Barriers to viral load suppression among adolescents living with HIV on anti-retroviral therapy: a retrospective study in Tanga, Tanzania.

BACKGROUND: Despite the decreased incidence of the human immunodeficiency virus (HIV) in Tanzania, the number of adolescents living with HIV is increasing. This study aimed to describe factors independently associated with viral load non-suppression among adolescents living with HIV (ALHIV) on ART in the Tanga region. METHODS: We conducted a retrospective study of routinely collected data from ALHIV on ART from October 2018 to April 2022. We extracted data from the Care and Treatment Clinics form number 2 (CTC2) database that included age, sex, BMI, World Health Organization HIV clinical disease stage, marital status, ART duration, viral load suppression, facility level, and Dolutegravir (DTG)-based regimen. We did descriptive analysis using frequencies to describe the study participants' socio-demographic and clinical characteristics. The Cox proportional hazard regression model was used to identify factors associated with viral load non-suppression (VLS). Viral load non-suppression was defined as viral load ≥ 1000 copies/ml. A total of 4735 ALHIV on ART were extracted from CTC2, then 2485 were excluded (2186 missed viral load results, 246 were lost to follow-up, and 53 deaths). RESULTS: 2250 ALHIV on ART were tested for viral load, of whom 2216 (98.62%) adolescents were on first-line ART, and 2024 (89.96%) participants were virally suppressed, while 226 (10.04%) were virally non-suppressed. In addition, 2131 (94.71%) of participants were using a DTG-based regimen; of them, 1969 (92.40%) were virally suppressed. Not using a DTG-based regimen (HR: 9.36, 95% CI 3.41-15.31) and dispensary facility level (HR: 3.61, 95% CI 1.44-7.03) were independently associated with increased hazard for viral load non-suppression. In addition, adolescents aged between 15 and 19 years are less likely to be virally suppressed (HR: 0.55, 95% CI 0.30-0.99). CONCLUSIONS: The dispensary facility level and not using a DTG-based regimen were significantly associated with viral load non-suppression. HIV intervention strategies should ensure a DTG-based regimen utilization in all adolescents living with HIV, and techniques used by higher-level health facilities should be disseminated to lower-level facilities.

Risk factors for interruption in treatment among HIV-infected adolescence attending health care and treatment clinics in Tanzania.

BACKGROUND: Interruption in Treatment (IIT) is a challenge in HIV care and treatment programs in sub- Saharan Africa. High IIT among HIV adolescents has both individual and potential public health consequences including discontinuation of treatment, increased HIV transmission and risk of death. In this era of test and treat policy it is important to ensure that patients remain connected to HIV clinics to enable achieve UNAIDS 95-95-95 targets timely. This study aimed to assess risk factors for IIT among HIV-positive adolescence in Tanzania. METHODS: We conducted retrospective longitudinal cohort study using secondary data of adolescent patients enrolled in care and treatment clinics in Tanga from October 2018 to December 2020. We defined Interuption in Treatment as missing clinic visits for 90 consecutive days after the last scheduled appointment date on anti-retroviral therapy (ART). Cox proportional hazard regression models were employed to identify risk factors of the outcome variable. RESULTS: Among 2,084 adolescents of age between 15 and 19 years were followed for two years, whereby 546 (26.2%) had interrupted treatment. The median age of the participants was 14.6 years (interquartile range, IQR: 12.6-16.6 years), with age between 15 and 19 years, male sex, with advanced HIV disease and were not on Dolutegravir (DTG) related regimens were associated with interruption in treatment; (Hazard ratio (HR) 1.43, 95% CI: 1.23-1.66, p < 0.0001, HR 2.47, 95% CI: 1.62-3.77, p < 0.0001, HR: 2.47, 95% CI: 1.91- 3.21, p < 0.0001 and HR: 6.67, 95% CI: 3.36- 7.04, p < 0.0001 respectively). Adolescents who were on ART for less or equal one year compared to those on ART for more than one year were protective toward interruption in treatment (HR: 0.68, 95% CI: 0.54-0.87, p = 0.002). CONCLUSIONS: The risk of interruption in treatment was high among adolescents in HIV care and treatment facilities in Tanga. This might lead to poor clinical outcomes, and increased drug resistance among ART-initiated adolescents. Placing more adolescents with DTG based drug, strengthening access to care and treatment and rapid tracking of patients is recommended to improve patient outcomes.

Underage Adolescents' Reactions to Adverts for Beer and Spirit Brands and Associations with Higher Risk Drinking and Susceptibility to Drink: A Cross-Sectional Study in the UK.

AIMS: In the UK, adolescents under the minimum legal purchasing age (<18 years) are aware of a variety of alcohol marketing activities. It is therefore important to examine how such marketing appeals and how it might shape consumption. This study assessed the relationships between positive reactions to alcohol adverts and susceptibility to drink among never drinkers and higher-risk drinking among current drinkers. METHODS: Online cross-sectional survey of 11-17 year olds (n = 2582) in the UK. Adolescents were shown three video alcohol adverts (Fosters Radler/Haig Club Clubman/Smirnoff). Reactions to each were measured by eight scale-items (e.g. 1 = makes [Brand] seem unappealing to 5 = makes [Brand] seem appealing), which were combined into a composite score (coded: positive versus other). Logistic regressions assessed associations between overall positive advert reactions and drinking behaviours. RESULTS: Half of adolescents had overall positive reactions to the Smirnoff (52%) and Fosters (53%) adverts, and a third (34%) had a positive reaction to the Haig Club advert. Across all three adverts, positive reactions were associated with ~1.5 times increased odds of being susceptible to drink among never drinkers. Among current drinkers, positive reactions to the Foster's Radler and Haig Club adverts were associated with around 1.4 times increased odds of being a higher-risk drinker. CONCLUSIONS: These alcohol advertisements commonly appealed to underage adolescents, and these reactions were associated with susceptibility among never drinkers and higher-risk consumption among current drinkers. Regulatory consideration should be given to what messages are permitted in alcohol advertising, including international alternatives (e.g. only factual information).

A qualitative account of young people's experiences of alcohol screening and brief interventions in schools: SIPS Jr-HIGH trial findings.

BACKGROUND: The United Kingdom (UK) has seen a decrease in the number of young people drinking alcohol. However, the UK prevalence of underage drinking still ranks amongst the highest in Western Europe. Whilst there is a wealth of evidence reporting on the effectiveness of both primary, and secondary interventions, there are few reports of the experiences of young people who receive them. METHODS: The present study reports findings from interviews with 33 young people who were involved in an alcohol screening and brief intervention randomized controlled trial in schools in England. All interviews were analysed using inductive applied thematic analysis. RESULTS: Three major themes were identified following the analysis process: 1) drinking identities and awareness of risk; 2) access to support and advice in relation to alcohol use; and 3) appraisal of the intervention and potential impact on alcohol use. CONCLUSIONS: There appeared to be a reluctance from participants to describe themselves as someone who drinks alcohol. Furthermore, those who did drink alcohol often did so with parental permission. There was variation amongst participants as to how comfortable they felt talking about alcohol issues with school staff. Overall participants felt the intervention was useful, but would be better suited to 'heavier' drinkers.

A qualitative exploration of school-based staff's experiences of delivering an alcohol screening and brief intervention in the high school setting: findings from the SIPS JR-HIGH trial.

BACKGROUND: Whilst underage drinking in the UK has been declining in recent years, prevalence is still higher than in most other Western European countries. Therefore, it is important to deliver effective interventions to reduce risk of harm. METHODS: Semi-structured interviews with staff delivering an alcohol screening and brief intervention in the high-school setting. The analysis was informed by normalization process theory (NPT), interviews were open coded and then a framework applied based on the four components of NPT. RESULTS: Five major themes emerged from the analysis. The majority of participants felt that the intervention could be useful, and that learning mentors were ideally suited to deliver it. However, there was a feeling that the intervention should have been targeted at young people who drink the most. CONCLUSIONS: The intervention was generally well received in schools and seen as an effective tool for engaging young people in a discussion around alcohol. However, in the future schools need to consider the level of staffing in place to deliver the intervention. Furthermore, the intervention could focus more on the long-term risks of initiating alcohol consumption at a young age.

Endothelin receptor antagonists -- their role in pulmonary medicine.

INTRODUCTION: Understanding of the function of endothelin-1 in the pathophysiology of endothelial disease, in particular pulmonary arterial hypertension (PAH), has paved the way for the development of endothelin-receptor antagonists (ERAs) and explains the leading role they now play in the treatment armamentarium for this disease. BACKGROUND: Three active ERA drugs (bosentan, sitaxentan, ambrisentan) are currently approved for the treatment of PAH in France. Several randomised clinical trials have demonstrated their efficacy and safety in PAH. PERSPECTIVES AND CONCLUSION: Besides its vasoconstrictor effect, endothelin-1 (ET-1) plays a pivotal role in cell proliferation and apoptosis. ERAs are innovative drugs potentially useful in some pulmonary disorders such as idiopathic pulmonary fibrosis or systemic sclerosis, even though the preliminary results published remain insufficient or controversial. CONCLUSION: ERAs play a major role in the management of pulmonary vascular disease. Other drugs, still under study, could prove useful in the treatment of infiltrating pneumonias.

[Endothelin receptor antagonists - their role in pulmonary medicine]. / Les antagonistes des récepteurs de l'endothéline: leur place dans les maladies pulmonaires.

INTRODUCTION: There has been an explosion of interest in the biology of endothelin-1 in endothelium disease's physiopathology and in particular pulmonary arterial hypertension (PAH). This interest led up to the development of endothelin-receptor antagonists (ERA) drugs as major therapy for advanced PAH. STATE OF THE ART: Three active ERA drugs (bosentan, sitaxentan, ambrisentan) are nowadays approved for the treatment of PAH. Several randomised clinical trials have demonstrated their efficacy and safety in such domain. PERSPECTIVES AND CONCLUSION: Besides its vasoconstrictive effect, endothelin-1 (ET-1) plays a pivotal role on cell proliferation and apoptosis. ET-1 is a particularly interesting molecule linking idiopathic pulmonary fibrosis or systemic sclerosis, although preliminary results are still insufficient or controversial to conclude. CONCLUSION: The role of endothelin-1 in the pathogenesis of fibrosis and angiogenesis needs to be clarified and the interest of ERA in the diseases in which such injuries are preponderant might be demonstrated by further clinical trials.

[When should patients be referred by the physician to the lung transplant team? Patient selection, indications, timing of referral and preparation for lung transplantation]. / Quand le pneumologue doit-il envisager la greffe pulmonaire pour un de ses patients adulte? Indications, critères de sélection, préparation à la greffe.

INTRODUCTION: Lung transplantation (LT) is accepted as a therapeutic option in a wide range of end stage lung diseases, with evidence supporting survival and quality of life benefits in transplant recipients. Appropriate patients who have good chance of survival with transplantation should be identified carefully. STATE OF THE ART: Four diagnoses account for approximately 80% of transplant recipients: chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis and alpha-1-antitrypsin deficiency emphysema. The aim of this review is to discuss the selection process of potential candidates and to assist physicians in referring these patients to a transplant team. The decision to refer patients for transplantation is difficult and depends on several parameters such as the results of transplantation, the referring physician's view of survival prospects with actual medical therapy according to the pathology, and also the patient's physical, nutritional and psychological status. The timing of listing patients remains a difficult decision which is imposed by both defined criteria and uncertain events such as the rapid worsening of the lung disease and the likely waiting time. PERSPECTIVES: The optimal modalities for pre-surgical rehabilitation programs and their postoperative impact should be evaluated. CONCLUSIONS: Careful selection of potential candidates for lung transplantation at the most appropriate time should lead to an improvement of survival of such patients.

CTLA-4-mediated regulatory phenotype of T-cells in tolerant lung recipients.

Obliterative bronchiolitis (OB) is the major cause of long-term lung allograft loss resulting from an unclear immune process occurring in the absence of the donor's immune cells. The present authors hypothesised that interactions of autologous dendritic cells (DCs) with T-cells could differ in OB patients compared with healthy lung transplant recipients (LTRs). Monocyte-derived DCs from 14 OB and 35 non-OB LTRs were cultured with autologous T-cells. T-regulatory (T(reg)) cells, co-receptors, cytokine production, DC phenotype and indoleamine 2,3-dioxygenase (IDO) expression were assessed by flow cytometry. Experiments were repeated in the presence of Pseudomonas aeruginosa or anti-co-receptor antibodies. DCs from non-OB LTR upregulated T(reg) cells, cytotoxic T-lymphocyte antigen (CTLA)-4 and interleukin (IL)-10. By contrast CD28 and inducible T-cell co-stimulator were downregulated concomitantly to IL-13 and IL-4. Compared to OB, non-OB DCs displayed an immature phenotype with lower CD80 and CD83 and higher IDO levels of expression. Stimulation by P. aeruginosa did not abolish the tolerogenic effects of DCs on non-OB T-cells. Finally, decreased T(reg) cells and IL-10 production were detected when adding anti-CTLA-4 antibodies in non-OB LTR. The present study demonstrates that dendritic cells from nonobliterative bronchiolitis lung transplant recipients induce a tolerant T-cell phenotype which is dependent on cytotoxic T-lymphocyte antigen-4 engagement.

Intracortically distributed neurovascular coupling relationships within and between human somatosensory cortices.

The coupling of neuronal cellular activity to its blood supply is of critical importance to the physiology of the human brain and has been under discussion for more than a century. Linearity in this relationship has been demonstrated in some animal studies, but evidence is lacking in humans. In this study, we compared scalp evoked potentials and the functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signal from healthy human volunteers with changes in the intensity of a somatosensory stimulus. By weighting the fMRI images according to the evoked potential amplitude at corresponding intensities, we tested for positive and negative covariation between these 2 data sets and the extent to which these were linear. Hemodynamic changes in primary somatosensory cortex covaried positively with neuronal activity in a predominantly linear manner, with a small quadratic contribution. Simultaneously, other cortical areas corresponding to the nonstimulated limbs were found to covary negatively and linearly in the hemispheres ipsilateral and contralateral to the stimulus. These concurrent and bilateral cortical dynamics, as well as the intraregional features of this neurovascular coupling, are both more complex than had been considered to date, with considerable implications.

Monitoring emergence from coma following severe brain injury in an octogenarian using behavioural indicators, electrophysiological measures and metabolic studies: a demonstration of the potential for good recovery in older adults.

This case study describes a multi-disciplinary investigation of the emergence from coma of an 80-year old female (KE) following severe traumatic brain injury. The relationship between cognitive/behavioural ability and the integrity of cerebral function was assessed using neuropsychological measures, positron emission tomography, electroencephalography, somatosensory evoked potentials and trans-cranial magnetic stimulation. These investigations were performed as KE was beginning to emerge from coma (4 weeks) and, again, approximately 1 year following brain injury, when she was judged to have achieved her maximum level of recovery. Neuropsychological measures revealed improvement during the first year post-injury in KE's speed of information processing, memory and executive abilities. Electrophysiological and metabolic studies indicated a restoration of functional integrity that was consistent with the gradual recovery in higher brain function documented using behavioural procedures. This case study demonstrates the rehabilitation potential of pre-morbidly healthy older adults following severe traumatic brain injury.

[2000 classification of idiopathic interstitial lung diseases]. / "Classification 2002 des pneumopathies interstitielles idiopathiques"

OBJECTIVES: Diagnosis of interstitial lung diseases was recently improved by the use of diagnostic tools, such as high-resolution Computed Tomography, and by new insights in their pathogenesis and histology. This led the American Thoracic Society and the European Respiratory Society to propose a new classification of these diseases, in the aim to facilitate early diagnosis and specific care. CURRENT KNOWLEDGE AND KEY POINTS: Standard radiography gives the first suspicion of chronic diffuse infiltrative lung disease, and anamnesis and physical examination are essential steps of etiological diagnosis. High-Resolution computed tomography confirms the diagnosis of diffuse infiltrative lung disease. Longitudinal lung function tests are essential to assess the consequences of the lung disease. Lung biopsies are often, but not systematically, a useful tool. The 2000 classification consists of seven entities of idiopathic interstitial diseases which are defined on clinical, radiological and pathological criteria: idiopathic pulmonary fibrosis, non-specific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis associated interstitial lung disease, desquamative interstitial pneumonia and lymphoid interstitial pneumonia. The most frequent is Idiopathic Pulmonary Fibrosis, which has a poor prognosis. FUTURE PROSPECT AND PROJECTS: This new classification results from a multidisciplinary confrontation with chest physicians, radiologists and pathologists. A better characterization of anatomoclinical entities should lead to a better pronostic evaluation, more informative comparisons of published studies, and therefore to rational therapeutic approach.

Attention differentially modulates the coupling of fMRI BOLD and evoked potential signal amplitudes in the human somatosensory cortex.

Blood oxygenation dependent contrast (BOLD) fMRI is used increasingly to probe "connectivity" based on temporal correlations between signals from different brain regions. This approach assumes that there is constant local coupling of neuronal activity to the associated BOLD response. Here we test the alternative hypothesis that there is not a fixed relationship between these by determining whether attention modulates apparent neurovascular coupling. Electrical stimulation of the median nerve was applied with and without a concurrent distractor task (serial subtraction). Increasing stimulation intensity increased discomfort ratings ( p<0.001) and was associated with a significant increase in both somatosensory evoked potential (SEP) N20-P25 amplitude and BOLD fMRI response in the contralateral primary (SI) and bilaterally in the secondary somatosensory cortices. Attention to stimulation was reduced during distractor task performance and resulted in an overall trend for reduction in discomfort ( p=0.056), which was significant at the highest stimulation level ( p<0.05). A volume of interest analysis confined to SI confirmed a reduction in BOLD response with distraction ( p<0.001). However, distraction did not measurably affect SEP magnitude. The quantitative relationship between the BOLD fMRI response and the local field potential measured by the early SEP response therefore varies with attentional context. This may be a consequence of differences in either local spatial or temporal signal summation for the two methods. Either interpretation suggests caution in assuming a simple, fixed relationship between local BOLD changes and related electrophysiological activity.

[Bronchial obstruction by an aberrant left pulmonary artery misdiagnosed as asthma in a 7 year old child]. / Un faux asthme lié à une compression bronchique par une artère pulmonaire gauche à trajet aberrant chez une enfant de 7 ans.

INTRODUCTION: Wheezing is common symptom in infants and is usually due to asthma. However an alternative diagnosis should be sought if there is no reversibility to B2-agonist. CASE REPORT: This case report describes a 7 years old child who had been treated for poorly controlled asthma for several years. The absence of B2-agonist reversibility, indirect signs of thoracic straining on spirometry and evidence of right heart decompensation raised doubts about the diagnosis. CT angiography demonstrated a pulmonary artery malformation. Formal pulmonary angiography confirmed the diagnosis of pulmonary artery sling. This malformation had been causing intermittent bronchial compression and the symptoms resolved after surgical intervention. CONCLUSION: Wheezing symptoms over two Years in a child, misdiagnosed as asthma, is an unusual presentation of this pulmonary vascular anomaly.

Dopaminergic effects on electrophysiological and functional MRI measures of human cortical stimulus-response power laws.

Power laws have been widely used to formulate relationships between objective intensity of stimulation and subjective intensity of sensation. We investigated the effects of dopaminergic drug treatment (sulpiride) on the relationship between somatosensory stimulus intensity and cortical response measured electrophysiologically by somatosensory-evoked potentials (SEP) and functional magnetic resonance imaging (fMRI). The intensity of stimulation was related by a simple power law to both electrophysiological and fMRI measures of cortical response, with overlapping confidence intervals for both power law exponents. Sulpiride did not modulate the power law exponent, but significantly attenuated the "gain" of both stimulus-response functions. Using path analysis we decomposed dopaminergic effects on fMRI data into an indirect component (16%), predictable by drug effects on SEP, and a direct component (84%), not explained electrophysiologically. Results indicate that sulpiride has comparable effects on power law parameters estimated from SEP and fMRI, but fMRI has superior sensitivity to detect drug effects on somatosensory cortical recruitment by graded stimulation.

Study of cytokine gene expression in small cell samples: use in induced sputum.

Sputum examination is being increasingly used as a non-invasive method for the study of airway inflammation. However, the technical applications of sputum are still limited because of the small number of cells recovered. In attempt to extend applications of sputum examinations, we developed and standardised, the reverse transcriptase-polymerase chain reaction (RT-PCR), a sensitive and specific technique of detection of mRNA, in induced sputum samples. Total RNA were extracted from samples containing as few as 50 to 80,000 cells, using a phenol-chloroform extraction method. RT-PCR was successfully tested on beta-actin, interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and tumour necrosis factor-beta (TGF-beta) genes. This protocol provides a simple technique to extract total RNA from a few number of induced sputum cells. It permits the semi-quantitatively study of cytokine gene expression in airways with simple means.

Assessment of T lymphocyte cytokine production in induced sputum from asthmatics: a flow cytometry study.

BACKGROUND: Asthma results from a bronchial inflammation in which Th2 lymphocytes play a pivotal role, as shown in invasive bronchial biopsies and broncho-alveolar lavages. Induced sputum (IS) is a non-invasive method of recovery of bronchial cells, which can be repeated in the same patients. However, lymphocyte activation has not been studied in IS to date, because of the low number of T cells recovered. Herein we took advantage of flow cytometry, a method suitable for the study of small cell populations, to assess T cell cytokine production in IS. OBJECTIVES: (1) To assess induced sputum T cell cytokine production by flow cytometry in asthmatic subjects and controls. (2) To compare the T cell cytokine production between symptomatic and non-symptomatic asthmatics. METHODS: Thirteen asthmatics and 19 controls were included. Sputum was induced by a hypertonic saline. Sputum cells were stimulated and intracellular IL-13 and IFN-gamma were detected in T cells by flow cytometry. RESULTS: Stimulation induced an increase of IL-13 and IFN-gamma production by T cells. This increase was higher in asthmatics. IL-13-producing T cells were increased in asthmatics after stimulation. In symptomatic asthma, IFN-gamma-producing T cells were in higher proportion than in controlled asthma. CONCLUSION: IS T cell cytokine production indicates a basic Th2 bias in asthma, accompanied during symptoms by a Th1-like activation. These results open the field for longitudinal studies of the variation of T cell activation in asthma.

T cell activation, from atopy to asthma: more a paradox than a paradigm.

During the last 15 years, it was largely shown that allergic inflammation was orchestrated by activated Th2 lymphocytes, leading to IgE production and eosinophil activation. Indeed, Th2 activation was shown to be necessary to induce allergic sensitization in animal models. In humans, a Th2 skewing was shown in atopic children soon after birth. In asthma, descriptive studies showed that Th2 cells were more numerous in patients than in controls. In addition, during specific allergen stimulation, an increase of Th2 cells was described in most cases. According to this Th2 paradigm, it was proposed that early avoidance of microbial exposure could explain the increase of atopic diseases seen in the last 20 years in developed countries, as the "hygiene hypothesis". Recently, it was proposed that early exposure to lipopolysaccharide (LPS) could be protective against atopic diseases. However, it is well established that exposure to LPS can induce asthma symptoms, both in animals and humans, although it induces a Th1 inflammatory response. In addition, most infections induce asthma exacerbations and Th1 responses. Recently, some studies have showed that some Th1 cells were present in asthmatic patients, which could be related to bronchial hyperreactivity. There is therefore an "infectious paradox" in asthma, which contributes to show that the Th2 paradigm is insufficient to explain the whole inflammatory reaction of this disease. We propose that the Th2paradigm is relevant to atopy and inception of asthma albeit a Th1 activation would account at least in part for bronchial hyperreactivity and asthma symptoms.

What aspect of the fMRI BOLD signal best reflects the underlying electrophysiology in human somatosensory cortex?

The interpretation of task-induced functional imaging of the brain is critically dependent on understanding the relationship between observed haemodynamic responses and the underlying neural changes. However, the precise nature of this neurovascular coupling relationship remains unknown. In particular, it is unclear which measure of functional magnetic resonance imaging blood oxygen level dependent (fMRI BOLD) activity is the best correlate of neural activity. We measured the somatosensory evoked potential (SEP) amplitude at the scalp, and fMRI BOLD signal to increases in intensity of contralateral median nerve electrical stimulation in healthy non-anaesthetised subjects. We compared correlation analyses between SEP amplitude and both peak voxel fMRI BOLD percentage signal change and mean voxel fMRI BOLD percentage signal change across a somatosensory cluster, and we also performed a voxel-by-voxel correlation between fMRI BOLD activity and SEP amplitude. We found that fMRI BOLD changes in primary somatosensory cortex correlate significantly with SEP amplitudes, suggesting a linear neurovascular coupling relationship under the conditions investigated. We also found that mean changes across a cluster correlate less well with SEP amplitude than peak voxel levels. This suggests that the area of haemodynamic activity correlating with SEP amplitude is smaller than the entire cluster observed.

[Pathophysiology of the IgE-dependent reaction in respiratory allergy]. / Physiopathologie de la réaction IgE-dépendante dans l'allergie respiratoire.

The IgE-dependent reaction is a specific type of inflammatory reaction occurring in allergic persons responding to an allergen. When the allergen penetrates the airways, it is captured by the antigen presenting cells and presented to CD4+ T cells. The most important conditions of antigenic presentation are the presence of IL-4 and not IL-12 at the presentation site and the implication of certain coreceptors determining T-cell differentiation to Th2 cells, which produce IL-4, IL-3, and IL-5. Il-4 and IL-3 induce IgE production by plasmocytes and IL-5 activates eosinophils. The specific IgEs of the allergens then bid to their high-affinity receptor on the surface of mast cells (sensitivization phase). If the allergens are still present or if there is an new exposure, coaggregation of high-affinity receptors via specific IgEs induces mast cell degranulation and release of vaso- and broncho-active mediators which lead to the acute signs of rhinitis or asthma (early phase of the immediate reaction). At the same time, activated eosinophils, attracted by IL-5 as well as chemokines, infiltrate the mucosa, producing basic proteins toxic for the epithelium. These cells are responsible for the late phase of the immediate allergic reaction, and during repeated or continuous exposure, are the cause of the chronic allergic disease.