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1.
Neth J Med ; 64(5): 153-6, 2006 May.
Article in English | MEDLINE | ID: mdl-16702615

ABSTRACT

Venomous snakebites are a rarity in the Netherlands. In this report we describe the case of a 26-year-old male amateur snakekeeper who was bitten in his left index finger by a Western bush viper (Atheris chlorechis). His clinical condition deteriorated rapidly with acute renal failure and considerable blood loss due to coagulopathy. Antidote was not readily available and was finally supplied by a zoo in Antwerp, Belgium. One day after admission the blood loss diminished.


Subject(s)
Antivenins/therapeutic use , Crotalid Venoms/poisoning , Snake Bites/complications , Viperidae , Acute Kidney Injury/chemically induced , Acute Kidney Injury/therapy , Adult , Animals , Fingers/physiopathology , Hemorrhage/chemically induced , Hemorrhage/therapy , Humans , Male , Netherlands , Snake Bites/drug therapy , Snake Bites/surgery , Time Factors
2.
Ned Tijdschr Geneeskd ; 149(37): 2037-42, 2005 Sep 10.
Article in Dutch | MEDLINE | ID: mdl-16184944

ABSTRACT

A 61-year-old man with no significant medical history was referred by the general practitioner with progressive dyspnoea despite treatment with steroids and antibiotics. The patient had severe hyponatraemia. Eventually hypervolemic hyponatraemia due to ischemic cardiac failure was diagnosed. After recompensation by fluid restriction and lisdiuretics coronary bypass surgery was carried out. The patient was discharged free of symptoms. This case is a reminder that heart failure may not present itself in a classical manner but as hypervolemic hyponatraemia.


Subject(s)
Decision Making , Dyspnea/etiology , Heart Failure/diagnosis , Hyponatremia/etiology , Clinical Competence , Coronary Artery Bypass , Heart Failure/complications , Heart Failure/surgery , Humans , Male , Middle Aged , Treatment Outcome
3.
Leuk Lymphoma ; 40(3-4): 287-94, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11426550

ABSTRACT

Adult T-cell leukemia/lymphoma (ATL) is frequently a very aggressive malignancy with a poor survival despite aggressive multiagent chemotherapy. The combination of the antiretroviral drug zidovudine (AZT) and interferon alpha (IFNalpha) has been reported to induce remissions in patients with ATL. The purpose of this study was to evaluate the clinical response and toxicity following administration of a combination of IFNalpha-2b and AZT in patients with human T-cell lymphotropic virus type I (HTLV-I)-associated ATL. Eighteen patients with ATL (chronic. crisis, acute or lymphoma type) were treated with the combination of AZT (50 - 200 mg orally 5 times a day) and IFNalpha-2b (2.5 - 10 million units subcutaneously daily). Three patients had objective responses lasting more than one month. One patient had a clinical complete remission, lasting 21.6 months and two patients had partial remissions lasting 3.7 and 26.5 months. Six patients were not considered evaluable for response due to short and/or interrupted periods of treatment. Seventeen patients have died with a median survival time after initiation of therapy of 6 months. Neutropenia and thrombocytopenia were the dose limiting toxicities. In conclusion, the response rate in this study was lower than noted in the two previous published series. This may be due to the amount and type of prior treatment our patients had received.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Interferon-alpha/administration & dosage , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Zidovudine/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/toxicity , Disease-Free Survival , Female , Humans , Interferon alpha-2 , Interferon-alpha/toxicity , Leukemia-Lymphoma, Adult T-Cell/complications , Leukemia-Lymphoma, Adult T-Cell/mortality , Male , Maximum Tolerated Dose , Middle Aged , Neutropenia/chemically induced , Recombinant Proteins , Remission Induction , Skin Tests , Thrombocytopenia/chemically induced , Treatment Outcome , Zidovudine/toxicity
4.
J Nucl Med ; 40(2): 268-76, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10025834

ABSTRACT

UNLABELLED: Monoclonal antibodies (MoAb) labeled with 90Y are being used for radioimmunotherapy. Because 90Y is a beta emitter, quantitative information from imaging is suboptimal. With the concept of a "matched pair" of isotopes, 111In is used as a surrogate markerfor90Y. We evaluated the differences in biodistribution between 111In- and 90Y-labeled murine antiTac MoAb directed against the IL-2Ralpha receptor. METHODS: The antiTac was conjugated to the 2-(4-isothiocyanatobenzyl)-6-methyl-diethylenetriamine pentaacetic acid (1B4M-DTPA, also known as MX-DTPA). Nine patients with adult T-cell leukemia were treated. Patients received approximately 185 MBq (5 mCi) 111In-labeled antiTac for imaging and 185-555 MBq (5-15 mCi) 90Y-labeled antiTac for therapy. The immunoreactivity of 111In-labeled antiTac was 90%+/-6%, whereas for 90Y-labeled antiTac, it was 74%+/-12%. RESULTS: The differences in blood and plasma kinetics of the two isotopes were small. The area undemeath the blood radioactivity curve was 1.91 percentage+/-0.58 percentage injected dose (%ID) x h/mL for 111In and 1.86%+/-0.64 %ID x h/mL for 90Y. Urinary excretion of 90Y was significantly greater than that of 111In in the first 24 h (P = 0.001), but later, the excretion of 111In was significantly greater (P = 0.001 to P = 0.04). Core biopsies of bone marrow showed a mean of 0.0029+/-0.0012 %ID/g for 111In, whereas the 90Y concentration was 0.0049+/-0.0021 %ID/g. Analyses of activity bound to circulating cells showed concentrations of 500-30,000 molecules of antiTac per cell. When cell-bound activity was corrected for immunoreactive fraction, the ratio of 111In to 90Y in circulating cells was 1.11+/-0.17. Three biopsies of tumor-involved skin showed ratios of 111In to 90Y of 0.7, 0.9 and 1.1. CONCLUSION: This study shows that differences typically ranging from 10% to 15% exist in the biodistribution between 111In- and 90Y-labeled antiTac. Thus, it appears that 111In can be used as a surrogate marker for 90Y when labeling antiTac with the 1 B4M chelate, although underestimates of the bone marrow radiation dose should be anticipated.


Subject(s)
Antibodies, Monoclonal/pharmacokinetics , Chelating Agents , Indium Radioisotopes/pharmacokinetics , Pentetic Acid/analogs & derivatives , Yttrium Radioisotopes/pharmacokinetics , Adult , Antibodies, Monoclonal/therapeutic use , Female , Humans , Indium Radioisotopes/therapeutic use , Leukemia-Lymphoma, Adult T-Cell/radiotherapy , Male , Middle Aged , Radioimmunotherapy , Receptors, Interleukin-2/immunology , Yttrium Radioisotopes/therapeutic use
5.
Ann Neurol ; 44(6): 942-7, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9851439

ABSTRACT

Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disease that results from an interaction of retroviral infection and immune activation. In this study, five doses (1 mg/kg) of humanized anti-Tac antibody were administered to 9 HAM/TSP patients at weeks 0, 2, 6, 10, and 14. Preliminary immunological studies on HAM/TSP patients treated with humanized anti-Tac indicate that there is a selective down-regulation of activated T cells and a decrease in the HTLV-I viral load in peripheral blood lymphocytes, most likely through the selective removal of HTLV-I-infected, activated CD4+ lymphocytes.


Subject(s)
Antibodies/therapeutic use , Human T-lymphotropic virus 1/isolation & purification , Paraparesis, Tropical Spastic/therapy , Paraparesis, Tropical Spastic/virology , Proviruses/isolation & purification , Receptors, Interleukin-2/immunology , Blood Cells/pathology , Cell Division/physiology , Humans , Immunophenotyping , Lymphocyte Subsets/pathology , Lymphocytes/pathology , Paraparesis, Tropical Spastic/blood , Treatment Outcome , Viral Load
6.
Blood ; 86(11): 4063-75, 1995 Dec 01.
Article in English | MEDLINE | ID: mdl-7492762

ABSTRACT

Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused by the retrovirus human T-cell lymphotropic virus-I. It is an aggressive leukemia with a median survival time of 9 months; no chemotherapy regimen appears successful in inducing long-term disease-free survival. The scientific basis of the present study is that ATL cells express high-affinity interleukin-2 receptors identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this difference, we administered anti-Tac armed with Yttrium-90 (90Y) to 18 patients with ATL initially (first 9 patients) in a phase I dose-escalation trial and subsequently (second group of 9 patients) in a phase II trial involving a uniform 10-mCi dose of 90Y-labeled anti-Tac. Patients undergoing a remission were permitted to receive up to eight additional doses. At the 5- to 15-mCi doses used, 9 of 16 evaluable patients responded to 90Y anti-Tac with a partial (7 patients) or complete (2 patients) remission. The responses observed represent improved efficacy in terms of length of remission when compared with previous results with unmodified anti-Tac. Clinically meaningful (> or = grade 3) toxicity was largely limited to the hematopoietic system. In conclusion, radioimmunotherapy with 90Y anti-Tac directed toward the IL-2R expressed on ATL cells may provide a useful approach for treatment of this aggressive malignancy.


Subject(s)
Leukemia-Lymphoma, Adult T-Cell/radiotherapy , Radioimmunotherapy , Yttrium Radioisotopes/therapeutic use , Adult , Animals , Antibodies, Anti-Idiotypic/biosynthesis , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Female , Humans , Immunocompetence , Leukemia-Lymphoma, Adult T-Cell/immunology , Leukemia-Lymphoma, Adult T-Cell/metabolism , Lymphocyte Count , Male , Mice , Middle Aged , Receptors, Interleukin-2/immunology , Receptors, Interleukin-2/metabolism , T-Lymphocytes , Yttrium Radioisotopes/administration & dosage , Yttrium Radioisotopes/adverse effects
7.
Cancer ; 75(7): 1598-607, 1995 Apr 01.
Article in English | MEDLINE | ID: mdl-8826916

ABSTRACT

BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature T-cells occurring in patients infected with the human T-cell lymphotropic virus-I. These patients frequently develop a variety of infections throughout their disease course. METHODS: Charts and autopsy reports were reviewed for 41 patients with ATL with follow-up varying from 2 to 120 months. Infectious episodes were identified and documented. Analyses of humoral and cell-mediated immunity were performed. Cell-mediated immunity was assessed in vivo with the Merieux multitest skin test panel. Humoral immunity was assessed by quantitative immunoglobulin levels, by determining human antimouse antibody after murine monoclonal antibody infusion and by an in vitro immunoglobulin biosynthesis coculture system. RESULTS: A total of 112 infectious episodes were documented. Fifty-seven serious infections were identified. The incidence of total infections was 1.40/patient-year and for serious infections was 0.71/patient-year. The mean serum IgG and IgA levels were within normal range, the mean IgM level was at the lower limit of normal. Peripheral blood mononuclear cells from all patients studied failed to make meaningful amounts of IgG, M, or A when activated. Peripheral blood mononuclear cells of all of the 13 patients studied suppressed production of immunoglobulin by cocultured normal PBMC. Twenty-three of the 27 patients tested were anergic. CONCLUSIONS: ATL is a profoundly immunosuppressing malignancy. This is manifested by an extremely high incidence of infectious episodes/patient-year. The incidence of infection appears to be greater than for mycosis fungoides, Hodgkin's lymphoma and non-Hodgkin's lymphoma.


Subject(s)
Immunologic Deficiency Syndromes/etiology , Infections/etiology , Leukemia-Lymphoma, Adult T-Cell/complications , Adult , Female , Humans , Leukemia-Lymphoma, Adult T-Cell/immunology , Male , Middle Aged
8.
Blood ; 82(6): 1701-12, 1993 Sep 15.
Article in English | MEDLINE | ID: mdl-8400227

ABSTRACT

Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused by the retrovirus human T-cell lymphotrophic virus-I (HTLV-I). It is an aggressive leukemia with an overall mortality rate of 50% within 5 months; no conventional chemotherapy regimen appears successful in inducing long-term disease-free survival in ATL patients. However, ATL cells constitutively express high-affinity interleukin-2 receptors (IL-2Rs) identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this difference in receptor expression, we administered anti-Tac intravenously (IV) to 19 patients with ATL. In general the patients did not suffer untoward reactions, and in 18 of 19 cases did not have a reduction in normal formed elements of the blood. Seven patients developed remissions that were mixed (1 patient), partial (4 patients), or complete (2 patients), with partial and complete remissions lasting from 9 weeks to more than 3 years as assessed by routine hematologic tests, immunofluorescence analysis, and molecular genetic analysis of T-cell receptor gene rearrangements and of HTLV-I proviral integration. Furthermore, remission was associated with a return to normal serum calcium levels and an improvement of liver function tests. Remission was also associated in some cases with an amelioration of the profound immunodeficiency state that characterizes ATL. Thus the use of a monoclonal antibody that blocks the interaction of IL-2 with its receptor expressed on ATL cells provides a rational approach for treatment of this aggressive malignancy.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Leukemia-Lymphoma, Adult T-Cell/immunology , Leukemia-Lymphoma, Adult T-Cell/therapy , Receptors, Interleukin-2/immunology , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blotting, Southern , Female , Follow-Up Studies , Gene Rearrangement, T-Lymphocyte , Human T-lymphotropic virus 1/genetics , Humans , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Leukemia-Lymphoma, Adult T-Cell/genetics , Male , Middle Aged , Restriction Mapping , Virus Integration
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