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Biomedical subjects

A Galazka

Publications and source records attributed to A Galazka.

At least 19 recordsLinked to original sources
PubMed1992

Phase I study of subcutaneously-administered bacterially-synthesised recombinant human granulocyte-macrophage colony-stimulating factor.

A phase I study was initiated to test the effect of bacterially-synthesised recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). 15 patients with advanced cancers were entered into the study and 14 were evaluable. Patients were administered a single subcutaneous injection (3.0-300 micrograms/m2) of rhGM-CSF. Starting at a concentration of 100 micrograms/m2, an approximate 2-fold increase in leucocyte count was noted 24 h after the injection. By 48 h the counts had returned to baseline. The 300 micrograms/m2 concentration also induced an approximate 2-fold increase. The leucocytosis was associated with a predominant increase in circulating neutrophils and bands. An increase in monocytes was also noted, but peak levels were recorded 48-72 h after the injection. At both the 100 micrograms/m2 and the 300 micrograms/m2 doses, significant levels of circulating rhGM-CSF were detected. The levels measured in the plasma of patients receiving 300 micrograms/m2 were over 10-fold greater than those measured at 100 micrograms/m2. There was no detectable antibody formation against the rhGM-CSF in any of the study patients. The drug was exceptionally well-tolerated. This study shows that rhGM-CSF can be safely administered by subcutaneous administration and a single injection is capable of inducing a leucocytosis with increased circulating neutrophils, bands, and monocytes when doses are used which result in significant levels of circulating rhGM-CSF.

Dose-Response Relationship, Drug↗
PubMed1992

Repetitive weekly cycles of 4-day continuous infusion of recombinant interleukin-2: a phase I study.

A phase I trial was performed with a new interleukin-2 (IL-2) given as a continuous intravenous infusion in patients with solid tumors. The objectives of the study were to examine the feasibility of administering IL-2 in 4-day cycles for 4 consecutive weeks, and to investigate the response pattern of peripheral blood lymphocytes. Tumor necrosis factor (TNF) and IL-2 serum concentrations were also measured. Prior to this study, IL-2 had been tested at increasing dosages during one 4-day cycle, and it appeared that a dose of 1300 mcg/m2/day was tolerated. However, when this treatment schedule was maintained for 4 consecutive weeks, the maximum tolerated dose was 430 mcg/m2/day. In this schedule, a dose-dependent progressive increase in rebound lymphocyte count occurred after each weekly cycle, resulting in a 5-70-fold increase after the 4th cycle. Serum TNF peak concentrations also showed a tendency to increase during each subsequent cycle, while serum IL-2 peak concentrations showed a paradoxical decrease. Clinical toxicity comprised several events, which, possibly, could be ascribed to autoimmune phenomena. Myocardial infarction as a late toxicity of IL-2 is suggested. One complete response (renal carcinoma) and two partial responses (renal and breast carcinoma) were documented, one of these occurring in a patient who previously had shown a transient response on interferon therapy.

Adult↗
PubMed1992

Combination of GM-CSF and cytosine in myelodysplasia results in improved neutrophil function.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was given concurrently with low-dose cytosine arabinoside for 3 weeks to patients with myelodysplasia. Neutrophil activation as evidenced by increased chemiluminescence and reduced surface expression of CD16 was consistently seen during therapy. An attendant fall in chemotaxis was also observed. These effects occurred even when neutrophil counts did not rise significantly at lower doses of GM-CSF. Although no improvement in anaemia or thrombocytopenia was observed, the neutrophil counts became normal during therapy without significant expansion of marrow cellularity or colony-forming ability. No major toxicities were observed, even at higher dosages of GM-CSF.

Antigens, CD↗
PubMed1992

Control of pertussis in the world.

Available data indicate that pertussis remains an important disease during infancy and childhood, particularly among those who are inadequately immunized. Over the past 15 years, successful immunization programmes have been implemented in most countries in the world. Some problems have arisen in the industrialized world where pertussis had been well controlled previously. The underlying causes of these problems are apathy and complacency on the part of physicians and parents, negative attitudes to immunization spread by anti-immunization pressure groups and litigation over liability for alleged vaccine-related injures. In developing countries, immunization coverage with primary series of three doses of DPT vaccine in infants exceeds 80%, but there are considerable differences in coverage rates between regions and between and within countries. Failures to reach and maintain high immunization coverage in developing countries are caused by multiple factors including weak management of immunization services, missing opportunities to immunize eligible children and ineffective information and motivation of mothers to return to complete the immunization series. To effectively control pertussis in the world, all countries should use available pertussis vaccines in immunization programmes for children. Since acellular pertussis vaccines are not generally available, the widespread use of DPT vaccine containing the whole-cell pertussis component should be continued. All efforts should be directed to increase or maintain high immunization coverage with DPT immunization at the level of at least 90% in all districts. Surveillance of pertussis morbidity should be strengthened in all countries and ideally, pertussis should be a reportable disease. More information on the present epidemiological pattern of pertussis, especially age distribution of pertussis cases in developing countries, is needed to develop the policy of booster doses of DPT vaccine in children > 1 year.

Child↗
PubMed1992

Serological and virological assessment of oral and inactivated poliovirus vaccines in a rural population in Kenya.

A study was carried out in a rural community in Kenya to compare the humoral and intestinal immunity provided by three doses of oral poliovirus vaccine (OPV) and two or three doses of enhanced-potency inactivated poliovirus vaccine (IPV). The immunization series was started at 8-12 weeks of age and the interval between doses was 2 months. In children with low levels of maternal antibodies (i.e., those most at risk), the first dose of either vaccine stimulated antibody response. Children with high levels of maternal antibodies responded to the first dose of OPV, but not to that of IPV. Subsequent doses led to increases in the mean antibody titres with both vaccines. After three doses of OPV, the proportion of children with antibody titres of greater than or equal to 1:8 was 92% for type 1 virus, 98% for type 2, and 90% for type 3. After two doses of IPV the proportion of children with antibody titres of greater than or equal to 1:8 was 94%, 88%, and 97% for type 1, type 2, and type 3, respectively; after three doses of IPV, 100% of children had antibodies greater than or equal to 1:8 for types 1 and 3, and 98% for type 2. Intestinal immunity was tested with a challenge dose of type 1 OPV, but the dose used was too small to detect a significant difference between the vaccines.

Antibodies, Viral↗
PubMed1991

The clinical effects of prolonged treatment of patients with advanced cancer with low-dose subcutaneous interleukin-2 [corrected].

Thirty-five patients with advanced malignant disease have been treated as outpatients with increasing doses (0.1-100 mcg) of interleukin 2 (IL2) by once daily self-administered subcutaneous (s.c.) injection, 5 days weekly for 8 weeks followed by a 4 week observation period. Systemic side effects were not experienced by patients at the 3 lower doses. Three patients required dose reduction from 100 mcg daily because of intolerance (fever, rash, lethargy, nausea and vomiting) and one patient was discontinued because of dyspnoea. We observed immunological effects at the 100 mcg dose (but not at the lower doses). These consisted of (a) a modest sustained lymphocytosis, (b) eosinophilia in six (out of nine) patients and (c) a significant rise in IL2-stimulated peripheral blood lymphocyte activated killer (LAK) cell activity in six (out of nine) patients to a mean of 2.0 times pretreatment levels (P less than 0.01). Two (out of nine) patients with renal cell carcinoma treated with 100 mcg daily had partial responses of duration 4 and 9 months respectively and a further three had disease stabilisation for at least 3 months. Low dose long-term s.c. IL2 is clinically and immunologically active, and in comparison to other IL2 regimens it has minor toxicity and is easy to administer. These characteristics make low dose s.c. IL2 suitable for study in the adjuvant setting.

Adult↗
PubMed1991

Clinical and immunopathological results of a phase II study of perilymphatically injected recombinant interleukin-2 in locally far advanced, nonpretreated head and neck squamous cell carcinoma.

Fifteen patients with locally far advanced, nonpretreated head and neck squamous cell carcinoma were treated with low-dose recombinant interleukin-2, using 10 daily perilymphatic injections. The therapy was well tolerated. No tumor regression was observed. Tumor biopsies were taken before and after treatment. Histopathological studies including evaluation of the mononuclear cell infiltrate and immunohistochemical detection of human leukocyte antigen (HLA) expression on tumor cells were performed. HLA class I was not detectable in 1 of 10 samples, and HLA class II expression was seen in 2 of 10 samples. As compared to pretreatment biopsies, no changes were found after treatment. This is in agreement with the lack of a clinical response.

Adult↗
PubMed1990

Intraperitoneal recombinant gamma-interferon in patients with recurrent ascitic ovarian carcinoma: modulation of cytotoxicity and cytokine production in tumor-associated effectors and of major histocompatibility antigen expression on tumor cells.

Seven patients with advanced epithelial carcinoma and ascites, relapsing after two or more regimens of standard chemotherapy, have been treated with recombinant gamma-interferon (rIFN-gamma) i.p., via a permanent catheter. rIFN-gamma (Immuneron; Biogen; 0.5 mg = 10(7) IU in 2 liters of saline) was administered 3 times a week, on alternate weeks, for a total of nine courses. No major toxicities were observed: mild fever, malaise, and a flu-like syndrome occurred in all patients. The modulation of immunological parameters was studied. Cytotoxic activity of immunocompetent cells against tumor cell lines was measured both in the peritoneal compartment and in peripheral blood mononuclear cells. A significant increase of cytotoxicity of tumor-associated macrophages was observed in 5 of 7 patients and in 4 of 7 patients with tumor-associated peritoneal lymphocytes. Circulating effector cells were only occasionally stimulated. Tumor-associated macrophages isolated from the ascitic fluid and stimulated with lipopolysaccharide produced higher amounts of interleukin 1 in 5 of 6 patients tested, while interleukin 6 production by unstimulated tumor-associated macrophages was augmented in 2 of 2 patients after rIFN-gamma treatment. Freshly isolated ovarian carcinoma cells from the ascitic fluid has a variable, although usually low, expression of HLA-DR antigens. rIFN-gamma treatment caused a marked increase in HLA-DR expression in all patients tested. Expression of HLA class I antigens was negative in 2 of 5 patients and was strongly increased in 1 of the 2 after treatment. The observation that rIFN-gamma administered i.p. activates in situ effector cells and augments major histocompatibility antigen expression in tumor cells, with minimal toxicity, encourages further efforts to investigate its therapeutic potential in ovarian carcinoma.

Ascites↗
PubMed1990

CD3-T cell receptor modulation is selectively induced in CD8 but not CD4 lymphocytes cultured in agar.

The CD3-T cell receptor (TcR) complex is central to the immune response. Upon binding by specific ligands, internalized CD3-TcR molecules increase, and either T cell response or unresponsiveness may ensue depending on the triggering conditions. Using semi-solid agar culture, we have shown previously that quiescent CD4 but not CD8 lymphocytes generate clonal colonies under phytohaemagglutinin stimulation. Here we have demonstrated that the agar induces selective CD3-TcR modulation in the CD8 and not in the CD4 subset. CD8 lymphocytes preactivated in liquid culture and recultured in agar with exogenous recombinant interleukin-2 generate colonies with a modulated CD3-TcR surface expression. The peptides composing the CD3-TcR complex are synthesized in CD8 colonies as well as in CD4; however, the CD3 gamma chain is phosphorylated at a higher level in CD8 colonies. A component of the agar polymer, absent in agarose, appears to be the ligand that induces differential CD3-TcR modulation in the CD8 subset. In contrast to agar culture, CD8 colonies can be derived from quiescent CD8 lymphocytes in agarose. These CD8 colonies express unmodulated CD-TcR. CD3-TcR modulation with anti-CD3 monoclonal antibody prior to culturing in agarose inhibits the colony formation. We conclude that given triggering conditions can result in both CD3-TcR modulation and inhibition of the proliferative response selectively in the CD8 lymphocyte subset and not in the CD4.

Agar↗
PubMed1989

A phase II study of the administration of recombinant interleukin 2 (rIL-2) plus lymphokine activated killer (LAK) cells in stage IV melanoma patients.

From January 1987 to February 1988, 15 stage IV melanoma patients were treated with two courses of bolus injection of rIL-2 plus LAK cell infusions at the National Cancer Institute of Milan. The original treatment regimen included a first course of rIL-2 administration (400 micrograms/m2 bolus injection 3 times a day [TID] for 4 days) and a second course of rIL-2 administration (800 micrograms/m2 bolus injection TID for 7 days) separated by 4 consecutive daily leukaphereses. Autologous lymphokine activated killer (LAK) cells were reinfused into each patient on three occasions during the second period of rIL-2 administration. Due to the appearance of grade III-IV neurological, hepatic and cardiopulmonary toxicity, 7 patients discontinued dosing before the end of treatment, one patient desired to be withdrawn and one patient died from rapidly progressive disease, although complications of rIL-2 administration may have contributed to her death. Only 6 patients completed the schedule without evidence of major intolerance, even though the planned dose during the second course of rIL-2 was reduced to 400 micrograms/m2. The complete duration of treatment ranged from 11 to 19 days. The total dose of rIL-2 injected ranged from 12.6 to 30.4 mg. The number of infused LAK cells ranged from 15.5 x 10(9) to 60 x 10(9)/patient. Two of the 14 evaluable patients showed a minor anti-tumor response. In 5 patients new metastases in other sites were documented from 2 to 5 months after completion of dosing. No apparent association was found between progression of the disease (or the appearance of new metastases) and the total dose of rIL-2 injected, the number of LAK cells administered or the number of days of treatment. By December 1988, all patients had died of their disease in a period ranging from 3 to 14 months from the last injection of rIL-2. The lack of significant clinical responses in this study and the high toxicity of this treatment lead us to conclude that at least as far as melanoma patients are concerned, adoptive immunotherapy with rIL-2 plus LAK cells (as described here) is not a justifiable treatment option unless new evidence presents itself.

Adult↗
PubMed1989

Tetanus incidence and immunity in Poland.

The level of tetanus antibody was determined with the passive hemagglutination method in 503 sera of 10 to 90-year-old persons. Immunity to tetanus was age-dependent: the percentage of immune persons amounted to 90%-100% in persons below 40 years and then declined to 70% and 60% in persons in the 40-50 and above 50 year-old groups, respectively. Males above 30 years are better immunized than females. The comparison of the results of the present study with results of several periodic surveys performed in the last 27 years showed gradually increasing immunity level in all age groups. The findings are in agreement with age-dependent incidence of tetanus, which has become now, in Poland, a disease primarily of older people.

Adolescent↗
PubMed1989

Immunity against diphtheria in adults in Poland.

The diphtheria immunity status was determined with the passive haemagglutination technique in 503 sera of 10-90-year-old persons from Warsaw and Olsztyn Provinces. Donors of sera were students, teachers, pregnant women, employees of industry and medical service. The immunity was highest (90% of titers 0.1 IU/ml or higher) in persons below 20 years of age and in persons above 60 years of age (55%). Between these two groups, gaps in immunity exist, the proportion of those immune varying from 36-50% in the 20- 60-year-old groups. Since a large pool of susceptible persons creates an epidemic potential it was suggested that the adult type of tetanus-diphtheria toxoid (Td) should be introduced into the routine immunization schedule for high risk groups. These groups might include professional or age groups who are vulnerable to reintroduction of virulent Corynebacterium diphtheriae such as kindergarten and creches personnel, teachers, students, military service personnel and persons travelling to developing countries.

Adolescent↗
PubMed1989

Evaluation of the effect of continuous infusion recombinant interleukin-2 (bioleukin) on peripheral blood leucocytes of patients with terminal malignancy.

Seventeen patients with terminal malignancy have been entered into a sequential investigation of two doses of continuous infusion recombinant interleukin-2 (bioleukin) given in the setting of a general ward. After an initial experience of a dose of 300 micrograms m-2 in eight patients the remainder received 400 micrograms m-2. Temporary interruption of treatment at the first sign of any serious toxicity led to rapid resolution of side-effects. No patient needed intensive care support, although nine of 17 required temporary interruption of infusion, lasting on average 4 h. Median lymphocyte rebound on day 14 was 3.6 times the pre-treatment level. It remained above pre-treatment levels in four of five patients who had no shown disease progression at day 56 after more than 28 days off treatment. Minor responses occurred in five patients, lasting on average 4 months.

Adult↗
PubMed1989

Intraperitoneal infusion of recombinant interleukin-2 in malignant ascites in patients with gastrointestinal and ovarian cancer.

In a phase-I-study recombinant interleukin-2 (rIL-2) in a dose from 0.01 to 0.3 mg/m2/day for 7 to 14 days was infused intraperitoneally. Side effects were fever and fluid retention. 2 patients showed a bacterial peritonitis after paracentesis. The investigations showed that the intraperitoneal (i.p.) administration of interleukin-2 activates the whole lymphokine cascade.

Catheters, Indwelling↗