In vitro evidence of propagation of superoxide dismutase-1 protein aggregation in canine degenerative myelopathy.

Canine degenerative myelopathy (DM) is a progressive and fatal neurodegenerative disorder that has been linked to mutations in the superoxide dismutase 1 (SOD1) gene. The accumulation of misfolded protein aggregates in spinal neurons and astrocytes is implicated as an important pathological process in DM; however, the mechanism of protein aggregate formation is largely unknown. In human neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), cell-to-cell propagation of disease-relevant proteins has been demonstrated. Therefore, in this study, propagation of aggregation-forming property of mutant SOD1 protein in DM in vitro was investigated. This study demonstrated that aggregates composed of canine wild type SOD1 protein were increased by co-transfection with canine mutant SOD1 (E40K SOD1), indicating intracellular propagation of SOD1 aggregates. Further, aggregated recombinant SOD1 proteins were released from the cells, taken up by other cells, and induced further aggregate formation of normally folded SOD1 proteins. These results suggest intercellular propagation of SOD1 aggregates. The hypothesis of cell-to-cell propagation of SOD1 aggregates proposed in this study may underly the progressive nature of DM pathology.

Probucol therapy in the prevention of restenosis after successful percutaneous transluminal coronary angioplasty.

The effect of probucol, a drug that inhibits the secretion of smooth muscle cell-derived growth factor, was evaluated in the prevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA). In 67 patients who successfully underwent prospective PTCA for the first time, the effects obtained in 31 patients given 750 mg or 1000 mg of probucol daily (group P) were compared with those in 36 patients given 150 mg of dipyridamole daily (group D). Drug treatment was initiated at least 7 days before PTCA and was continued for 3 to 6 months after PTCA, at which time a follow-up angiography was performed. There were no significant differences in patient characteristics (age, sex, pre-PTCA severity of angina pectoris), the number of affected vessels undergoing dilatation, or the residual degree of stenosis. The restenosis rate was significantly lower in group P (6 cases, 19.4%) than in group D (15 cases, 41.7%). In the nonrestenosis subgroup, the degree of stenosis progressed from 28.0 +/- 13.9% just after PTCA to 32.4 +/- 20.5% at follow-up angiography in group P, while it progressed significantly from 28.6 +/- 15.6% to 40.1 +/- 21.2% in group D (P < 0.05). A significant drop in serum cholesterol was observed in group P. The restenosis rate was lower in patients with high cholesterol levels at PTCA. No adverse reactions were noted in any patient. We conclude that probucol is effective in preventing restenosis after PTCA.

Development of acute myocardial infarction associated with coronary collateral regression after reperfusion by percutaneous transluminal coronary angioplasty.

Clinical and experimental observations have suggested that newly developed collaterals usually remain even after successful revascularization. We present a patient in whom coronary collateral regression was angiographically demonstrated within about 1 month after percutaneous transluminal coronary angioplasty, which led to the development of acute myocardial infarction. This case suggests that there may be a possibility of unexplained clinically important anatomical or functional regression of collaterals after reperfusion.

Effects of trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, in preventing restenosis after percutaneous transluminal coronary angioplasty.

Trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, is a potential inhibitor of intimal proliferation after percutaneous transluminal coronary angioplasty (PTCA). To study its efficacy, 72 patients were randomized to receive Trapidil (600 mg/day orally for 1 week before PTCA and for 4 to 6 months after PTCA; n = 36) or aspirin and dipyridamole (aspirin, 300 mg/day, and dipyridamole, 150 mg/day; n = 36). At entry, both groups were comparable with regard to age, sex, dilated vessels, severity of pre-PTCA stenosis, residual stenosis after PTCA, and prevalence of coronary risk factors. Repeat coronary angiography was performed 6 months after PTCA. Restenosis, defined as the loss of at least 50% of the gain in luminal diameter accomplished by dilation, was present in seven patients (19.4%) in the trapidil group and 15 patients (41.7%) in the aspirin-dipyridamole group (p less than 0.05). The progression of stenosis in patients with less than 30% residual stenosis was significant in both groups. Furthermore, in the patients with residual stenosis of more than 30%, progression of stenosis was less in the trapidil group than in the aspirin-dipyridamole group. Thus trapidil was useful in preventing intimal proliferation after PTCA, especially in patients with more than 30% residual stenosis after PTCA.

[The changes in molecular markers for hemostatic activation after t-PA therapy in case of pulmonary embolism].

We observed the changes of molecular markers for hemostatic activation in a patient with acute pulmonary embolism treated with 2 x 10(7) unit tissue plasminogen activator (t-PA). Blood samples were obtained before, just after, at 30 min, 1, 2, 6, and 24 hours after the infusion. Molecular markers included thrombin-antithrombin III complex (TAT), plasminogen-alpha 2 plasmin inhibitor complex (PIC), and thrombomodulin (TM). Marked elevation of TAT was observed from immediately after the t-PA infusion to 6 hours after, although it had been observed for only 1 hour in our previous report on the cases of acute myocardial infarction. PIC level was significantly increased during t-PA infusion but returned to almost baseline value 6 hours after the end of t-PA infusion. This finding was almost the same as the one previously reported concerning acute myocardial infarction cases. TM level increased throughout the evaluation, and remained so, even on the 7th day after t-PA infusion. Our present data revealed a clear difference between the reactive TAT increases after t-PA therapy in acute myocardial infarction cases and in acute pulmonary embolism cases. Our present data also revealed a prolonged elevation of TM during the acute period of pulmonary embolism. It is therefore necessary to keep an eye on the changes of molecular markers for hemostatic activation after t-PA therapy in acute pulmonary embolism.

ST segment alternans during percutaneous transluminal coronary angioplasty--a case report.

The occurrence of electrical alternans of the ST segment has been reported in patients with variant angina. The authors encountered a patient with typical electrical alternans of the ST segment in leads V4 through V6, which developed during percutaneous transluminal coronary angioplasty (PTCA) of the proximal left anterior descending artery. Hemodynamic pulsus alternans of the aortic pressure tracing was not observed during electrical alternans, and a Ca2+ blocker could not prevent this phenomenon during PTCA.

[Development of severe mitral regurgitation following percutaneous transvenous mitral valve commissurotomy].

The purpose of this study was to analyze the risk factors of unexpected occurrence of mitral regurgitation (MR) following percutaneous transvenous mitral valve commissurotomy (PTMC) in patients with mitral stenosis. The analyzed factors were clinical pictures, hemodynamic findings, echocardiographic findings and balloon inflation techniques during PTMC. Among 24 patients undergoing successful PTMC using an Inoue's balloon, severe MR developed in five patients (21%). No significant correlation in the occurrence of MR was observed in clinical findings, hemodynamic data and balloon inflation techniques including the times and size of ballooning. Echocardiographic findings of the mitral valve including the pliability of the mitral leaflet and localized calcification of the mitral orifice were the most contributory factors to the occurrence of severe MR. The localized alternation of valve stiffness produced localized tear or excessive dilatation of the mitral leaflet during PTMC, resulting in severe MR. Hemodynamic results and calculated mitral valve areas after PTMC showed significant improvement in both groups with and without MR. However, symptomatic improvement in patients with severe MR was less prominent when compared to the patients without MR. Thus, the complete echocardiographic evaluation of the mitral valve apparatus before PTMC is important to prevent severe MR.

[Exercise radionuclide ventriculography in evaluating successful percutaneous transluminal coronary angioplasty (PTCA)].

To evaluate late success of PTCA in 29 patients with coronary artery disease, exercise radionuclide ventriculography was performed. Twenty-nine patients were classified into two groups according to the presence of restenosis (Group N: 19 patients without restenosis, Group R: 10 patients with restenosis). LVEF improved significantly in Group N, and the sensitivity, specificity and overall accuracy for detecting restenosis were 100%, 68% and 79%, respectively. Regional wall motion abnormality during exercise did not worsened in Group N, and the sensitivity, specificity and overall accuracy for detecting restenosis were 89%, 96%, and 94%, respectively. The left ventricular end-systolic volume during exercise increased in group R but decreased in Group N. The exercise response of the ratio of systolic blood pressure to end-systolic volume in Group N was significantly larger than that of Group R, and was considered to be useful parameter for detecting restenosis.

[Clinical significance of reverse redistribution in exercise thallium-201 SPECT after percutaneous transluminal coronary angioplasty].

Clinical significance of reverse redistribution on thallium image was evaluated in 54 patients who had undergone PTCA. Thallium SPECT imaging was performed one week and three to six months after PTCA. Reverse redistribution was detected eight of 54 patients one week after PTCA and five of 38 patients three to six months after PTCA. In the segments with reverse redistribution, reduced regional wall motion and lesser degree of coronary stenosis was common features (p less than 0.05) angiography. In conclusion, reverse redistribution had a tendency to appear in the region with mild myocardial injury and relatively high coronary blood flow after PTCA. But in cases with new occurrence and disappearance of reverse redistribution during follow up period, we can not assess the factors to explain these phenomena. In these segments, "coronary flow reserve", "stunned myocardium", "hibernating myocardium" or other factors may be related.

[Clinical significance of exercise induced ST segment depression after successful percutaneous transluminal coronary angioplasty--assessment by thallium-201 SPECT].

To evaluate the clinical significance of ST segment depression during repeated Treadmill exercise after successful PTCA, Thallium-201 SPECT was performed. The Thallium-201 SPECT was performed before, one week after and 3-6 months after PTCA. All thirty-five patients had one vessel disease and positive Thallium-201 exercise test. During follow-up period for 3-6 months, 11 of 35 patients had persistent ST segment depression. Restenosis of dilated coronary lesion was demonstrated in 6 of 11 patients. In another 3 of 35 patients, exercise induced ST segment depression was disappeared during follow-up Treadmill exercise. In 14 patients with persistent or transient ST segment depression after PTCA, Thallium-201 SPECT demonstrated transient ischemia in 5 of 6 patients with restenosis. In other 8 patients without restenosis, SPECT images did not demonstrate myocardial ischemia and coronary arteriographic findings could not verify side branch stenosis or intimal dissection which might cause myocardial ischemia. The etiology of ST segment depression after successful PTCA in one vessel disease is not produced by exercise induced myocardial ischemia but still unknown mechanisms may be present.

Clinical experience of percutaneous coronary angioscopy in cases with coronary artery disease.

Direct visualization of the coronary arteries was performed by using a new ultrathin angioscopic catheter system in experimental animals and 4 patients with coronary artery disease during percutaneous transluminal coronary angioplasty (PTCA). In this catheter system, inspection of the coronary arteries was achieved during washout of blood by bolus infusion of 8-10 ml of saline into the coronary artery through the guide catheter. In the preliminary experience with this coronary angioscopic system, there were some limitations. In 2 patients, removal of coronary blood by manual injection of saline was not adequate, and diagnostic TV images could not be obtained. In 2 patients with tortuous coronary arteries, the catheter could not pass to the atheromatous plaques owing to lack of flexibility of the fiberoptic catheter. Furthermore, angina pectoris occurred in 2 patients during angioscopy, owing probably to interference with coronary blood flow by the guide catheter and/or fiberoptic catheter itself. For future clinical application of coronary angioscopy, further improvements in the instrument are necessary.

A case of idiopathic hypothalamic hypothyroidism.

The availability of thyrotropin hormone (TRH) has made it possible to determine whether tropic hormone deficiency is caused by pituitary or hypothalamic dysfunction. A case of hypothalamic hypothyroidism was described ina a 17 year old woman. This patient was admitted for the evaluation of hypothyroidism and secondary amenorrhea. Her T3 and T4 were decreased, with an undetectable level of base line thyrotropin. the TRH test revealed normal but delayed response of TSH. Her base line prolactin and its response to TRH were normal. Adenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), and urinary 17-hydroxysteroids were also normal. ACTH response to metyrapone was normal. Evaluation of the pituitary-gonadal axis revealed a normal increase in both lutenizing hormone (LH) and follicle stimulating hormone (FSH) following the intravenous administration of lutenizing hormone releasing hormone (LHRH). These results suggest that she had hypothalamic hypothyroidism as an isolated disturbance in the hypothalamic-pituitary axis. A deficiency of TRH is probably caused by a disorder of hypothalamic function of unknown etiology since the extensive studies did not reveal any secondary causes. It is recommended that patients with amenorrhea and hypothyroidism be evaluated for possible hypothalamic hypothyroidism.