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Biomedical subjects

T Tomaru

Publications and source records attributed to T Tomaru.

At least 37 records · Page 2Linked to original sources
PubMed1996

Induction of thrombolysis and prevention of thrombus formation by local drug delivery with a double-occlusion balloon catheter.

The efficacy of the local delivery of an antithrombotic drug in preventing thrombosis and enabling thrombolysis was investigated in 29 dogs. An antithrombotic drug (heparin, 25 U/kg), or an antithrombin (argatroban, 0.05 mg/kg) was infused into injured canine iliac arteries, using a double-occlusion balloon catheter, and the preventive effect of the drug was evaluated. Local delivery of low-dose tissue-type plasminogen activator (t-PA; Tisokinase, 50,000 U; Kowa, Nagoya and Asahi Chemical Industries, Fuji, Japan) into thrombosed canine iliac arteries, using the same catheter, or intravenous infusion of low-dose or high-dose t-PA (30,000 U/kg) was also performed. Angiographically, stenotic thrombosis was 2% by local delivery of argatroban and 7% by local delivery of heparin (P < 0.01 vs each control; 47% and 51% respectively). Thrombotic stenosis, as observed by angiography, decreased from 91% to 9% after local delivery of t-PA, and from 94% to 52% in controls. Local delivery of t-PA effectively reduced the thrombus size (P < 0.01 vs control). After systemic intravenous delivery of low-dose t-PA, no reduction of residual thrombotic stenosis, was observed. Reduction of residual thrombotic stenosis after intravenous delivery of high-dose t-PA, was similar to that achieved by local delivery of the drug. Angioscopy demonstrated a similar trend. High-dose drug delivery reduced systemic coagulability. Local delivery of an antithrombotic drug, using a double-occlusion balloon catheter, effectively prevented thrombus formation, and local delivery of t-PA induced thrombolysis without exerting a significant influence on coagulability.

Angioscopy↗
PubMed1996

Local treatment with an antithrombotic drug reduces thrombus size in coronary and peripheral thrombosed arteries.

Since the treatment of thrombotic disease by antithrombotic drugs may be associated with bleeding complications, a local delivery technique for administration of the drug may be useful. The efficacy of low-dose local delivery of an antithrombotic drug on thrombosis was investigated in 73 dogs. The antithrombotic drug (heparin, 25 U/kg, antithrombin: argatroban, 0.05 mg/kg, or defibrinogenating agent: batroxobin, 0.05 U/kg) was infused locally to a 1-h-old thrombus, and no drug was given in controls. The effect of the local delivery on the thrombus was evaluated. Low- and high-dose systemic drug delivery was also evaluated. The mean reduction in thrombotic coronary stenosis observed by angiography was 30.3% with argatroban, 22% with heparin, and 20.8% with batroxobin (P < 0.005 vs controls). Systemic delivery of low-dose heparin or argatroban did not induce any change in thrombus size. With high-dose systemic drug delivery (heparin 250 U/kg, argatroban 0.5 mg/kg), the mean reduction of thrombotic stenosis was 15.2% with heparin and 32.8% with argatroban (P < 0.005 vs controls). In the iliac arterial thrombosis, after local delivery of the drugs, the mean reduction of thrombotic stenosis observed by angiography was 24.4% in the argatroban group, and 19.2% in the heparin group (P < 0.05 vs controls, respectively). With high-dose systemic heparin delivery, the mean reduction of the thrombotic stenosis was 13.2% (P < 0.01 vs control). Angioscopy also demonstrated a similar trend. The high-dose drug delivery reduced systemic coagulability. Thus, local delivery of an antithrombotic agent can reduce the thrombus size in the coronary and iliac arteries without having any significant influence on coagulability.

Angioscopy↗
PubMed1996

Local delivery of antithrombotic drug prevents restenosis after balloon angioplasty in atherosclerotic rabbit artery.

We investigated the ability of various antithrombotic drugs, delivered locally, to prevent restenosis after angioplasty in hypercholesterolemic rabbits. After dilating atherosclerotic iliac stenoses by balloon angioplasty, a low dose of heparin or a new antithrombotic drug, such as low molecular weight heparin (fragmin), argatroban, or batroxobin, was delivered locally using the balloon double-occlusion technique. In 1 group, high-dose heparin was administered intravenously. Animals that received no drugs served as a control group. After angioplasty, the stenotic segment was dilated and the mean percentage luminal stenosis fell from 89% to 9% in the group that received locally delivered heparin, from 88% to 7% in the group that received locally delivered argatroban, from 87% to 11% in the group that received locally delivered fragmin, from 88% to 15% in the group that received locally delivered batroxobin, from 82% to 18% in the group that received i.v. heparin (p < 0.0001 compared with before angioplasty in each case), and from 84% to 17% in the control group (p < 0.005 compared with before angioplasty). Twenty-eight days after angioplasty, the percentage luminal stenosis remained at 14% in the group that received locally delivered argatroban, 15% in the group that received locally delivered fragmin, and 28% in the group that received locally delivered batroxobin, whereas it increased to 45% in the group that received i.v. heparin, 30% in the group that received locally delivered heparin and 72% in the control group (p < 0.05 compared with after angioplasty in each case). Thus, local delivery low doses of new antithrombotic drugs prevents restenosis after angioplasty without affecting systemic coagulability; heparin, whether administered locally or intravenously, was less effective than the new drugs in preventing restenosis.

Angiography↗
PubMed1996

Significance of serum free prostate specific antigen in the screening of prostate cancer.

PURPOSE: The significance of serum free prostate specific antigen (PSA) in the screening of prostate cancer was examined. MATERIALS AND METHODS: A prospective clinical trial was conducted on 701 male volunteers 50 years old or older. Serum free PSA was determined and biopsies were performed if PSA was greater than 4 ng./ml. or if digital rectal examination was suspicious for cancer. RESULTS: Of the men 187 (27%) had a PSA of greater than 4 ng./ml. (11%) and/or a suspicious digital rectal examination (19%). Of 116 biopsies performed in the 701 men cancer was detected in 13 (1.9%). PSA detected more tumors (12 of 13, 92%) than digital rectal examination (9, 69%). Receiver operating characteristic analysis showed that the optimal free PSA-to-PSA ratio (free PSA ratio) was 12%. The positive predictive value for cancer according to PSA with free PSA ratio (50%, 10 cancers in 20 biopsies) was significantly greater (p = 0.0473) than that according to PSA alone (24%, 12 cancers in 50 biopsies), which indicated that 30 of 50 biopsies were avoided with only 2 cancers missed when PSA and free PSA were used for biopsy indication. CONCLUSIONS: Free PSA determination might eliminate unnecessary biopsies in men with a PSA of more than 4 ng./ml. with minimal missed cancers.

Aged↗
PubMed1995

Local treatment with antithrombotic drugs can prevent thrombus formation: an angioscopic and angiographic study.

OBJECTIVES: This study was designed to evaluate the efficacy of local versus systemic treatment of thrombosis with various antithrombotic drugs. BACKGROUND: Local use of low dose antithrombotic drugs has been proposed as being effective and safe. METHODS: Heparin (30 U/kg), an antithrombin agent (argatroban, 0.05 mg/kg body weight) or a defibrinogenating drug (batroxobin, 0.05 U/kg) was locally infused into one side of the canine iliac artery after injury by balloon inflation. The other side was injured as a control. The efficacy of systemic delivery of high dose (heparin [300 U/kg] and argatroban [0.5 mg/kg]) and low dose drugs was also assessed. RESULTS: Sixty minutes after local treatment in 22 dogs, no thrombotic stenosis was observed by angiography in locally treated arteries (p < 0.005 vs. mean thrombotic stenosis of 27% in control segments for heparin, 25.3% in control segments for argatroban and 32% in control segments for batroxobin). Angioscopy demonstrated the same trend. In locally treated arteries, thrombus weight was significantly lower in the treated than control side. In the systemic high dose group (n = 10), angiographic thrombotic stenosis was < 5% after high dose drug delivery (p < 0.05 vs. control segments, 37.4% for heparin, 43% for argatroban). In another 10 dogs, low dose systemic delivery was not effective in inhibiting thrombus formation. Activated partial thromboplastin time and fibrinogen levels did not change with local treatment. CONCLUSIONS: Compared with systemic administration of antithrombotic drugs, local treatment is a safer and more effective method of preventing thrombosis.

Angiography↗
PubMed1995

Rheological significance of tandem lesions of the coronary artery.

It is not known whether the individual lesions that constitute tandem lesions of the coronary artery are developmentally or rheologically related. Luminal changes and their rheological significance were examined by percutaneous angioscopy in 44 tandem lesions of 21 patients with ischemic heart disease. Angioscopically, individual narrowing of angiographically documented tandem lesions appeared only as a tangentially expressed prominent portion of an atherosclerotic spiral fold. The directions of the fold were counterclockwise in the proximal to middle segments and clockwise in the distal segment of the right coronary artery, clockwise in the proximal to middle segments and counterclockwise in the distal segment of the left anterior descending artery, and counterclockwise in the proximal to middle segments of the left circumflex artery. The bloodstream always ran along the spiral folds in the tandem lesions. The results suggest that angiographically documented tandem coronary lesions are merely a tangential expression of atherosclerotic spiral folds and that they may act to prevent blood turbulence by generating a spiral laminal flow.

Adult↗
PubMed1995

Angiogenic therapy of acute myocardial infarction by intrapericardial injection of basic fibroblast growth factor and heparin sulfate: an experimental study.

To examine whether angiogenesis and myocardial salvage occur, 30 micrograms basic fibroblast growth factor (bFGF) and 3 mg heparin sulfate (HS) were injected through the right atrium into the pericardial cavity by a thin needle-tipped catheter in a canine model of acute myocardial infarction. One month later infarcted weight/left ventricle weight was 24% +/- 5.2%, 25% +/- 4.0%, 18% +/- 2.4%, and 10% +/- 1.8% (mean + SE) in saline solution, HS, bFGF alone, and bFGF plus HS groups, respectively. Vascular number in the infarcted area of the outer layer was 13 +/- 3.3, 20 +/- 2.2, 47 +/- 8.3, and 136 +/- 26.3/200 x 200 microns2 in saline solution, HS, bFGF alone, and bFGF plus HS groups, respectively. Thus the vascular number was the largest in the bFGF plus HS group. The vascular number was larger in the subepicardial than in the subendocardial infarcted areas. Vessels directed from the epicardium toward the subepicardial infarcted area were also observed. The transcatheter intrapericardial injection of bFGF plus HS caused angiogenesis and myocardial salvage. This method might bring about a selective therapeutic and preventive modality of myocardial infarction irrespective of coronary anatomy and contraindications for coronary interventions and surgery.

Animals↗
PubMed1995

Prediction of acute coronary syndromes by percutaneous coronary angioscopy in patients with stable angina.

To pinpoint the link between plaque characteristics and acute coronary syndromes, we performed a 12-month prospective follow-up study in 157 patients with stable angina pectoris in whom regular coronary plaques were observed by percutaneous coronary angioscopy. Acute coronary syndromes occurred more frequently in patients with yellow plaque than in those with white plaques (11 of 39 vs 4 of 118; p = 0.00021). Moreover, the syndromes occurred more frequently in patients with glistening yellow plaques than in those with nonglistening yellow plaques (9 of 13 vs 2 of 26; p = 0.00026). Thrombus arising from the ruptured identical plaques was confirmed by angioscopy as the culprit lesion of the syndromes. The results indicate that acute coronary syndromes occur frequently and in a short time in patients with glistening yellow plaques and that angioscopy but not angiography is feasible for prediction of the syndromes.

Acute Disease↗
PubMed1995

Local delivery of heparin inhibits neointimal hyperplasia in injured rabbit artery.

The efficacy of local delivery of an antithrombotic drug on neointimal hyperplasia was investigated in 17 rabbits. One rabbit iliac artery was injured by a balloon catheter as a control injured artery. The other iliac artery was also injured and treated by local delivery of 25 U/kg of heparin. One hour after the balloon injury, angioscopy demonstrated an occlusive or mural thrombus in all the controls, but few in the locally-treated arteries. Four weeks after balloon injury, the percent stenosis was 34 +/- 31% in the heparin treated group (n = 7, p < 0.005) vs control side 73 +/- 17%). Accumulation of FITC-labeled heparin at the injured site was confirmed by microscopy. The activated partial thromboplastin time and fibrinogen level did not change significantly. PDGF-B chain was prominent at the neointimal layer in all the controls, whereas it was less in the locally treated arteries. Thus local delivery of heparin can inhibit neointimal hyperplasia after balloon injury by reducing thrombus-related growth stimulation.

Angioscopy↗
PubMed1994

Modification of atrioventricular conduction using a combined laser-electrode catheter.

Ablation of the AV junction is an accepted technique for the management of selected supraventricular tachyarrhythmias. Radiofrequency ablation appears to be safe and effective for AV junction ablation in most patients, but the need for firm tissue contact may make it less effective for ventricular tachycardia and certain ectopic/atrial tachycardias. Laser energy can also be delivered through a catheter, and thus it may be an attractive alternative energy source for ablation. A new laser-electrode catheter was developed for modification of conduction through the AV node as a model for ablation of an arrhythmia substrate. A window for delivery of continuous-wave Nd:YAG laser energy was placed between the two electrodes of a bipolar electrode catheter. In vitro studies using a matrix of power versus time were performed to determine the energy that would create lesions of the appropriate size in vivo. Using this information, advanced AV block was successfully created in 16 of 17 dogs (94%) with the laser-electrode catheter. Advanced AV block was successfully created in all four dogs in the chronic study, and it persisted for 1-24 weeks of follow-up until sacrifice of the animals. Histologic examination demonstrated discrete thermal damage at the AV junction with no instances of septal perforation in the acute studies or progressive necrosis in chronically maintained dogs. Advanced AV block may be produced consistently and safely in dogs using a combined laser-electrode catheter.

Aluminum Silicates↗
PubMed1994

Antithrombin and thrombolytic effects of a new antithrombin agent: angioscopic and angiographic comparison with heparin or batroxobin.

The antithrombotic effect of three different types of antithrombotic agents (antithrombin:argatroban, heparin, defibrinogenating agent:batroxobin) were evaluated in canine coronary and iliac arteries. An occlusive thrombus was produced by balloon injury. One of the three agents was infused intravenously at 1 hour after thrombus formation (heparin 250 U/kg, argatroban 0.5 mg/kg, batroxobin 0.5 U/kg) and the effect of thrombus size reduction was evaluated. On the contralateral side of the iliac artery, the preventive effect of these agents on thrombus formation was evaluated after balloon injury. In the iliac artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 69% to 32% in the argatroban group, and from 64% to 51% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography demonstrated the same trend. The percent area stenosis with thrombus at 60 minutes following balloon injury was 0.75% in the argatroban group, 18.9% in the heparin group (P < 0.05 vs argatroban), and 12.9% in the batroxobin group. Thrombus size at the treated site was smaller than that at the control site in all three groups (P < 0.05 vs control). In the coronary artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 84% to 53% in the argatroban group, and from 86% to 68% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography also demonstrated the same trend. The activated partial thromboplastin time (APTT) was prolonged to 189% of the control value with argatroban and to 1253% of the value with heparin (P < 0.0001). Fibrinogen was markedly reduced with batroxobin. These results showed that both the antithrombin agent and the defibrinogenating agent have a preventive effect on thrombus formation and the effect on thrombus size reduction, without marked prolongation of the APTT.

Angiography↗
PubMed1994

The effects of dobutamine, propranolol and nitroglycerin on an experimental canine model of congestive heart failure.

A new experimental model of acute congestive heart failure was established in open-chest dogs, and it was employed to examine the effects of dobutamine, propranolol and nitroglycerin. The model was induced by intracoronary administration of saponin, volume loading and intravenous infusion of methoxamine. Left ventricular end-diastolic pressure (LVEDP) increased from 7.9 +/- 0.6 to 24.2 +/- 1.4 mmHg, and aortic blood flow (AoF) decreased from 0.89 +/- 0.06 to 0.53 +/- 0.04 l/min. Systemic vascular resistance (SVR) increased from 9618 +/- 585 to 16492 +/- 1213 dynes.sec/cm5 and right atrial pressure (RAP) increased from 2.5 +/- 0.2 to 4.2 +/- 0.4 mmHg. Furthermore, Vmax decreased from 71.6 +/- 5.1 to 45.8 +/- 2.9 1/sec, and the time constant of left ventricular pressure decay (T) increased from 40.0 +/- 2.6 to 90.2 +/- 7.9 msec. These hemodynamic changes were stable for up to 80 min. Dobutamine improved cardiac function by increasing Vmax and by decreasing T. Consequently, dobutamine increased AoF and decreased LVEDP, while there was no change in SVR. Nitroglycerin reduced LVEDP, SVR and T; increased AoF; and did not change Vmax. Propranolol produced no improvement in the hemodynamics or cardiac function. These results indicate that the present congestive heart failure model is characterized by global left ventricular dysfunction with lowered cardiac output and increased peripheral vascular tone, and it is beneficial for evaluating the pharmacological properties of drugs for acute congestive heart failure.

Analysis of Variance↗
PubMed1993

Reduction of vasoreactivity and thrombogenicity with laser-thermal angioplasty: comparison with balloon angioplasty.

UNLABELLED: The vasoreactivity and thrombogenicity of laser-thermal angioplasty were examined and compared with those of balloon angioplasty in an atherosclerotic rabbit iliac artery. Eight rabbits underwent laser-thermal angioplasty with a 1.7-mm hot-tip probe activated at 7 W with a probe temperature of 126 +/- 19 degrees C in one iliac artery. The other iliac artery was treated with balloon angioplasty using a 2.0-mm balloon. Angiographic luminal diameter increased from 0.19 +/- 0.15 to 1.54 +/- 0.35 mm by laser and from 0.29 +/- 0.22 to 1.84 +/- 0.20 mm by balloon (P less than 0.0001, respectively). However, it decreased to 1.34 +/- 0.42 for laser and 0.45 +/- 0.39 for balloon 60 minutes later (P less than 0.0001 vs immediately post). Both iliac arteries were visualized using angioscopy, which revealed thrombotic obstruction of 91% stenosis in the ballooned artery and 8% stenosis in the lased artery. Vasoreactivity of treated vessels was also investigated. Segments 3-mm long were obtained from either treated artery or control artery and examined for noradrenaline (10 -7 M) contraction. The segments were then mounted isometrically with 1 g tension in Krebs-bicarbonate buffer. Developed tension was 0.13 +/- 0.21 g for laser thermal and 2.33 +/- 0.4 g for its control (P less than 0.0001), and 0.15 +/- 0.16 g for balloon dilatation and 2.12 +/- 0.43 g for its control (P less than 0.0001). Neither acetylcholine at 10 -6 M or papaverine at 10 -4 M induced relaxation of treated segments. Histology showed slight thermal injury at thermally-treated sites without thrombus, and intimal and medial dissection with thrombus formation at balloon dilated site. IN CONCLUSION: (1) neither a laser-thermal recanalized or a balloon dilated obstructed artery is vasoreactive to constrictive or relaxant agents; and (2) laser-thermal angioplasty results in less thrombogenicity than balloon angioplasty under moderate probe temperature.

Angioplasty, Balloon, Coronary↗
PubMed1993

Loss of vasoreactivity by laser thermal energy or argon laser irradiation.

Vasoreactivity of laser-treated vessels was investigated in two different experimental conditions. The canine left circumflex coronary artery (LCx) was lased under perfusion with Krebs-bicarbonate buffer by means of a thermal laser (hot-tip probe, HT) at 7 W for 6 seconds and an argon laser beam through a 300 microns optical fiber at 3 W (tip power) for 1 second at 12 spots. A nontreated segment of the LCx served as a control. Two 3-mm long segments were obtained from the treated segment: one to measure the results of potassium (K) induced contraction, and another 3, 4 diaminopyridine (DAP; K channel inhibitor) induced contraction. In 11 instances, coronary angiography of the perfused artery showed less than 50% stenosis after laser treatment. The segments were then mounted isometrically with 1 g tension in Krebs-bicarbonate buffer. Contraction was induced either with 30 mM KCI or 10(-2) M DAP and expressed as developed tension (gram; g). KCI induced vasocontraction of 4.15 +/- 0.93 g in the control, 0.33 +/- 0.71 g in laser irradiated segments (P < 0.0001 vs control), and 0.02 +/- 0.06 g in thermally-treated segments (P < 0.0001 vs control). DAP induced vasocontraction of 5.21 +/- 1.32 g in the control, 0.39 +/- 0.83 g in laser irradiated segments (P < 0.0001 vs control), and 0.07 +/- 0.13 g in thermally treated segments (P < 0.001 vs control). In 4 instances, more than 50% stenosis remained and additional balloon dilatation reduced the stenosis to less than 50%. The lesions also showed reduced vasoreactivity. In vivo thermal angioplasty resulted in reduced vasoreactivity compared to control in 4 anesthetized dogs. Thus, laser and thermal angioplasty reduced vasoreactivity induced by either KCI or 3, 4 DAP. Neither acetylcholine at 10(-6) M nor papaverine at 10(-4) M was able to induce relaxation of treated segments. In conclusion, 1) the lased coronary artery loses its vasoreactivity to either a constrictive or relaxing agent, 2) although stenosis may be produced by laser energy, additional balloon dilatation can reduce residual stenosis, and 3) laser thermal or argon laser angioplasty may prevent severe coronary spasm.

4-Aminopyridine↗
PubMed1993

Reduction of thrombogenicity with argon laser angioplasty. Comparison with balloon angioplasty.

Direct argon or thermal laser angioplasty (LA) was evaluated for thrombogenicity using angioscopy, and compared with balloon angioplasty (BA). In each of 8 dogs, 4 segments (both proximal and distal iliac arteries) were treated by laser-thermal and/or balloon angioplasty. One segment was treated by balloon angioplasty and 3 other segments were treated with either thermal LA with 7 W using a "Hot-Tip" laser probe (2.0 mm), or BA and thermal LA, or a special optical probe which emits a 3 W argon laser beam. Mean percent area stenosis by thrombus was 44 +/- 23 in balloon-dilated, 23 +/- 21 in thermally-treated and balloon-dilated, 3 +/- 3 in thermally-treated, and 1 +/- 4 in directly-lased segments at 30 min. It was 62 +/- 28 in balloon dilated, 31 +/- 29 in thermally-treated and balloon-dilated, 5 +/- 6 in thermally-treated, and 1 +/- 2 in directly-lased segments at 60 min. Balloon-inflated segments had the highest percent area stenosis which was significantly higher than that of either the direct laser or thermally-treated segments (p < 0.0005). Histology showed thermal necrosis in laser-treated sites, and wall tears in BA sites. Thus, LA can provide a less thrombogenic arterial surface than BA.

Angioplasty, Balloon↗
PubMed1992

High levels of nervous system-specific proteins in cerebrospinal fluid in patients with early stage Creutzfeldt-Jakob disease.

Concentrations of several proteins that are characteristic of the nervous system were time-sequentially analyzed by radio- and enzyme-immunoassay in the cerebrospinal fluid (CSF) of patients with Creutzfeldt-Jakob disease (CJD). We found abnormally high levels of several proteins, such as neuron-specific enolase (NSE), S-100b protein, brain-type isozyme of creatine kinase (CK-BB) and alpha subunit of GTP binding protein G0 (G0 alpha) in the early stage of the disease. Generally, these protein levels were far higher in CJD patients than in normal controls and other neurological patients in the early stage before the typical clinical manifestations were evident. These levels increased to maxima when the disease activity was most prominent and returned to normal or mildly elevated levels in the terminal stage. The results imply that these protein levels can serve as biochemical markers for the presence of an active destructive process in CJD brain and provide us with a useful indicator for early diagnosis of CJD.

Brain↗