Summary
It has been suggested that tumour cell lysis by gamma‐radiation induces a tumoral antigen release eliciting an immune response. It is not clear how a specific immune response in cervical cancer patients is developed after radiotherapy. This study is an attempt to investigate the role of the human papillomavirus type 16 (HPV‐16) E7‐specific T helper response before and after radiotherapy. Lymphocytes were isolated from 32 cervical cancer patients before and after radiotherapy and from 16 healthy women. They were stimulated for 12 hr with autologous HPV‐16 E7‐pulsed monocyte‐derived dendritic cells or directly with HPV‐16 E7 synthetic peptides: E751–70, E765–84 and E779–98. The cells were stained for CD4, CD69, intracellular interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4) cytokines and analysed by flow cytometry. A specific CD4+ CD69+ IFN‐γ+ immune response against HPV‐16 E779–98 peptide was observed in 10 of 14 patients (71·4%) after treatment, compared with 4 of 14 (28·5%) before radiotherapy (P = 0·039); however, this response was not associated with a successful clinical response. Before treatment, 5 of 31 patients showed a HPV‐16 E779–98‐specific T helper type 2 (Th2) response. Interestingly, this response was significantly associated with a decrease in disease‐free survival (P = 0·027). These results suggest that a Th2‐type cellular response could be useful as a predictor of recurrence and poor prognosis. An increase of the HPV‐specific immune response was observed after radiotherapy; however, it is not enough to control completely the disease after treatment. Our results support that the E7‐specific T‐cell IFN‐γ response in cervical cancer patients, rather than reflecting the host’s capability of controlling tumour growth, might be an indicator for disease severity.
Background
P‐wave dispersion (PWD) is believed to be caused by inhomogeneous atrial conduction. This statement, however, is based on limited little solid evidence. The aim of this study was to determine the relationship between atrial conduction and PWD by means of invasive electrophysiological studies.
Methods
Cross‐sectional study in 153 patients with accessory pathways and atrioventricular node reentry tachycardia (AVNRT) undergoing an electrophysiological study. Different atrial conduction times were measured and correlated with PWD.
Results
Only the interatrial (P‐DCS) and left intra‐atrial conduction times (ΔDCS‐PCS) showed a significant correlation with PWD, but this correlation was weak. Multivariate linear regression analysis determined that both P‐DCS (β = 0.242; P = .008) and ΔDCS‐PCS (β = 0.295; P < .001) are independent predictors of PWD. Performing the multivariate analysis for arrhythmic substrates, it is observed that only ΔDCS‐PCS continued to be an independent predictor of PWD. Analysis of the receiver operating characteristic curves showed that regardless of the types of arrhythmic substrates, PWD discriminates significantly, but moderately, to patients with P‐DCS and ΔDCS‐PCS ≥75 percentile.
Conclusions
Interatrial and intraleft atrial conduction times were directly and significantly correlated with PWD, but only weakly, and were independent predictors of PWD. In general, PWD correctly discriminates patients with high values in interatrial and intraleft atrial conduction times, but moderately. This is maintained in cases with accessory pathways; however, in patients with AVNRT it only does so for intraleft atrial conduction times. Interatrial and intraleft atrial conduction times weakly explains PWD.
Highlights of the Study• Atrial fibrillation that occurs during electrophysiological studies is an indicator of electrical vulnerability. • We report a new predictor of atrial fibrillation within the second half of the P-wave.• The new parameter, maximum Ppeak-Pend, is an independent predictor of atrial fibrillation in electrophysiological studies. • Atrial conduction times predict the occurrence of atrial fibrillation during electrophysiological studies better than P-wave parameters.
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