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Anaesthesia and postoperative analgesia in older patients with chronic obstructive pulmonary disease: special considerations.

Chronic obstructive pulmonary disease (COPD) and older age are known to be independent risk factors for severe perioperative adverse outcomes after surgery. A basic understanding of the disease, careful preoperative evaluation and preparation of the patient, as well as a tailored anaesthetic management plan might help to decrease complications in this patient population. Aging affects the pharmacokinetics and pharmacodynamics of almost all drugs and therefore the dosage must be adapted in older patients. The type of anaesthesia (general versus regional anaesthesia) has no substantial effect on perioperative morbidity and mortality. Most patients, even with severe COPD, tolerate general anaesthesia without major problems. One important goal of the anaesthetic management is to prevent reflex-induced bronchoconstriction, which can be accomplished by the use of volatile anaesthetics. Early recovery can be facilitated by the use of short-acting drugs, such as propofol and the new opioid remifentanil. Judicious use of neuromuscular blocking agents is necessary because of the risk of residual paralysis, and those agents associated with histamine liberation should be avoided. Ventilation requires long expiration times to avoid air trapping, and hyperinflation to avoid the possible threat of pneumothorax and a decrease in cardiac output. For postoperative analgesia, a balanced regimen consisting of regional analgesia with local anaesthetics and NSAIDs should be preferred. This will enhance analgesia and reduce opioid toxicity, which is important in patients with COPD, where respiratory depression is especially dangerous.

Aged↗

Pharmacology of drugs for conscious sedation.

In endoscopic monitoring and treatment of gastrointestinal disease, it is important that patients will accept repeated examination. They are less likely to do so if the procedure is remembered as distressing or uncomfortable, as is likely when it is performed under topical anaesthesia alone. The aim of conscious sedation is a lightly sedated patient, who is awake, cooperative on demand, amnesic, and free from anxiety and fear. Various drugs in low doses can be used to meet these criteria. Among these are phenothiazines, butyrophenones, barbiturate and non-barbiturate hypnotics, benzodiazepines, and the hypno-analgesic, ketamine. As benzodiazepines offer both sedative and profound amnesic and anxiolytic effects, these drugs are used for conscious sedation worldwide. Diazepam has been the 'gold standard' of sedation, but the more modern benzodiazepines, particularly midazolam, are now more commonly used. In general, benzodiazepines demonstrate a broad therapeutic range. In accordance with dose, however, sedative drugs may induce side-effects, such as drowsiness, lowering of blood pressure, and respiratory depression. In addition, some may induce more wide-ranging side-effects, such as histamine liberation and anaphylactic reactions, thrombophlebitis, and pain on injection. They may have severe drug interactions when used in combination with local anaesthetics, hypnotics and opioids. In older patients, lower doses are necessary for sedation. Sedative drugs should be administered slowly, to avoid haemodynamic and respiratory side-effects.

Adult↗

Carboxamides and hydrazide of glycopeptide antibiotic eremomycin. Synthesis and antibacterial activity.

Carboxamides and hydrazide of glycopeptide antibiotic eremomycin were obtained by a direct reaction of the carboxy group of eremomycin with an appropriate amine or hydrazine using diphenyl phosphorazidate as a condencing agent. Eremomycin hydrazide was also obtained by hydrazinolysis of the eremomycin methyl ester. Use of dicyclohexylcarbodiimide or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide for amidation led to the corresponding eremomycin ureides. The ESI-MS data indicate that eremomycin and its amides exist as dimers. The carboxamide, methylamide and benzylamide of eremomycin were as active against Gram-positive bacteria as the parent antibiotic, and the methylamide, benzylamide and hydrazide were almost an order of magnitude more active than eremomycin against Staphylococcus epidermidis clinical isolates in vitro. Amide of eremomycin as well as ureides were devoid of histamine liberating properties, which demonstrates that protection of the carboxyl group leads to a decrease in the allergenic properties.

Amides↗

[Theories on the mode of action of desensitization].

Specific immunotherapy (SIT) has been practised successfully for about 80 years. In classic immunotherapy, an allergen-extract is repeatedly injected subcutaneously in increasing doses. A large number of clinically controlled studies have proved the efficacy of this kind of immunotherapy, while its mode of action is not precisely known yet. A successful SIT leads to an impairment of allergic symptoms (symptom score), and a concordant decrease in drug use. Furthermore, a reduced reactivity in specific dermal, nasal and bronchial provocation tests is induced as well as a diminished unspecific reagibility in the affected tissues. Several studies showed reduced values for allergen-specific IgE (serum) that followed an initial increase. A reduced immigration of eosinophils was found, both after provocation with allergen and during the pollen season, as well as diminished values of markers for the activity of eosinophils, e.g. eosinophil cationic protein (ECP). Also, a reduced allergen-induced histamine-liberation from mast cells and basophils has been reported. The underlying mechanism for these effects of SIT might be a reorientation of the allergen-induced lymphokine-production to a dominant TH1-cytokine-profile. Because the relation between the quantity of IL-4 and its regulator IFN-gamma controls the extent of IgE-synthesis by B-cells, the reorientation leads to a diminished production of IgE. IFN-gamma inhibits the differentiation of TH2-cells; by this less TH2-cells are present to help B-cells to produce IgE-antibodies, and to induce the differentiation of mast cells and basophils as well as immigration, differentiation and activation of eosinophils. Thus, the positive effects of SIT can be explained by the reorientation T-cell lymphokine profile. The mechanism under discussion for explaining this reorientation include: 1) an increased differentiation of allergen-specific CD4+ precursor-cells or a reorientation of established TH2-cells to the production of IFN-gamma, 2) the differentiation of IFN-gamma-producing CD8+ T-cells and of T-cells with receptors for T-cell-antigenes of the gamma, delta-type; and 3) the induction of an energy in TH2-cells.

Allergens↗

[Investigation on the mechanisms of leukocyte alteration in patients with intolerance to some drugs (with novocaine as a model)].

The mechanisms of novocain damaging action on blood cells in persons with increased sensitivity to this drug were studied in the leukocyte alteration test. The leading role of histamine liberated from basophils was established. The increased sensitivity to novocain was shown not to be passively transferred to the cells of healthy donors with patient serum with intolerance to the drug; moreover, the joint action of both cell-mediated and thermolabile humoral factors was found to be necessary for the realization of leukocyte alteration under the action of novocain. The comparison of the information content of a number of methods--skin testing, dosed provocation, leukocyte alteration test and chemiluminescence--for revealing increased sensitivity to novocain in 30 persons with adverse reactions to this preparation registered in their medical history. The two in vitro tests were shown to be comparable in their diagnostic significance with the method of dosed provocation.

Adolescent↗

[Actual problems of allergy in occupational pathology].

Data from different sources concerning the modern status of the allergy problem in the occupational pathology are represented. Features of immunologic pathogenesis in occupational respiratory tract diseases formation due to the simple and composite substances, protein denaturants, immune modulators and histamine-liberators organic and non-organic by origin are described. The most promising directions for the further investigation of the problem are stated and based.

Air Pollution↗

Alcohol consumption and risk-factors for ischemic heart disease in Chuckchi inhabitants: clinical, biological and population studies.

Clinical, biochemical and epidemiological research has shown variations of serum enzymatic constellations (relatively high level of GGT in Chuckchi natives compared to nonnative newcomers). This difference leads to different unspecific body resistance to exogenous factors, particularly to histamine-liberators. The GGT system has also been linked to alcohol-induced clinical IHD. Based on these findings patients will be screened for GGT activity, which may serve as a marker for population phenotypes representative of high-risk groups. This deficiency in GGT may indicate a high risk for alcohol-related heart disease.

Adult↗

Comparison of muscle relaxants in clinical use.

A prospective clinical comparison of d-tubocurarine, alcuronium, gallamine and pancuronium was performed in 400 surgical patients. Various parameters usually followed during clinical anaesthesia were recorded from the beginning of, to the recovery from anaesthesia. Endotracheal intubation was performed with or without suxamethonium. Intubation was always possible in 1-3 min when different muscle relaxants were used in the following initial doses: d-tubocurarine 0.4 mg/kg, alcuronium 0.3 mg/kg, gallamine 1.8 mg/kg, and suxamethonium 0.8 mg/kg. However, there was a statistically significant inferiority of the d-tubocurarine and gallamine groups. The use of suxamethonium seemed to shorten the duration of the initial dose of the nondepolarising agents and also to increase especially the dose of gallamine when calculated as mg/kg/h. It should be mentioned that the non-depolarising agents were given soon after suxamethonium without waiting for the return of spontaneous respiration. Pancuronium and alcuronium caused least changes in the cardiovascular parameters. Erythematous skin reactions were seen mostly after the use of d-tubocurarine and suxamethonium. This could depend on histamine liberating potency of these muscle relaxants.

Adjuvants, Anesthesia↗

Antihistaminic drugs in dermatology.

From the results of treatment of 1,770 patients with dermatologic diseases (1,458 as reported in the literature and 312 observed by the author) it is concluded that antihistaminic preparations are of great value in allergic diseases where it is hypothecated that liberated histamine is the offender, as in acute edematous types of urticaria, erythema multiforme, and some cases of allergic pruritus. The indiscriminate use of these drugs is to be avoided. Antihistaminic drugs are palliative-they do not cure. They often prolong the disease. They give temporary relief from swelling and pruritus. They develop no specific immunity and do not replace immunizing efforts. They do not replace or interfere with epinephrine or ephedrine.

Anti-Allergic Agents↗

Pulmonary hydatidosis in childhood. Review of 21 cases.

Spain is one of the countries with a very high incidence of hydatidosis in the childhood. It represents 16.8% of all cases intervened for thoracic surgery for hydatidosis cysts in our department during the last ten years with a total of 21 children (inferior to 14 years) operated due to hydatidosis. Cough and pain were the symptoms more frequently encountered. The ratio unruptured/ruptured cysts was 3/1, higher than in the adults, with an average of 2.62 cysts per patient. Specific immunoglobulin E and histamine liberation test were the most useful tests in the laboratory. The usual surgical technique was a cystopericystectomy with total extirpation of the parasite of its rests. No recurrence was found in the follow-up of our patients.

Adolescent↗

[Diagnosis of allergic rhinitis. I. Anamnesis--ENT medical examination--skin tests--intranasal provocation].

One of the most important factors in the diagnosis of allergic diseases of the nose is the history, which requires a detailed knowledge of the allergic disease, and of the personal and occupational environment of the patient. Skin tests usually confirm the allergens suggested by the history. If this is not the case, a further history must be taken with respect to the agents identified by the positive skin tests. Other additional investigations must be performed such as RAST, the human basophil degranulation test, the histamine liberation test and the intranasal provocation test (IPT) with anterior rhinomanometry. The guidelines of the working group on bronchial and nasal provocation tests of the German Society for Research into Allergy and Immunity for the performance of the IPT should be respected because they are reproducible and standardised.

Desensitization, Immunologic↗

[A mastocytoma of the liver--computed tomographic follow-up and biopsy].

CT findings of a mastocytoma of the liver are reported. Follow-up studies over 1 year showed density changes in both the pre- and postcontrast scan. Diagnosis was established by percutaneous CT-guided biopsy, which was complicated by a simultaneous anaphylactoid reaction, probably due to direct histamine liberation.

Adult↗

[Cyclic analogs of des-Arg9-[Leu8]bradykinin].

Four cyclic derivatives of des-Arg9[Leu8]bradykinin have been obtained by classical methods of peptide chemistry. They are cyclo-(-X-Arg-Pro-Pro-Gly-Phe-Gly-Pro-Leu-), where X=Lys or none, and cyclo-(Y-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Leu-), where Y= Lys or Orn. Peptide bonds have been formed by the pentafluorophenylester method, and cyclization has been carried out in a diluted dioxane solution with 40% yield. Subsequent cleavage of protecting groups was made by treatment with hydrogen fluoride. The products obtained were purified by droplet counter-current chromatography. These substances liberate histamine from the rat mast cells comparably to bradykinin and fail to produce myotripic and vascular effects.

Amino Acid Sequence↗

[Infection and asthma].

Infection is frequent in all stages and forms of asthma. It is a source of exacerbations of all degrees of severity. Bacterial infection, especially with commensal organisms from the upper respiratory tract, may cause bronchial hyperreactivity (HRB) by various mechanisms, specific--microbial delayed hypersensitivity, probably rate; IgE-dependent hypersensitivity others non-specific: bronchial inflammation, source of mediators of bronchial constriction; activation of complement, direct histamine liberation; beta blockage...; or mixed mechanisms. Respiratory viral infection probably plays the most important role in the natural history of asthmatic disease, especially in infants and young children by inducing or amplifying HRB and creating a transitory obstructive syndrome of the small airways. This virus-induced HRB may develop into a respiratory syncytial virus viraemia at first or remain latent found by tests of bronchial activity. The pathogenic mechanisms of this HRB are often multi-factorial and interlinked: they are chiefly linked to the various cytopathic effects of the virus on the respiratory epithelium, to the viral inflammation; but also to disturbance of the equilibrium of the autonomous nervous system (beta blockage, excitation of the cholinergic receptors); finally in some areas, to virus-induced amplification of the local and systemic immune responses by IgE that favours clinical consideration of atopy.

Asthma↗

The effect of atracurium, vecuronium and pancuronium on heart rate and arterial pressure in normal individuals.

Heart rate and rhythm (from ECG) and systolic, diastolic and mean arterial pressures (using an oscillotonometer) were measured for 30 min following administration of atracurium 0.5 mg kg-1 (n = 20), vecuronium 0.1 mg kg-1 (n = 20) or pancuronium 0.1 mg kg-1 (n = 20) during steady-state anaesthesia, with nitrous oxide, oxygen and either 0.75% halothane or fentanyl 4-5 micrograms kg-1, in the absence of any surgical stimulation. Whereas atracurium and vecuronium were associated with only small and clinically unimportant changes in heart rate, pancuronium produced a marked and significant increase associated with a junctional rhythm in four patients. Atracurium produced no significant changes in arterial pressure, vecuronium produced a significant fall (20 mmHg) in diastolic pressure during halothane anaesthesia and pancuronium a significant increase in mean arterial pressure with both anaesthetic techniques. No serious bradycardias were observed with either atracurium or vecuronium. Five patients showed cutaneous signs of histamine liberation after administration of atracurium.

Adult↗

[Occupational asthma: methods of diagnosis and principle etiologies].

The diagnosis of occupational asthma requires the integration of a multiplicity of data; the history, cutaneous skin tests, respiratory function tests and non-specific tests of bronchial hyper-reactivity and specific bronchial provocation tests. The history remains fundamental in the investigation of occupational asthma. It should particularly search for the presence of an atopic trait, the occurrence of similar disorders in members of the same firm and also the timing of symptoms in relation to the occupational activities. Cutaneous tests are particularly helpful in IgE-mediated asthma in relation to the inhalation of animal or vegetable materials of glycoprotein origin. For haptens, the need for their prior coupling to a protein carrier causes problems which have not been entirely resolved. Laboratory tests (RAST, histamine liberation, TDBH...) run into the same snags. Respiratory function and non specific bronchial provocation tests confirm the diagnosis of asthma and enable the medium and long term progress to be assessed. Specific bronchial provocation tests are the most appropriate tests to establish an aetiological diagnosis in occupational asthma. Different technical methods are possible: quantitative administration of allergen, aerosols, and realistic tests using exposure chambers to achieve true test doses and to obtain dose dependent responses. The products responsible for occupational asthma are multiple and are gathered into two tables. The different substances are characterised in a simplified manner. First animal matter (mammalian and arthropod allergens), secondly substances of vegetable origin (roots, leaves, flowers, grain and flour, wood and its derivatives) and finally chemical products. The chemical products are primarily from the pharmaceutical and metal industries and above all from the plastics industry.

Allergens↗

Stimulation of exocytotic degranulation by microinjection of the ras oncogene protein into rat mast cells.

To investigate the possible role of ras proteins in the secretory process, we have microinjected the proto oncogenic and oncogenic forms of the human H-ras protein into rat peritoneal mast cells. Mast cells are secretory cells which, upon appropriate stimulus, liberate histamine and other mediators of the acute inflammatory reaction by exocytotic degranulation. We report here that microinjection of the ras oncogene protein into mast cells induces exocytotic degranulation. In contrast, microinjection of similar amounts of the proto-oncogenic protein has little apparent effect on mast cells. Degranulation induced by injection of the ras oncogene protein occurs in the absence of an external stimulus and requires the presence of external calcium. The ultrastructural features of exocytotic degranulation in mast cells injected with the ras oncogene protein are similar to those seen when mast cells are activated by soluble ligands. Our results suggest that ras proteins may be involved, possibly as regulatory elements, in cellular functions that control exocytosis.

Animals↗

Eosinophilia and myocardial ischemia secondary to polyarteritis. A discussion of pathogenesis on the basis of a case history.

The importance of eosinophilia in patients with severe polyarteritis causing myocardial ischaemia is discussed in connection with a case history. A 20 year old man complaining of recurrent episodes of dyspnoea was found to have a very high eosinophil count, and no allergy as assessed by prick test, RAST and histamine liberation test. The eosinophilia responded to steroid treatment. The patient died 2 years later, at which time his eosinophilia had recurred, of heart failure, with pericardial and pleural effusions and a congested liver. Post-mortem examination showed severe ischaemic changes in the myocardium and chronic inflammatory changes in the small branches of the coronary arteries. The pathologic diagnosis was polyarteritis (in some degree of remission) confined to the heart. Since the clinical and electrocardiographic diagnosis of myocardial ischaemia and cardiomyopathy in patients with polyarteritis and/or eosinophilia can be difficult, other non-invasive investigations are indicated when there is a suspicion that the heart may be affected. Echocardiography, and possibly endomyocardial biopsy may be used at an early stage to assess the response to immunosuppressive treatment. Prophylactic treatment of any associated clotting disorder should be considered. The aetiology and pathogenesis of polyarteritis is unknown, but endothelial damage caused by eosinophilia early in the disease process may be important. Adequate treatment should therefore be given in order to reduce the eosinophil count and a close follow-up is essential in order to diagnose a relapse of the eosinophilia early and thereby possibly prevent fatal cardiac complications.

Adult↗