Publications

The aim of this study was to determine appropriate endoscopic treatment of patients with bleeding ulcers by synthesizing results of randomized controlled trials. We performed dual independent bibliographic database searches to identify randomized trials of thermal therapy, injection therapy, or clips for bleeding ulcers with active bleeding, visible vessels, or clots, focusing on results from studies without second-look endoscopy and re-treatment. The primary end point was further (persistent plus recurrent) bleeding. Compared with epinephrine, further bleeding was reduced significantly by other monotherapies (relative risk [RR], 0.58 [95% CI, 0.36-0.93]; number-needed-to-treat [NNT], 9 [95% CI, 5-53]), and epinephrine followed by another modality (RR, 0.34 [95% CI, 0.23-0.50]; NNT, 5 [95% CI, 5-7]); epinephrine was not significantly less effective in studies with second-look and re-treatment. Compared with no endoscopic therapy, further bleeding was reduced by thermal contact (heater probe, bipolar electrocoagulation) (RR, 0.44 [95% CI, 0.36-0.54]; NNT, 4 [95% CI, 3-5]) and sclerosant therapy (RR, 0.56 [95% CI, 0.38-0.83]; NNT, 5 [95% CI, 4-13]). Clips were more effective than epinephrine (RR, 0.22 [95% CI, 0.09-0.55]; NNT, 5 [95% CI, 4-9]), but not different than other therapies, although the latter studies were heterogeneous, showing better and worse results for clips. Endoscopic therapy was effective for active bleeding (RR, 0.29 [95% CI, 0.20-0.43]; NNT, 2 [95% CI, 2-2]) and a nonbleeding visible vessel (RR, 0.49; [95% CI, 0.40-0.59]; NNT, 5 [95% CI, 4-6]), but not for a clot. Bolus followed by continuous-infusion proton pump inhibitor after endoscopic therapy significantly improved outcome compared with placebo/no therapy (RR, 0.40 [95% CI, 0.28-0.59]; NNT, 12 [95% CI, 10-18]), but not compared with histamine(2)-receptor antagonists. Thermal devices, sclerosants, clips, and thrombin/fibrin glue appear to be effective endoscopic hemostatic therapies. Epinephrine should not be used alone. Endoscopic therapy should be performed for ulcers with active bleeding and nonbleeding visible vessels, but efficacy is uncertain for clots. Bolus followed by continuous-infusion intravenous proton pump inhibitor should be used after endoscopic therapy.

Both sphingosine and sphingosine-1-phosphate (S1P) were able to protect the ex vivo rat heart from ischemia reperfusion injury when added to the perfusion medium at the time of reperfusion after a 40min ischemia (postconditioning). Inhibitor studies revealed distinct mechanisms of protection, with S1P employing a G-protein coupled receptor pathway and sphingosine a cyclic nucleotide dependent protein kinase pathway. However, both restored ischemia-induced depletion of phospho-AKT. Extending the ischemia to 75min reduced protection by both S1P and sphingosine, but protection could be enhanced by employing them in combination. Extending the time of ischemia further to 90min almost eliminated cardioprotection by S1P or sphingosine; and their combination gave only modest protection. However, when S1P plus sphingosine was combined with a novel ramped ischemic postconditioning regimen, left ventricle developed pressure recovered by 66% and there was only a 6% infarct size. The data indicate that detrimental changes are accumulating during protracted ischemia but for up to 90min this damage is not irreversible and hearts can still recover with proper treatment.

BACKGROUND AND METHODS

In vivo neuroimaging studies have provided evidence of decreases in the gray matter volume of the cingulate gyrus in subjects with schizophrenia as compared to healthy controls. To investigate whether these changes might be related to heritable influences, we used high-resolution magnetic resonance imaging and labeled cortical mantle distance mapping to measure gray matter volume, as well as thickness and the area of the gray/white interface, in the anterior and posterior segments of the cingulate gyrus in 28 subjects with schizophrenia and their non-psychotic siblings, and in 38 healthy control subjects and their siblings.

RESULTS

There was a significant effect of group status on posterior cingulate cortex (PCC) gray matter volume (p=0.02). Subjects with schizophrenia and their non-psychotic siblings showed similar reductions of gray matter volume (approximately 10%) in the PCC compared to healthy control subjects and their siblings. In turn, trend level effects of group status were found for thickness (p=0.08) and surface area (p=0.11) of the PCC. In the combined group of schizophrenia subjects and their siblings, a direct correlation was observed between PCC gray matter volume and negative symptoms. However, the reduction in PCC gray matter volume in schizophrenia subjects and their siblings was proportionate to an overall reduction in whole cerebral volume, i.e., the effect of group on the volume of the PCC became non-significant when cerebral volume was included as a covariate (p=0.4). There was no significant effect of group on anterior cingulate cortex volume, thickness, or area.

CONCLUSIONS

Our findings suggest that decreases in the gray matter volume of the PCC occur in schizophrenia subjects and their siblings. The presence of such decreases in the non-psychotic siblings of schizophrenia subjects suggests that heritable factors may be involved in the development of cortical abnormalities in schizophrenia.