Positioning of glucocorticosteroids in asthma and allergic rhinitis guidelines (versus other therapies)

Asthma and allergic rhinitis are both characterized by airway inflammation, and glucocorticosteroids form the cornerstone of their pharmacologic treatment. All patients with asthma should be prescribed rapid-acting inhaled beta2-agonists as needed to use as rescue therapy in case of symptoms. As soon as patients experience symptoms at least once a week, controller medications should be started on a daily basis to achieve and maintain control of their asthma. Intranasal corticosteroids are given as first-line therapy for moderate to severe persistent rhinitis. Depending on the dominant symptom, H1-antihistamines, decongestants, or ipratropium can be added after re-evaluation.     

Pulmonary dendritic cells

Dendritic cells (DCs) are leukocytes that are emerging as chief orchestrators of immune responses. The crucial task of DCs is the continuous surveillance of antigen-exposed sites throughout the body, and their unique responsibility is to decide whether to present sampled antigen in an immunogenic or tolerogenic way. Any misstep can either lead to a flawed immune defense or to allergy, even autoimmunity. It comes as no surprise that the lungs become increasingly the subject of DC-related investigations, as they represent a vast interface between the body and the outer world. This constitutes an enormous challenge for the immune system: "firing up" immune responses inappropriately could have devastating results for the fragile gas exchange structures. Evidence accumulates that DCs play a pivotal role in maintaining the delicate balance between tolerance and active immune response in our respiratory system. The exponentially growing body of DC-related publications is a big challenge. This article aims to provide researchers and clinicians with an up-to-date view on DC biology and its relevance to pulmonary medicine. A developing trend in the field of DCs is the shift from fundamental immunologic research toward exciting clinical insights and applications. For the pulmonary clinician, this heralds the dawn of promising therapies in various domains such as infections, allergy, and cancer.     

In vivo demonstration of the absorptive function of the middle ear epithelium

The present study investigated in vivo fluid and ion transport across the middle ear epithelium. The tympanic membrane of rats was punctured under general anesthesia. A capillary tube was fitted to the external auditory canal and the bulla filled with various solutions. Middle ear (ME) fluid volume variations were then measured at constant pressure.

When saline was used, a linear decrease of fluid volume was apparent. Replacement of sodium with a non-permeable cation (N-methyl-d-glucamin) reduced the absorption rate from 0.065 ± 0.008 to 0.019 ± 0.003 μl/min (P < 0.05, n = 6). Similarly, amiloride (10⁻³ M), a sodium channel antagonist, reduced the absorption rate to 0.027 ± 0.006 μl/min (P < 0.05, n = 6). Net absorption was abolished when chloride was substituted with gluconate: −0.008 ± 0.004 μl/min (P < 0.02, n = 6), which might have been related (i) to the role of chloride as a diffusible anion through the paracellular pathway, or (ii) to the secretion of chloride through apical channels. However in this condition, 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid, a chloride channel blocker, did not affect the rate of fluid exchange −0.008 ± 0.007 μl/min (P = 0.75, n = 6).

This model provides the first in vivo evidence for the absorptive function of the ME. Fluid introduced into the ME cavity disappears due to active transport through the mucosa. This process is sodium-dependent and can be hindered by high concentration of amiloride. The rate of absorption is high enough to allow total clearance of fluid from the cavity of the middle ear within 13 h. This process might play a role in the maintaining a fluid-free and gas-filled middle ear cavity.     

Efficient growth inhibition of Bacillus anthracis by knocking out the ribonucleotide reductase tyrosyl radical

Bacillus anthracis, the causative agent of anthrax, is a worldwide problem because of the need for effective treatment of respiratory infections shortly after exposure. One potential key enzyme of B. anthracis to be targeted by antiproliferative drugs is ribonucleotide reductase. It provides deoxyribonucleotides for DNA synthesis needed for spore germination and growth of the pathogen. We have cloned, purified, and characterized the tyrosyl radical-carrying NrdF component of B. anthracis class Ib ribonucleotide reductase. Its EPR spectrum points to a hitherto unknown three-dimensional geometry of the radical side chain with a 60 degrees rotational angle of C(alpha)-(C(beta)-C(1))-plane of the aromatic ring. The unusual relaxation behavior of the radical signal and its apparent lack of line broadening at room temperature suggest a weak interaction with the nearby diiron site and the presence of a water molecule plausibly bridging the phenolic oxygen of the radical to a ligand of the diiron site. We show that B. anthracis cells are surprisingly resistant to the radical scavenger hydroxyurea in current use as an antiproliferative drug, even though its NrdF radical is efficiently scavenged in vitro. Importantly, the antioxidants hydroxylamine and N-methyl hydroxylamine scavenge the radical several orders of magnitude faster and prevent B. anthracis growth at several hundred-fold lower concentrations compared with hydroxyurea. Phylogenetically, the B. anthracis NrdF protein clusters together with NrdFs from the pathogens Bacillus cereus, Bacillus thuringiensis, Staphylococcus aureus, and Staphylococcus epidermidis. We suggest the potential use of N-hydroxylamines in combination therapies against infections by B. anthracis and closely related pathogens.     

Cerebral fat embolism: usefulness of magnetic resonance spectroscopy

We report a case of cerebral fat embolism which occurred in a 33-year-old man after a diaphyseal femoral fracture without cranial traumatism. The initial examination showed an incomplete picture of coma with tetrapyramidal syndrome and cutaneomucous purpura. There was no respiratory damage. We present a magnetic resonance spectroscopy analysis of the cerebral lesions observed in the initial phase of the embolism, as well as follow-up, which has strengthened the clinical and imaging features for the diagnosis.     

Experimental model for investigating trans-mucosal gas exchanges in the middle ear of the rat

OBJECTIVE: The total pressure in the middle ear depends on the air composition of this gas pocket, i.e. on gas exchanges occurring through either the Eustachian tube (ET) or mucosa. The aim of this study was to develop an experimental model to investigate the exclusive role of trans-mucosal gas exchanges in the middle ear (ME). MATERIAL AND METHODS: Both tympanic membranes of 20 Sprague-Dawley rats were punctured under general anesthesia. Rats were divided into two equal groups. Group 1 had no ET obstruction. In Group 2, the ET was blocked, after velar incision, by cauterization and application of cyanoacrylate glue into the lumen. One open transparent glass tube containing a droplet of colored water was placed horizontally and connected hermetically to each ear canal. The ME was then flushed with room air through the tube. Variations in ME gas volume were measured by reading the displacement of the liquid droplet in the horizontal tube. The kinetics of variations in gas volume between groups were displayed and statistically compared using a two-sided t-test. RESULTS: The pattern of variations in ME gas volume with time was similar in the two groups. Both were characterized by a decrease with three phases and an elimination rate of approximately 0.152 +/- 0.026 microl/min. There was no significant difference in the mean rate of ME volume changes between the two groups. CONCLUSION: This experimental model allows investigation of trans-mucosal gas exchanges. These exchanges exhibit an absorptive function resulting in a negative pressure that must be compensated, under physiological conditions, by air flow through the ET.     

Imaging of early stages of osteonecrosis of the knee

Osteonecrosis of the knee can present as a spontaneous and primary or a secondary clinical entity. The natural history of osteonecrosis follows a course of several sequential stages, and the later stages of both entities seem to be irreversible. Early diagnosis of osteonecrosis is crucial: the earlier the stage of the lesion at the time of diagnosis, the better the prognosis.Clinically, early diagnosis and treatment of osteonecrosis might prevent unnecessary surgery in cases with a concomitant degenerative meniscal tear. Early-stage osteonecrosis should be ruled out before surgery, because arthroscopy has lately been associated with osteonecrosis. Not every imaging method is equally suitable for detecting pathognomonic changes in each stage of osteonecrosis. Early-stage osteonecrosis is difficult to diagnose,because various differential diagnoses must be kept in mind. Moreover, there is a diagnostic window between the onset of symptoms and the appearance of pathognomonic changes on plain radiographs and MRI.