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Biomedical subjects

M Wälti

Publications and source records attributed to M Wälti.

At least 19 recordsLinked to original sources

[Acetylsalicylic acid and pyrazole allergy or pseudo-allergy?].

In a multicentric study by the European Study Group of Drug Allergy, 69 patients suffering from immediate type reaction after the intake of non-steroidal antiphlogistica were examined with regard to allergy or pseudo-allergy. Apart from the scratch test on the original substance, we performed cutaneous tests with salicyloyl and pyrazol conjugates, and determined IgE and IgG by means of a modified RAST method. There were 3 groups to be distinguished: (1) "intolerance" reaction of the aspirin type as a pseudo-allergic reaction (15 cases); (2) true IgE-mediated allergy (16 cases); (3) pyrazol "idiosyncrasy" (33 cases). 5 patients showed a combination of the three pathomechanisms.

Aspirin↗

Dot-immunobinding assay with monoclonal anti-IgE antibodies for the detection and quantitation of human IgE.

This paper describes a dot immunobinding assay for determining total human IgE with a tandem of monoclonal anti-IgE antibodies. Minute quantities of monoclonal anti-IgE antibodies were adsorbed on nitrocellulose discs. IgE bound to this solid phase monoclonal anti-IgE antibody was detected by a second monoclonal antibody conjugated with horseradish peroxidase. Using 4-chloro-1-naphthol as a chromogen results in a stable colour reaction that can be semiquantitatively analysed by the naked eye. The colour intensities of the reaction were also analysed by densitometry, yielding a very reproducible quantitation of human serum IgE. Using a serum dilution of 1:50, IgE could be detected in the range of 12.5-2500 U/ml. Using non-diluted serum samples IgE levels between 0.05-50 U/ml were reproducibly measured. Total serum IgE as determined by this dot assay correlated very well with IgE determinations performed by the commercial PRIST assay.

Antibodies, Monoclonal↗

[Radioimmunologic detection of IgE and IgG antibodies against drugs. Conclusions after experience with over 1200 patients].

Based on the radioallergosorbent test (RAST), the authors have developed a series of assays to detect IgE and IgG antibodies against a number of frequently used drugs. In this system drugs bound covalently to cellulose paper are incubated with serum and washed; the hapten-specific IgE and IgG antibodies are then qualified and quantified by means of 125I-labelled anti-human IgE and IgG respectively. Thus far the sera of 1,228 patients have been analyzed following therapy with betalactam antibiotics, co-trimoxazole, salicylates, pyrazolones, flavonoids and tetrahydroisoquinoline. The induction of IgG antibodies is a frequent occurrence and that of IgE rare. Isolated high titers of IgE are associated mainly with anaphylactic reactions; in the presence of simultaneously raised IgG titers such side reactions are often absent. Highest IgG titers were found in patients with immune hemolysis after betalactam antibiotics, flavonoids and tetrahydroisoquinoline. In the other types of side reaction specific IgG titers were not significantly higher than in patients without side reactions. The estimation of circulating antibodies against drugs cannot yet be utilized diagnostically except in the rare cases of anaphylactic side reactions. However, the method described permits specific and sensitive detection of sensitization and is suited for scientific purposes.

Clinical Trials as Topic↗

[IE and IgG antibodies against flavonoids following therapy with flavonoid-containing drugs].

During treatment with flavonoid drugs a number of patients developed adverse reactions such as fever, various skin eruptions and intravascular hemolysis. The appearance of flavonoid-specific IgE and IgG antibodies and its possible relation to the observed side effects was studied on a total of 168 individuals treated with flavonoid drugs: 71 patients received troxerutin (Venoruton) parenterally to improve tolerance of radiation therapy, 12 patients were treated intravenously with silymarin (Legalon) for amanita intoxication and 77 patients received various flavonoid drugs for other indications. Flavonoid treatment often induced specific IgG antibodies and less frequently IgE antibodies. After short treatment IgE antibodies were more frequently detected than after treatment of longer duration which nearly always induced IgG antibodies. Patients with hemolysis had the highest IgG titers. In cases with fever and skin eruptions no correlation with antibody titers became evident. Antibody production in patients undergoing radiation therapy appeared to be lower than in non-irradiated patients. Both the IgE and IgG antibody test show a remarkable cross-reactivity between four different flavonoids. Prospective studies will be necessary to decide whether or not this method for the detection of anti-flavonoid antibodies will be suitable for recognizing increased risk of side reactions upon reexposure to flavonoid drugs.

Catechin↗

Measurement of specific IgG antibody levels in serum of patients on regimes comprising high total dose beta-lactam therapy.

Sera from 125 patients receiving mean total doses of beta-lactam therapy of 215 g over a mean of 14 days were assayed by radioimmunoassay. Titres of anti-penicilloyl antibodies, expressed in arbitrary units of specific IgG per microliter of serum (u/microliter), ranged from undetectable (less than 3 u/microliter) to 1,650 u/microliter. There was a higher prevalence of elevated IgG levels in patients who developed haemolytic anaemia or neutropenia compared with patients with no adverse reactions but only in those patients who developed haemolytic anaemia were the antibody titres significantly higher. A subsidiary finding was that a correlation was established between mean total dose and prevalence of positive IgG titres, on a patient group basis (r = 0.87).

Anemia, Hemolytic↗

[Immediate-type reactions to pyrazole derivatives: results of skin tests and antibody determinations].

In a multicentric study by the European Study Group for Drug Allergy 58 patients suffering from an immediate type reaction after intake of pyrazol analgetics were examined with regard to allergy or pseudoallergy. Besides the scratch tests with the original substance we performed cutaneous tests with pyrazol conjugates and determined IgE and IgG antibodies by means of modified radioallergosorbent (RAST) method. Three groups could be distinguished: pseudoallergic reactions to nonsteroidal analgetics of the aspirin type (15 cases); IgE-mediated pyrazolone allergy verified by skin tests and/or IgE-RAST (21 cases), and pyrazolone idiosyncrasy (26 cases).

Anti-Inflammatory Agents, Non-Steroidal↗

Bullous esophageal lesions due to cotrimoxazole: an immune-mediated process?

A 78-yr-old man experienced a generalized bullous eruption of the skin (a Stevens-Johnson variant of erythema multiforme) with simultaneous involvement of the esophagus due to co-trimoxazole. Immunologic tests revealed specific antibodies of the immunoglobulin G class but not of the immunoglobulin E class against sulfamethoxazole, and in particular against trimethoprim. Lymphocyte transformation tests demonstrated sensitized lymphocytes against trimethoprim but not sulfamethoxazole. The esophageal mucosa showed intraepithelial vesicle formation with diffuse cytoplasmic deposits of immunoglobulin G. This adverse drug reaction involving both the skin and the esophagus appears to be immune-mediated.

Aged↗

Amoxicillin-induced immune hemolysis.

Severe hemolysis occurred in a 51-year-old female after a 17-day course of intravenous amoxicillin. A strongly positive direct antiglobulin test (anti-IgG titer 1:2,000) ensued which disappeared after withdrawal of the drug. Both the patient's serum and eluate obtained from the patient's red cells contained an IgG antibody which reacted with red blood cells coated in vitro with amoxicillin, but not with uncoated cells. In addition, high-titer antipenicillin, antiampicillin and antiamoxicillin IgG antibodies could be demonstrated in her serum by a RAST-based solid-phase radioimmunoassay. The patient's hemolysis gradually subsided within 1 week after discontinuing the drug. This is the first report of amoxicillin-induced immune hemolytic anemia.

Amoxicillin↗

Adverse reactions following intravenous penicillin-G relate to degradation of the drug in vitro.

We have recently shown that high-dose intravenous therapy with penicillin-G always results in both sensitised lymphocytes and rise of anti-penicilloyl IgG antibodies. If penicillin-G is strictly given as freshly prepared bolus doses this sensitisation is prevented. In 193 patients, intravenous treatment with penicillin-G without special precautions (bolus doses stored up to 36 h at 4 degrees C or continuous infusions) led to 8.3% definite, 6.7% probable and 14.0% possible adverse reactions. In 116 patients treated exclusively with freshly dissolved doses, 0.9% definite, 1.7% probable and 4.3% possible reactions occurred. Whereas haemolytic anaemia (7) and neutropenia (12) were observed in 19 cases of the first group no such reactions were seen in the second group. Strict application of freshly prepared single doses prevents the majority of adverse reactions following highdose intravenous penicillin-G therapy. Degradation and transformation products formed in vitro are therefore the causative agents rather than the penicillin molecule itself.

Adolescent↗

[Demonstration of drug-specific IgE and IgG antibodies using RIA: clinical importance as shown with nomifensin (Alival)].

Serum samples from 41 patients who developed adverse reactions during therapy with nomifensine were screened by RAST-based immunoassay for specific IgE and IgG antibodies against nomifensine and three of its metabolites. The results were compared with those of 10 patients without side effects and with 8 non-treated controls. Nomifensine-specific IgE antibodies were found in none of the subjects. However, all patients treated with nomifensine (with and without side effects) had specific IgG antibodies. The antibody cross-reacted in all cases with the metabolites. The titers did not discriminate clearly between the different side reactions and only partially between the presence or absence of a side reaction. The finding of specific anti-drug IgG antibodies warrants more detailed investigation of immunological mechanisms, to determine the clinical relevance of these antibodies and identify patients at risk for serious side effects.

Alveolitis, Extrinsic Allergic↗

[Semisynthetic penicillins and cephalosporins inhibit in vitro myelopoiesis in a dose-dependent manner].

Penicillin-G degradation products have been shown to inhibit in vitro myelopoiesis in a dose-dependent manner. Similar inhibition was seen with 6 semisynthetic penicillins and 2 cephalosporins. 50% inhibitory doses in vitro well matched total and daily doses given in vivo before neutropenia developed. These findings suggest a toxic rather than an immune-mediated pathogenesis for betalactam-induced neutropenia.

Bone Marrow Cells↗

[Immunoallergic intravascular hemolysis and tubulointerstitial nephritis due to penicillin G].

A 51-year old woman treated with high doses of penicillin G developed acute intravascular haemolysis and tubulointerstitial nephritis. Immunological investigations showed circulating immune complexes, decreased C3 and C4 components of complement, IgG deposits in the renal interstitium, positive direct Coombs test with anti-IgG sera and complement and circulating anti-penicillin antibodies demonstrated by indirect antiglobulin tests and IgG RAST. Plasma haemoglobin and anti-penicillin antibodies could be removed by an early exsanguino-transfusion. These findings suggest that the nephritis was due to immune complexes and the haemolysis, to a combined hapten-type and immune complex mechanism.

Anemia, Hemolytic, Autoimmune↗

Penicillin-G degradation products inhibit in vitro granulopoiesis.

38% of penicillin-G in solution decays at 20 degrees C within 24 h, 50% at 37 degrees C and 66% within 3 h at 56 degrees C. These degraded penicillin-G solutions strongly inhibit growth and maturation of granulocytic stem cells in vitro. Inhibitory concentrations are in the range obtainable with high dose penicillin therapy in vivo. No cytotoxicity of degraded penicillin solutions on bone marrow cells was seen over 24 h. It is suggested that penicillin-G degradation products are responsible for severe granulocytopenia observed after high dose penicillin-G therapy.

Bone Marrow↗