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Biomedical subjects

F Porzsolt

Publications and source records attributed to F Porzsolt.

At least 55 records · Page 3Linked to original sources
PubMed1995

Symposium on health economics in oncology. Freiburg, Germany, June 1995.

Dr. E. Enghofer (Wien, Austria) summarized the content of the presentations and discussions of the symposium in his concluding remarks. 1. The organizers should be congradulated on their initiative in bringing together at the symposium experts from different disciplines, i.e., medicine, ethics, health economics, jurisprudence, the pharmaceutical industry and, last but not least, cost providers. 2. Health economics as an issue in health care has been around for quite some while. One example can be found in the German Drug Guidelines dating back to 1990, where the following terms have already been defined: therapeutic benefit, medical needs, and achieving therapeutic goals. 3. Health economics serves as a "support function" in the medical decision-making process. It has as yet no decisive role in the application to license a drug nor in questions concerning a physician's liability. Health economics as a discipline, however, was a reminder of, and served as a catalytic function for: a) The differentiation between the benefit of a medical intervention and its pure effectiveness. b) The definition of medical standards as a means to compare the quality of health care between different institutions, to uncover quality deficits and to develop strategies for the optimization of medical quality (quality management). Routine deviation from these standards is unethical. The German Cancer Society has taken on the task of defining such standards in cancer care. c) The difference between rationalising and rationing health care. The spending of the current health-care budget needs to be screened for unnecessary and/or inappropriate diagnostic procedures and treatment modalities as well as for "below-standard" care. The money that can be saved here can then be shifted towards financing "state of the art" medicine or can be used in the decision to substitute certain procedures. 4. The a priori definition of the desired outcome of a medical intervention is of paramount importance for the evaluation of the actual treatment result. Economical evaluations are easier when cure rather than palliation is the aim of a particular treatment and when alternative therapies do exist such that cost comparisons are possible. In any case, therapeutic interventions need to be adapted to the desired treatment goal; only then can the question be answered whether or not the means (cost) are (is) justified. 5. Outcome studies need to take into account every relevant medical aspect (i.e. disease management studies), and they should be accompanied by evaluation studies. The latter must also include unselected patients in daily practice.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗
PubMed1995

Evidence for a paracrine pathway of B-cell stimulation in hairy cell leukaemia.

It is a well-known phenomenon that the growth of malignant B-lymphocytes, i.e. hairy cells, is regulated by cytokines. Several investigators have suggested that the stimulating cytokines are produced by the malignant B cells themselves, indicating an autocrine growth regulation. In this paper we demonstrate that T-lymphocyte clones produce soluble mediators which stimulate the growth of malignant B lymphocytes. The incidence of the growth-stimulating T-cell clones derived from peripheral blood is identical in patients with hairy cell leukaemia (HCL) and healthy controls. About 50% of the clones stimulate the growth of hairy cells, but not the growth of purified B lymphocytes of healthy donors. The stimulating activity of a single clone varies when tested on different hairy cells. Interferon alpha (IFN alpha), but not antibodies against tumour necrosis factor alpha (TNF alpha) or interleukin-2 (IL-2), completely inhibit the growth-stimulating activity. Our results indicate that a paracrine growth regulation has to be considered in addition to the postulated autocrine loop in the growth regulation of malignant B cells.

B-Lymphocytes↗
PubMed1995

Palliative therapies in elderly cancer patients.

Palliative therapy in elderly cancer patients deserves special attention because of differences between young and elderly cancer patients. In elderly patients, the treatment produces more adverse effects and the disease is cured less frequently, but the prognosis is usually better than in young patients with cancer. In the elderly population, cancer is seen more frequently than in the young population, yet elderly patients are less frequently included in trials. It is obvious that the results obtained from the treatment of young cancer patients do not necessarily apply to elderly cancer patients. The existing lack of formal data for the management of elderly cancer patients justifies 5 distinctive steps: collection of individual information; review of the available and appropriate knowledge; definition and specification of treatment goals; selection of treatment tools; and assessment of outcome. Following these steps will lead to coordination of oncology and palliative medicine.

Adult↗
PubMed1995

Autocrine and paracrine regulation of neoplastic cell growth in hairy cell leukemia.

Hairy cell leukemia (HCL), a rare haematological disorder of B-cell origin, mainly presents with bone marrow infiltration, haematopoietic insufficiency, and splenomegaly. In some cases, osteolytic lesions can be observed. Many of these clinical features, especially haematopoietic insufficiency and osteolytic lesions are likely to be caused by soluble factors, such as cytokines. There is evidence that these factors are produced by the malignant hairy cells themselves, suggesting a paracrine pathway. The importance of autocrine as well as paracrine growth loops in growth regulation of HCL-cells is supported by a series of excellent studies, performed within the last few years. It could be clearly shown that cytokines are involved in this autocrine and paracrine regulatory process. The most important cytokines which should be mentioned in this respect are tumor necrosis factor alpha, (TNF alpha). Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6) and B-cell-growth factor (BCGF). The role of other factors such as viruses and oncogenes remains rather unclear. Nevertheless, recent data suggest that the c-fms, which encodes for the macrophage colony stimulating factor (M-CSF) may be involved in the pathophysiological control of HCL growth. In this review, we summarise the important data and studies performed recently which shed light on the complex network of autocrine and paracrine growth regulation of HCL.

Cell Division↗
PubMed1995

[Assessment of medical measures].

PURPOSE: Recently, the discipline Health Economics gained considerable interest. This interest was stimulated by the experienced limitations of resources and cost containment which requires the analysis of the values of treatments based on their relative costs and outcomes. The experiences of limited resources could lead to purely cost-based decisions such as favoring inexpensive services instead of facilitating the access to better and more useful ones. In order to decrease the risk of such uneconomic decisions we propose a hierarchy of assessments for the evaluation of clinical services. RESULTS: This hierarchy is based on the distinction of effectiveness and utility of medical service. Effectiveness is expressed in variable dimensions such as duration of sleep, concentration of blood sugar or diameter of a lesion. Utility is expressed by prolongation of survival and/or improvement of quality of life. The hierarchy suggests to assess the clinical utility from the patient's point of view as a first step by measuring the effects of the service on quantity and quality of life. In a second step, the clinical value of alternative medical interventions from the patient's point of view should be assessed by measuring the patient preference prospectively or the patient compliance retrospectively. Finally, as a third step, the economic value is assessed by comparing costs with outcomes. CONCLUSIONS: The suggested hierarchy should support the selection of the most useful services among alternative measures. In addition it should stimulate cooperation between the involved disciplines.

Economics, Medical↗
PubMed1994

Sensitive antiproliferative neutralization assay for the detection of neutralizing IFN-alpha and IFN-beta antibodies.

Antibodies to interferon (IFN) may compromise IFN treatment in some patients. In tumor therapy, a critical function of type I IFNs is their antiproliferative effect. For the quantification of neutralizing IFN antibodies we have developed an antiproliferative neutralization assay (APA) based on the reduction of IFN-mediated growth inhibition of Daudi cells by IFN-alpha and IFN-beta antibodies. Proliferation was quantified by [3H]thymidine incorporation, and the neutralizing potency of IFN antibody-positive sera was expressed as the neutralizing titer inhibiting 50% of the antiproliferative activity of 10 IU/ml of IFN (NT50). The APA is easy to perform, reproducible, and more sensitive than a well-established antiviral neutralization assay (AVA). All 30 sera with recombinant IFN-alpha 2a-binding antibodies proved to be neutralizing antibody-positive in the APA whereas seven were scored antibody-negative or uninterpretable in the AVA. The APA is recommended as a second or third line assay for the estimation of the neutralizing potency of spontaneous or treatment-induced IFN-alpha and IFN-beta-specific antibodies.

Animals↗
PubMed1994

Capillary leak syndrome associated with elevated IL-2 serum levels after allogeneic bone marrow transplantation.

The pathophysiological mechanisms involved in the development of a spontaneous systemic capillary leak syndrome (CLS) are unknown. In contrast, CLS is a well-known side effect of high-dose interleukin-2 (IL-2) therapy in solid tumors. We report on a patient who developed CLS with high serum levels of endogenous IL-2 under immunosuppressive therapy for chronic graft-versus-host disease (GvHD) after allogeneic bone marrow transplantation (BMT). Generalized edema persisted for 10 weeks. The condition resolved after antibiotic therapy of a septic shock with beta hemolyzing streptococci group A. Thus, a latent infection may alter cytokine homeostasis and may cause CLS in BMT patients.

Adult↗
PubMed1994

Interleukin-6 stimulates the hypothalamus-pituitary-adrenocortical axis in man.

A recent study in humans, animal studies, and in vitro data have suggested that interleukin-6 (IL-6) stimulates the secretory activity of the hypothalamus-pituitary-adrenocortical (HPA) axis. In a phase II study, one female and six male patients with metastatic renal cell carcinoma received IL-6 to evaluate a possible antitumor effect of IL-6. This offered the possibility of investigating the influence of IL-6 on the HPA axis in man. The subjects were studied 1 day before, on day 1, and on day 21 of IL-6 therapy (150 micrograms administered sc every day at 0900 h). Blood samples were taken at 0900, 1100, 1300, 1600, and 2000 h the day before, on day 1 of IL-6 therapy, 24 h after the first IL-6 injection, and on day 21 of IL-6 treatment. Plasma ACTH and cortisol levels promptly followed the rise of IL-6, which peaked 4 h after administration. They were significantly (P < 0.05) higher at 1100 and 1300 h on day 1 of IL-6 therapy compared with the corresponding plasma levels the day before IL-6 treatment. Cortisol concentrations remained significantly increased at 1600 and 2000 h after IL-6 administration. Twenty-four hours after the first IL-6 administration, IL-6, ACTH, and cortisol levels had reached preinjection values. Although plasma cortisol levels were similar on days 1 and 21, ACTH levels were lower on day 21 (than on day 1), but significantly elevated at 1100 h compared with levels on the day before the first IL-6 injection. Results confirming the very recent data of another study demonstrate a stimulating effect of IL-6 on the HPA axis in man. They support the notion that IL-6 is one of the cytokines involved in the interaction between the immune system and the HPA axis.

Adrenal Cortex↗
PubMed1994

Cyclosporin A inhibits cytokine-induced proliferation in B-chronic lymphocytic leukemia.

We investigated the effects of the immunosuppressant cyclosporin A (CsA) on proliferation of neoplastic B-cells from patients with B-chronic lymphocytic leukemia (B-CLL). Cell growth was induced in vitro by tumor necrosis factor alpha (TNF-alpha (8/16), interleukin 2 (IL-2 (9/16) or both (7/16), in 4 cases spontaneous proliferation was observed. We were able to demonstrate that CsA inhibits cytokine-induced proliferation, as measured by [3H]-thymidine incorporation, in all cases responsive to TNF-alpha or IL-2 as well as in spontaneous proliferation. CsA did not increase the fraction of trypan blue positive cells or apoptosis. Growth inhibition by CsA occurred in a dose dependent manner: 100 ng/ml CsA was the optimal concentration which blocked about 90% of cytokine induced or spontaneous proliferation. We could also demonstrate that the effect of CsA was reversible and that no blocking effect was observed when CsA was added later than 48 hours after stimulation. Cell cycle analysis using propidium iodide as a DNA stain demonstrated that CsA prohibited the progression of B-CLL cells from the G1-phase to the S-phase of the cell cycle. However, we were also able to show that TNF-alpha induced proliferation of hairy cell leukemia (HCL) was not affected by CsA. This observation indicates that the inhibitory activity of CsA seems to be restricted to only a few haematological diseases such as B-CLL.

Apoptosis↗
PubMed1994

Paracrine regulation of B-cell growth in hairy cell leukemia.

There is evidence that the growth of malignant B lymphocytes e.g. hairy cells is regulated by cytokines. Several investigators suggested that the stimulating cytokines are produced by the malignant B cells indicating an autocrine growth regulation. Here we demonstrate that T lymphocyte clones produce soluble mediators which stimulate the growth of malignant B lymphocytes. The incidence of the growth stimulating T cell clones derived from peripheral blood is identical in patients with hairy cell leukemia (HCL) and healthy controls. About 50% of the clones stimulate the growth of hairy cells, but not the growth of purified B-lymphocytes of healthy donors. The stimulating activity of a single clone varies when tested on different hairy cells. Interferon alfa but not antibodies against tumor necrosis factor alfa or interleukin-2 inhibit completely the growth stimulating activity. We propose that interferon alpha inhibits the production of soluble mediators produced by normal T-cells. Our results indicate that a paracrine growth regulation has to be considered in addition to the postulated autocrine loop in the growth regulation of malignant B cells.

B-Lymphocytes↗
PubMed1994

Bone densitometry and histomorphometry in patients with hairy cell leukemia.

Tumor necrosis factor alpha, the cytokine that participates in the autocrine growth control of hairy cell leukemia has strong bone resorptive properties. This prompted us to look for bone involvement in HCL. Bone mineral density (BMD) was not decreased in 14 HCL patients who did not have radiographic evidence of bone destruction. Osteopenia was found in only two HCL patients with skeletal complications of the disease and bone pain preceded diagnosis in both cases. Lymphomatous infiltration of the vertebral bodies T 12/L1 was confirmed histologically in the female patient while bilateral necrosis of the femoral head preceded the diagnosis of HCL in the male patient. Histomorphometry of bone biopsy samples was performed in another 12, previously untreated male HCL patients. Trabecular bone volume was found to be reduced in 11, greatly reduced in 5 of them, while osteosclerosis was found in only one patient. The increase of trabecular bone pattern factor, a new parameter for simple quantification of trabecular interconnection indicated a poorly connected trabecular lattice in eight of these 12 patients.

Adult↗
PubMed1994

High-titre interferon-alpha antibodies in a patient with chronic graft-versus-host disease after allogeneic bone marrow transplantation.

In a patient undergoing allogeneic BMT for chronic phase CML, de novo chronic GVHD developed within 80 days after transplantation. Eighteen months post-BMT, high serum levels of neutralizing interferon-alpha (IFN-alpha) antibodies were detected, which persisted despite continuous immunosuppressive treatment. The antibodies were of oligoclonal or polyclonal origin, predominantly of the IgG1 type, and reacted broadly with various human IFN-alpha types, including the patients endogenous IFN-alpha, but failed to recognize natural IFN-beta and recombinant IFN-gamma. Pathogenesis and clinical impact of the IFN-alpha antibodies are unknown. Antibodies of cytokines are a novel class of autoantibodies that may develop after allogeneic BMT and interfere with cytokine homeostasis and immune regulation.

Adult↗
PubMed1993

Goals of palliative cancer therapy: scope of the problem.

This article describes some of the problems of palliative cancer therapy and proposes possible solutions. The topics discussed include the reasons for death in cancer patients, the definition of intermediate and indirect as opposed to direct and measurable goals of treatment, the insufficient outcomes of palliative therapies and the problems associated with the separation of palliative treatment and palliative care. As a solution to these problems, a concept of Tumor versus Host Disease (TvHD) is discussed, and different end points for palliation are defined for daily oncology practice and oncology research. Finally, a way to collect data outside randomized trials is proposed, and the need for data collection is emphasized.

Goals↗