The extent of emphysema in patients with COPD

Background and Aims: The global initiative for COPD (GOLD) adopted the degree of airway obstruction as a measure of the severity of the disease. The objective of this study was to apply CT to assess the extent of emphysema in patients with chronic obstructive pulmonary disease (COPD) and relate this extent to the GOLD stage of airway obstruction. Materials and Methods: We included 209 patients with COPD. COPD was defined as FEV₁/FVC < 0.70 and no reversibility to β₂‐agonists. All patients were current smokers with a smoking history of ≥20 pack‐years. Patients were assessed by lung function measurement and visual and quantitative assessment of CT, from which the relative area of emphysema below ?910 Hounsfield units (RA‐910) was extracted. Results: Mean RA‐910 was 7.4% (n = 5) in patients with GOLD stage I, 17.0% (n = 119) in stage II, 24.2% (n = 79) in stage III and 33.9% (n = 6) in stage IV. Regression analysis showed a change in RA‐910 of 7.8% with increasing severity according to GOLD stage (P < 0.001). Combined visual and quantitative assessment of CT showed that 184 patients had radiological evidence of emphysema, whereas 25 patients had no emphysema. Conclusion: The extent of emphysema increases with increasing severity of COPD and most patients with COPD have emphysema. Tissue destruction by emphysema is therefore an important determinant of disease severity in COPD. Please cite this paper as: Shaker SB, Stavngaard T, Hestad M, Bach KS, Tonnesen P and Dirksen A. The extent of emphysema in patients with COPD. The Clinical Respiratory Journal 2009; 3: 15–21.     

A critical role for the cholesterol‐associated proteolipids PLP and M6B in myelination of the central nervous system

The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment of cholesterol in the myelin membrane. However, it is unknown how oligodendrocytes concentrate cholesterol above the level found in nonmyelin membranes. Here, we demonstrate a critical role for proteolipids in cholesterol accumulation. Mice lacking the most abundant myelin protein, proteolipid protein (PLP), are fully myelinated, but PLP‐deficient myelin exhibits a reduced cholesterol content. We therefore hypothesized that “high cholesterol” is not essential in the myelin sheath itself but is required for an earlier step of myelin biogenesis that is fully compensated for in the absence of PLP. We also found that a PLP‐homolog, glycoprotein M6B, is a myelin component of low abundance. By targeting the Gpm6b‐gene and crossbreeding, we found that single‐mutant mice lacking either PLP or M6B are fully myelinated, while double mutants remain severely hypomyelinated, with enhanced neurodegeneration and premature death. As both PLP and M6B bind membrane cholesterol and associate with the same cholesterol‐rich oligodendroglial membrane microdomains, we suggest a model in which proteolipids facilitate myelination by sequestering cholesterol. While either proteolipid can maintain a threshold level of cholesterol in the secretory pathway that allows myelin biogenesis, lack of both proteolipids results in a severe molecular imbalance of prospective myelin membrane. However, M6B is not efficiently sorted into mature myelin, in which it is 200‐fold less abundant than PLP. Thus, only PLP contributes to the high cholesterol content of myelin by association and co‐transport. © 2013 Wiley Periodicals, Inc.     

Günter Tulip Filter Retrieval Experience: Predictors of Successful Retrieval

We report our experience with Günter Tulip filter placement indications, retrievals, and procedural problems, with emphasis on alternative retrieval techniques. We have identified 92 consecutive patients in whom a Günter Tulip filter was placed and filter removal attempted. We recorded patient demographic information, filter placement and retrieval indications, procedures, standard and nonstandard filter retrieval techniques, complications, and clinical outcomes. The mean time to retrieval for those who experienced filter strut penetration was statistically significant [F(1,90) = 8.55, p = 0.004]. Filter strut(s) IVC penetration and successful retrieval were found to be statistically significant (p = 0.043). The filter hook-IVC relationship correlated with successful retrieval. A modified guidewire loop technique was applied in 8 of 10 cases where the hook appeared to penetrate the IVC wall and could not be engaged with a loop snare catheter, providing additional technical success in 6 of 8 (75%). Therefore, the total filter retrieval success increased from 88 to 95%. In conclusion, the Günter Tulip filter has high successful retrieval rates with low rates of complication. Additional maneuvers such as a guidewire loop method can be used to improve retrieval success rates when the filter hook is endothelialized.     

Effect of olive oil and barley diets on the caecal mucosa histomorphology

Nutrition is an environmental factor of major importance in human health. Barley is a cereal, rich in dietary fibres (DF) such as β-glucan, arabinoxylans and cellulose. DF is rapidly fermented by the intestinal microflora, with the formation of short-chain fatty acids (SCFA). High levels of SCFA, particularly of butyrate, are important for a healthy large intestine mucosa. SCFA are rapidly absorbed by the colonic mucosa. Butyrate is the preferred energy source of the colonic epithelial cells and acts specifically as a signal metabolite, stimulating cell migration and proliferation. Both the significantly higher formation and the increased absorption of SCFA are important in the protection of the colon mucosa. Olive oil is an integral ingredient of the Mediterranean diet. It is known for its high levels of monounsaturated fatty acids and is also a good source of phytochemicals. Accumulated evidence suggests that it may have health benefits that include the reduction of several varieties of cancers affecting the mucosa in the colon. It might influence the polyamine metabolism in colonic enterocytes in ways that reduce the progression from normal mucosa to adenoma and carcinoma. Therefore, it is important to study the effects of olive oil and the barley on the colonic mucosa, because they are commonly combined in the diet of North African population. The aim of our study is to determine the effects of consumed olive oil and the barley on some histological colonic mucosa parameters as the proliferation, crypt depth and width in rats consuming these types of diets experimentally, the coecum was taken as an example of colonic portion for this study. Seventy-two female Wistar rats were considered to assess the effects of consumption of the olive oil and barley diet on colonic morphology. These diets (olive oil and barley) and a control diet were compared. The experimental period was 40 days. Eight rats from each group were killed at the, 20th and 40th day after consuming experimental diets, caecums were than extracted. Crypt depth and width, the average of mitoses per crypt in the caecal mucosa were determined, using a morphometric system (SAMBA, Grenoble, France). Our results showed that length of the crypts was very similar; this did not achieve statistical significance for olive oil or barley diet supplementation. However, the barley diet was associated with a statistically significant increase in the width of the crypt compared to the control diet (p < 0.05). Statistical differences were not observed for the number of mitoses per crypt, compared to the experimental diets. We concluded that Barley diet can have influence on the colonic crypt width. This might be explained by the high levels of SCFA. Olive oil and the barley diet do not influence on the number of mitoses per crypt and the crypt length in ceacal mucosa.     

Immunotherapy with Intralesional Candida Albicans Antigen in Resistant or Recurrent Warts: A Study

Background:

Warts are sometimes resistant or they tend to recur after every possible destructive therapy. Immunotherapy with skin-test antigens has been used as a viable therapeutic option in such recalcitrant cases.

Aim:

The aim of the study was to evaluate the response of resistant or recurrent warts to intralesional Candida albicans antigen immunotherapy.

Materials and Methods:

A total of 40 patients with resistant or recurrent warts who showed a positive test reaction to C. albicans antigen were given intralesional injections of purified C. albicans antigen solution in a single wart at 3-weekly intervals for a total of three doses. The patients were monitored for resolution of the injected wart as well as other untreated warts. The patients who responded positively were then followed up for any relapses over the next 6 months. Adverse events, if any, were also documented.

Results:

Of the 40 patients enrolled in the study, 34 completed the total treatment protocol of three injections and 6 months of follow-up. In these 34 patients, 19 (56%) showed a complete resolution of warts at all places on the body. In addition, two patients (6%) showed a partial or complete resolution of the treated wart, but there was no effect on the untreated warts. Thirteenpatients (38%) failed to show any response to the treatment regimen. In all patients showing resolution of all the warts, there were no relapses at any site over the next 6 months of follow-up. The most common adverse effect seen was pain during the intralesional injection.

Conclusions:

Intralesional Candida immunotherapy seems to be an effective treatment option in more than half of the patients who fail to show a positive response to destructive modes of treatment or in whom there are multiple recurrences.

Limitations:

The small sample size and lack of control group are the main limitations of the study.     

Hyperglycemia and Oxidized-LDL exert a deleterious effect on Endothelial Progenitor Cell migration in Type 2 Diabetes Mellitus

Introduction

Type 2 diabetes mellitus (DM) patients with coronary artery disease (CAD) have elevated plasma oxidized-LDL (OxLDL) levels and impaired neovascularization. Hyperglycemia and hyperlipidemia impair endothelial progenitor cell (EPC) migration, and endothelial nitric oxide (NO) bioavailability and NO synthase (NOS) activity are essential for EPC migration. Stromal-derived factor-1α (SDF1α) contributes to EPC mobilization and homing by stimulating the CXC receptor-4 (CXCR4) on the EPC plasmalemma to activate the Pi3K/Akt/eNOS signaling pathway. Therefore, we investigated the effect of high glucose (HG) and OxLDL on the migration and NO bioavailability of EPCs from healthy individuals, and then correlated the findings with those of EPCs from type 2 DM patients with and without CAD.

Materials and Methods

EPCs from 15 healthy and 55 patients were exposed to HG, OxLDL, or both before evaluating EPC count, migration and NO production, and expression of CXCR4 and members of Pi3K/Akt/eNOS signaling cascade.

Results

Counts, migration, CXCR4 expression, and NO production were significantly reduced in EPCs from DM and CAD patients compared with that obtained in EPCs from healthy, and were further reduced in DM patients with CAD. The expression of CXCR4 and activation of Pi3K/Akt/eNOS signaling cascade were suppressed in OxLDL- and HG-treated EPCs, and this suppression was exacerbated when EPCs were treated simultaneously with HG and OxLDL.

Conclusions

Hyperglycemia and elevated circulating OxLDL in DM patients with CAD severely impair EPC migration. These results suggest that the underlying mechanism for this impaired EPC migration is linked to the CXCR4/Pi3K/Akt/eNOS signaling pathway.     

Variability in densitometric assessment of pulmonary emphysema with computed tomography

OBJECTIVES: The objectives of this study were to investigate whether computed tomography (CT) densitometry can be applied consistently in different centers; and to evaluate the reproducibility of densitometric quantification of emphysema by assessment of different sources of variation, ie, intersite, interscan and inter- and intraobserver variability, in comparison with intersubject variability. MATERIALS AND METHODS: In 5 different hospitals, 119 patients with emphysema were scanned using standardized protocols. In each site, an observer performed a quantitative densitometric analysis (including blood recalibration) on the corresponding patient group (n=23-25) and one observer analyzed the entire group of 119 patients. After several months, the latter observer analyzed all data for a second time. Subsequently, different sources of variation were assessed by variance component analysis with and without volume correction of the data. RESULTS: Inter- and intraobserver variability marginally contributes to the total variability (<0.001%). The interscan variability was 0.02% of the total variation after application of volume correction. The intersite variability was 48% as a result of one deviating CT scanner. Air recalibration normalized deviating air densities in CT scanners. Within sites, the intersubject variability ranged between 93% and 99% based on the analysis of 2 subsequent CT scans of the patients. CONCLUSIONS: Almost all variability in the density measurement of emphysema originates from differences between scanners and from differences in severity of emphysema between patients. Lung densitometry with multislice CT scanners is a highly reproducible measurement, especially if corrected for lung volume, because this reduces interscan variability.     

Evaluation of a novel vaginal bromocriptine mesylate formulation: a pilot study

This prospective study shows that the early pregnancy inflammatory response following frozen embryo replacement (FER) cycles may be absent or suppressed, in contrast to that following IVF. To our knowledge, this is the first study to evaluate the maternal inflammatory response following FER cycles, but larger studies are still required to explore this novel finding, and investigate whether this may explain the lower ongoing pregnancy rates generally achieved following FER cycles.     

Long-term exposure to noise impairs cortical sound processing and attention control

Long-term exposure to noise impairs human health, causing pathological changes in the inner ear as well as other anatomical and physiological deficits. Numerous individuals are daily exposed to excessive noise. However, there is a lack of systematic research on the effects of noise on cortical function. Here we report data showing that long-term exposure to noise has a persistent effect on central auditory processing and leads to concurrent behavioral deficits. We found that speech-sound discrimination was impaired in noise-exposed individuals, as indicated by behavioral responses and the mismatch negativity brain response. Furthermore, irrelevant sounds increased the distractibility of the noise-exposed subjects, which was shown by increased interference in task performance and aberrant brain responses. These results demonstrate that long-term exposure to noise has long-lasting detrimental effects on central auditory processing and attention control.