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H Hedin

Publications and source records attributed to H Hedin.

25 records · Page 2Linked to original sources

Incidence, pathomechanism and prevention of dextran-induced anaphylactoid / anaphylactic reactions in man.

The symptoms of dextran-induced anaphylactoid/anaphylactic reactions (DIAR) range from skin reactions to severe circulatory shock (severity grades I-IV). The reported incidence of DIAR varies between 0.03% and 4.7%, severe reactions comprising 0.008% and 0.6% resp. Studies to elucidate the pathomechanism of DIAR and to possibly prevent them were made during the last decade: No evidence for a pathogenic role of contaminating macromolecules was found, but the dextran molecule itself could be incriminated as elicitor agent. High titres of dextran reactive antibodies (DRA) of predominantly IgG class are regularly found in sera of patients with grade III+IV reactions. Such DRA reflect immunization with dextran cross-reactive bacterial polysaccharides or native dextran. No DRA of IgE class were found. Presence of high IgG-DRA levels, reduction of complement factor Clq and histopathological findings in lungs, all indicate that DIAR should be classified as aggregate (immune complex) anaphylaxis. Hapten inhibition was therefore proposed to prevent DIAR. Based on positive results in animal models, clinical trials were started 1978. Hitherto, 60 485 patients have been studied. It is concluded that the combined use of preinjection of 20 ml Dextran 1 (Pharmacia AB, Uppsala, Sweden) and infusion of Macrodex or Rheomacrodex improves the safety of dextran administration.

Anaphylaxis↗

Complement profiles in monkeys subjected to aggregate (immune complex) anaphylaxis, and following injection of soluble and particulate polysaccharides.

Complement profiles were established in four groups of Macaca irus monkeys: (I) Aggregate (immune complex) anaphylaxis was induced following immunization, with ovalbumin. Upon challenge, systemic arterial pressure decreased from 115 to 50 mm Hg (mean values) in 10 min. The complement profiles revealed decreases in: C1q to less than 10% of initial value within 5 min; C4 proportional to hypotension; C3 slowly to 60% at 24 h; C5, C6, C7, C8 and factor B to about 80% of initial value in 5--30 min. Conversion products of C3 and factor B were detected on the day of anaphylaxis. In conclusion, mainly the classical and to a lesser extent the alternative pathway, were activated. Following injection of (II) native B 512 dextran, (III) biodegradable starch microspheres, and (IV) saline, no significant changes of complement profiles were seen. Conversion products of C3 and factor B were, however, demonstrable in groups II and III without appearance of clinical signs.

Anaphylaxis↗

[Sideeffects of colloids (author's transl)].

A prospective controlled trial during 1975 and 1976 has revealed that none of the colloids in clinical use (plasma protein solution, gelatine, hydroxyethylstarch and dextran) is free from the risk of anaphylactoid reactions. Even though the incidence of anaphylactoid reactions is low (0.03%), lethal outcome might be encountered. Between the colloids differences exist as far as manifestation (skin, circulatory and respiratory system) and degree of severity (I--IV) of anaphylactoid reactions are concerned. Since the underlying pathomechanisms have not been elucidated yet, true prophylactic measures are unknown. Therefore, it is mandatory to control the patient very carefully at the beginning of infusion; early symptoms of anaphylactoid reactions should trigger immediate therapeutic measures. Recent findings showed that the anaphylactoid reactions to dextran might be elicited by immune complexes. A new model was developed to investigate the chances of specific prophylactic procedures.

Anaphylaxis↗

Immunological properties of a high molecular weight component from yeast cell autolysate in dogs and evaluation of its potential role in human dextran reactions.

A high molecular weight component (HMC) of autolysate from Saccharomyces cerevisiae yeast cells was prepared. HMC was found to be immunogenic in dogs, inducing hemagglutinating antibody formation. Upon HMC challenge of immunized dogs, systemic anaphylactoid reactions were observed in 4/5 animals. The most prominent symptom was decreased cardiac output. Decrease in mean arterial pressure and increase in pulmonary arterial pressure were also observed. Consumption of total serum complement activity amounted to 22% of initial values. HMC also exhibited mitogenic activity in lymphocyte cultures from nonimmunized and immunized dogs. Since yeast autolysate is used as nitrogen source for Leuconostoc mesenteroides in the production of clinical B 512 dextran it is a theoretically possible trace contaminant of such solutions. Therefore, dogs hyperimmunized with HMC were also challenged with clinical dextran. No anaphylactoid signs were observed. These data suggest a negligible causal role of macromolecular contaminants derived from yeast cell autolysate in rare human anaphylactoid reactions following infusion of clinical dextran.

Anaphylaxis↗

Dextran-induced anaphylactoid reactions in man: role of dextran reactive antibodies.

Dextran reactive antibodies (DRA) were studied in 123 patients having experienced dextran-induced anaphylactoid reactions (DIAR) during 1970-1975. No evidence for reaginic DRA was obtained by radioallergosorbent technique and passive cutaneous anaphylaxis in Cynomolgus monkeys; total IgE levels were within normal range. It is concluded that DIAR are not mediated by dextran-specific reagins. Further, no reaginic antibodies against potential contaminants from the dextran manufacturing process were demonstrable. In two population samples of normal human sera from Sweden and Germany hemagglutinating DRA (IgG, IgA, and IgM classes) were found in 63 and 74%, high titres (16-256) comprising 14 and 25%. In dextran reactors a direct positive correlation between titres of hemagglutinating DRA and increasing severity of DIAR was observed. The accumulation of high DRA titres in severe reactions may be taken as circumstantial evidence for the causal role of hemagglutinating DRA in these cases. However, if high titres of DRA alone were responsible for triggering DIAR, the expected frequency would be more than thousand times higher than the reported global incidence of DIAR. To explain this discrepancy, involvement of certain Ig classes or subgroups, possibly in combination with other predisposing factors is suggested. In mild reactions DRA appear to play a negligible role. Positive dextran wheal and flare reactions, often correlated with high titres of hemagglutinating DRA, were seen in 32% of dextran reactors, indicating that skin tests are of limited predictive value. No significant difference between sexes, age groups, or pre- and intraoperatively started dextran infusions was observed; association with certain diseases was not apparent.

Adolescent↗