Effects of Vibration Training and Detraining on Balance and Muscle Strength in Older Adults

The purpose of this study was to analyze the effects of 2 days/week versus 4 days/week of Whole Body Vibration (WBV) during eight weeks of WBV training on health-related quality of life (SF-36), balance and lower body strength, as well as short-term detraining (3 weeks) on balance and lower body strength among older adults. Thirty-four older adults were randomly assigned to a control group (Control; n = 11) or to one of the vibration training groups: WBV 2 days/week (WBV_2d; n = 11) or WBV 4 days/week (WBV_4d; n = 12). The WBV groups exercised for 8 weeks, following 3 weeks of detraining. Lower body strength increased significantly (p < 0.05) for both groups, WBV_2d and WBV_4d, after 8-week training. A significant reduction in strength was observed following 3 weeks of detraining only in WBV_2d group (p < 0.05). All variables of the SF-36 and the balance test did not change after intervention in any group. 2 days/week and 4 days/week of WBV during 8 weeks showed the same improvements on muscle strength. 3 weeks of detraining did not reverse the gains in strength made during 32 sessions of WBV.

Key points

• 2 days and 4 days per week of WBV training during 8 weeks showed the same improvements on muscle strength.
• 3 weeks of detraining did not reverse the gains in strength made during 32 sessions of WBV exercise.
• 3 weeks of detraining did reverse the gains in strength made during 16 sessions of WBV exercise.

Key words: Whole-body vibrations, posturography, dose-response, equilibrium     

A novel initiation codon mutation in the ribosomal protein S17 gene (RPS17) in a patient with Diamond‐Blackfan anemia

Diamond‐Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by pure red cell aplasia, various congenital anomalies, and cancer predisposition. We report a novel mutation in the RPS17 gene in a Korean patient with DBA. The mutation occurred in the translation initiation codon, changing Atg to Gtg (c.1A>G), thus disrupting the natural start of the RPS17 protein biosynthesis. This is the third case of DBA from a RPS17 mutation in the literature and is the second case of a RPS17 mutation in the translation initiation codon, following c.2T>G. Pediatr Blood Cancer 2010;54:629–631. © 2009 Wiley‐Liss, Inc.     

Adaptation and validation of the Portuguese version of the Lithium Knowledge Test (LKT) of bipolar patients treated with lithium: cross-over study

Objective

Adherence problems are a common feature among bipolar patients. A recent study showed that lithium knowledge was the main difference between adherent and non adherents bipolar patients. The Lithium Knowledge Test (LKT), a brief questionnaire, was developed as a means of identifying aspects of patients' practical and pharmacological knowledge which are important if therapy is to be safe and effective. The original English version is validated in psychiatric population, but a validated Portuguese one is not yet available.

Methods

One hundred six patients selected were diagnosed with bipolar disorder (I or II) according to DSM-IV criteria and had to be on lithium treatment for at least one month. The LKT was administered on only one occasion. We analysed the internal consis tency, concurrent validity, sensitivity and specificity of the LKT for the detection of the knowledge about lithium treatment of bipolar patients.

Results

The internal consistency, evaluated by Cronbach's alpha was 0.596. The mean of total score LKT by bipolar patients was 9.0 (SD: 0.75) for men and 8.74 (SD: 0.44) for women. Concurrent validity based on plasma lithium concentration showed a significant correlation between the total LKT score and plasma lithium (r = 0,232; p = 0.020). The sensitivity was 84% and specificity was 81%.

Conclusion

LKT is a rapid, reliable instrument which appears to be as effective as a lengthier standard interview with a lithium clinic doctor, and which has a high level of acceptability to lithium patients. We found that the psychometric assessment of the Portuguese version of LKT showed good internal consistency, sensitivity and specificity.

     

Lower mitotic activity in BRCA1/2-associated primary breast cancers occurring after risk-reducing salpingo-oophorectomy

Risk-reducing salpingo-oophorectomy (RRSO) is associated with 50% reduction of BRCA1/2-associated breast cancer (BC) risk, possibly through decreased growth activity. In this pilot study, tumor characteristics and growth rates of BRCA1/2-associated primary BCs (PBCs) detected after RRSO were compared with those of PBCs originating without RRSO. From a cohort of 271 women with BRCA1/2-associated screen detected BC, we selected 20 patients with PBC detected ≥12 months after RRSO (RRSO group). Controls were 36 BRCA1/2 mutation carriers with PBC detected without RRSO (non-RRSO group) matched for age at diagnosis (± 2.5 y) and for BRCA1 or BRCA2 mutation. Pathology samples were revised for histological subtype, tumor differentiation grade, mitotic activity index (MAI), estrogen receptor (ER), progesterone receptor (PR), and HER2 status. Tumor growth rates, expressed as tumor volume doubling times (DT), were calculated from revised magnetic resonance and mammographic images. Median age at PBC diagnosis was 52 y (range 35–67). PBCs after RRSO had lower MAIs (12 vs. 22 mitotic counts/2 mm, P = 0.02), were smaller (11 vs. 17 mm, P = 0.01), and tend to be PR-positive more often than PBCs without RRSO (38% vs. 13%, P = 0.07). Differentiation grade, ER, and HER2 status were not different. Median DT was 124 d (range 89–193) in the RRSO group and 93 days (range 54–253) in the non-RRSO group (P = 0.47). BC occurring after RRSO in BRCA mutation carriers features a lower MAI, suggesting a less aggressive biological phenotype. When confirmed in larger series, this may have consequences for BC screening protocols after RRSO.     

Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

Missense mutation of the erythropoietin receptor is a rare event in human erythroid malignancies

Human erythroid malignancies (polycythemia vera [PV] and erythroleukemia) are associated with erythropoietin (Epo)-independent growth and differentiation. Missense or nonsense mutations in the Epo receptor (Epo-R) have been recently described in experimental erythroleukemia in mice and in cases of erythrocytosis in humans. To search for a similar genetic alteration in erythroleukemia and PV, we entirely sequenced the exons of the Epo-R gene as well as the intron- exon junctions in these disorders using polymerase chain reaction. In 1 of 10 cases of erythroleukemia, a single allele mutation was found in the 8th Epo-R gene exon that changed asparagine 487 into a serine. No Epo-r gene mutation was found in 12 PV cases studied, but the same mutation (N487S) was found in 1 patient with polycythemia that did not fulfill the criteria of PV (polycythemia of unknown origin). We did not detect this mutation after sequencing part of the 8th exon of the Epo-R gene from 21 other patients with polycythemia of unknown origin and 51 normal controls. The Epo-R mutation was also found in Epstein-Barr virus-derived cell lines from both cases, suggesting that it is not related to the malignant clone. Therefore, this mutation does not appear to be somatic, although no familial cases were found. The biologic effect of this mutation was subsequently studied. Erythroid progenitors from the polycythemic patient normally responded to Epo, whereas those from the erythroleukemic patient were Epo-independent due to autocrine stimulation by Epo. The normal and the mutated Epo-R were transfected into the murine Ba/F3 cell line. Both types of cells displayed the same response to Epo for proliferation, differentiation, and inhibition of apoptosis. Although this mutation may destroy a consensus binding site for Grb2, no obvious differences either in the pattern of Epo-induced tyrosine phosphorylated proteins or in the binding of Grb2 to the Epo-R were observed. In conclusion, a somatic Epo-R missense mutation does not appear to be a molecular mechanism involved in the abnormal growth of human erythroleukemia and PV. However, the Epo-R mutation (N487S) that we describe is located in the same tyrosine sequence beginning at AA 485 as the one previously observed (P488S) in as case of polycythemia (Sokol et al, Exp Hematol 22:447, 1994). These results suggest that this phosphopeptide sequence may play an important role in Epo signalling.     

The Tie receptor tyrosine kinase is expressed by human hematopoietic progenitor cells and by a subset of megakaryocytic cells

Growth factor receptors in human hematopoietic progenitor cells have become the focus of intense interest, because they may provide tools for the monitoring, enrichment, and expansion of stem cells. We have shown earlier that the Tie receptor tyrosine kinase is expressed in erythroid and megakaryoblastic human leukemia cell lines, in the blood islands of the yolk sac, and in endothelial cells starting from day 8.0 of mouse development. Here, the expression of Tie was studied in human hematopoietic cells of various sources. Peripheral blood mononuclear cells were Tie-. However, a large fraction of CD34+ cells from umbilical cord blood (UCB) and bone marrow (BM) expressed tie protein and mRNA. On average, 64% of the fluorescence-activated cell sorting- gated UCB CD34+ cells including CD38- cells and a fraction of cells expressing low levels of c-Kit were Tie+. Also, 30% to 60% of BM CD34+ cells were Tie+, including most of the BM CD34+CD38-, CD34+Thy-1+, and CD34+HLA-DR- cells. Under culture conditions allowing myeloid, erythroid, and/or megakaryocytic differentiation, purified UCB CD34+ cells lost Tie mRNA and protein expression concomitantly with that of CD34; however, a significant fraction of cells expressed Tie during megakaryocytic differentiation. These data suggest that, in humans, the Tie receptor and presumably its ligand may function at an early stage of hematopoietic cell differentiation.