OMA-AML-1: a leukemic myeloid cell line with CD34+ progenitor and CD15+ spontaneously differentiating cell compartments.

OMA-AML-1 was established from a patient with acute myelomonocytic (M4) leukemia at fifth relapse when blasts were greater than 85% CD34+, CD15-. Leukemic cells were established in suspension culture and independently grown as subcutaneous tumors in SCID mice. Cells growing in suspension culture underwent differentiation by phenotypic and morphologic criteria. In contrast, cells grown as subcutaneous solid tumors in SCID mice maintained progenitor cell characteristics with high-density CD34 expression and lack of morphologic differentiation. A tendency toward differentiation to CD15+, CD34- cells in vitro and self-renewal of CD34+, CD15- cells in vivo was consistently demonstrated regardless of whether cells were initially grown in vitro or in vivo. The cell line maintains both a CD34+, CD15- progentitor cell pool and a non-overlapping, CD15+, CD34- differentiating cell compartment after more than 1 year in continuous culture. Cell cycle analysis and cloning experiments were consistent with terminal differentiation occurring in the CD15+, CD34- population. The cell line shows concentration-dependent proliferative responses to interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6, but not to granulocyte CSF (G-CSF). OMA-AML-1 appears to mimic several features of normal myeloid hematopoiesis and should prove useful for the study of normal and malignant myeloid differentiation.     

Comparison of usefulness of dipyridamole stress myocardial contrast echocardiography to technetium-99m sestamibi single-photon emission computed tomography for detection of coronary artery disease (PB127 Multicenter Phase 2 Trial results)

We hypothesized that assessment of hyperemic myocardial blood flow (MBF) velocity using myocardial contrast echocardiography (MCE) can detect coronary artery disease (CAD). We also postulated that only a single MCE study during stress is required for the detection of CAD in patients with normal function at rest. Patients with known or suspected CAD referred for dipyridamole stress technetium-99m sestamibi single-photon emission computed tomographic (SPECT) studies were enrolled. MCE was performed concurrently with SPECT using continuous infusions of PB127 during intermittent harmonic power Doppler imaging at multiple pulsing intervals. MCE and SPECT were compared in 43 of 54 patients who had adequate studies using both techniques. In 15 of the 43 patients, coronary angiography was performed within 30 days of the MCE/SPECT tests. Overall concordance for classification of patients as normal versus abnormal was 84% (kappa = 0.63) between the 2 tests. When false-negative SPECT scans were corrected for results of angiography, concordance increased to 93% (kappa = 0.82). For territorial analysis, concordance between MCE and SPECT for location of perfusion defects was 65% (kappa = 0.41) and 74% (kappa = 0.61) after SPECT was corrected by angiography. In patients with normal function at rest, a single stress MCE perfusion study allowed identification of CAD with the same concordance as rest/stress perfusion studies. In conclusion, visual assessment of regional differences in MBF velocity using PB127 allows detection of CAD with good concordance compared with technetium-99m sestamibi SPECT. In patients with normal left ventricular function at rest, a single stress PB127 MCE perfusion study is adequate for the detection of CAD.     

Patterns of Schistosoma haematobium egg distribution in the human lower urinary tract. II. Obstructive uropathy

In a series of 32 unselected consecutive autopsies of Egyptian male adults, we found a significant prevalence of schistosomal obstructive uropathy (SOU) and of precursor lesions of stenosis, fibrosis and induration of the ureters (62.5%). Lower urinary tracts with obstructive uropathy had a significantly higher total egg burden (TEB) than did lower urinary tracts with any other type of gross lesion (i.e., benign prostatic hypertrophy, other urethral outlet obstruction, or SOU precursor lesions). In turn, lower urinary tracts with any type of gross change had higher egg burdens than did tracts which appeared grossly normal. Lower urinary tracts with any type of gross lesion had significantly larger seminal vesicles than did tracts which were grossly normal. Moreover, relative weight of seminal vesicles could be correlated with the S. haematobium egg burdens in the seminal vesicles. In a series of lower urinary tracts taken from unselected consecutive American autopsies, seminal vesicle weight could be correlated with increase in prostatic weight in those tracts with prostatic hypertrophy; the same correlation could not be found in tracts without prostatic hypertrophy. Thus, seminal vesicle hypertrophy appears to correlate with obstructive uropathy in general, not solely obstructive uropathy of schistosomal origin. Digital evaluation of seminal vesicle size may be useful in the clinical evaluation of such patients.     

Upper airway resistance during growth: A longitudinal study of children from 8 to 17 years of age

Objective:To study upper airway breathing in 115 children annually from 8 to 17 years of age with the hypothesis that upper airway respiratory needs increase steadily during growth and show sexual dimorphism.Material and Methods:To calculate nasal resistance, airflow rate (mL/s) and oronasal pressures (cmH₂O) were measured during rest breathing in a seated position using the pressure-flow technique.Results:Median values of oronasal pressure ranged at different ages in girls from 0.88 to 1.13 and in boys from 0.92 to 1.44 cmH₂O, being 0.95 and 0.93 cmH₂O at the age of 17 years, respectively. The gender differences were statistically significant in four age groups (P < .05 by the Mann-Whitney test). Mean values of nasal resistance decreased from 8 to 17 years of age in girls from 4.0 (±3.27) to 2.4 (±2.30) and in boys from 3.3 (±2.48) to 1.5 (±0.81) cmH₂O/L/s. However, there was an increase in resistance in 11-year-old girls and 12-year-old boys and at the age of 15 in both genders (P < .05 by paired t-test).Conclusions:Respiratory efforts stabilize oronasal pressure to maintain vital functions at optimal level. Nasal resistance decreased with age but increased temporarily at the prepubertal and pubertal phases, in accordance with other growth and possibly hormonal changes. When measuring upper airway function for clinical purposes, especially in patients with sleep apnea, asthma, allergies, cleft palate, or maxillary expansion, the measurements need to be compared with age- and gender-specific values obtained from healthy children.     

C‐reactive protein lowering with rosuvastatin in the METEOR study

Abstract. Peters SAE, Palmer MK, Grobbee DE, Crouse JR III, O’Leary DH, Raichlen JS, Bots ML (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands; Keele University, Keele, UK; Wake Forest University School of Medicine, Winston‐Salem, NC, USA; Caritas Carney Hospital, Boston, MA, USA; AstraZeneca, Wilmington, DE, USA). C‐reactive protein lowering with rosuvastatin in the METEOR study. J Intern Med 2010; 268 : 155–161. Objectives. In addition to its LDL‐C‐lowering effects, statin treatment reduces the level of C‐reactive protein (CRP). Long‐term data on this effect in low‐risk populations are limited. Furthermore, whether the CRP reduction is a consequence of LDL‐C lowering or occurs independently remains unclear. We studied these aspects in the Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin (METEOR) study, a randomized placebo‐controlled trial amongst 984 low‐risk subjects. Methods. METEOR is a randomized placebo‐controlled trial that evaluated the effect of 40 mg of rosuvastatin on 2‐year change in carotid intima media thickness (CIMT) amongst 984 low‐risk patients (10‐year Framingham risk <10%) with modest CIMT (CIMT ≥ 1.2 and <3.5 mm) and elevated LDL‐C. CRP levels were measured at baseline and after 2 years of treatment. Results. Median baseline CRP was 1.4 mg L^–1. Rosuvastatin lowered CRP significantly compared with placebo: ?36% in the rosuvastatin group versus no change in the placebo group. There was no relation between change in CRP and change in LDL‐C (Spearman correlation: 0.08; SE: 0.04). Stratified analyses showed that the CRP‐lowering effect was present amongst all strata of baseline characteristics, including baseline lipids and CRP levels. However, the magnitude of CRP reduction was larger amongst women and participants older than 60 years. Conclusions. Rosuvastatin (40 mg) lowers CRP independently from its effects on LDL‐C in low‐risk subjects with normal baseline CRP levels and modest CIMT.     

Modeling the intraurban variability of ambient traffic pollution in Toronto, Canada

The objective of this paper is to model determinants of intraurban variation in ambient concentrations of nitrogen dioxide (NO2) in Toronto, Canada, with a land use regression (LUR) model. Although researchers have conducted similar studies in Europe, this work represents the first attempt in a North American setting to characterize variation in traffic pollution through the LUR method. NO2 samples were collected over 2 wk using duplicate two-sided Ogawa passive diffusion samplers at 95 locations across Toronto. Independent variables employed in subsequent regression models as predictors of NO2 were derived by the Arc 8 geographic information system (GIS). Some 85 indicators of land use, traffic, population density, and physical geography were tested. The final regression model yielded a coefficient of determination (R2) of .69. For the traffic variables, density of 24-h traffic counts and road measures display positive associations. For the land use variables, industrial land use and counts of dwellings within 2000 m of the monitoring location were positively associated with NO2. Locations up to 1500 m downwind of major expressways had elevated NO2 levels. The results suggest that a good predictive surface can be derived for North American cities with the LUR method. The predictive maps from the LUR appear to capture small-area variation in NO2 concentrations. These small-area variations in traffic pollution are probably important to the exposure experience of the population and may detect health effects that would have gone unnoticed with other exposure estimates.     

Mismatch repair-dependent mutagenesis in nondividing cells

Mismatch repair (MMR) is a major DNA repair pathway in cells from all branches of life that removes replication errors in a strand-specific manner, such that mismatched nucleotides are preferentially removed from the newly replicated strand of DNA. Here we demonstrate a role for MMR in helping create new phenotypes in nondividing cells. We show that mispairs in yeast that escape MMR during replication can later be subject to MMR activity in a replication strand-independent manner in nondividing cells, resulting in either fully wild-type or mutant DNA sequence. In one case, this activity is responsible for what appears to be adaptive mutation. This replication strand-independent MMR activity could contribute to the formation of tumors arising in nondividing cells and could also contribute to mutagenesis observed during somatic hypermutation of Ig genes.     

Pravastatin, lipids, and atherosclerosis in the carotid arteries: design features of a clinical trial with carotid atherosclerosis outcome.

The Pravastatin, Lipids, and Atherosclerosis in the Carotids trial (PLAC-II) was initiated in 1987 and is the first double-masked randomized clinical trial with progression of early extracranial carotid atherosclerosis as an outcome variable. The trial will compare a lipid-lowering agent (pravastatin, a hydroxymethylglutaryl CoA reductase inhibitor) with placebo for ability to retard the rate of progression of extracranial carotid atherosclerosis over 3 years. Inclusion criteria consisted of prevalent coronary artery disease, moderately elevated low-density lipoprotein (LDL) cholesterol (between the 60th and 90th percentiles), and the presence of at least one extracranial carotid artery atherosclerotic plaque that had an intimal-medial thickness (IMT) > or = 1.3 mm as visualized by B-mode ultrasound. Of approximately 650 patients who qualified on the basis of coronary disease and elevated LDL cholesterol, 55% were excluded because of B-mode criteria. One hundred and fifty-one males and females 50-75 years of age were recruited. Random allocation produced placebo-treated and test-treated groups that were similar for baseline historical data, physical findings, laboratory tests, lipid values, and B-mode characteristics. Baseline concentrations of plasma total cholesterol, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol were 234, 166, and 41 mg/dl, respectively. Baseline plasma concentration of triglyceride was 170 mg/dl. Despite selection of participants whose arteries, overall, were suitable for the trial, individual segments in some participants could not be visualized. Ninety-seven percent of the individual carotid artery segments were visualized in the common carotid, 88% in the bifurcation, and 63% in the internal carotid artery. Far walls were slightly more often visualized than near walls, and nonvisualization was most common for the near wall of the internal carotid. Nonvisualized segments were comparable between both treatment groups. The distribution of arterial walls with qualifying plaque of > or = 1.3 mm IMT was similar for the two groups, and the two groups were also comparable for the primary outcome determinant, mean maximum IMT (mean of maximum of all visualizable sites, 1.32 mm for each treatment group). There are special problems related to recruitment and evaluation of patients for a clinical trial such as this, but the atherosclerosis outcome measurement markedly enhances power and compensates for difficulty in recruitment.