Functional outcome of bone marrow stem cells (CD45(+)/CD34(-)) after cell therapy in chronic spinal cord injury in Wistar rats

Background

Therapy with diverse cell types has been proposed to regenerate spinal cord injuries seeking to minimize the consequences for the lives of chronic patients. The types considered are: mononuclear and mesenchymal adult stem cells, embryonic stem cells, and Schwann cells.

Materials and Methods

Ninety male Wistar rats that underwent spinal cord contusion injury (NYU Impactor) were followed with the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale for 14 days. Animals with scores ≤16 were randomly divided into 2 groups: control (vehicle) versus cell therapy group. The mononuclear fraction (CD45⁺/CD34⁻) obtained by puncture-aspiration of the bone marrow was isolated by a density gradient (d = 1.077). The parenchymal cell infusion was performed using a syringe (100 U/1 mL) with a 30G1/2 needle. The animals were followed for 10 days before euthanasia. Statistical analyses comparing groups were performed by the Mann-Whitney test and group comparisons by the Wilcoxon test.

Results

Among 90 injured rats, 65 (72.2%) survived, including 44 whose scores were ≤16. Eleven animals finished the study in the control group (64.7%) and 17 in the therapy group (80.9%). The statistical analyses did not demonstrate significance (P > .05) for either test.

Conclusion

Mononuclear adult stem cell therapy was not demonstrated to be functionally effective for chronic spinal cord injury.     

Cardiovascular consequences of sleep apnea

A growing body of epidemiologic, experimental, and therapeutic data supports an association between sleep disordered breathing and cardiovascular morbidity and mortality. Pathophysiologic mechanisms including sympathetic activation, oxidative stress, systemic inflammation, hyperleptinemia, insulin resistance, lipidic peroxydation, may influence the development and progression of hypertension, ischemic cardiopathy, cardiac rythm disturbances, cardiac failure, renal failure and stroke. Treatment of apneas is associated with a decrease in new cardiovascular events. These results support the importance of recognising, treating, and if possible preventing OSA.     

Shear wave elastography of lumbar annulus fibrosus in adolescent idiopathic scoliosis before and after surgical intervention

To determine lumbar intervertebral disc properties with shear wave elastography in adolescent idiopathic scoliotic (AIS) patients before and after surgery, and compare them with asymptomatic controls. Twenty-five severe AIS patients with an indication for fusion surgery (15 ± 1.5 years old, the Cobb angle ranging between 40 and 93°) and fifty-nine asymptomatic adolescents (13 ± 2 years old) were included prospectively. Shear wave speed (SWS) was measured in the annulus fibrosus of L3-L4, L4-L5, and L5-S1 discs of each subject. In AIS patients, measurements took place before surgery, and 3 months (N = 13) or 1 year after (N = 12). No difference was observed between disc levels in any group. When pooling disc levels, SWS was significantly higher in preop AIS patients (4.0 ± 0.5 m/s) than in asymptomatic subjects (3.1 ± 0.5 m/s, p < 0.0001). SWS decreased 3 months postop (3.5 ± 0.3 m/s), and it decreased further towards normal values 1 year after (3.3 ± 0.4 m/s). SWS in preop AIS patients tended to decrease with the Cobb angle (Spearman’s rho = − 0.4, p = 0.05). Shear wave elastography measurements showed that discs in AIS patients were altered relative to asymptomatic ones, and this alteration tended to normalize 1 year post fusion surgery. Further studies should aim at determining if bracing of mild scoliosis has an effect on disc properties. • Shear wave elastography shows alteration of annulus fibrosus in adolescent idiopathic scoliosis. • Disc elastography tends to normalize 1 year after surgery.     

Endothelial function, carotid artery intima-media thickness, epicardial adipose tissue, and left ventricular mass and function in growth hormone-deficient adolescents: apparent effects of growth hormone treatment on these parameters

OBJECTIVE: The purpose of this study was to determine whether GH-deficient (GHD) adolescents have abnormalities of cardiac and vascular function detectable during the teenage years. DESIGN/METHODS: Ten GHD children on GH treatment with a chronological age (CA) of 14.6 +/- 1.7 yr and 12 untreated GHD adolescents with a CA of 15.0 +/- 3.0 yr were studied. Cardiac mass and function, carotid artery intima-media thickness, flow-mediated endothelium-dependent vasodilation (percent change from baseline diameter during hyperemia), and hyperemia-induced blood flow increase of the brachial artery (percent change from baseline) and epicardial adipose tissue were evaluated by echocardiography. Fourteen healthy adolescents served as controls. RESULTS: Untreated GHD adolescents present with a reduced left ventricular mass when compared with controls (P < 0.05) and a lower flow-mediated endothelium-dependent increase in the diameter of the brachial artery during hyperemia than both controls and treated GHD subjects (P < 0.02), whereas their epicardial adipose tissue is significantly higher than that of healthy controls (P < 0.02). Interventricular septum thickness, posterior wall thickness, left ventricular ejection fraction, and carotid artery intima-media thickness were similar in all three groups. Hyperemia-induced blood flow increase was greater in treated GHD adolescents than both untreated subjects and controls (P < 0.001). Body mass index correlated positively with epicardial adipose tissue in all three groups and with carotid intima-media thickness in treated and untreated GHD adolescents. CONCLUSIONS: GHD adolescents have a reduced left ventricular mass and vascular abnormalities manifested by lower flow-mediated endothelium-dependent vasodilation. These findings together with an increase in epicardial adipose tissue, a good indicator of abdominal/visceral fat, may contribute to an increased cardiovascular risk in the long term. An improvement in endothelial function and a reduction in arterial stiffness appear to occur after GH replacement.     

MOZ/TIF2-induced acute myeloid leukaemia in transgenic fish

The inv(8)(p11q13) chromosomal abnormality, described in acute myeloid leukaemias (AML), fuses the histone acetyl-transferase (HAT) MYST3 (MOZ) gene with another HAT gene, NCOA2 (TIF2). We generated a transgenic zebrafish in which the MYST3/NCOA2 fusion gene was expressed under control of the spi1 promoter. An AML developed in 2 of 180 MYST3/NCOA2-EGFP-expressing embryos, 14 and 26 months after injection of the fusion gene in a one-cell embryo, respectively. This leukaemia was characterised by an extensive invasion of kidneys by myeloid blast cells. This model, which is the first zebrafish model of AML, demonstrates the oncogenic potency of MYST3/NCOA2 fusion gene.     

Benefits of obstructive sleep apnoea treatment in coronary artery disease: a long-term follow-up study.

AIM: The aim of this long-term prospective study was to evaluate the effect of treating obstructive sleep apnoea (OSA) on the rate of cardiovascular events in coronary artery disease (CAD). METHODS AND RESULTS: We prospectively studied 54 patients (mean age 57.3 +/- 10.1 years) with both CAD (> or = 70% coronary artery stenosis) and OSA (apnoea-hypopnoea index > or = 15). In 25 patients, OSA was treated with continuous positive airway pressure (n=21) or upper airway surgery (n=4); the remaining 29 patients declined treatment for their OSA. The median follow-up was 86.5 +/- 39 months. The two groups were similar at baseline in age, body mass index, smoking history, hypertension, hypercholesterolaemia, diabetes mellitus, number of diseased vessels, left ventricular ejection fraction, and CAD therapy. Treatment of risk factors other than OSA was similar in the two groups. The endpoint (a composite of cardiovascular death, acute coronary syndrome, hospitalisation for heart failure, or need for coronary revascularisation) was reached in 6 (6/25, 24%) and 17 (17/29, 58%) patients with and without OSA treatment, respectively (P<0.01). OSA treatment significantly reduced the risk of occurrence of the composite endpoint (hazard ratio 0.24; 95% confidence interval, 0.09-0.62; p<0.01) and of each of its components. CONCLUSIONS: Our data indicate that the treatment of OSA in CAD patients is associated with a decrease in the occurrence of new cardiovascular events, and an increase in the time to such events.     

Regional variations in management of rectal cancer in France

BACKGROUND: Population-based registries provide excellent data for drawing an accurate picture of disease management practices. The purpose of this study was to determine whether diagnostic and therapeutic management practices for rectal cancer vary in different geographic regions of France. METHODS: Data Issued from nine cancer registries covering 11% of the French population. The files of 683 patients with a rectal cancer diagnosed in 1995 were selected for analysis. RESULTS: Colonoscopy was performed in a mean of 91.6% of patients (range: 80.9%-98.2%) (P=0.01). The practice of colonoscopy concomitantly with barium enema varied greatly, ranging from 1.9%-57.7% of patients (P<0.001). Pretherapeutic work-up practices were significantly different depending on the region with respect to: abdominal CT scans (13.4%-69.2%), thoracic CT scans (0.9%-13.2%) and tumor markers (46.8%-80.8%). There were no significant differences between geographic regions concerning rate of resection, use of colostomy, or tumor stage at diagnosis. Administration of adjuvant radiotherapy (mean, 46.8%; range: 21.6%-70%; P<0.001) and adjuvant chemotherapy (mean, 24.1%; range: 10.3%-40.6%; P<0.05) varied significantly between regions. CONCLUSION: Diagnostic practices and administration of adjuvant treatments vary significantly between geographic regions in France. The recommendations of the French consensus guidelines are only partially adhered to. Practitioners and healthcare Authorities should be aware of these differences in order to provide more harmonious patient care.     

The relationship between cardiometabolic and hemostatic variables: influence of race

Elevated concentrations of hemostatic variables such as fibrinogen, plasma activator inhibitor 1 (PAI-1), and tissue plasminogen activator (t-PA)/PAI-1 complex have been implicated in the pathogenesis of arterial lesion progression and subsequent cardiovascular disease. In the present study, traditional cardiometabolic variables (CMV) associated with cardiovascular disease risk were examined in relation to hemostatic variables in a group of 36 White American (WA) and 30 African American (AA) overweight/obese women. There were 9 CMV significantly related to PAI-1 and/or the t-PA/PAI-1 ratio, but not fibrinogen. A significant race effect was found for 5 CMV in relation to fibrinogen and/or the t-PA/PAI-1 ratio, but not PAI-1. Significant race and high-density lipoprotein cholesterol interactions were found for fibrinogen (P = .021); and significant race and waist to hip ratio (P = .015), diastolic blood pressure (P = .013), and insulin (P = .037) interactions were found for PAI-1. No interactions were found for the t-PA/PAI-complex. Both PAI-1 and the t-PA/PAI-1 ratio are favored above fibrinogen in the diagnostic evaluation of health risk in both WA and AA women. Because of differences by race, independent consideration should be given in the clinical management of WA and AA women presenting with elevated CMV. Our findings indicated the t-PA/PAI-1 complex to be the most global indicator of health risk in both WA and AA overweight/obese women.