Functional vascular diseases: Raynaud's syndrome, acrocyanosis and erythromelalgia.

Raynauds syndrome, acrocyanosis and erythromelalgia are functional vascular diseases that differ with respect to prevalence, clinical picture, therapy, prognosis, and impairment of quality of life. Raynauds syndrome occurs in 5 to 20 % of the population in Europe, is observed four times more often in women than in men and appears first at the age of 40 (3 to 80), on the average. Raynauds attacks are characterized by a paroxysmal white-blue-red or just white and blue discoloration of the fingers and toes; the attacks are induced by cold or stress, usually, cease after no more than some minutes (average 23 min.), but can also persist for hours. A distinction must be made between primary (aetiology unknown), secondary (aetiology known) and suspected secondary Raynauds syndromes (causal underlying disease suspected). There are several different therapy options, but not all of them have been substantiated by evidence. Acrocyanosis is rarer than Raynauds syndrome, and contrary to the latter, is characterized by nonparoxysmal, in most cases persistent, painless bluish-red symmetrical discolorations of the hands, feet and knees. It is more frequent in women than in men and becomes manifest before the 25th year of age, on the average (15th to 70th year of age). A distinction is made between primary acrocyanosis without detectable underlying disease and secondary acrocyanosis with a specific underlying disease. No effective therapy for primary acrocyanosis is known, but secondary forms can sometimes be treated. Patients with primary and secondary erythromelalgia, a very rare condition, sustain paroxysmal burning pain with marked reddening of the legs, feet and less often the hands. The attacks are triggered by warmth. Women are affected more often than men. The age of first manifestation is 40 to 55 years, but the first attacks may just as well occur during childhood. There are different therapeutic approaches with occasional success, but no general recommendations.

Asymptomatic venous thrombosis in cancer patients--a problem often overlooked. Results of a retrospective and prospective study.

BACKGROUND: Venous thrombosis with and without pulmonary embolism is a frequent complication of malignancies and second among the causes of death in tumour patients. Its incidence is reported to be 10 to 15%. Since for methodological reasons, this rate can be assumed to be too low and to disregard asymptomatic venous thrombosis, a combined retrospective and prospective study was performed to examine the actual frequency of venous thrombosis in tumour patients. PATIENTS AND METHODS: The histories of 409 patients (175 women, 234 men, mean age 69 years [19 to 96 years]) with different tumours, consecutively enrolled in the order of their altogether 426 inpatient treatments, were checked in retrospect for the frequency of venous thrombosis and pulmonary embolism. Subsequently, 97 tumour inpatients (36 women, 61 men, mean age 70 years [42 to 90 years]) were systematically screened, by means of duplex sonography and/or venography, for venous thromboses in the veins of the pelvis and both legs. RESULTS: In the retrospective analysis, where no systematic screening for thromboses was performed and only symptomatic thrombosis was recorded, venous thrombosis was found in 6.6% of all tumour patients, whereas in the prospective examination with systematic duplex sonography and / or venography of all patients, the percentage was 33%. In the prospective study, 31.3% of venous thromboses were symptomatic and 68.7% asymptomatic. In 39.3% of the cases in the retrospective analysis and 25% in the prospective analysis, venous thrombosis occurred during chemotherapy, surgery or radiation therapy. Venous thrombosis was most often seen in metastasizing tumours and in colorectal carcinoma (40%), haematological system diseases (28.6%), gastric cancer (30%), bronchial, pancreas and ovarian carcinoma (28.6%), and carcinoma of the prostate (16.7%). CONCLUSION: Regular screening for thrombosis is indicated even in asymptomatic tumour patients because asymptomatic venous thrombosis is frequent, can lead to pulmonary embolism and has to be treated like symptomatic venous thrombosis. This is particularly true for metastasization during chemotherapy, surgical interventions, or radiation.

[15 years Amputierten-Initiative e.V]. / 15 Jahre Amputierten-Initiative e.V.

The Amputierten-Initiative e.V. [Amputees' initiative] was founded in Berlin as a self-help group of amputee patients in 1991. Since then, its aim has been to prevent amputations by education, to give patients sociomedical advice before and after inevitable amputations and to refer them to problem-oriented angiologists, vascular surgeons, pain therapists, orthopaedists, orthopaedic technologists, and rehabilitation centres. Because of this activity, the Amputierten-Initiative has become a member of many scientific societies, taken part in research projects and received personal and institutional honours. The acceptance and necessity of the Amputierten-Initiative and the need for its work become manifest in the rising number of its members.

Circulating nerve growth factor in primary and secondary Raynaud's syndrome - results of a pilot study.

BACKGROUND: In this pilot study we examined circulating concentrations of nerve growth factor (NGF) in controls and patients suffering from primary or secondary Raynaud's syndrome and determined their relation to digital vasospasm. PATIENTS AND METHODS: Eighteen controls, 16 patients with primary RP and 19 patients with systemic sclerosis (SScl) were included. Degree of vasospasm was graduated according to the degree of plethysmographically measured vasospastic reaction after cold test. A diary was handed out for documentation of the daily number and duration of RP during a period of 16 days. Circulating NGF levels were analysed by a commercial ELISA (Promega Inc., USA). RESULTS: SScl-patients were significantly older (p < 0.0001) and more severely affected by spontaneously occurring RP (p = 0.03), whereas the severity of the vasospastic reactions after a standard cold test were not significantly different between the groups (p = 0.09). Within each study group and between the study groups elevated NGF levels were observed only in SScl-patients after thermal provocations (p = < 0.05). In a correlation analysis restricted to patients with PRP or SRP, the degree of vasospasm after cold testing as well as the intensity of Raynaud's symptoms were not correlated with NGF-levels (p = n.s.). CONCLUSIONS: Our results do not support the hypothesis that NGF plays a major role in the generation of vasospasm in Raynaud's phenomenon.

[Definition and terminology of Raynaud's syndrome]. / Definition und Terminologie von Raynaud-Syndromen.

Physicians have for a long time used different definitions, terminology and differential diagnoses for Raynaud's syndromes, which has resulted in diagnostic, therapeutic and prognostic problems. In order for difficulties of understanding to be prevented, the terminology should be restricted to the most common terms in international use, i. e. primary, secondary and suspected secondary Raynaud's syndrome. The characteristics of those three forms of Raynaud's syndrome are outlined.

Complete ulcer healing as primary endpoint in studies on critical limb ischemia? A critical reappraisal.

OBJECTIVES: Although complete ulcer healing is the mandatory primary efficacy criterion in current European guidelines for drug trials in critical limb ischemia (CLI), the appropriateness of this endpoint has been questioned for some time. We carried out a systematic review to assess the value of this endpoint in studies on reconstructive measures, considered to be the standard of care for CLI. METHODS: A computerized literature search (1985-2005) was performed to track down clinical studies on endovascular and surgical interventions by using the search terms CLI and ulcer healing and their synonyms. RESULTS: 1,914 papers on revascularization in CLI were identified. Complete ulcer healing was reported in 17 studies (0.9%). Among these, there were no randomized controlled trials, five prospective cohorts on endovascular procedures, and six retrospective cohorts for endovascular and surgical procedures, respectively. If healing rates or time to ulcer healing were available, they differed greatly between the studies without consistent correlation to types of therapy. CONCLUSIONS: In past and current literature, complete ulcer healing is not a consistently reported criterion for success of revascularization in CLI. Thus, its appropriateness for efficacy assessment of drug studies in CLI patients has to be questioned.

[Vasoactive agents and prostanoids in the therapy of PAD: facts, questions, disproven assumptions]. / Vasoaktive Substanzen und Prostanoide in der Therapie der pAVK. Was ist gesichert, was offen, was überholt?

In the view of the AkdA (Drug Committee of the German Medical Profession), the efficacy in intermittent claudication is currently proven only for Naftidrofuryl, whereas in the opinion of the DGA (German Society of Angiology) also that of prostaglandin E(1) is proven. Both drugs are indicated if neither walking exercise nor vascular or endovascular reconstruction are feasible. In critical limb ischaemia (Fontaine stage III/IV), the efficacy of prostaglandin E(1) and iloprost is proven according to both the treatment recommendations of the DGA and the ACC/AHA Guidelines. The AkdA also agrees with the administration of prostanoids, even though it considers their efficacy not sufficiently proven in accordance with CPMP criteria. Here, prostaglandin E(1) is approved for the treatment of Fontaine's stage III/IV regardless of its etiology, whereas iloprost is approved only for the treatment of thrombo-angiitis obliterans.

Concomitant neurological and orthopaedic diseases in the presence of peripheral arterial disease: a prospective study.

BACKGROUND: The symptoms of peripheral arterial disease (PAD) can be masked by neurological or orthopaedic diseases with identical symptoms, which may result in faulty therapy decisions, if the diagnosis is solely based on the reported complaints and angiographic or duplex ultrasonographic findings. A prospective study was therefore performed to find out how often established PAD is accompanied by neurological or orthopaedic pictures that can blend into the PAD symptoms. PATIENTS AND METHODS: The examination was performed in 235 patients with PAD of Fontaine's stages II to IV, 125 were women and 110 men; the mean age was 71 years (41 to 95 years). They were systematically examined for angiologic, neurological and orthopaedic diseases. RESULTS: 44% of the patients enrolled in the study suffered from a neurological disease, 45% from an orthopaedic disease and 24.7% from both a neurological and an orthopaedic disease. The frequency of concomitant diseases depended on the stage of PAD. In Fontaine's stage II, alterations due to arthrosis or arthritis were found in 12% of the patients, peripheral neuropathies in 14%, radiculoneuropathies in 16% and malpositions of the foot in 16%. In Fontaine's stage III, arthrosis and arthritis were predominant at a percentage of 38.5%; peripheral neuropathies were diagnosed in 15.4% of the patients. Patients with Fontaine's stage IV most often showed peripheral polyneuropathies at 42.1% and malpositions of the foot at 28.4%. CONCLUSIONS: Because of the frequency of neurological and orthopaedic pictures with identical symptoms, a differential diagnosis before the initiation of a PAD therapy is imperative.

Are there predictors for the outcome of a PGE1 treatment in peripheral arterial disease with critical limb ischaemia?

BACKGROUND: In a multivariate retrospective analysis was conducted to examine whether and to what extent PGE1 is therapeutically effective and whether there are predictors of response. PATIENTS AND METHODS: The examination included 767 patients (448 women, 319 men) of a mean age of 71.2 years and with peripheral arterial disease (PAD) having existed for 44.7 months on the average. They suffered from critical limb ischaemia (Fontaine's stages III/IV) and showed average tcpO2 values at the instep of 2 mmHg (0 to 15) and average systolic malleolar artery pressures of 18 mmHg (0 to 35 mmHg). Between 1989 and 2001, the patients had received treatments in hospital with i.v. PGE1 doses (2x20 microg or 1x60 microg/day) for an average of 34.2 days (mean of responder- and non-responder group). Patients were called responders when pain had markedly decreased or disappeared, necroses had been reduced or healed completely, and vascular reconstruction, PTA or amputations were not necessary. RESULTS: The clinical analysis showed 82.4% of the patients to be responders and 17.6% to be non-responders. It was demonstrated that the outcome of the therapy was not dependent on the supine or sitting tcpO2, the malleolar artery pressure, the patient's age or sex, the duration of PAD, the number or kind of concomitant diseases, the patient's general condition, the localization and number of vascular occlusions, the kind of prior therapy, or the number of previous amputations, although differences in some of the parameters, while clinically irrelevant, were found to be statistically significant. They are not predictors of the outcome of a PGE, therapy. CONCLUSIONS: Even in extremely bad haemodynamic situations at the beginning of a therapy (malleolar artery pressures from 0 to 35 mmHg, tcpO2 0 to 15 mmHg, multilevel occlusive disease, multiple previous operations and concomitant diseases), PGE, therapies of more than 20 days - on the average 35.6 days (mean of responder group) - duration allow clinically relevant positive results to be achieved.

Prostaglandin E1 infusion therapy in dry age-related macular degeneration.

OBJECTIVE: The pilot study is intended to show whether prostaglandin E1 (PGE1) infusions are able to stop the gradual vision loss in dry age-related macular degeneration (AMD) and, further, to stabilize or improve visual acuity. METHODS: With PGE1 infusions 11 patients with different forms of dry AMD were treated and compared with a control group of 10 untreated patients with dry AMD. The target parameter was the visual acuity, as determined with the ETDRS logMAR charts. Other examinations performed during the study were tests of contrast vision, colour vision and central visual fields, as well as autofluorescence and fluorescein angiography and multifocal electroretinography. RESULTS: On termination of the infusions, six patients showed an increase in visual acuity by at least one line, an improvement that was seen in eight patients 2 months after the end of the infusion therapy. After 6 months, one patient exhibited an improvement of visual acuity by three lines and three patients an improvement by one line. Five patients were found to show no change of their baseline acuity values after 6 months, while two patients exhibited an impairment by one line. The visual acuity in the dry AMD control group without PGE1 treatment had decreased by 0.8 lines on the average after 6 months. Contrast vision, central visual fields and the multifocal electroretinogram showed improvements on the termination of infusions and up to 2 months later; no substantial change of these parameters, as compared with the baseline findings, was seen 6 months after the termination of infusions. SUMMARY: This pilot study suggests that PGE1 infusions have a stabilizing or improving effect on the visual acuity of patients with dry AMD. Owing to the limitations of a pilot study, these results should, however, be validated in a larger, randomized and blinded study.

Frequency of non-vascular accompanying diseases in patients with peripheral arterial disease.

BACKGROUND: Since there are so far no relevant figures on the frequency of non-vascular associated diseases in patients with peripheral arterial disease (PAD), an analysis was carried out to determine how frequently co-morbidity is found in such patients. PATIENTS AND METHODS: In the course of a retrospective analysis, 1693 patients (55.4% men, 44.6% women/average 68.6years) with peripheral arterial diseases (PAD) of Fontaine stage II to IV were examined to find out how often cardiopulmonary, gastrointestinal, haematological, endocrinological, neurological, orthopaedic, urological-nephrological, psychiatric diseases and tumours were seen. RESULT: Coronary ischaemic heart disease was present in 63.1% of the cases, heart failure existed in 20.7%, hypertension in 57.9%, endocrine and metabolic diseases in 60.4%, gastrointestinal diseases in 14.8%, pulmonary diseases in 14.5%, psychological and behavioural deficiencies in 16.2%, orthopaedic diseases in 21.6%, haematological diseases in 9.0%, urological diseases in 16.9%, chronic renal insufficiency in 7.3% and malignant tumours in 5.8%. CONCLUSIONS: The frequency of non-vascular comorbidity in patients with PAD necessitates systematic interdisciplinary diagnosis prior to any therapy decision to take into account the patient's associated diseases, life expectancy and current quality of life.

Frequency of asymptomatic peripheral arterial disease in patients entering the department of general and internal medicine of a general-care hospital.

BACKGROUND: The fact that a high prevalence of asymptomatic peripheral arterial disease (PAD) in the population has repeatedly been noted in recent years, without there being data as to how often asymptomatic PAD has to be anticipated in inpatients treated for divergent internal diseases led us now to performing a screening study in a general-care hospital. PATIENTS AND METHODS: The study population consisted of 990 patients (51.8% women, 48.2% men) with a mean age of 65.2 years (40-93 years) who had to be treated in a hospital for various internal diseases in the period from January 1994 to January 1995. Their case histories were taken, and their clinical findings and the ankle/brachial indices as calculated from Doppler ultrasonographic measurements of the systolic pressures in the malleolar and brachial arteries were used to ascertain how many of the patients presented with asymptomatic and symptomatic PAD. Further the frequency of risk factors (smoking, hypertension, diabetes mellitus, lipid disorders) was recorded for either patient group. RESULTS: The study showed that 6% of the 990 patients suffered from symptomatic PAD and that of the remaining 931 patients, 43.7% were diagnosed, on the basis of the ankle/brachial index (ABI) (< or = 0.9), to have asymptomatic PAD, while 56.3% showed no indication of PAD. CONCLUSIONS: The high number of cases of asymptomatic PAD among inpatients who underwent internal treatment--a percentage well above the figures published so far for outpatients--allows the conclusion that the determination of the ABI is well suited to screen patients older than 50 years even in a hospital setting so that early secondary prophylaxis can be initiated.

[DRG-based cost analysis of inpatient conservative treatment of stage III/IV peripheral arterial occlusive disease]. / DRG-basierte Kostenanalyse zur stationären konservativen Behandlung der PAVK Stadium III/IV.

UNLABELLED: DRG-based cost analysis of inpatient conservative treatment of PAD stage III/IV BACKGROUND: In a prospective study carried out by the German Society of Angiology and the DRG Competence Center, Munich, the question was investigated whether the costs of conservative treatment of patients with PAOD stage III/IV (DRG F65) are adequately represented within the current G-DRG system. METHODS UND PATIENTS: Between September 1 and December 16, 2002, a total of 704 patients with DRG F65 (peripheral vascular diseases) were evaluated at 8 angiologic centers in Germany. Apart from the length of hospital stay, the total costs (cost equivalents) were calculated using a method developed by the DRG Research Group at the University of Münster. Moreover, the study population was compared with a German calculation sample for the DRGs F65A/B, as published by InEK. RESULTS: As it turned out, conservatively treated patients with PAOD stage III or IV (DRGs F65A/B) cause significantly (p < 0.001) higher costs and have significantly (p < 0.001) greater lengths of hospital stay than patients who were also assigned to DRG F65 because of other vascular diseases. At the same time it became clear that angiologic centers treat twice as many patients with critical limb ischemia in comparison with the German average. The reimbursement hitherto estimated by InEK covers not even half the cost actually produced by conservative treatment of PAD stage III/IV. CONCLUSION: To ensure a performance-related reimbursement, a new basis DRG for patients with PAD stage III/IV has to be created, as has ben proposed by the German Society of Angiology. Otherwise, adequate conservative therapy in accordance with existing guidelines, of patients who cannot be treated surgically or interventionally will not be possible any more in the future.

Hemostatic and fibrinolytic effects of systemic prostaglandin E1 therapy in patients with peripheral arterial disease.

BACKGROUND: The study was designed to evaluate if there is any evidence of a hyperfibrinolytic bleeding-risk under systemic treatment with prostaglandin E1 (PGE1) of patients with peripheral arterial disease (PAD). PATIENTS AND METHODS: The in vivo effect of PGE1 on the fibrinolytic and hemostatic process was tested on 15 patients before and after treatment with Alprostadil for 21 days using D-dimers (DD), fibrinogen, prothrombin time (PT), partial thromboplastin time (PTT), antithrombin (AT), ProC-Global, plasminogen, plasminogen activator inhibitor activity (PAI), alpha 2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity (fib. cap.). RESULTS: There was no significant difference in DD, fibrinogen, PT, PTT, AT, ProC-Global, plasminogen, PAI, alpha 2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity observed after the treatment. CONCLUSION: Summarizing this study there is no hyperfibrinolytic bleeding-risk after the systemic therapy with Alprostadil to be expected.

Vital capillary microscopic findings in the nailfold of patients with diabetes mellitus.

BACKGROUND: Preliminary investigation done in 100 healthy adults and 20 healthy children had shown that the interpretation of significance of changes in capillary morphology need to be corrected, since capillary changes previously considered to be pathological are also to be found in large numbers in healthy subjects. Against this background, the question has now been investigated whether the capillary microscopic findings in diabetics deviates from those found in normals, and whether the duration of the diabetes, its treatment, its sequelae, or concomitant diseases have any influence on the capillary microscopic appearance. PATIENTS AND METHODS: In 100 patients aged between 44 and 88 years with type 2 diabetes vital capillary microscopy was carried out on all ten fingers in the usual manner. The evaluation of the video recordings was done only when all the examinations had been completed--by two examiners blinded to the clinical data. RESULTS: It was shown that 66% of the patients demonstrated pathological capillary microscopic findings. These findings included pathologically increased apical and non-apical dilatations (32%), haemorrhagic extravasations (20%) and branchings (45%). No differences were found between the therapy groups (insulin--oral medication) nor was any relationship between the appearance of capillary changes and the duration of diabetes observed. Diabetics with concomitant diabetic sequelae (polyneuropathy), demonstrated no differences in capillary morphology as compared with diabetics with no such sequelae. CONCLUSION: Diabetics are found to have an increased incidence of pathological capillary morphology taking the form of increased apical dilatations, branchings and haemorrhagic extravasations. Neither the treatment, nor the duration of the illness, nor diabetic sequelae appeared to have any influence on the capillary microscopic changes.

[What is the value of determining walking distance in peripheral arterial occlusive disease on the treadmill and in daily life? Prospective correlation study]. / Was bedeuten Gehstreckenbestimmungen bei peripherer arterieller Verschlusskrankheit auf dem Laufband und im Alltag? Prospektive Korrelationsuntersuchung.

AIM: To investigate the question whether and how walking distances measured under standardized conditions on the treadmill and on the level correlate with the patients walking ability under everyday conditions. PATIENTS AND METHOD: In 49 patients (33 men, 16 women, age 34 to 84 years) with Fontaine Stage II peripheral arterial occlusive disease the pain-free and absolute walking distance on the treadmill were measured under standardized conditions, as also the walking distance on the level at freely selected speed. RESULT: It was found that the pain-free walking distance under everyday conditions was about 2 to 3 times longer than that measured under standardized conditions on the treadmill.