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Biomedical subjects

H Kirchner

Publications and source records attributed to H Kirchner.

At least 91 records · Page 5Linked to original sources
PubMed1998

Risk and outcome in metastatic malignant melanoma patients receiving DTIC, cisplatin, BCNU and tamoxifen followed by immunotherapy with interleukin 2 and interferon alpha2a.

Combined chemo-/immunotherapy has shown high objective response rates and a significant though small proportion of long-term complete responders in metastatic malignant melanoma. The purpose of this study was to determine response rates, freedom from treatment failure (FFTF) and overall survival in patients with advanced metastatic malignant melanoma treated with combined chemo-/immunotherapy, and to determine the value of a prognostic model for prediction of treatment outcome, FFTF and survival. Sixty-nine patients with metastatic malignant melanoma received combined chemo-/immunotherapy consisting of up to four cycles of DTIC (220 mg m(-2) i.v. days 1-3), cisplatin (35 mg m(-2) i.v. days 1-3), BCNU (150 mg m(-2) i.v. day 1, cycles 1 and 3 only) and tamoxifen (20 mg orally, daily). Two cycles of chemotherapy were followed by 6 weeks of outpatient immunotherapy with combined interleukin 2 (20 x 10(6) IU m(-2) days 3-5, weeks 1 and 4; 5 x 10(6) IU m(-2) days 1, 3, 5, weeks 2, 3, 5, 6) and interferon-alpha (6 x 10(6) IU m(-2) s.c. day 1, weeks 1 and 4; days 1, 3, 5, weeks 2, 3, 5, 6). All patients were evaluated on an intention-to-treat basis. Of 69 patients entered in the study, seven achieved complete remissions and 20 reached partial remissions with an objective response rate of 39% (95% confidence interval 28-52%). Median survival was 11 months, median FFTF was 5 months. Seven patients achieved ongoing long-term remissions, with maximum survival of 58 + months, and maximum FFTF of 58 + months. By Kaplan-Meier survival analysis and two-proportional Cox regression analysis, pretreatment performance status and serum lactic dehydrogenase were statistically significant and independent predictors of survival; risk groups could be defined as (a) the absence of both or (b) the presence of either one or both of these risk factors. Whereas survival and response were significantly influenced by patient risk, no influence could be demonstrated for FFTF. This combined outpatient chemo-/immunotherapy is feasible and results in objective response rates and survival similar to earlier trials. Pretreatment risk, as defined by serum lactate dehydrogenase (LDH) and performance status, has a significant impact on treatment outcome and patient survival.

Adult↗
PubMed1998

Pharmacokinetics of recombinant human interleukin-2 in advanced renal cell carcinoma patients following subcutaneous application.

AIMS: The aim of the study was to investigate the pharmacokinetics of recombinant human interleukin-2 (rhIL-2) in patients with metastatic renal cell carcinoma following different subcutaneous (s.c.) administration regimens. METHODS: RhIL-2 was administered subcutaneously to 10 patients according to two different dosing regimens: group A received 20 x 10(6) IU m(-2) once daily and group B 10 x 10(6) IU m(-2) twice daily (every 12 h). Additionally, in all patients the influence of soluble interleukin-2 receptor (sIL-2R) on the pharmacokinetics of rhIL-2 was investigated. RESULTS: The mean area under the serum concentration-time curve to 24 h (AUC(0,24 h)) was 627 IU ml(-1) h in treatment group A and 1130 IU ml(-1) h (P=0.029) in treatment group B. In both study groups Cmax and AUC(0,12 h) were not significantly different. Seventy-two hours after the beginning of s.c. rhIL-2 therapy the sIL-2R increased significantly (P=0.016), and sIL-2R levels over 1200 pmol l(-1) seemed to reduce the AUC. CONCLUSIONS: In patients with metastatic renal cell cancer administration of 20 x 10(6) IU m(-2) of rhIL-2 s.c. in two daily doses (10 x 10(6) IU m(-2) every 12 h) provides better bioavailability and is preferable to the single dose administration.

Aged↗
PubMed1998

Detection of karyotypic aberrations in acute myeloblastic leukaemia: a prospective comparison between PCR/FISH and standard cytogenetics in 140 patients with de novo AML.

In 140 patients with de novo acute myeloid leukaemia (AML) standard cytogenetics were compared with RT-PCR for the detection of t(8;21), t(15;17) and inv(16) and fluorescence in situ hybridization (FISH) for numerical aberrations of chromosomes 7, 8, X and Y. RT-PCR detected 18 cases with t(8;21), 12 with t(15;17) and seven with inv(16). In two cases with t(8;21), two with t(15;17) and four with inv(16) these aberrations had not been detected by standard cytogenetics. There were no false negative PCR results. In 12 patients with these chromosomal changes, standard cytogenetics revealed additional chromosomal aberrations. In 16 patients sole numerical aberrations of the chromosomes 7, 8, X or Y were found by FISH. In these patients the sensitivity of FISH and standard cytogenetics was comparable. In 87 patients no aberrations could be found by PCR and FISH whereas in 24 of these patients standard cytogenetics revealed an abnormal karyotype. These data recommend the combination of standard cytogenetics and molecular techniques to improve the sensitivity for the detection of genetic lesions in AML. Once chromosomal markers have been identified by combined analysis these markers could be used to monitor residual disease during/after chemotherapy, by RT-PCR and/or FISH.

Adult↗
PubMed1998

Cytokine induction by Mycoplasma arthritidis-derived superantigen (MAS), but not by TSST-1 or SEC-3, is correlated to certain HLA-DR types.

Superantigens bind to major histocompatibility complex (MHC) class II molecules on antigen presenting cells and T cells in a V beta-restricted manner. Both cell types are activated resulting in cytokine production. Although the MHC-II binding site for superantigens has been well described, little is known as to whether this binding complex has an influence on cytokine induction. In order to assess superantigen induced cytokine production and its correlation to HLA-DR types, the authors stimulated peripheral blood from 40 subjects with superantigens toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin C-3 (SEC-3) and Mycoplasma arthritidis-derived superantigen (MAS), and measured cytokine levels thereafter. The HLA-DR type was determined in each subject. A statistical evaluation was carried out between the highest superantigen cytokine induction and the presence of certain HLA-DR types. Whereas MAS presented a statistical association between the highest cytokine production with HLA-DR4, DR7 and DR12, no such associations were observed for TSST-1 and SEC-3. These results demonstrate that T cell stimulation, and consequently its cytokine production by MAS but not by TSST-1 and SEC-3, depends on the presenting HLA-DR type. Because the diverse HLA-DR specificities are given according to the variability of the beta chain of the HLA-DR molecule, the data suggest the participation of the human MHC-II beta chain in the MAS/MHC-II binding.

Adult↗
PubMed1998

Evaluation of two new integrated adapters for blood drawing in closed blood bag systems: influence on different molecular coagulation markers.

We compared a conventional blood donation bag system (A) with two newly developed ones (B, C) with integrated Y-shaped adapters. The new systems facilitate the withdrawal of blood samples in a closed system under aseptic conditions. The purpose of the study was to determine whether disturbances during blood donation in the different tubings influence the quality of the donated plasma due to activation processes of the coagulation system. In all bag samples from 34 probands for each system, we found higher levels of the global tests (aPTT, TT) compared to intraindividual controls. This was due to a greater amount of anticoagulant in the bag samples. An increase of procoagulant activity was demonstrated for bags A and C. Concerning the fibrinolytic system, values were reduced in all three systems compared to controls. In summary, the quality of the plasma in the three different bag devices was comparable to controls concerning factor activities measured as global tests. The activation of the coagulation system was only slightly higher in the new system B and C than in the conventional one (A). Therefore, the new closed systems are suitable for blood donation and reveal a high coagulation quality of the plasma.

Adolescent↗
PubMed1998

High incidence of active cytomegalovirus infection among septic patients.

Cytomegalovirus (CMV) infection is an important cause of disease in immunocompromised patients. In a prospective longitudinal study of 34 septic patients, the incidence of active CMV infection was examined. Eleven of 34 patients (32.4%) had active CMV infection, diagnosed by immunocytochemical staining of CMV pp65 antigen in blood leukocytes and/or detection of CMV DNA by PCR. Positive results for CMV infection were obtained in a median of 4 days (by PCR) or 11 days (by staining of pp65 antigen) after onset of sepsis. Twenty patients for whom more than one sample was examined were selected for further analysis. Among the patients with active CMV infection (nine of 20) there was a trend toward higher median values of tumor necrosis factor alpha, interleukin-1 beta, alanine aminotransferase, and aspartate aminotransferase in plasma, in comparison with the values for patients without CMV infection. Sepsis in patients with CMV infection may affect outcome of the disease.

Antibodies, Viral↗
PubMed1998

Effect of high-dose methylprednisolone administration on immune functions in multiple sclerosis patients.

OBJECTIVES: To investigate the in vivo effect of corticosteroid pulse therapy on immunocompetent cells in 18 patients given methylprednisolone to treat an acute episode of MS. MATERIAL AND METHODS: Blood was sampled before and after 3 days of methylprednisolone administration at doses of 1 g/day. Lymphocyte subtyping was performed and whole blood cell cultures were used to measure the cytokine producing capacity for interleukin-1 (IL-1), interleukin-2 (IL-2), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN-alpha). In addition, serum levels of the immunoglobulin classes IgG, IgA and IgM were determined. RESULTS: Before treatment, production of IL-1 was significantly increased in MS patients as compared to healthy controls. After therapy, production of all cytokines was significantly decreased, whereas there were significant increases in the numbers of monocytes, neutrophils and T and B lymphocytes. Treatment had no effect on serum immunoglobulin levels. CONCLUSION: An important mechanism for the antiinflammatory effect of corticosteroids in MS results from a suppression of the activation of the peripheral immune compartment through inhibition of cytokine production and lymphocyte endothelial adhesiveness.

Adult↗
PubMed1998

Immunological dysfunction in schizophrenia: a systematic approach.

BACKGROUND: In the present study, immunological alterations were investigated as one possible factor contributing towards the pathogenesis of schizophrenia. Specifically cellular changes, deviating cytokine production and interfering variables were studied in order to improve our understanding of how these factors interact. METHOD: 44 acutely ill schizophrenics were compared with matched healthy controls. Cell numbers were determined by flow cytometry and cytokine production by whole blood assay and ELISA. A criss-cross technique was employed for the assessment of interfering serum factors. RESULTS: Cell counts for leukocytes, lymphocytes, pan T cells, activated T cells and the absolute B cell count of the schizophrenic patients were all within normal limits. The absolute and relative monocyte counts, the number of IL-2 receptor carrying T cells and the relative B cell count were slightly elevated. IL-2 and IFN-gamma production were increased while IL-10 production, the sIL-2R and cortisol levels remained unchanged. No interfering serum factors were detected. CONCLUSION: The deficient production of TH-1 cytokines in schizophrenia is not due either to a changed number of immunocompetent cells or to a counterregulation of the TH-2 cytokine IL-10. Serum factors in in vitro testing are not responsible for the deficient cytokine production.

Acute Disease↗
PubMed1998

The use of dose-intensified chemotherapy in the treatment of metastatic nonseminomatous testicular germ cell tumors. German Testicular Cancer Study Group.

With the use of a cisplatin-based chemotherapy, metastatic testicular cancer has become a model for a highly curable malignant disease. Current data show that 70% to 80% of patients with this disease will achieve long-term survival following cisplatin/etoposide/bleomycin therapy. The role of high-dose chemotherapy with autologous stem cell support is being investigated in metastatic germ cell cancer in attempts to improve outcome for patients whose disease relapses after standard-dose chemotherapy and for those who present initially with advanced metastatic disease. Prognostic categories for patients receiving high-dose salvage chemotherapy have recently been developed: cisplatin-refractory disease, beta-human chorionic gonadotropin values greater than 1,000 U/L, and primary mediastinal germ cell tumors are factors characterizing patients who will derive less benefit from high-dose chemotherapy than those with chemosensitive disease at relapse. While standard-dose salvage chemotherapy achieves only a 20% long-term survival rate, high-dose salvage chemotherapy may yield a cure rate of approximately 40%. A randomized study comparing high-dose therapy with conventional-dose therapy (IT94 coordinated by the European Group for Blood and Marrow Transplantation) in patients with relapsed disease is ongoing to substantiate this observation. The use of dose-intensive therapy as first-line treatment is currently being studied by several institutions. High-dose therapy may be better tolerated when used first line compared with its use in the salvage situation, and may also achieve a rapid initial cell kill before cytostatic drug resistance develops. The German Testicular Cancer Study Group has developed a sequential high-dose combination regimen of cisplatin/etoposide/ifosfamide given with granulocyte colony-stimulating factor and peripheral blood stem cell support for four cycles every 3 weeks. This ongoing study, started in 1990, had accrued 218 patients with advanced testicular germ cell tumors as of June 1997. Of 141 evaluable patients receiving dose levels 1 through 5, 82 (58%) have achieved complete remission with no evidence of disease and 32 (23%) have achieved partial remission with marker normalization. The early death rate was 8%. Overall and event-free survival rates at 2 years are 78% and 73%, respectively, with a projected 5-year overall survival rate of 74%. Despite favorable preliminary results, this approach cannot be considered standard treatment. Currently, high-dose chemotherapy with peripheral blood stem cell transplantation should be administered to patients with testicular cancer only within controlled clinical trials to allow long-term cure rates and treatment-related late side effects to be evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Effects of blood donation on the physical fitness and hemorheology of healthy elderly donors.

BACKGROUND: International regulations for blood donation recommend a maximum donor age of 65 years. As the average population age is steadily rising in western societies, a considerable group of volunteers is lost to the donor base. STUDY DESIGN AND METHODS: In a prospective study we investigated the effect of a 450-ml whole blood donation on the physical fitness and hemorheology of regular elderly allogeneic blood donors (n = 24, aged 63-69 years, mean = 65). Results were compared with a younger group of regular donors (n = 23, aged 55-62 years, mean = 58) and a group of elderly subjects (n = 7, aged 63-66 years, mean = 65), who did not donate blood for this study. Assessing the physical fitness, we determined the submaximal physical working capacity at a heart rate of 130 min-1 (PWC 130) and the maximal working capacity (MWC) by treadmill exercise testing the day before (day -1) and after donation (d +1). The impact of the blood loss on hemorheology was examined by analyzing the plasma viscosity before, during and after donation. RESULTS: We found an increase of mean values of PWC 130 and MWC on day +1 in all study groups, but increases were only significant in the younger group (PWC 130 p = 0.03; MWC p = 0.04). Values did not differ significantly between the three groups. Plasma viscosity decreased significantly directly after donation in both groups of donors. CONCLUSION: A single blood donation did not alter the physical fitness of otherwise healthy elderly people. The older blood donors and the younger controls showed a similar compensation mechanism to blood loss. We found no general reason for disqualifying blood donors aged 65 years from donating.

Aged↗
PubMed1998

Impact of storage at 22 degrees C and citrate anticoagulation on the cytokine secretion of mononuclear leukocytes.

BACKGROUND AND OBJECTIVES: Peripheral blood mononuclear cells (PBMC) and cytokines accumulating in platelet concentrates (PC) during storage have been implicated in causing non-hemolytic transfusion reactions, in particular after prolonged PC storage. We investigated the impact of major storage parameters, such as storage time, anticoagulation and temperature, on the capability of PBMC to secrete cytokines. MATERIALS AND METHODS: In a first study, PBMC from whole blood donations (n = 16) were exposed to standard PC storage conditions: 22 degrees C, citrate phosphate dextrose (CPD) anticoagulation. Secretion of the cytokines interleukin-1 beta (IL-1 beta), IL-2, IL-6 and interferon-gamma (IFN-gamma) on mitogenic stimulation was measured directly after blood donation and after 1, 3 and 5 days of storage. In a second study, paired whole blood samples (n = 24) were investigated for the mitogenic induction of IL-2, IL-6, IFN-gamma and IFN-alpha. Cytokine values were compared with respect to incubation temperature (22 vs. 37 degrees C) and anticoagulant (CPD vs. lithium-heparin). RESULTS: PBMC stored at 22 degrees C with CPD anticoagulation showed an altered cytokine secretion pattern in comparison to freshly donated cells. After storage for 3 days, IL-2 release was decreased (p < 0.05) and after 5 days secretion of all cytokines was significantly decreased, though still detectable (p < 0.01). In the second study, CPD anticoagulation resulted in a significantly impaired cytokine secretion compared with lithium-heparin. Cytokine secretion at 22 degrees C were significantly lower (p < 0.001) compared with 37 degrees C for both anticoagulants. CONCLUSION: Storage of PBMC at 22 degrees C with CPD leads to an impaired cytokine response, but PBMC are still capable of secreting cytokines after 5 days of storage. PBMC remain a potential source of cytokines even after 5 days of storage in CPD at 22 degrees C.

Anticoagulants↗
PubMed1997

Production of interferon-gamma in families with multiple occurrence of schizophrenia.

Dysfunction of T-cell mediated immunity, which is indicated by deficient production of interleukin-2 (IL-2) and elevated levels of the soluble interleukin-2 receptor (sIL-2R), has been consistently demonstrated in schizophrenia. Recent studies on interferon-gamma (IFN-gamma), a cytokine which is also produced by T-helper cells, have indicated a lowered production in acute schizophrenia. It is not known whether this deficit is restricted to cases of acute schizophrenia or whether it is also present in residual schizophrenia and in first degree relatives, and therefore might be associated with genetic liability to the disease. We investigated 27 individuals (schizophrenics and first degree relatives) of 6 families with multiple occurrence of schizophrenia and 27 age- and sex-matched healthy controls. The production of IFN-gamma was lowered only in the acutely ill schizophrenic individuals, when compared to both controls and first degree relatives. In the context of current knowledge, this result indicates that the production of IFN-gamma can be discussed as a marker of acute exacerbation of schizophrenia, but it is not likely to represent a phenotypic marker of a genetic trait associated with the disease.

Acute Disease↗
PubMed1997

The effects of general anesthesia on human peripheral immune cell distribution and cytokine production.

Anesthetic agents are believed to have an adverse effect on human immune defense mechanisms. We investigated changes in peripheral immune cell numbers such as natural killer (NK) cells, B cells, and T lymphocyte subpopulations (CD4+ and CD8+ cells) and differences in cytokine production after stimulation with different mitogens before and during narcosis. We studied 30 patients undergoing elective orthopedic surgery. Stimulatory experiments were performed with the mitogens lipopolysaccharide, phytohemagglutinin A, and inactivated Newcastle disease virus. During general anesthesia with fentanyl, thiopental, and isoflurane, there was a significant decrease of circulating NK cells in the peripheral blood accompanied by a significant increase of B cells and CD8+ T lymphocytes. We detected a significant anesthesia-associated increase of interferon (IFN)-gamma, IFN-alpha, tumor necrosis factor-alpha, and soluble interleukin-2 receptor (sIL-2R) synthesis after stimulation with different mitogens while interleukin (IL)-1 beta and IL-6 protein did not change significantly. After the beginning of surgery, CD8-positive cells showed a return to control values and NK cell number increased slightly. These findings suggest that general anesthesia interferes with immune cell number and immune cell response. This may explain the clinically well-recognized disturbance of human immunity after surgery and general anesthesia.

Adolescent↗
PubMed1997

Stimulation of whole blood cultures in patients with ankylosing spondylitis by a mitogen derived from Mycoplasma arthritidis (MAS) and other mitogens.

In this study we compared cytokine production and cell proliferation of immunocompetent cells derived from patients with ankylosing spondylitis (AS) to those from healthy blood donors using a whole blood assay. To this end, blood cell cultures were stimulated with the superantigens MAS (Mycoplasma arthritidis supernatant) and staphylococcal enterotoxin B (SEB) and the plant lectins phytohaemagglutinin (PHA) and concanavalin A (Con A). The number of white blood cells (WBC) and lymphocyte subsets were also determined. Cell proliferation and levels of interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) were measured after stimulation with the different mitogens. An ELISA test was used to analyse supernatant cytokine levels. Individuals with AS showed significantly lower IFN-gamma concentrations and markedly lower cell proliferation rates with all tested mitogens than healthy controls, while there was no significant difference in IL-6 synthesis. IL-1 beta levels were slightly impaired in the patient group, but only blood cell cultures stimulates with MAS showed a statistical significance. Furthermore, there was a significant elevation of leucocytes and lymphocytes in patients with AS resulting in higher numbers of CD4-positive cells, which implies a higher CD4:CD8 cell ratio. CD19- and CD8-positive cells were not significantly distinct compared to healthy controls. This deviation in cytokine levels and cell proliferation points to a suppression of T lymphocytes. A disturbed T-lymphocyte function may play a part in the pathogenesis of AS.

Adult↗
PubMed1997

Moderate and exhaustive endurance exercise influences the interferon-gamma levels in whole-blood culture supernatants.

The aim of this study was to investigate whether moderate or exhaustive endurance exercise influences cytokine levels in whole-blood culture supernatants after stimulation. Therefore, eight healthy subjects were first exposed to moderate exercise on a cycle ergometer for 30 min at 70% of their 4-mmol/l lactic acid (anaerobic) threshold, and 1 week later to exhaustion (for 90 min) at their anaerobic threshold. Blood samples were taken before, 30 min after and 24 h after each exercise bout. The following lymphocyte subpopulations were determined: CD14-positive(+)/CD45+, CD4+, CD8+, and CD16+. Cytokine levels in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Production of interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha were induced with lipopolysaccharides (LPS), and that of IL-2 and interferon (IFN)-gamma with staphylococcal enterotoxin B (SEB) and phytohaemagglutinin (PHA). Cortisol levels were also determined by ELISA. The lymphocyte subset distribution was observed to be unchanged after moderate exercise. Thirty minutes after exhaustive exercise, the CD16+ count was found to be significantly lower, whereas 24 h later the CD4+ count was significantly higher than pre-exercise counts. Moderate exercise influenced the IFN-gamma production (PHA-stimulated), which increased significantly from 974 (391) pg/ml before exercise to 1450 (498) pg/ml 24 h later. Thirty minutes after exhaustive exercise the IFN-gamma level in the supernatants (SEB-stimulated) was significantly decreased (from 14470 (11840) pg/ml before exercise to 6000 (4950) pg/ml after exercise). The IL-1beta and TNF-alpha production per monocyte was also significantly reduced.

Adolescent↗