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Biomedical subjects

R E Brouwer

Publications and source records attributed to R E Brouwer.

15 recordsLinked to original sources
PubMed2006

Thalidomide as treatment for digestive tract angiodysplasias.

An 80-year-old man with von Willebrand's disease was admitted with severe melaena. Despite suppletion with von Willebrand concentrate he continued to be dependent on blood transfusions. Endoscopic examination did not show a bleeding focus. Video capsule endoscopy showed active bleeding from angiodysplasias in the proximal section of the small intestine. Ultimately, treatment with thalidomide was initiated at a dose of 100 mg/day. Soon after starting treatment his stools became normal and his haemoglobin level stabilised. No bleeding problems occurred for 11 months, after which the thalidomide treatment was stopped because of the potential side effects. Two months later he again developed melaena and treatment with thalidomide was restarted with a successful outcome. Trying to lower the dose to 50 mg resulted in rebleeding after three months with stabilisation after increasing the dose to 100 mg again. Monotherapy with thalidomide improves the clinical picture but may not be sufficient in the long term. Additional therapy, such as argon plasma coagulation or the use of the novel drug lenalidomide, might be necessary.

Aged, 80 and over↗
PubMed2001

[An adolescent with hemolytic anemia and coagulation disorders as manifestation of Wilson's disease, treated with liver transplantation].

A 16-year-old woman presented with anaemia, jaundice, vomiting and nosebleed. She had acute hepatic failure and haemolytic anaemia and developed acute respiratory distress syndrome (ARDS). Wilson's disease was diagnosed. After the ARDS resolved the patient underwent a successful orthotopic liver transplantation. Diagnostic combinations for Wilson's disease are ceruloplasmin < 0.2 g/l with Kayser-Fleischer rings, liver copper > 250 micrograms/g (dry weight) with Kayser-Fleischer rings, or homozygosity for a Wilson mutation on the 13th chromosome. In acute liver failure a copper excretion in 24 h-urine above 1 mg is diagnostic for Wilson's disease, while an elevated serum copper concentration makes this diagnosis very likely. Therapeutic options for Wilson's disease are chelation therapy and liver transplantation; in most cases of acute liver failure due to Wilson's disease orthotopic liver transplantation (preceded by albumin dialysis) is indicated. Nazer's index should be used in addition to the regular King's College criteria for liver transplantation indication.

Adolescent↗
PubMed2001

Comparison of allogeneic T cell-depleted peripheral blood stem cell and bone marrow transplantation: effect of stem cell source on short- and long-term outcome.

We report the results of a retrospective single-center study comparing engraftment, acute and chronic GVHD, relapse and survival in patients with malignant hematological disorders transplanted with allogeneic peripheral blood stem cells (alloPBSCT, n = 40) or bone marrow cells (alloBMT, n = 42). All transplants were T cell depleted by in vitro incubation with the Campath-1 monoclonal antibody. Primary graft failure occurred in none of the patients receiving an alloPBSCT compared with 3/42 of the recipients of an alloBMT. In addition, two patients in the alloBMT group showed no platelet engraftment. Recipients of PBSC had a more rapid recovery of neutrophils (median 14 days) compared to BM transplant recipients (median 32 days). Platelet recovery was also accelerated in PBSC recipients compared to BM recipients (11 vs 38 days). There was an increase in the incidence of grade II acute GVHD and chronic GVHD in patients after alloPBSCT (18% and 23%, respectively) compared to patients receiving alloBMT (5% and 8%, respectively). The 2-year cumulative incidence of relapse was similar in both groups (47%). At 6 months after transplantation, transplant-related mortality (TRM) was lower in PBSCT recipients than in BMT recipients. However, at a follow-up of 3 years TRM was similar in both groups. The disease-free survival rate at 3 years after transplantation did not differ between the groups (42% for PBSCT and 41% for BMT recipients). Our results indicate that T cell-depleted alloPBSCT compared to alloBMT is associated with a more rapid hematopoietic reconstitution and a decreased TRM at 6 months follow-up after transplantation. However, at a follow-up of 3 years, no sustained survival benefits were observed.

Adult↗
PubMed2001

Expression of co-stimulatory and adhesion molecules and chemokine or apoptosis receptors on acute myeloid leukaemia: high CD40 and CD11a expression correlates with poor prognosis.

The expression of adhesion and co-stimulatory molecules, and chemokine and death receptors such as tumour necrosis factor (TNF) and FAS on acute myeloid leukaemia (AML) may influence the biology of the disease and response to chemotherapy and immunotherapy. In this study, we analysed the expression of these molecules in 99 AML patients using monoclonal antibodies and flow cytometry, and correlated the expression with French-American-British (FAB) classification and survival. The following molecules were studied: the co-stimulatory molecules CD80, CD86 and CD40; the adhesion molecules CD11a-c, CD31, CD43, CD50, CD54, CD102, CD58 and CD62L; the chemokine receptor CXCR4; and the death receptors TNFR1 and TNFR2 and FAS. The expression of all molecules was significantly higher in the M4/M5 FAB subgroups except for CD80, CD43, CD54 and CD62L. The AML M3 subgroup had a significant lower expression of CD11a (P = 0.02) and CD11c (P = 0.03). Five-year survival was significantly shorter in cases of high CD40 expression [> 20% positive cells, relative risk (RR) 2.56, P = 0.02] or high CD11a expression (> 80% positive cells, RR 2.6, P = 0.03). This effect was most prominently present in the AML M4/M5 FAB subgroups. We conclude that the expression levels of adhesion and co-stimulatory molecules, CXCR4 and apoptosis-receptors are predominantly FAB subtype-related with high CD40 and CD11a expression as poor prognostic factors.

Acute Disease↗
PubMed2000

The generation of dendritic-like cells with increased allostimulatory function from acute myeloid leukemia cells of various FAB subclasses.

To increase the immunogenicity of leukemic cells, attempts were made to generate dendritic-like antigen presenting cells (DC) from AML blasts from 14 patients with AML FAB classifications M0-M5. Leukemic cells were cultured in the presence or absence of various cytokines including GM-CSF, SCF, TNF-alpha, IL-4, and gamma-interferon. After various intervals recovery of viable cells was measured and expression of CD80, CD86, CD40, CD54, CD58, and CD11a was analyzed by flow cytometry. Functionally, DC derived from six AML samples were tested in a mixed lymphocyte response (MLR) using HLA-DR mismatched donor T cells as responder cells. Proliferation (5/14) or increased survival (7/14) of AML cells was observed in the presence of GM-CSF, SCF, and TNF-alpha. Only in the AML M2, M3, and M4 FAB subtypes proliferation was found. GM-CSF, SCF, and TNF-alpha induced morphologic changes typical for DC and increased the expression of costimulatory and adhesion molecules. No significant effect of IL-4 or gamma-interferon was observed. The day of maximal expression of these molecules varied. In cases with minor upregulation of CD80 or CD86, no further stimulation using CD40-L activation was observed. In the three cases tested, the DC-like cells retained the chromosomal abnormalities present in the original AML cells. In five out of six cases tested an increase in allostimulatory capacity was found at the day of maximal expression of costimulatory and adhesion molecules. In two patients a decrease in stimulatory capacity was found at day 7 compared with day 2 correlating with a decreased expression of these molecules. In conclusion, AML cells can be induced to increase their stimulatory capacity by upregulating costimulatory and adhesion molecules.

Acute Disease↗
PubMed2000

Expression and induction of costimulatory and adhesion molecules on acute myeloid leukemic cells: implications for adoptive immunotherapy.

OBJECTIVE: Previously, we observed an increased recognition of malignant cells by cytotoxic T lymphocytes (CTL) when the target cells were cultured in vitro for 24 hours. In this study, we analyzed the expression of costimulatory and adhesion molecules on acute myeloid leukemia (AML) cells and determined whether 24-hour culture of the cells was associated with upregulation of these molecules. We analyzed whether this incubation period improved recognition of AML cells by CTL. MATERIALS AND METHODS: Expression of costimulatory and adhesion molecules on leukemic blasts of 34 patients comprising each AML FAB subclassification were analyzed directly and after 24 hours of culture, and the recognition of these AML cells by an HLA-A2 restricted CTL clone was determined. Blocking studies were performed with antibodies against CD54, CD58, and CD11a. RESULTS: Immunophenotyping showed a low expression of CD80 and CD40 and a variable CD86 expression on most AML cells. CD54 expression was generally low, CD58 expression was high, and CD11a expression was variable, with a higher expression in AML M0, M1, M4, and M5. Twenty-four hours of culture resulted in a significant upregulation of CD40, CD54, and CD58. Impaired recognition of AML cells by the HLA-A2 restricted CTL clone was enhanced 100-200% by 24 hours of preincubation of the leukemic cells. Blocking studies showed the importance of multiple adhesion molecules on the AML cells. CONCLUSION: Low expression of multiple costimulatory and adhesion molecules on AML could be upregulated by 24 hours of culture, which was associated with increased recognition of the AML blasts by CTL. Blocking multiple adhesion molecules completely abolished CTL recognition, showing the importance of the combination of these molecules for T-cell interaction with AML.

Acute Disease↗
PubMed1999

Phase III efficacy study of interleukin-3 after autologous bone marrow transplantation in patients with malignant lymphoma.

We evaluated the efficacy of recombinant human interleukin-3 (rhIL-3) in reducing the number of platelet transfusions and major infections after autologous bone marrow transplantation (ABMT) in patients with malignant lymphoma. 198 patients with non-Hodgkin's lymphoma (NHL, n = 111) and Hodgkin's disease (HD, n = 87) were randomized to receive rhIL-3 10 microgram/kg/d (n = 130) or placebo (n = 68) for a maximum of 28 d after ABMT. Several well-known conditioning regimens were used. From day 1 after ABMT patients were treated with placebo or rhIL-3 at a dose of 10 microgram/kg/d by continuous i.v. infusion for 7 d and then by s.c. administration for 21 d or until platelet (50 x 109/l) and neutrophil (0.5 x 109/l) recovery had occurred. Treatment was completed in 54% of the patients in the rhIL-3 group versus 75% in the placebo group (P < 0.004). Adverse events were the main reason for premature discontinuation in the IL-3 group (23% IL-3 v 5% placebo). The median number of platelet transfusions was not significantly different between the IL-3 group and the placebo group (8.0 IL-3 v 6.0 placebo, P = 0.09). Platelet engraftment (>/= 20 x 109/l) was not significantly faster in the IL-3 group (28 d in the IL-3 and 27 d in the placebo group, P = 0.06) and the incidence of haemorrhagic complications was similar in both groups. In patients receiving the full intended dose of rhIL-3, platelet engraftment to >/= 20 x 109/l was delayed (P = 0.007). The median time to neutrophil engraftment was 23 d in the IL-3 and 25 d for the placebo group (P = 0.39). There was no difference in the incidence of major infections. We conclude that treatment with IL-3 has no clinical benefit in patients receiving ABMT for malignant lymphoma.

Bone Marrow Transplantation↗
PubMed1998

Streptococcus pneumoniae, an emerging pathogen in mycotic aneurysms?

Two patients are described with a mycotic aneurysm caused by streptococcus pneumoniae infection. The patients presented with back pain and fever, and had an antecedent history of lower respiratory tract infection; neither of them were suffering from endocarditis. Mycotic aneurysms are a rare disorder with, over the years, a changing spectrum of presentation, localisation and bacterial aetiology. S. pneumoniae infection has only very rarely been reported as a cause of mycotic aneurysms. Since 1986, 14 patients with a mycotic aneurysm were treated at the Leiden University Hospital. Of these patients, 5 had mycotic aneurysms caused by S. pneumoniae infection. The mortality in these patients was high. In this communication, we would like to draw attention to S. pneumoniae infections as an emerging cause of mycotic aneurysms.

Aged↗
PubMed1997

[Acquired haemophilia A].

A 74-year-old man developed a severe bleeding disorder on the basis of acquired Factor VIII (F VIII) inhibitor. Coagulation assays showed a prolonged activated partial thromboplastin time (APTT) with a normal prothrombin time (PT);F VIII level was 0.07 IU and F VIII inhibitor level 8.8 Bethesda units (BU). At least half the cases of acquired haemophilia A are associated with pregnancy, the postpartum period or an underlying malignancy or autoimmune disease. Haemorrhagic diathesis can be severe and life-threatening. Treatment of acute haemorrhages consists of human or porcine factor VIII concentrate, activated prothrombin complex concentrate (FEIBA) or recombinant factor VIIa, depending on the antibody titre. Immunosuppressive therapy is successful in at least 60% of the patients in making the inhibitor disappear. In patients with a spontaneous haemorrhagic diathesis, a thorough medical history should be taken, coagulation assays should be performed and a specialist should be consulted.

Aged↗
PubMed1997

Central nervous system relapse in non-Hodgkin lymphoma. A single-center study of 532 patients.

OBJECTIVES: To define the cumulative risk of central nervous system (CNS) relapse in systemic non-Hodgkin lymphoma (NHL); to assess the risk factors of age, sex, malignancy grade, stage, localization, and response to initial therapy; and to evaluate the effect of CNS prophylaxis. PATIENTS AND METHODS: An unselected group of 532 patients with systemic NHL. A retrospective analysis. RESULTS: Eleven patients presented with systemic as well as CNS localization, whereas in 55 patients, CNS relapse occurred later. The cumulative risk of CNS relapse at 4 years for all 532 patients was 19%. High-grade NHL carried a 39% risk of CNS relapse, with the vast majority of relapses occurring in the first 14 months after the initial diagnosis. The cumulative risk in patients with intermediate-grade NHL was considerable (22%) and dispersed throughout a much longer period (6 years). Patients with low-grade NHL still carried a 7% risk of CNS relapse; in all these patients, low malignancy grade was transformed into a higher malignancy grade at that time. In a multivariate analysis, high- and intermediate-grade NHL and advanced stage were independent risk factors for CNS relapse. There was not any strong evidence for a beneficial role of CNS prophylaxis in patients with intermediate- and high-grade NHL, but a retrospective analysis cannot be conclusive with regard to the effect of therapy. Systemic relapse occurred rapidly after CNS relapse, resulting in a median survival time after CNS relapse of only 2 months. CONCLUSIONS: Patients with high- and intermediate-grade NHL carry a considerable risk of CNS relapse. Advanced stage is an additional independent risk factor. The role of CNS prophylaxis seems to be disappointing, but a retrospective analysis cannot be conclusive. Prognosis after CNS relapse is poor.

Adolescent↗
PubMed1996

Nature's high-voltage injuries: sometimes a deadly consequence.

A patient is described who presented with the clinical picture of respiratory failure, persistent comatose state and myocardial injury after being struck by lightning. The discussion reviews the management of lightning injuries with emphasis on cardiovascular and neurological complications.

Adult↗
PubMed1996

The spectrum of chronic mature T-cell disorders: a report of four cases.

We describe four patients with a mature T-cell disorder. These four specific entities belong to a group formerly called "T-cell chronic lymphocytic leukaemia" (T-CLL). Nowadays we understand that these chronic T-cell lymphoproliferative disorders consist of four different entities. They stand out as well-described and separate disorders on the basis of their clinical, immunophenotypic and cytogenetic properties. Unfortunately, the majority of patients have a bad response to chemotherapy. The purine analogs may offer a better prognosis for some patients.

Aged↗
PubMed1995

[2 patients with neurocysticercosis].

Cysticercosis of the CNS, caused by the pork tapeworm Taenia solium, was diagnosed on the basis of serological and imaging examination in two patients, a woman aged 50 and a man aged 40 years. The former patient suffered from aphasia, headache and epileptic attacks, the latter mostly from epilepsy. Cysticercosis of the CNS occurs mainly in the tropics but is occasionally observed in the Netherlands in people who have been to the tropics, such as the patients reported. Both ultimately recovered after drug therapy which included praziquantel.

Adult↗