Administered dose is an important determinant of the type of hypertension produced by angiotensin II. With chronic administration of pressor doses, there is salt and water retention and expansion of extracellular fluid volume, and the pressure-natriuresis curve is shifted to higher pressures. Important compensatory mechanisms, including resetting of baroreceptors, de novo synthesis of vasodilator prostaglandins, and atrial natriuretic factor release, are triggered by the acute rise of blood pressure. Histologic evidence for vascular injury confounds the interpretation of findings. When angiotensin II is administered in initially subpressor doses, the rise of blood pressure is gradual, there are no detectable changes in salt and water balance, and compensatory mechanisms do not seem to be activated. Autopotentiation of pressor and vasoconstrictor responses by angiotensin II is the characteristic feature of the early stages of hypertension induced by small doses of angiotensin II. Trophic stimulation of vascular tissue, in particular restructuring of extracellular matrix, precedes and may, therefore, be the mechanism responsible for the hemodynamic changes. The pressor and subpressor models of angiotensin II-induced hypertension draw attention to the relative importance of renal and extrarenal mechanisms in the pathogenesis of hypertension. The long-term administration of initially subpressor doses of angiotensin II mimics the development of human hypertension to a greater extent than does the administration of pressor doses.

Background: Beta-blockers are recommended therapy for patients with chronic heart failure (CHF). However, there remains concern regarding tolerability of these agents in the elderly, which has contributed to the limited uptake of these agents in clinical practice. Aims: We conducted a multi-national, prospective evaluation of tolerability to carvedilol in 1030 CHF patients aged >70 years selected by their treating physician to receive this agent in everyday practice. Methods and results: NYHA Class II -IV CHF patients were assessed at baseline for key demographic parameters that may predict tolerability, then followed for 6 months after starting carvedilol. Tolerability was defined as being on 6.25 mg bd of carvedilol at 6 months having received a total of 3 months therapy. Tolerability overall was 80% with age 70 -75 years 84.3%, 76 -80 years 76.8% and > 80 years 76.8%. Mean carvedilol dose achieved was 31.2 mg. In multivariate analysis, advanced age, low diastolic BP, LVEF, obstructive airways disease and presence of diabetes were predictors of tolerability.Conclusions: Carvedilol appears to be well tolerated in this elderly CHF patient cohort. Therefore, elderly CHF patients should not be denied treatment with carvedilol because of concerns regarding tolerability.

2Background: Type 2 diabetes mellitus is widely considered to be associated with pancreatic cancer.Objective: To determine the incidence of pancreatic cancer in new-onset type 2 diabetic patients by measuring the serum level of CA 19-9 and performing abdominal ultrasonography (US). Patients and Methods:Consecutive type 2 diabetic patients in whom diabetes was diagnosed within 36 months were included in this prospective study. Serum CA 19-9 measurement and US were performed in all patients. If any of two was positive, abdominal computer tomography (CT) was carried out. Endoscopic ultrasound-guided fine needle aspiration or direct surgical referral was performed on patients with CT-identified lesions.Results: A total of 115 patients were enrolled. CA 19-9 was elevated in 10 patients but pancreatic cancer diagnosed in neither of them. Pancreatic cancer was revealed by morphological means in three patients without elevated CA 19-9 level. The sensitivity, specificity, positive-, negative predictive values and validity were 0%, 90.4%, 0%, 97.9% and 87.9% for CA 19-9, 66.7%, 100%, 100%, 99% and 99% for US, respectively. The value of the Standardized Incidence Ratio for pancreatic cancer in new-onset type-2 diabetic patients was 198.6 (95% CI=6.25-46.9). Conclusions:The prevalence of pancreatic cancer in patients with new-onset type-2 diabetes is significantly higher than that in the general population and screening is beneficial for detecting PaC in this patient population. CA 19-9 and US is not reliable screening modality for pancreatic cancer screening in this population.

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