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Biomedical subjects

J Lacronique

Publications and source records attributed to J Lacronique.

At least 19 recordsLinked to original sources

[Primum non nocere...inhaled glucocorticosteroids in 2003].

The use of inhaled glucocorticosteroids for the treatment of asthma raises the important question of short- and long safety. Thus the assessment of the benefit-risk ratio is an essential part of the development of powerful agents with reinforced topical activity. Several factors determine the optimal profile for an inhaled glucocorticoid: topical activity, systemic bioavailability (influence of the first-pass liver metabolism, inhalation device, patient- and disease-related factors), and pharmacokionetic behavior, liposolubility being one of the determining elements. Taken together these different factors produce a therapeutic index expressing the topical and systemic effects of inhaled glucocorticosteroids and their variability under the particular conditions of each patient. Al high-dose inhaled glucocorticoids have an impact on the adrenal gland which is easy to demonstrate but with rather insignificant clinical relevance. In children for example, there is a transient inhibition of bone growth with no impact on final height in adulthood. In adults; the effect on bone metabolism raises the risk of osteoporosis which must be prevented and detected in patients at risk. More data must be acquired concerning the ocular risk. Overall, significant adverse systemic effects are not observed with administration of inhaled glucocorticoids, but there remains a certain degree of uncertainty concerning the effects of long-term administration of low effective doses.

Administration, Inhalation↗

[Characteristics and specificities of cystic fibrosis in adults: evolutive disease of childhood or recently diagnosed disease?].

We have studied the characteristics of 202 cystic fibrosis adult patients, all with chronic respiratory symptoms, with a median age of 27 yrs (18 to 55 yrs) and a male predominance (56%). At genetic analysis, delta F508 homozygotes were 41%, delta F508 heterozygotes 42% and 17% had no delta F508. The respiratory disease was more severe and complications were more frequent in adults: hemoptysis in 14%, pneumothorax in 15%, lung transplantation in 25 patients. Chronic bronchial colonisation with Pseudomonas aeruginosa, in 76% of patients, contributed to making treatments more severe because of antibiotic i.v. courses and nebulised antibiotics. Respiratory function showed a mean FVC of 62 +/- 22% and a mean FEVI of 48 +/- 94%. External pancreatic insufficiency was found in 83%, diabetes in 14%. Intestinal occlusion syndromes were observed in 11% of patients and hepatic cirrhosis in 8%. In spite of the severity of the respiratory disease, theses patients succeeded in social and occupational insertion; 62% were independent, 18% had children and 77% were working or studying. Analysis of the patients according to age at diagnosis showed that, in 38 patients diagnosed after the age of 18 yrs, the respiratory disease was less severe, pancreatic insufficiency and non-respiratory complications were less frequent (34% had pancreatic insufficiency, 5% had diabetes and none had cirrhosis). This may partly be due to the presence of milder CFTR mutations. In conclusion, cystic fibrosis in adulthood frequently looks like an evolutive form of cystic fibrosis in childhood. Nevertheless, some late diagnosed forms in adults, with better prognosis, have been recently identified.

Adolescent↗

Pulmonary lymphangioleiomyomatosis. A study of 69 patients. Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P).

Pulmonary lymphangioleiomyomatosis (LAM) is a rare disorder of unknown cause characterized by peribronchial, perivascular, and perilymphatic proliferation of abnormal smooth muscle cells leading to cystic lesions. The hypothesis of hormonal dependence and the effectiveness of hormonal therapy have not yet been demonstrated conclusively, and the prevalence of extrathoracic manifestations and the survival of patients with LAM are somewhat contradictory. A multicentric retrospective study was conducted in an attempt to describe better the initial features, the diagnostic procedures, the associated lesions, and, above all, the management and course of LAM in a large homogeneous series of 69 stringently selected patients, with a majority of cases diagnosed since 1990. The aim of the study, based on a review of the literature, also was to provide a comprehensive view of this uncommon disease. The clinical features were in keeping with previous studies, but we found that exertional dyspnea and pneumothorax were the most common features, and chylous involvement was less frequent. LAM was diagnosed after menopause in about 10% of cases. The onset of LAM occurred during pregnancy in 20% of cases, and a clear exacerbation of LAM was observed in 14% of cases during pregnancy. Pulmonary LAM was diagnosed on lung histopathology in 83% of cases, but renal angiomyolipoma, observed in 32% of our patients, may be a useful diagnostic criterion when associated with typical multiple cysts on chest CT scan or with chylous effusion. Chest CT scan was more informative than chest X-ray (normal in 9% of cases), and may be indicated in spontaneous pneumothorax or renal angiomyolipoma in women of childbearing age. About 40% of the patients had a normal initial spirometry, while an obstructive ventilatory defect (44%), a restrictive ventilatory defect (23%), was observed in other patients. Initial diffusing capacity for carbon monoxide was frequently decreased (82%). Hormonal therapy was administered in 57 patients, but a clear > or = 15% improvement of FEV1 was observed in only 4 evaluable patients, treated with tamoxifen and progestogens (n = 2), progestogen (n = 1), and oophorectomy (n = 1). Probably 1 of the most urgent needs for clinical research in LAM is to test the currently available hormonal treatments in the context of international multicenter prospective controlled studies. Pleurodesis was performed in 40 patients. Lung transplantation was performed in 13 patients, 7.8 +/- 5.2 years after onset of LAM, in whom the mean FEV1 was 0.57 +/- 0.15 L. After a follow-up of 2.3 +/- 2.2 years, 9 patients were alive. Mean follow-up from onset of disease to either death or closing date was 8.2 +/- 6.3 years. Overall survival was better than usually reported in LAM, and Kaplan-Meier plot showed survival probabilities of 91% after 5 years, 79% after 10 years, and 71% after 15 years of disease duration.

Adolescent↗

[Current aspects of lymphangioleiomyomatosis].

Lymphoangioleiomyomatosis (LAM) is a characteristic diffuse proliferation of abnormal smooth muscle fibers predominantly developing in the lung and leading to cystic destruction. An almost totally specific marker, HMB45, is available. This monoclonal antibody labels cells of the melanocyte line, LAM cells and renal angiomyolipoma cells. The antigen carried by all these cell lines is probably gp-100 involved in melanogenesis. Two gene loci are formally implicated in the pathogenesis of Bourneville tuberous sclerosis (BTS): TSC1 (9q 34.3) and TSC2 (16p 13.3). The TSC2 locus could be implicated in the pathogenesis of pulmonary LAM. LAM and BTS have similar clinical and histological features and could be two different phenotypic forms, distinguished strictly on a nosological basis, of the same disease. The hormone-dependence theory is suggested on the basis of purely clinical arguments, particularly the almost exclusive female predominance, generally during the period of genital activity. Certain counter arguments have also been put forward and consequently, since no in vitro cell culture model or animal model of LAM is available, it is not really possible to verify the hypothesis. Epidemiological data have been recently acquired in France with the constitution of the GERM"O"P registry of LAM cases in France. Recent technological progress in imaging techniques has also been helpful for earlier, more precise diagnosis. HMB45 immunolabeling improves diagnostic sensitivity on small tissue fragments obtained with transbronchial biopsies. The course of LAM appears to be different in certain patient subgroups. Certain patients develop rapidly fatal disease in months or years while in the majority of patients the disease is much less aggressive for years. A minority of patients also have very slowly evolving disease sometimes diagnosed after menopause. Lung transplantation remains the ultimate treatment in case of life-threatening prognosis.

Antigens, Neoplasm↗

Nasal effect of cetirizine and loratadine at 24 hours in patients with allergic rhinitis.

Numerous studies have compared the duration of the cutaneous effect of cetirizine and loratadine. We assessed their nasal effects 24 hours after administration in patients with allergic rhinitis, using a randomized, double-blind, crossover, placebo-controlled trial. Nasal challenge was performed by nebulization of increasing doubling dosages of histamine (0.04-1.28 mg/nostril) in 12 patients (seven males, five females, aged 31 +/- 7 years). Nasal airway resistance was measured by posterior rhinomanometry 24 hours after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline nasal airway resistance was identical on all study days (2.86 +/- 0.10 cm H2 O/L per second). Twenty-four hours after intake, the dose-response curve of nasal obstruction to histamine was significantly lower after treatment with cetirizine compared with placebo (P < 0.05). However, although the curve was lower on loratadine than on placebo, the curves did not differ significantly. In conclusion, our study shows significant efficacy of cetirizine, but not of loratadine, in the nose at 24 hours after a single dose. This suggests that the nasal action of cetirizine is longer lasting than that of loratadine in patients with allergic rhinitis.

Adult↗

Silver/silver chloride electrodes for measurement of potential difference in human bronchi.

BACKGROUND: An easy and reliable method to measure potential difference (PD) in the lower airways would be of interest in the field of cystic fibrosis. We have developed silver/silver chloride (Ag/AgCl) electrodes to measure PD in the lower airways. METHODS: To validate this technique the nasal PD measured with Ag/AgCl electrodes and with conventional perfused electrodes was compared in 16 patients. The range of PD measured with Ag/AgCl electrodes in the lower airways during fibreoptic bronchoscopy was determined in 14 adult patients and in nine the reproducibility of this technique was examined. RESULTS: Nasal PD values measured with Ag/AgCl and perfused electrodes were highly correlated (r = 0.985, p < 0.0001) and the limits of agreement (mean +/- 2SD of the difference) between the two methods were -1.91 mV and 1.53 mV. In the lower airways a progressive and slight decrease in PD values with decreasing airway diameter was observed in most patients. The mean (2SD) of the differences between the two tracheal measurements was 0.21 (1.73) mV. CONCLUSIONS: The use of Ag/AgCl electrodes gives a reliable and reproducible measurement of PD in the lower airways in humans.

Biosensing Techniques↗

Onset of action in the nasal antihistaminic effect of cetirizine and loratadine in patients with allergic rhinitis.

Several studies have compared the cutaneous efficacy of cetirizine and loratadine and their onset of action. We assessed the nasal effect of these two antihistamines in a randomized, double-blind, crossover, placebo-controlled trial in order to compare objectively their efficacy and onset of action in the noses of patients with allergic rhinitis. Nasal challenge was performed by nebulization of increasing doubling doses of histamine (0, 0.04-1.28 mg/nostril) in 12 patients (eight men, four women, aged 22-39 years). Nasal airway resistance (NAR) was measured by posterior rhinomanometry either 1.5 h or 4 h after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline NAR was identical between all study days (2.60-2.88 cmH2O.l-1.s). One and a half hours after intake, the increase in NAR induced by histamine was significantly reduced by both cetirizine and loratadine in contrast to placebo. However, with cetirizine the nasal obstruction was significantly lower than with loratadine (P < 0.05). Four hours after intake, a similar inhibition of the nasal obstruction caused by histamine was observed with both cetirizine and loratadine (P < 0.05). In conclusion, this study found cetirizine and loratadine to have similar nasal efficacy at therapeutic dosage 4 h after intake, whereas cetirizine was more effective than loratadine 1.5 h after intake. In agreement with the results observed in the skin, our study suggests a more rapid onset of action of cetirizine in the nose in allergic rhinitis.

Adult↗

Bronchial gamma delta T-lymphocytes and expression of heat shock proteins in mild asthma.

Heat shock proteins (HSPs), which are important targets for gammadelta T-lymphocytes, are thought to play a role in inflammatory and immune diseases. The purpose of this study was to characterize, in asthma, the presence and distribution of alphabeta and gammadelta T-lymphocytes and of hsp60, hsp70 and hsp90 in bronchial biopsies, and to seek for a co-localization of gammadelta T-cells and HSPs. Ten subjects with mild atopic asthma and nine control subjects underwent fibreoptic bronchoscopy and bronchial biopsies, to which specific monoclonal antibodies and immunohistochemical techniques were applied. T-lymphocytes present in bronchi both of asthmatic and control subjects were predominantly of the alphabeta T-cell receptor phenotype (median 642 cells x mm(-2) (range 85-1,510 cells x mm(-2)), and 855 cells x mm(-2) (286-2,424 cells x mm(-2)), respectively), whereas, gammadelta T-lymphocytes were always rare (median 26 cells x mm(-2) (range 0-114 cells x mm(-2)), and 0 cells x mm(-2 (0-57 cells x mm(-2), respectively). Both in asthmatic and control subjects, bronchial epithelium was positive for hsp60, hsp70 and hsp90. There was no significant difference in the percentages of positive epithelial cells between asthmatic and control subjects. No co-localization of HSPs and gammadelta T-cells was observed. Our findings do not support the hypothesis that heat shock proteins and gammadelta T-cells play an important role in inflammatory and immune responses in mild asthma.

Adult↗

Genotype-phenotype relationships in a cohort of adult cystic fibrosis patients.

In cystic fibrosis (CF), relationships between genotype and phenotype have been shown for pancreatic status but not for pulmonary disease. One hundred and ten adult CF patients were classified according to the expected effect of their mutations on cystic fibrosis transmembrane conductance regulator (CFTR) protein: Group 1 (n=48) included deltaF508 homozygotes; Group 2 (n=26), patients with two "severe" mutations and no expected CFTR production; Group 3 (n=17), patients with expected partly functional CFTR corresponding to at least one "mild" mutation; Group 4 (n=19), patients with no mutation identified or only one identified "severe" mutation. As compared to Groups 1 and 2: patients from Groups 3 and 4 had higher arterial oxygen tension (Pa,O2) (9.5+/-1.9 and 9.9+/-1.5 vs 8.8+/-1.5 and 8.3+/-1.7 kPa, respectively p<0.02); and a slower decline in their pulmonary function, estimated by the mean annual loss in forced vital capacity (FVC) (1.2+/-1.0 and 1.5+/-1.1 vs 2.0+/-0.9 and 2.2+/-1.0%, respectively; p<0.01) and in forced expiratory volume in one second (FEV1) (1.7+/-1.1 and 1.9+/-1.3 vs 2.6+/-1.0 and 2.8+/-1.0%, respectively; p<0.005). They had fewer episodes of colonization of the airways by Pseudomonas aeruginosa, and colonization occurred at a more advanced age (median age 25 and 19 vs 15 and 17 yrs, respectively; p<0.01) and required fewer intravenous antibiotic courses (p<0.01). Pancreatic insufficiency was less frequent in Groups 3 (23%) and 4 (63%) than in Groups 1 (100%) and 2 (96%). This study suggests that the phenotype of adult cystic fibrosis patients, including the severity of the lung disease, is related to the severity of the cystic fibrosis transmembrane conductance regulator mutations.

Adolescent↗

[Primum non nocere: inhaled corticoids].

Several studies have been devoted to the possible deleterious effects of inhaled corticosteroids. These products are effective and have been widely used for longer and longer periods. Tests used to detect systemic effects are now quite sensitive allowing us to identify infraclinical purely biological effects resulting from minimal doses. The real value of these tests in predicting long-term deleterious effects such as adrenal failure, osteoporosis or growth retardation are now recognized. However, it is difficult to incriminate corticosteroids alone in certain cases because "parasite" conditions are often created by systemic corticosteroid therapy and because asthma alone can lead to deleterious extrapulmonary effects which should not be considered to result from treatment alone, emphasizing the need for carefully controlled studies. Despite the description of multiple systemic effects, the clinical consequences of long-term inhaled corticosteroids are not at all in the same range as oral corticosteroids. Nevertheless, there is some debate as to the strict indications for inhaled corticosteroids in adults and in children. The use of minimal effective doses in asthma is a primum non nocere.

Administration, Inhalation↗

Selective recruitment of eosinophils by substance P after repeated allergen exposure in allergic rhinitis.

We have investigated the nasal response to substance P after pollen exposure in seasonal allergic rhinitic patients. Seven patients with strictly seasonal allergic rhinitis were studied during the pollen season, 24 h after nasal challenge with pollen. They received increasing doses of nebulized substance P (0 to 80 nmol) in each nostril. Responses were assessed by measurement of nasal airway resistance by posterior rhinomanometry and quantification of albumin, histamine, and inflammatory cells in the nasal lavage fluid. Nasal airway resistance increased in a dose-dependent manner after substance P challenge. Protein and albumin in nasal lavage fluids increased after administration of substance P: from 2.6 +/- 0.3 to 6.8 +/- 1.1 mg for protein (P < 0.01) and from 0.2 +/- 0.1 to 3.1 +/- 0.6 mg for albumin (P < 0.02). Expressed as a percentage of total protein, albumin increased from 10.5 +/- 3.6% to 39.9 +/- 3.5% (P < 0.02), suggesting occurrence of plasma leakage. No histamine release was observed after challenge with substance P. Total cell counts significantly increased from 11.4 +/- 2.4 to 41.8 +/- 17.3 x 10(3) cells/ml after substance P (P < 0.05). Eosinophils were already numerous before substance P challenge (2.1 +/- 0.7 x 10(3) cells/ml), and the number of eosinophils markedly increased in all patients after substance P (for the whole group, 25.8 +/- 13.3 cells/ml, P < 0.05). In contrast, the number of neutrophils only slightly increased in five patients, and changes did not reach significance for the group as a whole. Our results show that substance P induces nasal obstruction and albumin extrusion in allergic rhinitic patients after repeated pollen exposure. These vascular phenomena are associated with recruitment of eosinophils. Since substance P is known to be released after nasal allergen challenge, our data suggest a role for substance P in the chronic eosinophilic inflammation of the nasal mucosa observed in symptomatic allergic rhinitis.

Administration, Intranasal↗

[Pulmonary lymphangiomyomatosis. Long-term benefit of anti-estrogen treatments remains uncertain].

Lymphangiomyomatosis is a rare disease which affects young women of childbearing age. Ten women with pulmonary lymphangiomyomatosis were treated with antiestrogen therapy from 3 to 9 years (mean time of treatment: 5.3 years). Efficacy of treatment was evaluated by clinical, radiological, pulmonary function testing response as well as the overall long-term outcome. Four patients died of respiratory failure after 3, 5, 5 and 9 years of treatment. Of the 6 patients remaining alive, respiratory function deteriorated in 4 cases after a transient period of mild improvement lasting 3 years in 2 cases. Two patients appeared stable after 3 and 7 years of treatment. Without a control group, although a longer time of survival along these last years, it seems difficult to impute this benefit to the sole antiestrogen treatment and the overall long term prognosis of the disease remains really uncertain.

Adult↗

Do nasal mast cells release histamine on stimulation with substance P in allergic rhinitis?

The effects of nasal administration of increasing doses of exogenous substance P have been studied in patients with allergic rhinitis treated with placebo or with the H1 antagonist cetirizine (10 mg twice daily for 3 days). Responses to substance P were assessed by posterior rhinomanometry (measuring nasal airway resistance) and by measure of histamine, protein and albumin production and cell recovery in nasal lavage fluids before and after challenge. Substance P induced a dose-dependent increase in nasal airway resistance which was similar after treatment with either cetirizine or placebo (maximal increase in nasal airway resistance was 4.2-fold greater than the baseline with the placebo and 4.7-fold greater than the baseline with cetirizine). No histamine release was observed. Similar increases in protein and albumin production were observed after stimulation with substance P along with the placebo (protein: from 0.35 +/- 0.11 to 3.31 +/- 0.62 mg and albumin: from 0.09 +/- 0.04 to 2.08 +/- 0.39 mg) and when combined with cetirizine treatment (proteins: from 0.42 +/- 0.09 to 3.62 +/- 0.77 and albumin: from 0.17 +/- 0.04 to 2.19 +/- 0.51 mg). After stimulation with substance P, percentages of neutrophils recovered in nasal fluids increased from 26.2 +/- 11.5 to 54.5 +/- 9.5 with the placebo and from 35.5 +/- 11.0 to 53.6 +/- 9.5 with cetirizine. Eosinophils were inconsistently found after substance P stimulation during both treatments. In conclusion, nasal response to substance P is not modified by cetirizine which suggests that the effect of substance P is not secondary to histamine release in the nose in man.

Adult↗

[Multifocal epithelioid hemangioendothelioma with partial remission after interferon alfa-2a treatment].

INTRODUCTION: Epithelioid hemangioendothelioma (EHE) is a rare vascular tumour of the soft tissue having an intermediate malignancy. Cutaneous presentations have exceptionally been reported. OBSERVATION: A young woman, initially affected by an EHE with cutaneous and bone involvement, then with pulmonary and hepatic localizations, was in partial remission after one year of treatment with alpha 2a interferon. DISCUSSION: In a critical review of the literature, we describe the main features of this tumour and the difficulties to classify this entity in the vascular tumors' spectrum. Histologically, epithelioid hemangioendothelioma has a very characteristic appearance and is clearly different from other vascular tumors as angiolymphoid hyperplasia with eosinophilia and Kimura's disease. The assumption of a multicentric or a metastatic origin when multiple tumor deposits are found, is still not elucidated. Different therapeutic approaches are proposed: surgery, interferon, interleukin-2, retinoids. Randomized studies would be necessary to confirm our results with alpha 2a interferon but are probably difficult to realize because of the lack of cases.

Adult↗

[Langerhans cell pulmonary granulomatosis].

Langerhans' cell granulomatosis, formerly known as histiocytosis X include several granulomatosis of unknown aetiology. The original pathological finding is a Langerhans' cell granuloma. Recent progress has improved our understanding of the pathogenesis of this group of diseases and facilitated the diagnosis. We describe here the cell populations involved, the general pathology of Langerhans' cells, proposed pathogenesis, and the relationship between Langerhans' cell pulmonary granulomatosis and other localizations of Langerhans' cell granulomatosis. Finally, the clinical manifestations, elements of diagnosis and changing attitudes of current therapy are discussed.

Bronchoalveolar Lavage Fluid↗

[Asthma with permanent obstructive ventilation disorder].

Asthma accompanied by chronic airways obstruction (CAO) is frequent and raises difficult clinical problems. Persistent inflammation of the airways is the main factor responsible for obstruction. There are no symptoms that distinguish this form of asthma from non-asthmatic chronic obstructive lung disease, and only respiratory function tests can confirm the diagnosis of CAO. Pharmacological tests with bronchodilators evaluate the bronchomotor part of CAO which is substantial in asthma as opposed to other causes of obstructive lung diseases. A negative test cannot exclude the diagnosis and suggests that the obstructive component due to bronchial inflammation is predominant. In such case a reversibility test performed with corticosteroids is of considerable interest as it reduces the partly reversible inflammatory part of the obstruction. Peak flow curves provide more precise date on the evolutive type of CAO and therefore contribute to a great extent to the monitoring and education of patients. Severe chronic asthma with high annual systemic corticosteroid consumption requires special care and justifies the current attempts made to replace corticosteroids by other anti-inflammatory drugs.

Asthma↗

Pulmonary lymphangiomyomatosis. Follow-up and long-term outcome with antiestrogen therapy; a report of eight cases.

Lymphangiomyomatosis is a rare disease which affects young women of childbearing age. Eight women with pulmonary LAM were treated with antiestrogen therapy and were monitored by blood estrogen measurements along with clinical hypoestrogenic symptoms. Treatment ranged from three to nine years. The response to therapy was evaluated by the clinical course, chest x-ray films, pulmonary function tests and overall long-term outcome. Three patients died of respiratory failure after three, five and nine years of treatment. Of the five patients remaining alive, respiratory function deteriorated in four cases, after a transient period of mild improvement lasting three years in two cases. The last patient appeared stable after three years of follow-up. Time course ranged from 4 to 17 years. However, without a control group, we cannot determine whether or not the apparent improvement of the natural time course was due to the hormonal treatment.

Adult↗