Circulating immune complexes (CIC) in Hodgkin's disease. I. Levels and two-dimensional analysis.

A polyethylene glycol 6000 (PEG) mediated precipitation procedure was used to estimate the levels of CIC in sera of healthy donors and patients with Hodgkin's disease (HD). In comparison with the normal serum samples, sera from untreated HD patients showed elevated CIC levels scattered over a wider range and a mean which differed significantly. Sera from treated patients who were in clinical remission exhibited decreased CIC levels. However, the mean level in this category was still above the mean found in the normal sera. The analysis of the data showed that the sera from HD patients in Stage I and II, and with LP and MC type histology showed preferential increase in CIC levels. The analysis of these CICs in 2D-SDS-PAGE and a careful scrutiny of the polypeptide patterns obtained revealed significantly elevated amounts of a component with a Mr of 40 kD and a pI of 5.6 in CICs from the untreated HD patients. Congruent peptide maps of this component and its decreased amounts in CICs from sera of patients in remission suggests its quantitative involvement in the disease.

Uroporphyrinogen decarboxylase and porphyrins in the tissue of human clear-cell renal carcinoma and in its maternal renal cortex.

The activity of uroporphyrinogen decarboxylase and porphyrin concentration were determined in human clear-cell renal carcinomas and in their maternal renal cortex without evidence of malignancy in 24 men and 8 women. The obtained results were compared with the degree of morphological malignancy of various tumors. No positive correlation was found between the activity of uroporphyrinogen decarboxylase and the concentration of porphyrins in the studied tissues. There was no significant correlation between the activity of this enzyme and the porphyrin level and the degree of morphological malignancy of the tumors. However, in most cases the combined concentrations of three porphyrin fractions (uroporphyrin, coproporphyrin and protoporphyrin) were lower in carcinomas than in the unchanged renal cortex of the same kidney.

Alpha-2b interferon in the treatment of advanced chronic lymphocytic leukemia.

In four patients treated for progressive B-CLL, stage C, with alpha-2b interferon a detailed analysis of the distribution of surface molecules characterizing both the leukemic and the residual populations of peripheral blood lymphocytes as evaluated by flow cytometry did not reveal any significant changes during and after the interferon therapy. With the dosage of 3 x 10(6) IU of interferon injected subcutaneously three times per week, no effect on progression of the disease was detected. The treatment was well tolerated, thrombocytopenia was the only side-effect observed.

Descriptive epidemiology of childhood malignancies in Slovakia.

Over the period from 1978 to 1984, 673 neoplastic diseases were ascertained in boys and 517 in girls below the age of 15 years in the population-based cancer registry of Slovakia, giving average annual incidence rates of 142.7 and 114.2, respectively, per million population. With the large use of a standard international classification based on cell morphology, an analysis of very detailed structure of these tumors could be performed. Leukemias, tumors of the nervous system and lymphomas were responsible for nearly 70% of all malignancies in childhood during the period studied. Important increase of the total cancer incidence in boys accompanied only by its slight growth in girls during the longer period 1968-1984 was observed. The decline of the total childhood cancer mortality in Slovakia was less rapid than that observed in recent decades in some developed countries. These findings indicate at least the real existence of opportunities for the reduction of mortality from cancer in childhood in this country, too, obviously by a more effective and general application of actually available methods of treatment.

Trends and patterns in cancer incidence in Czechoslovakia, 1968-1985.

Cancer incidence rates and trends in Czechoslovakia investigated in the present study are based for the first time on valid data derived mainly from population-based cancer registries. All rates were age-adjusted using world standard population as a reference. The results confirmed first of all a real and apparent increase of the whole cancer incidence trends which was more expressed in males. The increase in the overall cancer incidence among males could be attributed to the steadily continuing growth of lung cancer, responsible for one-quarter of all new cases in recent years, and to a lesser extent, also to the rising rates of "other skin", prostatic, colonic and rectal cancer. The rates and trends among females were influenced by increase and dominant position of breast and "other skin" cancer, responsible together for one-third of new cases. Increasing trends were observed for the incidence of the uterine body, ovary, and for the great majority of digestive tract and other cancer sites. A reduction of incidence was seen only for stomach in both sexes, for the uterine cervix among females, and lip cancer among males. The actual rates and trends of cancer incidence in Czechoslovakia could be compared with those observed in other developed countries. The usefulness and unconditional necessity of adequately reliable data on cancer incidence for epidemiological research and administration of cancer control is emphasized.

Theoretical study of N-nitrosoureas and mechanism of their carcinogenic effect.

A mechanistic study into the carcinogenic action of N-nitrosoureas (NU) was carried out with the aid of the semiempirical MINDO/3 method. The proposed reaction pathways of NU biodegradation mechanisms were examined and the most probable one was identified on the ground of theoretical considerations. The calculations of reaction enthalpies confirmed NU as SN1 reagents. The reactivity of a series of NU molecules (both isolated and under the solvent influence) were studied with respect to the detection of possible determinants of the relative carcinogenic potency. The correlations revealed a key function of the nitrosogroup and of the N3-C7 fragment in the decomposition process. The role of the transport properties and lipophilicity of parent NU molecules in the initial steps of the mechanism of carcinogenic effects was demonstrated as well.

Influence of short-term topical exposure to phorbol ester tumor promoters on subcutaneously induced skin tumorigenesis in S/RVCri mice.

The effects of short-term exposure to phorbol ester tumor promoters on epithelial and mesenchymal skin tumor induction, studied histologically in female S/RVCri mice, rendered precancerous by a subcutaneous (sc) injection of 3-methylcholanthrene (MCA). At 6 weeks after MCA injection, mice in Groups I to VI received topical twice weekly applications of 0.1 ml acetone, 1.8 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol didecanoate (PDD), phorbol dibenzoate (PDB), phorbol diacetate (PDA) or 6.1 nmol mezerein (MEZ) in 0.1 ml acetone, respectively, for four weeks. Animals were sacrificed after the development of palpable tumors. Data from various phorbol ester treatment groups were compared with the acetone control. Of the promoters tested, TPA treatment increased the percentage of tumor bearers and the number of combinations and expression of diverse neoplasms in the mixed growths. TPA-related phorbol esters such as PDD, PDB or MEZ did not alter the percentage of tumor bearers although the histological distribution into pure epithelial or mesenchymal and mixed tumor bearers differed significantly from the control treated with the solvent alone. However, PDA significantly inhibited MCA-induced skin tumorigenesis and increased the average time of tumor induction. All the promoters, except TPA, decreased the percentage of mixed tumor bearers, the development of hibernoma and fibrosarcoma, while allowing a selective expression of rhabdomyosarcoma.

Study of metabolism and growth limitation of human leukemia cell lines.

The relationship between proliferation and metabolism of four leukemia cell lines (BALL-1, JOK-1, Jurkat, and MOLT-4) in batch culture was studied. The maximum cell density (1.5-2.3 x 10(6) cells/ml) without change of medium was observed on days 6-8 of cultivation. At the same time, the original concentration of glucose in the medium (10 mmol/l) fell to 3.5-4 mmol/l. While BALL-1 and MOLT-4 cells, on day 4 of cultivation, converted 82% of glucose into lactate, on day 7 this value was 50%, or there was no lactate production (MOLT-4), respectively. On the other hand, the values of the coefficient of glycolysis showed that Jurkat and JOK cells converted also other compounds into lactate. Part of the utilized glutamine was employed by all four cell lines: 1. as a precursor of glutamic acid, and 2. as a source of energy. BALL-1 and JOK-1 cells converted part of arginine into ornithine. At the time when the proliferation of the cells ceased, the level of ammonia reached a toxic concentration of 2.0-3.6 mmol/l. Since these cell lines utilized only a part of carbon and nitrogen sources in the medium, it was suggested that the final cell density was limited by a growth inhibitor (i.e. ammonia) and not by a lack of nutrients.

Evaluation of cytotoxic and antitumor effects of a tetravalent analog of carboplatin.

The cytostatic and cytocidal effects of a newly synthesized tetravalent platinum drug (CBDCA-ox) on two experimental ascites tumors as well as on normal tissues of the mouse were investigated. It was found that CBDCA-ox exhibited only negligible acute toxicity in comparison with its reduced analog. Also hemotoxicity of this tetravalent drug was markedly lower than that of CBDCA. The comparison of antitumor activity of CBDCA and CBDCA-ox tested against LS/BL lymphosarcoma and EAT tumor cells strongly supports the view that CBDCA-ox deserves further preclinical testing.

Effects of benfluron metabolites on glycolysis and level of thiol groups in P388 and Ehrlich ascites cells.

The effects of two benfluron metabolites, namely 7-dihydrobenfluron (DBF) and N-oxide of benfluron (NOBF), on the aerobic glycolysis of Ehrlich ascites carcinoma (EAC) and P388 cells were studied. Also their effect on the level of total (T-SH) and nonprotein (NP-SH) thiol groups was investigated. A significant inhibition of aerobic glycolysis in the presence of NOBF was found only in P388 cells. Both metabolites decreased more significantly the level of NP-SH than that of T-SH.

Antitumor effect of hippurate. An experimental study using various mouse tumor strains.

Hippurate had antitumor effects both in vitro and in vivo by killing dose-dependently the cells derived from Skalsky lymphoma, Németh-Kellner lymphoma, L-asparaginase sensitive 6C3HED Gardner lymphoma, and LP-2 plasmacytoma. There was no significant difference between the effect of hippurate and its maternal compound benzoate. Hippurate administered intraperitoneally twice a day at a dose of 1 g/kg body weight significantly inhibited the growth of solid 6C3HED Gardner lymphoma even in the case that the treatment was started when the tumors reached a weight of over 400 mg. It was concluded that benzoates could be an important endogenous group of substances with antitumor effects.

Hindering of tumor lung metastasizing with alpha-(4-cyclohexylphenyl)propionic acid in mice.

Alpha-(4-cyclohexylphenyl)propionic acid, a potent inhibitor of platelet aggregation, has appeared to reduce the quantity and size of Lewis lung carcinoma (LLC) tumor nodules in the lungs. The number of animals developing the tumor colonies in the lungs was decreased by 34% to 49% either when the tumor cells were injected i.v. and alpha-(4-cyclohexylphenyl)propionic acid was administered during 3 days, or when the tumor cells were transplanted i.m. The primary tumor was removed 6 days later and the drug administered during 8 or 21 days.

The contribution of discrimination analysis to the diagnostic decision in patients with lung carcinoma.

A set of 620 patients was examined. Out of them, 245 suffered from lung carcinoma of different type and stage, 28 suffered from other malignant tumors, 37 were affected with benign tumors, and 166 were suffering from a nonmalignant respiratory disease (tuberculosis, nonspecific pneumonia, chronic bronchitis, abscesses, cysts, asthma, lung fibrosis, bronchiectasis and sarcoidosis). In addition to these patients, 144 blood donors were examined who represented the control group of healthy individuals. In a blind test another set of 266 persons was examined. By completing the values of selected markers (orosomucoid, prealbumin, glycoprotein electrophoresis, erythrocyte sedimentation, age of the individual, and the number of smoked cigarettes) into the discrimination rule and by calculating the discrimination function, a sensitivity of 80.6% and a specificity of 75.6% were obtained. A comparative cytological examination of the same set revealed lower sensitivity (61.0%) but higher specificity (98.0%). These values were verified in a blind test, as the patients were admitted to the hospital. Sensitivity in lung cancer was found to be 83.9%; in nonmalignant diseases the respective value was 77.1%. This approach can be applied to individuals suspect of cancer, in secondary prevention and in individuals with a high risk of lung cancer.

Y chromosome in leukemia patients. A study on the heteromorphic nature of its heterochromatic segment.

Possible heteromorphism of Y chromosome regions was studied in 50 leukemia patients and 50 healthy controls. The mean length of the Y chromosome was insignificantly higher in the patients as compared to the controls. No difference was observed in the size of the euchromatic region; however, the size of the heterochromatic region was significantly larger in leukemia patients as compared to the controls.

Liver vitamin A concentration in patients who died of cancer.

The concentrations of vitamin A in liver samples obtained at autopsy of patients who died of cancer was investigated. It was found that liver vitamin A levels in cancer patients were significantly lower than in controls. Although our recent results have suggested that the decreased serum retinol level in cancer patients reflects rather a functional impairment of vitamin A release from the liver, the results of this study suggest that this phenomenon can also indicate a true vitamin A deficiency in patients with neoplastic process.

Zinc, vitamins A and E, and retinol-binding protein in sera of patients with cancer of the larynx.

Serum vitamin A concentrations were measured in 22 patients with laryngeal cancer and found to be significantly lower than those of patients of similar age with either nonmalignant laryngeal or other than laryngeal diseases. The levels of vitamin A in the patients with laryngeal cancer, but not in the controls, significantly correlated with serum concentrations of retinol-binding protein (RBP) and zinc. It is suggested that low levels of zinc might reduce the synthesis of RBP and thus reduce the mobilization of vitamin A from the liver stores.

Gastric cancer with special references to WHO and Laurén's classifications: glycogen and triacylglycerol concentrations in the tumor.

In eighty patients with histologically verified gastric carcinoma the concentrations of glycogen and triacylglycerols were evaluated in specimens taken endoscopically from the tumor and the surrounding unchanged gastric mucosa. The results were analyzed in relation to the histological type of carcinoma according to WHO's and Laurén's classifications. The control group consisted of sixteen patients with superficial chronic gastritis. An elevated glycogen concentration was found in tumors of all types of gastric carcinoma; its level in the neoplasm was significantly higher also in relation to unchanged gastric mucosa surrounding the tumor. A particularly high glycogen level was present in the slow growing well-differentiated cancers, e.g. papillary and tubular adenocarcinomas or intestinal-type carcinoma. Reversely, in the fast growing and poorly differentiated cancers, e.g. undifferentiated or diffuse-type carcinoma, the glycogen contents were lower. Also triacylglycerol concentrations in the tumors as well as in the surrounding unchanged gastric mucosa were significantly higher than those in the control gastric mucosa specimens; no significant difference in triacylglycerol concentrations was observed between groups of patients with various types of carcinoma. It was concluded that (1) glycogen concentrations in the neoplastic tissue are cancer-growth related and characteristic for each kind of carcinoma, (2) an elevated triacylglycerol content in the tumor is probably a result of general lipid changes in the host.

Case-control study of relationship of some biosocial correlates to rectal cancer patients in Belgrade, Yugoslavia.

This investigation of some biosocial factors such as level of education, profession, tobacco smoking, alcohol and coffee consumption, and previous illnesses, reports on 98 patients with histologically confirmed rectal cancer, and 196 hospitalized and neighborhood-matched controls. Past history of hemorrhoids, polyposis, colitis, diverticulosis and appendectomy, as well as the use of laxatives were significantly more frequent among rectal cancer patients than in their controls. None of the case-control differences related to the other parameters reached statistical significance.

Comparative study on cancer incidence in neighboring regions of Hungary, Austria, Yugoslavia and Czechoslovakia in 1969-1980. Pannonian Tumor Epidemiology Study Group.

The present collaborative study was performed in four confined, neighboring regions of Austria, Hungary, Yugoslavia and Czechoslovakia with different demographic and occupational characteristics of their respective populations, various structures of medical facilities, and cancer registration systems. Crude and age-standardized incidence rates and trends of six major cancer sites (stomach, colorectum and lung in both sexes as well as breast, uterine cervix and uterine body in women) in three 4-year periods (1969-1972, 1973-1976, 1977-1980) were computed and mutually compared in the mentioned regions. Relatively high, different but more or less decreasing incidence rates of stomach, and varying but mainly increasing rates and trends of colorectal cancer were observed, while lung cancer incidence rates and tendencies showed great variations in both sexes. For women, besides continuous increase, the tendencies towards culmination and stabilization were found in regions with the highest incidence rates of breast and uterine body cancer in comparison with the more or less declining rates of uterine cervix cancer over the period studied. The observed different incidence rates and trends of these and obviously of other cancer sites require further investigations using more sophisticated epidemiological methods and approaches.

Epidemiological aspects of childhood cancer incidence in Czech regions.

In this descriptive epidemiological report a total of 5100 childhood malignancies registered in Czech regions during the period of 1963-1985 was analyzed. The incidence of these tumors compared in years of this time period has been relatively constant, we did not find any significant changes in trends. That is why the average annual incidence rate, i.e., 10.8 in males and 8.7 in females per 100,000 sufficiently characterized the epidemiological situation in this respect. Those parameters allow, by knowledge of demographic prognosis, to estimate expected numbers of tumors in further years. The highest incidence occurred in boys and in the lower age groups of both sexes. All differences presented in this report were tested and were found to be significant. The percentage ratio of solid tumors, preferentially those of bone and skin of both sexes, and brain tumors in females in the period of 1976-1985, as compared to the period of 1961-1970, decreased, whereas there was a significant increase of systemic malignancies and soft-tissue sarcomas. Finally, the geographic differences of incidence are described, and the possible causes of the data presented are discussed.

Age-dependent antileukemic action and suppression of immune response by 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone (ambazone) in mice.

The antineoplastic activity of 1,4-benzoquinone-guanylhydrazone-thiosemicarbazone (ambazone) against murine leukemia P388 was found to be markedly reduced in 12- and 18-month-old mice as compared to young animals. The immune response against sheep red blood cells (SRBC), a T cell-dependent antigen, was also strongly diminished in tumor-free old mice and was further suppressed after ambazone treatment. Since the antileukemic effect of ambazone disappeared more or less in congenitally athymic nude mice, in neonatally thymectomized or silica-pretreated animals, it has been concluded that the action of the compound seems to be limited to young adult immunocompetent tumor-bearing hosts. Therefore immunosenescence, primarily of T cell functions of old tumor-bearers, may represent a decisive factor influencing the antileukemic, especially curative effect of ambazone in aged animals. A combined treatment with ambazone and immunomodulators (thymalin or a splenopentin derivative) failed to improve the antileukemic effect in young and old leukemia P388-bearing mice.

Growth, flow cytometric, and karyological characterization of L1210 cell sublines resistant to various Pt derivatives.

Growth, flow cytometric, and karyological characteristics were analyzed with respect to differences between sensitive L1210 cells and eight sublines resistant to cisplatin (DDP), 1,2-diaminocyclohexane(DACH)-Pt(II) citrate, DACH-Pt(II) glucarate, cis-dichloro-bis-(isopropylamine)-trans-dihydroxyplatinum (IV) (CHIP, iproplatin), and methotrexate (MTX). No great differences were found in growth properties. The sensitive and a majority of resistant sublines displayed similar flow cytometric and karyological characteristics, major differences were found only in the sublines resistant to CHIP. The relationship between the mechanism(s) of resistance and different pharmacokinetics of the drugs is discussed with special reference to DNA content and chromosome structure.

Effect of benfluron metabolites on ATP level in tumor cells.

Changes in ATP levels of both Ehrlich ascites carcinoma and P388 leukemia cells were evaluated after 2 h of incubation in the presence of different concentrations of benfluron (BF), 7-dihydrobenfluron (DBF) and N-oxide of benfluron (NOBF). Up to the concentration of 37.5 mumol/l, none of the substances significantly depressed the ATP levels. A more expressive decrease in ATP levels was noted only at concentrations of 75 mumol/l and higher. BF proved the most effective, less effective was DBF, while NOBF was practically without any effect. Of the remaining cytostatic drugs, Mitoxantrone, CCNU and Me-CCNU, in particular, proved efficient in depressing ATP level. The latter becomes depressed already after 15 min of incubation in the presence of the highest concentrations of benfluron and 7-dihydrobenfluron.

Hydroxyurea-induced toxic side-effects in animals and an attempt at reducing them with vitamins E and C.

Using the changes in several blood parameters and in the histological picture of the liver as markers of toxicity, the effect of hydroxyurea (HU) in healthy rabbits or mice was examined during two weeks after a single administration of this drug. In rabbits a transient significant decrease in blood erythrocyte count with a gradual increase in their osmotic resistance, a suppression of granulocyte phagocytic capacity, and an elevation of acid phosphatase activity in the serum were found. An increase in the proportion of lymphocytes without detectable lysosomes as tested by supravital staining also appeared. No significant difference was observed in the white cell count and lipoperoxide levels after HU administration. Histological picture of the liver, excised from HU-treated mice, indicated a marked hepatotoxicity of the drug. Some of the toxic effects were reduced in animals supplemented with vitamins E and C.

Flow cytometric analysis of primary cervical and vulvar carcinomas and their metastases.

In a series of 25 patients with cervical carcinoma and 35 patients with vulvar carcinoma, clinically classified (FIGO) as Stage I and Ib, respectively, DNA ploidy and S-phase cell fraction were estimated in paraffin-embedded samples of the primary tumors and their metastases by means of flow cytometry (FCM). The two groups of patients were selected cases in whom lymph nodes removed at radical operation were histopathologically verified as metastatic ones. Prevailing part of primary tumors of both anatomic sites had diploid DNA content and low S-phase fraction. Irrespective of the DNA content and low proliferative activity the early stage carcinomas behaved aggressively as indicated by the presence of metastases, the DNA content of which corresponded in most of the cases with that of primary tumor. It appears that prediction of the tumor growth based only on cytogenetic and cytokinetic parameters may be connected with difficulties.

A multivariate analysis of prognostic factors in adult Hodgkin's disease.

A multivariate analysis of the prognostic factors was carried out with a Cox model on 167 patients with Stage I-IV Hodgkin's disease. The following indicators were prospectively registered: Sex, age, clinical stage, systemic symptoms, histological type, number of involved areas, nodal size, mediastinal thoracic ratio (MTR), localization of mediastinal involvement according to the aortic arcus, hilar involvement, extent of radiotherapy, and extent and mode of chemotherapy. A linear logistic analysis showed that most of the indicators were interrelated. This emphasizes the necessity of a multivariate analysis in order to assess the independent influence of each of them. The three main prognostic indicators for complete remission achievement were age, clinical stage and involvement of lung hili. The three main prognostic indicators for disease-free survival were sex, size of mediastinal involvement (MTR) and use of alternating chemotherapy COPP/ABVD in the initial treatment strategy. The most important prognostic factor for survival was clinical stage followed by hilar involvement, age, and nodal size. The coefficients estimated by Cox regression analysis can be used to combine the important prognostic factors into a single index for each patient at presentation. The prognostic index for each patient would allow the identification of cases with poor prognosis who might benefit from additional initial treatment.

Peculiarities of hormonal regulation of adenylate cyclase and lipid composition in colonic and rectal tumors.

Peculiarities in hormonal regulation of adenylate cyclase (AC) were studied in large bowel tumors to establish criteria of their hormonal dependence. The investigation showed a diminished basal activity of AC matched by decreased response to sodium fluoride, glucagon, and vasoactive intestinal peptide (VIP) in tumors as compared with normal intestinal mucosa. Some cases revealed an increased response of AC to a nonspecific ("inappropriate") stimulator--calcitonin. This was rather typical of colonic tumors while a diminished response to specific ("appropriate") stimulation by VIP and glucagon was more frequent in rectal cancer. The results showed a relationship between hormonal regulation of AC activity and lipid composition of tumor tissue, thus suggesting the possibility of influencing the hormone dependence of intestinal tumors by drugs used to eliminate disturbance of fat-carbohydrate metabolism.

A comparative study of mucin-like carcinoma-associated antigen (MCA), CA 125, CA 19-9 and CEA in patients with ovarian cancer.

A mucin-like carcinoma associated antigen (MCA), which is recognized by the monoclonal antibody b-12, was found to be elevated in sera of breast cancer patients. Since an immunohistochemical reaction of the monoclonal antibody b-12 was found in epithelial tumors of the ovary we investigated MCA serum levels in 50 patients with ovarian cancer (mean age 59 years, range 31-81 years). In addition, CA 125, CA 19-9 and CEA were determined to compare sensitivity, specificity and the predictive value of the positive test of each parameter used in this study. Blood samples were obtained in 20 patients with progressive disease and in 30 patients during disease free intervals. The MCA serum levels of patients with progressive ovarian cancer (mean +/- SD: 14.7 +/- 14.6 U/ml) did not differ significantly from those of patients in remission (mean +/- SD: 8.2 +/- 5.3 U/ml) or from values of a healthy control group (mean +/- SD: 7.7 +/- 3.8 U/ml, n = 70). Women with progressive disease displayed significantly higher CA 125 (p less than 0.0001) and CEA (p less than 0.0063) serum levels than patients in remission. No significant difference was found for CA 19-9 in patients with ovarian cancer, irrespective of the clinical status. Considering marker surge and tumor progression, the highest sensitivity was found for CA 125 (75%). Sensitivities of the other markers were significantly lower and reached only 25-35%. The predictive value of elevated marker levels as well as specificity of the marker substances were similar. Sensitivity could be extended to 90% if elevation of CA 125, CA 19-9, CEA and MCA were taken into consideration, however specificity was lowered by using this marker combination.

High dose alpha-2-recombinant interferon in the treatment of malignant lymphoproliferative diseases. A pilot study.

In the presented clinical study, 10 patients with malignant lymphoproliferative diseases (2 with acute lymphoblastic leukemia, 3 with Hodgkin's disease, and 5 with non-Hodgkin's lymphoma), resistant to standard therapy, were administered alpha-2-recombinant interferon at a dosage of 120 x 10(6) IU as a continuous 48 h i.v. infusion. The second administration was performed after an interval of 1 month. A therapeutic response was seen in 50% of the patients, of them there were two complete remissions (in the two acute lymphoblastic leukemia patients) and 3 partial remissions (in 2 patients with Hodgkin's disease and in 1 patient with low malignant non-Hodgkin's lymphoma). In four patients with high malignant non-Hodgkin's lymphomas the treatment did not evoke any response, and in 1 patient with the same diagnosis progression was noted after the treatment. The toxic effects of the drug were in accord with literature data, and although high doses of alpha-2-recombinant interferon were administered, it was not necessary to interrupt the treatment in any of the patients. Considering the therapeutic effect of this immunomodulator used in the treatment of malignant lymphoproliferative diseases, our results are promising, nevertheless further studies will be required.

Bone alkaline phosphatase isoenzyme and urinary hydroxyproline in healthy subjects, patients with osteolytic metastases, and patients with primary hyperparathyroidism.

The values of urinary hydroxyproline excretion reflecting the bone remodelling by osteoclasts, and the bone isoenzyme of serum alkaline phosphatase reflecting the osteoblastic function, in 100 randomly selected healthy subjects, 100 patients with primary hyperparathyroidism, and 100 patients with osteolytic secondary tumorous deposits in the skeleton showed a bivariate lognormal distribution. Hotelling's test revealed highly significant differences in the biochemical values among these three conditions, even when Bonferroni's modification of the test was used. The individual biochemical values, however, displayed many mutual overlaps. Despite this, the discriminatory analysis based on bivariate biochemical data resulted in a correct diagnosis in all healthy subjects, in 82 patients with primary hyperparathyroidism, and in 93 patients with osteolytic metastases. The simultaneous determinations of urinary hydroxyproline excretion and the bone alkaline phosphatase insoenzyme improve the differential diagnosis between these conditions. The predominance of urinary hydroxyproline excretion relative to bone alkaline phosphatase isoenzyme suggests an osteolytic metastasis. Proportionately elevated both hydroxyproline and bone alkaline phosphatase isoenzyme indicate the presence of primary hyperparathyroidism. This shows the importance of a correct biometrical processing of data. Nevertheless, a complex clinical evaluation is always mandatory.