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Biomedical subjects

B R Lindgren

Publications and source records attributed to B R Lindgren.

At least 37 records · Page 2Linked to original sources
PubMed1991

Enalaprilat, but not cilazaprilat, increases inflammatory skin reactions in guinea-pigs.

The inflammatory effects of enalaprilat and cilazaprilat were tested in an experimental model of ovalbumin-sensitised guinea-pigs. Enalaprilat, but not cilazaprilat, enhanced the ovalbumin-induced inflammatory skin responses. The effect of enalaprilat was dose-dependent. Enalaprilat significantly increased the skin content of substance P and histamine. Cilazaprilat did not alter the level of these inflammatory mediators. Enalaprilat, applied locally, but not cilazaprilat, enhanced the inflammatory reactions caused by intradermal injections of allergen and substance P. Both angiotensin converting enzyme (ACE) inhibitors enhanced the inflammatory skin response evoked by bradykinin. Our study strongly indicates that enalaprilat has pro-inflammatory properties, whereas the new long-acting ACE inhibitor cilazaprilat does not. This might give a better safety profile of cilazaprilat.

Allergens↗
PubMed1990

Statistical methods for determining risk factors of chronic otitis media with effusion.

We use logistic regression with paired Bernouilli outcomes to analyse data on subjects who have either one or two organs (e.g. ears) each of which may develop disease. In this model, subject-specific covariates are related to the probability of developing disease. The proposed method is applied to determine risk factors for chronic otitis media with effusion.

Analysis of Variance↗
PubMed1990

Morphometric studies of the continuum of otitis media.

Morphometric changes in the epithelium and subepithelium of the middle ear mucosa from children younger than 10 years of age were measured at the promontory in 85 temporal bones with otitis media and in 29 normal temporal bones by use of quantitative and semiquantitative methods. Comparisons of morphologic analysis in different otitis media types showed that acute inflammatory changes were usually seen in purulent otitis media with effusion and serous otitis media with effusion, and chronic inflammatory changes were more severe in mucoid otitis media with effusion and chronic otitis media. There were overlaps, however, in histopathologic findings between different types of otitis media that suggest a continuum of otitis media types, with one type of otitis media changing into another type.

Child↗
PubMed1989

ACE-inhibitor-induced enhancement of spontaneous and IgE-mediated histamine release from mast cells and basophilic leukocytes and the modulatory effect of capsaicin sensitive nerves.

Frequently reported adverse inflammatory skin and airway reactions have been reported in subjects being medicated with angiotensin converting enzyme (ACE)-inhibitors. Intradermally evoked wheal and flare reactions to ovalbumin, capsaicin and bradykinin, in ovalbumin sensitized guinea pigs, was previously demonstrated to be enhanced by pretreatment with the ACE-inhibitor MK 422 (the active parent diacid of enalapril). In vitro results from this study demonstrate that the ACE-inhibitor MK 422 degranulated guinea pig lung and skin mast cells as well as human basophils, and enhanced allergen-evoked histamine release. Local capsaicin pretreatment in vivo of guinea pig skin decreased spontaneous and allergen-triggered release of histamine in vitro from skin mast cells. No clear enhancing effect of MK 422 was seen on the allergen-triggered histamine release in vitro from capsaicin pretreated skin, and the spontaneous release was unaffected by the ACE-inhibitor. The allergen-triggered wheal and flare reaction in ovalbumin sensitized guinea pigs was potentiated by MK 422 and the late phase reaction of the inflammatory response was especially augmented. Capsaicin pretreatment of the guinea pigs abolished this late phase reaction as well as the inflammatory enhancing effect of MK 422. Our in vitro results from capsaicin pretreated skin indicate that the reduced inflammatory response in vivo in capsaicin pretreated skin is due not only to capsaicin induced depletion of neuropeptides from sensory nerves, but also to secondary degranulation of mast cells by one or more of these peptides.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Effects of ranitidine treatment on patients with asthma and a history of gastro-oesophageal reflux: a double blind crossover study.

Forty eight patients with moderate to severe asthma were enrolled in a double blind crossover study designed to evaluate the effects of ranitidine treatment, 150 mg twice daily for four weeks, on gastro-oesophageal reflux, asthma control, and bronchial reactivity. All 48 had a history of reflux symptoms and 27 had in addition reflux associated respiratory symptoms. Thirty two patients had objective evidence of acid reflux on 24 hour pH monitoring (pH of less than 4 for more than 1% of the 24 hours) and 27 patients had a positive result in the acid perfusion test. Reflux symptoms were significantly improved after ranitidine treatment. Ranitidine treatment was associated with modest improvements in nocturnal asthma and daily use of inhaled bronchodilator drugs but there was no significant change in bronchial reactivity, lung function, peak flow, or the number of eosinophils in the blood. Comparisons between the effect of ranitidine treatment on asthma control were performed between patients with and without a history of reflux associated respiratory symptoms, with and without a positive result in the acid perfusion test, and with and without objective evidence of gastro-oesophageal reflux. A history of reflux associated respiratory symptoms was the only factor that predicted an improvement in asthma control after ranitidine treatment. These results indicate that antireflux treatment will produce only small improvements in asthma control in asthmatic patients with a history of gastro-oesophageal reflux.

Airway Resistance↗
PubMed1989

Increased bronchial reactivity and potentiated skin responses in hypertensive subjects suffering from coughs during ACE-inhibitor therapy.

The aim of this study was to investigate whether ACE-inhibitors could influence bronchial reactivity and interfere with inflammatory skin responses. Ten hypertensive subjects, who had reacted with coughs during ACE-inhibitor therapy, were treated in a double-blind crossover fashion for two weeks with enalapril and with placebo. Enalapril reduced the PC20 value for histamine and augmented the dermal response. Circulating eosinophilic leukocyte level in venous blood dropped markedly after the histamine bronchoprovocation performed during enalapril treatment. Plasma substance P was reduced after histamine provocation performed during placebo treatment, whereas this reduction was abolished by enalapril. In this study, we have demonstrated ACE-inhibitor-induction of moderately increased bronchial reactivity in subjects with suspected ACE-inhibitor-elicited coughs. It is suggested that coughing during ACE-inhibitor therapy is due to an increased inflammatory state in the airways.

Aged↗
PubMed1988

Randomization using packaged programs.

The problem of implementation of a randomization in controlled clinical trials is briefly discussed. A computer procedure is proposed and illustrated with simple programs using BMDP, SAS, and SPSS.

Clinical Trials as Topic↗
PubMed1988

New aspects on inflammatory reactions and cough following inhibiton of angiotensin converting enzyme.

The first inhibitor of angiotensin converting enzyme (ACE) was found in and isolated from the venom of the South American pit viper Bothrops jararaca. This was done after it was discovered that bites of the pit viper inhibit the breakdown of a proinflammatory peptide, bradykinin, in prey. Treatment with newly developed orally active ACE-inhibitors has been reported to cause symptoms such as adverse skin reactions, angioneurotic oedema, coughs and, in asthmatics, rapidly decreasing lung function. In this thesis the ACE-inhibitor MK 422 (active parent diacid of enalapril) was demonstrated to potentiate wheal and flare reactions induced by allergens, bradykinin or capsaicin, and to increase infiltration of "inflammatory cells", like eosinophils and neutrophils, into inflammatory dermal test sites in sensitized guinea pigs. MK 422 also augmented spontaneous and allergen-triggered histamine release in vitro from guinea pig skin and lung tissue. Capsaicin "desensitization" of guinea pig skin markedly reduced the wheal and flare reactions to allergens and attenuated the proinflammatory effect of the ACE-inhibitor. The histamine release in vitro from capsaicin-pretreated skin was also decreased, and no clear potentiating effect of MK 422 was demonstrated. In man, enalapril augmented anti-IgE-induced wheal and flare responses and increased bronchial reactivity to histamine. The drop of circulating eosinophils in venous blood was more pronounced after the provocations performed during enalapril treatment, and plasma substance P tended to increase. The alpha 2-adrenoceptor agonist clonidine, known to attenuate "neurogenic inflammation", reduced the wheal and flare reactions in guinea pig skin and decreased infiltration of neutrophils and eosinophils into inflammatory test sites. Furthermore, clonidine abolished the proinflammatory effect of MK 422 on the allergen- evoked wheal and flare reactions in guinea pig skin without counteracting the blood pressure lowering effect of the ACE-inhibitor. Contrarily, an additive hypotensive effect was demonstrated when clonidine was combined with MK 422. It is suggested that the proinflammatory properties demonstrated by ACE-inhibitors is due to augmentation of "neurogenic inflammation".

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Effects of an alpha-2 adrenoceptor agonist on angiotensin converting enzyme inhibitor-induced hypotension and potentiated allergen-evoked inflammatory skin responses.

Angiotensin converting enzyme (ACE) inhibitors have been demonstrated to possess proinflammatory properties. Persistent cough and increased broncho-obstruction have been reported frequently in hypertensive subjects on ACE inhibitor therapy. We have studied the effect of an alpha-2 adrenoceptor agonist, clonidine, on MK 422 (active parent diacid of enalapril)-induced hypotension and potentiated inflammatory skin responses in ovalbumin-sensitized guinea pigs. Clonidine was found to abolish dose-dependently MK 422-potentiated ovalbumin-evoked inflammatory dermal responses and it possesses additive hypotensive effects when combined with the ACE inhibitor. It would therefore be interesting to evaluate further alpha-2 adrenoceptor agonists and ACE inhibitors in a combination therapy in humans when single drug antihypertensive therapy of the drugs is insufficient.

Adrenergic alpha-Agonists↗
PubMed1987

Potentiation of inflammatory reactions in guinea-pig skin by an angiotensin converting enzyme inhibitor (MK 422).

There have recently been reports of persistent cough and increased broncho-obstruction likely to have been induced by ACE inhibitors. In order to study the effect of MK 422 (the active parent diacid of enalapril) on the inflammatory response, ovalbumin-sensitized guinea-pigs were tested intradermally with ovalbumin, capsaicin and bradykinin. All inflammatory responses were enhanced by treatment with MK 422 for 2 days prior to testing as compared to the responses of control animals. Infiltration of neutrophils, eosinophils, basophils and monocytes was increased following ovalbumin challenge in the MK 422-treated animals. We suggest that skin reactions and airway symptoms noticed during ACE inhibitor therapy might have been due to induced or potentiated inflammatory reactions in the skin or in the bronchial wall.

Allergens↗
PubMed1987

Inhibitory effects of clonidine on allergic reactions in guinea-pig skin.

An experimental guinea-pig model was used to show that clonidine inhibited dose dependently the wheal and flare reaction to i.d. ovalbumin in sensitized animals. The effect of clonidine was counteracted by an alpha 2-adrenoceptor antagonist, yohimbine, but not by an alpha 1-adrenoceptor antagonist, prazosin. An H1-receptor antagonist, clemastine, initially reduced the wheal and flare reaction but did not influence the effect of clonidine. Cimetidine, an H2-receptor antagonist slightly reduced the effect of clonidine on the wheal and flare reaction. It is suggested that clonidine reduces the wheal and flare reaction by stimulating alpha 2-adrenoceptors, which inhibits the axon reflex of the response.

Animals↗
PubMed1987

Inhibitory effects of clonidine on the allergen-induced wheal-and-flare reactions in patients with extrinsic asthma.

We investigated the possibility that clonidine, an alpha 2-adrenoceptor agonist, can reduce the wheal-and-flare reactions induced by intradermal injections of allergen in patients with extrinsic asthma. Ten adult subjects with asthma with positive skin tests to one or several pollens were selected. They received, in random order and double-blind manner, clonidine (two doses, each 75 micrograms) or placebo for 3 days, and then, after a 1-week washout period, they crossed over to the other treatment for 3 days. Treatment with clonidine reduced the area of wheal-and-flare reaction induced by allergen without significantly changing the blood pressure or the plasma cortisol level. There was a drop in the histamine content of leukocytes and in the number of eosinophils in peripheral blood after allergen challenge during the placebo treatment, whereas clonidine prevented these changes. The results suggest that treatment with clonidine can reduce the inflammatory reactions induced by allergens in subjects with extrinsic asthma.

Allergens↗
PubMed1987

Effects of some antihypertensive drugs on cutaneous blood flow and inflammatory skin responses following allergen challenge in guinea pigs.

The effects of the antihypertensive drugs clonidine, prazosin, and MK 422 (the active parent diacid of enalapril) were studied on the cutaneous blood flow and allergen evoked inflammatory skin reactions in ovalbumin sensitized guinea pigs. The hypotensive effect of the drugs did not significantly change the basal cutaneous blood flow at the time of allergen challenge. MK 422 (0.02 mg/kg) markedly enhanced the wheal and flare reaction following allergen challenge, whereas clonidine (0.005 and 0.05 mg/kg) inhibited the inflammatory response. Prazosin (0.03 mg/kg) did not significantly influence the wheal and flare reaction. Our results indicate that some antihypertensive drugs (clonidine) could be beneficial to antihypertensive patients with inflammatory diseases, while others (ACE-inhibitors) may enhance their inflammatory disorders.

Allergens↗
PubMed1987

Effects of clonidine on the dermal inflammatory cell response of experimental toxic and allergic contact reactions and intradermal hypersensitivity.

In previous studies, the alpha 2-adrenoceptor agonist clonidine has been shown to suppress the wheal and flare reaction in guinea pigs sensitized to ovalbumin. This phenomenon has been further studied with special reference to effects on the dermal inflammatory cell infiltrate and mast cells. Clonidine lessens the degranulation of mast cells seen in control untreated immediate hypersensitivity reactions. Less neutrophils and eosinophils arrive to the treated reactions. Basophils and mononuclear cells (chiefly lymphocytes) which characterize the late phase of the wheal and flare reaction were not influenced by clonidine. Clonidine had a possible minimal effect on allergic contact (delayed hypersensitivity) reactions. The toxic contact reaction to croton oil (nonspecific cutaneous inflammation) was not affected.

Animals↗
PubMed1987

Comparison of the effects of clonidine and guanfacine on the histamine liberation from human mast cells and basophils and on the human bronchial smooth muscle activity.

The inhibitory effects of clonidine and guanfacine on antigen-induced histamine release from human basophils and mast cells and on bronchial muscle tension were compared. Clonidine, but not guanfacine inhibited the antigen-induced histamine release from human basophils and mast cell preparations. This effect of clonidine was prevented by an H2-antagonist, cimetidine. Clonidine and guanfacine, like norepinephrine, inhibited the twitch contraction of electrically stimulated human segmental bronchi by stimulation of alpha 2-adrenoceptors. Clonidine and guanfacine had no effects on the basal bronchial muscle tone, but in very high concentrations they could reduce a carbacholine-induced bronchial tone. It is suggested that the inhibitory effects of clonidine on allergic reactions and on exicitatory nerve transmission in human airways may be useful in the treatment of asthmatic patients.

Adrenergic alpha-Agonists↗
PubMed1986

Inhibitory effects of clonidine on bronchospasm induced in guinea-pigs by vagal stimulation or antigen challenge.

The effects of clonidine on the bronchospastic responses induced by vagal stimulation or antigen challenge were studied in anaesthetized guinea-pigs. Electrical stimulation of the vagus nerves by 2-4 Hz induced a vigorous, mainly atropine-sensitive bronchoconstriction, which was strongly inhibited by clonidine (0.05 mg/kg i.v.). The inhibitory effect of clonidine was significantly reduced by the alpha 2-adrenoceptor antagonist yohimbine (1 mg/kg i.v.). Another series of experiments was done with ovalbumin-sensitized guinea-pigs. Respiratory anaphylaxis was induced by antigen inhalation resulting in an increase of pulmonary resistance from 100% (baseline) to about 190% in the control group. Animals pretreated with a clonidine aerosol (0.03%) showed a marked inhibition of the bronchospastic response. It is suggested that the inhibition of the bronchospastic responses induced by clonidine may be mediated by a stimulation of alpha 2-adrenoceptors, which exerts an inhibitory control of the excitatory vagal activity in the guinea-pig airways.

Anaphylaxis↗