Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model.

Resident cardiac macrophages (rcMACs) are among the most abundant immune cells in the heart. Plasticity and activation are hallmarks of rcMACs in response to changes in the microenvironment, which is essential for in vitro experimentation. The in vivo investigation is confounded by the infiltration of other cells hindering direct studies of rcMACs. As a tool to investigate rcMACs, we applied the ex vivo model of living myocardial slices (LMS). LMS are ultrathin ex vivo multicellular cardiac preparations in which the circulatory network is interrupted. The absence of infiltration in this model enables the investigation of the rcMACs response to immunomodulatory and mechanical stimulations. Such conditions were generated by applying interferon-gamma (IFN-γ) or interleukine-4 (IL-4) and altering the preload of cultured LMS, respectively. The immunomodulatory stimulation of the LMS induced alterations of the gene expression pattern without affecting tissue contractility. Following 24 h culture, low input RNA sequencing of rcMACs isolated from LMS was used for gene ontology analysis. Reducing the tissue stretch (unloading) of LMS altered the gene ontology clusters of isolated rcMACs with intermediate semantic similarity to IFN-γ triggered reaction. Through the overlap of genes affected by IFN-γ and unloading, we identified Allograft inflammatory factor 1 (AIF-1) as a potential marker gene for inflammation of rcMACs as significantly altered in whole immunomodulated LMS. MicroRNAs associated with the transcriptomic changes of rcMACs in unloaded LMS were identified in silico. Here, we demonstrate the approach of LMS to understand load-triggered cardiac inflammation and, thus, identify potential translationally important therapeutic targets.

Resident cardiac macrophages: crucial modulators of cardiac (patho)physiology.

Resident cardiac macrophages (rcMacs) are integral components of the myocardium where they have key roles for tissue homeostasis and in response to inflammation, tissue injury and remodelling. In this review, we summarize the current knowledge and limitations associated with the rcMacs studies. We describe their specific role and contribution in various processes such as electrical conduction, efferocytosis, inflammation, tissue development, remodelling and regeneration in both the healthy and the disease state. We also outline research challenges and technical complications associated with rcMac research. Recent technological developments and contemporary immunological techniques are now offering new opportunities to investigate the separate contribution of rcMac in respect to recruited monocytes and other cardiac cells. Finally, we discuss new therapeutic strategies, such as drugs or non-coding RNAs, which can influence rcMac phenotype and their response to inflammation. These novel approaches will allow for a deeper understanding of this cardiac endogenous cell type and might lead to the development of more specific and effective therapeutic strategies to boost the heart's intrinsic reparative capacity.

[Symptomatology of tuberculosis]. / La séméiologie de la tuberculose.

First described long before the beginning of our era, the clinical presentation of tuberculosis has not really changed much over the course of ages. Although early diagnosis and the introduction of bacteriocidal antibiotics have led to a decline in the most severe forms, at least in developed countries, the general and functional symptomatology, characteristic of chronic tuberculosis, remains unchanged in non-immunodeficient patients. Inversely, in patients with and immunodeficiency syndrome, the distribution and clinical course of the fundamental signs and symptoms have undergone a considerable modification as a result of intercurrent clinical signs of other opportunistic diseases involving both the lung and extrapulmonary organs.

Is intrinsic asthma a hereditary disease?

Although studies of families, inbred populations and twins have established that asthma has a hereditary basis, little evidence has shown that intrinsic asthma has an increased familial occurrence. To document this issue, we compared the prevalence of asthma in families of intrinsic asthmatics, extrinsic asthmatics and non-asthmatics. The intrinsic asthma group included those with negative skin tests to common aero-allergens (n = 117). The extrinsic asthma group included those with one or more positive skin tests (n = 164). The non-asthmatic group (n = 224) was recruited at a check-up center. The siblings of each subject completed a standardized questionnaire on history of asthma. The results showed that asthma was more prevalent (P less than 0.001) in siblings of intrinsic asthmatics (8.9%) than in siblings of the non-asthmatic group (2.4%). The prevalence of asthma in siblings of intrinsic and extrinsic asthmatics was similar. In conclusion, both intrinsic and extrinsic asthma have an increased family occurrence.

[Pleural fibroma: apropos of a case]. / Le fibrome pleural: a propos d'un cas.

The authors report a case of a pleural fibroma occurring in a 72 year old woman. The tumour presented with both an osteoarthropathy and hypoglycaemia. An X-ray revealed an abundant associated pleural effusion. Immune studies were positive for the presence of vimentin and negative for keratin, as occurred in this case, were in favour of a pure fibroblastic origin for these tumours.

[Opinions and behavior of asthmatic patients towards treatment using aerosols]. / Avis et comportement des malades asthmatiques vis- à-vis des traitements par aérosols.

An ever increasing number of drugs prescribed in the treatment of asthma are presented as aerosols, so that patients may be requested to inhale many puffs every day. In this study, the opinion of asthmatic patients was sought and their behaviour towards aerosols during attacks and in long-term treatment was recorded by means of a questionnaire. The answers confirmed that asthmatics liked aerosols and found them usually effective, but 60% of these patients exceeded the stated dose, and if the drug failed to bring the expected relief, 30% waited 24 hours before calling for a doctor. In long-term treatments, 80% of the patients studied said that 10 puffs a day were a nuisance, and 12% were switched to another treatment for that reason. These results are very important. Doctors should reinforce the patients' education and limit the number of daily puffs they prescribe to obtain better compliance of asthmatics with their treatment.

[Aerosol therapy in asthma]. / Aérosolthérapie dans l'asthme.

Today there is a general use of aerosols in the treatment of asthma. To understand their importance it is necessary to know the make-up of an aerosol, physical and chemical factors as well as anatomical factors that influence its deposition and clearance in the tracheo-bronchial tree. In the therapy of asthma, small, easy-to-handle and reliable inhalers are prescribed. Other methods of administering these drugs by inhalation are available: these include nebulisation of the active substance in a liquid form and inhalation of the drug in a powder form. Their efficacy and the rareness of side effects (owing to the fact of minimal systemic absorption) makes them the preferred form of treatment of crises as well as for basic treatment. Nevertheless, to obtain the best therapeutic results the inhalation technique of the aerosol should be correct and some practical improvements are envisaged to alleviate any disadvantages: mixing chambers, mouth pieces, etc. Several drugs are commercially available in aerosol form (beta-agonists, atropine-like drugs, corticosteroids and chromones) which have a place both in the treatment of crises and in the basic treatment of asthma.

[Evaluation of the medical costs of asthma in adults during a l-year follow-up in a hospital environment]. / Evaluation du coût médical de l'asthme de l'adulte au cours d'une année de surveillance en milieu hospitalier.

The medical cost of asthma is difficult to measure because this syndrome is generally studied in amongst a large group of patients with chronic respiratory disease. The aim of this study was to assess the theoretical cost of the medical treatment of asthma in a group of young adults who are free from any other disease; the study lasted for one year of follow up and the treatment was given in the public hospital service. Four particular situations are identified corresponding to four stages of severity of the disease and each of these stages was given a treatment selected as the usual therapeutic regime given in a respiratory service in a public hospital. The first stage was to suit patients suffering from quarterly paroxysmal crises which tended to resolve quickly after a few days of treatment. The second stage was more severe involving patients suffering from monthly paroxysmal attacks and for whom maintenance treatment was necessary. The third stage was for those with unstable asthma with twice monthly asthmatic crises, frequent hospitalisation and continuous treatment between the attacks. In the fourth stage the patients were suffering from continuous dyspnoea which required inpatient hospital care and also intensive care. In all these cases the asthmatic disorder is burdensome both for the patient and for society, a fact which should be appreciated both by doctors and by decision makers in public health. In the average or mild cases the essential annual costs are made up of the cost of diagnosis and follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

[Heredity of asthma]. / Héridité de l'asthme.

To compare the heredity of asthma among families of intrinsic, extrinsic and control subjects, we have studied the siblings and offsprings of the 3 groups of subjects (using a standardized questionnaire). The results shown that asthma was genetically transmitted but the clinical manifestations appeared later among the relatives of intrinsic than among the relatives of extrinsic asthmatic patients.

[Diffuse familial interstitial pulmonary fibrosis. Study of a family]. / Fibrose pulmonaire interstitielle diffuse familiale. Etude d'une famille.

A study of the genealogy of a 53 year old lady (A.M...) suffering from diffuse interstitial pulmonary fibrosis (FID) has revealed several cases of FID in her forbears and relations. Two brothers of A.M... died of histologically proven FID; FID was also discovered in one of their daughters. A sister died young of some unclassified respiratory problem. Two cousins died likewise at a young age of acute FID proven histologically. The level of spontaneous pneumothorax was particularly elevated in this family which represented a clinical peculiarity when compared to sporadic FID. The most probable mode of transmission of familial FID is autosomal dominant with variable penetrance. The HLA group seen in A.M... showed the A2 and B12 alleles. The B12 allele was also present in the niece of A.M...