Biomedical subjects

Z Adam

Publications and source records attributed to Z Adam.

At least 73 records · Page 4Linked to original sources

PubMed1996

Evolution of multiple myeloma treatment from melphalan monotherapy to bone marrow transplantation.

Melphalan has brought the first improvement in the therapy of multiple myeloma at the beginning of the sixties. The median of survival was prolonged from several months to 3 years. In the following 3 decades new drugs were tested, but no other drug brought better results than melphalan. The comparative studies have proved, that therapy response has been reached more rapidly after polychemotherapy than after monotherapy, but none of the treatment modalities differed in the survival parameters. The significance of interferon alpha for the treatment of multiple myeloma has been tested since the beginning of the eighties. Many clinical trials have brought controversial results. The latest metaanalysis and data published support the indication of interferon alpha for the multiple myeloma maintenance treatment. Important progress in the therapy of multiple myeloma has been done in the nineties. High doses of alkylating cytostatics with the support of autologous peripheral blood stem cells transplantation or bone marrow transplantation enhanced the number of therapy-responses and prolonged the survival. The results of autologous transplantations are so favourable, that this procedure can be recommended as the first line treatment in suitable patients. Allogenic bone marrow transplantation is linked with many complications and therefore this method will be performed only in a limited number of patients. Trials dealing with this new therapy-trends are viewed in this paper.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

New approaches to management of multiple myeloma.

A new era of multiple myeloma (MM) management includes new approaches such as genetic marking and gene therapy, immunotherapy, stimulation of graft versus myeloma effect, etc. Intensive clinical research is also focused on the detection of minimal residual disease and bone marrow purging. Autoregulatory loop of myeloma cells and detection of genes responsible for pathological transformation of B-line cells is of great research interest. Clinical trials have begun and the first results are promising, though preliminary. The safety of the patients and the public must be major concern of all investigators. The combinations of new types of therapeutical approaches with the most efficient regimens used until now could form a new type of MM management strategy that better involves minimal residual disease.

Bone Marrow Purging↗

PubMed1996

[The effect of clodronate on bone density in patients with multiple myeloma--a 2-year follow-up of therapeutic effects].

Biphosphonates are used for the treatment of hypercalcaemia as well as in normocalcaemic patients for the long-term inhibition of malignant osteolytic bone processes. In patients with multiple myelomas treated with biphosphonates in randomized studies a reduction of the number of new osteolytic foci was proved and improvement of the quality of life. The objective of the present study was to evaluate the effect of clodronat on the development of bone density in patients with multiple myeloma. In the study since 1993 27 patients were included. In August 1995 22 patients were evaluated who were treated for more than 12 months with clodronat (Bonefos Leiras). The patients were given clodronat in i.v. infusions (five infusions à 600 mg) in three-month intervals. After six-month intervals the amount of hydroxyapatite in the lumbar vertebrae was evaluated by CT densitometry. Statistical testing of trends of assessed bone density values revealed that not even after two years of the disease a statistically significant reduction of the bone density occurs. Treatment was very well tolerated, gastrointestinal problems were an exception. At the onset of the investigation three patients had symptoms of mild tetany, and a decline of the calcaemia below normal values was recorded. As soon as regular administration of calcium preparations was started during clodronat administration, the calcaemia did not decline below normal levels and enhanced neuromuscular irritability did not develop. Clodronat stabilizes the amount of bone mass, reduces pain and also improves the quality of the patients life. It should be included among standard treatment of patients with multiple myeloma.

Adult↗

PubMed1996

[Treatment of chronic lymphatic leukemia].

Chronic lymphocytic leukemia (CLL) is a slow lymphoproliferative disease. The therapy has only a palliative effect and therefore the common attitude to the therapy is conservative (watch and wait policy). Monotherapy with alkylating cytostatics, usually chlorambucil, is considered by most authors to be the therapy of first choice. Only the French study showed superiority of polychemotherapy CHOP over monotherapy. New drugs for the treatment of chronic lymphocytic leukemia are purine-analogs. Fludarabine has been used mostly of this purine-analogs. The response rate to fludarabine therapy is 30-45% in pretreated patients and the response rate in the chemotherapy-naive patients is about 80%. 2-chlorodeoxyadenosine was used in the same indications and it showed that this drug had a similar effect in this disease as fludarabine. The contemporary indication for fludarabine is standard-chemotherapy-refractory disease. Whether this drug will be used for initial therapy, is a question. Interferon alpha is therapeutically active in early stages of chronic lymphocytic leukemia, but it is unclear, if this response has any influence on survival. Interferon alpha is ineffective in advanced stages of this disease. The role of interferon alpha as the maintenance treatment after chemotherapy is heavily discussed.

Antineoplastic Agents↗

PubMed1996

[Myeloproliferative diseases].

Myeloproliferative diseases include primary polycythemia, primary thrombocytosis, primary myelofibrosis and chronic myeloid leukaemia. The average survival of patients with the former two diagnoses is more than 10 years, in the subsequent two it is only 5 years. Standard treatment of polycythemia still remains phlebotomy, only in patients with associated thrombocythemia and complications caused by it cytoreduction treatment is recommended (hydroxyurea, busulphan or interferon alpha). Patients with primary thrombocythemia due to hypofunctional thrombocytes suffer frequently from haemorrhagic and thrombotic complications. The objective of treatment is therefore to achieve a normal number of thrombocytes. Medicamentous procedures are the same as in primary polycythemia. In primary myelofibrosis and chronic myeloid leukaemia it is also necessary to reduce the pathological population in bone marrow by the above mentioned therapeutic procedures. Contrary to the former two diagnoses, the survival of patients with primary myelofibrosis is shorter and the patients need more supportive treatment. In chronic myeloid leukaemia also transplantation treatment can be used, if a suitable donor is available. The decision between classical and transplantation treatment must be made soon after establishment of the diagnosis. The objective of the following paper is to inform readers on the clinical course of different diseases, on differential diagnostic problems and changes in therapeutic procedure which have developed in recent years.

Diagnosis, Differential↗

PubMed1995

Mutations in the processing site of the precursor of ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit: effects on import, processing, assembly and stability.

The small subunit (SSU) of Rubisco is synthesized in the cytosol in a precursor form. Upon import into the chloroplast, it is proteolytically processed at a Cys-Met bond to yield the mature form of the protein. To assess the importance of the Met residue for recognition and processing by the stromal peptidase, we substituted this residue with either Thr, Arg or Asp. The mutant precursor proteins were imported into isolated chloroplasts, and the products of the import reactions were analyzed. Mutants containing Thr or Arg residues at the putative processing site were processed to a single peptide, comigrating with the wild-type protein. N-terminal radio-sequencing revealed that these mutants were processed at the Cys-Thr and the Cys-Arg bond, respectively. After import of the Asp-containing mutant, four processed forms of the protein were observed. Analysis of the most abundant one, co-migrating with the wild-type protein, demonstrated that this species was also a product of correct processing, at the Cys-Asp bond. All the correctly processed peptides were found to be associated with the holoenzyme of Rubisco, and remained stable within the chloroplast, like the wild-type protein. The results of this study, together with previous ones, suggest that proper recognition and processing of the SSU precursor are more affected by residues N-terminal to the processing site than by the residue on the C-terminal side of this site.

Amino Acid Sequence↗

PubMed1995

Increasing bone density in myeloma patients after the administration of clodronate.

The use of bisphosphonates in hypercalcemia is fully accepted, but the long term therapy with bisphosphonates is still controversial. The aim of our study was to evaluate the influence of clodronate on the bone density of myeloma patients. 20 patients were included in the study. A total dose of 3000 mg clodronate was administered in 4 to 6 hourly infusions of 600 mg a day, once in 3 months. The effect of clodronate on bone density was evaluated by CT-densitometry over a period of 6 months. At the beginning of May 1994, 15 patients had completed at least 2 estimations of bone density. The amount of hydroxyapatite had increased in 9 patients, remained unchanged in 1 of them, and decreased in 4 of them during the 6 months. The mean bone density before the administration of clodronate was -2.6 SD (standard deviation of European standard bone density for the respective age and sex). After 6 months of therapy, bone density had increased to -2.3 SD. The mean amount of hydroxyapatite in spongiosa rose from the mean value of 32.71 mg/ml before clodronate administration to 38.91 mg/ml after the 6-month treatment period. The mean increase in calciumhydroxyapatite in trabecular bone mass was 6.2 mg. Clodronate contributed to alleviating bone pain in the majority of patients, but this effect is difficult to evaluate because of other treatment modalities administered concomitantly. The tolerance of clodronate was very good. No impairments of renal function, nor other adverse effects were observed. Only in 2 patients the decrease in calcium concentration caused slight tetania.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

[Tolerance and results of treatment of Hodgkin's disease].

At present the accepted standard chemotherapeutic treatment of Hodgkin's disease is therapy according to the MOPP pattern (mustargen, vincristine, procarbazine and prednisone) alternating with the ABVD therapeutic pattern (adriamycin, bleomycin, vinblastine and dacarbazine). It is substantial for achieving optimal results to administer the planned treatment in non-reduced doses and at the scheduled time. In the submitted paper the authors describe the tolerance of chemotherapy and its results in 15 patients and the tolerance of radiotherapy in another four patients suffering from Hodgkin's disease. Complications of chemotherapy (leukopenia and infection) caused an overall average retardation of chemotherapy of 37 days per patient. This interval would be certainly longer if the patients were not given Leucomax Schering Plough. From a total of four patients given radiotherapy Leucomax had to be administered to two, otherwise radiotherapy would have had to be discontinued on account of a decline of leucocytes.

Adolescent↗

PubMed1995

[Evaluation of treatment of anemia with erythropoietin in patients with multiple myeloma].

Multiple myeloma is very frequently associated with anaemia which has the character of hypo-proliferative anaemia of chronic diseases. In this type of anaemia the erythropoietin formation is frequently inadequate. According to data in the literature pharmacological doses of erythropoietin lead to an increase of the haemoglobin concentration in blood. Erythropoietin (Eprex Cilag) was administered to 11 patients whose haemoglobin concentration was lower than 100 g/l. The results from 10 patients were finally evaluated. During the first month all patients were given erythropoietin - 150 U/kg three times per week. Unless during the first month of treatment the haemoglobin concentration increased by 10 g/l, the dose was doubled to 300 U/kg. In patients where the haemoglobin value had risen above 120 g/l, the authors assessed an individual maintenance dose. In case three-month erythropoietin treatment did not lead to an increase of haemoglobin by 20 g/l as compared with the baseline value, erythropoietin administration was discontinued. The haemoglobin concentration increased by 20 g/l in a total of 8 (80%) of 10 evaluated patients. In all five patients where the haemoglobin concentration increased by 20 g/l during the first month, the endogenous erythropoietin concentration was less than 60 U/l. In another three patients the mentioned therapeutic response was recorded only during the 2nd or 3rd month of treatment after the erythropoietin dose had been increased. These three patients had higher baseline concentrations of endogenous erythropoietin, 100 to 350 U/l. During treatment no undesirable effects of erythropoietin were observed. Erythropoietin is a useful drug for anaemic patients with the diagnosis of multiple myeloma. According to the results of the authors work and data in the literature it is obvious that in patients with endogenous serum erythropoietin below 100 U/l a rapid riae of haemoglobin can be observed already during the first month. Patients with a higher baseline concentration of endogenous erythropoietin (100 to 500 U/l) respond less frequently to treatment and larger doses of erythropoietin must be administered. In patients with an erythropoietin value above 500 U/l there is a minimal probability that a response will be produced.

Adult↗

PubMed1995

Vinorelbine and cisplatin in the treatment of advanced non-small cell lung cancer: results of a multicenter Czech study.

There is continuous discussion about the optimal treatment for patients with inoperable non small cell lung cancer. This is because chemotherapy can only improve the quality of life in a fraction of treated patients while prolonging survival by a couple of weeks at best. The new cytostatic drug "vinorelbine" has been tested in this indication during the last years. The drug has reached the response rate of 16 to 30% when used as monotherapy. The phase II studies proved the combination of vinorelbine with cisplatin to be the most efficient one and this combination was picked up for phase III clinical trials. The clinical trial with the aims to verify published data on treatment efficacy, to assess adverse effects of treatment and to evaluate appropriateness for routine application has been made in the Czech Republic. The treatment schedule was as follows: cisplatin (Platidiam Lachema) in a dose of 80 mg/m2 on day 1, vinorelbine (Navelbine Pierre Fabre) in a dose of 30 mg/m2 on days 1 and 8. The whole cycle was repeated on day 22. The treatment was applied for 12 weeks. After that the efficacy of treatment was evaluated and only the patients with regression or stabilization of the disease continued the treatment. 44 (35%) partial remissions and 3 (2.3%) complete remissions were achieved in a group of 126 evaluable patients. The effect of treatment was evaluated as stable disease in 35 (27%) patients while the progression of disease occurred in 38 (30%) patients. The tolerance of treatment using effective antiemetic support (ondansetron or granisetron) was fairly good.

Adult↗

PubMed1995

Therapy of anemia in patients with multiple myeloma.

Multiple myeloma is very frequently associated with anemia which has the character of hypoproliferative anemia of chronic diseases. In this type of anemia there is often insufficient production of endogenous erythropoietin. According to literature pharmacological doses of erythropoietin result in the increase of blood hemoglobin concentration. Erythropoietin (Eprex Cilag) was given to 11 patients whose hemoglobin concentration in blood was lower than 100 g/l. 10 patients could be evaluated at the end of the study. Within the first month all patients were given erythropoietin in the dose of 150 U/kg 3 times a week. The dose was doubled, when the blood hemoglobin concentration did not increase by more than 10 g/l within the first month. In patients with hemoglobin level above 120 g/l we were trying to find the individual maintenance dose. In patients who had not reached a blood hemoglobin concentration increase of at least 20 g/l, as compared with the initial level, further erythropoietin administration was stopped. The concentration of hemoglobin increased of 20 g/l in 8 (80%) out of 10 patients evaluated. All 5 patients who responded within the first month, had had pretreatment concentration of endogenous erythropoietin below 60 U/l. Three other patients had not been responding before their dose of erythropoietin was increased in the 2nd and 3rd months of therapy. The therapy response appeared only in the 2nd and the 3rd months of treatment. These 3 patients had higher pretreatment concentrations of endogenous erythropoietin, from 100 to 350 U/l. During the treatment no adverse effects of erythropoietin were observed. Erythropoietin is a useful drug for anemic patients with the diagnosis of multiple myeloma. According to the results mentioned above and also according to the data from literature it is evident that in patients with the endogenous blood erythropoietin value below 100 U/l it is possible to expect a sudden rise in hemoglobin concentration already within the first month. Patients with a higher concentration of endogenous erythropoietin (100 to 500 U/l) respond to the therapy less frequently and for the increase in hemoglobin it is necessary to give higher doses of erythropoietin. Patients with the initial value of erythropoietin above 500 U/l are not likely to respond.

Adult↗

PubMed1994

[Mechanisms of the antitumor effects interferons].

Interferons alpha, beta and gamma form an interferon system, which is part of the non-specific immune defense of the organism. They participate in the defense against virus infections and have a marked immunoregulating effect. By interfering with the transmission of genetic information in the cells they exert an antiproliferative action on sound as well as tumour cells (they inhibit oncogenes). Alpha interferon exerts the most marked antiproliferative action. All mentioned mechanisms participate in the anti-tumourous action of interferons. The most widely used interferon in oncological treatment is interferon alpha.

Animals↗

PubMed1994

[Bone manifestations of multiple myeloma and therapeutic possibilities].

In the text are summarized the results of studies dealing with supportive therapy of multiple myeloma bone disease. The similarities of primary osteoporosis and osteoporosis in multiple myeloma raised a hope that sodium fluoride will help to prevent or to slow down the osteoporotic process in multiple myeloma patients. The first studies in small groups of patients reported some advantage for the patients with sodium fluoride, later in randomized studies no benefit of sodium fluoride was confirmed. The effect of calcitonin was studied in small groups of patients. All studies confirmed analgetic effect and some of them proved positive effect on the amount of bone hydroxyapatite by a histomorphometric examination. The contribution of bisphosphonate to the therapy of myeloma patients was confirmed in extensive studies. With the exception of a Canadian study with ethidronate, all studies reported good analgetic effects and the inhibitory influence on bone destruction. The advantage of bisphosphonates in comparison to calcitonin is the possibility of p.o. administration or in i.v. periodical administration several times a year.

Calcitonin↗

PubMed1994

[Lack of therapeutic effect on primary amyloidosis by interferon-alpha].

The therapy of primary amyloidosis is still unsatisfactory. The response rate after cytostatics, dimethylsulphoxide, colchicin and vitamin E is usually low. None of these treatment modalities prolongs significantly the survival in the majority of treated patients. The success of interferon alpha in the maintenance therapy of follicular non-Hodgkin's lymphoma and in the remission of multiple myeloma, as well as successful treatment of primary cryoglobulinemia, brought us to the idea to test interferon alfa in the therapy of primary amyloidosis. Interferon alpha-2b was administered to a patient with three years history of primary amyloidosis. Interferon alpha was used in the dose of 3 x 10(6) i. V. daily for a treatment period of 10 weeks. The evaluation of the response was based on the weekly assessment of the light chain lambda concentration in the morning spot of urine. No significant decrease of the light chain concentration during the course of the therapy was observed. The administration of interferon alpha-2b was interrupted in the 10th week of the therapy because of manic psychosis. The question is, whether a higher dose than 3 x 10(6) IU daily would be able to decrease the light chain production, or if this disease is resistant to interferon alpha therapy. Because of the low incidence of primary amyloidosis, the experiences will be collected on the base of small groups of case reports.

Amyloidosis↗

PubMed1994

[The pharmacology of biphosphonates and their use in hypercalcemia].

Bisphosphonates, derivatives of pyrophosphates are substances which block the function of osteoclasts and thus break down bone. They can be administered by the oral and i.v. route. Oral treatment is limited by poor absorption which e.g. in clodronate varies between 1 - 5%. The long half-life of bisphosphonates adsorbed on bone makes it possible to achieve the desired effect by administration once in 1 - 3 months. Bisphosphonates are considered the most effective drugs for treatment of hypercalcaemia. Their effect is, however, manifested on the second or third day and thus in case of a serious acute condition caused by hypercalcaemia it is necessary to use yet other treatment commonly recommended in hypercalcaemia.

Acute Disease↗

PubMed1994

[Long-term administration of biphosphonates in oncology patients with bone involvement].

The usefulness of bisphosphonates in the treatment of acute hypercalcaemia has been known for some time. The problem of long-term administration of bisphosphonates to patients whose skeleton is afflicted with a malignant tumour is still being discussed. The benefit of ethidronate has not been confirmed. Clodronate and pamidronate administered in i.v. infusions or in adequate amounts by the oral route leads to a reduced incidence of hypercalcaemic crises and the number of pathological fractures. Both mentioned preparations diminish the intensity of pain, increase physical fitness and improve the quality of life of oncological patients. However, they do not prolong the survival period of these patients.

Bone Neoplasms↗

PubMed1994

[Increased bone density in patients with multiple myeloma treated with clodronate].

The indication of bisphosphonates in hypercalcemia is fully accepted, the long term therapy with bisphosphonates is still controversial. The aim of our study was to evaluate the influence of clodronate on the bone density of myeloma patients. Twenty patients were included in the study. Clodronate is administered in the total dose of 3,000 mg, which is delivered in 4-6 hour infusions, 600 mg/day, once in tree 3 months. The effect of clodronate on bone density is evaluated by CT-densitometry in a period of 6 months. At the beginning of May 1994, 15 patients had completed at least two estimations of bone density. The amount of hydroxyapatite in these six months increased in 9 patients, in one of them there was no change and in 4 of them decreasing bone density was detected. The mean bone density before the administration of clodronate was -2.6 SD (standard deviation of European standard of bone density for age and sex). After 6 months of therapy the bone density increased to -2.3 SD. The mean amount of hydroxyapatite in spongiosa was raised from the mean value 32.71 mg/ml before clodronate administration to 38.91 mg/ml after the 6 month treatment period. The mean increase in calciumhydroxyapatite in trabecular bone mass was 6.2 mg. Clodronate contributed to the amelioration of bone pain in the majority of patients, but this effect is difficult to evaluate because of other treatment modalities administered concomitantly. The tolerance of clodronate was good. No impairments of renal function or other adverse effects were observed. Only in 2 patients the decrease in calcium concentration caused slight tetania. Therefore close monitoring of the calcium level is recommended and in the case of its decrease below the physiological level peroral substitution of calcium was started.

Bone Density↗

PubMed1994

[Cisplatin and carboplatin in the treatment of malignant lymphoma and multiple myeloma].

Experiences with cisplatin and carboplatin are summarized in this paper. The treatment response to monotherapy with cisplatin or carboplatin was proved in non-Hodgkin's lymphomas. This is necessary condition for the application of the drug in polychemotherapy. Cisplatin and carboplatin based combinations are not used as an initial therapy. The indications for these two drugs are primary resistant malignant lymphoma and multiple myeloma, or relapses of these diseases not responding to conventional therapy. Cisplatin based combination therapy can in these indications prolong the survival in 30-40% of patients. The role of carboplatin in malignant lymphoma is not clear yet and is under investigation. The effective antiemetic therapy (ondansetron, granisetron) miligated the fear of vomiting and therefore these combinations are used in resistant malignant lymphoproliferative diseases more then some years ago. In the tables are shown the chemotherapeutic combinations used in non-Hodgkin's lymphomas, Hodgkin disease and multiple myeloma.

Antineoplastic Combined Chemotherapy Protocols↗