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Biomedical subjects

G Rassner

Publications and source records attributed to G Rassner.

At least 19 recordsLinked to original sources
PubMed1992

Demonstration of proteases in basal cell carcinomas. A histochemical study using amino acid-4-methoxy-2-naphthylamides as chromogenic substrates.

BACKGROUND: Proteases are reported to play an essential part in the proliferative, invasive, and metastasizing behavior of malignant tumors. The aim of the current study was to determine the activity and localization of proteases in basal cell carcinomas (BCC) histochemically. METHODS: Various proteases were identified histochemically in frozen sections of BCC. The following amino acid-4-methoxy-2-naphthylamides (MNA) were used as chromogenic substrates:alanine-MNA for the detection of aminopeptidase M (APM), glycyl-proline-MNA for dipeptidyl peptidase IV (DPP IV), lysyl-proline-MNA and lysyl-alanine-MNA for dipeptidyl peptidase II (DPP II), glycyl-arginine-MNA for dipeptidyl peptidase I (DPP I), and carbobenzoxy (CBZ)-arginyl-arginine-MNA for cathepsin B. RESULTS: APM activity was high in the peritumorous connective tissue, whereas the tumor epithelium and epidermis had negative results. DPP IV showed a highly positive reaction in both tumor epithelium and surrounding connective tissue. Cathepsin B and DPP I reacted strongly in the tumor epithelium but not in the peritumorous connective tissue. CONCLUSIONS: The marked activity of APM, DPP IV, DPP I, and cathepsin B may be related to the proliferation and invasive growth of BCC. The distribution of the activity of APM and DPP IV indicates dynamic interactions between the tumor epithelium and the adjacent connective tissue in the neoplastic process.

2-Naphthylamine↗
PubMed1992

The prognosis of primary and metastasising melanoma. An evaluation of the TNM classification in 2,495 patients.

The prognostic value of the TNM classifications of the UICC dated 1978 and 1987, was investigated in a population of 2,495 patients who were followed up over the long term. In the case of primary melanoma, Breslow's tumour thickness proved to be the most powerful predictor of patient survival in multivariate analysis, while the significance of Clark's level ranged after that of both localisation of the primary tumour and the sex of the patient. The continuous proportional relationship between tumour thickness and risk of death makes it possible to regrade thickness groups. Grading cutoffs at 1, 2 and 4 millimetres, with no account being taken of depth of invasion, proved to be particularly favourable for a classification in accordance with prognostic criteria. In advanced stages of the disease, the outcome of locoregional and distant metastasis is significantly different; and furthermore in the case of locoregional metastasis, in-transit and satellite metastases exert a significantly better prognosis than regional lymph node involvement. Isolated juxtaregional lymph node metastases occurred primarily or during the course of the observation period in only 19 patients of our group, and, in comparison with visceral metastases, proved to have only an insignificantly better prognosis. For this reason, it would appear meaningful to assign them to a common stage. On the basis of these results, proposals are made for modifications of the TNM classification.

Evaluation Studies as Topic↗
PubMed1992

Determination of 2'-5'-oligoadenylate synthetase in serum and peripheral blood mononuclear cells before and after subcutaneous application of recombinant interferon beta and gamma.

The interferon-inducible enzyme, 2'-5'-oligoadenylate synthetase, was estimated in healthy donors and in patients before and after subcutaneous application of recombinant interferon beta and gamma. Tests were carried out with lysates of peripheral blood mononuclear cells, using an established radioenzymatic assay, and in serum samples, using a new radioimmunoassay. Both test systems substantially yielded the same results: after a single injection of interferon beta (1-5 x 10(6) IU), 2'-5'-oligoadenylate synthetase increased in a dose-dependent manner reaching maximal catalytic concentrations in most patients after 24-48 hours (leukocytes) and 48-72 hours (serum). In contrast, interferon gamma (2-4 x 10(6) IU) caused only a small induction of 2'-5'-oligoadenylate synthetase. However, daily application of interferon gamma for 7 days led to a distinct time-dependent increase of 2'-5'-oligoadenylate synthetase activity concentration during this observation period. Characteristically, even during daily application, the 2'-5'-oligoadenylate synthetase activity concentration dropped just 48-72 hours after the first injection of interferon beta. The determination of 2'-5'-oligoadenylate synthetase proved to be useful for optimizing and monitoring subcutaneous therapy with interferon. The new radioimmunoassay which allows the determination of this enzyme in serum is superior to other methods used in the past.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

[Condylomata acuminata in children--detection of HPV 6/11 and 2. Local therapy with interferon-beta hydrogel].

Four cases of genital warts in children (girls) are reported. HPV 6/11-DNA was identified in two cases, and HPV 2-DNA in one. In one case no virus identification was possible. The clinical features of the HPV 2-induced genital warts showed the typical morphology of condylomata acuminata. The mode of transmission of the virus, in absence of sexual contact, could not be explained. The HPV 2-associated genital warts might have been transmitted by autoinoculation from warts on the hands. Topical treatment with IFN-beta-hydrogel was applied over 8 weeks, either as single-agent therapy (1 case) or as adjuvant therapy after removal of the condylomata (3 cases). No remission was seen with the single-agent therapy. In one case the genital warts reappeared after adjuvant therapy, but in the other two cases no recurrence was seen.

Administration, Topical↗
PubMed1992

[Neuron-specific enolase (NSE)--a suitable tumor marker in malignant melanoma?].

The neuron-specific enolase (NSE) level is elevated in neurons and in numerous cells of the APUD system; melanocytes are also considered to belong to this system. In order to test the relevance of NSE as a tumour marker for malignant melanoma, its concentration in serum was radioimmunologically determined in 89 patients with melanomas: 24 in stage I (primary tumours), 44 in stage II (regional metastases), and 21 in stage III (distant metastases). The average (+/- coefficient of variation) concentrations recorded were 7.4 micrograms/l (+/- 46%) in patients in stage I, 5.8 micrograms/l (+/- 32%) in those in stage II, and 11.0 micrograms/l (+/- 72%) in those in stage III. A threshold value of 11.5 micrograms/l was exceeded in 9 cases, including 8 patients in stage III. Since definitely increased values arose almost exclusively in distant metastases, determination of NSE levels in serum is hardly a suitable tool for early detection of latent metastases.

APUD Cells↗
PubMed1992

[Quantitative analysis of recurrence and spontaneous regression of basalioma parts left in situ].

To some extent, parts of basalomas found remaining in situ following tumour excision tend to spontaneous regression. This is a well-known phenomenon and has significance for the recurrence of incompletely excised tumors. The present study involved a quantitative investigation of the relationship between recurrence and spontaneous regression. Following precisely defined excision of basalomas, the entire exterior of the excised material was examined by contrast microscopy in HE-stained paraffin sections (3-dimensional histology). Whenever tumour outgrowths were found, it was possible to document exactly their type, localization, extent, and depth of invasion. In 66 such cases no follow-up operation was performed, but only a follow-up examination after a minimum of 31 and a maximum of 113 months (average: 60 months). Only 50% of these undisturbed tumour outgrowths resulted in a recurrence during the follow-up period. A very high rate of spontaneous regression (71%) was found among the solid tumour outgrowths, but a significantly lower rate (19%) among the fibrosing tumours. Moreover, regression was dependent on the tumour remnant's mass and the clinical diameter of the tumour removed. It was independent of the depth of infiltration. Although the rate of spontaneous regression of tumour outgrowths persisting after therapy is relatively high, it cannot be predicted in individual cases. It is not possible to be certain that tumour removal has been achieved unless micrographic surgery has been continued until complete absence of tumour is proved. In all procedures that are not subsequently monitored, an unacceptably high rate of recurrence must be expected, especially in the case of fibrosing basaloma. This is commented on at length.

Aged↗
PubMed1992

[Intralesional therapy of melanoma metastases with recombinant interferon-beta].

In ten patients with metastasizing melanomas, discontinuous intratumoral treatment with recombinant interferon beta (rIFN-beta) was administered into 19 cutaneous or palpable subcutaneous metastases. Among the 16 metastases treated with 5 x 10(6) IU per injection, 8 showed partial or complete remission. No recurrence was observed during the 4-9-month follow-up period. There was no regression in 3 metastases treated with 3 x 10(6) IU rINF-beta per injection. No systemic antineoplastic effects were observed in any of the cases. The IFN-beta serum levels were measurably increased following intratumoral application. Local treatment led to a significant increase in (2'-5')oligoadenylate synthetase in the mononuclear blood cells and in the serum. Side-effects of the treatment were moderate; there was a temporary increase in transaminases, a decrease in thrombocytes and influenza-like symptoms. The results show that IFN-beta has a dose-dependent antitumour effect on malignant melanomas.

Adult↗
PubMed1991

Destruction of tumour parenchyma in basal cell carcinoma by tumour-associated neutral proteases: a histochemical study.

Proteolytic activity was demonstrated histochemically in frozen sections of basal cell carcinomas (BCCs). After incubation of tissue sections in 0.1 M phosphate buffer with 0.25 M NaCl the tumour epithelium was almost completely destroyed. The basal and squamous cell layers of the epidermis disintegrated to varying degrees, particularly where they were directly in contact with tumour epithelium. Serine and metalloprotease inhibitors diminished this tissue destruction. Iodoacetate enhanced tumour destruction, urea and potassium thiocyanate even more so. The high proteolytic activity of BCC demonstrated in this study may be an important factor in the proliferative, invasive and destructive behaviour of this tumour.

Basal Cell Carcinoma↗
PubMed1991

[Condylomata acuminata--topical and systemic interferon therapy].

An open study was carried out to test the effect of systemic administration of interferon (IFN) gamma and local application of IFN beta as monotherapy and adjuvant treatment. The topical application of IFN beta gel had no effect as monotherapy and when it was given as adjuvant therapy the rate of recurrence was not significantly reduced. IFN gamma was given for monotherapy in two different doses (100 and 200 micrograms per s.c. injection). The response rate to the cyclic treatment was 45% in the group (20 patients) receiving a dosage of 100 micrograms, and 57% in the group (26 patients) receiving a dosage of 200 micrograms. Patients with a duration of the disease longer than 18 months and patients with immune deficiency did not respond to the monotherapy. A group of 15 patients with resistant genital warts received adjuvant treatment with IFN gamma over 7 days after surgical treatment. In patients with inconspicuous immune status it was possible to reduce the recurrence rate.

Condylomata Acuminata↗
PubMed1991

[Standardized epiluminescent microscopy for differentiating melanocytic and non-melanocytic pigment nevi].

Epiluminescent microscopy (ELM) has been widely accepted as a non-invasive, rapid technique for the differentiation of pigmented skin lesions. The method is valuable for distinguishing melanocytic and non-melanocytic tumors, as well as for identifying malignant melanoma. Due to great morphological variability of pigmented lesions considerable experience is required. Based on a morphological analysis of 600 pigmented skin lesions, a diagnostic procedure was developed that permits a reproducible description and diagnosis of a given lesion and facilitates training in ELM.

Basal Cell Carcinoma↗
PubMed1991

[Locally infiltrative growth of squamous cell carcinoma of the skin and treatment guidelines resulting from it].

The infiltrative growth behaviour of squamous cell of the skin carcinomas is characterized by subclinical outgrowths, very frequently extending horizontally and sometimes over long distances. They are presented in the form of a negative exponential function. These outgrowths have an irregular pattern. It is much more extensive in the case of tumours with a clinical diameter of more than 20 nm. All types of "blind" therapy such as cryopexy, irradiation, laser, and surgery monitored in only two dimensions involve an inevitable risk of recurrences, which can be calculated statistically from the results available. Routine histographical surgery of skin carcinomas in the form of continuous, 3-dimensional histology can dramatically reduce the risk of local relapse, especially in the case of small and medium-sized carcinomas. The test group presented here (411 carcinomas) was treated with histographic surgery using the paraffin section method; during the follow-up period (maximum: 7 years, minimum: 3 years) the danger of recurrence was 2.2% for all carcinomas but only 0.6% for those up to 20 mm in diameter (n = 340). Carcinomas with a diameter of more than 20 mm (n = 71) involved a much higher risk of recurrence with 9.8%. This is probably because of local micrometastases, which require more generous local excision with a safety margin of about 10 mm.

Carcinoma, Squamous Cell↗
PubMed1990

Microstaging of squamous cell carcinomas.

The clinical classification of squamous cell carcinoma, which was established primarily by the International Union Against Cancer (UICC), does not permit optimal estimation of expected metastasis. The authors' results indicate that metastasis can be more accurately estimated on the basis of invasion depth, histopathologic grading, and especially tumor thickness. One essential advantage of these criteria is that they can be established by a histopathologist. It is interesting to note that in the authors' collective no carcinoma less than 2 mm thick metastasized, that is, a relatively high percentage of carcinomas (48%) can be graded as no-risk carcinomas. The risk of metastasis for undifferentiated carcinomas greater than 6 mm thick that have infiltrated the musculature, the perichondrium, or the periosteum, however, is quite high. Tumors between 2 and 6 mm thick with moderate differentiation and a depth of invasion that does not extend beyond the subcutis can be classified as low-risk carcinomas.

Carcinoma, Squamous Cell↗
PubMed1990

Treatment of psoriasis and psoriatic arthritis with interferon gamma.

In a placebo-controlled double-blind randomized study, 24 patients with psoriatic arthritis were given 28 d of treatment, and in an open study, 56 patients were treated for 9 months. We treated patients with 100 micrograms IFN gamma per subcutaneous injections, which were given daily for the first 2 weeks and then 3 times per week. The principal criterion for evaluation of therapeutic success on arthritis was improvement of the Ritchie joint pain index by at least 25% in the double-blind and 30% in the long-term study. In the double-blind study, the interferon arm was superior to the placebo arm with a statistically significant, one-side error probability of less than 5% in the chi-square test. In the long-term study, IFN gamma caused an improvement in a portion of patients in the first 3 months of therapy. No further improvement was observed after the third month, and patients classified as responders in the first months showed a deterioration of the disease by continuing treatment. The humoral inflammatory parameters did not normalize during therapy. Regression of the skin manifestations could not be observed. IFN gamma is evidently capable of inducing a psoriasis on the injection site. Investigations of IFN gamma serum levels, IFN antibodies, 2'-5' A synthetase levels in serum, and mononuclear blood cells and NK cell activity under long-term therapy showed no explanation for the loss of efficacy after 3 months treatment.

Arthritis, Psoriatic↗
PubMed1990

Psoriasis induced at the injection site of recombinant interferon gamma. Results of immunohistologic investigations.

Recombinant human interferon gamma used for treatment of psoriatic arthritis was found to induce expression of HLA-DR, but not HLA-DP or HLA-DQ, on keratinocytes at the site of injection. Some patients showed an improvement of their joint symptoms, but the cutaneous manifestations remained unaffected. In 10 of 42 patients, punctiform psoriatic foci could be induced at the site of injection of interferon gamma. For this presentation, we selected a female patient with psoriatic arthropathy and type II diabetes mellitus in whom psoriasis was induced at the site of application of interferon gamma, but not after subcutaneous injection of insulin or placebo. We conclude that interferon gamma is an important lymphokine in the development of psoriasis.

Abdomen↗
PubMed1990

[Structural analysis of melanocytic pigment nevi using epiluminescence microscopy. Review and personal experiences].

Epiluminescent microscopy is now used frequently for the differential diagnosis of pigmented skin lesions. In order to improve the distinction between benign and malignant melanocytic tumours it seemed advisable to develop a standardized pathway of epiluminescent microscopical analysis and to determine the frequency of structures recognizable with the microscope. A total of 600 melanocytic lesions were examined by epiluminescent microscopy, photographed and classified histologically after excision, revealing 426 naevocellular naevi and 174 melanoma. The experience achieved during the course of the investigation was used as the basis of a procedure for stepwise analysis of keratin layer, pigment structures and blood vessels. The most important findings are described and referred to malignancy. The photographs were analysed for the frequency of occurrence of various pigment structures in different types of lesions. The results differ in several aspects from previous findings.

Diagnosis, Differential↗
PubMed1990

[The subclinical portion in the periphery of lentigo maligna and lentigo maligna melanoma].

Lentigo maligna is a precancerosis or a melanoma in situ, whose level of malignancy has not yet been definitively clarified. Recurrences are not rare after excision, even when an ample safe margin is observed. One reason for this is the existence of a subclinical ramification in the marginal area of the lentigo maligna. Such subclinical ramifications were investigated by means of excision with histological monitoring of the margins by the paraffin section technique. There was a clear relationship between the frequency of these ramifications and the clinical safe margin left in 64 excisions. With the aid of parametric evaluation methods the distribution of the subclinical portion referred to the distance from the clinical margin could be determined with a special formula. If an invasion, in the form of a lentigo maligna melanoma had already taken place, then the subclinical portion within the marginal area was significantly more extensive. For the treatment of lentigo maligna, and especially of lentigo maligna melanoma, we therefore recommend excision with histological monitoring of the margins. There were no local recurrences within an average follow-up period of about 2 1/2 years.

Adult↗
PubMed1990

[Epiluminescence image of lentiginous junctional nevi].

Occasionally, in patients with pigmented skin lesions referred for epiluminescence microscopy (ELM) the lesions are deep black naevi that even experienced dermatologists suspect might be malignant melanomas. The surface of these lesions is abnormal, often scaly, but their general aspect is regular and not characterized by any gross asymmetry. Inspection by ELM reveals additional features, which, if present in a typical combination, indicate a benign lesion. One simple examination can be enough to exclude malignancy. Histological examination allows the diagnosis of lentiginous junctional naevocytic naevi. Two typical cases are presented.

Adult↗