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Biomedical subjects

L J Youlten

Publications and source records attributed to L J Youlten.

At least 19 recordsLinked to original sources

The incidence and nature of adverse reactions to injection immunotherapy in bee and wasp venom allergy.

The incidence, time course and nature of systemic reactions to injections of bee and wasp venom during immunotherapy have been estimated in an open, prospective, single centre study. One hundred and nine survivors of moderate to severe systemic reactions to stings from hymenoptera, received courses of bee or wasp venom by monthly subcutaneous injection for up to 3 years. Systemic reactions were recorded after 7.5% of 946 weekly venom injections during the initial phase of treatment, and after 2.1% of 1789 monthly maintenance injections. In both phases of treatment, reactions were more frequent after bee (17% of initial phase, 7.8% of maintenance treatment) than after wasp (3% of initial phase, 0.3% of maintenance treatment) venom injections. The percentage of patients experiencing at least one reaction was also higher for bee (46%) than for wasp (14%) sensitive patients. Over 80% of reactions began within 30 min of injection, over 90% within 1 h and only two (2%), between 1 and 2 h, the remaining six (5.5%) starting more than 2 h after injection. Only 0.47% of venom injections produced a systemic reaction which was severe enough to require adrenaline treatment. The female patients experienced more reactions (21% of the wasp, 60% of the bee, sensitive) than the males (5.5% wasp, 20% bee). Age and atopy did not appear to be significant risk factors for systemic reactions. We conclude that wasp and bee venom immunotherapy in a conventional dosage regimen was generally well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Plasma concentrations and urinary excretion of histamine after inhalation and subcutaneous injection of histamine.

1. Increased histamine concentrations are found in the plasma and urine following allergen challenge in allergic subjects. This study compared a controlled challenge with clinically relevant doses of inhaled and injected histamine, as indicative of an allergic response, in an attempt to validate the use of urinary histamine or 1-methylhistamine measurements as an objective, non-invasive diagnostic test. 2. Inhalation of histamine produced peripheral vasodilation, increased heart rate, a fall in partial expiratory flow rate (pEFR) and blood pressure, 'tight chest' and cough. Subcutaneous injection produced vasodilation and headache but no change in heart rate or blood pressure. 3. Plasma histamine concentrations were similar in the two studies. Inhalation of increasing doses of histamine through a nebuliser (output 0.13 ml min-1) resulted in an increase from a mean of 0.30 to 1.65 ng ml-1, with return towards baseline within 20 min. Injection of 1 mg histamine s.c. produced an increase from 0.32 to 1.4 ng ml-1 within 5 min, remaining above 1 ng ml-1 for 30 min. 4. There was a significant increase of 15.2 ng mg-1 creatinine in urinary histamine concentration following the injection of histamine (P = 0.04) and an increase of 11.4 ng mg-1 creatinine when histamine was given by inhalation (P = 0.18). Histamine excretion rate increased by 108 ng min-1 (P = 0.04) after inhalation and by 37.2 ng min-1 (P = 0.09) after injection. Urinary 1-methylhistamine concentrations were significantly raised following both histamine inhalation (+ 238 ng mg-1 creatinine; P = 0.013) and injection (+ 180 ng mg-1 creatinine; P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation

Hyposensitization therapy of Parietaria-sensitive patients with a tyrosine adsorbed allergoid, Pollinex Parietaria (Bencard Parietaria).

Thirty patients suffering from allergy to Parietaria pollen were treated with either a new tyrosine-adsorbed allergoid of Parietaria judaica pollen (Pollinex Parietaria) or a commercially available alum-adsorbed extract (Alavac) as control. A reduced response to nasal provocation was seen in 7 out of 11 patients following treatment with Pollinex and 1 out of 10 after control treatment. 9 out of 11 and 3 out of 10, respectively, showed reduced skin test activity. Patients who received Pollinex tended to have fewer nasal symptoms during the pollen season. Pollinex induced larger increases in P. judaica-specific IgG antibody than did the control product. Side effects of therapy were similar between the two groups of patients. Pollinex Parietaria thus shows good potential for the control of allergy to Parietaria pollen.

Adult

Pollinex Parietaria (Bencard Parietaria), a new allergoid for treatment of patients sensitive to Parietaria pollen.

Two matching groups each of eleven patients suffering from allergy to Parietaria pollen were treated either with tyrosine-adsorbed glutaraldehyde-modified extract of Parietaria judaica pollen (Bencard Parietaria/Pollinex Parietaria) or with alum-adsorbed pyridine-extract (Alavac). The side effects of therapy were similar in both groups and were mostly local in nature. Nasal symptoms were significantly less at the end of treatment in the group of patients treated with Pollinex. P. judaica-specific IgG levels were significantly higher in patients following treatment with Pollinex. The majority of patients in both groups showed reduced nasal and/or skin sensitivity following therapy as measured by provocation testing. The results indicate that Pollinex Parietaria is an effective vaccine for the treatment of immediate hypersensitivity to Parietaria pollen.

Adult

IgG and IgE antibodies after immunotherapy with bee and wasp venom.

IgG and IgE antibody levels have been followed for a period of 2 years in patients receiving immunotherapy with bee and wasp venom. 106 adult patients who had had anaphylactic reactions to wasp stings had initially low IgG antibody levels to wasp venom which rose with therapy (p less than 0.001). IgE antibody levels also showed an initial rise but subsequently fell (p less than 0.001). The pattern was similar to that previously reported in children who had had anaphylactic reactions to bee stings, but who, after a course of immunotherapy, were able to tolerate stings with impunity. 60 adults who had had anaphylactic reactions to bee stings showed a different pattern, with initially high IgG antibody levels which did not rise further. Since two thirds of this group were beekeepers or members of beekeeper's families, the high initial IgG antibody levels could have been a response to the frequent stings to which such individuals are prone. The fact that high levels did not protect against anaphylaxis shows, however, that the classical concept of 'blocking antibody' is in need of revision.

Bee Venoms

Histamine release from peripheral blood leukocytes with purified bee venom allergens: effect of hyperimmune beekeeper plasma.

The response of 15 strongly bee-venom-allergic patients to highly purified venom allergens was compared using skin prick test titration, peripheral blood leukocyte (PBL) histamine release and radioallergosorbent test with three highly purified bee venom allergens: phospholipase (PLA2), hyaluronidase (HYAL) and acid phosphatase (ACID P). Sensitivity to the three allergens ranked in the same order for all three tests and in each case PLA2 was found to the most potent allergen. In the presence of hyperimmune beekeeper plasma, maximum histamine release was reduced significantly for all three allergens (p less than 0.001). Furthermore, hyperimmune beekeeper plasma increased the amount of allergen required for a comparable release of histamine (mean shift in dilution curve PLA2 917-fold; HYAL, 492-fold; ACID P, 61-fold). The release of histamine from whole blood was also compared with PBL + 10% normal human serum (NHS). For all three allergens maximum release was much lower from whole blood compared with washed cells + 10% NHS (p less than 0.001). These data confirm PLA2 as the major bee venom allergen by all three tests. Hyperimmune beekeeper plasma reduces maximum histamine release and increases its threshold. Histamine release in response to ACID P appears harder to block with hyperimmune beekeeper plasma than that provoked by PLA2 or HYAL (p less than 0.01). Whole blood releases less histamine and requires more allergen than washed cells, indicating that sensitivity of PBL in vivo is unlikely to be as great as washed PBL in vitro.

Adult

Studies in healthy volunteers can demonstrate bronchodilator activity of orally administered drugs.

A panel of healthy volunteers was screened by bronchial histamine provocation. The response used was the flow rate achieved during a partial forced expiratory manoeuvre at a lung volume 30% of the vital capacity above the residual volume. Those subjects who were relatively sensitive to the bronchoconstrictor effects of inhaled histamine took part in a reproducibility study. Those with consistent responses took part in a further study in which the bronchodilator, and bronchoconstriction-protective, effects of orally administered chlorpheniramine, terfenadine and salbutamol were investigated. The technique was able to demonstrate the efficacy of these drugs in non-patient volunteers. Thus it seems to be a suitable method for the early evaluation, in man, of certain drugs with an anti-asthma therapeutic potential. It also provides useful information on the dose and duration of action of compounds prior to the first efficacy trials in patients.

Administration, Oral

The generation and cellular distribution of leukotriene C4 in human eosinophils stimulated by unopsonized zymosan and glucan particles.

Human eosinophils (EOSs) stimulated under optimal conditions with 5 X 10(8) unopsonized zymosan particles at 37 degrees C for 30 minutes produced an average total immunoreactive leukotriene (LT) C4 of 1.6 ng per 10(6) EOSs, and 30% to 60% of the generated product remained cell associated. The dose-response characteristics of zymosan-induced LTC4 generation were different from those of phagocytosis, suggesting that the two events were independent. Pretreatment of EOSs with 10(-8) mol/L of formyl-methionyl-leucyl-phenylalanine for 30 minutes led to a twofold to fivefold augmentation of LTC4 generation by cells subsequently activated by unopsonized zymosan. Optimal EOS activation with 1 mumol/L of the calcium ionophore A23187 at 37 degrees C for 15 minutes produced more than 100 times greater quantities of LTC4 than with zymosan. The amount of immunoreactive LTC4 that remained cell associated after calcium ionophore A23187 stimulation reached a maximum after 5 minutes and then declined. Of the relatively small amount generated in the first minute, 71% was cell associated, but this figure declined to 9% after 15 minutes, by which time there had been a redistribution of the LTC4 to the supernatant. Inflammatory leukocytes may respond to zymosan because the cells recognize either one or both of its major polysaccharide components, glucan and mannan. Glucan, but not mannan, stimulated EOSs to generate LTC4 in a dose- and time-dependent manner. Under optimal conditions, there was no significant difference in the total quantities of LTC4 elaborated by EOSs stimulated by glucan and by unopsonized zymosan. This suggests that zymosan may induce leukotriene generation in the human EOS through a glucan recognition mechanism.

Calcimycin

Immunogenicity in guinea pigs and tolerance in grass pollen-sensitive volunteers of enteric-coated grass pollen allergens.

An acid-insoluble, methacrylic acid, methyl methacrylate copolymer (Eudragit L-100) was used to give an enteric coating to a grass pollen extract in order to protect it against gastric degradation. Substantial protection against the degradative effects of simulated gastric secretion was demonstrated using this preparation which was well tolerated by grass pollen-allergic volunteers. The enteric-coated allergen induced a greater secondary antibody response than did an aqueous presentation when administered orally to guinea pigs which had been primed previously by subcutaneous injection. This result indicates that an effective hyposensitisation regimen could consist of a short series of initial parenteral injections, followed by an oral course of the protected allergen.

Acrylic Resins

Plasma level of histamine in aspirin-sensitive urticaria.

Twelve patients with a history of aspirin-induced urticaria and/or angioedema were studied before and after the provocation of symptoms with aspirin. The resting plasma histamine levels in these patients (0.95 +/- 0.25 ng/mL) were significantly higher than in 30 control subjects (0.21 +/- 0.02 ng/mL) (P less than .0005) and nine patients with non-aspirin-sensitive urticaria (0.27 +/- 0.06 ng/mL) (P less than .01). The plasma histamine levels fell significantly at the time of adverse reactions to aspirin (P less than .01). The high resting histamine levels, like the high venous prostaglandin F2 alpha levels that we have previously reported in the same group of patients and the high plasma histamine levels we have found in aspirin-sensitive asthmatics suggest an abnormality of mediator release in aspirin-sensitive patients.

Adult

Assessment of nasal airway patency: a comparison of four methods.

Two established methods (active posterior and passive anterior rhinomanometry) and 2 new methods (peak nasal inspiratory flow rate and apparent nasal volume) were used in 12 volunteers to assess the patency of the nasal airways under each of 4 conditions (baseline, post-exercise, nasal histamine and nasal cocaine). All methods showed the congestant effect of histamine but the peak nasal inspiratory flow and apparent nasal volume techniques were more sensitive to the 'decongesting' manoeuvres, (exercise and cocaine). Useful objective quantitative data on the patency of the nasal airways and its changes in response to stimuli can be obtained by simple, cheap and readily available techniques. Subjective sensation is a poor guide to the state of patency of the nasal airways.

Adult

Type I allergy to egg and milk proteins: comparison of skin prick tests with nasal, buccal and gastric provocation tests.

Provocation tests with egg or milk antigens were performed on symptomatic patients or those who were skin prick test positive to these antigens. Skin test positive patients responded immediately in 12/13 to nasal, in 7/15 to buccal and in 5/15 to gastric provocation tests. An immediate gastric response was within 1 h. The threshold dose for a positive result showed that tissue sensitivity from greatest to least was in the order: skin, nasal, buccal and gastric. None of the skin test negative group responded to any of the provocation tests. The results, particularly the nasal provocation, validate the skin prick test as a sensitive measure of type I allergy to defined foods. The relative insensitivity of buccal and gastric mucosae may explain positive skin test responses in asymptomatic subjects.

Dose-Response Relationship, Immunologic

Effect of aspirin in "aspirin sensitive" patients.

Eighteen patients with a history of urticaria or asthma, or both, induced by aspirin were studied before and after provocation of symptoms with aspirin. The plasma prostaglandin F2 alpha concentration, which was characteristically raised before challenge, fell significantly at the time of adverse reactions. Repeated administration of aspirin up to a dose of 650 mg daily induced tolerance in most of the patients, and several developed bronchodilator responses to aspirin. Although median total IgE concentrations may be raised in patients with aspirin sensitivity, it appears likely that pharmacological rather than immunological mechanisms are chiefly responsible for the phenomena of aspirin sensitivity and desensitisation.

Adolescent

Skin and radioallergosorbent tests in patients with sensitivity to bee and wasp venom.

Intradermal (ID) and prick tests with bee or wasp venom (Pharmalgen) have been performed on 102 subjects with a history of adverse reactions to stings and forty-six control subjects giving no such history. Venom was diluted 100, 10 and 1 microgram/ml for prick testing and 10(-2), 10(-2), 10(-3) and 10(-4) micrograms/ml for ID injections. In forty-six control subjects all were tested with the highest concentration of prick testing solution (100 micrograms/ml), eight (17%) had positive reactions, a similar reaction rate to that reported in control subjects using 10(-1) micrograms/ml ID. In our 102 test subjects skin tests were therefore regarded as positive only if the reaction was elicited by 10 micrograms/ml or less by prick test of 10(-2) micrograms/ml or less ID. In general the results with skin prick tests and ID tests were comparable when the prick solution was 1000 times the concentration of that used for ID testing. ID tests were positive in thirteen with negative skin prick, seven of whom had detectable antibodies when tested by RAST. Conversely four with a positive skin prick test (two of whom were RAST positive) were considered negative on ID testing. As judged either by RAST or skin tests it appeared that sensitivity diminished with the time interval from the last sting (P less than 0.001).

Bee Venoms