PubMed Health⌕ Search

Biomedical subjects

M H van Oers

Publications and source records attributed to M H van Oers.

At least 19 recordsLinked to original sources
PubMed2001

Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma.

Acquired immunodeficiency syndrome-related non-Hodgkin lymphomas (AIDS-NHL) are thought to arise because of loss of Epstein-Barr Virus (EBV)-specific cellular immunity. Here, an investigation was done to determine whether cellular immunity to EBV is lost because of physical loss or dysfunction of EBV-specific cytotoxic T cells. Data on EBV-specific cellular immunity were correlated with EBV load. For comparison, individuals who progressed to AIDS with opportunistic infections (AIDS-OI) and long-term asymptomatics (LTAs) were studied. The number of virus-specific T cells was detected using tetrameric HLA-EBV-peptide complexes; function of these EBV-specific T cells was determined using the interferon-gamma (IFN-gamma) Elispot assay. It was observed that EBV-specific CD8(+) T cells were present in normal numbers in human immunodeficiency virus (HIV)-infected individuals. However, their functional capacity was decreased compared with HIV(-) individuals. In AIDS-NHL patients, EBV-specific T cells were not physically lost in the course of HIV-1 infection but showed progressive loss of their capability to produce IFN-gamma in response to EBV peptides. This loss of function correlated with lower CD4(+) T-cell numbers and was accompanied by increasing EBV load. In HIV-1-infected LTA individuals, in whom CD4(+) T-cell numbers were maintained, and progressors to AIDS-OI, IFN-gamma-producing EBV-specific T cells were stable and EBV load remained stable or decreased in the course of HIV infection, suggestive of immune control. Our data indicate that functional loss of EBV-specific CD8(+) T cells with a concomitant increase in EBV load may play a role in the pathogenesis of AIDS-NHL.

AIDS-Related Opportunistic Infections↗
PubMed2001

Molecular diagnosis of visceral herpes zoster.

Patients with disseminated herpes zoster may present with severe abdominal pain that results from visceral involvement of varicella-zoster-virus infection. In the absence of cutaneous eruptions of herpes zoster, visceral herpes zoster is extremely difficult to diagnose. This diagnostic difficulty has the potential to cause devastating delays in treatment. We report a case series of four patients with visceral herpes zoster in whom large concentrations of DNA from varicella zoster virus were detectable in blood by PCR before signs of infection appeared on the skin, thus enabling early diagnosis and treatment.

Abdominal Pain↗
PubMed2001

[Diagnostics for classification of anemia].

Examining peripheral blood smears provides valuable information in the diagnosis of anaemia despite large inter- and intraobserver variation. The classification of anaemia is usually based on the average erythrocyte size, referred to as the mean corpuscular volume (MCV). Microcytosis indicates a reduced haemoglobin synthesis caused by either an iron deficiency or haemoglobinopathy, a congenital disorder. Macrocytosis is the result of a disruption to the division and maturing of proerythroblasts in the bone marrow, due, for example, to vitamin B12 (folic acid) deficiency or excessive alcohol use. Furthermore, a high number of reticulocytes in the blood indicates an increased production of erythrocytes whereas a low total indicates an inadequate production level. In addition to the case history and the physical examination, the MCV and number of reticulocytes can provide guidance with respect to further diagnostic investigation.

Algorithms↗
PubMed2001

Constitutive CD27/CD70 interaction induces expansion of effector-type T cells and results in IFNgamma-mediated B cell depletion.

The interaction between the TNF receptor family member CD27 and its ligand CD70 provides a costimulatory signal for T cell expansion. Normally, tightly regulated expression of CD70 ensures the transient availability of this costimulatory signal. Mice expressing constitutive CD70 on B cells had higher peripheral T cell numbers that showed increased differentiation toward effector-type T cells. B cell numbers in CD70 transgenic (TG) mice progressively decreased in primary and secondary lymphoid organs. This B cell depletion was caused by CD27-induced production of IFNgamma in T cells. We conclude that apart from its role in controlling the size of the activated T cell pool, CD27 ligation contributes to immunity by facilitating effector T cell differentiation.

Animals↗
PubMed2001

Autologous peripheral blood stem cell transplantation in patients with relapsed lymphoma results in accelerated haematopoietic reconstitution, improved quality of life and cost reduction compared with bone marrow transplantation: the Hovon 22 study.

The present study analysed whether autologous peripheral blood stem cell transplantation (PSCT) improves engraftment, quality of life and cost-effectiveness when compared with autologous bone marrow transplantation (ABMT). Relapsing progressive lymphoma patients (n = 204; non-Hodgkin's lymphoma n = 166; Hodgkin's disease n = 38) were, after induction treatment with the DHAP-VIM (cisplatin, cytarabine, dexamethasone, etoposide, ifosfamide, methotrexate) regimen, randomly (2:1) assigned to the harvest of granulocyte-macrophage colony-stimulating factor-mobilized stem cells after the second DHAP course or autologous bone marrow cells before the second DHAP course. These stem cells were reinfused following high-dose myeloblative chemotherapy. After induction, 118 patients obtained a partial or complete response and were eligible for randomization. In the PSCT arm (n = 76) significantly faster engraftment of neutrophils [> or = 0.1 and > or = 0.5 x 10(9)/l: 10.7 d (7-36, median, range), 15 (9-45) versus 13 (8-25) and 26 (14-80), P < 0.01] and thrombocytes [> or = 20 x 10(9)/l: 13 d (7-51) versus 18 (11-65), P < 0.01] were observed. In addition, significantly fewer transfusions of red blood cells [6 (0-23) versus 8 (2-24), P < 0.01] and platelets [4 (0-60) versus 8 (2-55), P = 0.01] were required in the PSCT arm. These findings were associated with a significant reduction in the median days of intravenous antibiotics in patients with fever [8.5 (0-30) versus 14 (0-34), P = 0.04] and hospital stay [27 (8-51) versus 34 (24-78), P < 0.05]. Quality of life demonstrated a significant difference in favour of the PSCT arm. Total transplantation costs were significantly lower in the PSCT arm [$13,954 ($4913- 29,532) versus $17 668 ($10,170-44,083) P < 0.05], as a result of the reduced hospital stay and lower antibiotic costs. In summary, these results indicate that PSCT is superior to ABMT with regard to engraftment, supportive care, quality of life and cost.

Adolescent↗
PubMed2001

Complement activation plays a key role in the side-effects of rituximab treatment.

Treatment with rituximab, a chimaeric anti-CD20 monoclonal antibody, can be associated with moderate to severe first-dose side-effects, notably in patients with high numbers of circulating tumour cells. The aim of this study was to elucidate the mechanism of these side-effects. At multiple early time points during the first infusion of rituximab, complement activation products (C3b/c and C4b/c) and cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and IL-8] were measured in five relapsed low-grade non-Hodgkin's lymphoma (NHL) patients. Infusion of rituximab induced rapid complement activation, preceding the release of TNF-alpha, IL-6 and IL-8. Although the study group was small, the level of complement activation appeared to be correlated both with the number of circulating B cells prior to the infusion (r = 0.85; P = 0.07) and with the severity of the side-effects. We conclude that complement plays a pivotal role in the pathogenesis of side-effects of rituximab treatment. As complement activation can not be prevented by corticosteroids, it might be relevant to study the possible role of complement inhibitors during the first administration of rituximab.

Adult↗
PubMed2000

High prevalence of Epstein-Barr virus type 2 among homosexual men is caused by sexual transmission.

To investigate whether Epstein-Barr virus (EBV) type 2 infection is highly prevalent among homosexual men, the prevalence of EBV type 2 was studied among homosexual and heterosexual white men who were at high and low risk for sexually transmitted diseases; these data were correlated with sexual behavior. The prevalence of EBV type 2 among homosexual men was significantly higher than it was among heterosexual men (39% vs. 6%). Among high-risk heterosexual men, prevalence was significantly higher than it was among low-risk heterosexual men (15% vs. 0). In univariate analyses, EBV type 2 infection in homosexual men was significantly associated with human immunodeficiency virus (HIV) seropositivity, increased numbers of intercourse partners, non-Dutch nationality, and human herpesvirus 8 seropositivity. In multivariate analyses, an independent association with EBV type 2 was observed only for HIV seropositivity and number of sex partners. These data support the conclusion that EBV type 2 infection is more prevalent among white homosexual men and is caused by sexual transmission.

Adult↗
PubMed2000

Donor lymphocyte infusions for relapsed multiple myeloma after allogeneic stem-cell transplantation: predictive factors for response and long-term outcome.

PURPOSE: To determine the efficacy, toxicity, and long-term outcome and prognostic factors of donor lymphocyte infusions (DLI) in patients with relapsed multiple myeloma (MM) after allogeneic stem-cell transplantation (AlloSCT). MATERIALS AND METHODS: Twenty-seven patients received 52 DLI courses at a median of 30 months after the previous AlloSCT. Reinduction therapy was administered to 13 patients before DLI. RESULTS: Reinduction therapy was successful in eight of 13 patients. Fourteen patients (52%) responded to DLI, including six patients (22%) who achieved a complete remission (CR). Five patients responded after T-cell dose escalation in subsequent DLIs. Four patients experienced relapse or disease progression (three from partial response and one from CR). Five patients remain in remission more than 30 months after DLI. Major toxicity was acute and chronic graft-versus-host disease (GVHD), which was present in 55% and 26% of patients, respectively. Two patients died from bone marrow aplasia. Median overall survival of all patients was 18 months. Overall survival was 11 months for DLI-resistant patients and has not been reached for the responding patients. In two patients, sustained molecular remission was observed. The factors that were correlated with response to DLI were a T-cell dose of more than 1.10(8) cells/kg, response to reinduction therapy, and chemotherapy-sensitive disease before AlloSCT. CONCLUSION: These data confirm the potential and durable graft-versus-myeloma effect of DLI in patients with relapsed MM after AlloSCT. Future studies should be aimed at increasing response rates, especially in patients with chemoresistant disease, and reducing toxicity by limiting GVHD. Adjuvant DLI seems an attractive and promising approach for patients who do not achieve a molecular remission after AlloSCT.

Adult↗
PubMed1999

Direct Epstein-Barr virus (EBV) typing on peripheral blood mononuclear cells: no association between EBV type 2 infection or superinfection and the development of acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma.

In the literature, a correlation has been suggested between the occurrence of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (NHL) and Epstein-Barr virus (EBV) type 2 infection. To further investigate a possible role for EBV type 2 infection in the development of AIDS-NHL, we developed a sensitive and type-specific nested polymerase chain reaction (PCR) assay and analyzed EBV types directly on peripheral blood mononuclear cells (PBMC) in three subgroups of human immunodeficiency virus (HIV)-1 infected individuals: 30 AIDS-NHL patients, 42 individuals progressing to AIDS without lymphoma (PROG), either developing opportunistic infections (AIDS-OI) or Kaposi's sarcoma (AIDS-KS), and 18 long-term asymptomatic individuals (LTA). Furthermore, EBV type analysis was performed on PBMC samples obtained from AIDS-NHL patients in the course of HIV-1 infection. The results showed that: (1) direct analysis of PBMC is superior to analysis of B-lymphoblastoid cell lines (B-LCL) grown from the same PBMC samples; (2) in HIV-1 infected individuals, there is a high prevalence of EBV type 2 infection (50% in LTA, 62% in progressors, and 53% in AIDS-NHL) and superinfection with both type 1 and 2 (24% in LTA, 40% in progressors, and 47% in AIDS-NHL); (3) EBV type 2 (super)infection is not associated with an increased risk for development of AIDS-NHL; (4) type 2 infection can be found early in HIV-1 infection, and neither type 2 infection nor superinfection correlates with a failing immune system.

Adult↗
PubMed1999

[Epstein-Barr virus in a donor kidney as a cause of non-Hodgkin lymphoma].

A 22-year-old male who had received a kidney transplant from his father (HLA haploidentical), presented with fever and malaise. After transplantectomy was performed because of rejection, the patient developed abdominal pain due to perforation of the small intestine. Non-Hodgkin's lymphoma was found in both the transplant and the small bowel. The patient had suffered a primary Epstein-Barr virus (EBV) infection, probably transferred through the transplanted kidney. DNA analysis showed that the lymphoma was of patient origin. After withdrawal of immunosuppressive therapy, no recurrence of the lymphoma was seen. EBV is a well-known aetiologic agent of non-Hodgkin's lymphomas arising in the immunocompromised patient.

Adult↗
PubMed1999

Induction therapy with vincristine, adriamycin, dexamethasone (VAD) and intermediate-dose melphalan (IDM) followed by autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma.

We performed a phase II study to test the efficacy and feasibility of induction therapy with vincristine, adriamycin and dexamethasone (VAD) and intermediate-dose melphalan, 70 mg/m2 (IDM), to autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma (MM). A total of 77 patients received two cycles of VAD (n = 62) and/or two cycles of i.v. IDM 70 mg/m2 (n = 15) combined with G-CSF. PBSC were harvested after the first IDM, successfully in 87% of patients. Patients with a response to induction received myeloablative therapy with PBSCT (n = 50) followed by IFN maintenance or allo-BMT (n = 11). Seventy-two per cent of patients achieved a response after VAD which increased to 85% after IDM. Of patients who received PBSCT and allo-BMT, 24% and 45% achieved CR, respectively. Toxicity of induction consisted mainly of bone marrow suppression after IDM (median 8 days) with prolonged aplasia in 11% of patients after the second IDM. Only six infections WHO grade 3 occurred during induction. Treatment-related mortality of PBSCT and allo-BMT was 6% and 18%, respectively. Median time of follow-up is 44 months, and 50% of patients after PBSCT and 60% of patients after allo-BMT are still in remission. Survival rates of all patients were 82%, 75% and 63%, and for transplanted patients 86%, 79% and 68% after 12, 24 and 36 months. Well known prognostic factors, including alpha-IFN maintenance after PBSCT, were not significant for response or survival although patients in CR after allo-BMT had a strong tendency for better outcome. VAD/IDM is an effective and safe induction therapy for autologous and allogeneic stem cell transplantation. Based on these observations a phase III trial was started in October 1995 comparing IFN maintenance with PBSCT and allo-BMT after response to induction with VAD and IDM.

Adult↗
PubMed1999

Aberrant expression and reverse signalling of CD70 on malignant B cells.

In normal lymphoid tissues the tumour necrosis factor-receptor family member CD27 and its ligand CD70 have a restricted expression pattern. Previously, we reported that expression of CD27 is deregulated in B-cell leukaemias and lymphomas. Here we show that, although infrequently expressed by normal human B cells in vivo, CD70 is found on 50% of B-CLLs, 33% of follicle centre lymphomas, 71% of large B-cell lymphomas, and 25% of mantle cell lymphomas. Interestingly, in the majority of leukaemias and lymphomas examined, CD70 was found to have a capped appearance, a feature that coincided with co-expression of CD27. Functional analysis showed that a subset of B-CLLs could proliferate vigorously in response to CD70 mAb but not to CD27 mAb. This response was synergistically enhanced by ligation of CD40 but inhibited by the presence of IL-4. Additional experiments indicated that the proliferative response was due to an agonistic signal delivered via CD70, rather than blocking of negative signalling by CD27. Thus, next to its role as ligand, in a subset of malignant B cells CD70 can operate as receptor and as such might contribute to progression of these B-cell malignancies.

Antigens, CD↗
PubMed1999

Vincristine, doxorubicin and dexamethasone (VAD) administered as rapid intravenous infusion for first-line treatment in untreated multiple myeloma.

We examined the feasibility of achieving a rapid response in patients with previously untreated multiple myeloma by administering vincristine 0.4 mg and doxorubicin 9 mg/m2 as a rapid intravenous infusion for 4 d together with intermittent high-dose dexamethasone 40 mg (VAD) for remission induction treatment in patients who were scheduled to receive high-dose therapy. 139 patients (86 male, 53 female; median age 53 years, range 32-65 years; Durie & Salmon stage IIA: 42, IIB: one, IIIA: 89, IIIB: seven) were included in a prospective multicentre study in which VAD was administered as remission induction treatment and was followed by intensified treatment. The response was evaluated according to the criteria of the Eastern Cooperative Oncology Group (ECOG). The results of treatment were evaluable in 134 patients. Five patients died before evaluation. 86 patients (62%) achieved a partial response (PR) and seven patients (5%) achieved a complete response (CR), which equates to a response rate of 67%. The main side-effect was mild neurotoxicity, which was observed in 18% of the patients. Fever or infections were reported in 27% of the patients. VAD administered as an outpatient regimen, based on rapid intravenous infusion, is an effective induction regimen for untreated myeloma with a 67% response rate and acceptable toxicity.

Adult↗
PubMed1998

[Lack of adherence to the guidelines on the use of fresh frozen plasma].

OBJECTIVE: Evaluation of transfusion practice with regard to the guidelines for fresh frozen plasma. DESIGN: Prospective. SETTING: Academic Medical Centre, department of internal medicine, Amsterdam, the Netherlands. METHOD: During 4 weeks in April-May 1996 the indication of every request for fresh frozen plasma was established by an inquiry by telephone and compared with the indications defined by the National organization for quality assurance in hospitals (CBO). To objectivate the stated indication it was checked whether laboratory tests had been performed (prothrombin time (PTT) and activated partial thromboplastin time (APTT), and if so, what the results were. Moreover, the numbers of transfused units of red cells, platelets and fresh frozen plasma in the first 24 hours were checked. RESULTS: During the study period there were 195 requests for 844 units of plasma. 613 units were transfused in 100 patients. If the CBO guidelines were applied strictly, the proportions of plasma units inappropriately requested and inappropriately administered were 53% and 47% respectively (in 32 patients). If the CBO indications were applied less strictly, still 25% of the units were inappropriately requested and 18% inappropriately administered (in 23 patients). CONCLUSION: The guidelines were observed only moderately. Better compliance is important for medical, logistic and financial reasons.

Academic Medical Centers↗
PubMed1998

Dissection of pathways leading to antigen receptor-induced and Fas/CD95-induced apoptosis in human B cells.

To dissect intracellular pathways involved in B cell Ag receptor (BCR)-mediated and Fas-induced human B cell death, we isolated clones of the Burkitt lymphoma cell line Ramos with different apoptosis sensitivities. Selection for sensitivity to Fas-induced apoptosis also selected for clones with enhanced BCR death sensitivity and vice versa. In contrast, clones resistant to Fas-mediated apoptosis could still undergo BCR-induced cell death. Based on the functional phenotypes of these clones, we hypothesized that both receptor-induced apoptosis pathways are initially distinct but may eventually converge. Indeed, ligation of both Fas and BCR resulted in cleavage of the IL-1beta-converting enzyme/Ced-3-like protease caspase 3 and its substrates Ac-Asp-Glu-Val-Asp-aldehyde and poly(ADP-ribose) polymerase. Markedly, qualitative differences in the caspase 3 cleavage pattern induced by Fas or BCR ligation were observed; whereas Fas ligation generated caspase 3 cleavage products of 19/20 and 17 kDa, only the latter cleavage product was found upon BCR cross-linking. The caspase inhibitor Val-Ala-Asp-fluoromethylketone blocked both Fas- and BCR-mediated apoptosis, but differentially affected caspase 3 cleavage induced by either stimulus. Finally, overexpression of a Fas-associated death domain (FADD) dominant-negative mutant protein was found to inhibit Fas-induced apoptosis but not BCR-induced apoptosis. Together our findings imply that Fas and BCR couple, via FADD-dependent and FADD-independent mechanisms, respectively, to distinct proteases upstream of caspase 3.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Control of lymphocyte function through CD27-CD70 interactions.

In contrast to the expression of other TNFR/TNF family members, expression of CD27 and its ligand CD70 is predominantly confined to lymphocytes. High expression levels of CD27 appear to be dependent on proper ligation of antigen receptors, whereas for the induction of CD70 expression additional (co-stimulatory and/or pro-inflammatory) signals are required. Next to membrane-bound CD27 also a soluble form of CD27 is produced in the course of the immune response. Soluble CD27 (sCD27) is found in body fluids and can be used to monitor local and systemic immune activation. In addition, elevated serum concentrations of sCD27 are found in patients with B cell malignancies and levels of sCD27 strongly correlate with tumor load. Based on functional experiments and in vitro expression regulation data, we propose that interactions between activated lymphocytes in vivo can result in CD27-CD70 interactions that may regulate the size and function of antigen-primed lymphocyte populations.

Animals↗
PubMed1998

Treatment of AIDS-related non-Hodgkin's lymphoma with chemotherapy (CNOP) and r-hu-G-CSF: clinical outcome and effect on HIV-1 viral load.

PURPOSE: The optimal treatment of AIDS-related NHL (ARL) has yet to be defined. The purpose of this study was 1) to evaluate the efficacy and toxicity of the CNOP-regimen (cyclophosphamide, mitoxantrone, vincristine, and prednison) in combination with G-CSF; and 2) to study the effect of this regimen on HIV-1 viral replication. PATIENTS AND METHODS: A phase II study was performed in 21 previously untreated patients with ARL. RESULTS: Based on intention to treat, the response rate was 43%: four complete and five partial remissions. Median survival was only five months. Only one patient had an opportunistic infection during treatment; three patients had localized infections and one episode of septicaemia was seen. Remarkably, during treatment, in 94% of cases p24 antigen levels either remained undetectable or showed a substantial decrease, even though antiretroviral therapy had been discontinued just prior to the first cycle of chemotherapy in all patients. HIV-1 RNA load decreased or remained unchanged in 82% of patients and increased in three patients. CONCLUSIONS: Our data demonstrate, 1) that the CNOP-regimen in combination with G-CSF, although associated with a low risk of both opportunistic and bacterial infections, can not be recommended in the treatment of ARL; but 2) that G-CSF can be used safely to sustain haematopoiesis in patients with ARL treated with chemotherapy.

Adult↗