Differential gene expression of bone marrow-derived CD34+ cells is associated with survival of patients suffering from myelodysplastic syndrome

One feature of the molecular pathology of myelodysplastic syndromes (MDS) is aberrant gene expression. Such aberrations may be related to patient survival, and may indicate to novel diagnostic and therapeutic targets. Therefore, we aimed at identifying aberrant gene expression that is associated with MDS and patient survival. Bone marrow-derived CD34+ hematopoietic progenitor cells from six healthy persons and 16 patients with MDS were analyzed on cDNA macroarrays comprising 1,185 genes. Thereafter, our patients were followed-up for 54 months. We found differential expression of genes that were hitherto unrecognized in the context of MDS. Differential expression of 10 genes was confirmed by quantitative real-time RT-PCR. Hierarchical cluster analysis facilitated the separation of CD34+ cells of normal donors from patients with MDS. More importantly, it also distinguished MDS-patients with short and long survival. Scrutinizing our cDNA macroarray data for genes that are associated with short survival, we found, among others, increased expression of six different genes that encode the proteasome subunits. On the other hand, the most differentially down-regulated gene was IEX-1, which encodes an anti-apoptotic protein. We confirmed its decreased expression on RNA and protein level in an independent validation set of patient samples. The presented data broadens our notion about the molecular pathology of MDS and may lend itself to better identify patients with short survival. Furthermore, our findings may help to define new molecular targets for drug development and therapeutic approaches for patients with poor prognosis.     

Adenovirus genome in the placenta: association with histological chorioamnionitis and preterm birth

Adenovirus is isolated frequently from the amniotic fluid and has been implicated in severe neonatal infections. A case control study was carried out to examine the association of detection of adenovirus in placentas with preterm birth and histological chorioamnionitis. Placentas from preterm and full term deliveries were collected prospectively. Preterm cases were divided into three subgroups according to the gestational age. PCR was carried out on placental tissues for the detection of adenovirus genome. Placentas were evaluated histologically for the presence of chorioamnionitis. Chi‐square and odds ratios (OR) were used to determine if detection of adenovirus is associated with preterm birth and histological evidence of inflammation. Seventy‐one preterm and 122 full term placentas were studied. Adenovirus genome was detected in 29 (40.8%) of preterm cases and in 25 (20.5%) of the full term controls (OR = 2.6; 95% CI, 1.4–5.1; P = 0.002). Detection of adenovirus in preterm placentas was significantly higher compared to full term particularly in the lower gestational age. Detection of adenovirus in placenta followed the seasonal variation of adenovirus infections. Thirty‐seven preterm and 21 full term placentas were also selected for paraffin inclusion and histological examination. Chorioamnionitis was present more frequently in preterm adenovirus‐positive placentas compared to preterm adenovirus‐negative placentas (75% vs. 36%; P = 0.026) as well as compared to term adenovirus‐positive placentas (75% vs. 19%; P = 0.003). This study demonstrates that adenovirus infection of the placenta is associated strongly with histological chorioamnionitis and preterm birth. J. Med. Virol. 82:1379–1383, 2010. © 2010 Wiley‐Liss, Inc.     

'Lateral elbow tendinopathy' is the most appropriate diagnostic term for the condition commonly referred-to as lateral epicondylitis

A plethora of terms that have been used to describe lateral epicondylitis including tennis elbow (TE), epicondylalgia, tendonitis, tendinosis and tendinopathy. These terms usually have the prefix extensor or lateral elbow. Lateral elbow tendinopathy seems to be the most appropriate term to use in clinical practice because other terms make reference to inappropriate aetiological, anatomical and pathophysiological terms. The correct diagnostic term is important for the right treatment.     

The effect of raloxifene and tibolone on the uterine blood flow and endometrial thickness: a transvaginal Doppler study

OBJECTIVES: To evaluate and compare the effect of different than classical hormone therapy medications, such as raloxifene and tibolone, on the uterine arteries and endometrium of postmenopausal women using transvaginal ultrasonography. METHODS: The prospective study included 62 healthy, postmenopausal women recruited from the Menopausal Clinic of the 2nd Department of Obstetrics and Gynecology of the University of Athens. Subjects were randomly allocated to receive raloxifene HCl in a daily dose of 60 mg orally (Group A-31 women) or tibolone in a daily dose of 2.5 mg orally (Group B-31 women). The study period was 6 months and all subjects were assessed using transvaginal ultrasonography before treatment initiation as well as after 3 and 6 months for evaluation of the endometrial thickness and the pulsatility (PI) and resistance (RI) indices at the level of the uterine arteries. RESULTS: No significant differences in RI, PI and endometrial thickness were observed in the raloxifene group during the 6-month treatment. In the tibolone group, PI and RI values decreased linearly from baseline to the end of the study, whereas the endometrial thickness was significantly increased during the first 3 months remaining unaltered thereafter. Comparisons between the two study groups revealed significant percent change of values in the pre-treatment to month-3 period and no difference with regard to pre-treatment, month-3 and month-6 absolute values. CONCLUSION: Raloxifene and tibolone exert dissimilar effects on uterine blood supply parameters and endometrial thickness.     

The effect of low dose hormone therapy on mammographic breast density

OBJECTIVES: To evaluate the effect of two standard and one low dose continuous hormone therapy regimens on mammography. METHODS: One hundred and thirty-two non-hysterectomized postmenopausal women were randomly allocated either to conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 5 mg (CEE/MPA, n=38), 17beta-estradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA, n=44) or 17beta-estradiol 1 mg plus norethisterone acetate 0.5 mg (low E2/NETA, n=50). Treatment was continuous and the study period lasted 12 months. Main outcome measures were the changes according to Wolfe classification between baseline and 12-month mammograms. RESULTS: Five (13.2%) women in the CEE/MPA group showed an increase in breast density. Fourteen (31.8%) women on E2/NETA and 6 (12.2%) on low E2/NETA treatment revealed an increase in breast density. No woman exhibited an involution of fibroglandular tissue. CONCLUSIONS: Different hormone therapy regimens have a variable impact on breast density probably depending on the steroid used. Low dose hormone therapy associates with significantly lesser increase in breast density.     

Detection of unusual mutation within the VP1 region of different re-isolates of poliovirus Sabin vaccine

In the present study, a genomic analysis of full VP1 sequence region of 15 clinical re-isolates (14 healthy vaccinees and one bone marrow tumor patient) was conducted, aiming to the identification of mutations and to the assessment of their impact on virus fitness, providing also insights relevant with the natural evolution of Sabin strains. Clinical re-isolates were analyzed by RT-PCR, sequencing and computational analysis. Some re-isolates were characterized by an unusual mutational pattern in which non-synonymous mutations outnumbered the synonymous ones. Furthermore, the majority of amino-acid substitutions were located in the capsid exterior, specifically in N-Ags, near N-Ags and in the north rim of the canyon. Also mutations, which are well-known determinants of attenuation, were identified. The results of this study propose that some re-isolates are characterized by an evolutionary pattern in which non-synonymous mutations with a direct phenotypic impact on viral fitness are fixed in viral genomes, in spite of synonymous ones with no phenotypic impact on viral fitness. Results of the present retrospective characterization of Sabin clinical re-isolates, based on the full VP1 sequence, suggest that vaccine-derived viruses may make their way through narrow breaches and may evolve into transmissible pathogens even in adequately immunized populations. For this reason increased poliovirus laboratory surveillance should be permanent and full VP1 sequence analysis should be conducted even in isolates originating from healthy vaccinees.     

Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma

Endoglin (CD105) is a proliferation-associated protein abundantly expressed in angiogenic endothelial cells. Recent studies revealed that CD105 is intensively expressed in tumor vasculature, whereas intratumoral microvessel density (MVD) determined with the use of antibodies to CD105 has been found to be an important prognostic indicator for the outcome in a number of malignancies. In the current study, we investigated endoglin expression and evaluated MVD in 108 patients with head and neck squamous cell carcinoma. Endoglin was intensively expressed in intratumoral blood vessels, whilst lymphatics were rarely positive for CD105. High microvessel density was associated with a more aggressive tumor phenotype, including advanced clinical stage (p=0.008) and the presence of lymph node metastasis at the time of diagnosis (p=0.02). When microvessel counts were assessed for their prognostic values (high vs low MVD), there was a statistically significant difference in the overall survival among patients with tumors of the oral cavity and larynx (p<0.001) and in the disease-free survival among patients with tumors of the lower lip (p=0.01). The prognostic impact of microvessel density was not dependent on clinical stage or lymph node status. The results of the current study suggest that CD105 is a promising target for tumor imaging and prognosis.     

Effects of a postoperative resistive exercise program on the knee extension and flexion torque in children with cerebral palsy: a randomized clinical trial

OBJECTIVE: To investigate the effects of resistive exercise on the knee extension and flexion torque production during the rehabilitation period after multilevel orthopedic surgery. DESIGN: Randomized clinical trial. SETTING: Hospital rehabilitation department. PARTICIPANTS: Thirty-nine children with spastic diplegic cerebral palsy (CP) (age range, 6-16 y), randomly allocated to an exercise group (n=19) and a control group (n=20). All received conventional physiotherapy (PT), and the exercise group also followed a resistive exercise program. INTERVENTION: A 9-month standardized home-based resistive exercise program, which started about 3 months after the surgery. MAIN OUTCOME MEASURES: The Gross Motor Functional Measurement (GMFM) assessed before (E(0)) and 1 year (E(1)) after the surgery. The Modified Ashworth Scale and the isometric and isokinetic torque of the knee extensors and flexors were evaluated at E(0), E(1), and 6 months after the surgery. RESULTS: The knee extension and flexion moments had decreased 6 months after the surgery and recovered to the preoperative level 1 year after surgery. These changes were not group dependent. CONCLUSIONS: Additional long-term, home-based, low-cost resistive exercise that starts soon after the operation of patients with CP was not more beneficial than conventional PT only, in terms of strength and GMFM.     

Linezolid in prophylaxis against experimental aortic valve endocarditis due to Streptococcus oralis or Enterococcus faecalis

There are no experimental studies regarding the prophylactic efficacy of linezolid against infective endocarditis. Nonbacterial thrombotic endocarditis of the aortic valve was induced in rabbits by the insertion of a polyethylene catheter. Twenty-four hours later, animals were randomly assigned to a control group, and groups receiving either ampicillin (two doses of 40 mg/kg of body weight each, given intravenously, 2 h apart) or linezolid (a single per os dose of 75 mg/kg). The first dose of ampicillin and the single dose of linezolid were administered 0.5 and 1 h, respectively, prior to the intravenous inoculation of approximately 10(7) CFU of Streptococcus oralis or Enterococcus faecalis. Linezolid peak levels in rabbit serum were similar to the peak serum levels in humans following a 600-mg oral dose of linezolid. Linezolid prevented endocarditis in 87% of S. oralis-challenged rabbits (P < 0.001 versus controls; P = 0.026 versus ampicillin). In rabbits challenged with E. faecalis, linezolid prevented endocarditis in 73% (P = 0.003 versus controls; P = 0.049 versus ampicillin). Ampicillin prevented endocarditis due to S. oralis or due to E. faecalis in 47% (P = 0.005 versus controls) and in 30% (P = not significant versus controls) of the challenged animals, respectively. In conclusion, linezolid was effective as prophylaxis against endocarditis caused by a strain of S. oralis and to a lesser degree against that caused by a strain of E. faecalis. Its prophylactic efficacy was superior to that of ampicillin.