PubMed Health⌕ Search

Biomedical subjects

G C de Gast

Publications and source records attributed to G C de Gast.

At least 19 recordsLinked to original sources
PubMed1992

Detection of cytomegalovirus (CMV) in granulocytes by polymerase chain reaction compared with the CMV antigen test.

To compare the sensitivity and suitability of detection of active cytomegalovirus (CMV) infection by using monoclonal antibodies against CMV antigen (antigen test to detect antigenemia) and the polymerase chain reaction (PCR; to detect viral DNA) in granulocytes, 19 heart and 2 lung transplant recipients were closely monitored by these tests for at least 3 months after transplantation. All patients were CMV seropositive or had a seropositive donor. In total, 201 samples were tested; 46 were positive by both tests, 9 samples showed only antigenemia, 54 samples were positive by PCR only, and 102 samples were negative by both tests. PCR was positive earlier after transplantation in eight patients, whereas antigenemia was positive earlier after transplantation in one patient. In another four patients, both tests were positive at the same time. PCR was, on average, positive for a longer period of time. Discordant results showing a positive antigen test and a negative PCR were partly due to sampling error; some were positive by PCR on retesting. Samples which were negative by the antigen test and positive by PCR were taken at the beginning or at the end of an active CMV infection. In two patients, no active CMV infection was detected by the antigen test, cultures of urine and saliva, or serology, although PCR was positive for a long period of time in the two patients.

Antigens, Viral↗
PubMed1992

Salvage therapy with ProMACE-MOPP followed by intensive chemoradiotherapy and autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma who failed to respond to first-line CHOP.

PURPOSE: We used alternative chemotherapy immediately followed in early-response patients by high-dose chemoradiotherapy and autologous bone marrow transplantation (ABMT) to treat patients with non-Hodgkin's lymphoma (NHL) who had failed to respond to first-line chemotherapy. PATIENTS AND METHODS: Thirty-one patients with NHL of intermediate- or high-grade malignancy who had failed to respond to first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy were treated. Seventeen patients had primary refractory disease and 14 had relapsed from first complete response (CR). The treatment consisted of prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, and procarbazine (ProMACE-MOPP) salvage chemotherapy, followed, in case of responsive disease (at least partial response [PR]), by high-dose cyclophosphamide and total-body irradiation (TBI) with ABMT. RESULTS: Twenty-eight of 31 (90%) patients achieved PR (23 patients) or CR (five patients) with ProMACE-MOPP, and three failed to respond. Seventeen of 28 (61%) patients who responded underwent the ABMT procedure, which resulted in CR in 14 patients (82%); three failed to respond. Eleven responsive patients were not transplanted because of residual bone marrow infiltration (five patients), patient refusal (four patients), and ProMACE-MOPP-related mortality (two patients). To date, nine patients are alive and in CR, seven with a median follow-up of 41 months (range, 17 to 84 months). Referring to the original CHOP treatment, five of 17 (29%) patients with primary refractory disease remain free of disease at a median of 36 months after ABMT, and four of 14 (29%) patients in first relapse remain free of disease at a median of 33 months after ABMT. One patient died of AMBT-related toxicity. CONCLUSION: ProMACE-MOPP salvage chemotherapy produces a high early-response rate in patients who fail to respond to first-line CHOP, and more than half of the responding patients can be scheduled to receive ABMT, resulting in disease-free survival (DFS) at 3 years in 50% of the transplanted patients and in 25% of the original number of patients intended to receive this treatment.

Adolescent↗
PubMed1992

Autologous bone marrow transplantation for adult poor-risk lymphoblastic lymphoma in first remission.

PURPOSE: Adult patients with poor-risk lymphoblastic lymphoma (LBL) treated with intensive multiagent chemotherapy (acute lymphoblastic leukemia [ALL]-like regimens) have a poor prognosis, with a disease-free long-term survival rate of less than 20%, caused by a very high relapse rate. Thus, adult patients with poor-risk LBL are candidates for alternative intensive consolidation therapy. PATIENTS AND METHODS: Nine adult patients with poor-risk LBL in first remission after treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; six patients) or ALL-like regimens (three patients), were treated with high-dose cyclophosphamide and total body irradiation (TBI) followed by nonpurged autologous bone marrow transplantation (ABMT). RESULTS: Two of nine patients relapsed at 4 and 8 months, respectively, after BMT, and one patient died of acute myeloblastic leukemia (AML) 7 months after ABMT without recurrence of his lymphoma. Six patients are in unmaintained first remission with a follow-up of 12 to 113 months (median, 53 months) after transplantation. CONCLUSIONS: These results suggest that intensive consolidation therapy with high-dose cyclophosphamide and TBI followed by nonpurged ABMT may improve the long-term prognosis of this disease.

Adolescent↗
PubMed1992

Abortive human cytomegalovirus infection in patients after allogeneic bone marrow transplantation.

Infection with human cytomegalovirus (HCMV) after allogeneic bone marrow transplantation (BMT) was studied in 12 HCMV seronegative recipients of marrow from seropositive donors by weekly monitoring of cultures, expression of HCMV antigenemia (pp65) in granulocytes, polymerase chain reaction (PCR) on HCMV-DNA in granulocytes and IgM and IgG anti-HCMV antibodies. Eight patients remained negative in all tests as did 33 HCMV seronegative recipients of marrow from seronegative donors. In four patients, a transient expression of HCMV antigen pp65 in granulocytes from peripheral blood, together with a positive PCR on HCMV-DNA from the same samples were found without positive cultures, seroconversion or expression of other HCMV antigens in granulocytes. The data indicate the presence of an abortive HCMV infection in these four patients.

Antibodies, Viral↗
PubMed1992

Cytomegalovirus antigenemia assay or PCR can be used to monitor ganciclovir treatment in bone marrow transplant recipients.

The antigenemia assay, polymerase chain reaction (PCR) and rapid culture technique on buffy coat cells (DEAFF test) were used to monitor 37 cytomegalovirus (CMV) seropositive bone marrow transplant (BMT) recipients for active CMV infection during the first 3 months after BMT. The antigen assay and PCR demonstrated a comparable sensitivity for the detection of CMV in blood: discordant results were only obtained in the early or late phase of infection when the viral load was low. The antigen assay was more sensitive than the DEAFF test. Only 12 out of 40 antigen-positive samples yielded a positive result with DEAFF test, whereas viremia without antigenemia was never found. The discordance between these two tests increased further during antiviral therapy with ganciclovir. A correlation was observed between the duration of antigenemia during treatment and the recurrence of systemic CMV reactivation. Ten out of 11 patients with antigen-positive leukocytes present for more than 1 week after starting the treatment subsequently exhibited a relapse of active infection, whereas only three out of nine patients who resolved their antigenemia within 1 week did so. In conclusion, the antigen assay and PCR are useful techniques for detection of CMV infection in BMT patients. Test results obtained during therapy give reliable information regarding the viral load and the possibility of recurrence of antigenemia, and can be taken into account when prolonged administration of ganciclovir is considered.

Antigens, Viral↗
PubMed1991

Cytomegalovirus infection causes delayed platelet recovery after bone marrow transplantation.

The pathogenic effect of cytomegalovirus (CMV) infection on the hematopoietic recovery after bone marrow transplantation (BMT) was retrospectively studied in 87 recipients of (nonpurged) autologous BMT and in 56 recipients of allogeneic BMT from HLA-identical siblings. Indications for autologous BMT were lymphomas or acute leukemias and for allogeneic BMT various malignancies or aplastic anemia. Patients were divided for the study in two groups, CMV-positive and CMV-negative on the basis of the CMV status pretransplant, and CMV-negative patients were kept CMV-negative by the local transfusion policy. In allogeneic BMT recipients, platelet recovery was significantly slower in CMV-positive patients than in CMV-negative patients (platelets greater than 50,000 cells/microL after 41 days v 27 days, P = .007). This difference held true when patients with acute graft-versus-host disease above grade I were excluded (platelets greater than 50,000 cells/microL after 42 days v 24 days, P = .01). In autologous BMT, the negative effect on platelet recovery was present in patients with lymphomas, but absent in patients with acute leukemias. Patients with acute leukemias had a very delayed recovery of platelets and granulocytes after autologous BMT, irrespective of the CMV status, probably due to the original stem cell disorder. Platelet recovery was significantly slower in CMV-positive autologous BMT recipients with lymphomas than in those not infected (platelets greater than 50,000 cells/microL after 36 days v 24 days, P = .0002). The presence of CMV infection had no effect on the recovery of granulocytes in autologous or allogeneic BMT. These data show that CMV infection causes delayed platelet recovery after BMT; however, in autologous BMT, the underlying disease (ie, acute leukemia) is more determinant for hematopoiesis after BMT.

Adult↗
PubMed1991

Antibodies to platelets in patients with anti-phospholipid antibodies.

Binding of anti-phospholipid antibodies to circulating platelets and its consequences on platelet activation and aggregation was investigated in 11 patients with anti-phospholipid antibodies. Seven patients had mild thrombocytopenia. Nine healthy donors served as controls. Binding to platelets was investigated by performing enzyme-linked immunosorbent assays (ELISAs) with phospholipids as antigen on platelet eluates. Platelet activation was measured by flow cytofluorometry using monoclonal antibodies to an activation-specific lysosomal membrane protein. Findings in ELISA were compared with results of a conventional immunofluorescence method to detect platelet autoantibodies. In seven patients antibodies to negatively charged phospholipids were present in platelet eluates. In all thrombocytopenic patients and controls the platelets were not activated and aggregation was not impaired. There was a positive concordance of 50% between the results of immunofluorescence and ELISA. No apparent relation was found between the results of ELISA or immunofluorescence and platelet counts. It is concluded that anti-phospholipid antibodies can bind to circulating platelets. This binding is not associated with measurable aggregation abnormalities nor with platelet activation characterized by exposure of lysosomal membrane proteins. More studies are necessary to determine the exact role of anti-phospholipid antibodies in the pathogenesis of thrombocytopenia and thrombosis.

Adult↗
PubMed1991

A prospective study of in vitro anti-HBs producing B cells (spot-ELISA) following primary and supplementary vaccination with a recombinant hepatitis B vaccine in insulin dependent diabetic patients and matched controls.

A prospective study of the immune response after hepatitis B vaccination was carried out in 32 insulin dependent diabetes mellitus (IDDM) patients and their age and sex matched healthy controls. A sensitive, immunoenzymatic technique was used, able to detect in vitro specific antibody production by mitogen stimulated individual B cells. In-vivo serologic response after vaccination with a standard scheme (0, 1 and 6 months) of 20 micrograms recombinant hepatitis B (HB) vaccine was significantly impaired in the IDDM patients both with respect to the number of nonresponders (25 versus 3%, P less than 0.05) and antibody titers reached (1,377 vs. 9,060 IU/L, P less than 0.05). The total number of in vitro IgM- and IgG-class immunoglobulin producing B cells as detected by the spot-ELISA, was found to be comparable in both groups. Specific IgG anti-HBs (and to a lesser extent IgM anti-HBs) showed impairment in the diabetic population as a whole. The number of IgG anti-HBs producing B cells was markedly depressed one month following vaccination, which is probably a reflection of homing of B cells outside the circulation. Responding subjects were identified early during their vaccination by the detection of in vitro anti-HBs production using the spot-ELISA. Non-responding healthy subjects and IDDM patients as a group showed a low number of IgG anti-HBs spots, suggesting a reduced specific memory B cell frequency. In 13 of 15 hypo- and nonresponders with positive IgG anti-HBs spots supplementary vaccination(s) resulted in improved anti-HBs levels.

Adult↗
PubMed1990

A fixed low number of T cells in HLA-identical allogeneic bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) in humans is hampered mainly by graft-versus-host disease (GVHD). Ex vivo T-cell depletion of the marrow graft has decreased the incidence and severity of GVHD, but has resulted in a higher incidence of graft failure and of relapse of the disease. In order to find an optimal T-cell number that avoids the extreme risks on both sides, we performed BMTs with a fixed low number of T cells. Thirty-one patients received marrow grafts, containing 1 x 10(5) T cells per kilogram body weight, from their HLA-identical sibs. All patients, except one, received cyclosporin A. Engraftment of donor marrow cells occurred in all patients and (late) graft rejections are not observed to date. Eighteen of 30 (60%) evaluable patients had acute GVHD, grade I (10 patients) or grade II (8 patients), limited to the skin in all patients. Chronic GVHD, also limited to the skin, was found in 9 of 27 (33%) evaluable patients. Incidence but not severity of GVHD in our study seems similar to that observed in non-T-cell depleted marrow grafting. Relapse was observed in 1 of 13 leukemic patients transplanted in first (or second) remission or first chronic phase with a follow-up of at least 6 months. These results suggest that with a fixed low number of T cells severe GVHD and failure to engraft can be avoided. More patients and longer follow-up are necessary for conclusions regarding relapse rate and late graft failure.

Adult↗
PubMed1990

Autologous bone marrow transplantation in acute myeloid leukemia in first remission: first Dutch prospective study.

We have prospectively compared the values of autologous BMT (auto-BMT) and allogeneic marrow transplantation (allo-BMT) in patients (age 15-60 years) with acute myeloid leukemia (AML) who attained complete remission (CR) following remission-induction therapy. In 90/117 cases CR was reached. In 32 of those complete responders auto-BMT was undertaken and in 21 eligible cases HLA-matched allo-BMT. AML relapse was the predominant cause of failure after auto-BMT (17/32). The incidence of relapse after allo-BMT was 6/21. Patients treated with auto-BMT and allo-BMT have an overall survival of 37% and 66% at 3 years posttransplant (P = 0.05). Survival of the nongrafted complete responders is less than 10%. Allo-BMT in adult patients with AML in first complete remission provides a superior outcome when directly compared with the results of auto-BMT.

Adolescent↗
PubMed1990

Early detection of active cytomegalovirus (CMV) infection after heart and kidney transplantation by testing for immediate early antigenemia and influence of cellular immunity on the occurrence of CMV infection.

To determine the incidence of active cytomegalovirus (CMV) infection after organ transplantation and its relationship with the immune system, 55 renal and 14 cardiac transplant recipients were closely monitored for active CMV infection (expression of CMV immediate early antigen in granulocytes--antigenemia--and positive cultures) and immune parameters. All 19 CMV-seronegative recipients with seronegative donors remained seronegative, showing that no CMV transmission occurred by leukocyte-depleted blood products. Primary CMV infection occurred in 4 of 11 (36%) patients with positive donors and was symptomatic in 1 (9%) patient. Active CMV infection was found in 29 of 39 (74%) seropositive patients and was symptomatic in 3 (8%) patients. CMV antigenemia was always the first indication of active CMV infection (antigenemia, on average, at day 45 +/- 15; immunoglobulin G rise at day 71 +/- 36; and positive cultures at day 70 +/- 17). Cellular immunity, as measured by lymphocyte proliferation (LPT), proved to be of importance in the prevention of active CMV infection, as 14 of 15 patients with negative LPT obtained active CMV infections with antigenemia and positive cultures, whereas 1 of 10 patients with positive LPT did so (P less than 0.0001).

Antibodies, Monoclonal↗
PubMed1990

Allergen presentation by epidermal Langerhans' cells from patients with atopic dermatitis is mediated by IgE.

To investigate the role of IgE-bearing Langerhans' cells (LC) from atopic dermatitis (AD) patients in antigen presentation, IgE+LC and non-IgE bearing LC (IgE-LC) from AD patients were investigated for their antigen-presenting capacity and compared to antigen-presenting cells (APC) from peripheral blood. The T-cell response to Candida albicans, using IgE+LC from AD patients as APC, was in the same range as with IgE-LC. Also, the T-cell response to Candida with autologous APC from peripheral blood did not significantly differ between these groups. In contrast to this finding, the T-cell response to house dust allergen (HDA) was dependent on the type of APC used. If non-T cells from peripheral blood were used as APC, both AD patients and controls responded to HDA. However, when LC were used as APC, a T-cell response to HDA was only observed in the presence of IgE+LC. IgE-LC from AD patients or LC from normal controls were unable to present HDA. Preincubation of IgE+LC with anti-IgE or anti-kappa/lambda antibodies inhibited HDA-induced T-cell proliferation, whereas the response to Candida was not affected. These in vitro results, which demonstrate the necessity of cell-bound IgE on LC for the presentation of aero-allergens, strongly correlate with the in vivo presence of a positive delayed patch reaction to the same antigens. When the LC of a patient appeared to be IgE-, the in vitro proliferative response as well as, in most cases, the in vivo patch test reaction to the same antigens was negative. In conclusion, these experiments demonstrate that there are at least two different mechanisms by which LC capture antigens for antigen presentation. In one of them cell-bound IgE, as can be demonstrated on LC from AD patients, plays a crucial role. The binding and presentation of HDA by APC from peripheral blood can take place independently of cell-bound IgE. Candida can be presented by both types of APC in the absence of IgE.

Allergens↗
PubMed1989

Is booster injection with hepatitis B vaccine necessary in healthy responders? A study of the immune response.

Loss of protective anti-HBs levels (less than 10 IU/l) was noted in 5 (13%) of 38 well documented healthy responders to hepatitis B vaccine 30 months after completing the initial standard vaccination series. Revaccination with a single booster injection of 20 micrograms hepatitis B vaccine intramuscularly resulted in anti-HBs levels well above those initially obtained, thus confirming considerable immunological memory. Both decline prior to and rise after booster injection were proportional to the anti-HBs level obtained initially. The antibody production after a single booster injection was closely monitored in 13 individuals. A swift response was observed from day 4 onwards in all subjects. Based on passive immunization data and in vitro infection of human hepatocytes, this time delay is likely to permit infection of hepatocytes. Therefore, until further data on longterm follow-up of vaccinated in individuals in whom anti-HBs levels have dropped to less than 10 IU/l reveal compelling evidence to the contrary, booster injections remain mandatory for those individuals at risk.

Adult↗
PubMed1989

The influence of T cell depletion on recovery of T cell proliferation to herpesviruses and Candida after allogeneic bone marrow transplantation.

To test the influence of T cell depletion of the marrow in allogeneic bone marrow transplantation on functional T cell recovery, in vitro lymphocyte proliferation tests (LPTs) to microbial antigens were regularly performed in 23 recipients of normal BM and in 25 patients receiving BM with a fixed low number of T cells (1 x 10(5) T cells/kg body weight; recipients of T-depleted BM). The long-term recovery of positive LPT to at least 1 of the 4 tested microbial antigens--Candida, herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus--was nearly similar in both groups: 16/23 versus 18/25. Recovery of LPT to Candida and HSV in the first 3 months appeared to be greatly influenced by prophylactic measures; only 2/23 recipients of normal BM, receiving amphotericin B, showed a positive LPT to Candida versus 13/25 recipients of T-depleted BM (P less than 0.01). In contrast, only 1/23 seropositive recipients of T-depleted BM, receiving acyclovir, showed a positive LPT to HSV versus 9/22 recipients of normal BM (P less than 0.05). A positive LPT to CMV in the first 3 months was found in 9/9 seropositive recipients of normal BM, versus in 5/11 seropositive recipients of T-depleted BM (P less than 0.05). Five of the 6 patients with a negative LPT died of CMV-interstitial pneumonia versus 1/14 with positive LPT (P less than 0.01). We conclude that in CMV-seropositive recipients of allogeneic BM, T cell depletion of the graft affects the early recovery of T cell proliferation to CMV, which is associated with a higher risk of fatal CMV-interstitial pneumonia.

Antigens, Fungal↗
PubMed1989

Phenotypic study of CD4+ and CD8+ lymphocyte subsets in relation to cytomegalovirus carrier status and its correlate with pokeweed mitogen-induced B lymphocyte differentiation.

A characteristic of active cytomegalovirus (CMV) infection is its suppressive effect on in vitro assays of immune function. The expression of CD11b by the Cd4+ and Cd8+ lymphocytes allows the identification of subsets with distinct regulatory functions of pokeweed mitogen (PWM) induced B cell differentiation. In order to relate that result with our previous observation that CMV carriers have significantly increased numbers of CD4+, HNK1+ and CD8+, HNK1+ lymphocytes in their peripheral blood compared with non-carriers, we performed a three-colour flow cytometric analysis of the co-expression of Cd11b and HNK1 by CD4+ and CD8+ lymphocytes obtained from 27 CMV carriers and 42 non-carriers. The differences between CMV carriers and non-carriers were significant for the CD4+, HNK1+ lymphocytes (median [5th and 95th percentiles], 59 [18 and 123 versus 24/7 and 73 per mm3, respectively; P less than 0.001) and CD8+, HNK1+ lymphocytes (59 [18 259] versus 52 [23 and 139] per mm3; P less than 0.001), but not for the CD4+, CD11b+ lymphocytes (59 [18 and 135] versus 52 [17 and 104] per mm3) and the CD8+, CD11b+ lymphocytes (85 [34 and 293] versus 82 [21 and 248] per mm3). The CD4+, HNK1+ and CD8+, HNK1+ lymphocytes that were increased in CMV carriers compared with non-carriers included mostly CD11b-, but also CD11b+ lymphocytes. After sorting CD4+ and CD8+ lymphocytes for four CMV carriers into HNK1+ and HNK1- fractions, we analyzed their regulatory functions on PWM-driven B cell Helper function to PWM-driven B cell differentiation was exclusively associated with the CD4+, HNK1- lymphocytes; the CD4+, HNK1+ generally did not show helper or suppressor activity in this assay. Both CD8+, HNK1+ and CD8+, HNK1- lymphocytes showed suppressor activity. Thus, the NHK1 marker does not constitute a phenotypical correlate for suppressor cells of PWM-driven B-cell differentiation.

Adolescent↗