Arterial stiffness assessed by pulse wave analysis in essential hypertension: relation to 24-h blood pressure profile

BACKGROUND: Arterial stiffness is a risk factor for cardiovascular morbidity and mortality and appears to be increased in arterial hypertension. The purpose of the present study was to relate systemic arterial stiffness assessed by pulse wave analysis to variables of 24-h ambulatory blood pressure monitoring (ABPM) in patients with essential hypertension. METHODS: Seventy-two subjects with untreated mild to moderate arterial hypertension underwent evaluation with 24-h ambulatory blood pressure monitoring. In the same subjects, applanation tonometry and pulse wave analysis was performed for evaluation of systemic arterial stiffness expressed as augmentation index and estimated aortic pulse wave velocity. RESULTS: Clinic systolic blood pressure, mean heart rate during 24-h blood pressure monitoring and height were independent predictors of augmentation index and estimated aortic pulse wave velocity. The 41 patients with blunted reduction in nighttime blood pressure (nondippers) showed higher mean systolic blood pressure (p=0.02), lower systolic and diastolic blood pressure variability (p<0.001), higher pulse pressure during 24-h monitoring (p=0.05) and higher estimated aortic pulse wave velocity (p=0.03), indicating stiffer arteries in this group. CONCLUSIONS: These results suggest that blood pressure change from day- to nighttime is an important determinant of arterial stiffness assessed by pulse wave analysis; this association could contribute to the higher cardiovascular risk in nondippers.     

Constituents of red wine other than alcohol improve endothelial function in patients with coronary artery disease

BACKGROUND: Several studies suggest that red wine is beneficial in coronary artery disease (CAD). Although the long-term effect of moderate red wine consumption on endothelial function is currently under investigation, there is little knowledge about its effect on postprandial endothelial function and haemostatic factors. The aim of the present study was to investigate the postprandial effects of alcohol content and the antioxidants of red wine on endothelial function and fibrinogen levels in CAD patients. METHODS: Fifteen males with angiographically documented CAD were recruited for the study. All volunteers ingested 250 ml of either red wine or de-alcoholized red wine on two different days. Blood samples (for analysis of fibrinogen and blood lipids) were collected and flow-mediated dilatation (FMD) was determined before and 30, 60 and 90 min following consumption of each beverage RESULTS: FMD was higher following the consumption of de-alcoholized red wine [type of wine effect, P=0.05 repeated measures analysis of variance (ANOVA)]. Furthermore, the pattern of the response was different between the two beverages, as FMD increased following the ingestion of de-alcoholized red wine, but it decreased after consumption of regular red wine (type of wine by time interaction effect, P=0.006 repeated measures ANOVA). Fibrinogen concentrations were unaltered CONCLUSIONS: Acute ingestion of red wine without alcohol led to higher FMD than ingestion of regular red wine in CAD patients. The acute effect of red wine on endothelial function may be different than its long-term effect and it could be attributed to its constituents other than alcohol.     

Phase II study of paclitaxel in pretreated patients with locally advanced/metastatic cancer of the bladder and ureter.

Fourteen patients with previously treated, locally advanced/metastatic transitional cell carcinoma (TCC) of the bladder or ureter received paclitaxel at a dose of 200 mg m-2 administered as a 3-h infusion every 21 days. The activity of paclitaxel in this group of patients was modest. The response rates were one partial response (PR) (7%) and three stable disease (SD). There were two early deaths.     

Adjuvant therapy for resectable pancreatic adenocarcinoma: Review of the current treatment approaches and future directions

Adenocarcinoma of the pancreas carries a uniformly poor prognosis with high rates of loco-regional as well as systemic recurrence. Outcomes remain poor, even for early stage and resectable disease. It is perceived as inherently resistant to most of the currently available treatment options. Evidence supports the need for adjuvant chemotherapy but controversy remains in relation to the use of combined therapy, novel agents and the most appropriate timing of therapy. Despite no clear consensus, mainstay of treatment following resection is based primarily on single agent gemcitabine. Promising new agents and molecules of prognostic as well as predictive value under evaluation offer intriguing data, despite issues surrounding adjuvant therapy strategies. In this article, we sought to review the different therapeutic adjuvant modalities and future directions.     

Targeted agents: review of toxicity in the elderly metastatic colorectal cancer patients

Colorectal cancer remains a major cause of cancer mortality in the Western world. With a median age at presentation of 71, patients with metastatic disease are often elderly with significant co-morbidities. In addition, elderly patients are more likely to be undertreated and under-represented in clinical trials. Therefore, as the available data from clinical trials are scarce, the optimal treatment strategy for this group of patients has not been adequately defined. In the setting of metastatic colorectal cancer, the introduction of so called targeted agents has significantly improved outcomes in the context of randomized clinical trials, while at the same time increasing treatment options for such patients. This review focuses on the role of targeted therapies in elderly patients with metastatic colorectal cancer, with specific reference to toxicity and tolerability. It should be noted that studies reviewed herein will have mostly included fit elderly patients fulfilling specific inclusion criteria. The available data so far are limited but suggest that targeted agents have similar efficacy and tolerability in elderly fit patients when compared with younger ones, provided caution is exercised in specific high-risk sub-groups. Clearly, further studies aimed at this specific patient population using well-established geriatric end-points will hopefully identify those patients more likely to benefit and less likely to suffer severe side effects.     

Docetaxel and irinotecan as second-line therapy for advanced oesophagogastric cancer

Introduction

Systemic chemotherapy improves survival in oesophagogastric cancer however no standard second-line regimen exists due to a paucity of randomised data. Docetaxel combined with irinotecan (DI) provides a suitable option due to the lack of cross-reactivity with first-line therapeutics and a tolerable toxicity profile.

Methods

We retrospectively reviewed a cohort of patients with advanced oesophagogastric cancer in two institutions treated with the combination of docetaxel 35 mg/m² plus irinotecan 60 mg/m² day 1 and day 8 every 21 days, following progression with first-line platinum-based therapy.

Results

Between January 2000 and September 2009, 41 eligible patients were identified. Median age was 58 years, male:female 25:16, adenocarcinoma:squamous cell carcinoma 37:4, oesophageal:oesophagogastric junction:gastric 7:10:24. Locally advanced:metastatic disease 6:35. Previous radical surgery:radiotherapy:both 6:4:7. 27/41 had progressed within 90 days of receiving platinum-based therapy. Median number of chemotherapy cycles: 3 (range 1-12). Eight patients required dose reductions due to DI toxicity. 10/28 evaluable patients had a response, median progression-free survival (PFS) was 11 weeks (95% confidence intervals (CI): 9-13 weeks) with median overall survival 24 weeks (95%CI: 12-35 weeks). No significant prognostic factors were identified.

Conclusion

Weekly docetaxel combined with irinotecan has acceptable safety and modest efficacy in the second-line treatment of advanced oesophagogastric cancer. Further prospective evaluation of this regimen is warranted.     

Transmission of calibration errors (input) by generalized transfer functions to the aortic pressures (output) at different hemodynamic states

BACKGROUND: Aortic pressure waveforms are calculated non-invasively by applying generalized transfer functions (GTF) to tonometric radial pressure waveforms. Input errors mainly during acquisition and calibration of tonometric pressures are "transferred" to aortic pressure calculation. The present study aimed to quantify the proportion of specific input errors which is "transferred" by the GTFs in a wide range of hemodynamic conditions and for different error combinations in brachial systolic (SBP) and diastolic (DBP) blood pressure measurements. METHODS: Aortic pulse wave analysis was performed in 103 subjects (52 normotensive and 51 untreated hypertensive) by the SphygmoCor System. Each pressure waveform was initially calibrated by sphygmomanometrical brachial pressures. Isolated, parallel and reverse errors in brachial SBP/DBP from -10 to +10 mmHg were simulated, by recalibration of the recorded radial pressure waveforms, inducing specific "errors" of GTF-input values. For every recalculated aortic SBP and DBP, the difference from the initial estimated value was considered to represent the "transferred error" to the aortic pressure estimation. RESULTS: Parallel errors by +/-5 mmHg in both SBP and DBP resulted to an identical change in GTF-derived aortic pressures, as expected. When an overestimation in SBP by 5 mmHg and an underestimation in DBP by -5 mmHg occurred (reverse errors), almost 56% of this error (approximately 2.8 mmHg) was transferred. An isolated error in brachial SBP by +/-5 mmHg was transmitted by 76% ( approximately 3.8 mmHg) to GTF-derived aortic SBP. In subjects with mean blood pressure>117 mmHg or with heart rates<74 bpm, a greater percent of the calibration error was transferred to GTF-derived blood pressures. CONCLUSIONS: Input errors in brachial pressure values result in a quantifiable effect on transfer function output (aortic pressures). The percent of the "error transfer" by the GTFs depends on heart rate and BP levels, which should be taken into account when applying GTFs at populations with different hemodynamic conditions.