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S M Chan

Publications and source records attributed to S M Chan.

45 records · Page 3Linked to original sources

Effect of low-molecular-weight heparin on recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism.

We employed a canine model of pulmonary embolism induced by radioactive blood clots to determine if low-molecular-weight heparin augments recombinant tissue plasminogen activator (rtPA)-induced thrombolysis. Following embolization, dogs were randomized: group 1 dogs received heparin; group 2 dogs received low-molecular-weight heparin; group 3 dogs received 1.5 mg/kg of rtPA over 45 minutes; group 4 dogs received rtPA 3 mg/kg over 45 minutes; and group 5 dogs received 1.5 mg/kg of rtPA plus low-molecular-weight heparin. Over three hours, little thrombolysis occurred in groups 1 and 2. In contrast, significant thrombolysis occurred in groups 3 to 5, 46 percent, 49 percent, and 46 percent, respectively (all p less than 0.01 compared with groups 1 and 2). We conclude that there is an upper limit to the dose-thrombolytic rate relationship with rtPA, and that low-molecular-weight heparin does not augment rtPA-induced thrombolysis.

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Effects of hydralazine and increased cardiac output on recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism.

We employed a canine model of pulmonary embolism, induced by injection of autologous radiolabelled blood clots, to investigate effects of hydralazine and an increase in cardiac output per se on recombinant tissue plasminogen activator-induced thrombolysis. Emboli increased pulmonary artery pressure (PAP) and decreased CO from 2.7 to 1.8 L/min-1. Following embolization, dogs were randomly divided into three groups. Group 1 received .5 mg/kg of rtPA over 30 minutes. Group 2 received the same dose of rtPA and were pretreated with hydralazine to increase CO approximately 50 percent. In the group 3 dogs, CO was increased by opening a systemic A-V fistula. Following embolization, CO remained low in group 1, the mean 2 h time-averaged CO was 1.9 L/min-1. The CO was 2.9 and 3.1 L/min-1 in groups 2 and 3, respectively. Corresponding to the increased flow in groups 2 and 3, rate and extent of pulmonary thrombolysis significantly increased. These results indicate that an increase in CO augments rtPA-induced pulmonary thrombolysis.

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Thrombolytic therapy in canine pulmonary embolism. Comparative effects of urokinase and recombinant tissue plasminogen activator.

We compared thrombolytic and pulmonary hemodynamic effects of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) in canine micropulmonary thromboembolism. Dogs were embolized with radioactive autologous blood clot to increase mean pulmonary artery pressure (from 13 to 34 mm Hg, p less than 0.005) and decrease cardiac output (2.5 to 1.6 L min, p less than 0.005). Four groups of six dogs were treated. We employed two doses of UK, 30,000 U/kg (UK30) and 60,000 U/kg (UK60), and two doses of rtPA, 1 mg/kg (rtPA1) and 2 mg/kg (rtPA2). Drugs were infused over 15 min. Rate and extent of pulmonary thrombolysis were assessed by continuously counting over both lung fields with a gamma camera. Compared with treatment with UK, both rtPA regimes significantly increased thrombolysis. Mean total pulmonary thrombolysis was 14 and 23% with UK30 and UK60, respectively, and 35 and 43% with rtPA1 and rtPA2. Corresponding to the increased thrombolysis, pulmonary hemodynamics improved most with rtPA. From 90 min to 3 h, pulmonary artery pressure was significantly lower with both rtPA regimes than with either UK regime. These results indicate, at least in the model employed, that compared with treatment with UK, pulmonary thrombolysis and corresponding hemodynamic improvement are greatest with rtPA.

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Biochemical predictors of short term mortality in elderly residents of chronic care institutions.

A survey of 208 elderly subjects living in four long term care institutions was undertaken over three months to identify nutritional and other variables that could be used to predict mortality during the subsequent three months. There were 58 men (mean age (SD) 75.6 (9.6) years) and 150 women (79.5 (8.4) years). Twenty nine subjects died (12 men and 17 women) within three months of completing the study. Twenty eight out of 57 variables differed significantly between those who died and those who survived. Subjects who died had lower systolic blood pressure, poorer intake of protein calories, lower concentrations of haemoglobin, plasma retinol, zinc, total cholesterol, and higher albumin adjusted plasma calcium concentrations. Stepwise regression analysis identified five variables that predicted mortality: plasma fructosamine; transferrin; glycosylated haemoglobin; prealbumin; and haemoglobin. The sensitivity, specificity, and predictive values of the discriminant function score using 0 as the demarcation between survivors and non-survivors were 75%, 97%, and 95%, respectively. This score could therefore be used to identify those most in need of nutritional support.

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Radiolabeled porphyrin vs gallium-67 citrate for the detection of human melanoma in athymic mice.

We performed the biodistribution and imaging studies of 111In and 67Ga labeled tetra(4-N-methylpyridyl)porphine, (T4NMPYP), and compared it to that of 67Ga-citrate in athymic mice bearing a human melanoma xenograft. The biodistribution results of both 111In and 67Ga labeled T4NMPYP (3, 6, 24 and 48 h) were similar but differed from that of 67Ga-citrate (48 h). The optimum tumor uptake of both radiolabeled porphyrins was at 6 h post-injection and was lower than the tumor uptake of 67Ga-citrate at 48 h post-injection. Kidney was the only organ showing higher uptake of radiolabeled porphyrin compared to that of 67Ga-citrate. The imaging studies performed with 111In-T4NMPYP and 67Ga-citrate correspond to the biodistribution results. Osteomyelitis present in one mouse showed good localization of 111In-T4NMPYP.

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Inhibition of gallium-67 uptake in melanoma by an anti-human transferrin receptor monoclonal antibody.

The effect of an anti-human transferrin receptor (anti-TFR) monoclonal antibody (MoAb), designated B3/25, and an anti-melanoma antibody, designated 96.5, on the uptake of gallium-67 (67Ga) by tumor was studied. Three groups of six athymic mice bearing a human melanoma were injected via tail vein with (a) 0.55 mg human serum albumin (HSA) (control group), (b) 0.5 mg MoAb B3/25 + 0.55 mg HSA, and (c) 0.5 mg MoAb 96.5 + 0.55 mg HSA, respectively. Twenty-four hours later, each mouse was given an intravenous dose of 5 microCi [67Ga] citrate. Biodistribution of activity (percent injected dose per gram) determined 48 hr after injection of 67Ga showed a 75% decrease in tumor uptake in the group of mice that received B3/25 (anti-TFR MoAb) compared with the control group. In contrast, MoAb 96.5 did not show any effect on melanoma uptake of 67Ga. Histologic findings suggest that the decreased uptake was not due to cellular damage resulting from binding of B3/25 to TFR. The results of this study strongly suggest the involvement of TFR in the in vivo tumor uptake of 67Ga.

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Comparison of gallium-67 versus indium-111 monoclonal antibody (96.5, ZME-018) in detection of human melanoma in athymic mice.

We compared the biodistribution of two radiolabeled, whole, tumor selective monoclonal antibodies [( 111In]96.5, [111In]ZME-018) to 67Ga in nude mice bearing a human melanoma known to express p97 antigen. Localization of gallium was determined 48 hr following i.v. injection. Localization of the radiolabeled antibodies was determined at 3 days and 7 days following i.v. injection. All agents showed more or less similar absolute tumor uptake which varied between 22% and 36% of the injected dose per gram of tumor. Only the tumor uptake of [111In]96.5 antibody at 7 days was significantly lower than the 67Ga uptake at 48 hr. However, uptake in normal tissues was generally higher for both antibodies at 3 and 7 days than for 67Ga uptake at 48 hr. Therefore, the tumor-to-blood ratio for 67Ga was tenfold higher than that for either antibody, the tumor-to-muscle ratio was twofold higher. Bone was the only organ in which the tumor-to-organ ratio was consistently higher with radiolabeled antibody than with 67Ga. The tumor-to-liver and tumor-to-intestine ratios were comparable. Localization of the two tumor selective antibodies was greater than a nonspecific "control antibody" [( 111In]CEA) and change in specific activity from 0.17 mCi/mg to 3.3 mCi/mg did not influence localization. From these animal data it may be anticipated that tumor imaging with [111In]96.5 or [111In]ZME-018 will not be superior to imaging with 67Ga for detection of melanoma.

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