Characterization of primitive subpopulations of normal and leukemic cells present in the blood of patients with newly diagnosed as well as established chronic myeloid leukemia

Elevated numbers of primitive Philadelphia chromosome-positive (Ph+) progenitors, including long-term culture-initiating cells (LTC-IC) as well as colony-forming cells (CFC), have been previously described in the blood of patients with chronic myeloid leukemia (CML) in chronic phase with high white blood cell counts. In the present study, which focused primarily on an analysis of circulating progenitors present in such patients at diagnosis, we discovered the frequent and occasionally exclusive presence of circulating normal (Ph-) LTC-IC, often at levels above those seen for LTC-IC in the blood of normal individuals. The presence of detectable numbers of circulating Ph- LTC-IC was independent of the fact that the same peripheral blood samples also contained elevated numbers of predominantly or exclusively Ph+ CFC. Interestingly, both the Ph+ and Ph- LTC-IC in these samples were CD34+CD71- and variably CD38- and Thy-1+, as previously documented for LTC-IC in normal marrow. Thus, neither CD38 nor Thy-1 expression was useful for discriminating between Ph+ and Ph- LTC-IC in mixed populations. Nevertheless, an association of these phenotypes with LTC- IC function did allow highly enriched (> 5% pure) suspensions of either Ph+ or Ph- LTC-IC to be obtained from selected samples of CML blood in which the initial LTC-IC population was either predominantly Ph+ or Ph- , respectively. These findings suggest that the mechanisms causing mobilization of leukemic stem cells in untreated CML patients may affect their normal counterparts. They also indicate a possible new source of autologous cells for the support of intensive therapy of CML patients. Finally, they provide a method for obtaining the most highly purified populations of Ph+ LTC-IC described to date. This method should be useful for further analyses of the molecular activities of these very primitive neoplastic cells.     

Outcomes after liver transplantation for combined alcohol and hepatitis C virus infection

Alcohol abuse and chronic hepatitis C virus(HCV)infection are two major causes of chronic liver disease in the United States.About 10%-15%of liver transplants performed in the United States are for patients with cirrhosis due to combined alcohol and HCV infection.Data on outcomes on graft and patient survival,HCV recurrence,and relapse of alcohol use comparing transplants in hepatitis C positive drinkers compared to alcohol abuse or hepatitis C alone are conflicting in the literature.Some studies report a slightly better overall outcome in patients who were transplanted for alcoholic cirrhosis vs those transplanted for HCV alone or for combined HCV and alcohol related cirrhosis.However,some other studies do not support these observations.However,most studies are limited to a retrospective design or small sample size.Larger prospective multicenter studies are needed to better define the outcomes in hepatitis C drinkers.     

Copy number variants in patients with short stature

Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes.     

Swallowing in Patients with Parkinson’s Disease: A Surface Electromyography Study

Our goal was to study deglutition of Parkinson??s disease (PD) patients and normal controls (NC) using surface electromyography (sEMG). The study included 15 patients with idiopathic PD and 15 age-matched normal controls. Surface electromyography was collected over the suprahyoid muscle group. Conditions were the following: swallow at once 10 and 20?ml of water and 5 and 10?ml of yogurt of firm consistency, and freely drink 100?ml of water. During swallowing, durations of sEMG were significantly longer in PD patients than in normal controls but no significant differences of amplitudes were found. Eighty percent of the PD patients and 20?% of the NC needed more than one swallow to consume 20?ml of water, while 70?% of the PD patients and none of the NC needed more than one swallow to consume 5?ml of yogurt. PD patients took significantly more time and needed significantly more swallows to drink 100?ml of water than normal controls. We conclude that sEMG might be a simple and useful tool to study and monitor deglutition in PD patients.     

Safety and Effectiveness of Transvenous Lead Extraction in Octogenarians

Transvenous Lead Extraction . Introduction: As the population ages, the number of elderly patients with implantable cardiac devices referred for transvenous lead extraction will dramatically increase in Western countries. The safety and effectiveness of lead extraction in elderly patients has not been well evaluated. We report the safety and effectiveness of transvenous lead extraction in octogenarians. Methods and Results: From January 2005 to January 2011, we reviewed data from consecutive patients ≥ 80 years referred to our institutions for transvenous lead extraction because of cardiac device infection or lead malfunction. Clinical characteristics, procedural features, and periprocedural major and minor complications were compared between octogenarians and younger patients. Out of 849 patients undergoing lead extraction in the participating institutions during the study period, 150 (18%) patients were octogenarians (mean age 84 years; range 80–96; 64% males). A significantly higher percentage of octogenarians presented with chronic renal failure (55% vs 26%; P < 0.001), history of malignancy (22% vs 6%; P < 0.001), and chronic obstructive pulmonary disease (46% vs 19%; P < 0.001). Complete lead extraction rates were similar in the 2 age groups (97% in octogenarians vs 96% in patients <80 years; P = 0.39). Periprocedural death occurred in 2 (1.3%) patients ≥80 years and in 5 (0.72%) patients <80 years (P = 0.45 for comparison). No differences in terms of other periprocedural major and minor complications were found between the 2 age groups. Conclusion: Despite presenting with a significantly higher rate of comorbidities, transvenous lead extraction can be performed safely and successfully in octogenarians. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1103‐1108, October 2012)     

Osteogenic effect of high-frequency acceleration on alveolar bone

Mechanical stimulation contributes to the health of alveolar bone, but no therapy using the osteogenic effects of these stimuli to increase alveolar bone formation has been developed. We propose that the application of high-frequency acceleration to teeth in the absence of significant loading is osteogenic. Sprague-Dawley rats were divided among control, sham, and experimental groups. The experimental group underwent localized accelerations at different frequencies for 5 min/day on the occlusal surface of the maxillary right first molar at a very low magnitude of loading (4 με). Sham rats received a similar load in the absence of acceleration or frequency. The alveolar bone of the maxilla was evaluated by microcomputed tomography (μCT), histology, fluorescence microscopy, scanning electron microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR imaging), and RT-PCR for osteogenic genes. Results demonstrate that application of high-frequency acceleration significantly increased alveolar bone formation. These effects were not restricted to the area of application, and loading could be replaced by frequency and acceleration. These studies propose a simple mechanical therapy that may play a significant role in alveolar bone formation and maintenance.     

Changes in matrix phosphorylation during bovine dentin development

Phosphorylation of the organic matrix proteins of dentin is important for the initiation of mineralization, but its relevance in later mineralization stages is controversial. The objective of this study was to analyze changes in the total matrix phosphate content during dentin development and to identify their origin. Amino acid and total matrix phosphate analyses of microdissected developing mantle and circumpulpal fetal bovine dentin specimens were performed. The amino acid composition showed few changes during mantle and circumpulpal dentin maturation. However, the total matrix phosphate content showed a significant, positive correlation with tissue maturation in both mantle and circumpulpal dentin, with a two- and a three-fold increase, respectively, being observed. The data indicate that changes occur in the pattern of phosphorylation of matrix proteins during dentin maturation, which we suggest may play a functional role in later stages of tooth mineralization.