Current status of the medical expenses for the treatment of arteriosclerosis obliterans in Japan.

AIM: We aimed to determine the current status of the medical expenses for the treatment of arteriosclerosis obliterans (ASO) and evaluate the cost effectiveness of the medical practices employed in ASO treatment in Japan. METHODS: We performed a prospective observational study using 140 ASO patients. The cost of the medical practices comprised the costs of outpatient treatment, pharmacological agents, and hospitalization. To compare the average monthly costs, the patients were divided into preintervention, postintervention, or conservative-therapy groups. To compare the total costs and effectiveness of each treatment, the patients who had first visited our division during the study period were classified into surgery, endovascular-revascularization (EVR), or conservative-therapy groups. The adverse reactions of the 4 most popular agents for ASO were investigated, and bleeding events were assessed specifically. RESULTS: The average monthly costs for outpatient treatment and pharmacological agents were yen 168,002 in conservative cases, yen 149,871 in preoperation cases, and yen 128,527 in postoperation cases. The mean total costs were yen 5,407,950 in conservative cases, yen 7,375,290 in surgical cases, and yen 2,631,650 in EVR cases. The average change of the gauge in clinical status was 0.57 in conservative cases, 2.13 in surgical cases, and 2.25 in EVR cases. Warfarin induced more bleeding complications than the other agents. CONCLUSION: The costs of pharmacological agents represented much of the medical costs in any treatment groups.

Rhenium-186-mercaptoacetyltriglycine-labeled monoclonal antibody for radioimmunotherapy: in vitro assessment, in vivo kinetics and dosimetry in tumor-bearing nude mice.

Stability and immunoreactivity of 186Re-labeled monoclonal antibody were examined, and its in vivo kinetics was investigated in tumor-bearing Balb/c nu/nu female mice to assess the feasibility of using it in radioimmunotherapy (RIT). A murine IgG1, A7, against a 45 kD glycoprotein in human colon cancer was radiolabeled with 186Re by using a chelating method with a mercaptoacetyltriglycine (MAG3). 186Re-MAG3 complex was conjugated to A7 after esterification of 186Re-MAG3 with tetrafluorophenol (TFP). The efficiency of 186Re-MAG3-TFP production and the labeling efficiency of A7 were 51-59% and 57-60%, respectively. Immunoreactivity of purified 186Re-MAG3-A7 was 68.2% at infinite antigen excess. In 0.9% NaCl at 4 degrees C, the radioactivity (12.7 MBq/mg, 3.55 MBq/ml) dissociated with time from 186Re-MAG3-A7 as a small molecular weight moiety because of autoradiolysis. The addition of ascorbic acid, 5 mg/ml, as a radioprotectant or storage at -80 degrees C could effectively prevent the radiolysis of 186Re-MAG3-A7 for 7 days. Immunoreactivity of 186Re-MAG3-A7, 6.70 MBq/mg (6.66 MBq/ml), stored in the presence of ascorbic acid was well retained up to 8 days after the preparation. In colon cancer xenografted mice, 31.0% of the injected dose/g of 186Re-MAG3-A7 had accumulated in the tumors at 24 h postinjection. Estimated radiation dose to tumors was 14.9 cGy/37 kBq up to 8 days postinjection which was 12-fold greater than the whole-body radiation dose. These in vivo characteristics were superior to those of A7 labeled with radioiodine, affording greater therapeutic ratios than 131I-A7. Because of the better image quality of 186Re-MAG3-A7 as well as more favorable dosimetry, 186Re-MAG3-A7 would be a better choice for RIT of colon cancer than 131I-A7. These results indicated the feasibility of RIT with 186Re-MAG3-A7, though the prevention of radiolysis of the labeled antibody should be considered.

[Determination of energy window width and position for the triple energy window (TEW) scatter compensation method].

Since primary photons can provide information concerning the position of radioisotope (RI) accumulation and the energy of the photons, it would seem reasonable to vary the position and width of the energy window depending on the type of RI and the energy resolution of the detector to collect as many of the primary photons as possible. We propose a method for determining energy window width and position for scintigraphic imaging to collect as many of the primary photons as possible, and studied the influence on the Triple Energy Window (TEW) scatter compensation method of setting such energy window levels for 99mTc (single photopeak) and 201Tl (multiple photopeaks) using detector with different energy resolution through simulation. The Monte Carlo simulations were verified by comparing the regional energy spectrum at the phantom obtained from the simulation against experimental measurements. The energy window with our proposed method for 99mTc is 20% and 47.3% for 201Tl using gamma camera, and 9.8% for 99mTc using a semiconductor detector with a theorized energy resolution of 7.0 keV.

Assessment of plaque rupture by intravascular ultrasound.

To investigate the mechanism of plaque rupture, we carried out morphologic and quantitative assessments of ruptured plaque with a 30-MHz intravascular ultrasound catheter before coronary intervention. Plaque rupture, defined as an echolucent intraplaque area communicating with arterial lumen, was noted in all of 22 patients with coronary artery disease examined in the study. The plaque was eccentric in 16 patients (73%) and in 10 of these 16 patients there was a tear at the margin of the plaque (63%). Calcification was noted in only 6 patients (22%). Plaque area ranged from 8.7 to 44.1 mm2. The ruptured area ranged widely, from 1.0 to 14.0 mm2, and the percent ruptured area also ranged widely, from 3.9% to 50.9%. Fibrous cap was recognized in 20 patients. The thickness of the fibrous cap ranged from 0.1 to 0.6 mm (mean, 0.36 mm) and thinning of the fibrous cap was noted in 16 patients (80%). From these results, we conclude that intravascular ultrasound can provide detailed observations of plaque rupture consistent with pathologic studies. Accordingly, it is a suitable method for evaluation of plaque rupture in vivo. Plaque weakness, due to the presence of atheromatous core, thin fibrous cap, and no calcification, seems to be the major determinant of plaque rupture. In addition, the great variation in cap thickness and ruptured area suggests the role of other triggers, such as mechanical and hemodynamic stress, in plaque rupture.

201Tl and 99Tcm-human serum albumin for assessment of the effect of hypertensive treatment with angiotensin II infusion on tumour circulation.

The biodistribution of 201Tl and of 99Tcm-human serum albumin (99Tcm-HSA) was observed in tumour-bearing mice to investigate if tissue blood circulation could be evaluated in groups of mice infused with angiotensin II at a rate of 0.5 micrograms kg-1 min-1 (L) or 1 microgram kg-1 min-1 (H). Ten minutes after tracer injection, tumour uptake of 201Tl in the angiotensin II infused group showed a 2.20- and a 3.18-fold increase in the L and H groups, respectively, when compared to a group of mice infused with saline (P = 0.0478 and 0.0029, respectively). The effect of angiotensin II infusion on 201Tl uptake was minimal in normal organs. Decreased normal organ uptake of simultaneously injected 99Tcm-HSA in the L and H groups indicated the contraction of normal organ vessels, while increased tumour uptake of the tracer indicated mechanical dilatation of tumour vessels. We conclude that the effect of angiotensin II or other vasoactive agents can be non-invasively assessed by 201Tl and 99Tcm-HSA scintigraphy.

A role for the fyn oncogene in metastasis of methylcholanthrene-induced fibrosarcoma A cells.

Expression of various oncogenes (ras, myc, erbB2, src, fyn, yes and sis) in a high-metastatic clone (MH-02) derived from a murine methylcholanthrene-induced fibrosarcoma A (Meth A) was compared with those of its parent clone (ML-01) by Northern blot analysis. Two oncogenes, fyn, belonging to the tyrosine-kinase family, and sis, belonging to the cellular-growth-factor family, were found to have higher signals (3.6-fold and 1.8-fold respectively) in MH-02 than in ML-01 cells. To explore the possibility that higher expression of these oncogenes is involved in enhanced metastasis of the MH-02 clone, ML-01 was transfected by a fyn vector and the metastatic potential of the transfectant was examined. Mice administered fyn-transfected ML-01 cells had significantly increased metastatic nodules in the lung, as compared with those whose ML-01 cells were transfected with control vector without the fyn gene. The result indicates that the fyn gene is one of the factors governing the metastatic potential of Meth A cells.

[Assessment of split renal function before and after angioplasty or bypass grafting in the patients with renovascular hypertension].

Two different methods to assess the change of split renal function following angioplasty or bypass grafting were studied in a total of 12 patients with renovascular hypertension. The studies were performed before and within seven days after the therapeutic intervention. Split effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) after injections of I-131 hippuran and Tc-99m DTPA were measured using kidney counting corrected for depth and dose, described by Schlegel and Gates. In six of 10 patients with unilateral renal artery stenosis and in two patients with bilateral renal artery stenoses (two of 4 affected kidneys), the split renal function was improved after the therapeutic intervention, in accordance with the drop in blood pressure and the reduction of plasma renin activity. The improvement in ERPF and GFR was more likely in the patients without severely reduced renal function. In such patients, the improvement in ERPF was more pronounced than that in GFR. And in two patients with functional improvement, the Captopril-induced reduction of split GFR in the affected kidney was disappeared after the intervention. Moreover, in the long-term follow-up of three patients with functional improvement, one patient showed the deterioration of split renal function suggesting the relapse of renal artery stenosis. These results suggest that the combined studies of split ERPF and GFR determinations can be useful to evaluate the therapeutic effect as well as the presence or absence of functional improvement after the intervention.