Pulmonary Vascular remodelling in hypoxic rats: effects of amlodipine, alone and with perindopril

This study investigated whether pulmonary Vascular remodelling in hypoxic pulmonary hypertensive rats (10% oxygen; 4 weeks) could be prevented by treatment, during hypoxia, with amlodipine (IO mg/kg/day, p.o.), either alone or in combination with the angiotensin converting enzyme inhibitor, perindopril (30 mg/kg/day, p.o.). Medial thickening of pulmonary arteries (30-500 mum o.d.) was attenuated by amlodipine whereas it was totally prevented by the combination treatment (amlodipine plus perindopril); neomuscularisation of small alveolar arteries (assessed from critical closing pressure in isolated perfused lungs) was not affected. Pulmonary vascular resistance (isolated perfused lungs) was reduced by both treatment regimes but only combination treatment reduced right ventricular hypertrophy. Taus, amlodipine has anti-remodelling properties in pulmonary hypertensive rats. The finding that combining amlodipine with another anti-remodelling drug produced effects on vascular structure that were additive raises the question of whether combination therapy with two different anti-remodelling drugs may be of value in the treatment of patients with hypoxic (and possibly other forms of) pulmonary hypertension. (C) 2001 Elsevier Science B.V. All rights reserved.

Atypical prostatic glandular proliferations on needle biopsy - Diagnostic implications, use of immunohistochemistry, and clinical significance

In recent times, PSA screening and a substantial increase in prostate needle biopsies have not only resulted in detection of minute foci of cancer but have also very likely resulted in increased detection of atypical glandular proliferations. Not uncommonly, there are only a limited number of atypical glands in these biopsies, and these require careful evaluation to enable an accurate diagnosis. We describe diagnostic implications, use of immunohistochemistry, and clinical significance of these lesions. Foci of atypical glands, also labeled atypical small acinar proliferation of uncertain significance, have features suspicious for but not diagnostic of cancer. Atypical foci include a broad group of lesions of differing clinical significance. These include benign, small acinar proliferations mimicking prostate cancer and atypical glandular proliferations suspicious for carcinoma. Definite diagnosis requires accurate histopathologic assessment and judicious use of immunohistochemistry. Patients with atypical glands on prostate needle biopsy have a high risk for harboring cancer and therefore have an increased risk for having cancer detected in subsequent biopsies.