Biomedical subjects

H Hedin

Publications and source records attributed to H Hedin.

At least 19 recordsLinked to original sources

PubMed1998

Characterization of the N-methyl-D-aspartate (NMDA) receptor in the embryonic chick brain.

Relatively little is known about the properties of the NMDA receptor in avian species. In the present study, NMDA receptor pharmacology and function has been studied in the embryonic chick brain. The competitive antagonist ligand [3H]CGP 39653 bound to telencephali membranes from 17-day-old chick embryos with KD and Bmax values of 6.6 nM and 3.3 pmol/mg protein, respectively. The binding was inhibited by CGS 19755, L-glutamate, R-CPP and D-AP5 with pI50 values of 7.57, 7.49, 7.28 and 7.08, respectively. L-glycine, S-AMPA, kainate and MK-801 only weakly affected the binding. The inhibitory potency of NMDA (pI50 value 6.98), however, was greater than seen in other species, suggesting a species difference in receptor structure. Such a possibility was investigated by use of two NMDA-R1 antibodies, AB 1516 and 69921 A, which recognize the C-terminal region and an intracellular domain of the rat receptor, respectively. Immunoreactive signals (approximately 116 kDa) were found for a rat brain homogenate, whereas only 69921A gave an immunoreactive signal in the chick. The functional status of the NMDA receptors was investigated in serum-free cultures of neurons from 8-day-old chick embryos. Glutamate and NMDA were found concentration-dependently, and in a manner that could be antagonized by CGS 19755 and MK-801, to produce cell death. Thus, the present study indicates that chick embryonic brain expresses functional NMDA receptors that are pharmacologically and possibly structurally different from their rodent counterparts.

2-Amino-5-phosphonovalerate↗

PubMed1993

Hapten inhibition of dextran anaphylaxis. Nine years of post-marketing surveillance of dextran 1.

All spontaneous reports to the manufacturer and to WHO's database INTDIS regarding adverse reactions to clinical dextran after preinjection of dextran 1 and to dextran 1 alone 1983-1991 were collected. During 1983-1991 a total of 4.8 million doses of Promit were sold in fourteen countries. The incidence of severe DIAR (grades III-V) to clinical dextran after the prophylactic use of hapten inhibition was approximately one case per 200,000 doses of dextran 1. In Sweden, where reporting of severe adverse drug reactions is mandatory, the incidence was one case per 70,000. This indicates a 35-fold reduction in the incidence of severe DIAR compared with the use of clinical dextran without dextran 1. Only two fatal reactions were reported; the incidence was therefore one case per 2.4 million doses, indicating a 77-fold reduction. Both these occurred in patients with extremely high titers of DRA. Side effects to dextran 1, mostly mild, were reported in one case per 100,000 doses. These side effects were not antibody mediated. It is concluded that the introduction of hapten inhibition with dextran 1 has greatly reduced the risk for serious side effects to dextran, making dextran one of the safest colloids in use.

Anaphylaxis↗

PubMed1991

Serum concentrations of hyaluronan and proteoglycan in joint disease. Lack of association.

Circulating hyaluronan originating from the synovial membrane and circulating proteoglycan released from cartilage were determined by specific assays in patients with osteoarthritis (OA), rheumatoid arthritis (RA), reactive arthritis or juvenile chronic arthritis (JCA). Elevated hyaluronan concentrations were found in OA and RA, suggesting proliferation of the synovial membrane in both diseases. The proteoglycan concentrations were highest in OA and polyarticular JCA indicating increased turnover of cartilage matrix. The concentrations of the macromolecules did not correlate except in the group with JCA. Serum concentrations of hyaluronan and proteoglycan thus differ between disease groups and may reflect different aspects of the arthritic process.

Adolescent↗

PubMed1989

Does vaccination of splenectomized patients against pneumococci induce dextran-reactive antibodies?

Polyvalent pneumococcal vaccine containing polysaccharides from serotypes known to be cross-reactive with dextran was used for vaccination of 72 patients either shortly before or on the average 6.25 years after splenectomy. The titer of dextran-reactive antibodies was determined by passive hemagglutination before as well as 6 weeks and 6 months after vaccination. Already prior to vaccination the patients had moderately elevated titers of these antibodies and the titer was somewhat reduced during the study period. Small intergroup differences were observed but the titers of patients who had received cytostatic and/or radiation therapy did not appear to react differently to vaccination. It is concluded that this type of vaccine does not induce dextran-reactive antibodies when given to asplenic individuals.

Adolescent↗

PubMed1988

Histopathological lung changes in immune complex mediated anaphylactic shock in humans elicited by dextran.

Severe dextran-induced anaphylactic reaction (DIAR) is being recognized as a form of immediate IgG mediated immune complex reaction. Support for this pathogenesis is found in the correlation between the titer of dextran-reactive antibodies of IgG class and the severity of the reaction. Autopsy records were reviewed in 27 certified cases of fatal DIAR. The most frequent macroscopic findings were dilatation of the right side of the heart and acute pulmonary stasis. Autopsy lung specimens were collected from 17 of these patients. In 15 of the 17 lung specimens pulmonary microemboli were found. The microemboli had the appearance of hyaline eosinophilic globules, and the lung vasculature also contained leukocytes, platelets and disintegrated erythrocytes. These findings show similarity to the findings in a monkey model of known IgG mediated anaphylaxis, and give further support to the proposed pathogenesis of severe DIAR.

Adult↗

PubMed1988

Hapten inhibition and dextran anaphylaxis.

Hapten inhibition with dextran 1 has been used in Sweden since 1982 to prevent severe anaphylactic reactions to dextran. This has led to a reduction in the reports of severe reactions to dextran from 22 per 100,000 units of dextran used between 1975 and 1979, to 1.2 per 100,000 units between 1983 and 1985. The number of fatal reactions decreased from 23 to one. More than 600,000 units of dextran were used during each period.

Aged↗

PubMed1983

Adverse reactions to dextran in Sweden 1970-1979.

In a retrospective investigation of the period 1970-1979, 478 reports on cases of dextran-induced anaphylactoid/anaphylactic reactions (DIAR) were found. In 458 of these dextran was judged to be the causative agent. The number of units of dextran 40 and 70 used during this decade was 313 598 and 1 051 668, respectively. During the last five years, when reporting of severe adverse drug reactions was mandatory, the incidence of severe DIAR per unit administered was 0.013% for dextran 40 and 0.025% for dextran 70. The incidence of fatal DIAR was 0.003% and 0.004%, respectively. We found a male: female ratio of 1.5: 1 for all DIAR while for the most severe DIAR this ratio was 3: 1. The mean age of the patients was higher in severe than in mild DIAR. Allergic disease did not predispose for severe DIAR. Diabetes, cardiovascular and pulmonary diseases and chronic inflammation were more frequent among the patients who had suffered the most severe DIAR. 22 reactions were characterized by fever and/or shivering, and in 19 of these cases the reaction occurred after infusion of more than one unit of dextran. Severe DIAR occur after infusion of a few ml of dextran. Fatal DIAR during anaesthesia occurred almost exclusively in patients under spinal or epidural blockade. A favourable outcome of resuscitation in DIAR with cardiac arrest was possibly promoted by the infusion of large amounts of crystalloid fluids. We could not show that therapy with steroids, epinephrine or isoprenaline influenced the outcome. Fatal DIAR occurred even after infusion of only 0.5-1 ml of dextran, and we strongly advise against the use of "biological test-doses".

Aged↗

PubMed1983

Prevention of dextran-induced anaphylactic reactions by hapten inhibition. I. A Scandinavian multicenter study on the effects of 10 ml dextran 1, 15% administered before dextran 70 or dextran 40.

In an open prospective study the prevention of dextran-induced anaphylactic reactions (DIAR) by hapten inhibition was investigated in 29 252 patients. Forty-nine hospitals in Sweden, Norway and Finland participated in the study which was running for two years. Ten ml of dextran 1, 15%, (Promiten, Pharmacia AB, Uppsala, Sweden) with a weight average molecular weight of 1 000 dalton was injected intravenously two minutes before infusion of dextran 70 (Macrodex) or dextran 40 (Rheomacrodex). DIAR were graded according to severity from I to V. Six grade III and one grade IV reactions occurred, representing an incidence of severe DIAR of 0.024%. Compared to a large historical control material, preinjection of 10 ml of dextran 1 exerts a partially protective effect, but no statistical proof can be given. Consequently trials have been started with a 20 ml dose of dextran 1. Adverse reactions to the preinjection of 10 ml of dextran 1 were observed in 0.072%. These reactions were of a mild and shortlasting nature and considered to be of minor clinical importance.

Adolescent↗

PubMed1983

Prevention of dextran-induced anaphylactic reactions by hapten inhibition. III. A Scandinavian multicenter study on the effects of 20 ml dextran 1, 15%, administered before dextran 70 or dextran 40.

In an open, prospective multi-center study prevention of dextran-induced anaphylactic reactions (DIAR) was attempted by intravenous injection of 20 ml dextran 1, 15%, Mw 1000 dalton, (Promiten), two minutes before start of infusion of dextran 70 (Macrodex) or dextran 40 (Rheomacrodex). Of 34955 patients investigated, only one developed a severe DIAR of grade III (0.003%). The incidence of severe DIAR after preinjection of 20 ml dextran 1 is significantly lower than that after injection of 10 ml dextran 1 (p = 0.01), and is also markedly lower than that of a large Swedish historical control material (0.037-0.050%). The incidence of mild DIAR is not affected by dextran 1. Adverse reactions to dextran 1 of a generally mild and short-lasting nature were observed in 20 patients. It is recommended that patients who are going to receive dextran 70 or 40 are given a prophylactic i.v. injection of 20 ml dextran 1 before the first unit of clinical dextran to minimize the risk of severe DIAR.

Adolescent↗

PubMed1982

Immunoglobulin class and subclass distribution of dextran-reactive antibodies in human reactors and non reactors to clinical dextran.

The red cell-linked antigen-antiglobulin reaction (RCLAAR) with stearoyldextran-coated erythrocytes was used to characterize the immunoglobulin (Ig) classes and IgG subclasses of dextran reactive antibodies (DRA) in 27 dextran reactors (DR) and 96 on reactors (DNR). High titres of dextran reactive IgG were regularly found in sera of patients with severe dextran-induced anaphylactoid/anaphylactic reactions (DIAR) prior to the infusion. In four lethal cases IgG antibodies were found to be in the highest titre range of 16,384 to 32,768. In addition, high IgA and IgM titres were also in severe DIAR. DNR had much lower titres of dextran reactive antibodies of IgG, IgM and IgA classes and IgD antibody was absent in both groups. Dextran reactive IgE antibodies were not demonstrable in DR. Dextran reactive IgG2, IgG3, IgG4 and IgG1 (indirect measurement) were demonstrated in both DR and FNR. Dextran infusion caused variable neutralization in all Ig classes and IgG subclasses, but the contribution of IgG2 was considered most important because of its high titres and most pronounced neutralization in severe DIAR. It is concluded that DRA mainly of the IgG class, play a critical pathogenic role in the induction of severe DIAR, which accordingly is classified as immune complex (Type III) anaphylaxis. The method of RCLAAR allows to delineate a risk group of about 2% of potential reactors.

Adolescent↗

PubMed1982

Pathomechanisms of dextran-induced anaphylactoid/anaphylactic reactions in man.

Immune complex-mediated (type III) anaphylaxis is shown to be the pathomechanism of severe dextran-induced anaphylactic reactions in man. Mild reactions may be either antibody-dependent or not. Patients with severe reactions have regularly high titers of preformed, circulating dextran-reactive antibodies and represent a small subpopulation of high responders to dextran. Upon infusion of clinical dextran, noxious immune complexes are formed, leading to mediator release and symptoms of anaphylaxis. Consequently, application of the hapten inhibition principle is recommended for prevention of such reactions.

Anaphylaxis↗

PubMed1981

Comparison between human IgM and IgG antibodies to dextran, regarding their activities in antibody-dependent cellular cytotoxicity (ADCC).

Human sera containing dextran-reactive antibodies of various immunoglobulin classes were tested for their capacity to induce ADCC against dextran-coated chicken red blood cells (CRBC). It was found that only IgG antibodies were active in ADCC, while IgM antibodies were not, thus providing further evidence that IgM antibodies do not contribute to ADCC even when human antibodies are used.

Animals↗

PubMed1981

Low molecular weight dextran therapy for digital ischemia due to collagen vascular disease.

12 patients with digital ischemia due to collagen vascular disease were treated with repeated infusions of low molecular weight dextran at intervals from 5 to 6 weeks. The patients were followed clinically and by capillary microscopy. In 5 patients an increased capillary blood flow was seen by capillary microscopy. The clinical changes consisted of a lower number of ulcers in 5 of 9 patients with ulcers and a reduction of cold intolerance in 8 of the 12 patients studied. 4 patients had no improvement at all from the treatment. A determination of dextran-reactive antibodies was also performed.

Antibodies↗

PubMed1981