Biomedical subjects

R Stadler

Publications and source records attributed to R Stadler.

At least 91 records · Page 5Linked to original sources

PubMed1990

[Interferon therapy in malignant melanoma].

Recent clinical trials on the systemic application of various forms of interferon in metastatic malignant melanoma showed a moderate response rate of about 11% on an average. Intralesional application of alpha- and beta-interferon, however, resulted in partial or complete regression of the metastases in approx. 50% of the tumors. At present, various combination studies are being carried out in order to enhance the anti-tumor effects of interferon and thus establish a potential therapeutic method in dermato-oncology. In this respect, the combination of alpha-interferon with classic cytostatic drugs (dacarbazine and vindesine) is especially encouraging.

Cell Division↗

PubMed1990

[Pustular arthro-osteitis. Pustulosis palmaris et plantaris with arthritis of the sternoclavicular joint].

A 26-year-old female patient presented with pustulosis palmaris et plantaris simultaneously with arthritis of the sternoclavicular joint. This association is described as an entity and is called pustulotic arthroosteitis in the Japanese literature, as well as in publications from Scandinavia. To our knowledge, this is the first observation in the Federal Republic of Germany.

Adult↗

PubMed1990

[Kyrle disease in juvenile diabetes mellitus and chronic renal failure].

We report on a 32-year-old female patient with chronic diabetes mellitus, type I, and chronic renal failure, who developed the typical clinical picture of hyperkeratosis follicularis et parafollicularis in cuteum penetrans (Kyrle's disease) within one year. Histological examination revealed a defective epidermal differentiation with hyper- and parakeratosis as well as premature keratinization as early as in the epidermal basal cell layer. Studies on lectin binding showed that the glycosylation process was impaired in both the epidermis and the basement membrane zone of the lesional skin. In addition, electron microscopic investigation revealed diabetic microangiopathy of the dermal vessels as well as marked ultrastructural alterations of the dermo-epidermal basal lamina. These findings confirm the association of diabetes mellitus with Kyrle's disease previously described; they make us suggest that Kyrle's disease might be characterized by a defective differentiation of the epidermis and the dermo-epidermal junction--due to some alteration of the underlying glycosylation processes--rather than by a local disorder of keratinization. Regarding the clinical manifestation of the disease, both diabetes mellitus and chronic renal failure may play a part as precipitating factors.

Adult↗

PubMed1989

[Maturation and aging of elastic fibers].

We give a review of the maturation and aging processes of elastic fibers. Elastic fibers of adult human skin are composed of elastin (amorphous matrix) and surrounded by microfibrils (structural glycoproteins). The physiological aging of elastic fibers is a continuous process starting at the age of 40 or 50 and reaching its final state in the senium. This process is characterized by the following morphological changes: (1) decreasing number of microfibrils, (2) occurrence of osmiophilic inclusions, and (3) fragmentation and disintegration of the fibers. These alterations are due to reduced synthesis of elastin and increased deposits of lipids and calcium. As a result, the elastic fibres show increased susceptibility towards proteolytic enzymes.

Actin Cytoskeleton↗

PubMed1989

Interferons in dermatology.

Interferons are a large family of proteins and glycoproteins, naturally occurring or artificially produced by recombinant biotechnology. Their antiviral, antiproliferative, antitumoral, and immunomodulatory activities are induced by alterations in cell metabolism after binding to specific membrane receptors. Interferons have been used for the treatment of viral papillomas (e.g., verruca vulgaris and condyloma acuminatum), human immunodeficiency virus (HIV)-associated Kaposi's sarcoma and cutaneous tumors (e.g., melanoma, cutaneous T cell lymphoma, and basal cell carcinoma), and inflammatory dermatoses (e.g., Behçet's syndrome and psoriatic arthropathy). Clinical trials have been performed worldwide with various regimens and have not always led to conclusive results. In our experience long-term therapy with high doses of subcutaneously injected, recombinant interferon-alpha-2a in patients with HIV-associated Kaposi's sarcoma induces a remission or stabilization of the disease. In malignant melanoma a low response rate is obtained in metastatic disease with the use of interferon as a single therapeutic agent. Combined with other antitumor agents, however, interferon seems to be a useful drug. Excellent control of Behçet's disease has been obtained, and the treatment of condylomata acuminata has been effective.

Humans↗

PubMed1989

Effects of azelaic acid on proliferation and ultrastructure of mouse keratinocytes in vitro.

The effects of azelaic acid (C9-dicarboxylic acid, AZA) on the proliferation and ultrastructure of neonatal NMRI mouse keratinocyte cultures were studied to clarify the mechanisms of AZA action on normal and diseased epidermis. The dose- and time-dependency of the drug effects on DNA synthesis was examined by 3H-thymidine incorporation into DNA and by autoradiography. Electron microscopy was used to detect the target cell organelles of the drug. Azelaic acid decreased DNA synthesis in a dose- and time-dependent manner with a 50% inhibitory concentration of 20 mM. The inhibition of DNA synthesis was already observed after 1 h of treatment, reached its maximum after 4 h, and was stable for 24 h. A complete reversibility of the inhibitory effects was observed within 2 h after discontinuation of the treatment, and, interestingly, a rebound effect occurred with a temporary increase of DNA synthesis. Furthermore, treatment with AZA reduced the RNA and protein synthesis of the cells. Electron microscopic evaluation of treated cultures showed early marked damage of the mitochondria, followed by dilation of the rough endoplasmic reticulum (RER). These alterations were completely reversible after discontinuation of the treatment. Our findings show that AZA exerts a dose- and time-dependent, reversible antiproliferative effect on keratinocytes, acting primarily on mitochondria and RER. The antiproliferative action of AZA could explain its beneficial effect in some skin disorders characterized by alteration of keratinocytic differentiation.

Animals↗

PubMed1989

A rapid fluorometric assay for the determination of keratinocyte proliferation in vitro.

In the present study we describe a simple technique for the determination of keratinocyte proliferation in vitro, based on the hydrolysis of a fluorogenic substrate by cell esterases. Normal and transformed human keratinocytes were grown in microtiter plates and were incubated with 4-methylumbelliferyl heptanoate after 3, 5, and 7 days. The fluorescence was quantified using an automatic fluorescence detection unit. The fluorescence showed a strong correlation with the cell number at various growth phases. In addition, the method reliably detected the growth inhibitory effect of recombinant interferon gamma on human keratinocytes. The fluorometric assay is a simple, fast and reliable method to assess cell number in keratinocyte cultures.

Cell Count↗

PubMed1989

Markers and relative risk in a German population for developing malignant melanoma.

The relationship between cutaneous malignant melanoma (MM) and possible risk factors was assessed in a case-controlled study. Two hundred patients and 200 non-melanoma controls of German origin matched for age and sex were interviewed and examined for pigmented moles and pigmentation characteristics. In patients with MM significantly more melanocytic nevi greater than or equal to 2 mm (MCN) were found (mean, 53 MCN) compared to control cases (mean, 18 MCN). For persons with greater than 60 MCN the relative risk (RR) for developing MM increased 15 times compared to less than or equal to 10 MCN. Additional independent markers for an increased risk were presence of atypical MCN (RR = 7 vs. none) found in 45% of patients and in 5% of the control group, moderate to large numbers of actinic lentigines (RR = 6.2 vs. none), and lack of tanning as well as a tendency to sunburn (skin type I; RR = 2.2 vs skin type IV) No significant correlation was found between the relative risk for MM and hair color, eye color, duration of free time sun exposure and number of sunburns. Individuals with permanent outdoor profession and sun exposure, however, showed a clearly increased relative risk for developing MM.

Age Factors↗

PubMed1989

[Spectinomycin resistant gonococcal infections in West Germany. Detection in 7 patients and occurrence of post-gonorrheal epididymitis caused by the spectinomycin-resistant PPNG strain].

Seven patients (four men, three women) with gonococcal urethritis resistant to spectinomycin treatment were seen in May and June 1989 in the Department of Dermatology in Berlin (West), and strains of Neisseria gonorrhoeae (NG) resistant to spectinomycin were detected, cultured in vitro from these individuals. In five of the seven patients penicillin-resistant strains were found, including a penicillinase-producing strain in one case; the other two patients had penicillin-sensitive strains. In all cases the NG-populations detected were sensitive to cephalosporin and cipro(oxo)floxacin. In a 17-year-old young man with the PPNG strain severe gonococcal epididymitis developed after repeated infection that had been inadequately treated with spectinomycin. All seven patients mentioned sexual contact with individuals who lived in Southeast Asia or had their origins there; in at least four cases the contact persons came from Thailand. This is the first report on spectinomycin-resistant Neisseria gonorrhoeae infections (PPNG and non-PPNG) in the Federal Republic of Germany. The necessity for monitoring the results of penicillin and/or spectinomycin treatment of gonorrhoea are underlined for the dermatovenereologist, and some guidelines for therapy are given.

Adolescent↗

PubMed1989

Isolation of human sebaceous glands and cultivation of sebaceous gland-derived cells as an in vitro model.

An experimental technique is presented as an in vitro model for the study of human sebaceous gland-derived cells. Intact sebaceous glands were isolated from full-thickness human skin after incubation in dispase (2.4 U/ml) and in deoxyribonuclease (0.02%) by using microsurgical instruments under microscopical observation of the epidermal underface. Subsequently, the ducts of the glands were removed, the isolated gland lobules were seeded on a 3T3-cell feeder layer in Dulbecco's modified Eagle's medium and Ham's F 12 medium (3:1) supplemented with fetal calf serum (10%), L-glutamine, antibiotics, epidermal growth factor (10 ng/ml), hydrocortisone (0.4 microgram/ml), and cholera toxin (10(-9) M), and were then cultivated in a CO2-incubator at 37 degrees C. After 2-3 wk cell outgrowths resulting from the periphery of the gland lobules were obtained and dispersed cells were passaged for three subcultures with or without 3T3-cell feeder layer. The cultured cells preserved in vitro morphologic characteristics and differentiation patterns comparable to those described for normal human sebocytes in vivo, with a high rate of viable cells. Their labeling pattern with MoAb showed close similarities to the pattern reported for sebocytes in vivo but differences to the pattern of keratinocytes in vivo and in vitro. In their cytoplasm oil red and nile red stained droplets were detected, and the observed density and distribution evidenced in vitro lipogenesis. The technique presented here may provide a promising model for further experimental studies on sebaceous gland cell development and function.

Antibodies, Monoclonal↗

PubMed1989

[Borrelia burgdorferi-induced pseudolymphoma with pathogen cultivation in an HIV-1 positive patient].

Cutaneous symptoms and skin diseases are common findings in almost all HIV-1-positive patients. In many cases the clinical presentation and course of the skin diseases are atypical, and occasionally the development of the appropriate circulating antibodies is lacking or impaired. In this report we present a patient seen in our multidisciplinary outpatient clinic for HIV patients. This patient had a Borrelia burgdorferi infection with an unusual course. The acute inflammatory phase of the arthropod reaction was maintained over a period of 9 months with development into pseudolymphoma showing unusual cytological characteristics. Immunohistological evaluation revealed an almost complete lack of T-helper and Langerhans cells, but an increased number of activated cytotoxic cells with class II antigen expression. A marked serological response was observed on IgG-ELISA and in the IgG-immunofluorescence test. Borrelia burgdorferi was cultured in vitro from a skin biopsy of the involved area. To our knowledge this is the first reported case of skin borreliosis in an HIV-1-positive patient.

Bacteriological Techniques↗

PubMed1989

[Adjuvant therapy with recombinant interferon alfa-2a in metastasized malignant melanoma].

Recombinant alpha-2a interferon (IFN alpha-2a; Roferon-A) was administered as adjuvant therapy in 21 patients with malignant melanoma stage IIa or IIb after surgical removal of all detectable metastases. Patients received 9 x 10(6) units of IFN alpha-2a s.c. 3 times weekly over 6 months. One patient was treated over 12 months. Relapses occurred in 5 of the 21 patients during therapy, and 10 patients developed new metastases a few weeks or months after the end of therapy. Of the 15 patients with recurrent disease, 9 have since died. One patient without any relapse died of a myocardial infarction 5 months after the start of therapy. Comparison of the 21 treated patients with an untreated historical matched control group did not show any prolongation of the recurrence-free period in the interferon-treated group.

Adolescent↗

PubMed1989

[Local recurrence and metastasis of thin malignant melanomas (less than or equal to 1mm)].

A total of 704 patients with malignant melanoma (MM) were documented in our clinical registry at the Department of Dermatology in Berlin from 1969 to 1987. At the time of first diagnosis 631 patients in this group were found to have clinical stage I disease, and complete histological reports were available for 516 of these cases. Of the 516 patients, 191 had thin MM (less than or equal to 1 mm) and in 10% of this group local recurrences or distant metastasis were seen. Nevertheless, recurrences were delayed in patients with thin MM compared with those with thicker MM (greater than 1 mm) (mean: thin MM 37 months, thicker MM 17 months), and patients with thin MM died of distant metastasis after longer time periods (mean: thin MM 67 months, thicker MM 33 months). The thinnest tumours followed by distant metastasis and death measured 0.40 mm and 0.45 mm in male and 0.63 mm and 0.72 mm in female patients. For thin MM, wide surgical total excision with safety margins (3-5 cm) was performed in 151/191 patients. No local recurrences were observed in this group, but primary lymphogenous and/or haematogenous metastasis was recorded in 12 patients (= 8%). Narrow surgical excision (less than or equal to 1.5 cm safety margin) was performed in 37/191 patients with thin MM; 6 patients (= 16%) in this group developed local recurrences, and in 2 of those lymphogenous or haematogenous metastasis occurred later. Another patient in this group showed primary haematogenous metastasis. Of 6 patients with local recurrences, 1 died of MM 13 years after the first diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Follow-Up Studies↗

PubMed1988

[Acute primary phase as an indicator of HIV-1 infection. The general symptoms and polymorphic exanthema with mouth mucosal involvement 2 to 6 weeks before seroconversion].

The initial symptoms of an HIV-1 infection were observed in four patients. The following were characteristic for the acute primary phase: (a) initial maculopapular exanthema, especially of the trunk, with occasional transition into a papulovesical appearance; (b) involvement of the oral mucosa, often of aphthous character; and (c) general malaise with fever and lymphadenopathy. The observed cutaneous changes had, on one hand, features of a Coxsackie or mononucleosis exanthema, on the other of secondary syphilis. In three patients seroconversion occurred within 2-6 weeks, the fourth failed to return for follow-up. The listed acute primary symptoms can be used as the earliest indicators of an HIV-1 infection having occurred.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Electrophysiological and ultrastructural studies on reversible neural conduction disturbance after high voltage discharge.

High-voltage condenser discharges exerting a field strength of up to 1000 V/cm (discharge time constant 0.24-8 msec) applied to isolated sciatic frog nerve lead to disturbances of the propagation of action potentials including transient complete block of conduction. Such conduction disturbances are normally reversible within minutes. Inhibition of the activity of the membrane-bound Na+-K+ATPase prevents the recovery from conduction block. Withdrawal of external Ca2+ also prevents recovery, whereas blockade of protein synthesis by cycloheximide has no influence. The velocity of recovery depends on the temperature, with temperature coefficients (Q10) from 1.31 to 1.84 between 2 degrees and 30 degrees C. Transmission electron microscopy of nerves subjected to strong discharges shows alterations of the myelin sheath (splitting and cleft formation) which are, however, not specific for this mechanism of injury. No alterations are seen in the region of the free axoplasmic membrane of the node of Ranvier or in organelles. The results suggest a breakdown of the transmembrane ionic gradient causing the conduction disturbance.

Action Potentials↗

PubMed1988

[High resolution real time sonography in sports specific muscle injuries. Sonomorphologic-anatomic correlation and diagnostic criteria].

In 250 examinations of 86 patients, high resolution real time sonography with a 7.5 MHz linear transducer proved to be a readily available, low-cost and significantly relevant imaging method in diagnosis and follow-up of muscular lesions in sportsmen. The method offers a high measure of safety in excluding rupture or in enabling differential diagnosis between partial muscular rupture and muscular spasm, so that the choice of treatment can be decisively influenced by sonography. Hence, rapid rehabilitation, which is so essential in competitive sport, is speeded up even further. In extensive ruptures or rupture haematoma, therapeutic ultrasound-guided puncture can be performed or indication for surgery can be facilitated in subtotal or complete tears of a muscle that is important for high-level performance.

Athletic Injuries↗

PubMed1988

[Therapy of AIDS-induced Kaposi sarcoma and malignant melanoma with interferons].

Since 1980, disseminated Kaposi's sarcoma has been occurring in new epidemic proportions with a rapid clinical course in risk populations. Sixteen cases were under therapy and close surveillance from 1982 to 1986. Eight are still under therapy. In disseminated Kaposi's sarcoma with acquired immune deficiency syndrome (AIDS) our experience was encouraging. Following systemic, long-term treatment with recombinant alpha 2a interferon we observed complete remission of the lesions in 2 cases, partial remission and stabilization of the disease in 3 cases, at least temporary stabilization of the disease in 3 cases and progressive disease in 8 cases. Systemic rIFN-alpha 2a therapy was well tolerated; its long-term administration in patients with a relatively good immune status has an obviously beneficial effect on the course of Kaposi's sarcoma. In metastatic malignant melanoma Stage IV the results were only moderately encouraging. Regression of cutaneous metastases in 1 case and long-term stabilization of the disease in another patient point to antitumor activity of interferon in disseminated malignant melanoma. However, the administration of rIFN-alpha 2a in earlier stages appears more promising.

Acquired Immunodeficiency Syndrome↗

PubMed1988

[Adjuvant chemotherapy of malignant melanoma with DTIC. Lack of effect in stage I. Possible improvement of the prognosis for survival in stage IIb].

Out of more than 600 melanoma patients on whom records have been kept in the clinical registry of our department since 1969, 153 were treated by adjuvant chemotherapy with dacarbazine from 1977 to 1984. In 50 patients treatment was discontinued after 1-3 cycles of chemotherapy; all of the others underwent 4 or more cycles. From the latter group (n = 103) patients with the primary tumour alone (stage I) or with macroscopic nodal involvement of one region (stage IIb) were selected for evaluation. In stage I the overall survival rates were significantly better in 143 untreated controls than in 72 patients treated with dacarbazine; no significant differences were found for disease-free intervals. In the treated group the major prognostic factors were more significant (tumour thickness, localization, sex). Statistical analysis of 26 matched pairs corresponding in respect to tumour thickness, sex and anatomical site of the primary tumour revealed no significant differences in survival rates or disease-free intervals. Also, no difference was found when 23 patients with thick tumours (greater than or equal to 3 mm) adjuvantly treated with dacarbazine were compared with an untreated control group of 48 patients. In stage IIb 26 patients were treated and were compared with 64 untreated controls; they seemed to benefit from DTIC chemotherapy, showing a 5-year survival rate of 40% versus 18% for the untreated control group (P = 0.028).

Combined Modality Therapy↗