International cross-section analysis of the determination of mortality

An essential ingredient in the evaluation of policies concerning health services is knowledge of the impact of health services and other factors on the health of the population. One method of obtaining this information is from the regression analysis of international cross-section data on mortality rates, health service provision, income levels, consumption patterns, and other variables hypothesised to affect population health. The investigation of the determinants of population health is in many ways akin to the estimation of production functions which describe the relationship between the output of goods or services and the mix of inputs used in their production. The purpose of our paper is to use this analogy to discuss, and provide examples of, the problems which arise with the statistical investigation of mortality rates. Issues raised include simultaneous equation bias, multicollinearity, selection of explanatory variables, omitted variable bias, definition and measurement of variables, functional forms, lagged relationships and temporal stability. These problems are illustrated by replication and re-analysis, using new data, of the well known study by Cochrane, St Leger and Moore.     

Antibacterial diterpenoids from Fabiana densa var. ramulosa

A biologically monitored fractionation of the resinous exudate of Fabiana densa Remy var. ramulosa Wedd. led to the isolation of the two new diterpenes: ent-beyer-15-en-18-O-succinate and ent-beyer-15-en-18-O-oxalate as the unique compounds responsible for the observed antibacterial activity of this extract. Their structures were determined by 1D and 2D NMR spectroscopy.     

The effect of perindopril and hydrochlorothiazide alone and in combination on blood pressure and on the renin-angiotensin system in hypertensive subjects

Summary The pharmacodynamic effects and acceptability of perindopril (4 mg daily) and hydrochlorothiazide (25 mg daily) given alone or in combination for 1 month were investigated in a double-blind, placebo controlled, parallel group study. The pharmacokinetics of perindopril and its active metabolite perindoprilat and the time course of angiotensin converting enzyme inhibition were studied for 72 h following the last dose of treatment in the two appropriate groups.Similar decreases in blood pressure were seen 24 h after the last dose of perindopril or hydrochlorothiazide (11/7 mm Hg supine) given alone at these doses. The effect of these drugs given together was additive on diastolic blood pressure and synergistic on systolic blood pressure (24.5/12.6 mm Hg supine) taking into account the placebo response. The significant increase in plasma renin activity produced by perindopril alone was potentiated by concurrent administration of hydrochlorothiazide.The formation of perindoprilat was slightly reduced in the group also receiving hydrochlorothiazide and there was a very small reduction in ACE inhibition in this group.Perindopril, whether given alone or in combination with hydrochlorothiazide, was well tolerated and produced no clinically significant change in routine haematology or serum biochemistry.The additive or synergistic effects of perindopril and hydrochlorothiazide on blood pressure must be due to their complementary physiological actions and not to a pharmacokinetic interaction.     

High PTP4A3 phosphatase expression correlates with metastatic risk in uveal melanoma patients

A high percentage of uveal melanoma patients develop metastatic tumors predominantly in the liver. We studied the molecular profiles derived from gene expression microarrays and comparative genomic hybridization microarrays, to identify genes associated with metastasis in this aggressive cancer. We compared 28 uveal melanomas from patients who developed liver metastases within three years of enucleation with 35 tumors from patients without metastases or who developed metastases more than 3 years after enucleation. Protein tyrosine phosphatase type IV A member 3 (PTP4A3/PRL3), was identified as a strong predictor of metastasis occurrence. We demonstrated that the differential expression of this gene, which maps to 8q24.3, was not merely a consequence of 8q chromosome overrepresentation. PTP4A3 overexpression in uveal melanoma cell lines significantly increased cell migration and invasiveness in vivo, suggesting a direct role for this protein in metastasis. Our findings suggest that PTP4A3 or its cellular substrates could constitute attractive therapeutic targets to treat metastatic uveal melanomas.