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Results are reported of the treatment of 82 patients with grade 1 melanoma of the skin of extremities and trunk. Endolymphatic chemotherapy was carried out after surgery. During the first postoperative year metastases to the regional lymph nodes developed in 15.7% of patients while in the control group of 333 patients metastases were found in 38.6%.
Six cases of telangiectatic clinical variant of mastocytosis (TMV) are reported. Patients' age varied from 33 to 62, there were 2 men and 4 women. A number of clinical features of TMV were detected in the course of follow-up: a generalized type of the skin process; abundant maculopapular eruptions colored brownish, sometimes with a cyanotic shade, liable to fuse and form diffuse foci of involvement; development of telangiectasias on the surface of these eruptions; symptoms of elevated blood histamin levels, i.e. regular blood congestion, enhanced itching, tachycardia, gastrointestinal events, etc.; systemic mastocytosis (3 of the 6 patients developed lymphadenopathy and hepatomegaly). The detected features of the condition permit considering TMV as an individual clinical variety of mastocytosis.
The effects of new antitumor drugs spirobromin and prospidin on acute (carraghenin-induced rat paw edema) and chronic ("pellet granuloma") inflammation in rats were studied. The drugs were found to exert the anti-inflammatory effect on the model of chronic proliferative inflammation but to produce no significant changes in the degree of the acute inflammatory reaction. Spirobromin is superior to prospidin by the power of the anti-inflammatory effect. The electron microscopic studies showed that spirobromin and prospidin decrease the activity of fibroblasts in the focus of chronic inflammation.
The individual response to chemotherapy was investigated in 17 heterotransplants of human lung tumours of different histogenesis by the subcapsule test. It is established that the subcapsule test is of high informativity only when testing the individual resistance of lung tumours, especially adenocarcinomas, to cytostatics.
The effectiveness of combination chemotherapy with platidiam and prospidin was assessed in 58 patients with squamous-cell lung cancer. Complete or partial remissions were achieved in 48.3% of cases. Toxicity was moderate. The addition of gamma-ray teletherapy after chemotherapy in the total focal dose of 60-70 Gy was followed by an increase in the remission rate (88.9%) and mean survival (from 8.5 +/- 1.3 to 16.0 +/- 3.5 months).
Manifest changes in the immunity status are detected in lymphoproliferative diseases of the skin and in Kaposi's sarcoma. Therapy results in elevation of the initially lowered levels of T mu- and T gamma-cells, this being a favorable result. Scintillation of T mu- and T gamma-cells may be used to monitor the efficacy of therapy in such patients.
The report discusses the effectiveness of chemotherapy in 60 patients with advanced squamous cell carcinoma of the head and neck (platidiam + prospidin-40; platidiam + cyclophosphamide and bleomycin-20). The latter procedure proved slightly more effective.
Reactions of the laryngeal and neck skin mucosa were studied in 93 laryngeal cancer patients on combined therapy including hyperthermia. Patients in the control groups received no local hyperthermia. Reactions on the laryngeal mucosa (hyperemia, insular and confluent epitheliitis) were observed in all the patients; in patients receiving chemotherapy they were more noticeable. In patients receiving local hyperthermia these reactions appeared somewhat later and were less noticeable and not repeated. Skin reactions correlated only with a radiation dose and did not depend on chemotherapy and hyperthermia. Local electromagnetic hyperthermia in laryngeal cancer patients neither influenced the appearance of radiation reactions nor enhanced them.
Antitumor efficacy of a medical adhesive MK-8-based polymer drug composition with prospidin has been studied in 49 Wistar rats, and the kinetics of the drug elimination has been followed up in 112 rats. The findings evidence a prolongation of a relapse-free period and a longer survival of the animals. Clinical trials of the composition have been carried out. Of the 70 patients with esophageal carcinomas 52 ones had local disseminated forms, conforming to T4P3-4 indices. Application of the adhesive composition has not increased the rate of postoperative complications and in some cases considerably prolonged the life span of patients after palliative surgery.
Comparative assessment of the efficacies of several chemotherapeutic complexes permit recommending the following complexes for the treatment of mycosis fungoides: prospidin-vincristine-prednisolone, cyclophosphamide-vincristine-prednisolone, cyclophosphamide-vincristine-bleomycin-prednisolone, in doses and schemes suggested by the author. The first complex is more sparing and is recommended for elderly patients with concomitant diseases and initially depressed hemopoiesis. The second and third complexes are characterized by more intensive action and help achieve a clinical remission even in cases with significant involvement.
By the methods of heat denaturation and luminescence the interaction between an antitumor drug prospidine and DNA in aqueous solutions at two ionic strengths (0.1 and 0.001 M NaCl) and at various prospidine concentrations was studied. For the first time it has been demonstrated that the interaction occurs at 0.1 M NaCl and therapeutic prospidine concentrations. In the framework of Frank-Kamenetsky's theory of melting of a polymer with stabilizing ligands the size of the binding site and binding constants (K) with the decrease of ionic strength, the lack of alterations in the DNA UV absorption spectrum on complex formation and the data on the competitive binding of ethydium bromide suggest that at the first stage of the reaction an external complex is formed due to electrostatic interactions between quaternary nitrogen atoms of prospidine and DNA phosphate groups. Incubation of the complex at 37 0 C leads to a decrease of the DNA melting temperature and hyperchromic effect. Presumably this is due to the relatively slow formation of chemical bonds between alkylating groups of prospidine and nucleophilic groups of DNA bases, which results in the destabilization and denaturation of DNA. It is concluded that the interaction between prospidine and DNA must be taken into consideration when studying the molecular mechanism of prospidine antitumour activity.
Changes in the immunologic parameters of 39 patients with Kaposi's sarcoma over the course of leakadin therapy were under study, i. e. total leukocyte and lymphocyte counts, immunoregulatory cells in spontaneous and complementary rosette formation, and in that with monoclonal antibodies. The therapeutic efficacies and immunostimulating activities of prospidin and leakadin, a new Soviet drug, are compared. Besides sufficient therapeutic efficacy, leakadin has shown a manifest immunocorrective effect, increasing the counts of CD2+ and CD3+ cells, i. e. of the total T-lymphocyte pool (including the "young" cells) and, consequently, of its mature fraction, CD4+ and theophyllin-resistant T-lymphocytes, CD8+ cells; this fact recommends the drug for the treatment of patients with Kaposi's sarcoma. Since the immunomodulating effects of prospidin and leakadin are ambiguous, their combinations are advised for the treatment of Kaposi's sarcoma.
Lymph microcirculation in the bulbar conjunctiva at the site of surgery was studied by fluorescent lymphangiography in 217 patients with primary glaucoma before and in various periods after trabeculectomy. Lymph vessels are changed after the operation; the pattern and intensity of these changes reflect the activity of cicatrization at the site of the operation and are closely related with the hypotensive effect in remote periods postoperation. In cases with the complete compensation of ophthalmic tone without extra hypotensive therapy a moderate narrowing of the lymph vessels was observed, parallelled by a compensatory increase of their quantity and of the volumic rate of the lymph flow. If the hypotensive effect of surgery was insufficient, an essential decrease of all the lymph flow parameters was observed, the most manifest in the patients with intraocular pressure still increased after extra drug therapy. A regular lowering of the lymph flow in 2-4 years after surgery was recorded; this lowering anticipated the deterioration of the hydrodynamic parameters. Noteworthy that ophthalmic tone failed to normalize when the mean diameter of the lymph vessels decreased more than twofold vs. the preoperative value. A conclusion is made that fluorescent lymphangiography holds good promise as a method for the assessment of the intensity of cicatrization processes after antiglaucoma surgery in order to timely prescribe preventive anticicatricial therapy. Administration of cytostatics in the postoperative period helps considerably increase the number of satisfactory outcomes of surgery due to suppression of cicatrization processes at the site of intervention. A lesser rate and intensity of cicatricial deformations of the lymph vessels was recorded in the patients administered cytostatics.
Lymphoproliferative diseases of the skin and Kaposi's sarcoma were found to involve high excretion of polyamines. Therapy with reaferon combined with prospidine and indomethacin improved the clinical course of the process and was associated with a decrease of polyamine excretion. Measurement of the urine polyamines may be used for the assessment of the treatment efficacy in malignant lymphomas of the skin and in Kaposi's sarcoma.
The effect of prospidin on Lewis lung carcinoma spreading under hyper- and hypocalcemia was studied. At early stages, increased extracellular calcium level was associated with inhibition of tumor dissemination to the lungs; however, later, colony growth was stimulated. Extracellular calcium level was shown to modulate the antitumor and antimetastatic effect of prospidin.
Antitumour drugs prospidine and spirobromine were shown to suppress the activity of the mouse liver lysosome enzymes in vivo and in experiments in vitro. The revealed effect was underlied by a decrease of lysosomal membrane permeability for the corresponding substrates and enzymes rather than a reduction of the catalytic activity of acid hydrolases.
A 65-year-old female patient has been orally taking corticosteroids (8 pills of prednisolone) for a severe form of bronchial asthma. In 1979 Kaposi's sarcoma was diagnosed for the first time; the diagnosis has been histologically confirmed. Several times the patient has been effectively treated with prospidin. The disease course got worse from 1984 on: the eruptions disseminated and the condition recurred every 2-3 months. This case is remarkable because Kaposi's sarcoma has developed in a patient treated with corticosteroids for asthma for a long time.