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Biomedical subjects

N H Mulder

Publications and source records attributed to N H Mulder.

At least 343 records · Page 19Linked to original sources
PubMed1980

Normal levels of antithrombin III in acute leukemia complicated by coagulopathy.

A patient with acute monoblastic leukemia developed a coagulopathy during chemotherapy. Coagulation studies showed thrombocytopenia, hypofibrinogenemia, high levels of fibrinogen degradation products, a negative protemine test but a normal antithrombin III level. These observations suggest that coagulation abnormalities appearing in acute leukemia are not necessarily due to diffuse intravascular coagulation.

Acute Disease↗
PubMed1978

Response to pyridoxine hydrochloride in refractory anemia due to myelofibrosis.

Eleven of 14 patients with primary myelofibrosis were given a therapeutic trial with 250 mg of pyridoxine hydrochloride daily because of refractory anemia. The effect on the hemoglobin level and the hematocrit value was studied and compared to that in a group of untreated patients with the same degree of anemia. Six of 11 treated patients responded within three months with a rise in the hemoglobin level (at least 3 g/100 ml) and/or an increase in the hematocrit value (at least 10 per cent), and transfusions were no longer required. Deliberate discontinuation of pyridoxine treatment in one responding patient was followed by a relapse of the anemia; resumption of therapy once again induced an erythropoietic response. Spontaneous remissions of anemia were not observed in the untreated group. It is concluded that a trial with pyridoxine is warranted in patients with myelofibrosis and refractory anemia.

Anemia↗
PubMed1978

Analysis of extramedullary erythropoiesis in the spleen by a semiquantitative method using indium-111.

A semiquantitative method for evaluating the splenic uptake of 111In is described. With this method the uptake of indium in the spleen was significantly higher in seven patients with extramedullary erythropoiesis (EME) than in a control group of seven patients with comparable degrees of splenomegaly but without clinical and/or histological signs of EME. The discrimination between these groups could be further improved by also taking the degree of splenomegaly into account. It is concluded that the described technique is a valuable non-invasive aid for establishing the presence of EME in the spleen.

Adult↗
PubMed1978

'Classic' and 'acute' myelofibrosis. A retrospective study.

In a retrospective study of 38 patients with histologically proven myelofibrosis, 5 parameters (recorded on the first admission) were investigated as to their usefulness to predict the course of the disease. In 9 patients the development of 'acute' myelofibrosis could be predicted by the finding of pancytopenia, low reticulocyte counts (median 20,500/mul), extremely elevated SRE (median 125 mm) and normal serum levels of LDH and uric acid on the first admission. In 28 patients the development of classic fibrosis with splenomegaly could be predicted by the finding of high reticulocyte counts (median 133,200/mul) and increased levels of serum LDH (median 547 U) and uric acid (median 8 mg/dl in males and 6.8 mg/dl in females) on the first admission, even when splenomegaly was initially absent. The relationship between classic and acute myelofibrosis and the significance of the mentioned parameters is discussed.

Acute Disease↗
PubMedDate not supplied

T-cell evaluation in patients with colon cancer: dinitrochlorobenzene skin testing versus plasma levels of sIL-2r and sCD8.

BACKGROUND: Developing reliable methods to test the T-cell system may be important in the treatment of colon cancer patients with 5-fluorouracil/levamisole. In a pilot study we explored whether DNCB (dinitrochlorobenzene) skin testing correlated with plasma levels of soluble interleukin-2 receptor (sIL-2r) and soluble CD8 (sCD8) and, secondly, whether the application of DNCB had any influence on the production of sIL-2r and sCD8. METHODS: In 10 patients with advanced colon cancer and in 10 healthy volunteers, plasma levels of sIL-2r and sCD8 were measured before and 10 days after the application of 2 mg DNCB on the inner side of the forearm. RESULTS: As expected, colon cancer patients showed a depressed immune system compared to healthy volunteers (DNCB skin test: P = .005, sIL2r [medians 700 vs 295, P = .002], sCD8 [medians 158 vs 90, P = .03], M-W test). The plasma levels for sIL-2r and sCD8 were significantly lower in the skin-positive cases (P = .01 and P = .03, M-W test). However, a large overlap in plasma levels could be observed between the two skin categories. DNCB had no influence on the production of sIL-2r and sCD8; median change skin-negative and skin-positive -10 vs +25, P = .14, respectively; 48 vs 0, P = .32 (M-W test). CONCLUSIONS: DNCB skin testing and plasma levels of sIL-2r and sCD8 seem to be equally useful in evaluating the T-cell system and can be used simultaneously.

Adjuvants, Immunologic↗
PubMedDate not supplied

Approaches to lung cancer treatment using the CD3 x EGP-2-directed bispecific monoclonal antibody BIS-1.

The bispecific monoclonal antibody (bsAb) BIS-1 combines a monoclonal-antibody(mAb)-defined specificity for the CD3 complex, as present on all T lymphocytes, with a mAb-defined specificity for the pancarcinoma/epithelium associated glycoprotein EGP-2. In vitro studies indicate that BIS-1 can direct T lymphocytes to kill EGP-2-positive tumour target cells. T cell pre-activation is necessary for this activity and can be obtained either via incubation of isolated peripheral blood mononuclear cells with CD3 mAb, followed by short culturing in recombinant interleukin-2-containing medium, or via costimulation with CD5- and CD28-based bsAb. Clinical application of BIS-1 was started in a pilot study in which carcinoma patients suffering from malignant ascites or intrapleural effusion were treated. In this study, ex vivo activated autologous lymphocytes were applied locally, i.e. intraperitoneally or intrapleurally, in the presence of BIS-1. Local inflammation and antitumour activity were observed, whereas no or only minor systemic toxicity was seen in these patients. Intravenous administration of BIS-1 F(ab')2 in combination with subcutaneously given recombinant interleukin-2 (i.v. bsAb/rIL-2 treatment) induced transient but considerable toxicity including peripheral vasoconstriction, dyspnoea and fever with a maximal tolerated dose of 5-8 micrograms/kg. High plasma concentrations of the inflammatory cytokines tumor necrosis factor alpha and interferon gamma were observed at this dose. Whereas bsAb-dictated antitumour activity could be demonstrated to be present in blood samples of these patients in an in vitro assay, no clear clinical responses were observed. In a rat model it was found that i.v. bsAb/rIL-2 treatment of EGP-2-positive tumours was effective when a low systemic tumour burden was present, suggesting that systemic bsAb/rIL-2 treatment might be effective in situations of minimal residual disease.

Aged↗
PubMedDate not supplied

Recombinant T-cell receptors: an immunologic link to cancer therapy.

Cytotoxic T cells can specifically kill target cells that express antigens recognized by the T-cell receptor. These are membrane-bound proteins that are not ubiquitous and thus are difficult to purify and study at the protein level. The advent of recombinant DNA technology has facilitated these objectives, thereby enabling researchers to gain valuable information about major T-cell receptor characteristics. Genetic manipulation of T-cell receptors has also been used to exploit specificity of killing by cytotoxic T lymphocytes, which represents an attractive feature for therapeutic purposes. The objective of this review was to provide an overview of the major strategies adopted to genetically manipulate T-cell receptors.

Animals↗
PubMedDate not supplied

Hyperthermic potentiation of cisplatin toxicity in a human small cell lung carcinoma cell line and a cisplatin resistant subline.

A human small cell lung carcinoma cell line (GLC4) and its subline with in vitro acquired cisplatin (cDDP) resistance (GLC4-cDDP) were used to study the applicability of hyperthermia to interfere with acquired cDDP resistance. GLC4 and GLC4-cDDP did not differ in heat sensitivity (clonogenic ability). Both cell lines could be sensitized to cisplatin to a considerable extent, both at 42 and 43 degrees C. For 42 degrees C hyperthermia treatments up to 90 min no differences in TER between the cell lines were observed. Only prolonged (> or = 45 min) exposures to 43 degrees C hyperthermia sensitized the resistant cell line to a greater extent than the parent cell line, resulting in a reduction of the resistance factor from 3.6 (at 37 degrees C) to 1.7 (60 min 43 degrees C). The finding in this human system that for treatments up to 90 min, 43 degrees C heat is more suitable than 42 degrees C heat to reduce cDDP resistance, is in accordance with earlier findings with murine cells (Konings et al. 1993). Effects of heat, cisplatin and combined treatments on cell killing were not only measured with the clonogenic assay, but also with the microculture tetrazolium method (MTT assay), an assay of potential use in the clinic for rapid screening of cells obtained from patients. The data with the latter assay were comparable to those obtained with the clonogenic assay. However, its applicability to measure thermo-chemosensitization is limited due to its inability to measure more than one log of cell killing.

Carcinoma, Small Cell↗
PubMedDate not supplied

Combined treatment with goserelin and tamoxifen in patients with advanced chemotherapy resistant ovarian cancer.

UNLABELLED: The purpose of this study was to determine the response in patients with recurrent, chemotherapy-resistant ovarian cancer to a combination of the LHRH-analog goserelin and tamoxifen. PATIENTS AND METHODS: Twenty-five patients with recurrent, chemotherapy resistant ovarian cancer received a combination of goserelin and tamoxifen until clinical or serological evidence of progression as measured by serum CA-125 levels. Suppression of LH, FSH and prolactin levels in this group were compared with a second group of ten patients treated with decapeptyl for the same indication. RESULTS: The combination was well tolerated. The median progression free survival amounted to five (range 2-96+) months and overall survival to eight (range 3-96+) months. One of the responding patients is still alive without progression at 8 years. With this combination the median levels of LH and FSH were markedly suppressed, to respectively 2.6% and 3.7% of baseline values. With decapeptyl the LH levels were also suppressed, but the resulting FSH levels were significantly higher. PA combination of goserelin and tamoxifen in patients with relapsed ovarian cancer can not be recommended as standard therapy, but may result in long-term survival in individual patients.

Adolescent↗
PubMedDate not supplied

Selective use of preoperative radiotherapy in the treatment of cancer in the lower two thirds of the rectum.

PURPOSE: The authors review the result of the selection of patients with a low rectal cancer for pre-operative radiotherapy. METHODS: The selection was based on the findings of digital examination eventually combined with surgical staging consisting of bimanual palpation during a staging laparotomy or "trial" operation. This selection was used to divide the patients into three groups: one where local radicality could be expected from primary surgery (group 1), one with deeply infiltrating, but mobile tumours requiring 10 x 3 Gy pre-operative radiotherapy (group 2) and one with fixed or borderline resectable tumours requiring protracted pre-operative radiotherapy with 55-59 Gy (group 3). One hundred and one patients were eligible for this study. A resection aiming for pelvic radicality was carried out in 94 patients: primary resection in 38 (group 1), surgery subsequent to 10 x 3 Gy pre-operative radiotherapy in 20 (group 2) and 55-59 Gy in 36 (group 3). RESULTS: The calculated risk of local recurrence at 5 years was 15% (95% C.I. 4-27) for group 1, 8% (95% C.I. 0-20) for group 2 and 30% (95% C.I. 16-44) for group 3. The calculated 5 years survival for the 3 groups was respectively 60%, 49% and 39%. CONCLUSION: The overlap in local recurrence rate between the three groups suggests a substantial downgrading by this approach of selective use of pre-operative radiotherapy in the patients with the most advanced tumour. Notwithstanding recent improvements of imaging techniques there still is a place for the staging laparotomy in the selection of the treatment strategy for advanced rectal cancers.

Adult↗
PubMedDate not supplied

Retargeting of a T cell line by anti MAGE-3/HLA-A2 alpha beta TCR gene transfer.

BACKGROUND: The T cell receptor (TCR) is an heterodimeric protein on the cell membrane of cytotoxic T cells (CTLs). In CTLs TCRs mediate the recognition of target cells through interaction with specific, MHC class I presented peptides. MATERIALS AND METHODS: As a model system to show proof of principle we chose the Jurkat/MA cell line and the HLA-A2.1 binding MAGE-3 derived peptide 271-279, as target specificity. RESULTS: We show that this cell line can be successfully transduced with the dicistronic retroviral vector (LZRS) containing cDNAs encoding for the complete alpha and beta chains of the selected TCR. Following retroviral transduction, Jurkat/MA cells do express the anti-MAGE-3 TCR on their membrane. The transduced TCR is functional as travoductants are successfully triggered, upon stimulation with T2 cells or MAGE-3+ melanoma cells loaded with the MAGE-3 peptide. CONCLUSION: We conclude that TCR gene transfer is possible and it represents a powerful therapeutic tool for the genetical modification of T calls of patients sullering from cancer.

Antigens, Neoplasm↗