Maximum values for isometric strength, dynamic strength, and speed of movement (MEV) in the quadriceps muscle were measured in 114 male subjects who were between 11 and 70 yr. Biopsy samples were taken from the quadriceps muscle in 51 of the subjects (22-65 yr. old). Isometric and dynamic strength increased up to the third decade, remained almost constant to the fifth decade, and then decreased with increasing age. However, no measurable external atrophy of the quadriceps muscle, explaining the decline in strength, could be seen in old age. Histochemical changes in the muscle tissue such as decreased proportion of type II fibers and a selective atrophy of type II fibers, were seen with increasing age. The strength decline in old age was also observed to correlate significantly with the type II fiber area. Multiple regression analyses indicated, however, that mechanisms other than the type II fiber atrophy might be responsible for the decline in strength performance during aging. The implications of these findings are discussed.

The required dose of the oral anticoagulant warfarin varies greatly, and overdosing often leads to bleeding. Warfarin is metabolised by cytochrome P450 enzymes CYP2C9, CYP1A2 and CYP3A. The target cell level of warfarin may be dependent on the efflux pump P-glycoprotein, encoded by the adenosine triphosphate-binding cassette gene ABCB1 (multidrug resistance gene 1). Genetic variability in CYP2C9, CYP3A5 and ABCB1 was analysed in 201 stable warfarin-treated patients using solid-phase minisequencing, pyrosequencing and SNaPshot. CYP2C9 variants, age, weight, concurrent drug treatment and indication for treatment significantly influenced warfarin dosing in these patients, explaining 29% of the variation in dose. CYP3A5 did not affect warfarin dosing. An ABCB1 haplotype containing the exon 26 3435T variant was over-represented among low-dose patients. Thirty-six patients with serious bleeding complications had higher prothrombin time international normalised ratios than 189 warfarin-treated patients without serious bleeding, but there were no significant differences in CYP2C9, CYP3A5 or ABCB1 genotypes and allelic variants.

The purpose of this study was to evaluate the extent of anaerobic glycogenolysis, as indicated by intramuscular lactate concentration, after 10 and 30 s of supramaximal exercise and to compare male and female subjects in this regard. Fifteen males and seven females performed two cycle exercise bouts against a resistance which was standardized so that one pedal revolution resulted in 4.90 J work X kg body wt-1. A muscle biopsy was obtained after 10- and 30-s exercise bouts and analyzed for lactate concentration. The lactate concentrations averaged 36 and 61 mmol X kg dry wt-1 after the 10- and 30-s exercise bouts, respectively. The male subjects had higher (P less than 0.005) lactate concentrations and generated higher (P less than 0.001) power outputs for both exercise bouts. When the mean lactate concentrations were statistically adjusted after controlling for between-group variation in power output, no difference was evident between groups for the 10- or the 30-s lactate value. The results are evidence that pronounced lactate accumulation occurs during supramaximal exercise of a 10-s duration, suggesting that glycolysis can occur within this time frame. This is in contrast to the theory that glycolysis does not occur until endogenous phosphagen levels reach some critically low value, not thought to be obtainable within the first 10 s of supramaximal exercise.

ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol. Thus, specific genotypes might predict the response to specific antihypertensive treatment.

The acute and adaptive effects of electrical stimulation of the quadriceps muscle were investigated in healthy male volunteers. The acute effects, i.e., depletion of phosphagen and glycogen stores and formation of lactate as well as decreases in certain enzyme activities, were similar to those found earlier for intense muscular exercise. Intermittent electrical stimulation for 4 to 5 weeks did not cause any significant changes in enzyme activities, muscle fiber characteristics, or mitochondrial properties. A 4-week period of electrical stimulation resulted in improvements of muscle strength comparable to the results of a corresponding program of voluntary training. However, the effects of electrical stimulation appeared more "position-specific" and less "speed-specific" than those of voluntary training with slow isokinetic contractions.

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SummaryBackground: Studies suggest that the Ser49Gly and Arg389Gly polymorphisms in the ␤1-adrenergic receptor might be of functional importance for the cardiovascular system. Both have been associated with altered receptor activity in vitro, and with hypertension and cardiac failure in vivo.Hypothesis: The aim of this study was to test whether these polymorphisms were associated with the change in heart rate or blood pressure in patients with essential hypertension and left ventricular (LV) hypertrophy treated with the ␤1-adrenergic receptor blocker atenolol.Methods: Blood pressure and heart rate were measured in 101 hypertensive patients with echocardiographically verified LV hypertrophy, randomized in a double-blind study to treatment with either the ␤1-adrenergic receptor blocker atenolol or the angiotensin II type I receptor antagonist irbesartan. Changes in blood pressure and heart rate were evaluated after 12 weeks. Beta1-adrenergic receptor genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism.Results: We found no significant associations between the changes in the measured variables and either of the two poly-

The aldosterone synthase -344 C/T polymorphism was related to the BP-lowering response in hypertensive patients treated with the AT1-receptor antagonist irbesartan.