Biomedical subjects

M Eibl

Publications and source records attributed to M Eibl.

At least 19 recordsLinked to original sources

PubMed2003

High-risk AML complicated by pulmonary aspergillosis: successful treatment with nonmyeloablative stem cell transplantation and long-term administration of voriconazole.

Acute myeloid leukemia (AML) associated with central diabetes insipidus (DI) and chromosomal aberrations is characterised by a very poor prognosis. We present a 28-year-old female with AML FAB M0, preceding DI and cytogenetic abnormalities (monosomy 7 and inversion of chromosome 9). Complete remission was achieved with FLAG after she was refractory to two different induction regimens. Prolonged neutropenia resulted in invasive pulmonary aspergillosis. Allogeneic stem cell transplantation from a matched unrelated donor was performed using a reduced-intensity conditioning regimen. Desmopressin substitution for DI was withdrawn after transplant without recurrence of symptoms. Initial antifungal treatment, including liposomal amphotericin B, caspofungin and itraconazole, was replaced by voriconazole after deterioration of pulmonary aspergillosis, resulting in improvement, stabilisation and finally, also as the combined effect of discontinuation of the immunosuppressive therapy, in disappearance of signs and symptoms. Thirteen months after transplant, the patient is in continuous complete remission. The presented case study thus demonstrates that high-risk AML with concomitant invasive fungal infection may be safely and effectively treated by nonmyeloablative stem cell transplantation and long-term administration of voriconazole.

Adult↗

PubMed2003

Accuracy of whole-body 18F-FDP-PET for restaging malignant lymphoma.

BACKGROUND: The aim of this retrospective study was to evaluate the accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) images, which were interpreted under daily routine conditions, in patients with Hodgkin's disease (HD) or non-Hodgkin lymphoma (NHL) for restaging after chemotherapy and/or radiotherapy. For this purpose, 18F-FDG-PET results were compared with morphological imaging methods and the patients' clinical background. METHODS: 121 PET images of 93 lymphoma patients (44 HD, 49 NHL) were investigated after chemotherapy/radiotherapy. For PET imaging, 160-200 MBq 18F-FDG was administered intravenously, followed by an infusion of 20 mg Furosemid in 250 mL saline. Whole-body 18F-FDG-PET images were obtained using a partial-ring PET scanner without attenuation correction. The morphological imaging consisted in computed tomography and ultrasound (CT/US) in all patients, additional MRI in some patients, and iliac crest biopsy in cases of suspicious bone marrow involvement. The standard of reference was composed of biopsy data, clinical status at the time of investigation, and follow-up of at least 12 months. The PET images were evaluated for their sensitivity, specificity and accuracy based on written reports, which were compiled from other imaging data and the clinical history of the patients. RESULTS: Sensitivity, specificity, and accuracy of 18F-FDG-PET was 91 %, 81 %, and 85 %; of CT/US, 88 %, 35 %, 56 %, respectively. Major sources of error in 18F-FDG-PET were due to asymmetric muscular hypermetabolism and inflammatory lesions misinterpreted as persistent viable lymphoma tissue. Furthermore, secondary malignancies other than lymphomas were another reason for misinterpretations of 18F-FDG-PET studies. CONCLUSIONS: 18F-FDG-PET showed a comparable sensitivity but a higher specificity and accuracy compared with CT/US. To achieve a high accuracy in 18F-FDG-PET, the nuclear medicine specialist needs imaging and clinical data as background information, which can only be acquired through close co-operation with the referring clinicians. Pharmacological muscular relaxation in the course of 18F-FDG-PET imaging may be advisable, as nonspecific muscular hypermetabolism was one of the problems at the image readings and a source of incorrect 18F-FDG-PET interpretations.

Adolescent↗

PubMed2003

Acute pseudo-obstruction of the small intestine following high-dose chemotherapy and stem cell support.

BACKGROUND: Acute intestinal pseudo-obstruction is a potentially life-threatening disease which is characterized by massive dilation of the colon or small intestine without mechanical obstruction and may develop after surgery or severe illness. PATIENTS AND METHODS: We report 2 cases in which acute small intestinal pseudo-obstruction occurred after high-dose chemotherapy and autologous stem cell support. In 1 patient explorative abdominal laparoscopy was performed to rule out mechanical ileus. However, after having initiated treatment with acetylcholinesterase inhibitors a prompt small intestinal decompression was observed in both patients. CONCLUSIONS: Acetylcholinesterase inhibitors should be considered as an early conservative intervention in the treatment of acute intestinal pseudo-obstruction to avoid surgery of patients undergoing high-dose chemotherapy with autologous stem cell support.

Adult↗

PubMed2002

Monitoring of cardiac function by serum cardiac troponin T levels, ventricular repolarisation indices, and echocardiography after conditioning with fractionated total body irradiation and high-dose cyclophosphamide.

OBJECTIVES: Highly differing rates of cardiac complications associated with high-dose cyclophosphamide (CY) have been reported, and only one clinical study has been performed on the cardiotoxic effects of CY monotherapy following total body irradiation (TBI). PATIENTS AND METHODS: We prospectively evaluated the potential cardiotoxic effects of conditioning with fractionated total body irradiation and high-dose cyclophosphamide (TBI/CY) by serial measurement of serum cardiac troponin T (cTnT), assessment of systolic and diastolic echocardiographic parameters and analysis of ventricular repolarisation indices (QT-dispersion and corrected QT-dispersion) in 30 adult patients with haematological malignancies undergoing haematopoietic stem cell transplantation. RESULTS: There was no evidence of pretreatment cardiac dysfunction in any patient. Although cTnT was determined serially for a median of 14 d after completion of conditioning, no elevated levels were observed. Echocardiographic parameters did not show any significant change at a median follow-up of 5 months except for one patient with evidence of impaired diastolic filling. No significant differences for mean values before and after high-dose CY were noted for ventricular repolarisation indices. Two patients had a significant increase in corrected QT-dispersion after CY without any other signs of cardiotoxicity. Congestive heart failure or arrhythmias were not observed. CONCLUSIONS: These data suggest that TBI/CY is safe with respect to cardiotoxicity in patients without pre-existing cardiac dysfunction. Hitherto unknown synergistic cardiotoxic effects of CY with other cytostatic drugs may constitute the major pathogenic factor of myocardial dysfunction after high-dose chemotherapy.

Adult↗

PubMed2001

Hepatic veno-occlusive disease in two patients with relapsed acute myeloid leukemia treated with anti-CD33 calicheamicin (CMA-676) immunoconjugate.

Monoclonal antibodies recognizing hematopoietic antigens are increasingly being used to target therapy directly at leukemic cells, with the aim of achieving sustained remission with little systemic toxicity. Administration of anti-CD33 calicheamicin immunoconjugate is commonly regarded as being safe, with only moderate systemic non-hematological side effects. We report on two cases of hepatic veno-occlusive disease in heavily pretreated patients presenting with relapsed acute myeloid leukemia (AML). Since significant liver toxicity prevented further specific therapy in both patients, we recommend that antibody therapy with anti-CD33 immunoconjugate should be applied with caution in patients presenting with risk factors for the development of hepatic veno-occlusive disease.

Acute Disease↗

PubMed2001

Cytomegalovirus diagnosis in renal and bone marrow transplant recipients: the impact of molecular assays.

BACKGROUND: Cytomegalovirus (CMV) infections are a major threat in transplant recipients. In recent years, new assays for routine CMV diagnosis, based on molecular techniques, have become available. OBJECTIVE: The impact of molecular assays for CMV diagnosis in transplant recipient was evaluated. STUDY DESIGN: A total of 51 transplant recipients were screened for CMV infection. Serological (AxSYM CMV IgG and recombinant CMV IgM assays), antigenemia, CMV DNA (qualitative in house PCR and the quantitative COBAS AMPLICOR CMV MONITOR Test), and CMV mRNA (NucliSens CMV pp67 Test) tests were compared. RESULTS: In 11/20 bone marrow transplant (BMT) recipients and 10/31 renal transplant (RTX) recipients there was no evidence of active CMV infection. Ten RTX recipients and one BMT recipient were antigenemia positive, 21 RTX and seven BMT recipients were PCR positive (qualitative CMV PCR). There were more BMT recipients CMV DNA positive in serum (7/21) than antigenemia positive (1/21). CMV mRNA was found positive in two BMT recipients (one case with no other evidence of CMV infection, the other one CMV DNA positive and antigenemia negative). The only antigenemia positive BMT recipient was found negative for CMV mRNA, but positive in all other tests. Eight RTX recipients were found positive for CMV mRNA. Six of them were also antigenemia positive and five of those were also found positive for CMV IgM. One CMV mRNA positive RTX recipient was CMV IgM positive but antigenemia negative and the other one CMV mRNA positive RTX recipient was found negative in all other tests. Two antigenemia positive RTX recipients were found negative for mRNA and CMV IgM. CONCLUSION: Antigenemia was found to be a good screening test for CMV infection in RTX recipients. In BMT recipients, tests based on molecular techniques appeared to be superior compared to antigenemia.

Adolescent↗

PubMed2001

Amifostine in combination with erythropoietin and G-CSF promotes multilineage hematopoiesis in patients with myelodysplastic syndrome.

Ineffective hematopoiesis leading to profound cytopenias represents a major clinical problem in the management of patients with myelodysplastic syndrome (MDS). The aminothiol amifostine has shown to promote multilineage hematopoiesis both in vivo and in vitro in patients with MDS. We have treated 10 patients with 250 mg/m2 amifostine thrice weekly in combination with erythropoietin for 4 consecutive weeks followed by 2 weeks observation. Responding patients received the same 6 week schedule, while nonresponder received G-CSF in addition to erythropoietin and amifostine during the second treatment course. All patients experienced single or multilineage hematologic improvement, but only 2 reached transfusion independency. Moreover, response was durable only in a minority of patients and thus additional studies are warranted to further define the potential interaction of amifostine and growth factors.

Aged↗

PubMed2000

Preterm infants with low immunoglobulin G levels have increased risk of neonatal sepsis but do not benefit from prophylactic immunoglobulin G.

OBJECTIVE: In a prospective, randomized, placebo-controlled, multicenter study, we evaluated the prevention of neonatal infections with intravenous immunoglobulin G (IVIgG) prophylaxis for preterm infants (gestational age <33 weeks) with umbilical cord blood IgG levels < or =4 g/L. STUDY DESIGN: Intravenous IgG or placebo (albumin), 1 g/kg body weight, was given on days 0, 3, 7, 14, and 21 to 81 infants with umbilical cord blood IgG levels < or =4 g/L: (1) IVIgG group, n = 40, mean (SD) gestational age 27.5 (2.2) weeks and birth weight 1.06 (0.39) kg; (2) placebo group, n = 41, mean (SD) gestational age 27.7 (2.5) weeks and birth weight 1.13 (0.38) kg. Infants with umbilical cord blood IgG levels >4 g/L (n = 238) served as a separate comparison group. Neonatal infections according to European Society of Pediatric Infectious Disease criteria were monitored until 28 days of life. RESULTS: Infants with IgG levels < or =4 g/L at birth who received IVIgG had no significant reduction in infectious episodes or mortality rate when compared with those given placebo. However, infants with a serum concentration of IgG >4 g/L at birth had significantly fewer infectious episodes (culture-proven sepsis) than infants with low serum concentrations of IgG (< or =4 g/L) when compared at the same gestational ages (26 to 29 weeks, P <.003). CONCLUSIONS: Prophylactic immunotherapy with IVIgG did not improve the immune competence in preterm infants with low serum IgG concentrations at birth. We speculate that a spontaneously high serum IgG concentration at birth reflects placenta function and is an indicator of a more mature immune system capable of protecting the preterm infant against severe neonatal infections.

Cross Infection↗

PubMed1999

Defective self-reactive antibody repertoire of serum IgM in patients with hyper-IgM syndrome.

We have analyzed the self-reactive repertoires of IgM and IgG Abs in the serum of 19 patients with hyper-IgM syndrome (HIM) by means of a quantitative immunoblotting technique that allows for a quantitative comparison of Ab repertoires in health and disease by multiparametric statistical analysis. Normal tissue extracts of liver, lung, stomach, and kidney were used as sources of self Ags. Extracts of Pseudomonas aeruginosa and Staphylococcus epidermidis were used as sources of nonself Ags. We demonstrate a significant bias in repertoires of reactivities of IgM of patients with HIM with self Ags. Ab repertoires of IgM toward nonself Ags did not differ, however, between patients and controls. No difference was found between IgM repertoires of untreated patients and those of patients receiving substitutive treatment with i.v. IgG. IgG in the serum of HIM patients lacked reactivity with self Ags, although it exhibited a pattern of reactivity with nonself Ags that was similar to that of IgG of healthy controls. The data demonstrate that functional CD40-CD40 ligand interactions are essential for the selection of natural self-reactive B cell repertoires.

Adolescent↗

PubMed1999

Effect of intravenous immunoglobulin on steroid consumption in patients with severe asthma: a double-blind, placebo-controlled, randomized trial.

BACKGROUND: There is a significant group of patients with severe asthma who require chronic use of systemic steroids for control of their disease. These patients are at risk for severe side effects from oral steroids. Intravenous immunoglobulin (IVIG) has immunomodulatory properties, and a few open-label trials have suggested its possible benefit in individuals with severe asthma. OBJECTIVE: This study was designed to assess the potential benefit of IVIG as a steroid-sparing agent in patients with severe asthma. METHODS: Thirty-eight immunocompetent steroid-requiring patients with severe asthma were randomly enrolled in a double-blind, placebo-controlled trial of IVIG. RESULTS: Of the 38 patients enrolled, 28 patients completed the study. A significant reduction in oral steroid requirement was observed in both the IVIG-treated (n = 16) and the placebo-treated (n = 12) patients. Further exploration of the results showed that IVIG, but not placebo, had a significant steroid-sparing effect in patients requiring high doses of oral steroids (ie, >2000 mg in the year before the study). Within this subgroup, IVIG treatment (n = 9) resulted in a significant decrease in oral steroid requirement, with a median of 16.4 mg/day during the pretreatment period to 3 mg/day during the treatment phase (P =. 0078). No significant decrease in oral steroid requirement was observed in placebo-treated patients (n = 8) within this subgroup. Objective and subjective parameters of the patients' asthma were unchanged in spite of the steroid tapering achieved in the group treated with IVIG. CONCLUSION: IVIG may be a useful steroid-sparing agent in patients with severe asthma requiring high doses of oral steroids.

Administration, Oral↗

PubMed1999

Electron microscopic and immunohistochemical verification of diagnosis in two archival cases recognized as encephalitis necroticans acuta (ENA) on routine examinations.

Two archival cases diagnosed 20 years ago on routine neuropathological methods as Encephalitis Necroticans Acuta (ENA) were investigated in EM and by immunohistochemical methods. The previous diagnosis was confirmed only in one case because Herpes simplex virus was found. In the second case the intracellular inclusions visible in ME corresponded to Measles Virus thus previous diagnosis was changed to SSPE.

Adolescent↗

PubMed1998

Role of preimmunization virus sequences in cellular immunity in HIV-infected patients during HIV type 1 MN recombinant gp160 immunization.

The effect of patient preimmunization virus sequences on CTL responses during gp160 immunization were studied. Ten HLA-A2+, HIV+ asymptomatic patients with CD4+ T cells >500/mm3 were given two courses of HIV-1 MN rgp160 vaccine over a 2-year period. Envelope epitope-specific CTL responses, using PBMCs, were measured against peptide-coated autologous B lymphoblastoid cell lines. Optimum CTL epitopes were determined by HLA-A2-binding affinity of 9- to 10-mer peptides containing the HLA-A2.1-binding motif. Ten of the high- or intermediate-binding peptides were conserved among >50% of reported clade B HIV strains. These peptide-specific CTL activities and the patient virus sequences in peptide-coding regions were monitored. Six patients showed envelope peptide-specific CTL responses, which correlated with the presence of whole envelope antigen-specific CTL responses. Five of these patients, who showed responses to epitopes in the gp41 region (aa 814-824), had preimmunization virus similar to the vaccine sequence in this region. Three patients who did not show these epitope-specific responses had initially different sequences in the HIV gene encoding that region. The epitope-specific CTL responses appear to reflect recall responses, as only patients infected with virus containing the vaccine sequence developed them and they could be recalled with a second set of vaccine injections. This appears to be reminiscent of the concept of T cell "original antigenic sin." This vaccine was also immunogenic as measured by gp160-specific lymphocyte-proliferative responses. However, increased immune responses did not impact the HIV load or CTL epitope sequences during therapy.

AIDS Vaccines↗

PubMed1998

A pilot clinical trial of HIV antigen-pulsed allogeneic and autologous dendritic cell therapy in HIV-infected patients.

A pilot study was carried out to assess the safety and antigen-presenting properties of allogeneic or autologous dendritic cells (DCs) in six HLA-A2+, HIV-infected patients. Allogeneic DCs obtained from the peripheral blood of HLA-identical, HIV-seronegative siblings were pulsed with recombinant HIV-1 MN gp160 or synthetic peptides corresponding to HLA-A2-restricted cytotoxic epitopes of envelope, Gag, and Pol proteins. The antigen-pulsed cells were infused intravenously six to nine times at monthly intervals and HIV-specific immune responses were monitored. One allogeneic DC recipient with a CD4+ T cell count of 460/mm3 showed increases in envelope-specific CTL- and lymphocyte-proliferative responses, as well as in IFN-gamma and IL-2 production. Another allogeneic DC recipient with a CD4+ T cell count of 434/mm3 also showed an increase in HIV envelope-specific lymphocyte-proliferative responses. A recipient of autologous DCs with a CD4+ T cell count of 730/mm3 showed an increase in peptide-specific lymphocyte-proliferative responses after three infusions. Three other allogeneic DC recipients with CD4+ T cell counts <410/mm3 did not show increases in their HIV-specific immune responses. No clinically significant adverse effects were noted in this study and CD4+ T cell numbers and plasma HIV-1 RNA detected by RT-PCR of all six patients were stable during the study period. Thus, both allogeneic and autologous DC infusions were well tolerated and in patients with normal or near normal CD4+ T cell counts administration of these antigen-pulsed cells enhanced the immune response to HIV. However, since no effect on viral load was observed there was no evidence that this approach provided clinical benefit.

Cell Division↗

PubMed1995

Hodgkin's disease developing after spontaneous remission of chronic lymphocytic leukemia.

We present a 71-year-old patient with chronic lymphocytic leukemia diagnosed 27 years ago. Initially, the disease was staged as Rai II and the patient suffered from secondary immunoglobulin deficiency. Nevertheless, no treatment was necessary at that time. Because of disease progression a single course of chemotherapy was given in 1984. During the following year there was a constant decline of the WBC, accompanied by normalization of the immunoglobulins; both have remained stable ever since that time. However, there was still residual bone marrow infiltration, indicating persisting CLL. In 1993 cervical lymphadenopathy occurred with acute onset. A diagnostic lymphadenectomy revealed Hodgkin's disease of the nodular-sclerosing subtype. The patient was staged as II-III according to the Ann Arbor Classification and underwent radiation therapy. Cytogenetic examination of the bone marrow revealed a normal karyotype with an inversion of chromosome 9. This case demonstrates the rate coincidence of two lymphoproliferative disorders in the same patient. The clinical course and the immunologic findings of this patient are presented, together with a review of the literature.

Adult↗

PubMed1995

Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer: a prospective longitudinal study.

Immunosuppression has been often associated with the course of malignant diseases. In the present study, the proliferation of peripheral blood mononuclear cells (PBMCs) in response to mitogenic stimulation with phytohaemagglutinin (PHA) was assessed prospectively in 90 patients with stage I-III breast cancer. Whereas PHA-induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals (P < 0.001), the degree of the defect in PHA-induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement (P < 0.003 in each case). PHA-induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) after an observation period of 6 months (P < 0.01), but not in patients under adjuvant treatment with tamoxifen only. After an additional 6 months (i.e. 12 months after surgery), PHA-induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment (P > 0.1), but in all patients still significantly decreased as compared with healthy controls (P < 0.001). When data obtained preoperatively and after 12 months were compared, it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA-induced proliferation, 14 (61%) had developed metastatic disease within the subsequent 24 months (i.e. 36 months after surgery). In contrast, out of 59 patients whose PBMCs showed an increase in their PHA-induced proliferation within the first 12 months after surgery, only one (2%) presented with disease progression. We thus conclude that PHA-induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Growth kinetics of fibroblasts on bovine dentin.

In vitro dentin barrier tests published so far show several shortcomings. Therefore, we designed a new test method using bovine dentin disks on which cells were grown on one side. In this study, we evaluated the growth kinetics of L-929 mouse fibroblasts on dentin disks of 0.75-mm thickness and 4-mm diameter derived from lower incisors of freshly slaughtered bovines. The application of 50% citric acid for 30 s was optimal for the gentle removal of the smear layer from the cut dentin slices. Growth kinetics of mouse fibroblasts depended on the initially plated cell density: optimal cell growth on the disks was observed with approximately 200 cells/mm2, which was the same as the growth rate on the bottom of a cell culture vessel. Consequently, bovine dentin disks are a suitable substrate for normal cell growth, and this set-up can be used in a dentin barrier test.

Acid Etching, Dental↗

PubMed1994

HIV-1 recombinant gp160 vaccine given in accelerated dose schedules. NIAID AIDS Vaccine Clinical Trials Network.

The purpose of this randomized, double-blind study was to test the safety and immunogenicity of an HIV-1LAI recombinant gp160 (rgp160) vaccine in healthy, uninfected volunteers using accelerated dosing schedules. Thirty volunteers were randomly assigned to receive 50-micrograms doses of rgp160 in one of two immunization schedules. Group 1 received rgp160 at times 0, 1, 2 and 5 months; and group 2 received rgp160 at times 0, 1, 2, 3 and 4 months. The vaccine was safe and stimulated high levels of HIV-1 envelope-specific binding antibody and T cell memory. There was a trend (P < 0.10) suggesting neutralizing antibodies were better induced by the regimen incorporating a rest period before the final immunization in group 1 volunteers. Both accelerated immunization schedules induced immune responses at levels similar to or better than those achieved by four rgp160 vaccine injections given over 12-18 months in other studies.

AIDS Vaccines↗

PubMed1993

Determination of placental ferritin-positive peripheral lymphocytes in early stages of breast cancer.

"Ferritin-blocked lymphocytes" or placental ferritin (PLF) -positive T cells have repeatedly been described in the circulation of patients with female breast cancer. Since a monoclonal antibody directed against PLF became available, a study was performed to evaluate its usefulness in an easily reproducible system. One hundred patients with controversial or highly suspicious findings on mammography who subsequently underwent operation entered this trial. Sixty-one healthy blood donors served as controls. Patients with early (lymph-node negative) stages of breast cancer (in situ and T1N0 tumors) revealed significantly higher numbers of PLF-positive cells (9.00% +/- 4.5% and 6.21% +/- 3.4%) as compared with controls or patients with benign lumps (p < 0.001). Patients with negative lymph nodes differed significantly from node-positive patients (9.79% versus 2.55%; p < 0.001), whereas no difference as related to menopausal and estrogen-receptor status was observed. In order to define the sensitivity and specificity of this test, we analyzed four different cutoff levels (3%, 4%, 5%, and 6% of PLF-positive T cells). At a level of PLF-positive lymphocyte cells of 4%, 94% of cancer patients with stage T1N0 disease or ductal carcinoma in situ, 5% of patients with benign lumps, and 7% of healthy controls were identified. Furthermore, 88% of all lymph node-negative cancer patients had more than 4% positive cells, compared with only 25% in patients with axillary node involvement. The fact that more than 90% of all patients with in situ carcinomas and patients with stage T1N0 cancer had values above 4% offers promising aspects for this method to be used to complement mammography in the early detection of breast cancer.

Adult↗