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Role of thrombolysis in peripheral arterial occlusion.

In an initial study, 85 patients with 93 thromboembolic occlusions of peripheral arteries or grafts were treated with urokinase by direct intra-arterial infusion. Urokinase was infused directly into the proximal portion of the clot at 4,000 IU/minute for two hours. Arteriography was then repeated. If a channel had been lysed in the proximal part of the clot, but the distal part remained occluded, the catheter was gently advanced into the still occluded portion of the clot and the infusion was resumed at 4,000 IU/minute until antegrade blood flow was reestablished. Then the catheter was repositioned to be proximal to all of the remaining clot. The urokinase dosage was reduced to 1,000 IU/minute and the infusion continued with reexaminations at eight-hour intervals. The infusion was continued until complete clot lysis was accomplished. A search for a flow-limiting lesion on which to perform a percutaneous transluminal angioplasty was then performed. The lack of at least a 10 percent reduction in clot length after a 500,000-IU cumulative infusion dose of urokinase was an indication for termination of the regimen. Seventy-five percent of the 93 infusions resulted in complete clot lysis, even though in nine patients (10 percent) the infusion could not be completed. Eighty-one percent of the 84 completed infusions resulted in complete clot lysis, and the incidence of clinical improvement was 89 percent. The average duration of infusion was 18 hours. Major bleeding (requiring transfusion) occurred in only 4 percent of the patients. This regimen has now been applied to 150 occlusions, and the results are approximately the same. Review of our experience demonstrated that the ability to easily advance an angiographic guide wire through an occlusion has been the best predictor that a given clot would lyse irrespective of the clot's location or the duration of symptoms. Easy guide wire traversal appears to rule out the presence of either advanced changes of clot organization throughout the occlusion or a rare completely obstructing atherosclerotic lesion. A review of the published experience of 155 direct intra-thrombus infusions of 5,000 IU/hour of streptokinase demonstrated only a 45 percent incidence of complete clot lysis. Also, infusion times were quite prolonged (41 hours), and major bleeding complications were surprisingly common (13 percent). The results with urokinase thus indicate that it is preferable to streptokinase since it produces fewer complications and accomplishes more rapid recanalization and a higher incidence of total clot lysis.

Catheterization↗

Cell geometry and contractile abnormalities of myocytes from failing human left ventricle.

OBJECTIVES: Systolic and diastolic dysfunction of the failing human heart may be due to changes in myocyte function, or to extracellular influences such as necrosis, fibrosis or repositioning of viable cells. In order to determine the contribution of cellular factors we have characterised the contraction amplitudes, and contraction and relaxation velocities of single myocytes isolated from failing human left ventricle. METHODS: Myocytes were enzymatically isolated from the left ventricles of 42 subjects, superfused at 32 degrees C and paced at 0.2 Hz. Using a video/edge tracking system we obtained contraction amplitude and contraction and relaxation velocities as well as times to peak contraction (TTP) and to 50% and 90% relaxation (R50 and R90). Concentration-response curves to Ca2+ were constructed for each cell. RESULTS: There was little difference in contraction amplitude at any Ca2+ concentration between cells from failing and non-failing hearts at this low frequency. At maximally activating Ca2+ concentrations (6-20 mM) there was a 30% slowing of relaxation velocity in myocytes from patients with both mild-moderate (P < 0.001) and severe (P < 0.001) congestive heart failure. Contraction and relaxation times were increased in myocytes from failing hearts [TTP: 0.46 +/- 0.02 s (n = 34 patients) vs. 0.35 +/- 0.02 s (n = 6), P < 0.01 and R50: 0.25 +/- 0.02 s (n = 34) vs. 0.16 +/- 0.02 s (n = 6), P < 0.001]. Impaired relaxation was seen with most etiologies, including ischemic and dilated cardiomyopathies and mitral valve disease. Myocytes from failing hypertrophied ventricles were more severely affected than those from failing non-hypertrophied hearts for both contraction and relaxation velocities. Cells from failing hypertrophied ventricles had a significantly larger area than from non-failing or failing non-hypertrophied ventricles, although cell length and sarcomere length were similar between groups. Larger myocytes did not show a more pronounced change in relaxation velocity than normally sized cells from the same hypertrophied ventricle. CONCLUSIONS: Significant impairment of relaxation can be observed in ventricular myocytes from failing human heart under conditions where contraction amplitude appears normal. The defect is not confined to one etiology of disease, but is exacerbated during hypertrophy. An increase in cell size, although observed in myocytes from hypertrophied ventricle, does not itself account for changes in relaxation. Cellular changes contribute to diastolic dysfunction in the failing human heart.

Adolescent↗

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗