Osteoprotegerin is secreted into the coronary circulation: a possible association with the renin-angiotensin system and cardiac hypertrophy.

The circulating osteoprotegerin (OPG) level reflects a series of cardiovascular diseases; however, the source(s) of circulating OPG remain(s) to be determined. This study explored whether OPG is released in the coronary circulation and whether it is associated with cardiac structure and function. Fifty-six patients (67±10 years old, male 57%, hypertension 73%, coronary artery disease 50%) were enrolled, and blood samples were collected simultaneously from the orifice of the left coronary artery (CA) and the coronary sinus (CS) after angiography. The concentration of OPG was higher in the CS than in the CA (7.7±4.1 vs. 6.7±3.6 pmol/l, p<0.001). The trans-cardiac OPG concentration was significantly (p=0.019) decreased in patients who have been prescribed either an angiotensin converting enzyme inhibitor or an angiotensin II type 1 receptor blocker (ACEI/ARB). In patients subgroup who did not take an ACEI/ARB (n=27), the trans-cardiac OPG level was positively correlated with age (r=0.396, p=0.041) and relative wall thickness of left ventricle (r=0.534, p=0.004). In multivariate linear regression analysis, relative wall thickness remained to be the independent variable for the trans-cardiac OPG level (p=0.004). Moreover, trans-cardiac OPG was significantly (p=0.021) increased in patients with relative wall thickness greater than 0.45 but it did not differ if the left ventricular mass index was increased (≥116 for males, or ≥ 104 for females, g/m(2)) or not (p=0.627). This study suggests that OPG is secreted into the coronary circulation and is associated with concentric remodeling/hypertrophy of LV, possibly in interactions with the renin-angiotensin system.

Angiotensin II stimulates cardiac adrenomedullin production and causes accumulation of mature adrenomedullin independently of hemodynamic stress in vivo.

Adrenomedullin is a potent hypotensive peptide that may act on myocytes to inhibit hypertrophy and on fibroblasts to inhibit growth in vitro induced by mechanical stretching and angiotensin II. Adrenomedullin is processed from the inactive intermediate adrenomedullin precursor with a glycine extension, which is subsequently converted to biologically active mature adrenomedullin by enzymatic amidation. Total adrenomedullin is the sum of intermediate and mature adrenomedullin. We examined the effect of a subpressor dose of angiotensin II on the production of left ventricular adrenomedullin and on protein levels of mature adrenomedullin in the left ventricle in vivo. We also investigated whether the effect is mediated by the angiotensin II type 1 receptor. Concentrations of total and mature adrenomedullin in the left ventricle and mature adrenomedullin-to-intermediate adrenomedullin ratio were significantly increased by angiotensin II infusion, regardless of pressure overload. Total and mature adrenomedullin concentrations significantly correlated with the weight of the left ventricle. Furthermore, increased adrenomedullin gene expression and protein levels were completely suppressed by a subdepressor dose of angiotensin II type 1 receptor blocker. In conclusion, angiotensin II stimulates the production of cardiac adrenomedullin and accumulates mature adrenomedullin in the left ventricle independently of hemodynamic stress. These processes are partially regulated through the angiotensin II type 1 receptor in vivo.

Clinical manifestations of influenza a myocarditis during the influenza epidemic of winter 1998-1999.

OBJECTIVES: The clinical features of myocarditis that developed during the influenza epidemic of winter 1998-1999 were investigated to emphasize the need for medical attention to this disease. METHODS: Nine patients were treated under diagnoses of acute myocarditis during the winter of 1998-1999. Five (two males and three females, mean age 52 +/- 18 years) were examined with myocarditis associated with influenza A. The diagnosis of influenza A myocarditis was based on electrocardiographic and echocardiographic abnormalities, increased creatine kinase levels and at least a four-fold increase in influenza A virus titers using paired sera. RESULTS: All patients had preceding flu-like symptoms and fever. Cardiac involvement developed between 4 and 7 days after the onset of influenza symptoms. Dyspnea progressively worsened in three patients, one went into shock and one had persistent fever, cough and mild dyspnea without apparent cardiac symptoms. Three patients had ST elevation associated with Q waves and one had complete left bundle branch block. The creatine kinase levels were abnormally increased and global wall motion of the left ventricle on echocardiography was decreased in all patients. Two patients had diagnoses of fulminant myocarditis. One patient died of pneumonia following cerebral infarction, but the left ventricular dysfunction normalized in the remaining four patients. CONCLUSIONS: Cardiac involvement occurred between 4 and 7 days after the onset of influenza symptoms, and worsening dyspnea was the most common symptom. Electrocardiography, echocardiography and creatine kinase levels should be checked to determine the potential for cardiac involvement when patients present with suspected influenza associated with worsening dyspnea or prolonged weakness. Increasing the awareness of influenza myocarditis may help in the earlier identification and treatment of this disease during influenza epidemics.

Diastolic wall stress and ANG II in cardiac hypertrophy and gene expression induced by volume overload.

We investigated the effects of diastolic wall stress (WS) and angiotensin II (ANG II) on the left ventricular (LV) hypertrophy (LVH) induced by volume overload and on the gene expression of LV adrenomedullin (AM) and atrial natriuretic peptide (ANP) in volume overload. Diastolic WS was pharmacologically manipulated with (candesartan) or without (calcium channel blocker manidipine) inhibition of ANG II type 1 receptors in aortocaval-shunted rats over 6 wk. Diastolic WS reached a plateau at 2 wk and subsequently declined regardless of further LVH. Although diastolic WS was decreased to a similar extent by both compounds, candesartan blunted LVH over 6 wk, whereas manidipine blunted LVH at 2 wk but not after 4 wk. Levels of AM and ANP gene expression increased as LVH developed but were completely suppressed by candesartan over 6 wk. ANP expression level was also attenuated by manidipine over 6 wk, whereas AM expression level was suppressed at 2 wk but not after 4 wk by manidipine. We concluded that diastolic WS and ANG II might be potent stimuli for the LVH and LV AM and ANP gene expression in volume overload and that diastolic WS could be relatively involved in the early LVH and in the gene expression of ANP rather than of AM.

[One-hour protocol stress myocardial scintigraphy: prospective study of diagnostic accuracy for the detection of coronary artery stenosis].

A one-hour protocol for stress myocardial scintigraphy using technetium-99m-tetrofosmin (Tc-tetrofosmin) was compared with coronary arteriography for the detection of coronary artery stenosis in 90 consecutive patients without prior myocardial infarction, revascularization procedure or vasospastic angina. Tc-tetrofosmin stress myocardial scintigraphy acquired a rest image 20 min after intravenous administration of Tc-tetrofosmin (185 MBq, 1/5 vial) using a three-head gamma camera collecting 20-sec views over 360 degrees. The stress test using bicycle ergometer was performed and administration of Tc-tetrofosmin (740 MBq, 4/5 vial) was repeated at the peak stress point. The stress image was acquired 15 min after the second injection with 5-sec views over 360 degrees. Coronary arteriography revealed the presence of significant coronary artery stenosis (> 75%) in 56 vessels of 45 patients, including 35 patients with single-vessel disease, 5 with two-vessel disease, 2 with three-vessel disease, and 3 with left main trunk disease. The overall sensitivity and specificity for the detection of coronary artery disease by visual analysis were 91.1% and 77.8%, respectively, and by quantitative analyses (using bull's-eye method) were 95.6% and 91.1%, respectively. The individual stenotic vessel sensitivities in the right coronary artery, left anterior descending artery, and left circumflex artery were 84.6%, 90.9%, and 78.6%, respectively. The specificities were 97.3%, 95.9%, and 100.0%, respectively. These results suggest that stress myocardial scintigraphy using the present new protocol is a promising approach for the detection of coronary artery stenosis.

[Reexamination of hepatic falciform artery: angiographic study].

Supraumbilical skin complication during hepatic artery infusion chemotherapy or transcatheter arterial chemoembolization (TACE) for liver tumor has been reported by some authors. This complication is thought to be caused by the flow of chemotherapeutic, agent and embolus into the hepatic falciform artery (HFA). It is important for angiographers to be aware of the presence of HFA to prevent possible supraumbilical skin complication. The rate of visualization of the HFA on angiography has been considered to be only about 2%. In a retrospective study of celiac angiograms performed in 200 patients, we found an incidence of 32/200 (16%). The proximal side of this artery may be tortuous. In all cases, the flow of the HFA is slower than that of the hepatic artery. The paraumbilical vein was visualized with the HFA in 18 cases. Chemotherapy or transcatheter arterial chemoembolization was performed in 10 patients, and there was no postprocedure supraumbilical skin complication.

Retroaortic left renal vein with renal vein hypertension causing hematuria.

We describe a case of retroaortic left renal vein with hematuria. In this case, pullback pressure from the retroaortic left renal vein to the inferior vena cava revealed left renal vein hypertension according to criteria of the "nutcracker phenomenon." We stress that left renal vein anomaly including retroaortic left renal vein can cause clinical symptoms such as hematuria.

MR imaging of hepatocellular carcinoma. Correlation of metal content and signal intensity.

In order to clarify the factors contributing to the signal intensities (SIs) of HCC on T1-weighted images, the amount of water, lipid, copper (Cu), iron (Fe), and manganese (Mn) was determined in HCC and surrounding hepatic parenchyma of 13 patients. The relationships among these findings, the histopathologic findings, and the SIs of T1-weighted images were evaluated. Among the 13 HCC, 3 had a high SI, 5 were isointense, and 5 had a low SI on T1-weighted images compared to the surrounding hepatic parenchyma. The paramagnetic ions which contributed to the SI patterns were assumed to be Cu in HCC (38.0 +/- 62.4 micrograms/g ww), and Fe in the liver (61.1 +/- 42.4 micrograms/g ww) and HCC (40.0 +/- 34.3 micrograms/g ww). In 8 HCC with high- or isointensity, 2 were grades I, 5 were grade II, and one was grade III according to the Edmondson-Steiner's histopathologic classification. It is concluded that the SI patterns alone can not be a sign of low grade malignancy because of the existence of Fe in livers and HCC.

Colonic submucosal tumors: comparison of endoscopic US and target air-enema CT with barium enema study and colonoscopy.

PURPOSE: To compare the imaging characteristics of colonic submucosal tumors at endoscopic ultrasound (US) and target air-enema computed tomography (TACT) with those at conventional double-contrast barium enema study and colonoscopy. MATERIALS AND METHODS: Twenty consecutive patients with suspected colonic submucosal tumors at barium enema study and colonoscopy underwent endoscopic US, TACT, or both. Morphologic features and posture-related change in shape of tumor were evaluated with barium enema study, color and consistency of tumor with colonoscopy, internal echogenicity of tumor and layer of origin in normal colonic wall with endoscopic US, and CT attenuation number with TACT. RESULTS: Eight lipomas, seven carcinoids, three leiomyomas, four lymphangiomas, and one hemangioma were found at histologic examination. Lipomas and lymphangiomas had characteristic findings at endoscopic US and TACT. The differential diagnosis of the other submucosal tumors was facilitated by using endoscopic US. CONCLUSION: Endoscopic US and TACT may play a valuable role in the evaluation of colonic submucosal tumors.

Imaging study on the mode of development and changes in avascular necrosis of the femoral head in systemic lupus erythematosus: long-term observations.

To find out when and how avascular necrosis of the femoral head (ANFH) develops in patients with SLE who are receiving corticosteroids, we carried out a 3-yr prospective study using imaging methods. Twenty-three patients with SLE who were free of hip pain and radiographically negative were enrolled in the study. Initially, abnormal findings characteristic of ANFH were detected in eight (35%) and six (26%) patients on MRI and radionuclide uptake bone scanning, respectively. During a 3-yr observation period abnormalities on MRI, bone scanning and radiography were found in four, five and four patients, respectively and three patients developed hip pain. Analyses of imaging changes demonstrated that only a small proportion of patients (2/8, 25%) who initially showed abnormal MRI progressed to be radiographically positive for ANFH over the 3 years. High doses of corticosteroids over the 3-yr period were to be responsible for the emergence of change in MRI abnormalities. It is also suggested that abnormal MRI findings tend to develop either within a relatively short interval after the start of corticosteroid treatment or are associated with the exacerbation of SLE.

CT of intraabdominal desmoid tumors: is the tumor different in patients with Gardner's disease?

OBJECTIVE: A retrospective study of abdominal CT scans of patients with proved intraabdominal desmoid tumors was done to determine if any objective characteristics exist to differentiate desmoids related to Gardner's syndrome from isolated desmoids. Because the desmoid tumors of Gardner's syndrome can predate the diagnosis of Gardner's syndrome, it would be helpful to know which patients with desmoids need careful follow-up studies as well as initial workup for Gardner's syndrome and all its ramifications. Also, it would be important to differentiate benign from malignant desmoids associated with Gardner's syndrome. It was hoped that the location, enhancement characteristics, and/or the presence or absence of infiltration might be of value. We were interested in noting if, over time, the growth characteristics of desmoids found in Gardner's syndrome were different from those of isolated desmoids. MATERIALS AND METHODS: We reviewed 101 abdominal CT scans obtained in 23 patients during a 13-year period. Forty desmoid tumors were intraabdominal, including 30 lesions associated with Gardner's syndrome in 13 patients and 10 desmoids of the idiopathic form in 10 patients. These tumors were studied to define location; whether they were single or multiple; and whether they had any specific CT characteristics regarding margins, attenuation numbers, or contrast enhancement. RESULTS: Desmoid tumors associated with Gardner's syndrome were more likely to be multiple (38%, five of 13 patients) and to involve the mesentery (60%, 18 of 30 tumors) and the abdominal wall (40%, 12 of 30 tumors), whereas isolated desmoid tumors were singular (all 10 patients) and were located in the retroperitoneum (six cases), pelvis (three), and anterior wall (one). Desmoids related to Gardner's syndrome also tended to be smaller (mean diameter, 4.8 cm) than idiopathic desmoids (mean diameter, 13.8 cm). No differentiating CT characteristics regarding margins, attenuation numbers, or response to contrast material were ascertained. Ten new lesions (seven intraabdominal, three mesenteric) developed in three patients with Gardner's syndrome, whereas no new intraabdominal lesions developed in patients with idiopathic desmoids. Follow-up data on 16 surgically resected desmoids in nine patients (seven with Gardner's syndrome and two with isolated desmoids) revealed seven local recurrences (two in the two patients with isolated desmoids and five in two patients with Gardner's syndrome). CONCLUSION: No CT characteristics, such as attenuation values, margins, and response to the contrast material, were found that would enable differentiation between isolated intraabdominal desmoids and those associated with Gardner's disease. Desmoid tumors associated with Gardner's syndrome tend to occur in the mesentery and abdominal wall, whereas isolated desmoids involve the retroperitoneum and pelvis. When studying CT scans obtained over time, new lesions were noted to develop in a few of the patients with Gardner's syndrome (three of 13), whereas no new lesions were found in patients with isolated desmoids.

Histopathologic correlation of two-phased dynamic incremental CT in hepatocellular carcinomas using multivariate analysis.

In order to grade pathologic factors that influence CT findings in hepatocellular carcinomas (HCCs), the CT-pathologic correlation was assessed statistically using univariate and multivariate analyses of 75 lesions. CT findings of early and delayed phase scans using two-phase dynamic incremental CT (TDICT) were compared with pathologic findings in resected specimens to calculate a category score for each pathologic finding. According to category scores, histopathologic differentiation and growth pattern were the major determinants of tumor density. Determinants of the internal structure of tumors were cytological variants, histologic differentiation, and macroscopic classification, in that order. Macroscopic classification, histologic differentiation, fibrous capsule characteristics, and growth pattern were important in descending order for tumor margins. Histologic differentiation was the most important factor for determining TDICT findings in HCCs. The CT findings were modified by parenchymal liver disease and cytologic variants.

"CT angiogram sign" in obstructive pneumonitis and pneumonia.

OBJECTIVE: The "CT angiogram sign" in dynamic pulmonary CT consists of enhanced branching pulmonary vessels in a homogeneous hypoattenuating consolidation of lung parenchyma and is reportedly useful for diagnosing lobar bronchioloalveolar cell carcinomas. MATERIALS AND METHODS: To identify cases exhibiting the CT angiogram sign, we retrospectively reviewed the reports of 5,500 dynamic incremental CT examinations of the chest. RESULTS: We identified the CT angiogram sign in five patients with obstructive pneumonitis due to lung tumors and four patients with pneumonias. CONCLUSION: The CT angiogram sign can be observed in pulmonary consolidation of varying etiologies.

Leiomyosarcoma of the kidney: CT and MR appearance.

A case of leiomyosarcoma of the kidney is reported here with its CT and MRI manifestations correlated to the pathologic findings. The leiomyosarcoma appeared as a well-defined multinodular mass of varying density and signal intensity on CT and MRI, respectively. The low signal-intensity regions on T2-weighted MRI exhibited delayed enhancement on CT and contained more fibrous tissues than did other sites that had more spindle-shaped muscle cells. Knowledge of the MR and CT characteristics may permit radiologists to refine the diagnosis of renal leiomyosarcoma considerably.

Intrahepatic peripheral cholangiocarcinoma: two-phased dynamic incremental CT and pathologic correlation.

To elucidate the characteristic CT findings of intrahepatic peripheral cholangiocarcinoma, two-phased dynamic incremental CT scans of 20 cholangiocarcinomas in 16 patients were carefully analyzed. Dynamic incremental CT scanning was performed after intravenous administration of 100 ml iodinated contrast medium at a rate of 2 ml/s using a power injector. The CT scans (8-16 sections) were obtained during 45-110 s (early phase) and 6-7 min (delayed phase) after commencement of the injection of the contrast medium. On CT, 55% (11 of 20) of intrahepatic peripheral cholangiocarcinomas appeared hypodense in both phases. Most of the tumors (80%) appeared hypodense in the early phase and had increased CT numbers in their delayed images. Lymphadenopathy was observed in 69% (11 of 16) of patients whose main tumors exceeded 3 cm in diameter. All tumors appeared irregular or indistinct. Twenty percent (4 of 20) of the cholangiocarcinomas were difficult to distinguish from hepatocellular carcinomas or hemangiomas.

Large intra-abdominal desmoid tumors in a patient with familial adenomatosis coli: their rapid growth detected by computerized tomography.

A case of familial adenomatosis coli with large intra-abdominal desmoid tumors is described. The patient initially complained of an abdominal mass, which was diagnosed as a desmoid tumor after surgical resection. Further examinations revealed numerous polyps of the colon which were histologically diagnosed as adenomas. Despite intensive medical therapy, the desmoid tumors rapidly increased in size and number, and resulted in abscess and cavity formation that involved the ileum. Although desmoid tumors are classically benign in nature, we consider these tumors to be a therapeutic problem in patients with familial adenomatosis coli.

MRI of bronchogenic cysts.

The MR appearance of eight bronchogenic cysts is reported. All the cysts appeared homogeneous and were of very high signal intensity, approximating that of CSF on spin-echo T2-weighted imaging, and of relatively high intensity, between that of muscle and subcutaneous fat on T1-weighted imaging. The cysts were round or ovoid and were well demarcated. These findings are consistent with the fluid-containing properties of cysts.

Hepatocellular carcinoma: prospective assessments of the T-factor with CT, US, and MR imaging.

The capabilities of computed tomography (CT), ultrasonography (US), and magnetic resonance (MR) imaging were studied in order to determine the role of each of these noninvasive examinations for estimating the T-factor of hepatocellular carcinomas (HCCs). Fifty-one patients with surgically proven HCCs received CT (50 patients), US (46 patients), and MR (44 patients). The images of CT, US, and MR were prospectively evaluated for main tumor size, intrahepatic metastases, and vascular invasion, which compose the T-factor of HCC, and compared to pathological results. The sizes of the main tumor were estimated correctly by all examinations. For estimating intrahepatic metastases, US (74%) and MR (73%) were superior to CT (65%). For estimating portal invasion, CT (79%) was superior to US (70%) and MR (66%), because CT could demonstrate the segmental staining caused by portal invasion. The estimates of hepatic venous invasion were difficult during any of the examinations. We conclude that presurgical evaluations of the T-factor require the use of US and CT or MR and CT.