[Lupus erythematosus/lichen ruber planus overlap syndrome. 5 cases in a patient sample of the Erlangen University Dermatology Clinic (1894-1995)]. / Lupus-erythematodes-/Lichen-ruber-planus-Overlap-Syndrom. 5 Fälle im Patientengut der Dermatologischen Universitätsklinik Erlangen (1984-1995).

The simultaneous occurrence of lupus erythematosus (LE)- and lichen ruber (LP)-like symptoms is called LE/LP-overlap syndrome (LE/LP-OS). It is defined by concomitant clinical, histologic and immunhistologic features of both diseases. To date, 47 cases of this rare dermatosis have been reported with marked differences in the skin lesions: They are either of intermediate appearance between LE and LP (type I = intermediate type), or show a coexistence of LE- and LP-specific lesions (type II = polar type). To determine the frequency and characteristics of the LE/LP-OS we reviewed our LE-patients from 1984-1995. 5 cases were diagnosed. The frequency of LE/LP-OS in our patients is higher than generally assumed. Due to its variable clinical, histological and immunhistological appearance and the lack of unequivocal pathognomonic signs, this overlap-dermatosis may be underdiagnosed. Since therapeutic consequences result from the diagnosis, criteria are suggested to facilitate the recognition of the LE/LP-OS.

Respiratory-dependent laser-Doppler flux motion in different skin areas and its meaning to autonomic nervous control of the vessels of the skin.

The aim of this study is to evaluate and quantify the respiratory dependency of cutaneous laser-Doppler flux motion in two variable innervated sites of the upper extremity (the proximal volar forearm and the fingertip) by using a computer-supported system. Various spontaneous (6-17/ min) and externally triggered (12 or 6/min) respiratory frequencies were used for comparative frequency analysis of the laser-Doppler flux signal. Further, an index (MIRSF) was determined as an indicator of the correlation between flux motion and respiration. The MIRSF is defined as the ratio of the power spectrum of the LDF signal at the specific respiratory frequency divided by the time-averaged LDF for that time period. The MIRSF enables a comparison of different intra- and interindividual flux values. A very high correlation was seen between the respiratory frequency and the MIRSF during spontaneous respiration in the skin of the proximal volar forearm; the lower the spontaneous respiratory frequency, the higher the MIRSF. However, this correlation could not be found in the results of the fingertip. The presence of a constant and therefore externally triggered respiratory frequency increased the modulations of the LDF at both measurement locations. While triggered respiration produced a decline in the taLDF of the fingertip, the taLDF of the forearm was unaffected. Considering the different innervation and hydrostatic effects the results lead to the following conclusion: the finger vessels are richly innervated with adrenoceptors which causes alpha 1-mediated vasoconstriction. In contrast to the vessels of the fingers those of the forearm seem to be under andrenergic as well as cholinergic control. Hydrostatic components appear to be more prevalent in the volar forearm site.

[High frequency color coded duplex ultrasound of small finger arteries--new diagnostic possibilities? A noninvasive method for visualizing digital circulation]. / Die hochfrequente farbkodierte Duplex-Sonographie kleiner Fingerarterien--neue diagnostische Möglichkeiten? Eine nichtinvasive Methode zur Visualisierung der digitalen Strombahn.

Small vessels with luminal diameters of 0.2-2.0 mm have not been studied with routine ultrasound diagnostic procedures. Modern color Doppler imaging technology, however, should allow visualization of the blood flow even in such small vessels. The present study was therefore aimed at demonstrating the possibilities of examining small arteries in the fingertips of healthy volunteers with color Doppler imaging. The question was whether or not a standardized visualization was possible. We found that small arteries and their blood flow could be demonstrated in all (n = 10) healthy subjects. Furthermore, we demonstrated pathologic findings in the fingertip arteries of a patient with thrombangitis obliterans as an example of the diagnostic value of these new procedures.

Discovery and optimization of a novel class of orally active nonpeptidic endothelin-A receptor antagonists.

A novel class of endothelin-A receptor ligands was discovered by high-throughput screening. Lead structure optimization led to highly potent antagonists which can be synthesized in a short sequence. The compounds are endothelin-A-selective, are orally available, and show a long duration of action.

[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.

[Color-coded duplex ultrasound and laser Doppler flowmetry of finger tips of healthy probands]. / Farbkodierte Duplex-Sonographie und Laser-Doppler-Fluxmetrie in Fingerkuppen Gesunder.

In the study presented, color-coded duplex sonography (CCDS) and laser Doppler flux (LDF) signals from finger tips of 7 healthy individuals were recorded simultaneously. The aim of the study was to examine whether or not the results of a functional test ('deep inspiration') could also be observed with an ultrasonic Doppler. In the literature this test is known to provoke notable blood flow characteristics of the LDF ('inspiratory gasp'), a phenomenon which is caused by a sympathetically mediated vasoconstriction of acral vessels. With regard to the penetration depth of the LDF in skin it was of further interest to determine the distance between the surface of the skin and the vessels found near the surface. We found for CCDS parameters (color pixels/image; time-averaged flow velocity [TAV]; resistance index [RI]) as well as for LDF (flux [taLDF]) significant changes before versus after 'deep inspiration'. CCDS is a new diagnostic tool to visualize also very small vessels down to 0.2 mm, e.g. in finger tips. It should be evaluated which role this method may play in combination with functional tests in diagnostic handling, e.g. of patients with polyneuropathies or collagenoses.

[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.

[Initial visceral involvement with diffuse systemic scleroderma]. / Initialer viszeraler Befall bei diffuser systemischer Sklerodermie.

Progressive systemic sclerosis (PSS) is characterized in most patients by initially unspecific symptoms like acrocyanosis. Raynaud's phenomenon, general malaise or acral paresthesia. Clinical manifestations appear with an edematous-inflammatory stage of disease leading to a chronic-progressive phase with increasing fibrosclerosis of the skin and internal organs. Dermal involvement and the demonstration of immunopathological abnormalities in the peripheral blood precede visceral fibrosis in most cases. We report on an unusual case of diffuse PSS with preceding involvement of internal organs. Early visceral fibrosis is demonstrated by histomorphological results and is correlated with laboratory findings. Serum antinuclear antibodies could not be obtained until 4 months ante finem and the liver was also involved in the fibrotic process.

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.

[Idiopathic pustular and bullous variants of Sweet syndrome]. / Idiopathische pustulöse und bullöse Variante eines Sweet-Syndroms.

We report on the case of a 62-year-old patient with disseminated pustular plaques affecting especially his face and hands. These lesions exhibited severe blistering later in the course. The diagnosis of an unusual variant of an acute febrile neutrophilic dermatosis (Sweet's syndrome) was histologically confirmed. Pustular lesions are known to occur in Sweet's syndrome. Secondary development into bullous lesions, however, has not previously been described. No associated disease has so far been detected.

[Respiration-dependence of cutaneous laser Doppler flow motion]. / Atemabhängigkeit kutaner Laser-Doppler-Fluxmotion.

The aim of this study was to show and to quantify the breath-dependency of cutaneous fluxmotion in the volar proximal forearm using a new computer-aided system. A meanflux-related index (MI) representing the intensity of the influence of respiration on fluxmotion was calculated. There was a good correlation between MI and the rate of respiration under spontaneous breathing: the lower the rate of respiration, the higher the value of MI. Prescribing a constant breathing rhythm amplifies this frequency-dependent effect. According to occurrence of low rates of respiration (< 12/min) also under physiological conditions the respiration should be simultaneously recorded while assessing fluxmotion.

[Cutaneous microcirculation in pretibial necrobiosis lipoidica. Comparative laser Doppler flowmetry and oxygen partial pressure determinations in patients and healthy probands]. / Kutane Mikrozirkulation bei prätibialer Nekrobiosis lipoidica. Vergleichende Laser-Doppler-Fluxmetrie und Sauerstoffpartialdruckmessungen bei Patienten und Hautgesunden.

Necrobiosis lipoidica (NL) is a chronic, skin disease usually localized pretibially and often associated with diabetes mellitus. Primary vascular disturbances are considered pathogenetic for NL. In order to determine microcirculatory alterations in "idiopathic" NL linked with neither arterial hypertension nor diabetes mellitus, we performed simultaneous measurements of laser-Doppler flux (LDF) and oxygen tension (pcuO2) in 10 non-diabetic patients with NL and in 10 age- and sex-matched healthy volunteers. We examined the centre of the pretibial NL plaque, its border and the non-affected skin of the proximal lower leg at probe temperatures of 36 degrees C (flux) and 37 degrees C (pcuO2). Corresponding sites and temperatures were chosen for the controls. In addition, the degrees of hyperaemia caused by arterial occlusion (3 min) and during local heating (42 degrees C) were continuously measured. The initial pcuO2 values were found to be lowered, in contrast to increased fluxes within and around the NL lesions. In addition, responses of both flux and pcuO2 to the hyperaemic stimuli were weaker than in the corresponding skin of the healthy controls. Only minor differences from controls or none at all were found in clinically unaffected lower leg skin of the patients. Our results indicate a local alteration of microcirculation in patients with "idiopathic" NL that occurs independently of diabetes.

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.

[A special form of Bazex acrokeratosis in small cell bronchial cancer]. / Sonderform einer Akrokeratose Bazex bei kleinzelligem Bronchialkarzinom.

A 66-year-old pensioner developed distinct, erythematosquamous and keratonic lesions on the hands and feet within 2 months, and also a progressive red-bluish discoloration of the whole integument. Clinical and X-ray exploration revealed a still asymptomatic small-cell bronchial carcinoma, so that the otherwise inexplicable skin lesions made an acrokeratotic paraneoplastic syndrome of the Bazex type seem most likely. This very rare syndrome has hitherto been observed only in patients with carcinomas of either the bronchial or the upper digestive tract, with or without cervical and mediastinal lymph node metastases. We report on our third patient with Bazex-type acrokeratosis, mainly because of the uncommon distribution and severity of his otherwise typical lesions. In addition, recent reports on this syndrome in the literature are reviewed.

L-dopa potentiating analogs of Pro-Leu-Gly-NH2 with oral efficacy.

Chemical modification of PLG, comprising replacement of proline or/and leucine by unnatural amino acids led to analogs with high oral efficacy. The most active analog identified in the course of our works was 1-prolyl-2-phenyl-1-2-aminobutanoylglycinamide (Doreptide). Doreptide is presently further evaluated as a new drug for the treatment of Parkinson's disease.

[Noninvasive intraoperative measurement of intracapillary hemoglobin oxygenation and relative hemoglobin concentration in surgical skin flaps]. / Nichtinvasive intraoperative Messung der intrakapillären Hämoglobinoxygenierung und relativen Hämoglobinkonzentration in Hautlappenplastiken.

We describe the Erlangen microconducting spectrometer (EMPHO I), a device that measures the oxygen saturation and relative haemogloblin content in the capillaries. These factors determine the oxygen supply and survival of cutaneous flaps. The EMPHO I was used for intraoperative measurements in pectoralis major myocutaneous flaps and showed reproducible results, so that it is valid for intraoperative monitoring in plastic surgery.

Measurements of angular distributions of Rayleigh and Mie scattering events in biological models.

Remission spectroscopy in living tissues can only be performed because scattering processes induce a pronounced amount of backscattered light. New types of scattering chambers were constructed in order to investigate the angular distribution of light intensities caused by scattering events typical for living tissues. Different solutions and suspensions containing microspheres, haemoglobin molecules, erythrocytes and liver homogenate were used in order to gain basic information applicable to remission spectrophotometry in tissue. Reflection spectroscopy in biological tissues is only possible because of the scattering properties of the material under observation. Light which penetrates the sample is remitted from the tissue. The remission is caused by the scattering of the light by different biological structures and particles. This scattered light gives information about the optical properties of the particles and structures in an integral form. A scattering chamber for small sample volumes has been developed for measurements of the optical properties of various particles in suspension. Measurements of scattering diagrams from microspheres with an average diameter of 7 microns, artificial particles, haemoglobin solutions, mixtures of microspheres and haemoglobin as well as erythrocytes and mitochondria have been performed. The different optical behaviour of the measured signals is qualitatively discussed.

[Labelling meproscillarin with tritium at the C-19 position (author's transl)]. / Radioaktive Markierung von Meproscillarin in der C-19-Methylgruppe mit Tritium.

Labelling of 14-hydroxy-3beta-[4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (meproscillarin, Clift) by introduction of dueterium and tritium at the metabolically stable C-19 position is described.