Comparison of flow-mediated dilatation of the brachial artery in coronary patients with low-density lipoprotein cholesterol levels <80 mg/dl versus patients with levels 80 to 100 mg/dl

Testing of peripheral vascular endothelial function was performed in subjects who had coronary artery disease and a low-density lipoprotein (LDL) cholesterol level <100 mg/dl. LDL cholesterol was an independent predictor of flow-mediated dilation of the brachial artery (p = 0.010). The 63 subjects who had an LDL cholesterol level <80 mg/dl had better endothelial function (flow-mediated dilation 8.4 +/- 3.8%) than did 47 subjects whose level of LDL cholesterol was 80 to 100 mg/dl (flow-mediated dilation 6.8 +/- 4.0%, p = 0.03). The beneficial effects of LDL cholesterol levels <80 mg/dl on endothelial function were more apparent in subjects who had low levels of high-density lipoprotein cholesterol than in those who had normal levels. These data support recent reports that decreasing levels of LDL cholesterol below those currently recommended provides additional benefits and suggest that this benefit may be due in part to increased endothelial function.     

Assessment of myocardial perfusion by myocardial contrast echocardiography using harmonic power and the transvenous contrast agent SHU 563A in acute coronary occlusion and after reperfusion

BACKGROUND: Harmonic power Doppler imaging is a novel technique for the assessment of myocardial perfusion by contrast echocardiography. In this study, we examined whether myocardial contrast echocardiography using harmonic power Doppler and the new transvenous contrast agent SHU 563A can identify myocardial perfusion defects during coronary occlusion and reperfusion. METHODS: To assess the potential of this technique, we occluded either the left anterior descending coronary artery or the circumflex coronary artery for 2 to 3 h followed by 1 h reperfusion in 10 dogs in an open chest model. After transvenous administration of SHU 563A, an air-filled, polymeric contrast agent, myocardial contrast echocardiography was performed in short and long axis views with triggered harmonic power Doppler imaging after coronary occlusion and reperfusion. Post-mortem triphenyl tetrazolium chloride staining was performed to verify infarction. Harmonic power Doppler and anatomic data were analyzed by independent observers. RESULTS: During coronary occlusion, harmonic power Doppler showed perfusion defects in all 10 dogs. The defect size in the short axis view at papillary muscle level ranged 4-51% (14+/-13%) and 3-43% (16+/-10%) in the long axis view (% total LV slice area). After reperfusion (1 h) and infusion of dipyridamole (0.56 mg/kg), power Doppler demonstrated perfusion defects in seven dogs: 0-20% (9+/-8%) (short axis view) and 0-48% (13+/-14%) (long axis view). Five dogs showed anatomic infarction. The anatomic infarct area was 0-18% (6+/-8%) (slices corresponding to the echocardiographic short axis images). Perfusion defect size by harmonic power Doppler correlated well with residual infarct size (r=0.82, P<0.01). CONCLUSIONS: Myocardial contrast echocardiography using harmonic power Doppler and the new contrast agent SHU 563A accurately displays perfusion defects during acute coronary occlusion and after reperfusion. The site and size of residual myocardial infarction is reliably identified on line, in color. This approach has excellent potential for clinical application.     

Serum FSH bioactivity and response to acute gonadotrophin releasing hormone (GnRH) agonist stimulation in patients with polycystic ovary syndrome (PCOS) as compared to control groups

OBJECTIVE We evaluated the biological activity of FSH in the serum of women with polycystic ovary syndrome before and after acute administration of a GnRH agonist as compared to control groups. DESIGN FSH, oestradiol and androstenedione response to buserelin (100 μg s.c.) comparing seven polycystic ovary patients, six idiopathic hirsute women, 11 normal women in the follicular phase and nine normal men. MEASUREMENTS Rat granulosa cell aromatase bioassay in the presence or absence of polyethyleneglycol (PEG) pretreated 2% serum. Serum biological FSH (B-FSH), immunological FSH (I-FSH) and B/I ratio at times 0,1, 2, 3, 4, 8, 12 and 24 hours. Serum androstenedione and oestradiol at times 0 and 24 hours. RESULTS Human gonadotrophin-free (oral contraceptive user and after FSH immunoabsorption) and PEG-pre-treated serum increases the aromatase activity in response to increasing doses of purified FSH. The maximum enzymatic activity is however higher with 2% serum than with 4% serum. The amplitude of the B-FSH response to the GnRH agonist is markedly decreased in the polycystic group as compared to the group of normal women. There is also a small decrease in the l-FSH response in the polycystic women. When compared to that of normal women, the area under the curve in the polycystic ovary patients is reduced by 71% for B-FSH (P<001) and by 23% for l-FSH (P<0.05). The B-FSH and I-FSH responses in men are very small. After an initial decrease the B/I ratio returns to baseline level in normal women but remains low in the other groups. At time 24 hours, there is no significant change in the serum concentration of androstenedione but serum oestradiol, the baseline of which is significantly higher in the polycystic patients than in normal women, is also significantly higher at 24 hours (P< 0.05) in response to the pharmacological release of FSH. CONCLUSION The gonadotrophin-free and PEG-pre-treated human serum has an inherent stimulatory effect on the rat granulosa aromatase bioassay with a higher activity at 2% serum. Acute GnRH agonist stimulation reveals a deficiency in the FSH response in polycystic ovary patients. The greater deficit in B-FSH than in l-FSH would indicate a possible modification in the FSH isoforms in this syndrome. The meaning of this observation for the understanding of the physiopathology of the polycystic ovary syndrome remains to be evaluated.     

Morphological variation of layer III pyramidal neurones in the occipitotemporal pathway of the macaque monkey visual cortex

We compared the morphological characteristics of layer III pyramidal neurones in different visual areas of the occipitotemporal cortical 'stream', which processes information related to object recognition in the visual field (including shape, colour and texture). Pyramidal cells were intracellularly injected with Lucifer Yellow in cortical slices cut tangential to the cortical layers, allowing quantitative comparisons of dendritic field morphology, spine density and cell body size between the blobs and interblobs of the primary visual area (V1), the interstripe compartments of the second visual area (V2), the fourth visual area (V4) and cytoarchitectonic area TEO. We found that the tangential dimension of basal dendritic fields of layer III pyramidal neurones increases from caudal to rostral visual areas in the occipitotemporal pathway, such that TEO cells have, on average, dendritic fields spanning an area 5-6 times larger than V1 cells. In addition, the data indicate that V1 cells located within blobs have significantly larger dendritic fields than those of interblob cells. Sholl analysis of dendritic fields demonstrated that pyramidal cells in V4 and TEO are more complex (i.e. exhibit a larger number of branches at comparable distances from the cell body) than cells in V1 or V2. Moreover, this analysis demonstrated that the dendrites of many cells in V1 cluster along specific axes, while this tendency is less marked in extrastriate areas. Most notably, there is a relatively large proportion of neurones with 'morphologically orientation-biased' dendritic fields (i.e. branches tend to cluster along two diametrically opposed directions from the cell body) in the interblobs in V1, as compared with the blobs in V1 and extrastriate areas. Finally, counts of dendritic spines along the length of basal dendrites revealed similar peak spine densities in the blobs and the interblobs of V1 and in the V2 interstripes, but markedly higher spine densities in V4 and TEO. Estimates of the number of dendritic spines on the basal dendritic fields of layer III pyramidal cells indicate that cells in V2 have on average twice as many spines as V1 cells, that V4 cells have 3.8 times as many spines as V1 cells, and that TEO cells have 7.5 times as many spines as V1 cells. These findings suggest the possibility that the complex response properties of neurones in rostral stations in the occipitotemporal pathway may, in part, be attributed to their larger and more complex basal dendritic fields, and to the increase in both number and density of spines on their basal dendrites.      

Functional, biochemical, and histopathologic consequences of high-dose interleukin-2 administration in rats

A variety of side effects have been reported with the use of interleukin-2 alone or in combination with lymphokine-activated killer cells in patients with disseminated neoplasms. The present study was undertaken to determine the effects of high-dose interleukin-2 administration in normal rats. Sprague-Dawley rats were treated with intravenous recombinant interleukin-2 (900,000 IU/kg/day) for 9 consecutive days. Animals were placed in individual metabolic cages, and arterial blood pressure, food intake, body weight, and urine output were monitored. On day 10, animals were killed by exsanguination, various tissues were harvested, and a variety of hematologic and chemical assays were performed. The results were compared with those of placebo-injected normal control and pair-fed groups. The interleukin-2-treated group exhibited anorexia, weight loss, hypotension, anemia, leukocytosis, lymphocytosis, eosinophilia, hypercalcemia, azotemia, and a marked urinary concentration defect. Histologic examination of various tissues revealed widespread infiltration with mono-nuclear cells and eosinophils in most organs, especially in the lungs and liver of interleukin-2-treated animals. Other abnormalities included severe panlobular hepatitis, hepatocellular necrosis, and thymic involution. Renal involvement was mild and consisted of focal interstitial infiltration by mononuclear cells. According to these observations, administration of high-dose interleukin-2 in normal rats results in a score of significant functional, biochemical, and histologic abnormalities.