Effect of dihydroergotamine on leg blood flow during combined epidural and general anaesthesia and postoperative deep vein thrombosis after cholecystectomy.

The effects of dihydroergotamine (DHE) on the circulation of the leg during combined epidural and general anaesthesia were studied to determine if DHE would enhance leg blood flow and prevent postoperative deep vein thrombosis in a double-blind trial of 40 elderly female patients subjected to cholecystectomy. Central and big toe temperature, arterial blood pressure, heart rate, calf volume and arterial inflow of the leg by electrical impedance plethysmography and the venous outflow by Doppler method were measured. DHE 0.5 mg subcutaneously reduced the volume of the leg, i.e. increased the electrical impedance, probably due to venous vasoconstriction. Simultaneously the need for etilefrine hydrochloride was reduced. No significant changes in the pulsatile inflow of the leg or the outflow were detected. Deep vein thrombosis (DVT) was detected by fibrinogen uptake test in five patients (three in DHEH and two in the control group) and verified by ascending phlebography in four patients. Intraoperative characteristics in patients with postoperative DVT were tachycardia (P < 0.001), enhanced need for etilefrine (P < 0.01) and a more rapid increase in big toe temperature (P < 0.05) after induction of epidural analgesia, compared with patients without DVT. Femoral vein flow velocity remained at the preinduction level, whereas pulsatile arterial inflow slightly increased. Together with a low basal impendance of the leg, the changes were indicative of a more intense vasodilatation, probably leading to stagnant flow and development of postoperative deep vein thrombosis.

Dihydroergotamine in the prevention of hypotension associated with extradural anaesthesia.

The efficacy of a single dose of dihydroergotamine (DHE) 0.5 mg i.v. in preventing the decrease in arterial pressure resulting from extradural anaesthesia was studied in 47 patients; 24 received DHE and 23 a placebo, in a randomized double-blind manner. Although the decrease in systolic arterial pressure was more pronounced in the placebo group than in the DHE group, the difference was not significant. Diastolic and mean arterial pressures were both significantly lower in the placebo group than in the DHE group during the initial phase of extradural anaesthesia. Administration of DHE did not cause any significant changes in heart rate. In both groups the heart rate decreased significantly during the 5-h period following the induction of extradural anaesthesia. The patients in the placebo group needed additional medication to increase unacceptably low arterial pressures or heart rate more frequently than the patients in the DHE group.

Clinical and immunological response to oral and subcutaneous immunotherapy with grass pollen extracts. A prospective study.

Forty children allergic to grass pollen were divided into two groups, and matched by their serum IgE antibody concentrations to grasses. For two preseasonal treatment periods one group received immunotherapy with an alum adsorbed grass pollen extract, while the second group was treated orally with an aqueous extract of the same allergens. The patients' postseasonal self evaluation as well as the mean symptom scores calculated from symptom diaries indicate, that oral treatment is significantly less effective in controlling seasonal allergic symptoms than subcutaneous immunotherapy. During oral treatment neither an increase of specific serum IgG antibodies, nor a suppression of the seasonal increase in specific serum IgE antibodies could be demonstrated.

Studies of allergen and allergoid preparations from purified timothy (Phleum pratense) pollen extracts. I. Physicochemical characteristics and binding to allergen-specific human IgE.

Physicochemical and in vitro allergenic properties of two different preparations of timothy (Phleum pratense) pollen were compared. The refined allergen extract, timothy B, contained proteins of molecular weights from 10,000 to 45,000 daltons. The allergoid preparation, which was prepared by mild treatment of the partially purified extract with formaldehyde, possessed only a trace of activity in the RAST inhibition assay. The formaldehyde treatment also resulted in a shift of the net charge of proteins to the more acidic site, as demonstrated by isoelectric focusing. Furthermore, it was shown that the activities of naturally occurring enzymes of native allergen extracts were reduced considerably. Only traces of acid phosphatase activity could be demonstrated in timothy B allergoid.

Studies on allergen and allergoid preparations from purified timothy (Phleum pratense) pollen extracts. II. Anaphylaxis studies in rats and histamine release from human leukocytes.

In vivo and in vitro allergenic activities of allergen and allergoid preparations from partially purified timothy pollen extract were measured in three different systems. In heterologous PCA titration, the allergen preparation was found to be 32 times more allergenic than the allergoid preparation. By intravenous chaled that treatment of allergen preparations with formaldehyde led to a preparation with the properties of an allergoid. In addition, it was found that the carbohydrate fraction of the refined allergen preparation of timothy a reduction in blood pressure. Thus, the allergen preparation was at least 50 times more potent in inducing systemic anaphylaxis in sensitized rats than the allergoid preparation. In the histamine release assay of grass-sensitive human leukocytes, approximately 1,000 times more allergoid protein than allergen protein was required to achieve 30% histamine release. Although to different degrees, in all three test systems in could be demonstrated that treatment of allergen preparations with formaldehyde led to a preparation with the properties of an allergoid. In addition, it was found that the carbohydrate fraction of the refined allergen preparation of timothy pollen decreased the blood pressure even in nonsensitized animals. The effect of this carbohydrate fraction on blood pressure was immediate but short-lived and immunologically nonspecific.

Measurement of alum precipitated allergen extracts of RAST inhibition methods.

The feasibility of measuring the allergenic activities of alum precipitated pollen extracts by means of the radioallergosorbent test (RAST) was investigated. Different batches of aqueous and alum precipitated birch and mixed grass pollen extracts were used as antigens. The alum precipitates could be readily dissolved with 0.1 M EDTA (pH 9.0) without any loss in allergenicity. No significant differences in RAST activities of undissolved and dissolved alum precipitated allergen extracts could be detected in terms of ability to inhibit the binding of allergen specific IgE to solid-phase allergens.

Measurement of 'blocking antibodies' to pollen antigens by radiolabelled protein A from Staphylococcus aureus.

Radiolabelled protein A from Staphylococcus aureus (125I-SpA) was utilized to measure the relative concentrations of the so-called 'blocking antibodies' (BA) in sera from patients subjected to two different forms of desensitization therapy. In addition, sera from rabbits immunized actively with pollen antigens were assayed. Antigens coupled to CNBr-activated papear discs were used as solid phase, and BA bound to the solid-phase antigens were detected by 125I-SpA. The results obtained with this technique correlated excellently with those of a double-antibody technique for IgG, indicating the 125I-SpA assay to be suitable for the measurement of the antigen-specific IgG. The BA concentration in sera from patients subjected to conventional injection therapy increased significantly during the treatment period, whereas no increase could be detected in sera from patients subjected to sublingual treatment. The increases in BA concentrations of rabbit antisera to pollen antigens could be readily traced by this technique.

Purification of birch pollen allergen extract by gel filtration. I. Chemical and immunological characterization of the fraction.

Birch pollen extract was fractionated by gel filtration on a Sephadex G-75 column. The physicochemical characterization of fractions included the determination of protein, carbohydrate, molecular weight and pI. The immunological properties of the fractions were measured by skin prick testing of allergenic individuals and by indirect RAST. The cross-reactivity of the fractions was investigated by heterologous PCA in rats after producing specific reaginic sera in mice. The allergenically most active fractions were composed mainly of proteins with a molecular weight range of 10,000--50,000 daltons. These active fractions represented only 3% of the total protein and carbohydrate content of the crude extract. These results indicate that it is possible to purify birch pollen allergen extract from the bulk of nonallergic contaminants, mainly low molecular weight carbohydrates, by a single step gel filtration procedure.