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Biomedical subjects

R Kuzmits

Publications and source records attributed to R Kuzmits.

At least 37 records · Page 2Linked to original sources

Recombinant interferon alfa-2C versus polychemotherapy (VMCP) for treatment of multiple myeloma: a prospective randomized trial.

Forty-two previously untreated patients with multiple myeloma were entered in a prospective, randomised trial comparing recombinant interferon alfa-2C monotherapy with VMCP (vincristin, melphalan, cyclophosphamide and prednisolone). Both treatment arms were comparable for the stratification variables such as paraprotein type, stage of disease, and renal function. Rec. interferon effected 14% responses and 29% minor responses, while 57 and 32% of VMCP-treated patients achieved a pathologically documented remission (P less than 0.001). The time on initial treatment was significantly shorter in the IFN group (3.2 months) than in the VMCP group (7.6 months). In four patients in the IFN arm, primary treatment had to be changed according to progressive or severe stationary disease. Since all four patients responded to second line therapy (VMCP) no significant difference has been observed between the two groups in survival (median follow-up greater than 12 months). Despite this clear superiority of the conventional four-drug polychemotherapy, there was some suggestion that IFN might be particularly active in cases with low tumor-burden (stage I, II), and light-chain or IgA paraprotein type.

Adult↗

Assessment of the sensitivity of leukaemic cells to cytotoxic drugs by bioluminescence measurement of ATP in cultured cells.

A short-term test in vitro is described, which can be used to detect resistance to cytostatic agents in leukaemic cells. Leukaemic cell suspensions were incubated with cytostatic agents and the resulting intracellular ATP concentrations were measured by a bioluminescence ATP assay. There was a clear dose-effect relationship in acute leukaemia and chronic lymphocytic leukaemia cells for drugs used in the treatment of leukaemias. A good correlation was found between the ATP content of leukaemic cells and cell viability as determined by the trypan blue dye exclusion test. Preliminary individual clinical correlations suggest a correlation between the chemosensitivity in vitro and the response patterns in vivo in leukaemia patients. This simple, fast and sensitive method may have application for determination of drug-induced cytotoxicity in leukaemic cells in vitro.

Acute Disease↗

Neopterin as tumour marker serum and urinary neopterin concentrations in malignant diseases.

Serum and urinary neopterin concentrations were measured in 142 patients suffering from various malignant diseases. Increased serum and urinary neopterin levels were found in 48% and 55% of patients respectively. Neopterin showed sufficient sensitivity in the detection of haematological disorders and hypernephroma, whereas the sensitivity of neopterin was rather poor in patients with other solid tumours. Comparison of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) concentrations and serum or urinary neopterin levels in testicular cancer patients showed that determination of neopterin provides no further information in the management of these patients. In testicular cancer patients receiving adjuvant chemotherapy, a significant increase in serum (p less than 0.005) and urinary (p less than 0.0005) neopterin concentrations was measured after chemotherapy, reflecting the release of neopterin from macrophages during the damage by cytotoxic drugs. In the adjuvant testicular tumour patients, known to be tumour free, 1 out of 16 patients showed elevated serum and 3 out of 15 patients showed false positive urinary neopterin levels. False positive serum (24%) and urinary (37%) neopterin values were also obtained in 28 patients with various nonmalignant diseases, but no evidence for an inflammatory process. In 23 patients with inflammatory diseases pathological serum and urinary neopterin levels were measured in 55% and 59% respectively. When a RIA was compared with a HPLC method, higher urinary neopterin values were obtained with the RIA, indicating that non-oxidized pterines are also determined by the RIA method. In conclusion, neopterin might be a helpful biological marker in monitoring patients with malignant haematological disorders and renal cell carcinoma, but provides no additional information in other solid tumours studied.

Adolescent↗

The use of bioluminescence to evaluate the influence of chemotherapeutic drugs on ATP-levels of malignant cell lines.

Influence of various cytostatic agents on intracellular ATP concentrations of malignant cell lines was studied. The HL-60 promyelocytic cell line, the SW-480 cell line, derived from an adenocarcinoma of the colon and the SW-620 cell line, derived from a lymphonodal metastasis of the colon carcinoma, were investigated. Cell lines were incubated with cytostatic agents and changes in intracellular ATP concentrations were measured after various incubation times by means of bioluminescence. A marked fall in intracellular ATP concentrations was observed, when HL-60 cells were incubated with drugs used in clinical protocols for treatment of acute leukaemia (daunorubicin, vinblastine, vincristine), whereas only a slight decrease of ATP concentrations was measured after incubation with bleomycin, dacarbazin and prednisolone. The decrease in intracellular ATP concentrations of SW-480 and SW-620 cells was much less pronounced after incubation with cytostatic agents compared to the HL-60 cells. This is in accordance with the clinical experience of the known resistance of colon carcinoma against cytostatic agents. Dose-response curves were obtained for the single cytostatic agents. Comparison of intracellular ATP concentrations and cell viability as determined by the trypan blue and eosin dye exclusion test showed that the trypan blue dye exclusion test underestimated cell kill compared to the eosin dye exclusion test and the bioluminescence assay.

Adenosine Triphosphate↗

[Angiotensin-converting enzyme in patients with temporal arteritis].

It is well documented in the literature that patients with active sarcoidosis exhibit elevated serum ACE activity. Since both temporal arteritis and sarcoidosis represent granulomatous inflammatory conditions, this study was undertaken to determine serum ACE activity in patients with temporal arteritis as well as in a control group. The serum ACE levels in patients with temporal arteritis were significantly lower than in the controls. Hence, granulomatous inflammation in temporal arteritis seems to differ radically from the granulomatous inflammation present in sarcoidosis. Serum ACE activity was increasing during cortisone treatment of patients with temporal arteritis, but dropped again as soon as cortisone therapy was discontinued.

Aged↗

[Significance of hormone receptors of breast cancer cells for the duration of a disease-free interval].

The importance of the presence of hormone receptors of cells derived from breast cancer tissue for the duration of the relapse-free interval was evaluated in 41 patients with stage II breast cancer. After modified radical mastectomy with axillary lymphadenectomy the patients received radiotherapy and adjuvant polychemotherapy and/or hormone therapy. There was no indication of metastases in any patient at the time of operation. There was a significant correlation of the relapse-free interval to tumor size (p less than 0.05), to the number of involved lymph nodes (p less than 0.0005), and also to the presence of the progesterone receptor (PgR), which seemed to play a more important role in this context than the oestrogen receptor (ER) (p less than 0.001). We conclude from this study that the evaluation of the PgR in breast cancer cells is important for the prognosis of the duration of the relapse-free interval.

Antineoplastic Combined Chemotherapy Protocols↗

Effects of variations in thyroid hormone serum concentrations on serum ACE-activity.

Serum angiotensin converting enzyme activities were significantly increased in 26 untreated hyperthyroid patients (20.3 +/- 5.4 U/ml; P less than 0.001) compared with healthy control subjects (13.1 +/- 2.3 U/ml). In 12 patients a significant fall in enzyme activities was observed after treatment compared with pretreatment serum ACE levels (P less than 0.001). Eight patients with hypothyroidism (15.7 +/- 5.1 U/ml) and 11 athyreotic patients, totally thyroidectomized for well-differentiated thyroid cancer, showed no significant differences in serum ACE activities (14.3 +/- 2.2 U/ml) compared with control subjects. After thyroid hormone supplementation a significant increase in serum ACE activity (P less than 0.05) was found in the athyreotic patients. Addition of increasing amounts of L-thyroxine to a serum sample of an athyreotic patient showed no significant effect on ACE activity in vitro. We suggest that the elevated serum ACE activity in hyperthyroidism is not from the thyroid gland, but represents a direct effect of thyroid hormone on ACE synthesis and/or release from endothelial cells.

Adult↗

Treatment with recombinant interferon-alpha-2C: multiple myeloma and thrombocythaemia in myeloproliferative diseases.

Forty-two patients with multiple myeloma were allocated to two groups to receive either polychemotherapy with vincristine, melphalan, cyclophosphamide and prednisolone, or recombinant interferon-alpha 2C monotherapy. The response rate of 43% in the interferon group was significantly lower than that in the chemotherapy group (89%). Patients with stage I disease showed better response rates than those with stage II or stage III disease. Eleven patients with thrombocythaemia due to polycythaemia vera, chronic myeloid leukaemia or essential thrombocythaemia were treated with recombinant interferon-alpha 2C and complete remissions were achieved in 7 of the 8 evaluable patients. Side-effects were common on interferon therapy, but could be reduced by dose reduction and were reversed by cessation of treatment.

Adult↗

Phase II results with recombinant interferons: renal cell carcinoma and malignant melanoma.

There is as yet no effective treatment for renal cell carcinoma and metastasizing malignant melanoma. This fact, coupled with in vitro investigations showing growth inhibitory or cytotoxic effects of interferon (IFN) on renal cell carcinoma and melanoma cell lines, led to phase II clinical trials with recombinant (r) IFN-alpha 2C and rIFN-gamma. So far 8 patients with renal cell carcinoma have been treated with IFN-alpha 2C and 3 patients with rIFN-gamma. There has been one complete response to IFN-alpha 2C, two mixed responses and one partial response. One patient on rIFN-gamma has stable disease and the other 2 have progressed. Eleven patients with metastasizing malignant melanoma were treated with IFN-alpha 2C. One patient achieved a complete remission and 3 others had stable disease which later progressed in 2 of them. Side-effects were reversible.

Adult↗

[Interferon in the treatment of multiple myeloma].

The effect of recombinant interferon-alpha-2C monotherapy was compared with the efficacy of VMCP-polychemotherapy in 42 patients with multiple myeloma in a prospective randomized multicenter trial. IFN-treatment induced remissions (R) in 2 (14%) and partial remissions (PR) in 4 (29%) out of 14 evaluable patients. 7 patients remained stable. Polychemotherapy induced R in 11 (57%) and PR in 6 (32%) of 19 evaluable patients. 2 (11%) patients remained stable. IFN was preferentially active in patients with low tumor burden and patients with IgA paraprotein. The proportion of responders (R + PR) was significantly lower in the IFN-arm (43%) compared to the polychemotherapy group (89%; p less than 0,001).

Antineoplastic Combined Chemotherapy Protocols↗

[Interferon (IFN) therapy (recombinant IFN-alpha-2C or recombinant IFN-gamma) in metastasized hypernephroma].

Recombinant interferon-alpha-2C (rec. IFN alpha-2C) and recombinant interferon-gamma (IFN-gamma) was studied in 12 patients with metastasized renal cell carcinoma. 8 patients were treated with IFN-alpha-2C: 1 patient achieved a complete remission, 2 patients showed mixed responses, and 2 had stabilisation of their disease. In 3 patients progressive disease was observed. IFN-gamma was studied in 4 patients; 2 patients showed stable and 2 progressive disease. Side effects of IFN-alpha treatment included influenza-like symptoms, moderate hematological toxicity and neurological symptoms. During treatment with IFN-gamma similar side effects were observed, although fever generally was more pronounced. All symptoms ceased after dosis reduction or discontinuation of treatment.

Adult↗

Evaluation of serum fucosyltransferases in malignancy.

Incorporation of [14C]-fucose into the endogenous acceptor of serum and into the exogenous acceptors desialofetuin (alpha 2-fucosyltransferase) and desialodegalactofetuin (alpha 3-fucosyltransferase) was determined in controls and in patients with various malignant diseases. Seventy-five percent of untreated cancer patients showed increased incorporation rates into the endogenous acceptor of serum. Increased rates of alpha 2-fucosyltransferase activity were observed in 67% and of alpha 3-fucosyltransferase activity in 49% of patients respectively. After successful chemotherapy a fall of fucosyltransferase activities could be observed and in non-responding patients an increase of fucosyltransferase activities during and after therapy was found. Determination of fucosyltransferase activities might provide an additional biological marker in monitoring cancer patients.

Breast Neoplasms↗

Increased angiotensin-converting enzyme activities in diabetes mellitus: analysis of diabetes type, state of metabolic control and occurrence of diabetic vascular disease.

Serum angiotensin-converting enzyme activities were measured in 41 type 1 diabetics (16.4 +/- 4.0 U/ml), in 40 type 2 diabetics (15.0 +/- 5.2 U/ml) and in 52 controls (13.0 +/- 2.7 U/ml, mean +/- SD). Twenty six (32%) of 81 patients presented with serum angiotensin-converting enzyme activities above the normal range. No relation between serum angiotensin-converting enzyme activities and the presence or lack of diabetic vascular diseases in type 1 and type 2 diabetics could be detected. No significant differences in serum angiotensin-converting enzyme activities were found when comparing various types of diabetic vascular disease (retinopathy, neuropathy, renal failure, arterial vascular disease, diabetic vascular disease, coronary artery disease). However, mean serum angiotensin-converting enzyme activities were significantly increased in diabetics with retinopathy when compared with controls (p less than 0.0005). Correlation between metabolic long term control as determined by measuring glycohaemoglobin (HbA1) concentrations and serum angiotensin-converting enzyme activities could not be established. Serum angiotensin-converting enzyme activities did not show any correlations with duration of diabetes, age or sex of patients. A representative number of diabetics (32%) showed elevated serum angiotensin-converting enzyme activities, but a correlation with diabetic vascular disease, metabolic control or type of disease could not be established.

Adult↗

[Laboratory findings in the "Vienna Health Study 79" (author's transl)].

In the course of a health study carried out 1979 in Vienna on more than 2,500 persons at the age of 25, 40 and 60 years respectively, the following blood parameters were investigated: erythrocytes, hemoglobin, hematocrit, serum iron, OGTT, HbA1, uric acid, cholesterol, HDL-cholesterol, SGOT, SGPT, AP, creatinine, BUN; furthermore the usual clinical urine findings. Results are exposed and discussed.

Adult↗

[The serum uric acid level in the Viennese population (author's transl)].

Serum uric acid determinations were made in 2,626 subjects (males and females) within the framework of the "Wiener Gesundheitsstudie 1979", at three distinct age levels (25, 40 and 60 years). The serum uric acid level in male subjects was found to have an arithmetic mean of 6.25 mg/dl, whereas in female subjects the serum uric acid levels, with an arithmetic mean of 4.66 mg/dl, were considerably lower. Levels of more than 7 mg/dl occurred in 3% of the female subjects, whereas hyperuricaemia was detected in 25.4% of the males. In addition, hyperuricaemia was correlated with other risk factors. A relation between hyperuricaemia and coronary heart disease and myocardial infarction was found in the subgroup of the 60 year-old men. There is, furthermore, a pronounced association between hyperuricaemia and a tendency to overweight. The "protective effect" of diabetes mellitus on hyperuricaemia was confirmed only in the subgroup of the 60 year-old men.

Adult↗

[Proteinase inhibitors and fibrinogen split products in patients with malignant diseases (author's transl)].

Fibrinogen degradation products could be detected frequently in patients with metastasized tumour disease. Plasminogen, antithrombin III and fibrinogen were not found to be elevated. The proteinase inhibitors alpha 2-macroglobulin, alpha 1-antitrypsin and C1-esterase inactivator were measured before and after chemotherapy. alpha 1-antitrypsin and C1-esterase inactivator were elevated in patients with pulmonary and/or retroperitoneal metastases. Regardless of the stage of the tumour disease serum level of alpha 1-antitrypsin and C1-esterase inactivator in increased under cytotoxic chemotherapy.

Antifibrinolytic Agents↗