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Biomedical subjects

G Kunkel

Publications and source records attributed to G Kunkel.

At least 91 records · Page 5Linked to original sources
PubMed1991

Nasal challenge studies with bradykinin: influence upon mediator generation.

Previous studies have shown that nasal allergen provocation leads to dose-dependent increases of inflammatory mediators, e.g. histamine, kinins, LTC4 and PGD2 in nasal lavages. To investigate further the interaction of these mediators, a titration study with intranasal bradykinin (Bk) application (maximal dose 100 nmol/nostril) and consecutive lavage were performed in eight grass-pollen-allergic patients out of season, and five controls. The nasal lavages were analysed for albumin, N-alpha-tosyl-L-arginine methyl ester (TAME) esterase activity, histamine, 9 alpha,11 beta-PGF2, and LTC4. The clinical reactions were measured with a subjective symptom score. A dose-dependent elevation of albumin was found which was significantly higher in patients with allergic and non-allergic rhinitis compared with normal volunteers. TAME-esterase activity also increased in relation to the dosage of Bk given without significant difference between the various groups. No influence on histamine, LTC4 and 9 alpha,11 beta-PGF2, release (PGD2 metabolite) was seen. Short-lasting clinical symptoms like irritation, sneezing, and obstruction were noticed after the two highest Bk dosages (10 and 100 nmol). We conclude that intranasally applied Bk induces a dose-dependent plasma leakage into the nasal cavity, which is significantly higher in patients with seasonal allergic rhinitis out of season compared to normals. Bk does not seem to affect the mast cell since histamine, LTC4 and 9 alpha,11 beta-PGF2 levels do not alter. The ability to induce relevant symptoms of rhinitis provides strong support for the hypothesis that kinins may be important mediators of inflammatory disorders of the upper airways.

Adult↗
PubMed1991

Occupational wood-dust sensitivity from Euonymus europaeus (spindle tree) and investigation of cross reactivity between E.e. wood and Artemisia vulgaris pollen (mugwort).

A 44-year-old goldsmith suffered from rhinitis and conjunctivitis after having worked with wood dust from Euonymus europaeus (E.e.) for 15 years. The material was used for drying pieces of jewelry. Very strong reactions could be seen after friction test, scratch test and nasal challenge using wood dust of E.e. RAST-class 3 could be measured with the serum of this patient using E.e. wood and Artemisia vulgaris (A.v. pollen) allergen disks. RAST-inhibition, western-blot (WB) and immunoprint (IP) indicated common allergens in extracts of E.e. wood and A.v. pollen of different degree. In addition this study indicated that subjects suffering from A.v. pollen allergy also show sensitization to E.e. wood since in 22 of 37 A.v. pollen allergies A.v. (RAST class 2-4) IgE-antibodies could be seen. The present case probably demonstrates for the first time an IgE-mediated type I allergy to E.e. wood.

Adult↗
PubMed1991

Population genetics of the Malmö polymorphism of coagulation factor IX.

The distribution of 1,198 Malmö alleles was examined in 822 men from 16 indigenous populations and 188 women from 7 of the ethnic groups. Subjects were from several European countries, the Mediterranean, East Asia, and the USA (Anglo- and African-Americans). The frequencies of the rarer (Malmö B) allele were approximately equal across Europe, the highest frequencies (0.36) being in the French and Anglo-Americans; no population was observed with clearly the highest frequency. They diminished slightly at moderate distances from Europe (Tunisia, Ethiopia) and greatly at longer distances (East Asia and West Africa). In Orientals, the frequencies ranged from 0.07 (East Indians) to 0.03 (the Chinese) and from 0.0 to 0.15 in African-Americans. Assuming selective neutrality, the data are consistent with the European origin of the 'B' allele when the population was small and outward spread.

Africa, Northern↗
PubMed1991

Presence of vasoactive intestinal peptide receptors in nasal mucosa.

In recent years several tachykinins have been identified in the airway sensory nerves. Since the physiological and pathophysiological effects of neuropeptides depend on their functionally relevant concentrations and presence of specific receptors in the target tissue, specimens of enlarged turbinates and nasal polyps were removed in 11 patients and examined for the presence of vasoactive intestinal peptide (VIP) receptors. An intensive color reaction was observed in the cytoplasm of the tubular mucosa cells in polyps and turbinates as well as in the epithelium and submucosal glands. Since both these tissues reacted with VIP receptor antibody, noncross-reacting antibody against dendritic reticular cells (DRC 6-B7), nonspecific binding is possible, however it also must be speculated that the unspecific binding is overlaying specific binding. In addition a large number of cells located diffusely or in close association in the subepithelium and interstitial tissue stained only with VIP-specific antibody, indicating specific receptor binding. The color reaction is limited to the cell membrane and the cytoplasm of these cells was clearly eosinophilic. These cells were located in close proximity of the blood vessels, very indicative for active migration. Since VIP-positive nerves are also located near the blood vessels an activation process of these cells with subsequent release of enzymes and other active proteins is possible, thus influencing the inflammatory response.

Adult↗
PubMed1991

The possible role of substance P in the allergic reaction, based on two different provocation models.

It was shown in two different provocation models (nasal and bronchial provocation) that substance P (SP) may play an important role in the neurogenic inflammatory response in upper and lower airway disease. (1) Pretreatment with SP augments the antigen challenge response of the nasal mucosa. (2) The baseline bronchoalveolar lavage (BAL) concentrations of SP are elevated 8-fold in allergies (pollen asthma) as compared with normals, even outside of season. (3) The SP concentration in BAL increases significantly (p less than 0.05) after bronchial allergen provocation. These findings support a previous hypothesis of an abnormally elevated activity of nonadrenergic-noncholinergic excitatory nerves and are in accordance with the results of a decreased activity of neutral endopeptidase exaggerating neurogenic inflammatory responses in the airways, including bronchomotor tone hyperresponsiveness.

Adult↗
PubMed1991

IgE-mediated inhalant allergy against human corticotropin-releasing hormone.

A 25-year-old female developed IgE-mediated sensitization against human recombinant corticotropin-releasing hormone (CRH) with symptoms of allergic rhinoconjunctivitis and bronchial asthma. The occupational allergy was proved by positive skin prick test, bronchial provocation, dose-dependent histamine release, RAST measurements with CRH allergen (RAST class 3) and RAST inhibition. Using the immunoblot technique, a single allergen band with a molecular weight of less than 14.4 kD in the range between the isoelectric point 5.2 and 5.7 was detected for the CRH extract. Since no endocrinological and behavioral disorders were found, increased CRH-specific IgE was not able to influence the regulatory control of this neuropeptide. After 18 months of avoiding the occupational CRH exposure allergen-specific histamine release and RAST were negative.

Adult↗
PubMed1991

[Efficacy of a theophylline retard preparation administered at 3 different intake times additionally to basic medication].

In this randomised crossover study in 26 outpatients with bronchial asthma the efficacy of a new once-daily theophylline formulation given in addition to a baseline medication was investigated; moreover, under steady state conditions, the effect of three evening intake times (6, 8 and 10 p.m.) on 24-hour pharmacokinetics and peak-expiratory flow profiles was evaluated. The theophylline dose had been individually titrated. The pharmacodynamic results show a marked improvement in 24-hour lung function data after adding theophylline to a drug therapy including inhalative anti-cholinergics in 50% of the treated outpatients. No significant differences between the pharmacokinetic characteristics and the 24-hour averages (mesors) of peak expiratory flow at the three different intake times 6, 8 and 10 p.m. were found; however, intake at 10 p.m. resulted in the highest nocturnal excess of serum theophylline concentrations and the highest peak expiratory flow during the early morning hours between 2 and 6 a.m.

Adult↗
PubMed1991

[Long-term stability of morning serum theophylline level in asthma patients under minimally 1-year therapy with Euphylong].

The long-term stability of morning serum theophylline concentrations (STC) and peak expiratory flow (PEF) was investigated for at least one year in 21 asthmatic patients who received individualised theophylline doses in addition to a baseline medication (beta 2-agonists, corticosteroids, anticholinergics by MDI). All patients had previously participated in a randomised crossover study with the new sustained-release theophylline formulation Euphylong, so that 24-hour steady-state STC profiles were available. During the 15 (13-18) months' follow-up, the theophylline dose was increased by about 6% on average; the largest increase of 33% (from 750 mg to 1000 mg) occurred in 4 patients. The morning STCs between 8 and 9 a.m. were intra-individually averaged over the longest interval with a constant dose; median and range were 11.6 (9.7-15.8) mg/l. The coefficient of variation was less than 10% in 8 patients and between 11 and 20% in 10 patients. The corresponding peak-flow values were 474 (239-622) l/min with a coefficient of variation of up to 10% in 16 patients and between 11 and 20% in 3 patients. The long-term study over more than one year confirmed the reproducibility of the Euphylong plateau profile previously found in controlled short-term pharmacokinetic studies and clinical trials.

Adult↗
PubMed1990

Influence of histamine H3-antagonists on human leukocytes.

To determine the role of the histamine H3-receptor on basophils, different specific H3-antagonists were investigated. Incubation of washed leukocytes with N alpha-acylated histamine-derivatives (N alpha-ahd) induced elevated histamine levels. This process turned out to be dependent on dose, time and temperature, but independent of Ca2+ and Mg2+ ions. IgE-mediated histamine release was not modulated. [3H]-L-histidine was not decarboxylated into [3H]-histamine in spite of the observed histamine increase. Highly purified basophils did not show any histamine elevation but purified neutrophils and eosinophils were found to have increased histamine levels even after disintegration and subsequent incubation with N alpha-ahd. It seems that the increased histamine levels result from the cleavage of the applied histamine amides. Other potent H3-antagonists (e.g. thioperamide) neither produced increased histamine levels nor influenced IgE-mediated release from basophil leukocytes. The existence of H3-receptors on human basophils therefore seems unlikely.

Basophils↗
PubMed1990

Efficacy of sustained release theophylline given at three different evening intake times in addition to a baseline medication.

In this randomized crossover study of 26 outpatients with bronchial asthma the efficacy of a new once-daily theophylline formulation given in addition to a baseline medication was investigated; moreover, under steady state conditions, the effect of three evening intake times (6, 8 and 10 p.m.) on 24 h pharmacokinetics and peak-expiratory flow profiles was evaluated. The theophylline dose had been individually titrated. The pharmacodynamic results show a marked improvement of 24 h peak expiratory flow values after adding theophylline to a drug therapy including inhalative beta 2-agonists and corticosteroids in nearly all and inhalative anticholinergics in 50% of the treated outpatients. No significant differences between the pharmacokinetic characteristics and the 24 hr averages (mesors) of peak expiratory flow at the three different intake times 6, 8 and 10 p.m. were found; however, intake at 10 p.m. resulted in the highest nocturnal excess of serum theophylline concentrations and the highest peak expiratory flow during the early morning hours between 2 and 6 a.m.

Asthma↗
PubMed1989

Evaluation of the efficacy and safety of loratadine in perennial allergic rhinitis.

Loratadine, a new nonsedating antihistamine, was evaluated for efficacy and safety in 228 patients with perennial allergic rhinitis. Taken at a dose of 10 mg once daily, loratadine was significantly more effective than placebo and comparable to terfenadine, 60 mg taken twice daily, in reducing combined symptom scores in this patient population. Efficacy was maintained throughout the 28-day course of treatment. The overall incidence of side effects with loratadine was low (14%) with few occurrences of sedation (3%) and dry mouth (4%).

Adolescent↗
PubMed1988

Arachidonic acid metabolites and their circadian rhythm in patients with allergic bronchial asthma.

The aim of this study was to investigate circadian variation in concentrations of arachidonic acid (AA) metabolites in relation to the circadian pattern in bronchial patency. Blood samples were obtained at 4-hr intervals from 2000 of 1 day until 1400 of the next from 12 diurnally active asthmatic and six diurnally active non-asthmatic patients. Bloods were analyzed for the prostanoids thromboxane A2 (measured as stable metabolite 6-keto-PGF1a), PGE2 and PGF2a. Airways patency was assessed by self-measurement of peak expiratory flow (PEF). In asthmatics, circadian variation was detected in PEF as well as PGE2 and TXB2. The circadian trough of the PEF rhythm closely coincided with the circadian peak of the PGE2 and TXB2 rhythms. In the controls, the PEF was not circadian rhythmic. Of the AA metabolites only 6-keto-PGF1a exhibited 24-hr bioperiodicity in the controls. The controls exhibited a significantly higher circadian mean of PEF (P less than 0.001), while the asthmatics had a lower 24-hr average PGE2 but greater mean TXB2/PGE2 ratio. The obstructive effect caused by the overall 24-hr deficiency of PGE2 in asthmatics is possibly amplified by the increased of TXB2 during the early morning hours. This dissociation of the temporal patterns in TXB2 and PGE2 levels over the 24 hr is discussed as a characteristic finding for asthmatics.

Adult↗
PubMed1988

Biochemical and cellular basis for circadian rhythms in obstructive lung disease and implications for theophylline therapy.

In the majority of patients one of the primary features of bronchial asthma is the occurrence of nocturnal symptoms. There are significant bioperiodicities for hormonal, neural, cellular and humoral factors and for mediators, which are all in favour of reducing bronchial patency during the night. In the morning hours between 2 and 6 a.m. the histamine concentration shows a peak, the adrenaline and cyclic AMP have their minimum, while the cortisol secretion with its delayed onset of action is already ascending. The kallikrein kinin system is activated by histamine. Circadian variations have also been found for the receptor density of beta-receptors, cAMP, adenylcyclase and phosphodiesterase. While circadian rhythms are not known for the platelet activating factor (PAF) at the present time, the known nocturnal peak of thromboxane A2 may influence PAF-liberation as well. The bronchodilating metabolite of the cyclooxygenase pathway, PGE2, was found to have depressed levels during the night. Total plasma, total protein as well as IgA, IgM, IgG and IgE have a minimum during the night, cellular elements like T11-, T4-, B-lymphocytes and Leu8 have a maximum. Slow release theophylline is today the most important drug for nocturnal asthma. Theophylline is known to interfere with histamine release from mast cells, mediator release of arachidonic acid metabolites, the cyclic AMP concentration and suppressor cell activity. Important work remains to be done to clarify the therapeutic and immunological role of theophylline in nocturnal asthma and to identify the subgroups of patients having the greatest benefit of theophylline treatment.

Asthma↗
PubMed1987

Results of biological standardization with standardized allergen preparations.

The aim of biological standardization (BS) is to equilibrate the activity (potency) of allergen extracts from different source materials. This was done by performing skin prick tests (SPT) on patients who were sensitive to one of the following 10 allergens: Birch, alder, hazel, timothy, rye grass, velvet grass, cultivated rye, mugwort, D. farinae and Cladosporium herbarum. Patient sensitivity varied within a range of three to four powers of ten for each allergen investigated. The weal size in each patient corresponding to that elicited by histamine 1 mg/ml was calculated using the model log (mean weal diameter) = a + b log (concentration). The correlation coefficients of the regression lines of the allergen dose response relationship were found to be greater than 0.85 in most cases. The median slope for all extracts was 0.24. The slope for Cladosporium was significantly steeper than that for pollens. The amount of material in microgram dry weight (d.w./ml) equal to 1000 biological units/ml (BU/ml) varied within a factor of three between species for all tested purified allergen preparations but Cladosporium. For Cladosporium, about 30 times more material was needed than for D. farinae. When using crude rather than purified material, it was necessary to use five to ten times more to elicit a reaction corresponding to 1000 BU/ml, but the difference was significant only for Cladosporium. The narrow range of allergen concentrations used by us as well as other investigators does not assure positive skin prick test results in all patients with clinical symptoms due to the allergen in question. Skin prick testing should therefore be done over a wide range of concentrations to improve the methods for BS.

Allergens↗
PubMed1987

Day-night patterns in bronchial patency and dyspnea: basis for once-daily and unequally divided twice-daily theophylline dosing schedules.

Asthma typically worsens overnight. Although 24-hr variation in environmental conditions may contribute to the worsening of dyspnea at night, this does not fully explain day-night patterns of this disease. Circadian (about 24-hr) rhythms in bioprocesses which influence airways patency constitute major contributory factors. The nighttime exacerbation of asthma may represent the influence of circadian bioperiodicities in bronchial patency, airways hyperreactivity to acetylcholine, histamine and house dust, and altered levels of several plasma constituents such as cortisol, epinephrine, histamine and cyclic AMP.

Asthma↗
PubMed1987

Chrono-optimization of the time of evening administration with unequally divided twice-daily theophylline.

The effect of different times of evening administration (2000 hr versus 2200 hr) of sustained-release aminophylline (Euphyllin CR) on pharmacokinetics and lung functions was investigated in 30 patients presenting with moderately severe asthma. The study protocol followed a randomized three-period change-over design including a placebo period. As the dosing of the investigated SR-formulation is circadian rhythm adapted, the major part of the daily dose, namely 2/3, is affected by the change in time of administration. With regard to the nocturnal peak expiratory flow (PEF), no statistically significant difference between the times of evening administration was detected. However, the concomitant requirement for corticosteroids and inhaled beta-2-mimetics complicates the assessment of the relative clinical efficacy of the major dosing of theophylline during the 24 hr even though this drug is usually not given as a monotherapy in severe patients with reversible airway obstruction.

Adult↗