Inhaled iloprost reverses vascular remodeling in chronic experimental pulmonary hypertension

RATIONALE: Inhaled iloprost is an effective therapy for pulmonary arterial hypertension (PAH). However, no study to date has addressed the effects of inhaled iloprost on changes to pulmonary vascular structure that occur in PAH. OBJECTIVES: The present study was designed to investigate chronic antiremodeling effects of inhaled iloprost in monocrotaline (MCT)-induced PAH in rats. Methods: Four weeks after a single injection of MCT, after full establishment of PAH, rats were nebulized with iloprost at a dose of 6 microg . kg(-1) . day(-1), or underwent sham nebulization with saline. RESULTS: After 2 weeks of inhalation therapy, right ventricular pressure and pulmonary vascular resistance were reversed in rats treated with iloprost, but not in sham-treated control animals. Systemic arterial pressure was unaffected. In addition, right heart hypertrophy, the degree of pulmonary artery muscularization, and the medial wall thickness of intraacinar pulmonary arteries regressed in response to iloprost. Furthermore, the MCT-induced increase in matrix metalloproteinase-2 and -9 activities and tenascin-C expression was suppressed. CONCLUSIONS: We conclude that the inhalation of iloprost reverses PAH and vascular structural remodeling in MCT-treated rats. This regimen suggests the possibility of an antiremodeling therapy in PAH.     

Biochemical markers in the follow-up of medullary thyroid cancer.

Medullary thyroid cancer (MTC) shares biochemical features with other neuroendocrine tumors but the particular characteristics are largely unexplored. We investigated the biochemical neuroendocrine profile of MTC and whether specific markers could be useful in follow-up. In addition to the standard tumor marker calcitonin, plasma carcino-embryonic antigen (CEA), plasma catecholamines, (platelet) serotonin, chromogranin A, tryptase, and urinary markers of catecholamine, histamine, and serotonin metabolism were prospectively determined in 46 patients with histologically proven MTC. Patients were divided according to the stage of disease: group 1, no evidence; group 2, stable disease (SD); and group 3, progressive disease (PD). Plasma dopamine was increased in the majority of the patients with SD and PD; however it did not correlate with extent of disease. Elevated plasma platelet levels of serotonin were only present in patients with multiple endocrine neoplasia 2 with SD or PD but did not differ between those groups. Histamine metabolites were elevated in 20% of patients with SD and PD. In addition to plasma calcitonin, only CEA and chromogranin A could differentiate between stable and progressive MTC. MTCs are capable of synthesizing catecholamines, serotonin, and histamine metabolites underscoring that MTCs have metabolic characteristics in common with other neuroendocrine tumors. Thus far, clinical usefulness and relevance seems limited. The most useful markers in the follow-up of MTC are plasma calcitonin and CEA.     

Bone marrow transplantation from HLA-identical siblings as treatment for myelodysplasia

Allogeneic hematopoietic stem cell transplantation is the only curative therapy for myelodysplasia (MDS). To identify factors influencing transplantation outcome, we studied 452 recipients of HLA-identical sibling transplants for MDS from 1989 to 1997, reported to the International Bone Marrow Transplant Registry. Patients with treatment-related MDS or unclassified MDS were excluded. Median age was 38 years (range, 2-64 years). Sixty percent had refractory anemia with excess blasts (n = 136) or with excess blasts in transformation (n = 136). Conditioning regimens included total body irradiation in 199 (44%) cases. Marrow was T-cell depleted for 58 (13%) transplants. Cumulative incidences of neutrophil engraftment, grades II-IV acute graft-versus-host disease (GVHD), and chronic GVHD were 91% (95% confidence interval [CI], 88%-93%), 36% (95% CI, 31%-40%), and 39% (95% CI, 33%-44%), respectively. Three-year transplantation-related mortality (TRM), relapse, disease-free survival, and overall survival rates were 37% (95% CI, 32%-42%), 23% (95% CI, 19%-27%), 40% (95% CI, 36%-45%), and 42% (95% CI, 37%-47%), respectively. Multivariate analyses showed that young age and platelet counts higher than 100 x 10(9)/L at transplantation were associated with lower TRM and higher disease-free and overall survival rates. Relapse incidence was higher in patients with high percentages of blasts in the marrow at transplantation or presentation, with high International Prognostic Scoring System scores at diagnosis, and with T-cell-depleted transplants. These findings indicate that transplantation from an HLA-identical sibling offers the possibility of long-term, disease-free survival to patients with MDS. Best candidates are younger patients with a low percentage of blasts and preserved platelet counts.     

Disease Detection or Public Opinion Reflection? Content Analysis of Tweets,Other Social Media,and Online Newspapers During the Measles Outbreak in the Netherlands in 2013

Background

In May 2013, a measles outbreak began in the Netherlands among Orthodox Protestants who often refuse vaccination for religious reasons.

Objective

Our aim was to compare the number of messages expressed on Twitter and other social media during the measles outbreak with the number of online news articles and the number of reported measles cases to answer the question if and when social media reflect public opinion patterns versus disease patterns.

Methods

We analyzed measles-related tweets, other social media messages, and online newspaper articles over a 7-month period (April 15 to November 11, 2013) with regard to topic and sentiment. Thematic analysis was used to structure and analyze the topics.

Results

There was a stronger correlation between the weekly number of social media messages and the weekly number of online news articles (P<.001 for both tweets and other social media messages) than between the weekly number of social media messages and the weekly number of reported measles cases (P=.003 and P=.048 for tweets and other social media messages, respectively), especially after the summer break. All data sources showed 3 large peaks, possibly triggered by announcements about the measles outbreak by the Dutch National Institute for Public Health and the Environment and statements made by well-known politicians. Most messages informed the public about the measles outbreak (ie, about the number of measles cases) (93/165, 56.4%) followed by messages about preventive measures taken to control the measles spread (47/132, 35.6%). The leading opinion expressed was frustration regarding people who do not vaccinate because of religious reasons (42/88, 48%).

Conclusions

The monitoring of online (social) media might be useful for improving communication policies aiming to preserve vaccination acceptability among the general public. Data extracted from online (social) media provide insight into the opinions that are at a certain moment salient among the public, which enables public health institutes to respond immediately and appropriately to those public concerns. More research is required to develop an automatic coding system that captures content and user’s characteristics that are most relevant to the diseases within the National Immunization Program and related public health events and can inform official responses.     

Bacterial colonization dynamics associated with respiratory syncytial virus during early childhood

Respiratory syncytial virus (RSV) is an important cause of early life acute respiratory infections. Potentially pathogenic respiratory bacteria, including Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae are frequently detected during RSV infections and associated with increased illness severity. However, the temporal dynamics of bacterial colonization associated with RSV infection remain unclear. We used weekly nasal swab data from a prospective longitudinal birth cohort in Brisbane, Australia, to investigate bacterial colonization patterns within children aged less than 2 years in the 4‐week period before and after an RSV infection. During 54 RSV infection episodes recorded in 47 children, both S. pneumoniae and M. catarrhalis were detected frequently (in 33 [61.1%] and 26 [48.1%] RSV infections, respectively). In most cases, S. pneumoniae and M. catarrhalis colonization preceded the viral infection, with the nasal load of each increasing during RSV infection. Generally, the dominant serotype of S. pneumoniae remained consistent in the 1 to 2 weeks immediately before and after RSV infection. Little evidence was found to indicate that prior colonization with either bacteria predisposed participants to developing RSV infection during the annual seasonal epidemic. Possible coacquisition events, where the bacteria species was first detected with RSV and not in the preceding 4 weeks, were observed in approximately 20% of RSV/S. pneumoniae and RSV/M. catarrhalis codetections. Taken together our results indicate that RSV generally triggered an outgrowth, rather than a new acquisition, of S. pneumoniae and M. catarrhalis from the resident microbial community.     

Effect of Omega-3 Fatty Acids on Kidney Function after Myocardial Infarction: The Alpha Omega Trial

Background and objectives

Kidney function gradually decreases with age, and myocardial infarction accelerates this deterioration. Omega-3 (n-3) fatty acids may slow down the decline of kidney function. The effect of marine and plant-derived n-3 fatty acids on kidney function in patients after myocardial infarction was examined.

Design, setting, participants, & measurements

In the Alpha Omega Trial, 2344 patients with history of myocardial infarction ages 60–80 years old (81% men) were randomized to one of four trial margarines. The patients received an additional targeted amount of 400 mg/d eicosapentaenoic acid and docosahexaenoic acid, 2 g/d α-linolenic acid, eicosapentaenoic acid–docosahexaenoic acid plus α-linolenic acid, or placebo for 40 months. Serum cystatin C and serum creatinine were assessed at baseline and after 40 months. Creatinine–cystatin C-based GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration equation.

Results

Patients consumed 19.9 g margarine/d, providing an additional 239 mg/d eicosapentaenoic acid with 159 mg/d docosahexaenoic acid, 1.99 g/d α-linolenic acid, or both in the active treatment groups. After 40 months, compared with baseline, mean (±SD) creatinine–cystatin C-based GFR was −6.9 (±12.6), −4.8 (±13.4), −6.2 (±12.8), and −6.0 (±13.0) ml/min per 1.73 m² in the placebo, eicosapentaenoic acid–docosahexaenoic acid, α-linolenic acid, and eicosapentaenoic acid–docosahexaenoic acid plus α-linolenic acid groups, respectively. After 40 months, in patients receiving eicosapentaenoic acid–docosahexaenoic acid compared with placebo, the decline in creatinine–cystatin C-based GFR was 2.1 less (95% confidence interval, 0.6 to 3.6; P<0.01) ml/min per 1.73 m²; other comparisons were not statistical significant. Odds ratios (95% confidence intervals) of incident CKD (<60 ml/min per 1.73 m²) and rapid decline of kidney function (≥3 ml/min per year) for eicosapentaenoic acid–docosahexaenoic acid compared with placebo were 0.83 (0.58 to 1.18) and 0.85 (0.67 to 1.08), respectively.

Conclusions

Long-term supplementation with 400 mg/d eicosapentaenoic acid–docosahexaenoic acid provides a small beneficial effect on kidney function in patients with a history of myocardial infarction.