What makes a chemical a respiratory sensitizer?

PURPOSE OF REVIEW: In this article we consider the characteristics that are associated with chemical respiratory allergens, and that may be essential for effective sensitization of the respiratory tract. RECENT FINDINGS: Chemical respiratory allergens share some characteristics with other chemical allergens, specifically chemical allergens that cause skin sensitization and allergic contact dermatitis. The unique and defining characteristic of chemical respiratory allergens, which in most instances distinguishes them from contact allergens, is the ability to provoke the preferential development of T helper 2-type immune responses. There are, in addition, other characteristics, such as the ability to increase matrix metalloproteinase expression or to cause perturbation of redox homeostasis, that may in some instances facilitate the induction or expression of respiratory allergy, but it is not yet clear if these attributes are common or essential properties of all chemical respiratory sensitizers. SUMMARY: Predicting which chemical allergens may selectively induce respiratory sensitization is an important objective, but remains a significant challenge because our understanding of the relevant physicochemical characteristics and biological properties that confer on chemicals respiratory allergenic potential is incomplete.     

Feed a cold, starve a fever?

An English old wives' tale advises us to "feed a cold and starve a fever." Here we report that the nutritional status modulates the T helper 1 (Th1)-Th2 balance of activated T cells in human volunteers. Food intake resulted in increased levels of gamma interferon production, whereas food deprivation stimulated interleukin-4 release.     

How accurate is a CT-based dose calculation on a pencil beam TPS for a patient with a metallic prosthesis?

The accuracy of a CT-based dose calculation on a treatment planning system (TPS) for a radiotherapy patient with a metallic prosthesis has not previously been reported. In this study, the accuracy of the CT-based inhomogeneity correction on a pencil beam TPS (Helax TMS) was determined in a phantom containing a metallic prosthesis. A steel prosthesis phantom and a titanium prosthesis phantom were investigated. The phantoms were CT-scanned and dose plans produced on the TPS, using the CT images to provide density information for the inhomogeneity corrections. Verification measurements were performed on a linear accelerator for 6 and 15 MV x-rays. Measured dose profiles at three different depths were compared to the calculations of the TPS. For the titanium prosthesis and for 6 MV x-rays, the TPS overestimated the beam attenuation by approximately 20% at 15 and 20 cm depths in the phantom. This is due to a limitation in the density allocation of this TPS: any Hounsfield number (HN) above a certain threshold is allocated the density of steel. For the steel prosthesis, the TPS performed the correct mapping of HN to mass density. The dose calculation was within 6% for 6 MV x-rays at 15 and 20 cm depths. However. the accuracy of dose calculation varied with beam energy and depth, with large errors in the region close to the prosthesis. The TPS overestimated the dose by 11% for 6 MV and 15% for 15 MV x-rays at 11 cm depth. 2.5 cm beyond the steel prosthesis. These results highlight the limitations in the density allocation of this TPS and demonstrate shortcomings in the pencil beam dose calculation.     

Is living in a border region a risk for a high prevalence of resistance?

This study assessed the antimicrobial resistance and population structure of Staphylococcus aureus isolated from general practice (GP) patients and nursing home (NH) residents in the province of Limburg (near the border with Germany and Belgium) in comparison with those obtained in the remaining provinces of the Netherlands. A total of 617 and 418 S. aureus isolates were isolated from 2,691 to 1,351 nasal swabs from GP patients and NH residents, respectively. Quantitative antibiotic susceptibility testing was performed using a microbroth dilution method. Putative methicillin-resistant S. aureus (MRSA) isolates were tested for the presence of the mecA gene and spa typing was performed on all S. aureus isolates. No significant differences in the prevalence of resistance were found between the two groups of GP isolates, but the isolates from the NH residents showed a lower resistance for trimethoprim–sulfamethoxazole (p = 0.003) in Limburg province compared with the remaining provinces in the Netherlands. Among the isolates from NH residents in Limburg province, the prevalence of spa-CC 084 was higher (p = 0.003) and that of spa-CC 002 was lower (p = 0.01) compared with isolates from NHs in the remaining provinces of the Netherlands. We observed no differences in resistance and population structure between S. aureus isolates from GP patients in Limburg and the remaining provinces of the Netherlands, and only a few differences were observed between the NH populations. There was no higher prevalence of resistance among the GP and NH isolates from Limburg compared with the remaining provinces.     

Isn't a picture still worth a thousand words?

The transmission electron microscope is a valuable diagnostic and research tool that is presently underappreciated. In the area of human immunodeficiency virus research alone, it has provided critical information about viral pathogenesis and opportunistic infections and malignancies. However, because it has not always been used with care, the literature contains misinterpretations, especially as to what is a virus and what is actually a cell organelle, e.g., lysosome and Golgi vesicles. It is important to review the subject periodically to maintain its quality.     

Galactose-1-phosphate is a regulator of inositol monophosphatase: a fact or a fiction?

Classic galactosemia is due to the deficiency of galactose-1-phosphate uridyl transferase and is transmitted as an autosomal recessive disorder. Patients suffering from classic galactosemia display acute symptoms such as poor growth, feeding difficulties, jaundice, hepatomegaly etc., which disappear when the individual is on galactose free diet. However, these patients continue to suffer from defects such as neurological disturbances and ovarian dysfunction, due to the accumulation of galactose-1-phosphate, which is a normal intermediate of galactose metabolism. The biochemical mechanism of galactose-1-phosphate mediated toxicity is still an enigma. Recent experiments strongly suggest that galactose-1-phosphate is also a substrate for inositol monophosphatase (IMPase). Phosphatidylinositol bisphosphate [PI(P)2] dependent signaling serves as a second messenger for several neurotransmitters in the brain. Therefore, the brain is critically dependent on IMPase for the supply of free inositol in order to sustain [PI(P)2] signaling. Circumstantial evidence strongly supports the possibility that being a substrate, galactose-1-phosphate could modulate IMPase function in vivo. The implication of this idea is discussed in relation to classic galactosemia as well as bipolar disorder, which has been thought to be due to the hyper-activation of [PI(P)2] mediated second messenger pathways(s).     

When is a meniscal cyst not a meniscal cyst?

Two patients are presented where lesions adjacent to the joint line of the knee were diagnosed clinically and on magnetic resonance imaging (MRI) as meniscal cysts. No concomitant meniscal tears were seen, and the MRI signal was not completely homogenous. The diagnostic imaging influenced the surgical management in a manner inappropriate for the definitive diagnoses of fibromyxoid sarcoma and monophasic synovial sarcoma. Not all cysts produce a purely homogenous signal on MRI due to haemorrhage or high protein content fluid, and not all meniscal cysts are associated with a meniscal tear. In the absence of a meniscal tear and with mixed signal on MRI we advise caution in the diagnosis of a meniscal cyst and advocate shared management with either orthopaedic or radiological colleagues with a special interest in oncology to obtain a tissue diagnosis before definitive treatment.     

Leishmaniasis treatment—a challenge that remains: a review

Leishmaniasis is a disease caused by flagellate protozoan Leishmania spp. and represents an emergent illness with high morbidity and mortality in the tropics and subtropics. Since the discovery of the first drugs for Leishmaniasis treatment (i.e., pentavalent antimonials), until the current days, the search for substances with antileishmanial activity, without toxic effects, and able to overcome the emergence of drug resistant strains still remains as the current goal. This article reports the development of new chemotherapies through the rational design of new drugs, the use of products derived from microorganisms and plants, and treatments related to immunity as new alternatives for the chemotherapy of leishmaniasis.