Pulmonary disease due to nontuberculous mycobacteria

Nontuberculous mycobacteria (NTM) are increasingly associated with pulmonary disease. This is a worldwide phenomenon and one that is not related just to better diagnostic techniques or HIV infection. The mode of transmission of NTM is not well defined, but environmental exposure may be the major factor. While most exposed and infected individuals never acquire NTM disease, some ostensibly immunocompetent persons will. Although our understanding of the pathogenesis of NTM disease is incomplete, we believe that both host and mycobacterial factors are involved. Among the former, interferon-gamma"trafficking" may well play a central role. When disease occurs, it is likely to present in one of three prototypical forms: a tuberculosis-like pattern often affecting older male smokers with COPD; nodular bronchiectasis classically occurring in middle-aged or older women who never smoked and present with cough; and hypersensitivity pneumonitis following environmental exposure. While Mycobacterium avium complex has been described with all three forms, many other NTM can produce one or another of them; variants of these prototypes also exist. Diagnosis of NTM disease relies on microbiology and chest CT scanning, and criteria to aid diagnosis are available. Treatment of disease depends on the species involved, extent and form of disease, and overall condition of the patient. Surgery for localized disease may be useful for those species expected to be refractory to medical therapy. Observation without treatment may be appropriate for some patients with slowly progressive disease that is expected to be particularly difficult to treat.     

Intrathecal co-administration of NMDA antagonist and NK-1 antagonist reduces MAC of isoflurane in rats

BACKGROUND: Intravenous administration of N-methyl-D-aspartate (NMDA) receptor antagonists and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists reportedly reduce the minimum alveolar anaesthetic concentration (MAC) for inhalation anaesthetics. If pain perception can be prevented by the intrathecal administration of antinociceptive receptor antagonists, these agents may reduce the requirements for inhalation anaesthetics. We studied the effect of intrathecal administration of an AMPA/kainate receptor antagonist, a metabotropic glutamate (mGlu) receptor antagonist and co-administration of NMDA and a neurokinin-1(NK-1) receptor antagonist drugs at low doses on the MAC. METHODS: After Wistar rats (n=36) were fitted with indwelling intrathecal catheters, the MAC of isoflurane was determined following intrathecal administration of a non-NMDA receptor antagonist (CNQX) at 10 microg, a mGlu receptor antagonist (AP3) at 10 microg, or a combination of NMDA receptor antagonist (APV) at 0.01 microg to 1 microg with NK-1 receptor antagonist (CP96345, CP) at 0.1 microg to 10 microg. Subsequently, a reversal dose of intrathecal NMDA with substance P (SP) was administered, and the MAC of isoflurane was redetermined. Conscious rats (n=15) were also examined for the presence of locomotor dysfunction following the intrathecal co-administration of APV and CP. RESULTS: Neither CNQX nor AP3 reduced the MAC of isoflurane. APV at 0.01 microg plus CP at 1 microg, as well as APV at 0.1 microg plus CP at 10 microg, reduced the MAC of isoflurane, with respective reductions of 7.6% and 14%; (P<0.05). Co-administration of NMDA plus SP reversed the decrease in the MAC of isoflurane. Locomotive activity was not changed. CONCLUSIONS: The NMDA receptor and the NK-1 receptor are important determinants of the MAC of isoflurane, exerting this influence by inhibition of pain transmission in the spinal cord, while mGlu and AMPA receptors have no effect on the MAC of isoflurane.     

Enhancement of Ceramics Based Red-Clay by Bulk and Nano Metal Oxides for Photon Shielding Features

We prepared red clays by introducing different percentages of PbO, Bi₂O₃, and CdO. In order to understand how the introduction of these oxides into red clay influences its attenuation ability, the mass attenuation coefficient of the clays was experimentally measured in a lab using an HPGe detector. The theoretical shielding capability of the material present was obtained using XCOM to verify the accuracy of the experimental results. We found that the experimental and theoretical values agree to a very high degree of precision. The effective atomic number (Z_eff) of pure red clay, and red clay with the three metal oxides was determined. The pure red clay had the lowest Z_eff of the tested samples, which means that introducing any of these three oxides into the clay will greatly enhance its Z_eff, and consequently its attenuation capability. Additionally, the Z_eff for red clay with 10 wt% CdO is lower than the Z_eff of red clay with 10 wt% Bi₂O₃ and PbO. We also prepared red clay using 10 wt% CdO nanoparticles and compared its attenuation ability with the red clay prepared with 10 wt% PbO, Bi₂O₃, and CdO microparticles. We found that the MAC of the red clay with 10 wt% nano-CdO was higher than the MAC of the clay with microparticle samples. Accordingly, nanoparticles could be a useful way to enhance the shielding ability of current radiation shielding materials.     

Cerebral Embolic Risk During Transcatheter Mitral Valve Interventions: An Unaddressed and Unmet Clinical Need?

As new transcatheter mitral valve (MV) interventions continuously evolve, potential procedure-related adverse events demand careful investigation. The risk of cerebral embolic damage is ubiquitous in any left-sided structural heart intervention (and potentially linked to long-term neurocognitive sequelae); therefore, efforts to evaluate these aspects in the field of catheter-based MV procedures are justified. Given the peculiarities of MV anatomy, MV disease, and MV procedures, the lessons learned from other transcatheter heart interventions (i.e., transcatheter aortic valve replacement) cannot be directly translated to MV applications. Through a systematic assessment of available evidence, the authors present and discuss procedure- and patient-related factors potentially associated with cerebral embolic risk during catheter-based MV interventions. Given the paucity of available data in this field, future large, dedicated studies are needed to understand whether cerebral embolic injury represents a real clinical issue during MV procedures.     

Isolation prevalence of pulmonary nontuberculous mycobacteria in Ontario in 2007

BACKGROUND:

The reported prevalence of pulmonary nontuberculous mycobacteria (NTM) infections is increasing.

OBJECTIVE:

To determine the ‘isolation prevalence’ of NTM in 2007 and compare it with previously published research that examined the increasing rates of isolation of NTM from clinical pulmonary specimens between 1997 and 2003.

METHODS:

Isolation prevalence was investigated retrospectively by reviewing a cohort of all positive pulmonary NTM culture results from the Tuberculosis and Mycobacteriology Laboratory, Public Health Laboratory (Toronto, Ontario) in 2007, which identifies at least 95% of NTM isolates in Ontario. Isolation prevalence was calculated as the number of persons with a pulmonary isolate in a calendar year divided by the contemporary population and expressed per 100,000 population. Changes in isolation prevalence from previous years were assessed for statistical significance using generalized linear models with a negative binomial distribution.

RESULTS:

In 2007, 4160 pulmonary isolates of NTM were collected from 2463 patients. The isolation prevalence of all species (excluding Mycobacterium gordonae) was 19 per 100,000 population in 2007 – an increase from previous observations reported for Ontario – corresponding to an average annual increase of 8.5% from 1997 to 2007 (P<0.0001). Average annual increases in isolation prevalence of Mycobacterium avium complex (8.8%, P<0.0001) and Mycobacterium xenopi (7.3%, P=0.0005) were largely responsible for the overall increase, while prevalence rates of rapidly growing mycobacteria remained relatively stable.

CONCLUSION:

The isolation prevalence of pulmonary NTM continues to increase significantly in Ontario, supporting the belief that pulmonary NTM disease is increasingly common.     

Extracellular proteases in epilepsy

During the last decade, multiple data have been obtained, pointing to an involvement of extracellular, including extrasynaptic, proteolysis in epilepsy pathogenesis. The most productive avenues of investigations have been analyses of seizure-evoked gene and protein expression patterns, both hypothesis-driven and unbiased (e.g., DNA microarrays), complemented by functional analyses in animal models, as well as expression and gene polymorphism studies carried out on human tissue In result, serine proteases (e.g., tPA, thrombin, trypsin-like proteases, etc.), metalloproteinases, natural protease inhibitors, as well as complement components, and reelin have been identified as a novel molecular system, emerging as a key factor in the development of epilepsy, in addition to well known contribution of ion channels and signal transduction pathways. The extracellular location of the enzymes makes them particularly attractive potential targets for future pharmacological therapeutic interventions.     

Low serum leptin serves as a biomarker of malnutrition in elderly patients

Anthropometric and classical biologic markers of malnutrition, such as serum albumin, are limited because they are influenced by nonnutritional factors. We propose that a biologic parameter that both predicts nutritional status and is unaffected by nonnutritional factors would facilitate the diagnosis of malnutrition in the elderly. This cross-sectional study included 179 randomized elderly patients. Nutritional status was assessed by the Mini-Nutritional Assessment (MNA) instrument; other end points included anthropometric measures and biologic parameters. Subjects were divided into 3 groups based on MNA-defined nutritional status, and end point means were compared using 2-way analyses of variance adjusted by sex. Correlations between the most accurate biologic marker in predicting malnutrition and other biologic and clinical variables were assessed using Pearson correlation test. Multiple linear regressions were then performed to relate the best biomarker of malnutrition to specific parameters. Finally, leptin levels that predict malnutrition were determined using receiver operating characteristic curve cutoff values. The well-nourished group had significantly higher leptin (P = .001), weight, body mass index, mid-arm circumference, and calf circumference (all, P < .001) compared with the malnourished group and the at risk of malnutrition group. Serum leptin was the optimal biomarker of MNA-defined malnutrition and had significant positive correlations with weight (P = .003) and with all anthropometric values (all P < .001), but no significant correlation with C-reactive protein. Sex, weight, and triglyceride were the best predictors of serum leptin (all P < .001). The optimal cutoff value of serum leptin to detect malnutrition was 4.3 ng/mL in men and 25.7 ng/mL in women. Serum leptin may be a good predictor of nutritional status in elderly patients.     

Identification of novel immunoreactive proteins of Streptococcus zooepidemicus with potential as vaccine components

Background

Streptococcus zooepidemicus is an important opportunistic pathogen of the equine respiratory and reproductive tracts. A normal tonsillar and mucosal commensal, it becomes invasive under conditions of stress such as virus infection, weaning, high temperature, prolonged transportation and failure of uterine involution. The aim of this study was to evaluate the vaccine potential of several surface exposed and secreted proteins of a novel mucoid clone of SzNC78 (ST-307) from an epizootic of equine respiratory disease.

Methods

An expression gene library of SzNC78 was probed with a pool of convalescent equine sera from a clonal epizootic of respiratory disease. Eleven proteins were selected and purified based on putative function, surface expression or secretion and possible importance as virulence factors. Three additional proteins (AhpC, GAPDH and enolase) were also included based on their putative virulence function. Groups of ICR mice were vaccinated subcutaneously with each recombinant antigen and QuilA and later challenged with SzNC78.

Results

SzM protected 100% mice (P < 0.01), followed by SzP and HylC which protected 90% mice (P = 0.01). MAP, SzMAC and ScpC each protected 63% (P < 0.05) mice. No control mouse survived challenge. SzM, MAP and ScpC in combination protected mice against a 10 fold higher dosage of SzNC78 than each antigen given separately. Protection against heterologous challenge (SzW60) was conferred by combinations of HylC + ScpC (60%; P = 0.05), followed by HylC + MAP (50%; P = 0.06) and ScpC + MAP (40%; P = 0.1). Serum antibody responses of horses recently recovered from Sz respiratory infection were highest against ScpC, MAP and SzP. A combination of SKC and Sz115 stimulated no protection against challenge with SzW60.

Conclusion

A subset of Sz proteins reactive with convalescent equine antibody have potential as components of experimental vaccines to aid in prevention of opportunistic Sz infections.