Long-term histological prognosis and serum fibrosis markers in chronic hepatitis C patients treated with interferon.

BACKGROUND: Interferon (IFN) therapy is effective in 20-40% of patients with chronic hepatitis C, but the relationship between histological changes and the response to interferon is still unclear. We investigated the long-term histological prognosis and the changes of serum fibrosis markers after interferon therapy relation to the response. METHODS AND RESULTS: One hundred and eighteen patients with chronic hepatitis C who received interferon therapy were divided into four groups based on the detection of viremia and the serum alanine aminotransferase (ALT) level after treatment. A histological examination was performed by using the histological activity index and the criteria of the METAVIR score. Serum fibrosis markers were used to measure the levels of hyaluronic acid and type IV collagen 7s. Responders, whose serum ALT levels became normal after treatment, demonstrated histological improvement. Histological improvement was more rapid in sustained virological responders with hepatitis C virus (HCV) RNA seronegativity than in biochemical responders with HCV-RNA seropositivity. Only sustained virological responders exhibited histological cure. In partial responders, whose serum ALT levels decreased to less than twice the upper of normal, and non-responders whose serum ALT levels were not reduced, liver fibrosis was unchanged or showed progression. Serum fibrosis markers increased with progression of the histological stage and varied depending on the response to interferon. CONCLUSION: Normalization of serum ALT levels after interferon therapy led to a histological improvement, and that with viral clearance achieved histological cure. Serum fibrosis markers were useful indicators for long-term according to the response of IFN therapy.

Differences in inflammatory activity at the onset of acute myocardial infarction according to the clinical presentation of preinfarction angina.

It is unknown whether the pathogenetic mechanisms underlying acute myocardial infarction (AMI) differ according to the clinical presentation of preinfarction angina, so the present study measured plasma levels of C-reactive protein (CRP) in 280 patients with AMI in whom serum creatine kinase levels were normal on admission and increased subsequently. Patients were classified into 3 groups according to the type of preinfarction angina: no angina (n=95), stable angina (n=48), and unstable angina (n= 137). Patients with unstable angina were subdivided according to the Braunwald classification: class IB (n=39), class IIB (n=22), and class RIB (n=76). There were no differences among the 5 groups in baseline characteristics. CRP on admission was significantly higher and the level of physical activity at symptom onset was significantly lower in the Braunwald class RIB group than in the other groups, but no differences were observed among the other groups. Patients with preinfarction Braunwald class IIB unstable angina had higher CRP levels on admission and symptom onset at a lower level of physical activity. In such patients, the pathogenetic mechanisms may differ from those in other subsets of patients with AMI and active inflammation may play a more important role in AMI onset.

ST-segment depression in lead aVR predicts predischarge left ventricular dysfunction in patients with reperfused anterior acute myocardial infarction with anterolateral ST-segment elevation.

BACKGROUND: Patients with an anterolateral acute myocardial infarction (AMI) have a worse prognosis, and those with additional inferolateral wall involvement might be higher risk because of more extensive area at risk. Lead -aVR obtained by inversion of images in lead aVR has been reported to provide useful information for inferolateral lesion. METHODS: We examined the relation between ST-segment deviation in lead aVR on admission electrocardiogram (ECG) and left ventricular function in 105 patients with an anterolateral AMI undergoing successful reperfusion < or = 6 hours after onset. Patients were classified according to ST-segment deviation in lead aVR on admission ECG: group A, 23 patients with ST elevation of > or = 0.5 mm; group B, 47 patients without ST deviation; and group C, 35 patients with ST depression of > or = 0.5 mm. RESULTS: There were no differences among the 3 groups in age, sex, or site of the culprit lesion. In groups A, B, and C, the peak creatine kinase level was 3661 +/- 1428, 4440 +/- 1889, and 6959 +/- 2712 mU/mL, and the left ventricular ejection fraction (LVEF) measured by predischarge left ventriculography was 54% +/- 9%, 48% +/- 7%, and 37% +/- 9%, respectively(P < .01). During hospitalization, congestive heart failure occurred more frequently in group C than in groups A or B (P < .05). ST-segment depression in lead aVR had a higher predictive accuracy than other ECG findings in identifying patients with predischarge LVEF < or = 35%. CONCLUSIONS: We conclude that in patients with an anterolateral AMI, ST-segment depression in lead aVR on admission ECG is useful for predicting larger infarct and left ventricular dysfunction despite successful reperfusion.

Implications of the absence of ST-segment elevation in lead V4R in patients who have inferior wall acute myocardial infarction with right ventricular involvement.

BACKGROUND: ST-segment elevation of > or = 1.0 mm in lead V4R has been shown to be a reliable marker of right ventricular involvement (RVI), a strong predictor of a poor outcome in patients with inferior acute myocardial infarction (IMI). However, patients with no ST-segment elevation in lead V4R despite the presence of RVI have received little attention. HYPOTHESIS: The study was undertaken to study the clinical features of patients with no ST-segment elevation in lead V4R despite the presence of RVI, which means false negative, as such patients have received little attention in the past. METHODS: We studied 62 patients with a first IMI, who had total occlusion of the right coronary artery (RCA) proximal to the first right ventricular branch and successful reperfusion within 6 h from symptom onset, to examine the implications of the absence of ST-segment elevation in lead V4R despite the presence of RVI. RESULTS: A standard 12-lead electrocardiogram (ECG) and right precordial ECG (lead V4R) were recorded on admission, and three posterior chest ECGs (leads V7 to V9) were additionally recorded in 34 patients. Patients were classified according to the absence (Group 1, n = 18) or presence (Group 2, n = 44) of ST-segment elevation of > or = 1.0 mm in lead V4R on admission. Patients in Group 1 had a greater ST-segment elevation in leads V7 to V9 (2.9+/-2.4 vs. 1.4+/-3.0 mm. p < 0.05), a higher frequency of a dominant RCA (defined as the distribution score > or = 0.7) (72 vs. 11%, p < 0.001), and a higher peak creatine kinase level (3760+/-1548 vs. 2809+/-1824 mU/ml, p < 0.05) than those in Group 2. CONCLUSIONS: In patients with IMI caused by the occlusion of the RCA proximal to the first right ventricular branch, no ST-segment elevation in lead V4R can occur because of concomitant posterior involvement. In such patients, the incidence of RVI may be underestimated on the basis of ST-segment elevation in lead V4R.

Early peak creatine kinase activity is not always a marker of successful reperfusion with myocardial salvage in patients with reperfused anterior acute myocardial infarction.

BACKGROUND: Although early peak creatine kinase activity (peak CK) is considered a reliable marker of coronary reperfusion in patients with acute myocardial infarction (AMI), whether early peak CK indicates good myocardial salvage is unclear. Moreover, some patients have late peak CK despite successful reperfusion, and its clinical implication remains to be elucidated. METHODS AND RESULTS: We examined the association of the time to peak CK with predischarge left ventricular function in 124 patients with a first AMI who had successful reperfusion within 6 hours from symptom onset. Patients were classified according to the time from reperfusion to peak CK: group A, 61 patients with peak CK < 6 hours; group B, 42 with peak CK from 6 to 12 hours; and group C, 21 with peak CK > 12 hours. There were no differences among the 3 groups in age, sex, method of reperfusion, time from symptom onset to reperfusion, collateral circulation, or the extent of risk area estimated by number of leads with ST-segment elevation. Left ventricular ejection fraction measured by predischarge left ventriculography was lowest in group A, followed by group B, and highest in group C (median values, 43%, 52%, and 60%, P < .01). Left ventricular dysfunction (left ventricular ejection fraction < or = 40%) occurred in 26 (43%) patients in group A, 8 (19%) in group B, and none in group C (P < .01). CONCLUSIONS: We conclude that compared with early peak CK, late peak CK consistently reflects good myocardial salvage in patients with anterior AMI who had successful reperfusion within 6 hours from symptom onset.

Relationship between myocardial damage and C-reactive protein levels immediately after onset of acute myocardial infarction.

The present study investigated the relationship between myocardial damage and C-reactive protein (CRP) levels, with no increase in creatine kinase (CK) activity, immediately after the onset of acute myocardial infarction (AMI) in 85 patients with their first reperfused anterior AMI without CK elevation on admission and no ischemic events during hospitalization. Patients were classified into those with low levels (<0.3 mg/dl) of CRP (Group L; n=67) and those with high levels (> or =0.3 mg/dl) of CRP (Group H; n=18). Group H had a higher proportion of patients with a history of preinfarction angina (89 vs 55%, p<0.01), especially unstable angina. SigmaST in leads V1-6 on admission ECG was lower in Group H than in Group L (14+/-7 vs 21+/-13 mm, p<0.05). Predischarge left ventriculography showed that the left ventricular global ejection fraction (55+/-11 vs 48+/-10%, p<0.01) and SD/chord at the left anterior descending artery lesion (-1.7+/-0.9 vs -2.3+/-0.9, p<0.01) were better in Group H. Multivariate analysis demonstrated that both CRP on admission (p=0.011) and preinfarction angina (p=0.002) were independently associated with better regional wall motion (SD/chord >-2.0) before discharge. These results suggest that the clinical situation of elevated CRP immediately after onset is associated with less myocardial damage and better left ventricular function in reperfused anterior AMI.

Application of a single-cell gel electrophoresis (comet) assay to screen the antimutagenic activity in foods.

Three cell lines (HL60, U937 and RAW264.7) were studied for their sensitivity against mutagens by using a single-cell gel electrophoresis (comet) assay. RAW264.7, the most sensitive one, was chosen to screen the antimutagenic activity in swine and bovine offal. Aqueous extracts of the swine stomach (0.2 mg/ml) and heart (10 mg/ml) were found to have antimutagenic activity against MeIQx (+ S9mix)-treated cells.

Comparison of results of early reperfusion in patients with inferior wall acute myocardial infarction with and without complete atrioventricular block.

We investigated the effect of reperfusion in patients with complete atrioventricular block within 6 hours after the onset of inferior wall acute myocardial infarction. Early reperfusion may promote the restoration of normal sinus rhythm and effectively reduce infarct size in these patients.

Augmentation of vessel squeezing at coronary-myocardial bridge by nitroglycerin: study by quantitative coronary angiography and intravascular ultrasound.

BACKGROUND: Nitroglycerin is known to augment vessel wall squeezing at the site with coronary-myocardial bridging (CMB). This study was designed to define the mechanism of nitroglycerin-induced augmentation of CMB in clinical settings. METHODS: We analyzed nitroglycerin reactivity at the site with CMB in 39 patients. Maximal and minimal diameters of CMB during a cardiac cycle were measured by quantitative angiography before and after intracoronary administration of 250 microgram nitroglycerin. In 15 patients, CMB sites were observed by intravascular ultrasound to determine the intimal thickness and the time-serial change in vessel area. RESULTS: Before nitroglycerin, CMB was demonstrated with angiography in 25 patients, and the remaining 14 patients showed CMB after nitroglycerin. The maximal diameter during diastole increased from 1. 4 +/- 0.4 mm to 1.9 +/- 0.4 mm after nitroglycerin, whereas the minimal diameter during systole decreased from 1.0 +/- 0.4 mm to 0.7 +/- 0.4 mm (P <.01). Thus nitroglycerin augmented the percent vessel narrowing during systole from 24% +/- 21% to 65% +/- 16% (P <.01). Under these conditions, intravascular ultrasound showed the reduction of the cross-sectional area of the sites with CMB by -38% +/- 16% (P <.01) during systole, and this phenomenon continued to early diastole (-30% +/- 16%). The intimal thickness was 0.32 +/- 0. 10 mm, which suggests the absence of atherosclerotic disease at CMB sites. CONCLUSIONS: These results indicate that nitroglycerin-induced augmentation of the percent narrowing of CMB can be derived from further systolic compression of the vessel lumen as well as diastolic expansion, probably because of the increase in vessel compliance after nitroglycerin. We suggest that the delayed dilation of coronary lumen during the early diastole may contribute to the occurrence of myocardial ischemia.

New electrocardiographic criteria for predicting the site of coronary artery occlusion in inferior wall acute myocardial infarction.

In patients with inferior wall acute myocardial infarction (AMI), the site of the culprit lesion is an important determinant of outcome. Patients with right ventricular infarction have a poor prognosis, whereas those with occlusion of the left circumflex coronary artery (LCx) have a good prognosis. Therefore, we assessed whether standard 12-lead electrocardiograms obtained on admission could identify the site of coronary artery occlusion, (i.e., a site proximal to the origin of the right ventricular branch of the right coronary artery [RCA], a site distal to the origin of the right ventricular branch of the RCA, or a site in the LCx). The ratio of ST depression in lead V3 to ST elevation in lead III (V3/III ratio) was evaluated immediately before coronary angiography in 152 patients with a first inferior wall AMI confirmed by coronary angiography within 12 hours after the onset of symptoms. For occlusion of the proximal RCA, distal RCA, and LCx, V3/III ratio was 0.2+/-0.3, 0.8+/-0.5, and 2.5+/-2.5 (p = 0.0001), respectively. The V3/III ratio <0.5 identified proximal RCA occlusion, 0.5

[A patient with disopyramide intoxication rescued by percutaneous cardiopulmonary support].

A 28-year-old man was admitted to our hospital in a hypotensive state 2 hours after taking 8,400 mg disopyramide. Infusion of catecholamine and gastric lavage restored normal blood pressure. However, 8 hours after taking the disopyramide he became hypotensive again and electrocardiographic findings revealed bizarre ventricular complexes resulting in ventricular flutter. Although standard cardiopulmonary resuscitation was not effective, his circulatory status was maintained by percutaneous cardiopulmonary support (PCPS). After 36 hours electrocardiography showed sinus rhythm, and his cardiac function became normal. Patients with severe cardiac dysfunction or cardiac arrest caused by disopyramide intoxication can be supported by PCPS until cardiac function is restored.

[Optimal reperfusion therapy in acute myocardial infarction: time to reperfusion and recanalization rate].

Rapid and complete reperfusion is important for the reduction of infarct size and mortality in acute myocardial infarction. The optimum reperfusion therapy with regard to the recanalization rate and the time elapsing between onset and complete reperfusion was evaluated. One hundred fifty-four patients with total occlusion of the infarct-related artery within 6 hours of the onset were classified into four therapy groups: PTCA group (n = 58) undergoing primary percutaneous transluminal coronary angioplasty (PTCA), t-PA-IC group (n = 44) receiving tissue plasminogen activator (t-PA) intracoronary infusion, t-PA-IV group (n = 14) receiving intravenous t-PA infusion, and mt-PA-IV group (n = 38) receiving intravenous mutant t-PA infusion. Although the recanalization rate was high in the PTCA group, there were no differences between the four groups as a supplement to immediate or rescue PTCA. The time elapsing between initiation of thrombolysis and complete reperfusion was shorter in the mt-PA-IV group than in the t-PA-IV group. Assuming the time from hospital arrival to initiation of intravenous thrombolysis was 20 min, the recanalization rate at 60 min after arrival in hospital was higher in the mt-PA-IV group than the PTCA and t-PA-IC groups. Although additional coronary angiography and PTCA may be required to improve the low recanalization rate compared with primary PTCA, intravenous infusion of mutant t-PA was the most promising therapy to achieve early reperfusion.

Open coring-out (function-preserving) technique for low fistulas.

PURPOSE: Fistula operations can be very destructive to the anal sphincters; functional abnormalities occur easily after such surgery (even with an internal spincterotomy, minor incontinence occurs), hence, function-preserving operations are best. A low fistula goes through the thin sphincter muscle layer, making it more difficult to preserve than a deeper fistula. In 1984, we developed a technique to treat long string-type low fistulas showing heavy inflammation and induration from the internal opening to the primary focus, namely, the infected intersphincteric anal gland. This report shows the main surgical techniques used. TECHNICAL METHOD: For the fistula procedure, we developed an "open coring-out" technique in which the whole fistula is pulled out, making the inside and outside clearly visible. The portion from the internal opening to the primary focus is easily opened (fistulotomy), and the primary focus is excised by coring-out (fistulectomy). For the repair procedure, the sphincter muscle edges are fixed to the underlying tissues with two kinds of sutures. The cored portion is provided with adequate drainage and two sutures that narrow and prevent pocket formation. RESULTS: Since 1984, 319 of 5,055 patients with low fistulas have been treated using this technique, and 52 patients required postoperative treatment; delayed healing occurred in 48 patients; recurrence occurred in 4 patients. Of patients responding to our survey, 16 (6.4 percent) reported postoperative complaints. Delayed healing has always been a major problem. Because the repair procedure inhibits pocket formation and allows for adequate drainage of the cored portion, cases of delayed healing have been reduced to approximately 7 percent in the last four years. CONCLUSION: This technique, which is continually being improved and evaluated, is simple, has a low risk of infection, preserves functions, and prevents deformity of the anal verge and perineum.

Intravascular ultrasonic evidence for importance of plaque distribution (eccentric vs circumferential) in determining distensibility of the left anterior descending artery.

Although previous studies have shown that coronary atherosclerosis is accompanied by impaired vessel wall compliance, few data exist regarding the regional vessel distensibility that may be important in order to gain an insight into the mechanism of atherosclerotic plaque rupture. Therefore, we analyzed 45 coronary sites of the proximal left anterior descending artery from 40 patients. Using intravascular ultrasound, luminal area in diastole (A) and in systole was measured at the diseased sites. With the ratio of luminal area changes (dA) to coronary pressure changes (dP) during a cardiac cycle, the total distensibility index was obtained by the formula: [(dA/A)/dP] x 10(3). At the sites with noncircumferential disease perimeters in diastole (L) and in systole were measured at the normal and narrowed portions. Using the changes in perimeters (dL) during a cardiac cycle, the regional distensibility index was obtained by the formula: [(dL/L)/dP] x 10(3). In 22 sites with circumferential disease, the total distensibility index was 1.03 +/- 0.61/mm Hg (mean +/- SD), and significantly lower than that from 23 sites with noncircumferential disease that showed 1.45 +/- 0.89/mm Hg (p <0.05). In noncircumferential disease, the regional distensibility index at narrowed portions was significantly lower, 0.33 +/- 0.47/mm Hg, than that at normal portion, 1.11 +/- 0.75/mm Hg (p <0.01), suggesting the heterogenous distribution of regional wall distensibility in noncircumferential lesions. These results indicate that the heterogeneous regional wall distensibility exists at the sites with noncircumferential disease where the total vessel distensibility is preserved by the presence of the compliant normal portion.

Intravascular ultrasound evidence for importance of plaque distribution in the determination of regional vessel wall compliance.

Regional vessel wall distensibility was determined by measuring luminal area and pressure, using intravascular ultrasound (Sonicath; Boston-Scientific, Watertown, MA, USA; 3.5 Fr, 30 MHz) in 45 left coronary sites from 40 patients. Luminal area in diastole (A) and in systole was measured at the diseased sites. With the ratio of luminal area changes (dA) to coronary pressure changes (dP) during a cardiac cycle, the total distensibility index was calculated by the formula: [(dA/A)/dP] x 10(3). At sites with non-circumferential disease, perimeters in diastole (L) and in systole were measured at the normal and diseased portions, and the changes in perimeters (dL) during a cardiac cycle were calculated. The regional distensibility index was obtained by the formula: [(dL/L)/dP] x 10(3). In 22 sites with circumferential disease, the total distensibility index was 1.03 +/- 0.61/mmHg, significantly lower than that for 23 sites with non-circumferential disease (1.45 +/- 0.89/mmHg; P < 0.05). In non-circumferential disease, the regional distensibility index at the diseased portion was significantly lower (0.33 +/- 0.47/mmHg) than that at the normal portion (1.11 +/- 0.75/mmHg; P < 0.01). Coronary sites with residual non-circumferential disease after angioplasty also exhibited heterogeneity of regional distensibility (0.73 +/- 0.76 at disease sites versus 1.58 +/- 0.95/mmHg at normal sites, n = 10, P < 0.05). These results indicate that heterogeneous regional wall distensibility exists at sites with non-circumferential disease where the total vessel distensibility is preserved by the presence of compliant normal portion. This heterogeneity of regional wall distensibility may represent a biomechanical factor that explains the mechanism of plaque rupture that occurs mainly at the shoulder of the non-circumferential disease.

Intravascular ultrasound evidence of angiographically undetected left main coronary artery disease and associated trauma during interventional procedures.

To determine the clinical significance of angiographically undetected left main coronary artery (LMCA) disease, we analyzed data from 47 patients, with a mean age of 58 years, who were examined with intravascular ultrasound (3.5 Fr, 30 MHz). For assessment of atherosclerosis, the lesion area was calculated from the ultrasound images of the formula, [(total vessel area--lumen area)/total vessel areas] x 100(%). In 37 LMCA segments of patients with significant distal coronary stenosis (> 50%), the percent intima-media area (the index) was 39 +/- 11% (mean +/- SD), significantly greater than that of 10 patients without distal disease (27 +/- 4%, P < 0.01). Among those with significant coronary stenosis, the index was markedly greater in patients with multi-vessel coronary stenosis (46 +/- 12%, n = 19) than in patients with single-vessel disease (33 +/- 9%, n = 18; P < 0.01). At three LMCA sites associated with multi-vessel disease, ultrasound analysis demonstrated disruption of the intima at the site where the guiding catheter for balloon angioplasty had been positioned. These results indicate that LMCA disease is more prominent in patients with multi-vessel distal coronary disease than in those with single vessel disease, even in the absence of angiographic stenosis. We suggest that LMCA trauma can occur where the guiding catheter for angioplasty is positioned, particularly in patients with multi-vessel distal disease.

Epstein-Barr virus genome-positive tubulointerstitial nephritis associated with Kawasaki disease-like coronary aneurysms.

A patient with recurrent renal failure due to massive interstitial nephritis caused by Leu 3a + 3b-positive T-cell infiltration and associated with multiple thromboembolic attacks is reported. He died of gastrointestinal bleeding after treatment with anticancer agents. At autopsy, diffuse necrosis of the bilateral kidneys was noted as well as giant coronary aneurysms filled with thrombus that resembled those seen in Kawasaki disease and multiple old myocardial infarcts were also present. Among the various Epstein-Barr virus (EBV)-specific antibodies, the titers anti-viral capsid antigen (VCA) and anti-early antigen (EBEA) IgG antibody were always very high in contrast to the relatively low titers of anti-EB nuclear antigen (EBNA) antibodies. DNA extracted from kidney tissue obtained at autopsy was analyzed by Southern blot hybridization after the amplification of EBV-specific DNA by the polymerase chain reaction. In situ hybridization of kidney tissue obtained at biopsy was also performed using an enzyme-linked probe derived from the EBV-encoded RNA 1 (EBER1) gene. As a result, the EBV genome was found both at autopsy and in the biopsy tissue, which clearly revealed EBER1 in the interstitial cells. Taking account of the progressive ST-T changes of the electrocardiograms which were normal early in his course, multiple myocardial infarction associating multiple giant aneurysms probably occurred during this disease process. Thus, it could be concluded that chronic active EBV infection contributed massive interstitial nephritis mediated by the activation of Leu 3a + 3b-positive T cells.

Closure of ventricular septal rupture caused by acute myocardial infarction using a transaortic balloon catheter.

We report a case of successful transaortic closure of a postinfarction ventricular septal rupture using a Swan-Ganz catheter. The method markedly reduced a left-to-right shunt and the improved hemodynamic condition of the patient, an 81-year-old woman, was maintained for about a week before surgical treatment. Inflation of the balloon with water made the balloon visible via echocardiography and was effective in maintaining inflation and echocardiographic follow-up.

[Antigenicity study of trandolapril (RU44570)].

Antigenicity of trandolapril (RU44570) was evaluated using the following six standpoints: 1. active systemic anaphylaxis (ASA) in guinea pigs; 2. passive cutaneous anaphylaxis (PCA) in guinea pigs with serum of sensitized guinea pigs; 3. histamine release from lung tissue of sensitized guinea pigs; 4. Schultz-Dale reaction with isolated ileum of sensitized guinea pigs; 5. passive cutaneous anaphylaxis (PCA) in rats with serum of sensitized mice; and 6. delayed type skin reaction by Maximization test in guinea pigs. In the test of immediate type reactions, guinea pigs were sensitized by RU44570 (p.o.), an FCA emulsion of RU44570 (s.c.) or an FCA emulsion of incubate solution of RU44570 and normal guinea pig's serum, and mice were sensitized by a mixture of RU44570 and alum (i.p.). In the test of delayed type reaction, guinea pigs were sensitized by intradermal injection and patch application. 1. ASA in guinea pigs: No anaphylaxis symptoms were observed in any of the sensitized guinea pigs. 2. PCA in guinea pigs: PCA titer of sera from all the sensitized animals was less than 1. 3. Histamine release from lung tissue: No histamine release was observed in any of the isolated lung tissue. 4. Schultz-Dale reaction: No contraction was observed in any of the isolated ileums. 5. PCA in rats: PCA titer of sera from sensitized BALB/c and C3H/He mice was less than 5. 6. Delayed type skin reaction test: No skin reactions were observed in any of the sensitized guinea pigs. From these results, it is concluded that RU44570 has no antigenicity under the conditions of the present study.