Indications for pacing.
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Biomedical subjects
Publications and source records attributed to A Ahsan.
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Some 10 low molecular weight heparin products are currently available for commercial use. Enoxaparin and fraxiparin appear to be the most developed low molecular weight heparins. Many well-designed clinical trials have been carried out for different clinical indications with both of these products. As shown in both experimental and clinical settings, the prophylactic antithrombotic efficacy of enoxaparin is distinct from other low molecular weight heparins. Enoxaparin has provided consistently impressive clinical results. Moreover, at comparable dosages, other products have exhibited safety/efficacy profiles different from that of enoxaparin. The clinical performance of each low molecular weight heparin is characteristic of only that particular agent. Besides the commercially available low molecular weight heparin preparations, some 14 other agents are under development at this time. Although each product has similar basic characteristics, their biological actions should be studied carefully. Apart from differences in the physicochemical properties, the pharmacologic actions of these agents may differ significantly. Only results from valid clinical trials will show similarities or differences between the low molecular weight heparins. Other manufacturers should follow the lead of enoxaparin and conduct their own clinical trials on each of their products.
A power source modified to increase voltage delivery and minimise arcing (for a given energy) was used for transvenous ablation of atrioventricular conduction to control refractory supraventricular arrhythmias in 14 patients. Twelve had atrial fibrillation or flutter, one had atrioventricular nodal reentry tachycardia, and the other had permanent junctional reentry tachycardia. Despite treatment with 5-7 (median 6) antiarrhythmic drugs symptoms had persisted in all the patients. Cathodal discharges of 0.5-39.5 J were delivered to the distal electrode (in one case in parallel with the middle electrode). In all patients shocks produced complete atrioventricular block; this was permanent in eleven (79%). Four patients required a second procedure. In one patient, only a transient atrioventricular block could be produced and catheter ablation with a conventional power source also failed. In the other two atrioventricular conduction was modified such that previously ineffective treatment produced satisfactory control of heart rate. The cumulative energy delivered to those in whom permanent complete heart block resulted ranged from 3.6 to 97.8 (mean 38.3) J with a mean of three shocks (range 1-7) delivered per patient. During follow up of 1-28 (mean 14) months 11 patients remained in complete heart block and free of arrhythmia.
Peptide aldehyde transition state analogue inhibitors of serine and cysteine proteases have been used to selectively inhibit proteases for which prior evidence supports a role in tumor cell metastasis. These enzymes include cathepsin B, urokinase plasminogen activator (PA), and thrombin. The inhibition constants of the peptidyl aldehyde inhibitors show that they are highly selective for a particular targeted serine or cysteine protease. The inhibitors are introduced by i.p. injection or by miniosmotic pumps into syngeneic C57BL/6 mice also given injections of B16-F10 melanoma cells, and the number of metastatic foci in the lung was determined. While the injection protocol gave an initially high but changing in vivo concentration of inhibitor over time, the minipump implant gave a constant steady state concentration of inhibitor over 5-7 days. Minipump infusion of leupeptin (acetylleucylleucylargininal), a strong inhibitor of cathepsin B at a steady state plasma concentration 1000-fold greater than its Ki(cathepsin B), gave no significant decrease in lung colonization by the B16 tumor cells. Ep475, a stoichiometric irreversible peptide inhibitor of cathepsin B-like proteases, also did not significantly inhibit metastatic foci formation. Introduction of selective inhibitors of urokinase PA, tert-butyloxycarbonylglutamylglycyl-argininal and H-glutamylglycylargininal at concentrations near its Ki, produced no significant decrease in mouse lung colonization. The selective thrombin inhibitor D-phenylalanylprolylargininal infused to a steady state concentration 100-fold greater than its Ki dramatically increased B16 melanoma colonization of mouse lung. The results indicate that neither secreted cathepsin B-like nor urokinase PA have roles in B16 colonization of mouse lung, while thrombin may have a role in preventing metastasis. These experiments do not eliminate roles for a cathepsin B-like enzyme or urokinase PA in the initial steps of the metastatic process.
The ability of B16-F10 mouse melanoma cells to cross an amnion basement membrane was determined in the presence of strong inhibitors of both serine and cysteine proteases. The concentrations of inhibitors were at orders of magnitude higher than their Ki values to serine and cysteine proteases implicated in metastasis, thus ensuring a complete inhibition for tumor secreted proteases such as cathepsin B-like proteases, plasminogen activators, and plasmin. Under these conditions of high serine and cysteine protease inhibitor concentrations, no significant decrease in B16-F10 melanoma cell invasion through the amnion was observed. Separate experiments showed that the inhibitors were neither toxic to the cells nor degraded. The results show that neither tumor cell secreted cathepsin B-like proteases nor plasminogen activator have a controlling role in basement membrane crossing in this metastatic model. A possible role for tumor cell membrane proteases in basement membrane invasion, in which the substrates of the protease bind to receptor sites near a membrane associated proteolytic activity, is not eliminated.
In this article we review the early history of the coronary artery stent in clinical cardiology, cite a clinical case and assess the potential role of stents in revascularization in the future.