Ischaemic colitis during interferon treatment for chronic hepatitis C: report of two cases and literature review.

Ischaemic colitis is known to be a severe emergency complication of interferon (IFN) therapy. However, as ischaemic colitis is an infrequent complication of IFN therapy, limited information is available regarding the safety of resuming IFN therapy after resolution of ischaemic colitis and subsequent recurrence. Here, we report two cases of ischaemic colitis during IFN therapy for chronic hepatitis C. Ischaemic colitis was fully healed within 1 week after its onset and IFN withdrawal, and IFN therapy was resumed following patients' wishes to do so. Ischaemic colitis did not recur after the resumption of IFN therapy, and sustained virological response was achieved in both patients. In this report, we also summarize the findings of 11 cases of IFN-associated ischaemic colitis (nine previously published cases plus our two cases) and review the clinical characteristics of ischaemic colitis during IFN therapy in patients with chronic hepatitis C.

Comparison of the effects of pioglitazone and voglibose on circulating total and high-molecular-weight adiponectin, and on two fibrinolysis inhibitors, in patients with Type 2 diabetes.

BACKGROUND: To investigate short-term effects of pioglitazone and voglibose on serum concentrations of both total and high-molecular-weight (HMW) adiponectin measured with a novel sandwich enzyme-linked immunosorbent assay (ELISA) ,and on plasma fibrinolysis indicators, in Type 2 diabetic patients with inadequate glycaemic control on sulphonylureas. METHODS: Thirty-four diabetic patients were randomized to receive pioglitazone or voglibose treatment for 12 weeks, after which serum HMW adiponectin was measured. Plasma plasminogen activator inhibitor (PAI) 1 and thrombin-activatable fibrinolysis inhibitor (TAFI), a recently identified inhibitor of fibrinolysis, were measured as fibrinolysis inhibitors. RESULTS: At baseline, serum HMW adiponectin correlated negatively with plasma TAFI in all patients with Type 2 diabetes (r = -0.367, P = 0.0423). Both groups showed similar improvements in glycaemic control. Serum total and HMW adiponectin increased in patients treated with pioglitazone, but did not change in patients treated with voglibose. The HMW : total adiponectin ratio increased significantly after treatment with pioglitazone (P = 0.0004). The change in HbA(1c) correlated negatively with changes in serum HMW adiponectin in patients treated with pioglitazone (r = -0.694, P = 0.0034). Plasma PAI-1 and TAFI did not change with pioglitazone treatment. CONCLUSION: Increased serum HMW adiponectin may contribute to the improvement in glycaemic control after pioglitazone treatment. Plasma PAI-1 and TAFI were unchanged by either drug.

Association between diabetic microangiopathy and vascular endothelial function evaluated by flow-mediated vasodilatation in patients with type 2 diabetes.

The main purpose of the study was to investigate the association between vascular endothelial function and diabetic microangiopathy (nephropathy, retinopathy and neuropathy) in patients with type 2 diabetes. In addition, the association between endothelial function and macroangiopathy evaluated by intimal-medial complex thickness (IMT) was also investigated. Endothelial function was evaluated non-invasively by the measurement of flow-mediated vasodilatation (FMD) of the brachial artery. Diabetic nephropathy and neuropathy were assessed by urinary albumin excretion (UAE) and motor or sensory nerve conduction velocity (MCV, SCV), respectively, and retinopathy was evaluated by an ophthalmologist using the Davis classification. FMD was measured in 102 patients with type 2 diabetes and in 20 control subjects, and showed a tendency to be lower in the diabetic patients. There was a significant decrease in FMD in patients with proliferative diabetic retinopathy, compared with those in patients with no diabetic retinopathy. FMD showed significant positive correlations with MCV and SCV, and significant negative correlations with log UAE, systolic blood pressure and diabetic duration, but no correlation was obtained between FMD and IMT. In stepwise regression analysis, MCV alone showed a significant association with FMD. In conclusion, our results show that in patients with type 2 diabetes FMD is closely associated with all types of microangiopathy, with neuropathy being most strongly associated with FMD; however, FMD is not associated with macroangiopathy evaluated by IMT.

Small low-density lipoprotein and small low-density lipoprotein/total low-density lipoprotein are closely associated with intima-media thickness of the carotid artery in Type 2 diabetic patients.

BACKGROUND: The intima-media thickness (IMT) of the carotid artery, as determined by ultrasonography, is useful for reflecting the extent of subclinical atherosclerosis. We investigated the relationship between IMT and the serum concentrations of small low-density lipoprotein (LDL) in diabetic patients. METHODS: The study was conducted with 27 Type 2 diabetic patients (14 males and 13 females; mean age=62.6+/-8.3 years) and 12 age-matched healthy controls. The LDL subfraction was measured using a polyacrylamide gel electrophoresis method. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) concentrations were measured by an enzyme immunoassay. The IMT was expressed as the maximum IMT (Max-IMT) and average IMT (Ave-IMT) of the carotid artery, measured by ultrasonography. RESULTS: Both the IMT and the small LDL concentrations were significantly increased in the diabetic patients compared with the healthy participants. The IMTs were significantly correlated with small LDL concentration and small LDL/total LDL more than LDL concentrations by multivariate analysis. The IMTs were not significantly correlated with the serum VEGF or PDGF concentrations. The patients with a larger IMT had a significantly higher prevalence of hypertension or ischemic heart disease than did the patients with a normal IMT. CONCLUSIONS: The increased small LDL concentrations and small LDL/total LDL, in addition to total LDL concentrations, in Type 2 diabetic patients are closely associated with increased IMT of the carotid artery.

Enhancement of Rho/Rho-kinase system in regulation of vascular smooth muscle contraction in tachycardia-induced heart failure.

OBJECTIVE: The Rho/Rho-kinase system regulates Ca(2+) sensitivity in vascular smooth muscle. A new drug, Y-27632, specifically inhibits Rho-kinase and hence decreases the phosphorylation of myosin light chain, thus reducing contraction. Here, we compare the effects of Y-27632 and nifedipine on the vasoconstrictor response of the femoral artery in heart failure. METHODS: Heart failure (HF) was produced by chronic rapid RV pacing (250 bpm, 28 days, six dogs). Indo1-AM was loaded into endothelium-denuded femoral artery segments for measuring intracellular [Ca(2+)]. Tension and changes in intracellular [Ca(2+)] [the change in the ratio (418 nm/468 nm) of Indo1 fluorescence (F(ratio))] were simultaneously measured in Krebs-Ringer solution. RESULTS: In HF: (i) norepinephrine (10 microM) produced greater tension (784+/-52 g/cm(2)) than in control (502+/-64 g/cm(2)) despite a similar increase in F(ratio), indicating increased Ca(2+) sensitivity in vascular smooth muscle; (ii) nifedipine attenuated this enhanced response by only a maximum of 27% at 1 micromol/l with a 56% reduction in F(ratio); (iii) Y-27632 attenuated it by a maximum of 80% at 100 micromol/l without a significant change in F(ratio); (iv) RhoA protein and mRNA expression levels in the femoral artery were up-regulated by +110% and +56%, respectively, while those of Rho-kinase were unchanged. CONCLUSIONS: The Ca(2+)-sensitizing mechanism involving the Rho/Rho-kinase system may be deeply involved in the enhanced arterial vasoconstriction seen in HF. Since Y-27632 attenuated this response in small arteries, it shows potential as a novel, potent vasodilator for the treatment of HF.

Altered stoichiometry of FKBP12.6 versus ryanodine receptor as a cause of abnormal Ca(2+) leak through ryanodine receptor in heart failure.

BACKGROUND: In the pathogenesis of cardiac dysfunction in heart failure, a decrease in the activity of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase is believed to be a major determinant. Here, we report a novel mechanism of cardiac dysfunction revealed by assessing the functional interaction of FK506-binding protein (FKBP12.6) with the cardiac ryanodine receptor (RyR) in a canine model of pacing-induced heart failure. METHODS AND RESULTS: SR vesicles were isolated from left ventricular muscles (normal and heart failure). The stoichiometry of FKBP12.6 per RyR was significantly decreased in failing SR, as assessed by the ratio of the B(max) values for [(3)H]dihydro-FK506 to those for [(3)H]ryanodine binding. In normal SR, the molar ratio was 3.6 ( approximately 1 FKBP12.6 for each RyR monomer), whereas it was 1.6 in failing SR. In normal SR, FK506 caused a dose-dependent Ca(2+) leak that showed a close parallelism with the conformational change in RyR. In failing SR, a prominent Ca(2+) leak was observed even in the absence of FK506, and FK506 produced little or no further increase in Ca(2+) leak and only a slight conformational change in RyR. The level of protein expression of FKBP12.6 was indeed found to be significantly decreased in failing SR. CONCLUSIONS: An abnormal Ca(2+) leak through the RyR is present in heart failure, and this leak is presumably caused by a partial loss of RyR-bound FKBP12.6 and the resultant conformational change in RyR. This abnormal Ca(2+) leak might possibly cause Ca(2+) overload and consequent diastolic dysfunction, as well as systolic dysfunction.

[A 62-year-old survivor with Ebstein's anomaly without right ventricular failure].

A 62-year-old woman was admitted our hospital because of concussion of the brain. The level of consciousness improved within several days. Cardiac examination was performed because the patient had experienced feelings of fainting since one year previously, and heart murmur also was heard. The electrocardiogram showed WPW configuration. At the same time that she complained of feelings of fainting, the electrocardiogram showed supraventricular tachycardia. The echocardiogram showed displacement of the septal tricuspid leaflet and mild tricuspid valve, regurgitation. Cardiac catheterization was performed and, using the intracardiac electrocardiogram, we confirmed atrialized right ventricle. We diagnosed this patient as having Ebstein's anomaly with WPW syndrome. The clinical manifestations of this anomaly are quite variable, depending upon the spectrum of pathology and the presence of associated malformations. It is well documented that a considerable proportion of these patients are able to survive into adult life. However, the patient who survives into the sixth decade without a sign of heart failure is extremely rare. We speculate that this patient had not developed right ventricular failure until her 60's because she had a milder form of Ebstein's anomaly and did not have any other congenital heart disease.

Kawasaki disease complicated by acute myocardial infarction due to thrombotic occlusion of coronary aneurysms 19 years after onset.

A 25-year-old man with a history of Kawasaki disease from the age of 7 had acute inferior myocardial infarction. Emergency right coronary arteriogram showed successive coronary aneurysms at the proximal to middle portion of the right coronary artery, and total occlusion at the proximal segment. Intracoronary thrombolysis was performed and the right coronary artery was recanalized. On left coronary arteriography, coronary aneurysms and mild localized stenoses at the inlet and outlet of the aneurysms were found. It was suggested that the myocardial infarction was caused by thrombotic occlusion of coronary aneurysms complicated with Kawasaki disease.

[Myocardial perfusion and left ventricular function during exercise evaluated by 201Tl myocardial scintigraphy and 99mTc radionuclide ventriculography in patients treated with PTCA].

To evaluate the effects of percutaneous transluminal coronary angioplasty (PTCA), we investigated myocardial ischemia and left ventricular function during exercise before and after successful PTCA in 30 patients. We used extent and severity scores of 201thallium (201Tl) exercise myocardial scintigraphy to assess myocardial ischemia and determined global and regional left ventricular ejection fraction (EF and REF) of 99mTc-RBC exercise radionuclide ventriculography to assess left ventricular function. The extent and severity scores of stress images were significantly less after PTCA than before PTCA. The scores of the redistribution images were unchanged before and after PTCA. Global EF during exercise was significantly higher after PTCA than before PTCA. There was no difference in resting global EF between before and after PTCA. Myocardial ischemia induced by exercise was semi-quantitatively analyzed as transient perfusion defect with severity score. Severity score was significantly less after PTCA than before PTCA. delta EF, which was obtained by subtraction of resting global EF from exercise one, was significantly higher after PTCA than before PTCA. However, the degree of improvement in myocardial ischemia and left ventricular function varied from patient to patient. In 17 patients with one-vessel left anterior descending artery disease, delta REF, which was determined by subtracting resting regional EF from exercise one, was significantly higher in septal and apical segments after PTCA than before PTCA. Myocardial ischemia and left ventricular function under exercise were alleviated by PTCA. However, the degree of improvement varied from patient to patient and it might have been affected by various factors including coronary dissection, edema, thrombus, restenosis, spasm, side branch stenosis or occlusion, distal thrombus, and myocardial hibernation.

A case of clinically diagnosed pure septal infarction.

Interventricular septal involvement in myocardial infarction is usually associated with infarction of the left ventricular anterior free wall, as the obstruction is at the major portion of the left anterior descending coronary artery. Acute myocardial infarction with obstruction only of the first septal branch is rare. We describe here a case of pure septal infarction. The case was diagnosed by emergency coronary arteriogram (CAG). Although the patient had a large first septal branch, his global left ventricular function was preserved. Abnormal findings were localized in only septal region as determined by left ventriculography (LVG), two-dimensional echocardiography (2DE), and 99mtechnetium pyrophosphate (99m Tc-PYP) and 201thallium (201Tl) myocardial scintigraphy.

Beta-protein amyloid is widely distributed in the central nervous system of patients with Alzheimer's disease.

To clarify the distribution, morphology, and density of amyloid deposits in patients with Alzheimer's disease (AD), tissue sections from various areas of the central nervous system of 14 patients with AD and from 20 nondemented aged controls were investigated immunohistochemically using anti-beta protein antiserum. beta-protein amyloid deposits were present not only in the cores of the senile plaques and in the vascular wall (amyloid angiopathy), but also in various sized plaque-shaped fibrillary, perivascular, subpial, and subependymal deposits. Amyloid deposits were found mainly in the cerebral cortex in nondemented controls, while in AD they were distributed widely in the regions that were not affected in nondemented controls. The positivity of amyloid deposits in AD was 100% in the cerebral cortex, hippocampus, amygdala, thalamus, caudate nucleus, claustrum, hypothalamus, nucleus basalis of Meynert, and cerebellar cortex. Putamen and brain-stem nuclei were affected frequently, and the spinal cord, dentate nucleus, and globus pallidus were sometimes (less than 50%) affected. This result provides an evidence that Alzheimer's disease is a beta-protein amyloidosis of the central nervous system. An assessment of the distribution of amyloid deposits should prove to be useful for the histopathologic diagnosis of AD.

[Atrial septal defect diagnosed and quantitatively-evaluated by transesophageal two-dimensional Doppler echocardiography].

Transesophageal two-dimensional (2-D) echocardiography (TEE: horizontal sector scan) combined with the pulsed Doppler method was performed to determine the size of atrial septal defect (ASD) and to measure directly shunt flow signals through the defects in six ASD patients (32 +/- 16 yrs) confirmed by cardiac catheterization. The size of the defect in the horizontal dimension was measured by TEE; the vertical dimension of the defect was determined from the distance of the transesophageal probe positions of the rostral and caudal margins of the defect. The size of defect determined by TEE was compared with that observed at surgery. Shunt flow signals were recorded by the pulsed Doppler technique by setting the sample volume at the center of the defect. Left-to-right shunt flow was determined as follows: shunt flow volume (ml/min) = mean velocity (cm/s) x the area of a defect (cm2) x 60. The shunt flow was compared with that obtained by the Fick's method. In all patients, TEE accomplished unequivocal visualization of a defect. The defect sizes by TEE correlated well with measurements obtained at surgery (r = 0.66). A clear laminar shunt flow with its peak in late systole and atrial systole was observed. Significant correlations were obtained between shunt volumes by TEE and those by the Fick's method (r = 0.91, p less than 0.05). Thus, TEE proved a useful method for diagnosing ASD and for evaluating shunt flow volumes.

[Detection of mural thrombi and analysis of blood flow velocities in the left atrial appendage using transesophageal two-dimensional echocardiography and pulsed Doppler flowmetry].

To correlate blood flow velocities with thrombogenesis in the left atrium (LA) and left atrial appendage (LAA), we performed transesophageal two-dimensional echocardiography (Eso 2-D Echo) combined with pulsed Doppler flowmetry, which was developed in our laboratory. Thirty-eight patients were studied; 1) 15 who had sinus rhythm including four with mitral stenosis (MS) and 11 normal subjects, and 2) 23 with atrial fibrillation (Af). The patients with Af were classified as lone Af (nine cases); Af-CI: Af with cerebral infarction having no MS (four cases); and Af-MS: Af with MS (10 cases). In four of 10 patients with Af-MS, mural thrombi were detected in the LA or LAA by Eso 2-D Echo, but they were not visualized by conventional echocardiography. In lone Af and Af-CI, however, abnormal echoes in the LAA were not observed by Eso 2-D Echo. Thus, Eso 2-D Echo proved superior to conventional 2-D echocardiography in detecting mural thrombi in the LA or LAA. In sinus rhythm, a biphasic flow pattern followed the P wave on the ECG. It was observed in the vicinity of the junction between the LA and LAA. In Af a flow with a saw-tooth appearance was observed throughout the cardiac cycle. The peak flow velocity in the LAA was significantly less in Af than in sinus rhythm (p less than 0.05). Especially in Af-MS, the peak flow velocity was markedly decreased (1 +/- 4 cm/sec: mean +/- SD) compared with those of the other Af groups (p less than 0.01), and it was significantly less in Af-CI (11 +/- 5 cm/sec) than in patients with lone Af (21 +/- 9 cm/sec) (p less than 0.05). These results indicate that analysis of blood flow velocities in the LAA by Eso 2-D Echo is of great value in assessing thrombogenesis in the LAA, and the patients with Af, even without MS, who have markedly reduced peak flow velocities in the LAA, should be prophylactically anticoagulated, because stagnation of blood is strongly suspected.

[Left ventricular isovolumic relaxation time estimated by the aortic root echocardiogram].

Dual echocardiogram was recorded simultaneously with phonocardiogram (PCG) to analyze the isovolumic relaxation time (IRT) of the left ventricle (LV) in 85 patients with various heart diseases and in 23 normal subjects. The measurements used were time intervals from the onset of the aortic component of the second heart sound (IIA) to the onset of the posterior deflection of the posterior aortic wall in the aortic root echocardiogram (X) (IIA-X interval), and to the onset of the most rapid opening motion of the anterior mitral leaflet (D') (IIA-D' interval) during early diastole. 1. The IIA-X interval was directly proportional to the IIA-D' interval in the entire study population. 2. The IIA-X interval was prolonged with advancing age in normal subjects. 3. The IIA-X interval was significantly increased in patients with hypertensive heart disease, old myocardial infarction, hypertrophic cardiomyopathy, and dilated cardiomyopathy, but significantly decreased in patients with mitral stenosis. Thus, the IIA-X interval, which was measured easily and noninvasively from the aortic root echocardiogram is a reliable indicator of the isovolumic relaxation time of the left ventricle, as well as of the IIA-D' interval.

An autopsy case of chronic nodular encephalomyelitis simulating neuro-Behçet syndrome.

A 29-year-old man suffered from neurological symptoms such as urinary disturbance, changes in personality, gait and speech disturbances, amnesia, myoclonus, dysphagia and muscle atrophy for nine years with exacerbations and remissions. A postmortem examination revealed many inflammatory and necrotic foci in the brain and spinal cord, especially in the brainstem and cerebral cortex. Numerous minute scar foci were also scattered in the gray matter, accompanied by some demyelinating lesions in the white matter. The presence of microthrombi and plasma exudation into the vessel wall suggested the importance of vascular factors in the pathogenesis of these CNS lesions. Peripheral neuropathy was also present. The neuropathological features were almost the same as those of neuro-Behçet syndrome, but he lacked the extraneural symptoms of Behçet disease.

[Functional significance of left ventricular distortion in patients with right ventricular volume or pressure overloading].

To evaluate the effects of left ventricular (LV) distortion on its pump function, the LV cavity shape was analyzed by two-dimensional echocardiography in normal subjects and in patients with right ventricular (RV) volume or pressure overload. The functional significance of LV distortion in the short-axis sections was evaluated by an index of the efficiency of ejection (E) of endocardial circumferential fiber length (ECL) shortening in reducing LV cavity area during systole; E = measured systolic area reduction/ideal systolic area reduction X 100 (%), where an ideal area at end-diastole or end-systole was computed for the measured ECL, assuming its shape to be perfectly circular (ideal area = ECL2/4 pi), and then an ideal systolic area reduction was determined. E at the chordal level was termed Ech. In patients with atrial septal defect (ASD), the LV cavity was distorted at end-diastole and became more circular at end-systole. Since this characteristic change during systole diminished the E, and the values of E at the chordal level (Ech) were significantly lower in ASD than those in normal subjects (89.4 +/- 4.4% vs 98.3 +/- 0.8%, p less than 0.001), strongly suggesting impairment of the efficiency of LV pump function in ASD. In patients with pulmonary hypertension, the LV cavity was more distorted at systole, and a decrease in cavity area at end-systole with the distorted LV contributed to increased systolic area reduction. Thus, the values of Ech in this group exceeded 100% in five of nine patients (103.8 +/- 12.3%). In other words, when marked RV systolic overload exists, an increase in LV systolic area reduction due to progressive LV compression will occur against LV systolic pressure. This phenomenon suggests the existence of "cardiac massage on the LV by the RV with elevated pressure". In conclusion, it was strongly suggested that the efficiency of LV pump function is modulated by RV overload through dynamic changes in the LV shape.

[Echocardiography in a case of acute tuberculous pericarditis which progressed to constrictive pericarditis].

A case of acute tuberculous pericarditis with massive pericardial effusion progressed to constrictive pericarditis under echocardiographic observation during one year. This 59-year-old man was hospitalized because of dyspnea. On admission, his physical examination revealed a paradoxical pulse, engorged jugular veins, hepatomegaly, and pitting edema in the pretibial regions. Chest radiography revealed an enlarged cardiac silhouette and a marked left pleural effusion. His echocardiogram showed a massive pericardial effusion. A biatrial echogram recorded by esophageal echocardiography showed a massive pericardial effusion anterior to the right atrial free wall. Echocardiography performed four months after commencing therapy revealed a reduction in the pericardial effusion, and normal motion of the interventricular septum and posterior wall. However, the motion of the interatrial septum was already abnormal and the excursion of the right atrial free wall was markedly reduced. These finding were similar to those in constrictive pericarditis, as previously reported. Eleven months after admission, both conventional and esophageal echograms showed findings typical of constrictive pericarditis. Thus, in this case, the abnormal biatrial dynamics were recognized earlier than the abnormal left ventricular wall motion.