Final results of the CAPAS trial.

BACKGROUND: The Cutting Balloon (Interventional Technologies Inc) is a new-concept balloon that incorporates 3 to 4 blades to create sharp incisions on the luminal surface of the lesion during dilation without causing severe tearing injury to the vessel wall. It may reduce restenosis and improve clinical outcome. METHODS: Two hundred forty-eight lesions were randomly assigned to Cutting Balloon angioplasty (CBA, 120 lesions) or conventional balloon angioplasty (PTCA, 128 lesions). Inclusion criteria were type B/C lesions (American College of Cardiology/American Heart Association classification) and reference diameter <3.0 mm by visual image on angiogram. Quantitative coronary angiography was performed before and after percutaneous coronary angioplasty and at 3-month follow-up. The primary end point was restenosis, defined as >/=50% diameter stenosis at follow-up. Clinical event rates at 1 year were assessed. RESULTS: Baseline characteristics were similar. Reference diameter was small in both groups (2.16 vs 2.18 mm, CBA vs PTCA). Preprocedural percent diameter stenosis (%DS) was similar (69.8% vs 69.6%). However, postprocedural and follow-up %DS were lower (26.2% vs 28.9%, P =.072; 40.8% vs 47.5%, P =.011) in the CBA group. Restenosis was significantly lower (25.2% vs 41.5%, P =.009) in the CBA group. At 1 year, event-free survival was achieved in 72.8% of the CBA group and in 61.0% of the PTCA group (P =.047). CONCLUSION: These findings suggest that CBA provides superior angiographic and clinical outcomes in comparison with PTCA in small coronary arteries.

Impact of pre-stent plaque debulking for chronic coronary total occlusions on restenosis reduction.

BACKGROUND: While stenting improves the long-term angiographic outcomes of successfully recanalized chronic coronary total occlusions (CTO), the restenosis rate still remains high. The massive plaque burden in CTO is considered to be one of the causes of in-stent restenosis. METHODS: We examined the pre-stent plaque debulking strategy with high-speed rotational atherectomy (RA) for 50 CTO (Thrombolysis in Myocardial Infarction flow grade 0; estimated occlusive duration, 3 months). Angiographic follow-up results were compared to those of 120 consecutive CTO recanalized with primary stenting in which RA could be indicated retrospectively. Angiographic restenosis was defined as diameter stenosis > 50% at 6-month follow-up. RESULTS: RA could be performed safely in all lesions without any major complications. Adjunctive ballooning and stenting could be performed without high-pressure dilatation (8.4 +/- 1.7 atmospheres). Follow-up angiography was performed in 48 lesions 184 +/- 61 days after the procedure. There were no significant differences in baseline characteristics between the two groups; however, the implanted stent type was different. Quantitative coronary angiography revealed that diameter stenosis was smaller at follow-up (36.2 +/- 20.0% versus 52.2 +/- 26.7%; p = 0.0003) as well as post-procedure (7.8 +/- 11.5% versus 17.8 +/- 13.6%; p < 0.0001) compared with the control group. Angiographic restenosis was also significantly reduced (29.2% versus 52.5%; p = 0.0061). CONCLUSIONS: RA is a safe procedure for plaque debulking of CTO in selected cases. Plaque debulking of CTO facilitates subsequent stent expansion and may reduce the restenosis rate.

Dihydropyrimidine dehydrogenase activity in human pancreatic tumor tissues.

Dihydropyrimidine dehydrogenase (DPD) activity was investigated using pancreatic tumors and normal pancreatic tissues surrounding the tumors obtained from 12 patients with pancreatic cancer. The mean DPD activity (+/- SD) was 2.69 +/- 1.88 nmol/mg protein/hr in normal pancreatic tissue and was 6.59 +/- 5.36 nmol/mg protein/hr in pancreatic tumor tissues. The DPD activity in tumor tissue was two- to threefold higher (p < 0.01) than that in normal tissue, but no marked difference was observed in DPD activity among cancer stages. The DPD activity of pancreatic tumors may be a useful clinical marker of the responsibility of fluorinated pyrimidine dosing in pancreatic cancer.

Percutaneous myocardial ablation in double-chamber right ventricle.

Double-chamber right ventricle (DCRV) exhibits intracavitary outflow obstruction. We report the first case of percutaneous myocardial ablation of DCRV in a 73-year-old patient. An alcohol-induced conus branch occlusion provided the reduction of pressure gradient from 81 to 48 mm Hg and clinical improvement. This strategy may be an alternative therapy to surgery in the adult patients with DCRV. Cathet. Cardiovasc. Intervent. 49:97-101, 2000.

Final results of the STent versus directional coronary Atherectomy Randomized Trial (START)

OBJECTIVES: This study was designed to compare primary stenting with optimal directional coronary atherectomy (DCA). BACKGROUND: No previous prospective randomized trial comparing stenting and DCA has been performed. METHODS: One hundred and twenty-two lesions suitable for both Palmaz-Schatz stenting and DCA were randomly assigned to stent (62 lesions) or DCA (60 lesions) arm. Single or multiple stents were implanted with high-pressure dilation in the stent arm. Aggressive debulking using intravascular ultrasound (IVUS) was performed in the DCA arm. Serial quantitative angiography and IVUS were performed preprocedure, postprocedure and at six months. The primary end point was restenosis, defined as > or =50% diameter stenosis at six months. Clinical event rates at one year were also assessed. RESULTS: Baseline characteristics were similar. Procedural success was achieved in all lesions. Although the postprocedural lumen diameter was similar (2.79 vs. 2.90 mm, stent vs. DCA), the follow-up lumen diameter was significantly smaller (1.89 vs. 2.18 mm; p = 0.023) in the stent arm. The IVUS revealed that intimal proliferation was significantly larger in the stent arm than in the DCA arm (3.1 vs. 1.1 mm ; p < 0.0001), which accounted for the significantly smaller follow-up lumen area of the stent arm (5.3 vs. 7.0 mm2; p = 0.030). Restenosis was significantly lower (32.8% vs. 15.8%; p = 0.032), and target vessel failure at one year tended to be lower in the DCA arm (33.9% vs. 18.3%; p = 0.056). CONCLUSIONS: These results suggest that aggressive DCA may provide superior angiographic and clinical outcomes to primary stenting.

Impact of cilostazol on restenosis after percutaneous coronary balloon angioplasty.

BACKGROUND: Restenosis after percutaneous transluminal coronary (balloon) angioplasty (PTCA) remains a major drawback of the procedure. We previously reported that cilostazol, a platelet aggregation inhibitor, inhibited intimal proliferation after directional coronary atherectomy and reduced the restenosis rate in humans. The present study aimed to determine the effect of cilostazol on restenosis after PTCA. METHODS AND RESULTS: Two hundred eleven patients with 273 lesions who underwent successful PTCA were randomly assigned to the cilostazol (200 mg/d) group or the aspirin (250 mg/d) control group. Administration of cilostazol was initiated immediately after PTCA and continued for 3 months of follow-up. Quantitative coronary angiography was performed before PTCA and after PTCA and at follow-up. Reference diameter, minimal lumen diameter, and percent diameter stenosis (DS) were measured by quantitative coronary angiography. Angiographic restenosis was defined as DS at follow-up >50%. Eligible follow-up angiography was performed in 94 patients with 123 lesions in the cilostazol group and in 99 patients with 129 lesions in the control group. The baseline characteristics and results of PTCA showed no significant difference between the 2 groups. However, minimal lumen diameter at follow-up was significantly larger (1.65+/-0.55 vs 1.37+/-0.58 mm; P<0.0001) and DS was significantly lower (34.1+/-17.8% vs 45.6+/-19. 3%; P<0.0001) in the cilostazol group. Restenosis and target lesion revascularization rates were also significantly lower in the cilostazol group (17.9% vs 39.5%; P<0.001 and 11.4% vs 28.7%; P<0. 001). CONCLUSIONS: Cilostazol significantly reduces restenosis and target lesion revascularization rates after successful PTCA.

Transluminal percutaneous septal myocardial ablation in a patient with hypertrophic obstructive cardiomyopathy.

Reduction of septal mass by inducing septal infarction using catheter techniques is a new therapy for hypertrophic obstructive cardiomyopathy (HOCM). We report a case of severe HOCM that was dramatically improved by this non-surgical treatment. A 60-year-old woman with HOCM had suffered dyspnea (NYHA class III) with syncopal attack despite medical treatment. Left heart catheterization showed a resting pressure gradient across the left ventricular outflow tract of 156 mmHg. Two proximal septal branches of the anterior descending coronary artery were catheterized with a balloon catheter by the usual percutaneous coronary angioplasty techniques and were completely blocked by injection of absolute alcohol. The pressure gradient decreased to 26 mmHg after the procedure. Symptoms were markedly improved (NYHA class I) without any medical treatment. The reduced pressure gradient was maintained at the 3-month follow-up catheterization (36 mmHg). Further long-term follow-up is needed, but this treatment would seem to to be a promising technique for reducing pressure gradient in symptomatic patients with HOCM.

Impact of cilostazol on intimal proliferation after directional coronary atherectomy.

Cilostazol, a novel platelet aggregation inhibitor, inhibits intimal proliferation in animal models. We randomly assigned 41 patients with lesions suitable for directional coronary atherectomy to the cilostazol group (200 mg/day) or the aspirin (250 mg/day) group. Medication was started before directional coronary atherectomy and was continued to a 6-month follow-up. Serial quantitative coronary angiography and intravascular ultrasound study were performed. Baseline characteristics were not different between the two groups. However, the minimal lumen diameter at follow-up was larger (2.33 +/- 0.60 mm vs 1.81 +/- 0.68 mm, p = 0.016) and the percent diameter stenosis (24.5% +/- 16.6% vs 40.9% +/- 21.0%, p = 0.010) was smaller in the cilostazol group. The change in vessel area was not different, but the percent plaque area at follow-up was smaller in the cilostazol group (55.7% +/- 11.2% vs 64.5% +/- 14.5%, p = 0.044). The restenosis rate was significantly lower in the cilostazol group (0% vs 26%, p = 0.020). We conclude that cilostazol appears to have an inhibitory effect on intimal proliferation after directional coronary atherectomy and may reduce restenosis.

Lipopolysaccharide increases cell surface-associated fibronectin in fibroblasts in vitro.

This study assessed the fibronectin expression by fibroblasts derived from noninflamed and inflamed gingiva by measuring the amount of cell surface-associated fibronectin and fibronectin released into the medium. The effects of added lipopolysaccharide from Porphyromonas gingivalis, Prevotella nigrescens and Escherichia coli on both types of fibroblasts were also studied. In the absence of lipopolysaccharide, the amounts of the two types of fibronectin were significantly larger in the fibroblasts from inflamed than from noninflamed gingiva. The specific lipopolysaccharide had no effect on the amount of fibronectin released into the medium by either fibroblast type. The amount of cell surface-associated fibronectin increased significantly when lipopolysaccharide (0.1 and 1 microgram/ml) was added to the cells from the noninflamed gingiva (the effect was evident in the order: P. gingivalis>P.nigrescens>E. coli). Lipopolysaccharide from P. gingivalis significantly increased the cell surface-associated fibronectin even at a low concentration of lipopolysaccharide (0.01 microgram/ml). In fibroblasts from the inflamed gingiva, only the lipopolysaccharide from P. gingivalis was effective in increasing the amount of cell surface-associated fibronectin. Our findings showed that the fibronectin expression was increased in the fibroblasts from inflamed gingiva and that lipopolysaccharide from P. gingivalis increased the cell surface-associated fibronectin.

Coronary angioplasty of chronic total occlusions with bridging collateral vessels: immediate and follow-up outcome from a large single-center experience.

OBJECTIVES: The purpose of the present study was to assess the effect of bridging collateral vessels on the success of coronary angioplasty of chronic total occlusions in the context of state of the art technology and operator skill. BACKGROUND: Coronary angioplasty of chronic total occlusions has been associated with relatively low success rates. Because the presence of bridging collateral vessels in chronic total occlusion has been reported to be the major predictive factor in procedural failure, angioplasty is often not recommended in patients with such vessels. METHODS: Three hundred ninety-seven consecutive patients undergoing coronary angioplasty for chronic total occlusion were classified into two groups. Patients in group I had chronic total occlusion with bridging collateral vessels (97 patients, 109 total occlusions), and patients in group II had chronic total occlusion without such vessels (300 patients, 324 total occlusions). RESULTS: The mean +/- SD duration of occlusion was 46 +/- 66 months (range 2 to 170) in group I and 27 +/- 39 months (range 2 to 112) in group II (p < 0.05, high power value 0.83, group I vs. group II). Angioplasty for single-vessel disease was performed in a smaller proportion of patients in group I than in group II (22% vs. 36%, p < 0.05; power value 0.77). Procedural success was achieved in 82 chronic total occlusions in group I and 270 chronic total occlusions in group II (75% vs. 83%, p = 0.07; power value 0.53). The rates of restenosis and reocclusion were 54% and 16%, respectively, for group I and 56% and 13%, respectively, for group II (p = 0.76, 0.46; power value 0.51, 0.47). Complications were minor with no Q wave infarction or requirement for urgent bypass surgery in either group. Of 81 patients with unsuccessful coronary angioplasty, 1 patient from group I (1%) and 3 patients from group II (1%) required pericardiocentesis because of cardiac tamponade. Guide wire manipulation did not impair the flow of bridging collateral channels in group I. CONCLUSIONS: Coronary angioplasty can open chronic total occlusions, with or without bridging collateral channels, for safe and effective recanalization without major complications.

Attenuation of acetylcholine-induced vasoconstriction by L-arginine is related to the progression of atherosclerosis.

To determine if L-arginine, a precursor of the endothelium-derived relaxing factor, restores endothelium-dependent dilation in human coronary arteries, we studied 21 patients in whom the lumina of the coronary arteries were angiographically smooth or slightly irregular and in whom there was a constrictor response to acetylcholine (ACh) in the left anterior descending coronary artery or the circumflex coronary artery. We examined the response to intracoronary ACh before and after infusion of L-arginine by measuring coronary diameter with quantitative angiography. Intracoronary injection of ACh produced vasoconstriction in the majority of patients with coronary risk factors. The percentage diameter change in smooth segments in patients with entirely smooth coronary arteries (group 1, n = 44) from baseline was -20.7% +/- 17.4%. During systemic infusion of L-arginine, the constrictor response to ACh in these segments was significantly attenuated (-2.2% +/- 15.1% from baseline, p < 0.01, ACh alone vs ACh during L-arginine infusion). In smooth segments in patients with luminal irregularities in the other coronary arteries (group 2, n = 19), ACh produced a marked constriction (-32.5% +/- 22.5% from baseline, p < 0.05, group 1 vs group 2). Infusion of L-arginine also attenuated ACh-induced vasoconstriction in these segments (-9.7% +/- 14.1% from baseline, p < 0.01, ACh vs ACh during L-arginine infusion). In segments with irregular lumina (group 3, n = 26), ACh produced more prominent vasoconstriction. The percentage diameter change was -40.9% +/- 26.5% from baseline (p < 0.01 vs group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Antiarrhythmic effects of eicosapentaenoic acid during myocardial infarction--enhanced cardiac microsomal (Ca(2+)-Mg2+)-ATPase activity.

The effects of dietary supplementation with eicosapentaenoic acid (EPA) on ventricular arrhythmias during myocardial infarction were examined in a canine model. EPA was incorporated into cellular membranes after ingestion of EPA-ester (100 mg/kg body weight/day) for 8 weeks. The ratio of EPA to arachidonic acid (AA) in platelet cell membranes and myocardial microsomes was significantly increased (7% to 37% in platelet cell membranes; p < 0.01, 3% to 12% in non-infarcted cardiac microsomes; p < 0.01, and from 2% to 8% in infarcted cardiac microsomes; p < 0.01). Dietary supplementation with EPA significantly reduced the incidence and severity of arrhythmias during coronary artery occlusion. Immediately after coronary artery occlusion, all of the animals in the control group that were given a toxic dose of digitalis developed ventricular tachycardia (VT) or ventricular fibrillation (Vf), whereas none of the animals in the EPA-supplement group developed VT or Vf within 15 min after administration of digitalis. Regardless of the presence of an infarcted area, the specific activity of the Ca(2+)-pump enzyme ((Ca(2+)-Mg2+)-ATPase) within the myocardial microsomal fraction of the EPA-supplemented group was significantly higher than in that of the control group (Vmax: 140.5 +/- 19.1 vs 94.8 +/- 28.9 nmol/mg/min in non-infarcted cardiac microsomes, p < 0.01, 130.9 +/- 18.4 vs 90.2 +/- 26.4 nmol/mg/min in infarcted cardiac microsomes, p < 0.01, EPA vs control group, respectively). The specific activities of the Na(+)-pump enzyme ((Na(+)-K+)-ATPase) and NADPH-dependent cytochrome C reductase in infarcted and non-infarcted cardiac microsomes did not differ between these groups. These results indicate that EPA supplementation increases the (Ca(2+)-Mg2+)-ATPase activity within myocardial membranes that is involved in Ca2+ metabolism in myocardial cells by increasing the ratio of EPA to AA within cellular membranes. These cellular alterations are likely to reduce the severity of ventricular arrhythmias by inhibiting the rapid accumulation of intracellular Ca2+ following ischemia.

Highly purified eicosapentaenoic acid attenuates tissue damage in experimental myocardial infarction.

We examined the effects of dietary supplementation with eicosapentaenoic acid (EPA) on experimental myocardial infarction in dogs. Twenty-five dogs were fed standard diets, 10 of which were supplemented with EPA-ester (100 mg/kg body weight/day) for 8 weeks, while 15 served as controls. After ingesting EPA for 8 weeks, the ratio of EPA to arachidonic acid (AA) in platelet cell membranes significantly increased (from 0.033 to 0.105; p < 0.01). The chemotactic response of neutrophils to leukotriene B4 (LTB4) was reduced in the EPA group (34% reduction at 10(-6) M LTB4, p < 0.01). Also in the EPA group, the amount of 12-hydroxyeicosatetraenoic acid, one of the chemotactic products of AA in infarcted myocardium, was reduced to 40% (p < 0.05). EPA treatment resulted in significant reduction in the ultimate size of the infarcted area. Contractile function of infarcted myocardium was well-preserved in the EPA group. Myeloperoxidase activity, an indication of the infiltration of neutrophils into the infarcted myocardium, was less in the EPA group than in the controls (0.68 +/- 0.25 U/0.1 gr. vs 1.22 +/- 0.55 U/0.1 gr., p < 0.05). Therefore, we conclude that dietary supplementation with EPA attenuates ischemic myocardial damage through inhibition of neutrophilic infiltration into the infarcted myocardium.

Higher levels of erythrocyte membrane fluidity in sprinters and long-distance runners.

Erythrocyte membrane fluidity was measured in male sprinters and long-distance runners by a spin-label method. The membrane fluidity was higher in long-distance runners than in sedentary subjects for both measurements by use of two stearic acid spin labels (SAL), 12- and 16-SAL, which represent the fluidity at two different depths of lipid bilayer. In the 12-SAL measurement, higher levels were also evident in sprinters than in sedentary subjects. Increases in the C20:5, C22:5, and total polyunsaturated acyl chains were evident in membrane phospholipids, whereas the C18 and total saturated acyl chains were decreased in long-distance runners compared with sedentary subjects. Only levels of C22:5 were higher in the sprinters than the sedentary subjects. Membrane cholesterol and phospholipid classes did not differ among the three groups. A higher level of erythrocyte membrane fluidity was observed in the athletes, more obviously in the long-distance runners, which was related to the altered phospholipid acyl chain composition. The change may contribute to the beneficial effects on erythrocyte functions related to microcirculation in athletes.

[Laboratory diagnosis of left atrial thrombi in patients with mitral stenosis].

Left atrial (LA) thrombi sometimes occur in patients with mitral stenosis (MS) and may cause systemic embolization resulting in serious and fatal complications. Several clinical techniques are used to detect the presence of LA thrombi, but even echocardiography, the most widely used, has some drawbacks depending on the sizes and locations of the thrombi. This study evaluated D-dimer, fibrinopeptide A(FPA), and thrombin-antithrombin III complex (TAT) as molecular markers for diagnosing the presence of LA thrombi in 26 patients with MS who underwent cardiac surgery. Atrial fibrillation was detected in all patients. Patients with episodes of obvious thromboembolic diseases were excluded. Blood was obtained from the brachial vein before the surgery (3 +/- 1 days; mean +/- SD). The presence or absence of thrombi was confirmed at surgery in all patients. Levels of both D-dimer and TAT were significantly higher in patients with thrombi than in those without thrombi or in normal subjects. FPA levels did not differ significantly between the three groups. The levels of D-dimer and TAT correlated significantly with the weights of the LA thrombi. LA thrombi (ca > or = 2 g) were always confirmed at surgery in patients with levels of D-dimer higher than 200 ng/ml and/or levels of TAT higher than 4 ng/ml. These results indicate that D-dimer and TAT are simple and useful diagnostic markers for determining LA thrombi in patients with MS.

Changes in polyphosphoinositides and phosphatidic acid of erythrocyte membranes in diabetes.

We studied metabolic pool size of polyphosphoinositides and phosphatidate of erythrocyte membranes from normal and diabetic subjects using 32P for 20-h incubation, a sufficiently long period to reach isotopic equilibrium between monoesterphosphate bond and gamma-phosphate of ATP. Phosphatidylinositol 4-monophosphate (PtdIns4P), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidate were the phospholipids labelled. Metabolic pools of individual phospholipids were estimated, based on their proportionate and absolute radioactivity. A significant decline in radioactivity of phosphatidate and PtdIns(4,5)P2 was seen in erythrocytes from the diabetic subjects, indicating suppression of the metabolically labile pool of these two phospholipids. There was no significant change in PtdIns4P radioactivity between the groups. The direct effect of insulin on phosphorylation of polyphosphoinositides and phosphatidate was also evaluated by a short incubation period of erythrocyte membranes with [gamma-32P]-ATP. Added insulin increased the incorporation of 32P into phosphatidate in a dose-dependent manner that reached a steady state at 2 nM. We conclude that the metabolically labile pool size of phosphatidate is decreased and that of polyphosphoinositides is altered in erythrocyte membranes from diabetic patients.

Lowered membrane fluidity of younger erythrocytes in diabetes.

In vivo age-related changes in membrane fluidity of erythrocytes were investigated by a spin label method after fractionation of the cells by discontinuous density gradient centrifugation. Membrane fluidity was lower in older than in younger erythrocytes in both the normal and diabetic subjects. Cells from diabetic subjects showed a significantly lower level of membrane fluidity for all three age groups (younger, middle and older) than the corresponding cells from normal subjects. The magnitude of progression in the decrease in membrane fluidity in erythrocytes did not differ significantly between both groups of subjects. Both erythrocyte ATP and acetylcholinesterase activity declined, while glycosylated hemoglobin (HbA1c) increased with cell age in both groups of subjects. The HbA1c level in each corresponding fraction was higher in diabetic subjects than normal subjects, but was not correlated with membrane fluidity in either group. Neither the ATP level nor acetylcholinesterase activity in each corresponding fraction differed between groups. Membrane fluidity was significantly correlated with acetylcholinesterase activity in both normal and diabetic subjects. Our results indicate that decreased erythrocyte membrane fluidity in diabetic patients does not form gradually during their life span but develops soon after the cells enter the circulation or during their maturation in the bone marrow.

Changes in erythrocyte membrane fluidity by endotoxin in rats.

The effect of endotoxin on fluidity and lipid composition of the erythrocyte membrane was studied in rats following the intraperitoneal administration of endotoxin (30 mg.kg(-1) body weight). Erythrocyte membrane fluidity measured with 16-stearic acid spin label (16-SAL) was significantly decreased in the endotoxin-treated rats as compared with control. A decrease of lysophosphatidylcholine in the membrane lipid was evident in the endotoxin-treated rats. The cholesterol to phospholipid molar ratios and other phospholipid fractions did not differ significantly in the two groups. The levels of plasma Beta-glucuronidase activity and lipoperoxide were significantly increased in the endotoxin-treated rats when compared to controls. There were significant correlations between the parameter of 16-SAL in erythrocytes and plasma Beta-glucuronidase activities or lipoperoxide from both endotoxin-treated and control groups, P < 0.005 or P < 0.02 respectively. In conclusion endotoxin decreased rat erythrocyte membrane fluidity in vivo. Since membrane fluidity is closely related to the vital functions of the membranes, the change described could be related to the abnormality of cell membrane functions in endotoxin shock state.

[A case of insulin receptor abnormality (type A)].

A sixteen year old woman came to the hospital for glucosuria and amenorrhea. Physical examination demonstrated that she had hirsutism, deepening of voice, and pigmented skin in her axillary lesion which was histologically diagnosed as acanthosis nigricans. Ultrasonography showed polycystic ovaries. A diabetic pattern of 75 g oral glucose tolerance test, very high levels of serum insulin (fasting: 320, peak: 1,220 microU/ml), and hyperandrogenism characterized by increases of urine 17-KS, serum testosterone and DHEA-S were found. Both serum insulin and insulin-receptor antibodies were found to be negative. Insulin binding to both erythrocytes and cultured skin fibroblasts were significantly decreased (about 30% of normal controls). Scatchard plot analysis demonstrated decreased number of insulin receptors to about 30% of the normal controls. We therefore diagnosed that she had insulin receptor abnormality, Type A in Kahn's classification.

[A case of hepatoma patient who showed an abnormally high level of serum IRI with the beads method].

A fifty four years old hepatoma patient admitted to the hospital for a surgical operation. Preoperative laboratory examination demonstrated that his serum IRI level was very high (423 microU/ml) when measured with a beads method, however RIA or a microplate method demonstrated normal values. We studied the mechanism of the discrepancy of IRI values. 1) Both the beads and microplate methods demonstrated the same IRI values when the patient's serum insulin was roughly purified with Sep-Pak. The beads method showed high IRI values in serum which passed through Sep-Pak, therefore contained no insulin. 2) The similar results were observed when the patient's serum fractionated by a gel-chromatography (Biogel P-30). The beads method demonstrated high IRI values in both insulin fractions and the fractions containing serum proteins bigger than 40,000 molecular weight. The microplate method demonstrated only one large peak of insulin. 3) When non-specific IgG of guinea pig was used as a fixed antibody instead of human insulin antibody of guinea pig that was used in the beads method, the patient's serum showed the similar values as that obtained with the beads method. We thereby concluded that the abnormal level of IRI by the beads method was derived from the unknown substance reacting with IgG of guinea pig in the patient's serum. After the surgical resection of hepatoma, the levels of IRI measured by the beads method decreased significantly, suggesting that the substance is related to hepatoma cells.