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H Link

Publications and source records attributed to H Link.

At least 37 records · Page 2Linked to original sources
PubMed1995

Granulocyte growth factors: achieving a consensus.

A consensus meeting held under the auspices of the European School of Oncology concluded that the use of granulocyte growth factors is definitely indicated, or acceptable given existing evidence, in the following circumstances: to alleviate congenital neutropenia; in the mobilisation of peripheral blood progenitor cells for autotransfusion; to encourage engraftment following bone marrow transplantation and in cases of failed engraftment; to support continuation of ganciclovir anti-CMV therapy in certain patients with AIDS, where the switch to foscarnet is contraindicated or where toxicity to foscarnet develops. It was also agreed that there is an overwhelming need for carefully controlled clinical trials in a wide range of indications in which growth factor use may improve outcome. In the majority of tumours, the possible benefit of dose optimisation and intensification, and therefore the role of growth factors in support of such measures has still to be defined. Extramedullary toxicities may in these instances become dose limiting.

AIDS-Related Opportunistic Infections↗
PubMed1995

High numbers of autoantigen-reactive mononuclear cells expressing interferon-gamma (IFN-gamma), IL-4 and transforming growth factor-beta (TGF-beta) are present in cord blood.

Umbilical cord blood of neonates and peripheral blood of healthy adults were analysed by in situ hybridization for numbers of mononuclear cells (MNC) expressing the cytokines IFN-gamma, TGF-beta and IL-4 mRNA without culture and after culture in the presence of acetylcholine receptor (AChR), myelin basic protein (MBP) and peripheral myelin protein P2. These antigens were chosen since they represent autoantigens in putatively immune-mediated neurological diseases. The numbers of cells expressing cytokine mRNA after 72 h culture in the presence of AChR, MBP and P2 were higher in cord blood than in peripheral blood of healthy adults. IFN-gamma, TGF-beta and IL-4 were always elevated in parallel. In cord blood there was a pronounced reactivity to several of the tested antigens, while such broad reactivity was not found in peripheral blood of healthy adults. No differences in cytokine mRNA expression were found between cord blood and peripheral blood of adults when cells were analysed without culture. The results show a capacity of cord blood cells to react to several autoantigens by the up-regulation of cytokine mRNA expression.

Adult↗
PubMed1995

Increased mRNA expression of IL-10 in mononuclear cells in multiple sclerosis and optic neuritis.

The inflammatory nature of multiple sclerosis (MS) implicates the participation of immunoregulatory cytokines, including the Th2 related IL-10. We describe the use of in situ hybridization with cDNA oligonucleotide probes to detect and enumerate mononuclear cells (MNC) expressing mRNA for IL-10, which is known to down-regulate Th1 cell related cytokines such as interferon-gamma. Expression of IL-10 was studied in blood MNC of MS and blood and cerebrospinal fluid (CSF) MNC of optic neuritis (ON) patients without culture and after culture in the presence of myelin basic protein (MBP), the control antigen acetylcholine receptor (AChR), and without antigen. Numbers of IL-10 mRNA expressing MNC were elevated in the MS patients' blood both when enumerated without culture and after culture with MBP. Control patients with myasthenia gravis had elevated numbers of AChR-reactive IL-10 mRNA expressing cells, while numbers of MBP-reactive IL-10 positive cells did not differ from numbers registered in cells without antigen. Patients with ON, in many instances representing early MS, had IL-10 positive blood MNC that were elevated to the same extent as in clinically definite MS, and further increased in the CSF. ON patients examined within 1 month after onset had lower numbers of MBP induced IL-10 mRNA expressing blood MNC compared with patients examined later suggesting that IL-10 is related to the degree of inflammation and outcome in ON.

Adolescent↗
PubMed1995

Suppression of experimental autoimmune myasthenia gravis after CD8 depletion is associated with decreased IFN-gamma and IL-4.

CD8+ T cells can perform both Th1- and Th2-like functions by producing cytokines such as interferon-gamma (IFN-gamma) and interleukin-4 (IL-4), as well as the immune response down-regulating transforming growth factor-beta (TGF-beta), which are all involved in the development of experimental autoimmune myasthenia gravis (EAMG), a model for human MG. We have reported that depletion of CD8+ T cells results in the suppression of EAMG accompanied by the down-regulation of AChR-specific B cell responses and AChR-reactive IFN-gamma secreting Th1-like cells. To identify the involvement of IFN-gamma, IL-4 and TGF-beta in the development of EAMG after CD8+ T cell depletion, the expression of mRNA for these cytokines was studied in mononuclear cells from popliteal, inguinal and mesenteric lymph nodes, spleen and thymus by adopting in situ hybridization with complementary DNA oligonucleotide probes. Depletion of CD8+ T cells resulted in decreased levels of IFN-gamma and IL-4 mRNA expressing cells in different lymphoid organs except thymus, but no change in the numbers of TGF-beta mRNA expressing cells. The results imply that the suppression of EAMG after depletion of CD8+ T cells is caused by decreasing the effector factors but not by increasing the suppressor factor(s).

Animals↗
PubMed1995

Lyme neuroborreliosis: evidence for persistent up-regulation of Borrelia burgdorferi-reactive cells secreting interferon-gamma.

The T-cell response to the aetiologic pathogen Borrelia (B.) burgdorferi in patients with Lyme neuroborreliosis (LN) and in control patients with other neurological diseases was examined by enumerating B. burgdorferi-reactive T cells secreting interferon-gamma (IFN-gamma) with an ELIspot assay. LN patients had elevated numbers of B. burgdorferi-reactive IFN-gamma secreting cells in blood and approximately 20-fold enriched in the cerebrospinal fluid (CSF). A positive correlation existed in CSF between B. burgdorferi-reactive IFN-gamma secreting cells and B cells secreting anti-B. burgdorferi IgG antibodies. The up-regulation of antigen-specific IFN-gamma secreting cells persisted in peripheral blood up to at least 9 months and in the CSF for at least 4 months after termination of treatment with antibiotics, when the patients were mostly free from clinical signs and symptoms due to LN. How IFN-gamma interplays with other cytokines and influences the pathogenesis of LN remains to be studied.

Adult↗
PubMed1995

Cytokine mRNA profiles in mononuclear cells in acute aseptic meningoencephalitis.

Cytokines are important modulators of inflammation and immune responses. Using in situ hybridization with radiolabelled cDNA oligonucleotide probes, we studied the expression of mRNA encoding the cytokines gamma interferon (IFN-gamma), interleukin 4 (IL-4), IL-6, IL-10, transforming growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), lymphotoxin, and perforin in mononuclear cells (MNC) from blood and cerebrospinal fluid (CSF) of patients with acute aseptic meningoencephalitis (AM) and from blood of healthy controls. Patients in the acute phase of AM had elevated numbers of IFN-gamma mRNA-expressing cells in the blood compared with that of controls and higher numbers of IFN-gamma mRNA-expressing cells in their CSF compared with that of convalescent-phase patients, which is in accordance with the antiviral effects of this cytokine. Upregulation of IL-4, IL-6, and IL-10 was found in convalescent-phase patients, which is consistent with the longstanding B-cell response found in AM. TGF-beta and perforin were upregulated in both stages of AM, while the numbers of blood and CSF MNC expressing cytokine mRNA of the TNF family (TNF-alpha and lymphotoxin) did not differ between patients with AM and controls. An even higher elevation in CSF was noticed for MNC expressing most of the cytokines, particularly IL-4 and TGF-beta, reflecting the autonomy of the immune response in the CSF. The definition of cytokine profiles in AM, a self-limiting and benign disease, provides a foundation for future comparisons with other infectious and inflammatory nervous system diseases.

Acute Disease↗
PubMed1995

Evaluation of the Cult-Dip Plus dip slide method for urinary tract infection.

AIM: To evaluate the Cult-Dip Plus (Merck, Germany), a bacteriological culture test for detecting uropathogens. METHODS: Cult-Dip Plus consists of Brolacin (CLED) and MacConkey agar, each containing methylumbelliferylglucuronide (MUG). Using 1022 urine samples, this product was compared with the routine method of calibrated loop inoculated CLED and blood agar for screening urine for uropathogens. The MUG test for identifying Escherichia coli was also evaluated. RESULTS: Compared with the routine method, Cult-Dip Plus has a sensitivity, specificity, positive predictive value and negative predictive value of 88.3%, 98.0%, 91.9%, and 97.1%, respectively. The MUG test correctly identified 92% of E coli isolates with a sensitivity, specificity and positive predictive value of 91.6%, 95.2%, and 93.6%, respectively. CONCLUSION: Cult-Dip Plus appears to be an alternative method to the calibrate loop method for detecting uropathogens. The MUG test permits rapid, reliable and inexpensive identification of E coli.

Bacteriological Techniques↗
PubMed1995

Flow cytometry quantification of CD34+ cells and other leukocyte subpopulations in frozen-thawed blood cell suspensions: investigation of a new teflon container for cryopreservation of hematopoietic progenitor cells.

BACKGROUND: Cryopreservation is the only available method for the long-time maintenance of blood cells. The present study was designed to prove: (i) the reliability of multiparameter flow cytometry (MFC) for estimation of CD34+ cells in frozen-thawed cell suspensions and (ii) the acceptability of a new teflon container for the cryopreservation of hematopoietic progenitor cells. MATERIALS AND METHODS: Each of 15 ABO-compatible buffy coats (BC) were pooled, and mononuclear cells (MNC) were then separated with the Fresenius AS 104 device (n = 10). MNC harvested by apheresis were then divided into 2 portions and transferred pairwise into either the new Fresenius or into Gambro cryopreservation containers. Paired samples were frozen at controlled rates (9% DMSO final concentration) and stored at -196 degrees C in liquid nitrogen for 2 weeks. Leukocyte, MNC and differential blood counts and proportions of CD3+, CD4+, CD8+, CD14+ and CD34+ cells were assessed from the pooled BC, the apheresis products, and the frozen-thawed samples. Methyl cellulose culture assays as well as trypan blue viability staining were also carried out. RESULTS: The mean content of the divided apheresis products was 4.9 x 10(9) leukocytes with 86% MNC, 6.89 x 10(6) CD34+ cells, 2.1 x 10(5) granulocyte-macrophage colony-forming units (CFU-GM) and 7.1 x 10(5) erythroid burst-forming units (BFU-E). As expected, there were virtually no granulocytes after freezing in both types of container. The corresponding mean cell content was as follows: 6.3 x 10(6) CD34+ cells, 2.5 x 10(5) CFU-GM, and 8.1 x 10(5) BFU-E in Fresenius containers, and 6.1 x 10(6) CD34+ cells, 1.3 x 10(5) CFU-GM, and 7.7 x 10(5) BFU-E in Gambro containers. The mean MNC viability of the samples frozen in Fresenius was 81.5% and 82.7% in the Gambro containers. MFC was found to compare with stained smear differentials. CD34+ cell counts correlated with CFU-GM (0.69, p = 0.03) and BFU-E (0.63, p = 0.02) colony formation. CONCLUSIONS: The study reported here revealed no significant differences between the 2 types of storage containers. The new Fresenius teflon container could thus be recommended for cryopreservation of hematopoietic progenitor cells. MFC provided reliable data on CD34+ cell content and leukocyte subset composition of the frozen-thawed cell suspension.

Antigens, CD↗
PubMed1995

Influence of ion channel modulation on in vitro interferon-gamma induced MHC class I and II expression on macrophages.

The in vitro effect of K+ channel blockers quinidine and verapamil, anion channel blocker SITS and K+ channel openers diazoxide, pinacidil, and BRL 38227 on interferon-gamma (IFN-gamma) induced MHC class I and II expression of Lewis rat peritoneal macrophages was investigated by cell ELISA assay. MHC class I expression was significantly enhanced by diazoxide at concentrations of 10(-5)M to 10(-6)M and by pinacidil and BRL 38227 at the concentration of 10(-6)M. MHC class II expression was enhanced by pinacidil and BRL 38227 at concentrations of 10(-5)M to 10(-6)M. The enhancing effect of pinacidil could be blocked by inhibitors of the protein kinases PKA and PKC suggesting that activation of both is required for optimum induction of MHC molecule expression. K+ and anion channel blockers were less active in modulation of MHC molecule expression. Verapamil had no influence, quinidine suppressed MHC class I expression at concentrations of 10(-4)M to 10(-5)M, and SITS suppressed MHC class I expression at the concentration of 10(-3)M. Since MHC class II expression is essential for efficient antigen presentation to T helper cells and MHC class I expression is required for target cell lysis by cytotoxic T cells, ion channel modulating drugs may be potential candidates for immunopharmacological intervention in inflammatory diseases.

Animals↗
PubMed1995

DNA fingerprint analysis in acute leukemias.

Restriction fragment length polymorphism (RFLP) analysis by Southern blotting or direct in-gel hybridization is a routine procedure in any genetic laboratory. Minisatellites and simple repeat probes for RFLP analysis have proved to be highly informative genetic markers, depending on their degree of homology and index of heterozygosity. Several of these probes have considerable individualization potential, thus yielding 'fingerprint' pattern. In the setting of acute leukemia DNA fingerprint (DNA-F) analysis is able to provide considerable information concerning the genetic instability of the leukemic clone. DNA-F is capable of detecting randomly occurring genetic alterations of unknown localization and to identify new hotspots of malignant transformation. As DNA-F analysis is not likely to be hampered by the effects of chemotherapy or DNA methylation, altered fingerprints may be regarded as characteristic of the leukemic clone. With the introduction of polymerase chain reaction (PCR) and increasing sensitivity, DNA-F analysis is likely to be of significant importance in monitoring minimal residual disease in human leukemia.

DNA Fingerprinting↗
PubMed1995

Treatment of newly diagnosed acute promyelocytic leukemia (APL) by all transretinoic acid (ATRA) combined with chemotherapy: The European experience. European APL Group.

All transretinoic acid (ATRA) gives complete remission (CR) rates of 80 to 90% in newly diagnosed acute promyelocytic leukemia (APL). However, it has two major drawbacks (1) a rapid rise in WBC in some patients, with potentially fatal ATRA syndrome (2) rapid relapse with maintenance therapy using ATRA alone or low dose chemotherapy. The French APL group therefore designed a treatment approach with ATRA followed by intensive chemotherapy. The latter was administered after CR achievement with ATRA, or was rapidly added to ATRA in case of rapid rise in leukocyte counts. This combined approach, in a pilot study and in a randomized trial, proved superior to intensive chemotherapy alone, by slightly increasing the CR rate but more importantly by reducing the relapse rate. These results were confirmed by the Chinese, Japanese and New York groups. Our group (and other European groups) are now testing in a new randomized trial the better timing of ATRA and chemotherapy administration (ATRA followed by chemotherapy or ATRA plus chemotherapy) and the role (after an intensive consolidation) of maintenance treatment with intermittent ATRA, continuous low dose chemotherapy or both.

Adult↗
PubMed1995

Immunisations after bone marrow transplantation: results of a European survey and recommendations from the infectious diseases working party of the European Group for Blood and Marrow Transplantation.

Increased numbers of recipients of BMTs and autologous BMTs are becoming long-term survivors. Existing data support that loss of protective immunity to agents such as tetanus and poliovirus is common in patients who received BMTs and autologous BMTs. Thus, a reimmunisation programme is needed to ensure immunity. A questionnaire concerning immunisation practices was sent to EBMT member centres. The immunisation practices varied extensively in the 59 responding BMT and 48 responding autologous BMT centres. Sixty five per cent of responding centres routinely immunise patients who received allogeneic BMTs whereas 37% were routinely immunising recipients of autologous BMTs. Tetanus toxoid and inactivated poliovirus vaccine were the most frequently used vaccines in both BMT and autologous BMT centres. Immunisations of recipients of both BMTs and autologous BMTs with tetanus toxoid, diphtheria toxoid, inactivated poliovirus vaccine and influenza vaccine are recommended. Other vaccines, and in particular live attenuated vaccines, may be considered on an individual basis.

Bone Marrow Transplantation↗
PubMed1995

Allogeneic liver transplantation for hepatic veno-occlusive disease after bone marrow transplantation--clinical and immunological considerations.

Veno-occlusive disease (VOD) is a frequent complication early after bone marrow transplantation. In cases of severe liver failure treatment by allogeneic liver transplantation is possible. We report the clinical and immunological course of a patient after bone marrow transplantation for AML and subsequent allogeneic liver transplantation for severe hepatic VOD. After liver transplantation the patient recovered well clinically. Early after liver transplantation he had large numbers of liver donor T and NK lymphocytes in his circulation. He had no liver graft rejection, but he developed mild acute GVHD which was caused by liver graft-derived T lymphocytes. Two years after transplantation he had persistent microchimerism with donor liver cells detectable in his bone marrow. Now 36 months after transplantation, the patient has no evidence of recurrent leukemia, stable liver function, and no signs of graft-versus-host disease or bone marrow dysfunction.

Acute Disease↗
PubMed1994

A controlled trial of recombinant human erythropoietin after bone marrow transplantation.

Recombinant human erythropoietin (rHuEPO) stimulates erythropoietic bone marrow cells and increases erythrocyte production. This prospective study was designed to evaluate the effects of rHuEPO on regeneration of erythropoiesis after allogeneic or autologous bone marrow transplantation (BMT). Seventeen centers participated in this randomized, double-blind, placebo-controlled multicenter trial. The randomization was performed centrally for each center and stratified according to allogeneic or autologous BMT and major ABO-blood group incompatibility. One hundred and six patients received rHuEPO after allogeneic BMT and 109 patients received placebo. After autologous BMT, 57 patients were treated with rHuEPO and 57 with placebo. Patients received either 150 IU/kg/day C127 mouse-cell-derived rHuEPO or placebo as continuous intravenous infusion. Therapy started after bone marrow infusion and lasted until independence from erythrocyte transfusions for 7 consecutive days with stable hemoglobin levels > or = 9 g/100 mL or until day 41. After allogeneic BMT, the reticulocyte counts were significantly higher with rHuEPO from day 21 to day 42 after BMT. The median time (95% confidence intervals) to erythrocyte transfusion independence was 19 days (range, 16.3 to 21.6) with rHuEPO and 27 days (range, 22.3 to > 42) with placebo (P < .003). The mean (+/- SD) numbers of erythrocyte transfusions until day 20 after BMT were 6.6 +/- 4.8 with rHuEPO and 6.0 +/- 3.8 with placebo. However, from day 21 to day 41, the rHuEPO-treated patients received 1.4 +/- 2.5 (median, 0) transfusions and the control group received 2.7 +/- 4.0 (median, 2) transfusions (P = .004). In the follow-up period from day 42 up to day 100, 2.4 +/- 5.6 transfusions were required with rHuEPO and 4.5 +/- 9.6 were required with placebo (P = .075). A multivariate analysis (ANOVA) showed that acute graft-versus-host disease (GVHD), major ABO-blood group incompatibility, age greater than 35 years, and hemorrhage significantly increased the number of transfusions. However, after day 20, rHuEPO significantly reduced the number of erythrocyte transfusions in these patient groups, as well as reducing incompatibility in the major ABO-blood group. For the whole study period, rHuEPO reduced the transfusion requirements in GVHD III and IV from 18.4 +/- 8.6 to 8.5 +/- 6.8 U (P = .05). After autologous BMT, there was no difference in the time to independence from erythrocyte transfusions and in the regeneration of reticulocytes. Marrow purging strongly increased the requirement for transfusions as well as the time to transfusion independence.

ABO Blood-Group System↗
PubMed1994

Pulmonary infiltrations in febrile patients with neutropenia. Risk factors and outcome under empirical antimicrobial therapy in a randomized multicenter study.

BACKGROUND: Different empirical approaches to antimicrobial treatment of lung infiltrates in patients with neutropenia were studied within a prospective, randomized multicenter trial. METHODS: Patients with neutropenia with hematologic malignancies and fever of 38.5 degrees C or higher associated with newly diagnosed lung infiltrates were randomized for an initial therapy with acylaminopenicillin plus aminoglycoside (Group A), third-generation cephalosporin plus aminoglycoside (Group B), or the double beta-lactam combination (Group C), each in combination with rifampin. Nonresponders were given empirical amphotericin B plus 5-fluorocytosine beginning on day 4, day 5, or day 6 under study. RESULTS: Of 295 patients entered, 91.2% were evaluable. Complete response was obtained in 61.3% with no significant difference between treatment groups. The addition of rifampin did not improve treatment results. Only 27.1% of patients achieved a complete response by antibiotic therapy without additional antifungal therapy. Fungi dominated in cases of microbiologically documented infections and were associated with a poorer outcome compared with bacterial pneumonias. The trend of leukocyte counts under study had a highly significant effect on the outcome of infection. CONCLUSIONS: Lung infiltrates in febrile patients with neutropenia represent a high risk of treatment failure. Persistent neutropenia has a significantly adverse effect on the outcome of infection. Incorporation of systemic antifungal agents into first-line therapy, particularly in selected high-risk subgroups, might improve future treatment results. The quality of diagnostic techniques to establish the etiology of pulmonary infiltrates needs to be improved.

Adolescent↗
PubMed1994

[Empirical antimicrobial therapy in neutropenic patients. Results of a multicenter study by the Infections in Hematology Study Group of the Paul Ehrlich Society].

BACKGROUND: Severe infections are the predominant cause of treatment failure in patients with high grade malignant hematological disorders undergoing intensive chemotherapy. PATIENTS AND METHODS: In a multicenter trial of the Paul Ehrlich Society (PEG) study group, febrile neutropenic patients with acute leukemias or other high grade hematological malignancies were randomized for a three phase sequential antimicrobial intervention comparing different widely applied regimes for empirical therapy. Patients with clinically documented infections were treated according to a modification depending on the respective source of infection, whereas in patients with microbiologically documented infections, treatment could be adapted to the sesceptibility patterns of detected pathogens. Criteria for evaluation as well as time points for response assessment and treatment escalation were strictly prescribed by the study protocol. RESULTS: Of 1573 evaluable patients, 50.9% had fever of unknown origin (FUO) throughout the study period, 17.1% had lung infiltrates, 14.1% primary bacteremia or fungemia (B/F), 12.6% other clinically documented (CDI) and 5.3% other clinically as well as microbiologically documented infections (CMDI). Cumulative response rate (CR) in patients with FUO was 91.3%, a significant difference between various regimens could not be detected in either of the three treatment phases. Patients with lung infiltrates had a significantly worse treatment outcome as compared to patients with other documented infections or with FUO (61.3% vs 82.9% vs 91.3%). Gram-positive pathogens dominated in case of microbiologically documented infections (MDI), whereas the proportion of fungal infections increased dramatically in MDI with pathogens detected only after more than six days under study. Of numerous prognostic factors analyzed, only the trend in white blood cell counts had a significant impact on treatment outcome. CONCLUSION: Infection-related mortality in neutropenic patients with high grade hematological malignancies can be markedly reduced by a systematically escalating interventional antimicrobial therapy. Early systemic antifungal treatment, especially in patients with lung infiltrates, might further improve treatment results.

Adolescent↗