Leukotriene B4 level in neutrophils from allergic and healthy subjects stimulated by low concentration of calcium ionophore A23187. Effect of exogenous arachidonic acid and possible endogenous source.

Peripheral blood neutrophils from patients with allergic rhinitis and from normal subjects were incubated for 5 min at 37 degrees C with 0.15 microM calcium ionophore A23187 in the absence or presence of exogenous arachidonic acid (2.5 to 10 microM). In neutrophils from allergic patients, the leukotriene B4 (LTB4) level was significantly increased by exogenous arachidonic acid in a concentration-dependent manner (16.2 +/- 4.2 and 38.1 +/- 6.8 pmol/5 min per 2 X 10(6) cells in the absence and presence of 10 microM arachidonic acid, respectively; P less than 0.005; n = 8). The LTB4 level in neutrophils from healthy subjects was only 0.97 +/- 0.17 pmol/5 min per 2 x 10(6) cells (n = 5) and was not enhanced by exogenous arachidonate. When cells from allergic patients were challenged in the presence of exogenous [1-14C]arachidonic acid, released LTB4 was radiolabeled and the incorporated radioactivity increased with the labeled arachidonate concentration. Labeled LTB4 was never detectable after incubating neutrophils from normal donors with exogenous labeled arachidonate. When neutrophils were incubated with [1-14C]arachidonate for 1 h, the different lipid pools of the two cell populations were labeled but both types of neutrophils produced unlabeled LTB4 in response to ionophore stimulation. The hydrolysis of choline and ethanolamine phospholipids into diacyl-, alkenylacyl- and alkylacyl-species revealed that solely the alkylacyl-subclass of phosphatidylcholine was unlabeled. We conclude (i) that neutrophils from allergic patients stimulated by low ionophore concentration produce more LTB4 than neutrophils from healthy subjects and incorporate exogenous arachidonate, (ii) that endogenous arachidonate converted to LTB4 by the 5-lipoxygenase pathway may provide only from 1-O-alkyl-2-arachidonoyl-glycero-3-phosphocholine.

Flow cytometry analysis of T lymphocytes in sarcoidosis.

To examine the immunologic alterations in patients with sarcoidosis we characterized the cell cycle phase of T lymphocytes that were collected from peripheral blood and from bronchoalveolar lavage fluid. T-cell DNA and RNA contents were measured at the single cell level using flow cytometry after staining with the metachromatic fluorochrome acridine orange. T-enriched lymphocyte suspensions were obtained from peripheral blood and from bronchoalveolar lavage in 17 patients with histologically-proved sarcoidosis (10 patients, stage I and 7 patients, stage II) and in 4 patients with acute extrinsic hypersensitivity pneumonitis (AEHP). The percentages of cells in the S + (GS + M) phase in the peripheral blood of the patients with sarcoidosis did not differ from those of healthy control subjects. With bronchoalveolar lavage, however, elevated numbers of T cells in the S + (G2 + M) phase were found in the patients with AEHP and in those with stage II sarcoidosis when compared to patients with stage I sarcoidosis. The cellular RNA content of T lymphocytes from the peripheral blood showed a typical bimodal distribution without difference between patients and control subjects. Conversely, T lymphocytes obtained by bronchoalveolar lavage from patients with AEHP and sarcoidosis had a homogeneous low RNA content which differed from that of T lymphocytes from the blood from that of in vitro phytohemagglutinin-stimulated lymphocytes. These findings provide a new approach to the study of the mechanisms of local T-cell activation in sarcoidosis.

Increased plasma levels of atrial natriuretic factor, renin activity, and leukotriene C4 in chronic obstructive pulmonary disease.

We studied atrial natriuretic factor (ANF), plasma renin activity (PRA), and plasma levels of leukotrienes (LTs) B4 and C4 in 23 patients with COPD undergoing right cardiac catheterization for suspected pulmonary hypertension. Hemodynamic measurements together with concomitant ANF levels (both in venous and pulmonary artery blood and right atrial and pulmonary artery plasma levels of LTC4 and LTB4, were determined at rest (T0), after 30 min of breathing oxygen (3 L/min) (T1), and after 30 min recovering and breathing air (T2). Patients with effective exacerbation or definitive evidence of left ventricular disease, hypertension, arrhythmias, or vasodilator or diuretic therapy were excluded. Increased levels of ANF, both in peripheral venous blood (117 +/- 65 pg/ml) and the pulmonary artery (153 +/- 75 pg/ml), were found in patients with COPD, with or without pulmonary hypertension. Levels of LTC4 were also significantly increased (366 +/- 406 pg/ml) when compared with our control values. No correlations among ANF, LTC4 values, functional tests, and hemodynamic measurements were found. Brief increased levels of oxygen did not modify ANF or LTC4 plasma levels, either in patients with or without pulmonary hypertension.

Long-term results of surgical treatment for gastroesophageal reflux in asthmatic patients.

We report the long-term results of surgical repair of gastroesophageal reflux in 44 asthmatic patients who underwent surgery more than five years earlier (mean = 7.9 +/- 1.5 years). The severe asthma was associated with clinically evident reflux, and repair was attempted by surgical technique Nissen transabdominal gastropexy, with the following results: total cure, 11 cases (25 percent); marked improvement, 7 (16 percent); moderate improvement, 11 (25 percent); no improvement, 15 (34 percent). Cure was attained in intrinsic asthma with a predominance of nocturnal crises, associated with nocturnal tracheitis and with significant reflux, objective signs of which had appeared before the beginning of the asthma. Other results concerned asthmas complicated secondarily by GER in which it was impossible to determine whether the reflux was only a complication, without effect on the respiratory illness, or exacerbating the asthma. The question of surgery in these patients should be considered with care, being reserved for cases of severe asthma, poorly controlled by antiasthmatic drugs, and complicated by a severe reflux that encompasses ulcerative esophagitis.

Double-blind, randomised, placebo-controlled study of two concentrations of azelastine eye drops in seasonal allergic conjunctivitis or rhinoconjunctivitis.

This double-blind, randomised, placebo-controlled study was carried out to assess the efficacy and safety of 0.025% and 0.05% azelastine eye drops twice daily administered for 14 days to patients with seasonal allergic conjunctivitis or rhinoconjunctivitis. A total of 278 patients were recruited and 226 patients were evaluable for per protocol analysis. The target parameter was the response rate. Four eye symptoms, including the main symptom (itching) were recorded by patients in diaries and eight symptoms were assessed by physicians before and after seven and 14 days of treatment. Severity of symptoms was measured on a four-point scale. The response rates for itching (improvement of at least one score point within the first three days) according to patient assessment were 43% for placebo, 52% for 0.025% and 56% for 0.05% azelastine (NS). However, a more objective assessment of the three main eye symptoms by physicians showed a concentration-dependent improvement in response rate compared with placebo (a decrease of > or = 3 points from a baseline total score of > or = 6), which reached statistical significance for 0.05% azelastine on Day 7 (p < 0.002). In the evaluable patient population, the scores of the three main eye symptoms as well as of all eight recorded eye symptoms, as assessed by the physician, were significantly (p < 0.05) lower in the 0.05% azelastine eye drops group in comparison with the placebo group at Day 7. Inefficacy was the cause of withdrawal in five and three patients on 0.025% and 0.05% azelastine, respectively, and in six patients on placebo. Adverse drug effects, mainly a mild, transient irritation and a bitter or unpleasant taste, were reported by 14% (0.025%), 20% (0.05%) and 15% (placebo) of the patients. No serious side-effects occurred. Azelastine eye drops are effective and well tolerated at a concentration of 0.05% for the treatment of seasonal allergic conjunctivitis.

Phosphatidylethanolamine methyltransferase and cAMP, cGMP phosphodiesterases in lymphocytes and monocytes in sarcoidosis.

Among the various hypotheses proposed to explain immune cell defect in sarcoidosis, we examined thoroughly that of Faguet who described abnormalities of signal transmission at lymphocyte membrane level. Phosphatidylethanolamine methyltransferase and cAMP cGMP phosphodiesterases were studied in blood lymphocytes and monocytes from 8 subjects with sarcoidosis disease. Phosphatidylethanolamine methyltransferase (PMT1) plays an important regulatory role in membrane signal transmission. cAMP and cGMP phosphodiesterases (PDE) regulate cytoplasmic cyclic nucleotide levels and so participate in the modulation of the cell cycle. We observed a decreased PMT1 activity in lymphocytes and monocytes and a decreased cAMP and cGMP PDE activities in monocytes. It is not now possible to say if these abnormalities are primary or secondary. Whatever the origin of this dysfunctioning, these results evoke simultaneous disturbances of membrane signal transmission and cell cycle in monocytes and membrane abnormalities in lymphocytes. These abnormalities could explain some immune cell defects in sarcoidosis disease.

Activity of cyclic AMP phosphodiesterase and methyltransferases in leukocyte membranes from allergic patients.

Cyclic AMP metabolism and methylation of phospholipids are central events which occur at the membrane level. Since a dysfunction of cell membranes seems to characterize some allergic diseases, we investigated cyclic AMP phosphodiesterase and methyltransferase activities in leukocyte membrane fractions obtained from healthy volunteers and from allergic patients. The allergic group presented a significantly decreased methyltransferase activity compared with a control group, whereas cyclic AMP phosphodiesterase and noradrenaline (NA)-stimulated methyltransferase were found to be increased with respect to the control group. A significant correlation has been found between cyclic AMP phosphodiesterase and NA-stimulated methyltransferase with both control and allergic subjects, which suggests close relationships between these two enzymes within the cell membrane.

Phosphatidyl ethanolamine methylation in membrane from bronchoalveolar lavage mononuclear cells, in asthmatic patients: a new marker of macrophage activity.

Phosphatidyl ethanolamine methylation was compared in alveolar macrophage membrane from asthmatic and control subjects. Phosphatidyl ethanolamine methylase activity was determined by measuring the incorporation of (3H) methyl group from (3H) adenosyl methionine into membrane phospholipids. (3H) methyl group incorporation was significantly higher in macrophages from asthmatic patients. This result is consistent with macrophage membrane activation and could signify: a membrane phospholipid pool regeneration after allergenic or toxic disturbance or an enzymatic activation by inflammatory mediators.

A comparison of flunisolide inhaler and beclomethasone dipropionate inhaler in bronchial asthma.

Ninety-nine patients, who had never previously taken inhaled steroids were enrolled in a randomized, single-blind, parallel study, the aim of which was to compare the efficacy and safety of flunisolide inhalation, 500 mcg twice daily, with beclomethasone dipropionate inhaler 100 mcg four times daily for the treatment of chronic asthma. The treatment period was for 6 weeks. The patients were examined clinically at entry, week 3 and week 6 and both treatment groups showed a marked improvement in almost all parameters during the course of the study. Flunisolide was statistically significantly superior to beclomethasone dipropionate for wheezing at week 6, coughing at week 6 and chest tightness at weeks 3 and 6. The number of asthma attacks per day decreased significantly more with flunisolide treatment than with beclomethasone dipropionate. The over-all evaluation of efficacy by both doctors and patients also showed flunisolide to be superior to beclomethasone dipropionate. In several other parameters there was a trend shown favouring flunisolide, and beclomethasone dipropionate did not show a superiority over flunisolide in any efficacy parameter. Both drugs were well-tolerated, with unpleasant taste being the most frequent complaint in the flunisolide group. No patient in either group withdrew from the study because of adverse events. In this study, flunisolide inhaler was more effective than beclomethasone dipropionate inhaler for the treatment of chronic asthma exhibited by patients who had never been treated with inhaled steroids.

[Chiasmal radionecrosis after irradiation of the sella turcica using a conventional dosage. Contribution of magnetic resonance imaging]. / Radionécrose chiasmatique après irradiation de la selle turcique à doses conventionnelles. Apport de l'imagerie par résonance magnétique.

A 47 year-old man developed rapid visual loss, visual field defects and memory disturbances after radiotherapy with conventional doses for a pituitary metastasis from a renal carcinoma. CT and MRI did not show recurrent tumour, pituitary apoplexy or empty sella. Eventually, T2-weighted MRI images showed abnormal high signals in the optic chiasm, the left mesial temporal lobe and the right inferior frontal lobe, supporting the diagnosis of delayed radionecrosis. The role of chemotherapy associated with radiotherapy is discussed.

[Modification of the Friedland-Silverstein technic for the determination of the activity of angiotensin I converting enzyme]. / Modification de la technique de Friedland et Silverstein pour la détermination de l'activité de l'enzyme de conversion de l'angiotensine I.

The authors studied the parameters of Friedland and Silverstein's technique for measuring the activity of the angiotensin I conversion enzyme and found a number of anomalies. The technique was modified by correcting the wide pH difference between the pH of the reagent and the pH of the reference solution. This modification made the technique optimal for the measurement of the enzyme activity by allowing a 20 to 40 per cent increase in this activity and a 15% increase in the positivity in cases of clinical sarcoidosis. The application of this modified test to the determination of the activity of the angiotension I conversion enzyme in control subjects, patients with sarcoidosis and patients with order respiratory diseases gave the following mean values, respectively: 39 +/- 10 IU; 81 +/- 23 IU; 41.5 +/- 2.5 IU in the serum and 0.2 IU; 1.1 +/- 0.5 IU; 0.2 +/- 0.1 IU in bronchoalveolar lavage fluid. The increase in enzyme activity in sarcoidosis is found in the serum in 75% of cases and in bronchoalveolar lavage fluid in 85% of cases. This modified technique can be applied in routine practice and in research.

[Sleep apnea syndrome in obese patients: are there any predictive factors ?]. / Syndrome d'apnées du sommeil chez les obèses: existe-t-il des facteurs prédictifs?

The aim of this study was to determine whether clinical, spirometric, or arterial blood gas data could predict sleep apnea syndrome (SAS) among obese patients with at least one functional complaint. Eighty three obese patients, 46 males and 37 females, aged 53.2 +/- 13.7 years, with a body mass index (BMI) above 30 kg/m2 were investigated with: clinical questionnaire; pulmonary function tests; arterial blood gas measurements; nocturnal monitoring of oronasal airflow, thoracic and abdominal movements, and arterial oxygen saturation. Thirty five patients (42.2%) had a SAS, 18 (26.7%) had nocturnal oxygen desaturations, and 30 (36.1%) had a normal nocturnal monitoring. There were 63% males in the SAS group and 32% in the group without SAS (P < 0.01). Age, weight, frequency of systemic hypertension, frequency of each clinical symptom, spirometric and arterial blood gas data were identical in the two groups. In conclusion, rate of SAS is very high in obese patients presenting a BMI above 30 and at least one functional complaint. No predictive test is identified.

[Bronchiolitis obliterans in adults]. / Bronchiolite oblitérante de l'adulte.

Bronchiols are defined as small upper airways with a diameter less than 2 mm. Two zones are described, membranous bronchioli with a continuous wall and respiratory bronchioli with a discontinuous wall. On the basis of pathology examinations, three disease processes can be recognized. In the first category, the initial inflammatory reaction in chronic obstructive bronchitis may spread to the bronchioli as can immune or infectious diseases resulting in bronchiolitis obliterans. Lesions originating conjointly in the bronchioli and alveoles form a second group including bronchiolitis obliterans organizing pneumoniae, the BOOP syndrome recently described. Histologically these disease entities show characteristic desquamation of the alveolar endothelium and a fibrinoid exudate. Hypoxaemia due to respiratory failure develops progressively and usually responds to corticosteroid therapy. In a third group, the disease is limited to the bronchioli alone with no large airway involvement. Chronic obstructive disease of the small airways has been described in smokers and people exposed to mineral dust. The clinical course often runs to classical chronic obstructive bronchopneumonia. Bronchiolitis obliterans itself, or constrictive bronchiolitis, is differentiated from BOOP due to the proliferative aspect within the lumen. No aetiological agent has been identified. The term bronchiolitis obliterans covers a wide range of more or less well identified entities which unfortunately have the common feature of generally poor response to treatment.

[Asthma and infection: interrelations]. / Asthme et infection: interrelations.

The frequent interaction of infection in asthma is a result of a complex interrelationship. Infectious agents are capable both of inducing asthmatic crises and, at least for viruses, of initiating the asthmatic process. They also favour a specific IgE response to allergens. Similar immunity is involved in defence against these infectious agents but this immunity can be disturbed in asthmatic subjects; as seen with defects in immunoglobulin subclasses, disturbance in T lymphocyte function, monocytes and blood neutrophils. The determination of the genetic or acquired character of these disturbances is pre-condition for the development of a therapeutic substitute.

[Metachronous primary pulmonary cancers. Apropos of a new case report]. / Cancers pulmonaires primitifs métachrones. A propos d'une nouvelle observation.

The appearance of a second primary lung cancer more than four months after the initial cancer is called a metachronous cancer (as opposed to a synchronous cancer). We provide a case report of an epidermoid carcinoma coming more than three years after the initial diagnosis of an anaplastic small cell cancer of the lung. This second cancer developed in a different territory from the initial lesion. Amongst the hypotheses proposed chemotherapy may through an oncogenic action favour the appearance of a new type of cancer.

[T-lymphocytes disorders in pulmonary sarcoidosis]. / Perturbations lymphocytaires T au cours de la sarcoïdose pulmonaire.

Sarcoidosis is a granulomatous disorder of unknown aetiology accompanied by variable immunological changes which concern both the monocyte and lymphocyte cell line. During the course of this disease anomalies of distribution (with accumulation in the disease tissue contrasting with a peripheral lymphopenia) and also of T cell functions (a predominance of CD4 T lymphocytes within the lesions and spontaneous expression of activation criteria) have been described. Recent works show some disturbances of T cell function and evoke the possibility of the initial pathology being related to this cell. Some current hypotheses place the T cell receptor for the antigen and the interleukin 2 receptor whose dysfunction will lead to an anomaly of the transduction of the activating signal of the T lymphocyte. The intrinsic origin (genetically determined) or extrinsically (retroviral) of these disturbances remains however to be determined.

[Purulent pleurisy due to Legionella bozemanii]. / Pleurésie purulente due à Legionnella bozemanii.

Since the advent of antibiotics, the bacteriological profile of empyema has changed. It is necessary to recall the recently discovered organisms. Although rarely mentioned in the literature, the Legionnellas may be causative in an empyema. We report a case of empyema to Legionnella bozemanii proven seriologically.

[A simple test for the detection of respiratory allergy to current pneumallergens]. / Un test simple de dépistage de l'allergie respiratoire aux pneumallergènes courants.

Phadiatop is a new in vitro test used for screening patients with allergic respiratory diseases. This test, based on the RAST procedure, is performed with a paper disc to which a balanced mixture of relevant inhalant allergens has been coupled. One hundred and one adults ranging in age from 18 years to 73 years and 38 children (4 months to 15 years) were studied. We found a good correlation between this new test and total IgE (adults: 74.3 p. 100, children: 68.4 p. 100), specific IgE (adults: 91.1 p. 100, children: 100 p. 100) and skin test (adults: 79.2 p. 100, children: 97.1 p. 100). There was a high correlation between clinical atopy assessment and the result of Phadiatop, its efficiency was 83 p. 100 in adults and 97 p. 100 in children.

[Asthma and gastroesophageal reflux]. / Asthme et reflux gastro-oesophagien.

This work summarises present-day knowledge concerning relationships between asthma and gastro oesophageal reflux (GOR). The data acquired during the last ten years are briefly reviewed. They concern: the high frequency of GOR during asthmatic disease, the clinical signs which allow one to suspect such a possibility, the significance of these refluxes, and their provocative factors (mechanical, iatrogenic, and neurogenic). In the second part, the author exposes various problems which have not yet been absolutely solved. They concern: the methods of diagnosis of GOR (prolonged pH measurements and isotopic explorations seem to be the best techniques) and the question of management concerning the latter problem medical treatment of reflux should be widely prescribed. Surgical indications however, should on the contrary be carefully discussed.

[Beta-mimetics and tachyphylaxis]. / Bêta-mimétiques et tachyphylaxie.

This study covers current knowledge concerning the risks of tachyphylaxis induced by prolonged use of beta-mimetics in the asthmatic. The organization of the adrenergic membrane system is reviewed, as well as the various mechanisms which may lead to desensitization. Experimental evidence of the latter is described. The most extensive studies have involved circulating cells and, more precisely, lymphocytes and polynuclear neutrophils. Clinical trials are then dealt with. Studies concerned with bronchomotility and the possible loss of sensitivity of the bronchi after a therapeutic sequence using a sympatho-mimetic. No definite conclusion concerning this aspect can be made by review of the literature, because of contradictory results, and this regardless of the beta-mimetic used. However, it would seem that relative tachyphylaxis may develop in the bronchi. Nevertheless, the latter would not seem to be sufficiently marked in order to have clinical manifestations. Studies concerned with lymphocytes and polynuclears. Published studies are more in agreement here, demonstration of tachyphylaxis by measurement of cellular cyclic AMP or measurement of the density of receptors after impregnation by a beta-adrenergic being constant. The practical consequences of this risk is discussed, but cannot yet be accurately fixed. Therapeutic deductions from the findings described are then discussed. The protective role of corticosteroid therapy and of Ketotifen against the risk of tachyphylaxis is emphasized in particular.