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P W van der Linden

Publications and source records attributed to P W van der Linden.

14 recordsLinked to original sources
PubMed1998

A patient with acquired haemophilia A and pemphigus.

Haemophilia A is usually a genetic deficiency of coagulation factor VIII (F VIII). The development of antibodies against F VIII is a well known and frequent complication in the treatment of haemophilia A. Rarely, a F VIII inhibitor arises spontaneously, causing a condition which is known as acquired haemophilia A. We describe a patient with acquired haemophilia A and pemphigus, who presented with spontaneous haematomas of the extremities. Laboratory tests showed an activated partial thromboplastin time (aPTT) of 71 s (normal: 26-36 s), a F VIII concentration of 9% (normal: 60-140%), and a F VIII inhibitor-activity of 7.5 Bethesda Units/ml (B.U./ml, normal: 0). The haematomas disappeared within a few days and the laboratory tests normalized within 6 weeks, after administration of a booster of oral corticosteroids. One and a half years after the corticosteroids were stopped, both the clinical and the laboratory course of the patient has been uneventful. As far as we know, the combination of acquired haemophilia A and pemphigus has been reported in the literature only three times before. The diagnosis acquired haemophilia A should be considered in a patient presenting with a newly arisen haemorrhagic diathesis.

Aged↗
PubMed1997

Discontinuation of yellow jacket venom immunotherapy: follow-up of 75 patients by means of deliberate sting challenge.

BACKGROUND: Venom immunotherapy is effective in preventing systemic reactions in patients with a history of an anaphylactic reaction to Hymenoptera stings. It is uncertain how long venom immunotherapy should be continued. OBJECTIVE: We evaluated whether the duration of venom immunotherapy given to yellow jacket-sensitive patients related to the risk of an anaphylactic reaction to a later sting. METHODS: Seventy-five yellow jacket-sensitive patients (29 male and 46 female) received a median number of three in-hospital sting challenges from a live insect in 3 subsequent years after discontinuation of venom immunotherapy. An anaphylactic reaction to one or more of the sting challenges was considered a relapse. We analyzed whether patients with and patients without a relapse differed in terms of gender, age, preimmunotherapy skin test data, preimmunotherapy level of venom-specific IgE, severity of the field-sting reaction that preceded immunotherapy, severity of the reaction to the sting challenge that preceded immunotherapy, adverse reactions to immunotherapy, changes in IgE and IgG4 levels during immunotherapy, duration of immunotherapy, and presence of venom-specific IgE after cessation of therapy. RESULTS: Venom immunotherapy was given for a median duration of 40 months (range, 7 to 120 months). Relapses were observed in six patients. In two of them, a rather severe anaphylactic reaction was observed after the second sting challenge. No relation was found between duration of venom immunotherapy and relapse risk. The relapse rate was higher among patients with high levels of specific IgE before and after immunotherapy. During therapy, the mean level of specific IgE decreased. This decline persisted in the 3 following years. No relapses of sting reactions were observed among patients without detectable specific IgE. CONCLUSION: Discontinuation of venom immunotherapy appears safe for patients with pretreatment IgE antibodies if these antibodies can no longer be detected during immunotherapy. For the remaining patients, a treatment period of 3 years may suffice. After discontinuation of immunotherapy, a clinical sting challenge can be considered to estimate the patient's current grade of hypersensitivity.

Adolescent↗
PubMed1996

Hymenoptera sting challenge of 348 patients: relation to subsequent field stings.

BACKGROUND: Patients with a history of a serious anaphylactic reaction after a Hymenoptera sting are usually given venom immunotherapy. Because the natural history of Hymenoptera sting anaphylaxis is often of a declining severity, there is a chance of overtreatment. OBJECTIVE: Identification of patients at risk for a future anaphylactic reaction may reduce the number of patients who need venom immunotherapy. METHODS: We investigated the relation between the grade of hypersensitivity to an in-hospital sting challenge and the reaction to a subsequent accidental field sting. From 1982 through 1992, 348 patients with mild or no symptoms after a sting challenge were not given venom immunotherapy. All patients were asked by letter whether they had experienced a subsequent field sting. In case of a sting, the severity of the reaction was further evaluated. RESULTS: Information could be obtained from 327 patients: 129 had been re-stung, and 110 of them had only had a local reaction. Thirteen patients had experienced mild systemic symptoms, and six patients had experienced serious manifestations. In two of the latter group hypotension was observed. CONCLUSION: In 95% of patients with a previous anaphylactic reaction, the result of the in-hospital sting challenge provided a good prediction of tolerance to a subsequent Hymenoptera field sting.

Adult↗
PubMed1994

Insect-sting challenge in 324 subjects with a previous anaphylactic reaction: current criteria for insect-venom hypersensitivity do not predict the occurrence and the severity of anaphylaxis.

Three hundred twenty-four patients with a history of yellow jacket- (n = 272) or honeybee- (n = 52) sting anaphylaxis were prospectively subjected to an in-hospital sting challenge. Plasma levels of specific IgE and IgG4, skin venom tests, severity of previous reaction, sex, age, atopic constitution, histamine skin test results, location and number of previous stings, time interval between previous anaphylactic reaction and sting challenge, and time interval between sting challenge and onset of anaphylaxis were studied in relation to the clinical severity of a reaction after sting challenge. A recurrent anaphylactic reaction after sting challenge was observed in 25% of yellow jacket- and in 52% of honeybee-sensitive persons. The severity of this reaction correlated significantly with age and the time interval between sting challenge and onset of anaphylaxis only: older persons with faster reactions had more severe symptoms after sting challenge. None of the current criteria for insect-sting hypersensitivity (IgE, IgG4, skin test) significantly related on an individual basis or in combinations to the reaction after sting challenge. We conclude that the current criteria to assess insect-venom hypersensitivity do not relate to the occurrence and severity of anaphylactic symptoms after an insect-sting challenge.

Adolescent↗
PubMed1993

Controlled insect-sting challenge in 55 patients: correlation between activation of plasminogen and the development of anaphylactic shock.

The pathogenesis of anaphylactic shock is not completely understood. Mast cell degranulation products may stimulate endothelial cells, leading to activation of fibrinolytic and coagulation systems. We investigated the activation of these systems in insect-sting anaphylaxis. Fifty-five patients with a previous insect-sting anaphylactic reaction and 8 volunteers were challenged with an in-hospital sting. Plasma levels of von Willebrand factor (vWF), coagulation, and fibrinolytic parameters were assessed. After the sting challenge, 20 patients developed anaphylactic symptoms, 7 of whom developed hypotension. In only these 7 patients, but not in the volunteers or in the other patients with no or mild anaphylactic symptoms, vWF levels increased from 107% +/- 33% (mean +/- SD) before, to 235% +/- 134% 60 minutes after the onset of clinical symptoms. This increase of vWF was accompanied by an increase of circulating tissue-type plasminogen-activator (tPA) levels from 5 +/- 3 micrograms/L to 50 +/- 59 micrograms/L and of plasminogen-alpha 2-antiplasmin complex (PAP-c) levels from 6 +/- 3 nmol/L to 297 +/- 225 nmol/L. Both tPA and PAP-c levels peaked 5 minutes after the onset of clinical symptoms. Such increases of tPA and PAP-c were not observed in the volunteers or in the patients who did not develop shock. The increase of tPA and PAP-c levels in the hypotensive patients correlated positively with the degree of mast cell degranulation and inversely with the mean arterial pressure. We conclude that activation of plasminogen may be involved in the pathogenesis of anaphylactic shock induced by insect venom.

Adult↗
PubMed1993

Activation of the contact system in insect-sting anaphylaxis: association with the development of angioedema and shock.

A postulated role of the contact system in anaphylactic reactions to insect stings was investigated. During prospective, in-hospital sting challenge, we collected serial blood samples from five normal volunteers and 16 patients with a history of insect-sting anaphylaxis. Activation of the contact system was assessed by measuring plasma levels of factor XIIa-C1-inhibitor and kallikrein-C1-inhibitor complexes as well as those of cleaved high molecular weight kininogen (HK). In addition, antigenic levels of (pre)kallikrein, factor XII, and HK were measured. No significant changes in contact system parameters were observed in any of the five volunteers or the four patients who did not develop an anaphylactic reaction after sting challenge. In contrast, significant changes in contact system parameters occurred in 7 of the 12 patients with anaphylactic symptoms after challenge. Peak levels of either C1-inhibitor complex were found 5 minutes after the onset of anaphylactic symptoms. The increase in C1-inhibitor was most pronounced in the 4 patients with angioedema, 2 of which also developed shock. However, activation of HK was observed in all four patients with angioedema, the two patients with shock but no angioedema, as well as in 1 of the remaining 6 patients with anaphylactic symptoms other than angioedema or shock. Thus, activation products of the contact system may be involved in the pathogenesis of angioedema and shock in insect-sting anaphylaxis.

Adult↗
PubMed1993

Anaphylactic shock after insect-sting challenge in 138 persons with a previous insect-sting reaction.

OBJECTIVE: To study the rate and severity of anaphylactic reaction in relation to plasma levels of cardiovascular mediators in persons with a history of insect-sting anaphylactic shock who were rechallenged with a sting by the same insect. DESIGN: A cohort study with measurements before and after intentional sting challenge. SETTING: Intensive care unit of an 830-bed general hospital, a national center of insect-sting anaphylaxis in The Netherlands. PATIENTS: A total of 138 patients referred after a previous anaphylactic reaction to a Hymenoptera sting; and 8 volunteers. MEASUREMENTS: Signs of anaphylaxis and plasma levels of catecholamines and angiotensins. MAIN RESULTS: Only 39 of 138 (28%) of patients with a previous insect-sting anaphylactic reaction developed anaphylactic symptoms after sting challenge. Values of cardiovascular mediators and mean arterial pressure did not differ after the challenge from initial values in the volunteers or in the patients with a mild or no reaction after challenge. In the 17 patients with anaphylactic shock, mean arterial pressure decreased from 97 +/- 11 (mean +/- SD) to 65 +/- 17 mm Hg (P < 0.001), epinephrine levels rose from a median of 0.3 nmol/L (range, 0.2 to 2.3 nmol/L) to 2.5 nmol/L (0.2 to 35.7 nmol/L; P < 0.05), norepinephrine from 1.5 nmol/L (0.5 to 6.7) to 5.9 nmol/L (1.6 to 30.9 nmol/L; P < 0.01), and angiotensin II from 61 pmol/L (7 to 217 pmol/L) to 105 pmol/L (11 to 286 pmol/L; P < 0.01), all within 5 minutes after the onset of anaphylactic symptoms. The rise of these mediators correlated with the drop in blood pressure (P < 0.001). Dopamine and angiotensin I levels did not change in any participants. CONCLUSIONS: A recurrent insect-sting anaphylactic reaction occurred in only 28% of patients with a previous reaction. During this recurrent reaction, plasma levels of endogenous epinephrine, norepinephrine, and angiotensin II rose in relation to hypotension.

Anaphylaxis↗
PubMed1992

Insect-sting challenge in 138 patients: relation between clinical severity of anaphylaxis and mast cell activation.

One hundred thirty-eight patients with a previous anaphylactic reaction to a yellow jacket or a honeybee sting, as well as eight volunteers, were subjected to an in-hospital sting challenge. Plasma levels of histamine, tryptase, and prostaglandin D2 (PGD2) during sting challenge were studied in relation to clinical symptoms. Prechallenge levels (mean +/- SD) of histamine, tryptase, and PGD2 were 2 +/- 1 nmol/L, 0.3 +/- 0.3 U/L, and 320 +/- 223 ng/L, respectively. In the volunteers and in none except for one of the nonreacting patients, these levels did not change significantly after challenge. In contrast, mean increases in the group of 18 patients with a mild reaction were significant for histamine and tryptase at one or more time points after the challenge. (Five patients demonstrated no increase in histamine; nine demonstrated no increase in tryptase.) Except for histamine levels in one patient, these increases were considerably more in all 17 patients with a severe reaction, starting from the first anaphylactic symptoms. Fifteen minutes later, peak values were reached of 1275 +/- 2994 nmol of histamine per liter (range, 3 to 12800 nmol/L; median, 11 nmol/L) and 406 +/- 1062 U of tryptase per liter (range, 1.8 to 4400 U/L; median, 17 U/L). This rise in levels inversely correlated with the mean arterial pressure. Plasma levels of PGD2 in severely reacting patients did not differ significantly from those in patients with a mild or no reaction. In conclusion, only 28% of patients with a history of Hymenoptera anaphylaxis developed an anaphylactic reaction after an in-hospital challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗
PubMed1990

Preliminary report: complement activation in wasp-sting anaphylaxis.

The generation of the anaphylatoxin C3a was measured after a wasp-sting challenge in eight patients with previous anaphylactic reactions to wasp stings. Whereas there was no change in C3a in one patient who showed no reaction and only a slight rise in three patients with mild reactions, C3a rose substantially in the four patients with severe anaphylactic reactions. This complement activation is the first in-vitro variable which correlates with the severity of wasp-sting anaphylactic reactions. A role for complement activation in the pathophysiology of wasp-sting anaphylaxis is therefore suggested.

Adult↗
PubMed1987

Characterization of a slow-growing, transplantable rat mammary tumor (MCR-83): a model for endocrine-related cell kinetic studies.

Out of 24 primary mammary tumors, arising in rats of the WAG/Rij Wistar strain after low dose irradiation, with or without prolonged treatment with estrogen, a slow-growing, well differentiated adenocarcinoma (MCR-83) was selected. This tumor, induced by radiation alone, is independent of estrogen pellets for growth after transplantation into adult female rats, but nontransplantable into males or ovariectomized females. Measurements of tumor growth and contents of both estrogen and progesterone receptors on three successive passages are not indicative of a rapid progression in growth rate or to hormone independency. Ovariectomy and treatment with tamoxifen give a pronounced inhibition of tumor growth, whereas neither methotrexate nor cyclophosphamide is effective. Growth rate is significantly increased when rats are given 17 beta-estradiol. Flow cytometric DNA analysis as well as in situ S-phase cell detection with anti-bromodeoxyuridine antibodies show a 3-fold increase in S-phase fraction cells within 4 days after the onset of estrogen treatment. No spontaneous metastases have been found so far, but lung nodules develop after i.v. inoculation of tumor cells. From one of these nodules a fast-growing, hormone independent subline (MCR-86) has been derived, showing both lymphatic and hematogenous dissemination upon s.c. transplantation. By showing several features of hormone responsive human disease in its early stage of progression the MCR-83 tumor system may be a clinically relevant model for studies on endocrine regulation of tumor growth and its therapeutic manipulation.

Adenocarcinoma↗
PubMed1982

Alternative fluorochromes to ethidium bromide for automated read out of cytotoxicity tests.

Propidium iodide (PI) and diamidinophenylindol (DAPI) were compared with ethidium bromide (EB) in cytotoxicity tests. Double blind studies showed similar results with the 3 dyes in terms of percentages of dead (fluorescing) cells. The dyes were also investigated for their potential combination with the immunofluorescent membrane markers FITC and TRITC. Both EB-FITC and PI-FITC are suitable for conventional HLA-DR typing procedures. Because of its spectral properties, the DAPI-TRITC combination is promising for automated read out of DR-typing tests by image analysis systems.

Cell Survival↗