Citations

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.

Objective To investigate 35‐year epidemiological trends in tonsillectomy and adenotonsillectomy. Study Design/Subjects Cross‐sectional survey. Subjects included all patients from birth to age 29 years who had tonsillectomy or adenotonsillectomy from 1970 to 2005. Results Study included 8106 patients (median age 8.0 years; range, 6 months to 29 years; male 3646 patients [45%]). Overall tonsillectomy incidence increased from 126 (95% confidence interval [CI], 111‐140) per 100,000 person‐years in 1970 through 1974 to 153 (95% CI, 139‐166) in 2000 through 2005. A dominant factor, adenotonsillectomy incidence rose sharply from 243 (95% CI, 223‐261) per 100,000 person‐years in 1970 through 1974 to 485 (95% CI, 462‐509) in 2000 through 2005. The indication of upper airway obstruction increased from 12 percent of patients in 1970 to 77 percent in 2005. Conclusions Epidemiological trends in tonsillectomy and adenotonsillectomy have shifted substantially. Overall numbers have increased, and surgical indications have shifted from infection to upper airway obstruction.