To characterize the role of cardiac function in septic shock, serial radionuclide cineangiographic and hemodynamic evaluations were done on 20 patients with documented septic shock. Although all patients had a normal or elevated cardiac index, 10 patients had moderate to severe depression of their ejection fraction with values below 0.40. Thirteen of twenty patients survived their episode. Paradoxically, 10 of 13 survivors, but none of the 7 nonsurvivors, had an initial ejection fraction less than 0.40 (p less than 0.005). The mean initial ejection fraction for the survivors was 0.32 +/- 0.04, and their mean end systolic and end diastolic ventricular volumes were substantially increased with a normal stroke volume. The survivors' serial scans showed a gradual return to normal ejection fraction and ventricular volume by 10 days after the onset of shock. Nonsurvivors had normal initial ejection fractions and ventricular volumes that did not change during serial studies.
The derivation of dopamine neurons is one of the best examples of the clinical potential of embryonic stem (ES) cells, but the long-term function of the grafted neurons has not been established. Here, we show that, after transplantation into an animal model, neurons derived from mouse ES cells survived for over 32 weeks, maintained midbrain markers, and had sustained behavioral effects. Microdialysis in grafted animals showed that dopamine (DA) release was induced by depolarization and pharmacological stimulants. Positron emission tomography measured the expression of presynaptic dopamine transporters in the graft and also showed that the number of postsynaptic DA D 2 receptors was normalized in the host striatum. These data suggest that ES cell-derived neurons show DA release and reuptake and stimulate appropriate postsynaptic responses for long periods after implantation. This work supports continued interest in ES cells as a source of functional DA neurons. STEM CELLS 2007;25:918 -928 Disclosure of potential conflicts of interest is found at the end of this article.
Although coronary angiography defines regions of potential ischemia in patients with coronary-artery disease, accurate assessment of the presence and functional importance of ischemia requires appraisal of regional and global left ventricular function during stress. To perform such assessment, we developed a noninvasive real-time radionuclide cineangiographic procedure permitting continuous monitoring and analysis of left ventricular function during exercise. In 11 patients with coronary disease who had normal regional and global ventricular function at rest, new regions of dysfunction developed during exercise (P less than 0.001), and in 10, global ejection fraction dropped 7 to 47 per cent. Fourteen age-matched normal subjects were studied; during exercise none had regional dysfunction, and each increased global ejection fraction (average increase, 23 +/- 3 per cent [+/-S.E.], P less than 0.001 as compared with patients with coronary disease). Radionuclide cineangiography during exercise permits accurate assessment of the presence and functional severity of ischemic heart disease.
Marked reductions in brain uptake of this radioligand in transgenic mice may be due to reduced cerebral blood flow relative to that in wild-type mice. Specific [11C]6-OH-BTA-1 binding to Abeta plaques, if any, is probably very low, as reflected in the small FR/CE and PA/CE ratio differences. FR/CE and PA/CE ratios are considerably higher in AD patients while Abeta plaque densities in 22-month-old transgenic mice may be expected to show essentially the same density as is observed in the AD brain. This implies that the absence of tracer retention in 22-month-old transgenic mice may be due to the smaller number of Abeta plaque binding sites and/or to lower affinity of the binding sites for [11C]6-OH-BTA-1 as compared with AD patients. [11C]6-OH-BTA-1 shows excellent brain uptake in mice.
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