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Biomedical subjects

R Stadler

Publications and source records attributed to R Stadler.

At least 73 records · Page 4Linked to original sources
PubMed1993

[Cutaneous condylomata acuminata of an unusual site and extent. Successful CO2 laser therapy].

We report on a 33-year-old patient with unusually extensive and predominantly cutaneous condylomata acuminata spreading from the penis over the mons pubis to the entire lower abdominal wall but almost completely sparing the genital mucous membranes. Single lesions were found on the left arm and on the buttocks. Southern blot hybridization detected HPV-6a DNA sequences within the fibroepithelial tumours. Carbon dioxide laser treatment resulted is cosmetically acceptable healing without recurrence.

Abdominal Neoplasms↗
PubMed1992

Epidemiologic evidence for the role of melanocytic nevi as risk markers and direct precursors of cutaneous malignant melanoma. Results of a case control study in melanoma patients and nonmelanoma control subjects.

BACKGROUND: Melanocytic nevi (MN) are markers of melanoma risk, but their potential role as precursors of cutaneous malignant melanoma (CMM) is still controversial. OBJECTIVE: The overall and site-specific relative risk (RR) of developing CMM was evaluated according to site-specific MN counts. METHODS: MN prevalence by anatomic site and by age was compared in 200 CMM patients and in 200 nonmelanoma control subjects; RRs were calculated. RESULTS: In CMM patients both MN and CMM were mainly found on the legs in women and on the posterior trunk in men, whereas in the control subjects most MN were found on the arms. MN counts on the trunk in men and on the legs in women were best predictors of the overall CMM risk (RR: 33-fold and 15-fold, respectively, for greater than 20 vs up to 4 MN). For both genders combined, the RR for CMM developing on the trunk and legs (predominant CMM locations) was best predicted by MN counts in the respective body region (RR: 24-fold and 27-fold, respectively). MN prevalence peaked in the fourth to fifth decade of life and most CMM were diagnosed during the fifth and sixth decades. CONCLUSION: The site-specificity of melanoma risk found for high MN counts on the trunk and the legs and the close similarities in age distribution suggest that the role of MN as direct precursors of CMM has been underestimated and exceeds the number of histologically evident MN associated with CMM.

Adult↗
PubMed1992

Isolation of plasma membranes from keratinocytes: a newly developed method allows the sensitive detection of the membrane antigen pattern in normal and psoriatic skin.

Distinct differences of proteins in the plasma membranes have been described in psoriatic keratinocytes as compared with normal epidermis. These changes are presumably involved in the pathogenesis of psoriasis. To identify and distinguish glycosylated proteins of the plasma membranes of keratinocytes, a method for mild preparation was developed that avoids the use of degrading or digestive enzymes. After cell lysis, three steps of centrifugation were performed, including the use of a sucrose step gradient. A fine-vesicular membrane fraction was obtained. Using marker enzymes for cell compartments, no contamination of cell nuclei or mitochondria and only 0.4% of endoplasmic reticulum was detectable in the final membrane fraction. Based on this preparation, disc-polyacrylamide-gel electrophoresis, followed by Western blotting, were performed. Staining with five different lectins to visualize glycosylated proteins allowed 75 different membrane glycoproteins to be distinguished. The patterns of normal, transformed (HaCaT), foreskin and psoriatic keratinocytes after cell culture with one passage were compared. Up to six proteins per lectin staining were expressed differently in psoriatic as compared to normal keratinocytes. Psoriatic cells shared similarities with highly proliferative foreskin cells, but not with transformed HaCaT cells. Main alterations of glycosylation were detected in the fucose content. In conclusion, the method developed for isolation of plasma membranes allows selective and sensitive examination of plasma membranes of normal and pathological keratinocytes. The glycosylation patterns observed suggest that distinct membrane proteins may be involved in the pathogenesis of psoriasis.

Antigens, Surface↗
PubMed1992

[Combination of interferon-alpha with cytostatic drugs: a potentially successful therapeutic approach in metastatic melanoma].

Pharmacological treatment of disseminated melanoma is characterized by rather low objective response rates with mono- and combined chemotherapy and by significant toxicity. For these reasons, many centres do not now offer any systemic treatment to melanoma patients with distant metastases. Systemic treatment with interferons has not fulfilled all that was expected of it, but type-I interferons (-alpha, -beta) have proved to be effective in about 10-15% of patients treated. The antitumour activity of these substances seems to be related mainly to their antiproliferative effect, whereas no immunomodulatory effects have been substantiated in clinical trials. Combined therapy with interferons and cytostatic drugs was introduced into clinical trials only a few years ago, and the initial results are promising. Large studies with a total of over 200 patients have already been performed to evaluate the combination of interferon-alpha and dacarbazine. This treatment was effective in around 50% of the patients, complete or partial remission being achieved in 30% and stabilization of the disease, in 20%. Toxicity is significant, but still manageable; the new generation of antiemetic drugs (serotonin receptor blockers), in particular appears promising. Up to now, no improvement of efficacy has been found following addition of interferon-alpha to cisplatin in four clinical trials. In a study in our own department, however, the combined action of interferon alpha and vindesine was found to be superior to that of either used as a single agent, and the combination was well tolerated on an outpatient basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1992

Combined treatment of metastatic melanoma with interferons and cytotoxic drugs.

The treatment of disseminated melanoma with monotherapy and combined chemotherapy is still associated with rather low objective response rates and significant toxicity. Therefore, more effective substances and regimens with less toxicity are desired in the pharmacologic treatment of metastatic melanoma. The initial high expectations placed in systemic cancer treatment with interferons (IFNs) were not fulfilled, but IFN-alpha as a single substance revealed an objective response rate of 10% to 15% in melanoma patients. Clinical and experimental results suggest that the antitumoral activity of IFNs is mainly related to their antiproliferative effect, whereas immunomodulatory effects were not substantiated in clinical investigations. Results of in vitro trials showed that type-I IFNs may produce antagonistic effects combined with some agents (eg, cisplatin) and synergistic effects combined with others (eg, vindesine and BCNU). Clinical trials with combined IFN and cytostatic drug therapy were started a few years ago and have yielded promising initial results. Several studies with an entire number of more than 200 patients have already been performed to evaluate the combination of IFN-alpha and dacarbazine. This regimen was effective in over 50% of the patients, leading to complete or partial remissions in 27% and stabilization of the disease in an additional 28%. Toxicity is significant but still manageable, especially with a new generation of antiemetic drugs (serotonin receptor blockers). Several clinical trials performed so far did not find an improved efficacy by adding IFN-alpha to cisplatin or to vinblastine. The combination of IFN-alpha and vindesine seems to be more favorable and superior to the response rates of single agents and was well tolerated in an ongoing trial in our clinic. Recently, a new generation of multidrug combinations including IFN-alpha has been initiated and several reports with overall response rates greater than 50% have been published. In conclusion, combined regimens with IFN-alpha and different cytostatic drugs seem to be superior to treatments with cytostatic drugs alone and rather safe in disseminated melanoma. Additional combinations of IFNs and cytostatic drugs should be evaluated in future in vitro studies and in clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Combination therapy with interferon alfa 2a and PUVA in cutaneous T-cell lymphoma].

Eleven patients with cutaneous T-cell lymphoma stages Ib-IV a were treated with a combination of interferon alfa-2a and photochemotherapy. The diagnosis was confirmed by histological and immunohistological investigations. During the initial treatment, interferon alfa-2a was given at a maximum dose of 9 million IU 3 times a week. Few patients received for a short time 9 million IU daily s.c. The total dose amounted to an average of 125 million IU. Simultaneously, photochemotherapy with a maximum single dose of 2 J/cm2 was applied. The total dose ranged between 7 and 62.9 J/cm2, which corresponds to an average dose of 22.6 J/cm2. After achieving a complete or partial remission the dose of interferon was reduced to 1.5 or 3 million IU, which was then maintained for long-term treatment 2 or 3 times a week. Photochemotherapy was given twice weekly for a minimum of 2 months and then stopped, depending on the course of the disease. The success of therapy was judged from the clinical and histological picture. The combination treatment was well tolerated and led to complete remission in 5 patients (45%) and a partial remission in 6 patients (55%) after the initial therapy which lasted for an average of 48 days. During the follow-up period, which now amounts to 2-13 months with under 1.5 or 3 million IU interferon, three patients have shown disease progression. One patient responded well to newly applied photochemotherapy and in two patients local tumors regressed after radiation.

Aged↗
PubMed1992

[Multiple woolly hair nevi with linear epidermal nevus and persistent pupillary membrane].

The woolly hair nevus is a very rare disease that only occurs sporadically. So far, approximately 48 patients with woolly hair nevus have been described in the world literature. Both sexes are equally affected. Mostly, the dermatosis manifests itself from birth or within the first 2 years of life. Up to 5 circumscribed areas with clearly lighter curly hairs can be observed. About 50% of the patients present a linear epidermal nevus at the same time. Microscopically, the hair shaft diameter of the woolly hair is significantly reduced. Next to oval structures the cross-sections of the hair often show triangular and irregular forms. Furthermore, pili canaliculi and pili torti as well as circumscribed cuticula defects can be observed. We present a 5-year-old boy, who manifested 4 woolly hair nevi on the capillitium in the 9th month of life. From the 2nd year of life onwards he developed a linear epidermal nevus. The ophthalmological examination showed a persistent pupillary membrane. Based on this case and a bibliographical overview, the light and electron microscopical peculiarities are presented.

Biopsy↗
PubMed1991

Normal psoriatic epidermis expression of hyperproliferation-associated keratins.

Keratin expression in lesional, marginal and uninvolved psoriatic epidermis was analysed by one- and two-dimensional gel electrophoresis and immunoblotting. Keratins K1, K5, K6, K10, K14, and K16 were identified in lesional epidermis. Keratins K6 and K16 were found in all epidermis probes of uninvolved skin, but never occurred in normal epidermis of control skin samples. By means of laser-densitometric evaluation of one-dimensional gels a downregulation of K1 and K10 and an upregulation of K6 and K16 was found in psoriatic epidermis. Unexpectedly, the level of K5 was considerably lower and the level of K14 considerably higher in lesional skin than in normal epidermis. These results demonstrate that not only basal keratinocytes in lesional epidermis but also suprabasal keratinocytes in uninvolved psoriatic epidermis express an altered differentiation pattern. The latter phenomenon could be very important in understanding the development of the so-called "Köbner effect" in psoriatic epidermis.

Adult↗
PubMed1991

Long-term therapy of HIV-associated Kaposi's sarcoma with recombinant interferon alpha-2a.

Five young male patients with HIV-associated Kaposi's sarcoma (KS) were treated with recombinant interferon alpha 2a (rIFN-alpha-2a) over a period of 2-2.5 years. An IFN dose of 18 x 10(6) IU was given subcutaneously every day during the first 3 months of treatment and then on alternate days. Additional treatment with radiotherapy and laser therapy was given and, in some cases, isolated skin nodules were excised. Within 7 months of initiation of therapy one patient had a complete remission of his tumours, however, tumour progression recurred after the patient discontinued treatment. In another patient the tumour cleared within 9 months of rIFN therapy, and after 52 months he is still free of KS. The condition of a third patient tended to become stabilized during the first 6 months of therapy, but after 60 months there has been a slow progression. The fourth and fifth patients died 25 and 28 months, respectively, after the histological diagnosis of KS and the initiation of treatment. While on therapy with rIFN-alpha-2a, no life-threatening opportunistic infections occurred. The side-effects were mostly well tolerated, and no severe changes in haematological parameters were caused by the therapy.

Adult↗
PubMed1991

[Nevus associated malignant melanomas--diagnostic validation and prognosis].

The diagnosis and prognosis of naevus-associated malignant melanomas are examined in the present study. For this purpose, 581 cases of primary malignant melanoma seen in the University Department of Dermatology, Berlin Steglitz, were histologically investigated for naevus association. A naevocytic association was proven in 135 (23%) of the malignant melanoma biopsies. Naevocytic malignant melanomas were found at a significantly higher rate (P less than 0.01) in patients under 50 years of age. The 5-year survival rate for naevocytic melanomas was not significantly different from that for other malignant melanoma types: around 80% in both groups. An immunohistological evaluation of the diagnosis of naevus-associated melanoma was also performed on the basis of specimens from 89 melanocytic lesions. The use of HMB-45 for diagnosis of melanocytic tumours made it possible to differentiate resting dermal naevus cells from malignant melanoma infiltrates in paraffin sections in the present study, thus simplifying the diagnosis of naevus-associated malignant melanomas. However, dysplastic naevi, junctional naevi and juvenile melanomas are also stained by HMB-45, which means that malignant melanomas associated with junctional melanocytic naevi still cannot be reliably identified even today.

Adult↗
PubMed1990

Effect of retinoids on hyperproliferation-associated keratins K6 and K16 in cultured human keratinocytes: a quantitative analysis.

The keratin patterns of human epidermal keratinocytes cultured on a 3T3-feeder layer in the presence of 10(-8) M non-aromatic (all-trans retinoic acid and 13-cis retinoic acid) and polyaromatic (arotinoid, arotinoid-sulfone, and free arotinoic-acid) retinoids were analyzed by high resolution one- and two-dimensional gel electrophoresis and immunoblotting. Laser densitometric evaluation of one-dimensional gels allowed to quantitate the changes within the keratin patterns and revealed an increase in the expression of keratins K13, K15, and K19 as induced by both non-aromatic and polyaromatic retinoids, except for the parent compound arotinoid. This would then indicate that such keratinocytes are pursuing a more embryonic type of differentiation. In evaluating the data for the hyperproliferation-associated keratins K6 and K16 we noticed an unexpected result: except for all-trans retinoic acid, these two keratins showed opposite responses. As compared to control cultures, the amount of K6 did generally increase, while K16 was reduced, with arotinoid acid being the most effective retinoid. The apparently uncoupled expression of K6 and K16 appeared also to be concentration dependent when 13-cis retinoic acid at concentrations of 10(-9), 10(-8), and 10(-7) M was analyzed. Considering the overall antiproliferative potency of retinoids, we therefore conclude that K16 alone, rather than the pair K6/K16, should be regarded as a proliferation-related keratin and as such may be used as a sensitive marker to evaluate keratinocyte proliferation.

Antibodies, Monoclonal↗
PubMed1990

Long-term combined rIFN-alpha-2a and zidovudine therapy for HIV-associated Kaposi's sarcoma: clinical consequences and side effects.

Interferon alpha (IFN-alpha) has been shown to be effective in treating HIV-associated KS in at least 30% of patients, and Zidovudine has proved beneficial for AIDS patients. Moreover, both drugs have demonstrated an inhibitory effect on HIV replication. Based on the above, we combined IFN-alpha and zidovudine for treatment of HIV-associated KS in order to evaluate tolerance and clinical efficacy. Twenty-one homosexual men with histologically proved HIV-associated KS were treated in an open trial with rIFN-alpha-2a 18 X 10(6) IU every second day and zidovudine 800-1200 mg/d. Treatment was discontinued within the first month in six patients: three of them developed subjective intolerance, and three others contracted severe opportunistic infections or HIV-cachexia. Fifteen evaluable patients received combination treatment over a period of 2-20 months (average 10 months). The dosage was reduced as required based on drug-induced cytotoxicity. Complete remission was observed in four patients, partial remission in three, stable disease in two, and progression in six, resulting in an overall response rate of 46%. Negative p24 expression prior to treatment was a positive predictor. Although extracutaneous involvement had a negative influence on tumor remission, even patients with a mean initial T-helper cell count below 100 mm3 responded positively. In conclusion, combination therapy of rIFN-alpha-2a with AZT may effectively control HIV-related Kaposi's sarcoma in more than 40% of patients. In contrast to monotherapy with IFN-alpha, patients with severely reduced immune systems will also benefit from combined treatment.

Adult↗
PubMed1990

Antitumor activities of interferon alpha, beta, and gamma and their combinations on human melanoma cells in vitro: changes of proliferation, melanin synthesis, and immunophenotype.

The antitumor activities of human interferon (IFN) alpha, beta, and gamma alone or in combination were studied on four human melanoma cell lines (StML-11, StML-12, StML-14, and SKMel-28) in various concentrations (1-50,000 IU/ml IFN alpha, 0.1-1000 IU/ml IFN beta, 1-10,000 IU/ml IFN gamma) in vitro. In all experiments IFN beta exhibited the most potent antiproliferative effect of all IFN tested. After 3 d of incubation a 50% growth inhibition was achieved with 20-40 IU/ml for natural IFN beta and with 600-1200 U/ml for recombinant IFN gamma. Substantially higher doses (7,000 to more than 50,000 IU/ml) of recombinant IFN alpha 2a were required to achieve a 50% growth inhibition. A strong synergistic antiproliferative activity resulted from the combination of IFN alpha with IFN gamma and IFN beta with IFN gamma. None of the IFN tested induced terminal differentiation of melanoma cells in vitro. The formation of dendrites was inhibited, and the portion of differentiated cells in vitro was reduced after treatment with IFN in comparison to the untreated controls (untreated controls: 100%; portion of differentiated cells after treatment with IFN alpha: 58%-74%, IFN beta: 48%-96%, IFN gamma: 10%-33%). The melanin synthesis was slightly elevated after treatment with IFN alpha (untreated controls: 100%; after treatment with IFN alpha: 103%-157%, ns.) and decreased significantly after treatment with IFN beta (49%-71%, p less than 0.05) as well as with IFN gamma (80%-88%, ns.). Cell surface markers were modulated varyingly by the IFN: HLA-I antigens were enhanced by all IFN, with IFN beta emerging as the most potent inducer. Only IFN gamma, however, induced a de novo expression of HLA-DR and -DQ antigens and increased the expression of the ICAM-1 molecule and of the melanoma progression marker A.1.43. Possibly, these findings indicate a biologically more aggressive phenotype of melanoma cells.

Cell Differentiation↗
PubMed1990

Initial hyperproliferation and incomplete terminal differentiation of cultured human keratinocytes from lesional and uninvolved psoriatic skin.

Human epidermal keratinocytes (KCs) were isolated from lesional and from uninvolved skin of 8 patients with chronic plaque-like psoriasis and from the normal skin of 8 healthy volunteers. Primary KC cultures, grown on 3T3 cell feeder layers, were examined over a period of 4 weeks and their plating efficiency, colony growth area, DNA synthesis and ultrastructural cell differentiation were evaluated. Psoriatic KCs formed colonies one day earlier than non-psoriatic controls and proliferated faster during the first 2 weeks, as assessed by the mean colony growth area and 3H-thymidine incorporation. After 4 weeks, however, no significant differences were observed between the in vitro proliferation parameters of normal and psoriatic KCs. At the ultrastructural level, cultures of lesional psoriatic KCs consisted of more cell layers with adherent transitional cells and incomplete formation of cornified envelopes, even after 4 weeks, while KCs from uninvolved psoriatic skin were characterized by a transient delay of in vitro maturation. These results indicate that the characteristic hyperproliferation of psoriatic KCs may only be maintained over a short period of primary culture, whereas defective terminal differentiation of lesional psoriatic KCs was maintained throughout the culture period.

Biopsy↗