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Biomedical subjects

A Didier

Publications and source records attributed to A Didier.

At least 37 records · Page 2Linked to original sources

[Allergic rhinitis in children].

The diagnosis of allergic rhinitis (AR) in children is mainly based upon history which leads to distinguish between seasonal (periodic or intermittent) pollinic AR and perrenial (permanent or chronic) AR. The consequences of an AR can be severe with major nasal discomfort, repercussion on quality of life and school attendance, and impact on facial bone growth. In addition it can be complicated by asthma. Specific desensitization is the only treatment which may modify the immune response towards allergens. However it must be compared with the other treatments including local or general antihistaminic drugs and intranasal corticosteroids, the choice resting upon the severity of the symptoms, the respiratory repercussion, and the age of the child.

Adrenal Cortex Hormones↗

The score for allergic rhinitis (SFAR): a simple and valid assessment method in population studies.

BACKGROUND: No validated assessment of allergic rhinitis (AR) is presently available that can be used in population studies in the absence of medical diagnosis and of objective measurements of allergy. To compensate for this lack, a quantitative Score For Allergic Rhinitis (SFAR) ranging between 0 and 16 has been developed by experts. METHODS: The SFAR, encompassing eight features of AR, was validated in three different ways: 1) among 269 outpatients taking the specialist's diagnosis of AR and skin prick tests (SPT) positivity as a gold standard (diagnosis validation); 2) using psychometric methods (internal validation); and 3) in a random population-based sample of 3001 individuals by telephone interview (population acceptability). RESULTS: A SFAR value > or = 7 allowed satisfactory discrimination between the outpatients with AR from those without (sensitivity = 74% [95% confidence interval CI: 0.69,0.79], specificity = 83% [0.79, 0.87], positive predictive value = 84% [0.80, 0.88], negative predictive value = 74% [0.69, 0.79] and Youden's index = 0.57, respectively). Internal consistency of the score was also high (among others, Cronbach's alpha coefficient = 0.79). On average, it took only 3 min for the individuals interviewed on the phone to complete the questionnaire, the questions of which were well understood. Among these subjects, the prevalence of AR was 21% [95% CI: 19.5%, 22.5%], which is comparable to other determinations in France. CONCLUSIONS: The newly a priori proposed Score For Allergic Rhinitis (SFAR) is easy to use and can be useful to estimate prevalence and to study causation of AR in population settings.

Adolescent↗

A dendrodendritic reciprocal synapse provides a recurrent excitatory connection in the olfactory bulb.

Neuronal synchronization in the olfactory bulb has been proposed to arise from a diffuse action of glutamate released from mitral cells (MC, olfactory bulb relay neurons). According to this hypothesis, glutamate spills over from dendrodendritic synapses formed between MC and granule cells (GC, olfactory bulb interneurons) to activate neighboring MC. The excitation of MC is balanced by a strong inhibition from GC. Here we show that MC excitation is caused by glutamate released from bulbar interneurons located in the GC layer. These reciprocal synapses depend on an unusual, 2-amino-5-phosphonovaleric acid-resistant, N-methyl-d-aspartate receptor. This type of feedback excitation onto relay neurons may strengthen the original sensory input signal and further extend the function of the dendritic microcircuit within the main olfactory bulb.

2-Amino-5-phosphonovalerate↗

Molecular cloning and characterization of human VPS18, VPS 11, VPS16, and VPS33.

In multicellular organisms, the delivery of proteins to lysosomes is essential. Many of the genes necessary for this process have first been identified by their requirement for vacuolar delivery in yeast. A subset of these genes, the four class C vps genes, is necessary for the delivery of endocytic and biosynthetic cargo in yeast, and also in Drosophila. Here, we describe the sequence and expression pattern of four human homologs of these genes. This initial molecular description of these four genes is an important step towards their evaluation as candidate genes that may be involved in the pathogenesis of Hermansky-Pudlak syndrome-related diseases.

Amino Acid Sequence↗

Immunohistochemical detection of simian immunodeficiency virus (SIV) in rectal mucosa of experimentally infected rhesus macaques (Macaca mulatta).

Experimental simian immunodeficiency virus (SIV) infection is the most appropriate animal model for human HIV infection. Eight male rhesus monkeys (Macaca mulatta) were intravenously or intrarectally infected with SIVmac251/MPBMC to comparatively investigate the distribution and spread of the virus within the rectum during the course of the disease. SIV-positive cells were immunohistochemically detected in rectal biopsies obtained at days 3 and 7 and week 2, 4 and 12 postinfection. SIV-expressing cells were detected for the first time at one week after experimental infection and were present in the lamina propria and lymph follicles. Numbers of positive cells per individual animal varied strongly in time, with a more rapid rise in animals with rapid progression of the disease. Differences were not observed between intravenous and intrarectal infection. Our observations support the significance of the intestinal tract as target organ in initial pathogenesis of SIV infection.

Animals↗

Nasal polyp-derived superoxide anion: dose-dependent inhibition by nitric oxide and pathophysiological implications.

The epithelium of the paranasal sinuses produces nitric oxide (NO), which probably plays a major role in the nonspecific defense of these cavities through its bacteriostatic and cilia motility stimulation properties. Abundant eosinophils of nasal polyps potentially generate superoxide anion (O2-*), but NO and O2-* inactivate reciprocally. The purpose of the present work was to evaluate the relationship between NO concentrations and nasal polyp production of O2-*. Polyp fragments from 24 patients were studied using histological examination and lucigenin-enhanced chemiluminescence (to assess O2-* production). The effect of various concentrations of exogenous NO on chemiluminescent signals was assessed. Basal and phorbol ester-stimulated O2-* production varied largely among patients, but both were highly related to eosinophilic infiltration. A slow releasing NO donor DETA NONOate (DETA/NO NOC-18) dose dependently inhibited lucigenin-enhanced chemiluminescence from phorbol ester-stimulated polyp fragments, with an EC50 of 1.5 mM. The NO concentration in normal maxillary sinus was estimated about 10 ppm (i.e., 0.5 microM in aqueous phase) (Lundberg, et al. Nature Med 1995;1:370). Calculations revealed that the DETA NONOate 0.75 mM and 1.5 mM generate steady-state concentrations of NO of 0.5 microM and 2.5 microM, respectively. In conclusion, the NO concentration present in paranasal sinuses appears to partially suppress (approximately 20-40%) O2-* production from polyp eosinophils. Conversely, phagocytic-derived O2-* could contribute to decrease sinus NO concentration, further altering this natural local defense. Together, these events could participate in chronic inflammation and contribute to the pathophysiology of nasal polyps.

Acridines↗

[An unusual opacity of the right base].

The scimitar syndrome or pulmonary venolobar syndrome is a rare, complex and variable malformation of the right lung characterized by an abnormal right sided pulmonary venous drainage in the inferior vena cava, malformation of the right lung, abnormal arterial supply and sometimes cardiac malformations. We present a case in which this diagnosis was suspected on an abnormal routine chest radiograph in a 38-year-old asymptomatic woman. Most patients are asymptomatic; symptomatic patients have a marked left-to-right shunt or a severe congenital heart disease. They usually suffer from shortness of breath, asthenia or repeated chest infections. Usually, the posteroanterior chest radiograph can confirm the diagnostic. It shows the abnormal vein draining into the inferior vena cava as a curved vascular shadow with a scimitar like appearance. However, in some cases, when the scimitar vein is masked by the overlying cardiac shadow, computed tomography, angiography and magnetic resonance imaging can be helpful by showing the abnormal vein and its insertion into the inferior vena cava. Scimitar syndrome seldom necessitates surgical intervention. However, repeated lung infections can sometimes require lobectomy or pneumonectomy, left-to-right shunt vascular surgery to redirect the scimitar vein into the left atrium.

Adult↗

[Allergic rhinitis].

Allergic rhinitis is one of the commonest diseases. The main allergens responsible are respiratory allergens. Pollinic or seasonal allergic rhinitis is currently distinguished from perannual or nonseasonal rhinitis, generally related to sensitization to allergens of the home environment. The diagnostic approach of allergic rhinitis is based on a careful clinical examination, in order to eliminate other causes of nasal dysfunction, and on complementary investigations, most importantly allergic skin tests. Several types of drugs, topically or systemically administered are currently available to treat allergic rhinitis. Surgical techniques should be reserved to patients who resist to medical treatment or to correct nasal architectural abnormality.

Adolescent↗

Aureobasidins: structure-activity relationships for the inhibition of the human MDR1 P-glycoprotein ABC-transporter.

Cyclic depsipeptide cyclo-[D-Hmp(1)-L-MeVal(2)-L-Phe(3)-L-MePhe(4)-L-Pro(5)-L-aIle+ ++(6)-L-MeVal(7)-L-Leu(8)-L-betaHOMeVal(9)], the antifungal antibiotic aureobasidin A (AbA), was reported to interfere with ATP-binding cassette (ABC) transporters in yeast and mammalian cells, particularly the MDR1 P-glycoprotein (Pgp), a transmembrane phospholipid flippase or "hydrophobic vacuum cleaner" that mediates multidrug resistance (MDR) of cancer cells. In a standardized assay that measures Pgp function by the Pgp-mediated efflux of the calcein-AM Pgp substrate and uses human lymphoblastoid MDR-CEM (VBL(100)) cells as highly resistant Pgp-expressing cells and the cyclic undecapeptide cyclosporin A (CsA) as a reference MDR-reversing agent (IC(50) of 3.4 microM), AbA was found to be a more active Pgp inhibitor (IC(50) of 2.3 microM). Out of seven natural analogues and 18 chemical derivatives of AbA, several were shown to display even more potent Pgp-inhibitory activity. The Pgp-inhibitory activity was increased about 2-fold by some minor modifications such as those found in the naturally occurring aureobasidins AbB ([D-Hiv(1)]-AbA), AbC ([Val(6)]-AbA), and AbD [gammaHOMeVal(9)]-AbA). The replacement of the [Phe(3)-MePhe(4)-Pro(5)] tripeptide by an 8-aminocaprylic acid or the N(7)()-desmethylation of MeVal(7) led to only a 3.3-fold decreased capacity to inhibit Pgp function, suggesting that the Pgp inhibitory potential of aureobasidins, though favored by the establishment of an antiparallel beta-sheet between the [D-Hmp(1)-L-MeVal(2)-L-Phe(3)] and [L-aIle(6)-L-MeVal(7)-L-Leu(8)-] tripeptides, does not critically depend on the occurrence of the [L-Phe(3)-L-MePhe(4)-L-Pro(5)-L-aIle(6)] type II' beta-turn secondary structure. In contrast, the most potent Pgp inhibitors were found among AbA analogues with [betaHO-MeVal(9)] residue alterations, with some data suggesting a negative impact of the [L-Leu(8)-L-betaHOMeVal(9)-D-Hmp(1)] gamma-turn secondary structure on Pgp inhibitory potential. The [2,3-dehydro-MeVal(9)]-AbA was the most potent Pgp inhibitory aureobasidin, being 13-fold more potent than AbA and 19-fold more potent (on a molar basis) than CsA. Finally, there was no correlation between the SAR for the human MDR1 Pgp inhibition and the SAR for Saccharomyces cerevisiae antifungal activity, which is mediated by an inositol phosphoceramide synthase activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Long-term follow-up study on SIV intestinal proviral load in rhesus macaques.

After experimental infection with simian immunodeficiency virus (SIV), intestinal endoscopy proved to be an easily tolerated, minimal invasive procedure to obtain biopsies from the gastrointestinal tract of rhesus macaques during all stages of disease. As the GI tract is affected by many opportunistic infections and immunological impairment after SIV/human immunodeficiency virus (HIV) infection, knowledge on the proviral load is an important parameter for a better understanding of disease pathogenesis. In this paper, we describe the set-up and evaluation of a quantitative competitive polymerase chain reaction (PCR) and the quantification of SIV intestinal proviral load in a long-term follow-up study of eight rhesus monkeys (Macaca mulatta) after two different routes of virus inoculation. A SIV-specific signal could be detected as early as day 3 after infection. Of 143 biopsies from the follow-up study, 85.3% showed a positive PCR. DNA copy numbers ranged from 300 to 15,000 molecules per 100,000 cells. No significant influence of the inoculation route could be shown on either proviral load or survival time, but higher SIV proviral load was associated with a more rapid progression to disease. Therefore, the amount of proviral load in intestinal biopsies may be an important prognostic value for the further course of the disease.

Animals↗

[A rare cause of asthma exacerbation: systemic anguilluliasis].

Strongyloides is an helminthic infection that may induce bronchospasm during systemic migration of larvae. We report a case of a 60 years old man originating from Caribbean who had corti-codependent asthma since 30 years. He was hospitalized for severe exacerbation that worsen when steroid dosage was increase. Sputum examination revealed the presence in great number of Larvae of Strongyloides stercoralis. A good clinical evolution was achieved after specific anti-helminthic treatment. Later on, it was even possible to stop completely steroid treatment. This clinical case demonstrates the interest to look for Strongyloides superinfection in asthmatic patients that worsen when receiving increasing dose of steroids. This is particularly important for patients who have resided, even many years earlier, in areas where intestinal helminthic infection are endemic.

Animals↗

[Results of 248 patients with sleep apnea syndrome treated by continuous positive pressure ventilation between 1990 and 1995. A study of compliance and outcome of the apnea-hypopnea index].

Between 1990 and 1995, 369 patients were investigated for obstructive sleep apnea syndrome (OSAS) by polysomnography. Among them, 248 patients with a mean Apnea-Hyponea index (AHI) of 37.7 per hour were treated by nasal continuous positive airway pressure (n-CPAP). Mean follow up was 39.5 +/- 20.4 months. In this group, 23 patients (9.2%) refused nCPAP immediately or after the first night and 39 (15.7%) gave up later. 15 patients (6%) died during the period of the study. The cumulative compliance reached 70% at 72 months. Non compliant patients usually gave up n-CPAP before the end of the first year. We compared the group of 150 patients always treated at the date of 31/12/95 with the group of 62 patients who refused nCPAP initially or gave up later. There was no difference in clinical parameters or polysomnographic data between the two groups. In 94 patients treated by nCPAP for more than a year we evaluated the outcome of AHI by a polysomnography performed after 72 hours of nCPAP cessation. Mean AHI of the group at this time was 38.2 +/- 20.3/h and was well correlated with the initial index (r = 0.41, p < 0.0001). However for 28 patients (29.7%) we observed, at the time of this second AHI determination, a variation (plus or minus) of at least 50% of the index. 6 patients, without any significative weigth loss, had an AHI below 5/h at this second determination. In this small group nCPAP was interrupted for 6 to 12 months, then another polysomnography was performed. At this time mean AHI was 42.4/h and clinical symptoms had reappeared in all patients. This study demonstrated that compliance to nCPAP in OSAS patients is good. No clinical or polysomnographic factors allow to predict non compliance. AHI is not modified by long term treatment with nCPAP.

Female↗

[Vocal cord dysfunction simulating severe corticoid-dependent asthma].

We report a case of severe asthma initially considered as cortico-resistant. Clinical analysis of dyspneic attacks demonstrated they were atypical, sometimes associated with dysphonia and syncopes. Severity of clinical presentation was discordant with lung function tests. The diagnosis of vocal cord dysfunction was confirmed by ENT specialized examination. It showed paradoxal inspiratory adduction of the vocal cords triggered by exercise. Treatment remained however difficult, based on speech therapy, relaxation and psychotherapy. This observation underlines the influence of searching a vocal cord dysfunction in cortico-dependent asthma, especially if clinical presentation is atypical. Treatment of this condition may allow to decrease steroid treatment in such patients.

Adrenal Cortex Hormones↗

[Allergologic diagnosis].

There are two phases in allergologic diagnosis of respiratory diseases related to immediate hypersensitivity reactions: establishment of the allergic origin of the symptoms and identification of the causal allergen or allergens. In addition to the basic information obtained from history taking and physical examination, prick tests provide an easy, rapid, and low cost means of correctly identifying specific allergens. Laboratory tests such as serum assay of specific IgE can be useful when history and prick tests provide conflicting information, in exceptional cases when prick tests cannot be performed, or when specific desensitization is indicated. IgE assay is however of little use if prick tests are negative or clinical history poorly suggestive. The role of screening for atopy using multiple-allergen prick tests which give a global positive or negative result is poorly defined. Screening tests would be interesting if symptoms suggest, among other hypotheses, an allergic disease, especially if prick tests cannot be performed rapidly. Other atopy tests, such as total serum IgE, have little use. Finally, specific provocation tests are rarely needed for routine allergologic diagnosis. They may be useful in complex clinical situations or in particular conditions such as occupational allergy.

Bronchial Provocation Tests↗

[Chronic necrotizing pulmonary aspergillosis and ankylosing spondylarthritis].

Fibro-bullous disease is a late complication of ankylosing spondylarthritis. Its radiologic features frequently mimics tuberculosis or excavated neoplasm. About 50 to 65% of patients with ankylosing spondylarthritis have chronic aspergillus colonization of their airways. Pulmonary aspergillosis infection occurs in 10 to 30% during evolution. We report two cases of patients with spondylarthritis who developed chronic necrotizing pulmonary aspergillosis. Diagnosis was based on serology, mycologic examination of expectoration and in one case on histology obtain by transbronchial biopsies. Pulmonary complications due to aspergillus species frequently reveal an associated fibro-bullous disease in patients with ankylosing spondylarthritis. This can be reported to diminished chest wall movements in such patients. Treatment is based on administration of anti-fungal drugs. In case of medical treatment failure, thoracic surgery may be indicated.

Adult↗