Patients carrying the CYP3A*1B allele may have enhanced docetaxel clearance and may be underexposed, whereas those carrying GSTP1*A/*B and 3435TT genotypes may have excessive hematologic toxicity. Further studies are warranted to determine the usefulness of genotyping before docetaxel treatment.

Total effective compliance, hemodynamic parameters, extracellular fluid volume, cardiopulmonary (CPBV) and total blood (TBV) volumes were determined in 32 men, including 14 normotensive controls and 18 sustained essential hypertensive patients. The effective compliance was calculated from the changes in central venous pressure recorded simultaneously with the changes in blood volume obtained after a rapid Dextran infusion. In normotensive controls, compliance was 2.08 +/- 0.09 ml/mm Hg/kg and was positively correlated with plasma (r = 0.79) and extracellular fluid (r = 0.84) volumes. In hypertensives, compliance was significantly reduced (1.49 +/- 0.06 ml/mm Hg/kg; P is less than 0.001) and was correlated negatively with the CPBV/TBV ratio (r = -0.75) and positively with the plasma volume/interstitial fluid volume ratio (r = 0.84). These results suggest that in normotensives, there is a regulatory mechanism between volume and compliance and that this contributes to maintaining filling pressure and cardiac output within normal ranges. In hypertensives, the reduced compliance could participate in the maintenance of normal values of cardiac output and extracellular fluid volume by influencing the partition of intravascular and extracellular fluid volumes.

The advent of effective agents for the treatment of osteoporosis has led to the view that placebo-controlled trials to test new agents for efficacy are no longer appropriate since proven treatments are available. In this review we argue that, if new agents are to be developed, there is still a place for the placebo-controlled trial. A move to studies of equivalence or non-inferiority raises more problems than it resolves.

Fifteen patients with hypertension due to phaeochromocytoma and 35 controls with essential hypertension were studied to assess the diagnostic value of urinary and plasma biochemical determinations in phaeochromocytoma. In every case of phaeochromocytoma the urinary concentration of vanillylmandelate, metanephrines, or adrenaline plus noradrenaline was diagnostic of the disease irrespective of whether the patient was normotensive or hypertensive at the time. Plasma determinations of adrenaline and noradrenaline, however, gave falsely negative results on three occasions.These findings suggest that urinary biochemical deter-