Radionuclide cardiac volumes: effects of region of interest selection and correction for Compton scatter using a buildup factor.

The effects of region of interest (ROI) selection and correction for Compton-scattered photons using a buildup factor on radionuclide left ventricular volumes calculated by the Links method were compared in 19 humans with contrast ventriculography and in phantoms. Three different methods of ROI selection were compared: a manual ROI, a second derivative ROI and a 50% count-threshold ROI. In phantoms without Compton scatter correction, volumes were overestimated by 30% (manual ROI), 20% (derivative ROI) and 1% (count threshold ROI). In subjects, results without Compton scatter correction were similar with overestimates of 50% (manual ROI) and 20% (derivative ROI) and an underestimate by 3% (count threshold method). Correction for Compton-scattered photons with the use of a phantom-derived buildup factor resulted in improved accuracy for the manual ROI (+15%) and the derivative ROI (0%). A 50% count threshold ROI following interpolative background subtraction allows the accurate calculation of cardiac volumes without the need for scatter correction, while a second derivative ROI method requires a correction for Compton scatter with the use of a buildup factor.     

A series of novel, highly potent and selective agonists for the kappa-opioid receptor.

1. This paper describes the opioid receptor pharmacology and in vivo activity of several novel benzene-acetamidopiperidine and benzeneacetamidopiperazine analogues. 2. These compounds all showed potent, naloxone-reversible, full agonist activity in the field-stimulated rabbit vas deferens, indicating that they are kappa-opioid agonists; but showed very little activity in the rat or hamster vas deferens, indicating good selectivity with regard to mu- and delta-opioid receptors. 3. They were all potent antinociceptive agents, the most potent compound, GR 103545, having an ED50 value in the mouse abdominal constriction test of 0.25 micrograms kg-1 s.c. The compounds also produced sedation and diuresis, but had little effect on respiration rate or gastrointestinal motility. 4. It is concluded that the seven novel compounds described are all potent and selective agonists for the kappa-opioid receptor.     

Early beneficial effect of streptokinase on left ventricular function in acute myocardial infarction

The effect of intravenous streptokinase therapy on the time course of functional recovery was investigated in a controlled study of 64 patients randomized within 3 hours after the onset of acute myocardial infarction (AMI). Contrast ventriculography was performed 1 to 4 days after AMI and repeated 5 weeks later. Wall motion was analyzed by the centerline method in the central infarct, peripheral infarct and noninfarct regions. In patients with ventriculographic data at the early catheterization, streptokinase-treated patients had less severe hypokinesia in the central infarct region than control patients (-2.9 +/- 0.9 [n = 29] vs -3.4 +/- 0.7 standard deviations below normal [n = 21], p less than 0.05). The benefit of streptokinase was more marked in the peripheral infarct region (-1.5 +/- 0.7 vs -2.1 +/- 0.6, p less than 0.001). As a result, the ejection fraction was slightly higher in treated versus control groups (46 +/- 10 vs 43 +/- 7%, respectively; difference not significant). At 5 weeks, function in the streptokinase and control groups had diverged further because of continued improvement in the streptokinase-treated patients. This study shows that streptokinase benefits left ventricular (LV) function by 1 to 4 days after AMI, earlier than previously reported. The benefit was not limited to the peripheral infarct region, where ischemia might have been less severe, but was also seen in the central infarct region. The implication is that thrombolytic therapy can improve LV function during the period of myocardial stunning, while myocardial function is still recovering.     

Lack of correlation after reperfusion between ventricular function and infarct size estimated by thallium single-photon emission computed tomography

In 32 patients with acute myocardial infarction, who had undergone successful intracoronary thrombolysis, the results of regional wall motion measured from contrast cineangiograms 10 to 21 days after thrombolysis were related to the results of thallium single-photon emission computed tomography (SPECT) after intravenous dipyridamole. Wall motion was measured by means of the centerline method, and thallium defect size was estimated by comparing the patient's circumferential profile with that of 20 normals. No correlation was found between ejection fraction or regional wall motion and thallium defect size. The time from symptom onset to thrombolysis was inversely correlated with the degree of hypokinesis (r=–0.51) but not with thallium defect size. In patients treated within 3 hours, hypokinesis was significantly less than in patients treated later (–1.1±0.6 SD vs –2.2±0.8 SD, p<0.01) whereas thallium defect size was not significantly different in both groups. It is concluded that, in patients after thrombolysis, thallium defect size determined by SPECT does not reflect the degree of left ventricular dysfunction.     

A pilot study of medical student 'abuse'. Student perceptions of mistreatment and misconduct in medical school

A pilot survey of one third-year medical school class was carried out to explore student perceptions of mistreatment and professional misconduct in medical school training. Students were asked to rate the frequency and cite sources of mistreatment and misconduct among classmates, faculty, residents, and interns. They were also asked to assess the effects of such episodes on their physical health, emotional well-being, social and family life, and attitudes toward becoming a physician. The results indicate that students perceive mistreatment (particularly verbal abuse and unfair tactics) to be pervasive and professional misconduct all too common. As many as three fourths of the students report having become more cynical about academic life and the medical profession as a result of these episodes. Two thirds feel they are worse off than their peers in other professions. More than a third have considered dropping out of medical school and one fourth report they would have chosen a different profession had they known in advance about the extent of mistreatment they would experience. Rather than dismiss these problems as isolated events, we need to examine this issue more closely.     

Association analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample: preferential transmission of the MAO-A 941G allele to affected children.

Pharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of attention deficit hyperactivity disorder (ADHD). Monoamine oxidases A and B (MAO-A and MAO-B) degrade biogenic amines such as dopamine and serotonin and thereby control the levels of these neurotransmitters in the central nervous system. We examined four polymorphisms in the MAO-A gene (30 bp promoter VNTR, CA microsatellite in intron 2, 941G/T SNP in exon 8, and A/G SNP in intron 12) as well as two markers in the MAO-B gene (CA microsatellite in intron 2 and T/C SNP in intron 13) for association with ADHD in an Irish sample of 179 nuclear families. TDT analysis of the examined MAO-A markers revealed a significant association of the more active MAO-A 941G allele with the disorder (chi2 = 5.1, P = 0.03, OR = 1.7). In addition, haplotype analysis revealed a significantly increased transmission of a haplotype consisting of the shorter allele of the promoter VNTR (allele 1), the 6-repeat allele of the CA microsatellite and the G-allele of the 941G/T SNP (famhap global statistic 34.54, P = 0.01) to ADHD cases. No significant distortion in the number of transmitted alleles was observed between the two examined MAO-B polymorphisms and ADHD. These findings suggest the importance of the 941G/T MAO-A polymorphism in the development of ADHD at least in the Irish population.