = 163) received no prophylaxis, the prophylaxis group received low-molecular-weight heparin once daily (n = 176). The incidence of deep-vein thrombosis in the prophylaxis group was 0% (one tailed p < 0.006) vs 4.3% in the control group. No severe side-effects of low-molecular-weight heparin were observed. Thromboprophylaxis with low-molecular-weight heparin once daily is effective in reducing the risk of deep-vein thrombosis in outpatients with plaster-cast immobilisation of the leg.

During the 1970s the prevention of atherosclerosis focused merely on the elimination of risk factors such as nicotine or cholesterine. The use of functional diagnostics like oscillography only identified those plaques which had already caused hemodynamic changes.

The results of many studies have verified the vasodilating, antithrombotic, leucocyte-stabilizing and endothelium-stabilizing properties of prostaglandin Ei (PGEx; reviewed in [19]). In clinical studies in which PGE1 was administered over a sufficiently long period, it has been possible to demonstrate its beneficial effects, which result from these properties, in patients with peripheral arterial disease [1, 3, 4, 7, 9, 10, 12, 16, 17, 20, 21]. However, it is not clear which of the properties is mainly responsible for the therapeutic effect. Also, the dose and route of administration, intra-arterial or intravenous, are still matters of debate.

In a double blind, randomized multicenter study naftidrofuryl, a vasoactive substance, was compared with placebo in the treatment of 104 patients with chronic arterial occlusive disease. After a run-in period of four weeks the pa tients received either naftidrofuryl (600mg daily) or placebo over 12 weeks. The pain-free and the total walking distances improved significantly in both groups. However, the difference in the improvement of the pain-free walking distance was significant (p < 0.02) in favour of naftidrofuryl. There also was a difference in the improvement of the total walking distance in favour of naftidrofuryl which was not significant. The results indicate that naftidrofuryl has a beneficial effect on the symp toms and lengthens the painfree walking distance in patients with arterial occlu sive disease.

A multicenter, prospective, pla cebo-controlled, double-blind trial was conducted to investigate the effi cacy of intravenous infusion therapy with pentoxifylline over fourteen days in patients suffering from angio graphically confirmed chronic pe ripheral occlusive arterial disease, Fontaine stage II, with at least a six- month history. After a washout phase of one week, the patients received in accordance with a randomization scheme either an i.v. infusion of 300 mg of pentoxifylline (15 mL am poules) or 15 mL of a 0.9% NaCl so lution in 250 mL of 5% laevulose, administered over three hours twice daily. The main efficacy parameters were treadmill-assessed initial claudi cation distance (ICD) and absolute claudication distance (ACD). Base line testing revealed a mean ICD of 131 m in the pentoxifylline group and 126 m in the placebo cohort; mean ACD values were 239 m and 225 m respectively. The group of patients treated with pentoxifylline (n=75) displayed a significantly greater im provement (p < 0.0001) in ICD (+70%) and ACD (+60%) than the placebo group did (+33% and 32%, respectively) (n=79). The infusions were well tolerated in both groups.

Rabbits were immunized for 10 weeks with a complex between the bufadienolide glycoside proscillaridin (p.) and human serum albumin. Antibodies were obtained with a binding capacity of 47 ng of p. per μl of undiluted serum. The antibodies migrated with the Ig A immunoglobulin fraction. Precipitation of the antigen-antibody complex was demonstrated by agargel electrophoresis, immunoelectrophoresis and immunodiffusion. When added to a 86Rb-erythrocyte system the antiserum prevented the inhibition of Rb-uptake due to p. with a linear doseresponse relationship. Displacement studies with different chemically related steroids were performed using a 3H-p.-antibody system in order to test the specificity of the antibody. Changes in the conformation and the substituents in position 3 and 4 did not influence antibody binding to a major degree. Quabain, digoxin and digitoxin, however, had a much lower affinity to the antibody. The radioimmunological system described is able to detect amounts of p. above 15 ng.

Plasma levels of proscillaridin, measured by a modified86Rb-erythrocyte method, have been studied in 6 healthy volunteers who received single oral doses of 2.5 mg. There were two maxima in the plasma curve, one after 0.5 h (median level 410 pg/ml) and another after 10 h (median value 390 pg/ml); and, a distinct minimum at 3 h (median value 98 pg/ml). After 24 h the median plasma concentration was 305 pg/ml, and after 48 h it was 115 pg/ml.

In an ischaemic, exercising limb the metabolic changes found in the femoral venous blood of healthy volunteers are similar to those found in patients with intermittent claudication. This model of ischaemia was therefore used to demonstrate the pharmacodynamic effects of an intra-arterial or intravenous infusion of PGE1 in comparison with a placebo in six healthy male volunteers.

Zur Unterscheidung kongenitaler und erworbener Beckenvenenblockade bzw. Aplasie oder Hypoplasie wurden 4 Falle mit fruhmanifester Veneninsuffizienz morphologisch und funktionell untersucht: 1. Fur kongenitale Genese sprechen die Kombination mit anderen Fehlbildungen, Kompensation durch eine atypisch verlaufende singulare Drainagevene, geringgradige funktionelle Veranderungen. 2. Fur erworbenen Beckenvenenverschlus sprechen der Nachweis multipler Kollateralvenen mit geschlangeltem Verlauf, irregularen Wandkonturen und erheblichen funktionellen Veranderungen.