Individual differences in psychotic effects of ketamine are predicted by brain function measured under placebo

The symptoms of major psychotic illness are diverse and vary widely across individuals. Furthermore, the prepsychotic phase is indistinct, providing little indication of the precise pattern of symptoms that may subsequently emerge. Likewise, although in some individuals who have affected family members the occurrence of disease may be predicted, the specific symptom profile may not. An important question, therefore, is whether predictive physiological markers of symptom expression can be identified. We conducted a placebo-controlled, within-subjects study in healthy individuals to investigate whether individual variability in baseline physiology, as assessed using functional magnetic resonance imaging, predicted psychosis elicited by the psychotomimetic drug ketamine and whether physiological change under drug reproduced those reported in patients. Here we show that brain responses to cognitive task demands under placebo predict the expression of psychotic phenomena after drug administration. Frontothalamic responses to a working memory task were associated with the tendency of subjects to experience negative symptoms under ketamine. Bilateral frontal responses to an attention task were also predictive of negative symptoms. Frontotemporal activations during language processing tasks were predictive of thought disorder and auditory illusory experiences. A subpsychotic dose of ketamine administered during a second scanning session resulted in increased basal ganglia and thalamic activation during the working memory task, paralleling previous reports in patients with schizophrenia. These results demonstrate precise and predictive brain markers for individual profiles of vulnerability to drug-induced psychosis.     

Prospects of micromass culture technology in tissue engineering

The paradigmatic shift to evidence-based dentistry (EBD) that relates to occlusal therapy, selective occlusal adjustment (OA) and stabilization splints therapy (SS) for TMDs has had an unfavourable impact on the teaching of many of the important aspects of occlusion needed in dental practice. The teaching of OA systematically in dental schools has been nearly abandoned because of the belief that OA is an irreversible procedure and gives the impression that it is without merit elsewhere in the management of occlusion. However, a particular dose of knowledge and practice of occlusion that is necessary for all aspects of dental care should be taught systematically in dental schools. The uses and misuses of OA and SS and their limitations should be emphasized because of their importance to bring clinical reality into the dental curriculum. Thus, and irrespective of EBD induced contradictions, OA and SS should still have a significant place in systematically teaching of occlusal therapy. However, there are many more aspects of the management of occlusion that should to be considered. Hopefully, because of their importance, other aspects of the management of occlusion will once again become a significant part of the dental curriculum.     

Sputum induction: effect of nebulizer output and inhalation time on cell counts and fluid-phase measures

BACKGROUND: A knowledge of the factors that can affect induced sputum results is essential in order to standardize the procedure. OBJECTIVE: We investigated the influence of nebulizer output on sputum cell counts and fluid phase measurements at increasing times of sputum induction. METHODS: Eighteen adults with stable asthma inhaled an aerosol of 3% hypertonic saline to induce sputum after 7, 14 and 21 min on 2 days separated by 48 h. On one day, in random order, the ultrasonic nebulizer used had a relatively low output of 0.87 mL/min (particle size 5.58 microm mass median aerodynamic diameter, MMAD) and, on the other, a higher output of 1.90 mL/min (particle size 4.14 microm MMAD). The sputum was selected from each expectorate and examined blind to the induction procedures. RESULTS: With both nebulizers, the 14- and 21-min samples were lower in weight, neutrophils, eosinophils, eosinophil cationic protein (ECP) and interleukin (IL)-8 and higher in macrophages. The higher output nebulizer induced sputum with higher cell viability and lower ECP and IL-8. CONCLUSION: The results identify that the volume of hypertonic saline inhaled in sputum induction influences the fluid-phase measurements. The duration of induction does alter the cell counts and suggests that the later expectorated sputum samples originate from more peripheral airways. The results draw attention to the need to standardize the volume and time of nebulization to accurately interpret and compare results.     

Coarctation of the aorta: MR imaging

Thirteen patients, aged 3-31 years, with coarctation of the thoracic aorta were examined by magnetic resonance (MR) imaging (total of 14 studies). Eight studies were performed preoperatively and six postoperatively. Catheterization data were available on 12 patients for verification of MR imaging findings. Electrocardiographically gated sagittal and left anterior oblique images best depicted the coarctations; however, involvement of arch vessels was best evaluated on transaxial images. MR imaging readily identified all coarctations but one, their site and extent, and involvement of the arch vessels. In addition, MR images depicted poststenotic dilatation and dilated collateral vessels. In patients studied postoperatively, restenosis could be evaluated, and complications such as postoperative aneurysm and perianastomotic hematoma were identified. MR imaging provides excellent anatomic detail of coarctation of the aorta, potentially obviating the need for angiography.     

Antioxidant effects of simvastatin in primary and secondary prevention of coronary heart disease

Objective The aim of the present study was to determine the effect of simvastatin on the levels of oxidized low-density lipoprotein (ox-LDL) and free radicals in hypercholesterolemic subjects undergoing primary and secondary prevention of coronary heart disease (CHD).Methods Fifteen subjects with hypercholesterolemia and no obvious CHD and 29 subjects with hypercholesterolemia and stable angina received 40 mg of simvastatin daily for 12 weeks. Serum total cholesterol, HDL-cholesterol and triglyceride concentrations were determined by automated enzymatic assays whereas LDL-cholesterol was calculated using the Friedwald formula. The ox-LDL levels were determined by a commercially available ELISA kit. Free radicals were assessed by the Free Radical Analytical System (FRAS).Results Both in primary and secondary prevention, subjects had borderline levels of free radicals but in neither group there was a significant reduction of free radicals after simvastatin treatment. In subjects undergoing primary prevention of CHD, ox-LDL levels were reduced by 31.1±5.0% (P<0.001) whereas in secondary prevention were reduced by 6.5±5.2% (P<0.02) after simvastatin treatment. The reduction of ox-LDL levels did not correlate with the reduction of total cholesterol levels in either group studied. In both groups, ox-LDL levels were not associated with free radical levels either before or after simvastatin treatment.Conclusion This study demonstrates that simvastatin can significantly reduce circulating ox-LDL levels both in subjects undergoing primary and secondary prevention of CHD. These results could partly explain the slowing down of the progression of atherosclerosis caused by HMG-CoA reductase inhibitors.     

Implantation of a Novel Allogeneic Mesenchymal Precursor Cell Type in Patients with Ischemic Cardiomyopathy Undergoing Coronary Artery Bypass Grafting: an Open Label Phase IIa Trial

Heart failure is a life-limiting condition affecting over 40 million patients worldwide. Ischemic cardiomyopathy (ICM) is the most common cause. This study investigates in situ cardiac regeneration utilizing precision delivery of a novel mesenchymal precursor cell type (iMP) during coronary artery bypass surgery (CABG) in patients with ischemic cardiomyopathy (LVEF?<?40 %). The phase IIa safety study was designed to enroll 11 patients. Preoperative scintigraphy imaging (SPECT) was used to identify hibernating myocardium not suitable for conventional myocardial revascularization for iMP implantation. iMP cells were implanted intramyocardially in predefined viable peri-infarct areas that showed poor perfusion, which could not be grafted due to poor target vessel quality. Postoperatively, SPECT was then used to identify changes in scar area. Intramyocardial implantation of iMP cells with CABG was safe with preliminary evidence of efficacy of improved myocardial contractility and perfusion of nonrevascularized territories resulting in a significant reduction in left ventricular scar area at 12 months after treatment. Clinical improvement was associated with a significant improvement in quality of life at 6 months posttreatment in all patients. The results suggest the potential for in situ myocardial regeneration in ischemic heart failure by delivery of iMP cells.