Ascorbic acid inhibits polymorphonuclear leukocytes influx to the place of inflammation--possible protection of lung from phagocyte-mediated injury.

Ascorbic acid as a scavenger of oxidants derived from human polymorphonuclear leukocytes (PMNL) may have clinical significance in antioxidant prevention of emphysema. However, there is a risk relevant to its administration because this drug was reported to enhance PMNL chemotactic response and thus could create protease burden in the lower airways. In this study we have investigated the effect of ascorbic acid on the PMNL influx to the place of inflammation developed in the mouse pleural cavity after injection of zymosan-activated serum (ZAS). We also evaluated the influence of ascorbic acid on human PMNL spontaneous migration, chemotaxis to ZAS and n-formyl-methionyl-leucyl-phenylalanine (FMLP) under agarose. The previous ascorbic acid intraperitoneal administration (single dose 10 mg per day for 3 following days) inhibited leukocyte influx. Total number of cells found in the cavity, number of PMNL and lymphocytes was 2.4, 3.5, 1.7-fold lower than in animals without ascorbic acid, respectively. In vitro ascorbic acid (concentrations of 1 to 10 mg/dl) enhanced PMNL spontaneous migration, concentrations 10 mg/dl and higher inhibited PMNL chemotaxis to ZAS and had no influence on migration of the cells toward FMLP. These results suggest that ascorbic acid may be useful for prevention of lung oxidant injury not only as oxidant scavenger but also as an inhibitor of PMNL influx to the pulmonary tissue.

The influence of aminophylline on human neutrophils--possible protection of lung from proteolytic injury.

Protease-antiprotease imbalance in the lung is considered to be a likely pathogenetic mechanism in the development of lung injury--particularly emphysema. Aminophylline is often used in bronchitis, bronchial asthma and emphysema. To assess, whether aminophylline indeed affects this mechanism we evaluated in vitro its influence at therapeutical concentrations (12 and 20 micrograms/ml) on phagocytosis, release of total protein and lysosomal enzymes after phagocytosis, spontaneous migration and chemotaxis of human neutrophils to zymosan-activated serum. There were no significant differences in phagocytosis, release of leukoprotease and acid phosphatase between neutrophils with and without aminophylline at both concentrations. However, the release of total protein was different (p less than 0.02, 12 micrograms/ml) and lower (p less than 0.02, 20 micrograms/ml) than the control. The mean decrease in protein release was 13.5 +/- 6% of the control and aminophylline inhibited the release of the protein with molecular weight below 35.000 daltons. Significant migration inhibition was found in 22% cases (12 micrograms/ml, n = 9) and in 53% (20 micrograms cm-3, n = 13). Neutrophil chemotaxis was different (p less than 0.02, 12 micrograms/ml) and lower (p less than 0.05, 20 micrograms/ml) than the control. The obtained results suggest that high doses, of aminophylline may diminish inflammatory recruitment of neutrophils--a rich source of elastase to the lung, and thus diminish proteolytic pulmonary injury.

[Effect of locally applied lidocaine on expression of the oculocardiac reflex]. / Einfluss von lokal appliziertem Lidocain auf die Ausprägung des okulokardialen Reflexes.

INTRODUCTION: The oculocardiac reflex causes severe bradycardic arrhythmias and is a frequent complication during surgical manipulation at the medial rectus muscle. The purpose of this study was to evaluate the influence of lidocaine administered topically on the muscle on the incidence of the oculocardiac reflex. PATIENTS AND METHODS: After obtaining informed consent, 140 patients with strabism or retinal surgery were included in this study. All patients received standard premedication and anesthesia and were randomly assigned to two groups. Patients (n = 70) randomly assigned to the first group received 1 mg/kg lidocaine applied topically to the muscle after opening the conjunctiva. Individuals in the placebo group received the same volume of saline (0.9%). Surgical stimulation occurred 5 min after administration of the drug. The study parameters (blood pressure/heart rate) were recorded before and after stimulation of the oculocardiac reflex caused by routine surgical preparation. RESULTS: Topical administration of lidocaine reduced the incidence of the oculocardiac reflex (86.1% vs 37.1%), and the frequency of severe bradycardiac arrhythmias was also significantly reduced (40 vs. 2.9%). Cardiac arrest for longer than 10 s did not occur in the lidocaine group. In the control group this phenomenon was observed in 14.8%.

Latex allergy.

Over the last ten years allergy to latex has become a serious, life-threatening medical problem. Exposure to latex may result in immediate hypersensitivity reactions such as urticaria, dyspnoe, rhinitis, angioedema and anaphylactic shock in sensitized individuals. People occupationally exposed to latex--health care and rubber industry workers and children suffering from spina bifida--are the most important risk groups. Clinical manifestations, immunological mechanisms, trials for identifying latex allergens and laboratory testing are reviewed here. Moreover, the authors present two cases of latex allergy diagnosed with the use of a nasal challenge test. 0.0005% latex solution (Stallergen) and latex extract prepared at the Clinic were used. Nasal washings were performed before, 30 minutes, 3 and 24 hours after provocation. The test evaluation was based on changes in the number and type of cells present in the washings. As there is no laboratory test to be used in latex allergy diagnosis approved by the Food and Drug Administration (FDA) the nasal provocation test seems to be worthy of further investigation. Ways of reducing of the allergenicity of latex products and preventing hypersensitivity reactions are also presented.

Occupational allergy to latex--life threatening reactions in health care workers. Report of three cases.

During the last decade natural rubber latex (NRL) allergy has been acknowledged as a major problem among rubber glove-wearing medical personnel. Epidemiological studies carried out in the European Union member states as well as in the United States reveal that 2% to 15% of health care workers are allergic to latex. Latex allergy symptoms range from mild contact urticaria to severe systemic reactions. Serious, generalised reactions occur in 6-8% of patients allergic to latex. The risk factors for latex-induced anaphylaxis have not as yet been identified. NRL allergy symptoms may occur in the workplace as well as outside the occupational environment. The authors present clinical cases of 2 nurses and 1 laboratory worker, who developed severe allergic reactions to latex: case 1--during prophylactic gynaecologic examination, case 2--in the course of inhalative bronchial challenge test with latex aqueous extract and case 3--while blowing up balloon at home.

Problems in diagnosing occupational allergy to flour: results of allergologic screening in apprentice bakers.

Baker's respiratory allergy is reported as one of the most common forms of occupational allergy in many countries. At the first stage of a three-year study of risk factors of occupational allergy we investigated the symptoms reported, and the results of skin prick tests (SPT) to common and flour allergens in 461 current apprentice bakers from three different regions of Poland before starting occupational exposure. The occurrence of cough was reported by 14 subjects (3%), dyspnoea by 4 (0.87%), rhinitis by 18 (3.9%), conjunctivitis by 12 (2.6%) and skin symptoms by 12 subjects (2.6%). Generally, 48 subjects (10.41%) reported at least one symptom, which might suggest the existence of allergic disease. Positive SPT to at least one allergen was found in 99 subjects (21.5%), including 82 subjects (17.78%) with positive SPT to common allergens, 13 subjects (2.81%) to flour allergens and 4 subjects (0.88%) sensitised only to Dermatophagoides farinae. The statistical analysis revealed significant correlation between positive SPT to common allergens and reported rhinitis and conjunctivitis, and between positive SPT to occupational allergens and reported dyspnoea. Moreover, a significant correlation between positive SPT to D. pteronyssinus and D. farinae was found. In our opinion, the results of SPT should be very carefully examined, when diagnosing occupational allergy, as in some apprentice bakers positive results of SPT to flour allergens are found before vocational training. In all apprentice bakers, SPT to common and occupational allergens should be performed before starting occupational exposure. It would ensure the exclusion of subjects already sensitised to occupational allergens. Positive SPT to Dermatophagoides farinae has a very limited value in recognising baker's allergy.

[Immediate hypersensitivity in the development of contact sensitivity to disinfectant agents]. / Udzial alergii natychmiastowej w powstawaniu uczulenia kontaktowego na srodki odkazajace.

In 53 female health service workers with contact allergy to disinfectants (formaldehyde, glutaraldehyde, benzalkonium, lisoformine) the results of skin prick tests using common environment allergens were analysed, and concentrations of total IgE in blood serum were identified. In 29 (54.7%) persons positive prick tests (Dermatophytes--21, pollens--21, latex--7, domestic dust--5, goose and duck feathers--3, dog hair--2, and cat hair--1) were noted. In the whole group mean IgE concentration accounted for 88.2 kU/1, whereas in the group with positive skin prick test the value increased to 136.1 kU/1. The authors are of the opinion that in patients with contact allergy to disinfectant some symptoms of atopic diathesis are observed.

[Principles of establishing the registries of chemical substances in the United States and Europe]. / Zasady tworzenia rejestrów zwiazków chemicznych w USA i Europie.

The paper presents the principles of building up the inventories of chemical substances in the USA, the countries belonging to European Economic Community (EEC) and Austria. In all countries, the appropriate legal regulations putting the manufacturers and importers of chemicals under obligation to provide some strictly determined information underlie the decision to build up these inventories. The data provided usually inform of: manufacturer's name and address, chemical substance identity, production volume and ways of distribution. The paper presents also the criteria of selection of substances to be placed in the inventory, organizational scheme of building up the inventory and the ways of exacting the respective regulations. The inventories of chemical substances issued in the USA and Austria may serve as banks of information on the place, kind and quantity of chemical substances on the territory of the whole country. Based on these data a map of chemical hazards zones may be prepared which may adversely affect either human health or environment. The inventory of EEC countries may serve only as lists of chemicals occurring in the common market.

[Natural history of occupational allergy to latex in health care workers]. / Historia naturalna alergii zawodowej na lateks u pracowników sluzby zdrowia.

The analysis of natural history of allergy to natural rubber latex (NRL) in health care workers, including the influence of exposure cessation on the clinical status and objective allergy markers was the objective of the study. The study covered 58 patients with recognised allergy to NRL. Of this number, 26 were followed up for 2 years after diagnosing NRL allergy. Medical examination, skin prick tests for common allergens and NRL, determination of total serum IgE and NRL-specific IgE antibodies, rest spirometry and non-specific bronchial hyperactivity test with histamine were performed. The retrospective analysis of clinical manifestation of NRL allergy revealed in 36% of patients progression of symptoms from local urticaria and rhinitis to systemic reactions. Two years after the cessation of exposure to NRL, symptoms became less severe in the majority of patients and even a clearance of allergic symptoms was observed, as well as the decrease in doses of inhalative glicocorticosteroids was noted. This was accompanied by the decline in non-specific bronchial hyperactivity. Although the skin prick tests showed the tendency to remain positive, the decrease in the level of specific anti-NRL IgE was found in 10 patients (including the RAST negativisation in one case). In conclusion, clinical progress from NRL-induced contact urticaria and allergic rhinitis to systemic reactions was observed only in part of patients with NRL allergy, which cannot be taken as a rule. Significant reduction of clinical symptoms or even total remission of NRL-allergic symptoms could be observed after exposure cessation.

[Behavior of esterase inhibitor C1 in patients with urticaria due to aspirin hypersensitivity]. / Zachowanie sie inhibitora C1 esterazy u osób z pokrzywkowo-obrzekowa postacia nadwrazliwosci na aspiryne.

The aim of the study was to evaluate concentration and activity of C1 esterase inhibitor (C1 INH) in patients with aspirin-sensitive urticaria. Deficiency of C1 INH is the basis for hereditary angioneurotic oedema. The study was performed in 32 subjects with aspirin-sensitive urticaria. The value of C1 INH in examined patients was the same as in control group. It seems there is no coexistence of aspirin-sensitive urticaria and C1 esterase inhibitor deficiency.

[Nasal lavage, rhinomanometry and rhinoscopy in diagnosing occupational airway allergy]. / Badanie popluczyn nosowych oraz badanie rynomanometryczne i badanie rynologiczne w diagnostyce zawodowych alergoz ukladu oddechowego.

The aim of the study was to estimate the usefulness of nasal lavage, rhinomanometry and rhynoscopy in diagnosing occupational allergic rhinitis and bronchial asthma. 26 subjects with suspected bronchial asthma and allergic rhinitis due to occupational allergens were examined. Each subject had medical history collected and underwent physical examination, skin prick tests (SPT) with common and occupational allergens, determination of total and specific IgE, specific bronchial or nasal provocation with determination of spirometric parameters, morphological and biochemical changes in nasal lavage fluid (NLF). Moreover the anterior rhinomanometry and rhynoscopy were performed before and after the provocation. A significant increase in the percentage of eosinophils and albumin was observed in NLF up till 24 hr after the specific challenge, but only in the group of 16 subjects with diagnosed occupational airway allergy. The authors observed also the presence of mucosal oedema and rhinorrhea in this group of patients more frequently than in the group of patients without diagnosed occupational airway disease. No significant changes were observed in the frequency of positive rhinomanometry test between the analysed groups of patients.

Nicotine inhibits alpha-1-proteinase inhibitor inactivation by oxidants derived from human polymorphonuclear leukocytes.

Cigarette smoke can inactivate the alpha-1-proteinase inhibitor (alpha 1PI) by oxidative mechanisms and thus predisposes to the development of pulmonary emphysema. There are differences between the whole smoke and gas phase acting as alpha 1PI inactivators in vitro which suggests that the whole smoke is less oxidizing than the gas phase. Also studies on alpha 1PI oxidative inactivation in the lung of cigarette smokers gave controversial results. The reductive properties of cigarette tar which contains most of smoke nicotine may be some explanation of it. Therefore in this study we have investigated the effect of nicotine (0.4 mumol/l to 4 mmol/l) on the oxidative inactivation of human alpha 1PI by phorbol myristate acetate-activated polymorphonuclear leukocytes (PMNL), chloramine-T (15 mumol/l), hydrogen peroxide (15 mmol/l) and the superoxide radical (O2-.) generating system-xanthine (0.2 mmol/l)-xanthine oxidase (80 U/l). Nicotine at concentrations of greater than 40 mumol/l protected alpha 1PI from stimulated PMNL. The preincubation of PMNL with these concentrations of nicotine did not diminish their ability to inactivate alpha 1PI after stimulation. Nicotine (above 0.4 mumol/l) also protected alpha 1PI from chloramine-T but not from H2O2. The inhibition of O2-.-mediated alpha 1PI inactivation by nicotine was low and was observed only at a concentration of 4 mmol/l. This nicotine concentration did not affect xanthine oxidase activity. It is suggested that cigarettes with low nicotine contents can cause greater oxidative lung injury than their high nicotine counterparts and be a greater risk factor for the development of lung emphysema.

Effect of ipratropium on nasal reactivity to histamine and eosinophil influx in perennial allergic rhinitis.

In a double-blind, placebo-controlled study nasal saline and histamine provocation tests were performed in patients with perennial allergic rhinitis in order to assess changes in eosinophil influx and non-specific nasal reactivity after 8 days of treatment with ipratropium bromide. A "nasal pool" method was used to trace changes in protein level and eosinophil influx into nasal secretions. Treatment with ipratropium 80 mg q.i.d. caused a significant decrease in the albumin and total protein level in saline washings and induced a five-fold increase in eosinophils as compared to the placebo treatment. The nasal mucosal response to histamine, assessed as the number of sneezes and protein level, was more responsive to ipratropium treatment than the mucosa from placebo-treated subjects. Since eosinophil numbers were correlated with an increase in the vascular and sneezing responses, it appears that ipratropium potentiates inflammatory mechanisms when used in subjects with an allergy in the nasal mucosa.

Inhibitory effect of levocabastine on allergen-induced increase of nasal reactivity to histamine and cell influx.

For evaluation of the effect of levocabastine pretreatment on allergen-induced rhinitis symptoms, changes in nasal washings, and nasal responsiveness to histamine, 12 asymptomatic patients with documented allergic rhinitis participated in a single-blind, placebo-controlled study. Eight-day treatment with levocabastine (twice in each nostril, four times a day) caused significant reduction in nasal symptoms and inflammatory cell influx after allergen challenge, as compared with placebo administration. Levocabastine inhibited increased nasal reactivity to histamine induced by allergen provocation, as controlled by rhinitis symptoms and albumin level in nasal washings. These data reveal a high effectiveness of levocabastine in the prevention of allergen-induced rhinitis symptoms. Moreover, its inhibitory effect on inflammatory cell influx and hyperresponsiveness to histamine suggest that levocabastine is more than a simple H1-receptor antagonist.

Nasal and bronchial responses to flour-inhalation in subjects with occupationally induced allergy affecting the airway.

OBJECTIVES: The aim of the study was to follow the similarities and differences, of cellular and mediator changes and mucosal/vascular permeability in the upper and lower airway after specific and nonspecific bronchial provocation, in bakers with diagnosed occupationally induced allergy affecting the airway. In addition, the authors try to find whether there is a relationship between cellular changes in nasal and bronchoalveolar lavage, and bronchial hyperreactivity. METHODS: The study participants were 10 bakers with occupational bronchial asthma and allergic rhinitis. All patients were sensitized to investigated allergen-flour. Nasal- and bronchoalveolar lavage techniques were used to evaluate the changes of the cellular and mediator response (tryptase, eosinophil cationic protein, ECP) and albumin level after specific (flour) and placebo provocation. In addition. bronchial hyperreactivity for histamine, and forced expiratory volume in 1 s (FEV1) were measured after the challenge. RESULTS: There was a significant increase in the percentage of eosinophils, basophils and albumin in nasal and bronchoalveolar lavage of occupationally sensitized bakers. A statistically significant increase in the percentage of neutrophils in bronchoalveolar lavage was observed only 24 h after the allergen challenge. The level of tryptase in nasal lavage was significantly higher during the early allergic response. The levels of ECP in both nasal and bronchoalveolar lavage were significantly increased during the late allergic response. There were also severe bronchial reactions and increase of bronchial hyperreactivity for histamine in occupationally sensitized bakers in the late phase of allergic reaction. CONCLUSION: Eosinophils and basophils proved to be the predominant cells in nasal and bronchoalveolar lavage of patients with occupationally induced bronchial asthma and rhinitis. The prolonged increase of albumin level seems also to be a good predictor of protracted nasal and bronchial inflammation. The results obtained confirmed that tryptase and ECP are good markers for monitoring mast cell and eosinophil degranulation during the allergic reaction. Increase of airway responsiveness reflects an eosinophil and basophil contribution to airway allergic response.

Nicotine increases human polymorphonuclear leukocytes chemotactic response--a possible additional mechanism of lung injury in cigarette smokers.

Human polymorphonuclear leukocytes (PMNL) which are a potential source of proteolytic enzymes and reactive oxidant species contribute to the development of pulmonary emphysema in cigarette smokers. We found that nicotine at concentrations that occur in smokers' plasma enhances human PMNL chemotactic response to zymosan-activated serum (ZAS) and n-formyl-methionyl-leucyl-phenylalanine (FMLP). Maximal increase in chemotactic migration was at nicotine concentration 1 mumol/l. Higher concentrations, above 0.1 mmol/l inhibited PMNL chemotactic response and spontaneous migration. Nicotine also enhanced PMNL influx to the place of inflammation developed in the mouse pleural cavity after injection of ZAS. The number of PMNL found in the pleural cavity was 1.9-fold higher (p less than 0.001, n = 5) when animals were pretreated with 0.15 mg of nicotine. However, this drug itself (concentrations of 0.1 mumol/l to 10 mmol/l) had weak chemotactic activity for PMNL. It seems that the stimulatory action of nicotine on PMNL chemotaxis may be partly responsible for increased PMNL numbers in the lower airways of cigarette smokers and following formation of the elastase/antielastase imbalance in lung tissue.

Changes in nasal lavage fluid due to formaldehyde inhalation.

The aim of the study was to characterize the nature of the formaldehyde-induced nasal response consisting in symptoms of rhinitis and changes in nasal lavage fluid. Eleven healthy subjects and nine patients with specific skin sensitization were provoked in a toxicological chamber with formaldehyde at a dose of 0.5 mg/m3 over 2 h. Nasal lavage was performed prior to and immediately after provocation and 4 and 18 h later. Provocation with formaldehyde caused transient symptoms of rhinitis and prolonged changes in nasal washings. There were increases in the number and proportion of eosinophils and elevated albumin and total protein levels in nasal lavage fluid 4 and 18 h after provocation. No difference in the nasal response to formaldehyde was found between patients with skin sensitization and healthy subjects. These data confirm the irritative effects of formaldehyde and are also suggestive of nonspecific proinflammatory properties when formaldehyde is inhaled at a low (0.5 mg/m3) dose.

Attenuation of the oculocardiac reflex after topically applied lignocaine during surgery for strabismus in children.

The effect of topical lignocaine applied to the eye muscles, on the incidence of the oculocardiac reflex during squint surgery of the medial rectus was investigated in 56 healthy children aged between 3-14 years. Three groups were studied. One (n = 16): stimulation of the reflex without lignocaine; 2 (n = 10): stimulation of the reflex after topical administration of 1 mg kg-1 lignocaine 2% to the medial part of the eye after induction of anaesthesia; 3 (n = 30): stimulation of the oculocardiac reflex without, and after a 5 min interval under the influence of lignocaine. Topical administered lignocaine significantly attenuated the OCR (105 vs. 68 bpm group II vs. group 1:82 vs. 63 bpm in group III). Severe bradycardiac rhythm disturbances, in particular cardiac stand-still, were not observed after lignocaine had been applied. Systemic side effects of lignocaine were not seen.