[Dynamic function tests for detection of physiologic and pathophysiologic reactions in cutaneous microcirculation]. / Dynamische Funktionstests zur Erfassung physiologischer und pathophysiologischer Reaktionsmuster kutaner Mikrozirkulation.

Functional tests simulating local stresses are especially suitable for the evaluation of physiological and pathophysiological patterns in the cutaneous microcirculation, particularly if combined with non-invasive methods such as laser-Doppler fluxmetry and oxygen tension measurements. Arterial occlusion (3 min) and local heating (up to 42 degrees C) are appropriate as stimuli to simulate specific local demands on the cutaneous perfusion similar to those produced by pressure, myokinesis, heat, and inflammation. When the current microcirculatory status is described the initial values (LDF and pO2) and their time-courses during each functional test can be used to determine the so-called post-stimulatory parameters. These-- corresponding to physiological equivalents--allow statements on the vascular reactivity towards hypoxia and ischaemia. Furthermore, dynamic performance parameters can easily be derived from the poststimulatory values. They describe the capacity of cutaneous microcirculation with regard to perfusion reserves and ischaemic tolerance in local stress situations in an appropriate manner. As an example of the usefulness of functional tests for cutaneous microcirculation, the physiological and pathophysiological patterns found in systemic sclerosis are described.

[Disordered cutaneous microcirculation in diabetic neuropathic foot ulcer. Is modification by retrograde transvenous perfusion therapy possible?]. / Kutane Mikrozirkulationsstörung bei diabetischen neuropathischen Plantarulzera. Ist eine Beeinflussung durch retrograde transvenöse Perfusionstherapie möglich?

Due to the high risk of amputation they involve, diabetic neuropathic plantar ulcers (DNPU) must be regarded as a late manifestation/complication of diabetes mellitus. The suspected cause of these ulcers--disturbed cutaneous microcirculation--was studied by simultaneously measuring laser-Doppler flux (LDF) and cutaneous oxygen tension (pCUO2) in 14 patients with DNPU at three differently affected sites (dorsal forefoot, ulcer edge, lower leg). Dynamic tests (arterial occlusion, local hyperthermia) as a measure of vascular reactivity showed significantly reduced pCUO2 parameters coinciding with elevated LDF values. This reflects a shift of blood flow from the nutritive capillaries towards deeper vessels. Abolition of normal vasoconstriction in the arteriovenous shunt vessels by diabetic polyneuropathy is the assumed cause of increased AV perfusion, with a consequent rise in LDF values. In a subgroup of the above patients (n = 7) undergoing daily intravenous retrograde perfusion therapy (RVP) over 10 days several basic and dynamic microcirculatory functions were studied before and after this treatment. This subgroup showed on the forefoot and the lower leg a remarkable improvement of the microcirculatory parameters investigated, suggesting a better oxygen supply to the tissues after RVP therapy.

Influx of antibiotics into diabetic legs with plantar ulcerations: regional and systemic Netilmycin levels compared after retrograde-venous and systemic-venous application.

Retrograde venous perfusions (RVP) of antibiotics were proven to be therapeutically more effective than systemic venous infusions (SVI) in patients with infected diabetic neuropathic plantar ulcers (DNPU: no additional macronagiopathy of leg arteries). In order to study some pharmakokinetic features of RVP application paratibial tissue levels of Netilmycin (NL; from suction blister fluid) and cubital venous NL were compared under each SVI and RVP therapy in 8 patients with DNPU. Tissue (11.6 +/- 6.4 micrograms/l) were significantly higher (p < 0.001) an within the therapeutic range after RVP (SVI: 4.31 +/- 1.68). In ulcer transsudate (RVP only; n = 4) NL mounted to 36.4 +/- 11.6 microgram/ml. Peak and base NL in cubital blood were within the normal range for both SVI and RVP (no significant difference). The date indicate that RVP is superior to SVI application of Netilmycin (and probably other antibiotics) as surmounting the damaged microcirculation in DNPU to achieve effective drug levels in the target tissue.

Disturbances of cutaneous microcirculation in patients with diabetic legs: additional parameters for a new therapeutic concept?

To study disturbed microcirculation involved in the pathogenesis of diabetic neuropathic plantar ulcers (DNPU), we recorded dynamic changes in laser-Doppler flux (LDF) and cutaneous oxygen tension (pcuO2) caused by short-time arterial occlusion and local heating at three different sites (forefoot, ulcer edge, lower leg) in patients (n = 14) with DNPU and healthy controls (n = 18). Significantly reduced dynamic pcuO2 parameters coincided with a significant increase of flux in the patient group. This post-stimulatory "hypoxic hyperemia" indicates a shifting of blood flux, reducing circulation of the nutritive capillaries comparable to an internal "steal effect". This may predispose to the development of DNPU when additional stresses influence the initial borderline balance, characterized by similar pcuO2 and increased flux values compared to controls. Abolishment of normal vasoconstriction in the shunt vessels by diabetic polyneuropathy is the assumed cause of increased arteriovenous perfusion and therefore raised flux values. Non-invasive testing of microcirculatory functions demonstrates characteristic disturbances in DNPU patients and could be used as additional parameters for new therapeutic concepts as the intravenous retrograde perfusion (RVP). After RVP therapy, applied to a subgroup (n = 7) of the patients, some dynamic microcirculatory parameters improved, allowing a preliminary quantitative evaluation of a therapeutic regimen.

[Anticardiolipin syndrome with only skin involvement]. / Anticardiolipin-Syndrom mit alleinigem Hautbefall.

In anticardiolipin syndrome (ACS) a typical antibody constellation is associated with thrombotic and hematologic disorders. Furthermore, recurrent abortion, cerebral ischemia and different skin disorders occur. We report the case of a 29-year-old female suffering for the first time from painful, necrotic deep ulcers on the upper and lower legs and livedo racemosa on the arms as a rare example of a merely cutaneous manifestation of ACS with no demonstrable underlying disease. After systemic treatment with high-dose methylprednisolone, azathioprin and hydrocolloid dressings, healing of the scar tissue occurred. Simultaneously, a maintenance dose of acetylsalicylic acid (100 mg/day) was administered. So far, neither cutaneous relapse nor other signs of ACS have occurred.

[Therapeutic superiority of regional retrograde venous antibiotic pressure infusion versus systemic venous infusions in diabetic patients with infected neuropathic plantar ulcers]. / Therapeutische Uberlegenheit regionaler retrograd-venöser Antibiotika-Druckperfusionen versus systemisch-venöser Infusionen bei Diabetikern mit infizierten neuropathischen Plantarulcera.

Since systemic treatment of neuropathic plantar ulcers in diabetics (DNPU) has so far been rather ineffective, recent reports of successful management of DNPU by short-term retrograde transvenous leg perfusion (RVP) by South American angiologists encouraged us to apply this treatment method in diabetics suffering from chronic DNPU. Hence, in a prospective comparative clinical trial started in 1989 we have treated 45 male diabetics suffering from DNPU with the same daily doses of netilmycin, administered either in systemic venous infusions (SVI: n = 21, three times/day) or in RVP (n = 24, once/day). After 10 consecutive days of treatment, ulcers had closed in 8 of the 24 patients treated with RVP, as against 3 of the 21 treated with SVI. Diminution of the ulcer area by > 30% including full debridement was achieved in 10/24 of the RVP cases (SVI: 4/21). During 6 months of follow-up, amputation of toes or forefoot was necessary in only 1 patient in the RVP group, but in 4 in the SVI group. Partial restitution of osteolytic damage was observed in some cases after RVP. Our results show that regional netilmycin therapy given by the RVP procedure is clearly superior to equal netilmycin doses administered by SVI for the treatment of DNPU. RVP can be recommended in DNPU, particularly when the ulcers are complicated by infections.

Microcirculatory functions in systemic sclerosis: additional parameters for therapeutic concepts?

To study the functional reactivity of the cutaneous microcirculation in progressive systemic sclerosis (PSS), hyperemic responses after arterial occlusion (3 min) and during local heating (42 degrees C) were investigated with simultaneous measurements of red blood cell flux and cutaneous oxygen tension (pcuO2) of the skin in female patients (n = 19) with PSS and in healthy female controls (n = 15). Additionally, serum levels of 6-keto-prostaglandin 1 alpha (PGF1 alpha), a stable metabolite of prostacyclin, were compared to the microcirculatory data, and both were used to evaluate further a standardized therapy with 10-d intravenous calcitonin (100 IU/d) infusion in six PSS patients. In PSS, the initial mean pcuO2 value was significantly reduced and was inversely proportional to flux and to PGF1 alpha levels, whereas the flux and pcuO2 responses to the above hyperemic stimuli showed significant reductions, revealing a pattern of "hyperemic hypoxia" probably due to exhausted functional reserves of cutaneous perfusion. During calcitonin infusion significant rises in pcuO2 and temporarily in PGF1 alpha and flux were found. After 10 d of therapy, increased pcuO2 was associated significantly with decreased flux, indicating a shifting of blood from deeper regulatory vessels to the subepidermal capillaries. Both clinical improvement and the results of microcirculatory measurements demonstrate a beneficial effect of calcitonin on the cutaneous microcirculation in PSS patients, possibly due in part to a short-term increase in release of endogenous prostacyclin from the vascular endothelium during the infusion. The disturbed reactivity of the dermal vessels in PSS is important for the evaluation of therapeutic concepts and stresses, together with the elevated PGF1 alpha plasma levels, vascular factors in the pathogenesis of PSS.

[Systemic infusion therapy versus retrograde intravenous perfusion: comparative results in patients with diabetic neuropathic plantar ulcer]. / Systemische Infusionstherapie versus retrograde intravenöse Perfusion: Vergleichende Ergebnisse bei Patienten mit diabetisch-neuropathischen Plantarulzera.

Concerning the resistance of diabetic neuropathic plantar ulcers (DNPU) against systemically applied drugs, the "Retrograde Venous Perfusion" (RVP) was introduced as a therapeutic alternative by C. P. Ferreira in 1988. An isotonic saline solution containing gentamycin, buflomedil, dexamethasone, heparin and lignocain is injected into a dorsal foot vein under arterial occlusion of the lower leg. In the present study RVP treatment was done in 20 patients with DNPU and the results were compared to a group treated with systemic intravenous infusions (SVI; n = 20). After 10 days of treatment, 8 out of 20 ulcers were closed (SVI: 4). In 9 ulcers (SVI: 4) size had diminuted by > 30%. Non responders were not observed under RVP in contrast to SVI (7/20 cases). In 4 of 5 patients with osteolytic bone lesions (SVI: 0/7), partial restoration was observed. Rate of toe amputation dropped to 0% (SVI: 20%). Considering the striking differences between either regimen, RVP can be recommended for treatment of DNPU especially when complicated by osteomyelitis.