Preexisting poliovirus-specific IgA in the circulation correlates with protection against virus excretion in the elderly

BACKGROUND: Epidemiological studies have indicated that at least 10% of the Dutch elderly do not have poliovirus serotype-specific neutralizing antibody titers and might be at risk for poliovirus infection. Previously we established that memory immunity does not protect the elderly against poliovirus replication. In this study, we investigated whether preexisting immunoglobulin (Ig) A protects against poliovirus infection. METHODS: Elderly individuals (n = 383), divided into seronegative and seropositive groups, were challenged with monovalent oral poliovirus vaccine (mOPV), either serotype 1 or serotype 3. After challenge, poliovirus serotype-specific circulating and salivary IgA responses were measured by enzyme-linked immunosorbent assays, and poliovirus excretion in stool was measured. RESULTS: The majority of elderly persons without preexisting IgA excreted poliovirus in the stool. In contrast, most elderly persons seropositive for IgA did not excrete poliovirus. Significant inverse correlations were found between preexisting titers of poliovirus serotype-specific circulating IgA and virus excretion. Challenge with mOPV (re)induced IgA responses; low salivary IgA responses correlated with that in the circulation but not with virus excretion. CONCLUSIONS: These results indicate that preexisting IgA values in the circulation correlate with protection against poliovirus infection in the elderly. This further implies that persons without preexisting IgA might contribute to the circulation of poliovirus and therefore may threaten its eradication.     

Imaging of atherosclerosis. Raman spectroscopy of atherosclerosis

Raman spectroscopy can provide detailed, quantitative information about the chemical composition of an atherosclerotic plaque. Recent development of compact clinical Raman systems and specially developed Raman catheters allow the remote, intravascular application of the technique. This shows prospects for the detection of coronary plaques that are prone to rupture and for the quantitative study of atherosclerosis in terms of chemical composition. This review discusses the basic principles and advances of Raman spectroscopy in the field of atherosclerosis, and its future directions in cardiovascular medicine.     

Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures

AimBoth tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of fractures. The serotonin transporter (5-HTT) has been located in the bone and may play a role in bone physiology. We assessed the association between antidepressant drug use, categorized in a therapeutical-based way and on basis of their affinity for the 5-HTT, and the risk of both osteoporotic and non-osteoporotic fractures.MethodsA case–control study was conducted using the PHARMO RLS. Cases were patients with a first hospital admission for a fracture during the study period. Up to four controls were matched to each case on gender, age, geographical area, and index date.ResultsWe identified 16,717 cases, of whom 59.5% had an osteoporotic fracture, and 61,517 controls. Compared to no use, current use of SSRIs was associated with a statistically significant increased risk of osteoporotic fractures (OR 1.95, 95% CI 1.69–2.26), as was current use of TCAs and non-SSRI/non-TCA antidepressant drugs (ORs 1.37, 95% CI 1.16–1.63 and 1.40, 95% CI 1.06–1.85, respectively). The risk of an osteoporotic fracture was statistically significantly higher for antidepressants with a high affinity for the 5-HTT (OR 1.86, 95% CI 1.63–2.13) compared to antidepressants with a medium or low affinity (OR 1.43, 95% CI 1.19–1.72 (medium) and OR 1.32 95% CI 0.98–1.79 (low) (p < 0.05 for trend). The risk of non-osteoporotic fractures did not show the same trend.ConclusionsThe extent of affinity for the 5-HTT may contribute to the increased risk of osteoporotic fractures related to antidepressant drug use. The pharmacological mechanism-based classification could to be an appropriate alternative for traditional classification to study the association between the use of antidepressants and the risk of fractures.     

Percutaneous coronary intervention with off-site cardiac surgery backup for acute myocardial infarction as a strategy to reduce door-to-balloon time

We investigated whether primary percutaneous coronary intervention (PCI) for patients admitted with an acute ST-segment elevation myocardial infarction could be performed more rapidly and with comparable outcomes in a community hospital versus a tertiary center with cardiac surgery. We started the first PCI with an off-site surgery program in The Netherlands in 2002 and report the results of 439 consecutive patients. In the safety phase, 199 patients presenting with ST-segment elevation myocardial infarction were randomly assigned to treatment at our off-site center versus a more distant cardiac surgery center. In the confirmation phase, 240 consecutive patients were treated in the off-site hospital. Safety and efficacy end points were the rate of an angiographically successful PCI procedure (diameter stenosis <50% and Thrombolysis In Myocardial Infarction grade 3 flow) in the absence of major adverse cardiac and cerebrovascular events at 30 days. The randomization phase showed a 37-minute decrease in door-to-balloon time (p <0.001) with comparable procedural and clinical successes (91% Thrombolysis In Myocardial Infarction grade 3 flow in the 2 groups). In the confirmation phase, the 30-day rate without major adverse cardiac and cerebrovascular events was 95%. None of the 439 patients in the study required emergency surgery for failed primary PCI. In conclusion, time to treatment with primary PCI can be significantly shortened when treating patients in a community hospital setting with off-site cardiac surgery backup compared with transport for PCI to a referral center with on-site surgery. PCI at hospitals with off-site cardiac surgery backup can be considered a needed strategy to improve access to primary PCI for a larger segment of the population and can be delivered with a very favorable safety profile.     

Germline polymorphisms in patients with advanced nonsmall cell lung cancer receiving first-line platinum-gemcitabine chemotherapy: a prospective clinical study

BACKGROUND:

The authors assessed the impact of germline polymorphisms on clinical outcome in patients with advanced nonsmall cell lung cancer (NSCLC) who received platinum‐gemcitabine (PG) chemotherapy.

METHODS:

In total, 137 patients with stage IIIB/IV NSCLC were included who received first‐line PG chemotherapy (74% of patients received cisplatin, and 26% received carboplatin). Twenty‐three germline polymorphisms that were identified in peripheral blood samples were analyzed for progression‐free survival (PFS), treatment response, overall survival (OS), and toxicity.

RESULTS:

The median PFS was 5.8 months, the median OS was 10.2 months, and 44 patients (32%) had a partial treatment response. Carriers of the excision repair cross‐complementation group 1 (ERCC1) mutant thymine (T) allele had a lower treatment response rate (29% vs 52%; P = .02), shorter PFS (adjusted hazard ratio [HR], 1.60; P = .04), and shorter OS (adjusted HR, 1.54; P = .05) compared with carriers of the wild‐type cytosine/cytosine (CC) genotype. The xeroderma pigmentosum group A member 10 (XPD10) mutant adenine (A) allele (adjusted HR, 0.64; P = .04) and the x‐ray cross‐complementing group 1 (XRCC1) mutant guanine (G) allele (adjusted HR, 0.51; P = .02) also were independent predictors of OS. Carriers of the mutant adenosine triphosphate‐dependent DNA helicase Q1 (RECQ1) C allele or the mutant cytidine deaminase (CDA) C allele were more likely to experience severe leukocytopenia (26% vs 10% [P = .03] and 28% vs 11% [P = .02], respectively) compared with wild‐type genotype carriers. Patients who carried the homozygous mutant glutathione S‐transferase π 1(GSTP1) GG genotype were at considerable risk for severe platinum‐associated polyneuropathy (18% vs 3% in wild‐type vs heterozygous mutant patients, respectively; P = .01).

CONCLUSIONS:

To the authors' knowledge, this is the first prospective study to date in patients with advanced NSCLC describing predictive germline polymorphisms not only for the clinical activity of PG chemotherapy (ERCC1, XPD10) but also for its toxicity (GSTP1, RECQ1, CDA). Nonplatinum‐containing chemotherapy in carriers of the ERCC1 T allele or the XPD10 G allele should be studied prospectively. Cancer 2012;. © 2011 American Cancer Society.     

Effects of growth conditions and processing on Rehmannia glutinosa using fingerprint strategy

Metabolite profiling in combination with multivariate statistics is a sophisticated method for quality assessment of natural products. For the development of a quality control strategy in Traditional Chinese Medicine (TCM), we have measured the metabolite fingerprints of Rehmannia glutinosa by GC-MS. Plants were grown under different climate and soil conditions in a phytotron and were processed by a variable number of repetitive steps to investigate the effects on both growth conditions and processing for material medica of R. glutinosa. The GC-MS data have been analyzed by principal component analysis (PCA) and the new approach of the ANOVA-simultaneous component analysis (ASCA) which can combine the information from a structured data design with multivariate analysis. The results clearly show the effect of the different factors and indicate directions for process improvement. When plants were grown under various temperatures, humidity and light intensities for a short period (3 weeks), no significant changes on studied metabolites were observed. However, significant changes were found between different processing cycles. The present data clearly indicate the importance of strictly controlling processing in R. glutinosa and illustrate the impact of growth conditions. This is the first report on the metabolite profile of R. glutinosa that provides a base for the establishment of a quality control strategy.