Citations

As humans age, the tonic level of activity in sympathetic vasoconstrictor nerves increases and may contribute to age-related increases in blood pressure. In previous studies in normotensive young men with varying levels of resting sympathetic nerve activity, we observed a balance among factors contributing to blood pressure regulation, such that higher sympathetic activity was associated with lower cardiac output and lesser vascular responsiveness to α-adrenergic agonists, which limited the impact of high sympathetic activity on blood pressure. In the present study, we tested the hypothesis that older normotensive men would exhibit a similar balance among these variables (sympathetic nerve activity, cardiac output, and α-adrenergic responsiveness) but that this balance would be shifted toward higher sympathetic nerve activity values. We measured muscle sympathetic nerve activity, cardiac output, arterial pressure, and forearm vasoconstrictor responses in 17 older men and compared these with previous data collected in 14 younger men. Muscle sympathetic activity (burst incidence) was positively related to diastolic blood pressure in the older men ( r =0.49; P =0.05); this relationship was not observed in young men. In addition, there was no relationship between cardiac output and muscle sympathetic activity ( r =0.29; P >0.05) or between muscle sympathetic activity and vasoconstrictor responses in the older men (eg, norepinephrine: r =−0.21; P >0.05). Although our older subjects were normotensive, the relationship between muscle sympathetic nerve activity and diastolic blood pressure and the lack of “balance” among the other variables suggest that these changes with aging may contribute to the risk of sympathetically mediated hypertension in older humans.

Lenalidomide is the first karyotype-selective therapeutic approved for the treatment of myelodysplastic syndromes (MDS) owing to high rates of erythroid and cytogenetic response in patients with chromosome 5q deletion [del(5q)]. Although haploinsufficiency for the RPS14 gene and others encoded within the common deleted region (CDR) have been implicated in the pathogenesis of the del(5q) phenotype, the molecular basis of the karyotype specificity of lenalidomide remains unexplained. We focused our analysis on possible haplodeficient enzymatic targets encoded within the CDR that play key roles in cell-cycle regulation. We show that the dual specificity phosphatases, Cdc25C and PP2Acα, which are coregulators of the G 2 -M checkpoint, are inhibited by lenalidomide. Gene expression was lower in MDS and acute myeloid leukemia (AML) specimens with del(5q) compared with those with alternate karyotypes. Lenalidomide inhibited phosphatase activity either directly (Cdc25C) or indirectly (PP2A) with corresponding retention of inhibitory phospho-tyrosine residues. Treatment of del(5q) AML cells with lenalidomide induced G 2 arrest and apoptosis, whereas there was no effect in nondel(5q) AML cells. Small interfering RNA (shRNA) suppression of Cdc25C and PP2Ac α gene expression recapitulated del(5q) susceptibility to lenalidomide with induction of G 2 arrest and apoptosis in both U937 and primary nondel(5q) MDS cells. These data establish a role for allelic haplodeficiency of the lenalidomide inhibitable Cdc25C and PP2Acα phosphatases in the selective drug sensitivity of del(5q) MDS.

We conducted a retrospective study of symptom assessment calls for adult patients at a US call centre, Ask Mayo Clinic. A total of 27,979 symptom assessment calls were received from July 2006 to June 2007. Calls concerning female patients predominated in all age groups and accounted for 71% of calls, but decreased significantly with increasing age. The average duration of an adult call was 10 min, and the duration increased with increasing age of the adult patient. The greatest frequency (8%) of calls were related to symptoms of abdominal pain, followed in frequency by skin problems (6%), pregnancy-related issues (6%), cold symptoms (4%), and chest pain or chest discomfort (4%). Surrogate calls accounted for 14% of adult calls but the proportion was significantly higher (40%) if the patient's age was 80 years or greater. Call centres should recognize the sex- and age-related trends in calls and adjust the training of their registered nurses accordingly.

Pulse wave velocity (PWV) is widely used for estimating the stiffness of an artery. PWV is measured by the time of travel of the “foot” of the pressure wave over a known distance. This technique has a low time resolution and is an average measurement of artery stiffness between the two measuring positions. In this paper an arterial wave is generated non-invasively in the vessel wall by the radiation force of ultrasound. The wave velocity in the vessel is measured non-invasively by ultrasound with high time resolution over a short distance of a few millimeters.