Differences in atherosclerotic profiles between patients with thoracic and abdominal aortic aneurysms

Differences in atherosclerotic profiles between patients with thoracic aortic aneurysm (TAA) and patients with abdominal aortic aneurysm (AAA) have not been studied. We retrospectively studied the clinical records of 343 consecutive patients (132 TAA and 211 AAA) who were admitted to our hospital for elective repair of aortic aneurysms between July 2001 and December 2004. Clinical variables were compared between patients with TAA and those with AAA by using a univariate analysis, and those achieving statistical significance were subsequently assessed in a multivariate analysis. The incidence of coronary artery disease (CAD) (53% vs 23%, p <0.0001), 3-vessel coronary disease (41% vs 10%, p <0.0001), male gender (86% vs 74%, p <0.01), smoker (88% vs 76%, p <0.01), chronic obstructive pulmonary disease (COPD) (30% vs 15%, p <0.01), and diabetes mellitus (39% vs 23%, p <0.01) were significantly higher in patients with AAA than in those with TAA. In contrast, the incidence of hypertension (91% vs 81%, p <0.05), saccular-type aneurysm (61% vs 7%, p <0.0001), and body mass index (24.1 +/- 3.1 vs 23.2 +/- 3.5, p <0.05) were significantly higher in patients with TAA than in those with AAA. Multivariate stepwise logistic analysis revealed that CAD (odds ratio [OR] 3.65; 95% confidence interval [CI] 2.12 to 6.42; p <0.0001), COPD (OR 2.05; 95% CI 1.11 to 3.89; p <0.05), and diabetes mellitus (OR 1.85; 95% CI 1.06 to 3.27; p <0.05) were associated with AAA, and that body mass index (OR 9.39; 95% CI 2.0 to 46.8; p <0.01), hypertension (OR 3.09; 95% CI 1.48 to 6.87; p <0.01), and cerebral infarction (OR 2.83; 95% CI 1.25 to 6.50; p <0.05) were associated with TAA. In conclusion, atherosclerotic profiles are significantly different between patients with TAA and patients with AAA. This result suggests the possibility that mechanisms underlying the development of aortic aneurysms may differ between TAA and AAA, and, from the perspective of prevention, provides further stimulus for the modification of key risk factors for atherosclerosis.     

Cytotoxic Chemotherapy Successfully Induces Durable Complete Remission in 2 Patients with Mosquito Allergy Resulting from Epstein-Barr Virus-Associated T-/Natural Killer Cell Lymphoproliferative Disease

Recent findings indicate that Epstein-Barr virus (EBV)-infected T-/natural killer (NK) cells play an important role in the pathogenesis of mosquito allergy, and most patients with mosquito allergy die early in life if not properly treated. Over the last 7 years, we have been using combination chemotherapy and allogeneic stem cell transplantation for the treatment of EBV-associated T-/NK cell lymphoproliferative disease (LPD) in which chronic active EBV infection and mosquito allergy were included. As of this writing, we have successfully treated 2 patients with mosquito allergy with chemotherapy in which EBV-infected T-/NK cells were eradicated. The findings suggest the possible role of chemotherapy in the treatment of EBV-associated T-/NK cell LPD.     

Captopril improves impaired endothelium-dependent vasodilation in hypertensive patients.

Animal studies suggest that some angiotensin converting enzyme inhibitors augment endothelium-dependent vasorelaxation. We aimed to determine if captopril augments endothelium-dependent vasodilation in middle-aged hypertensive patients. By using strain-gauge plethysmography, forearm vasodilation evoked with intra-arterial acetylcholine (4, 8, 16, and 24 micrograms/min) or nitroprusside (0.2, 0.4, 0.8, and 1.2 micrograms/min) was examined before and after captopril administration (25 mg per os). Before captopril, forearm vasodilation with acetylcholine was less in hypertensive patients (n = 12) than in age-matched (n = 7) or young (n = 7) normotensive subjects, but forearm vasodilation with nitroprusside did not differ among the three groups. Captopril improved forearm vasodilation in hypertensive patients (n = 7) with acetylcholine but nitroprusside did not. In contrast, nifedipine (10 mg per os) did not alter forearm vasodilation with acetylcholine or nitroprusside in hypertensive patients (n = 5). The decreases in mean blood pressure caused by captopril and nifedipine in hypertensive subjects were comparable. Captopril did not alter forearm vasodilation with acetylcholine or nitroprusside in young normotensive subjects (n = 7). These results suggest that captopril in hypertensive patients may acutely improve impaired endothelium-dependent forearm vasodilation that does not result from reduction in blood pressure per se.     

Attenuated forearm vasodilative response to intra-arterial atrial natriuretic peptide in patients with heart failure

It has been shown that renal responses to atrial natriuretic peptide (ANP) are markedly attenuated in patients with heart failure. This study aimed to determine if vasodilative response to ANP is altered in patients with heart failure. In patients with heart failure (n = 7) and age-matched normal subjects (n = 7), forearm blood flow was measured using a strain-gauge plethysmograph during intra-arterial infusion of alpha-human ANP (50, 100, 200, and 400 ng/min) or nitroglycerin (100, 200, 400, and 600 ng/min). Forearm vasodilatation evoked with intra-arterial alpha-human ANP in patients with heart failure was considerably less (p less than 0.01) than that in normal subjects. In contrast, nitroglycerin produced comparable forearm vasodilatation in the two groups. Plasma ANP and cyclic guanosine monophosphate (GMP) levels at rest were higher in patients with heart failure than in normal subjects (p less than 0.05 for both), but the increases in plasma ANP and cyclic GMP in the venous effluents during intra-arterial ANP infusion did not differ between the two groups. These results indicate that the direct vasodilative effect of ANP on forearm vessels was attenuated in patients with heart failure as compared with that in normal subjects. The mechanisms responsible for this alteration are not clear but might involve mechanisms other than down-regulation of the ANP receptors because the increases in venous plasma cyclic GMP caused by intra-arterial ANP were comparable between patients with heart failure and normal subjects.     

Clinicopathological features of "intraductal papillary neoplasm of the bile duct" and patient outcome after surgical resection

BACKGROUND/AIMS: Intraductal papillary neoplasm of the bile duct (IPNB) represents a biliary papillary tumor mainly growing in the bile duct lumen resembling intraductal papillary mucin-producing neoplasm of the pancreas. However, its clinical spectrum and characteristics have not been fully evaluated. METHODOLOGY: To define the clinicopathologic characteristics and prognosis of IPNB patients, 6 cases of IPNB who underwent surgical resection are presented. RESULTS: Patients were 3 males and 3 females, aged between 47 and 79 years. Five patients had histories of hepatobiliary disease. Imagery showed cystic or diffuse dilatation of the bile ducts. Tumor markers were not valuable for diagnosis. All patients underwent hemihepatectomy with or without resection of the caudate lobe or extrahepatic bile duct. Examination showed polypoid tumors in 5 cases though 1 case had no evident tumor. Mucin was observed in 3 cases. Five cases were well-differentiated adenocarcinoma and 1 had poorly differentiated adenocarcinoma. Vascular invasion was rare and lymph node metastasis was not observed. In-situ spread of carcinoma was seen along biliary mucosa in 3 cases. Five cases survived without tumor relapse for long periods but 1 died of tumor recurrence at 31 months. CONCLUSIONS: Complete resection of IPNB based on accurate preoperative assessment of tumor extension provides a good prognosis.     

1,25-dihydroxyvitamin D suppresses circulating levels of parathyroid hormone in a patient with primary hyperparathyroidism and coexistent sarcoidosis

CONTEXT: PTH is excessively secreted to develop hypercalcemia and accelerate bone turnover in patients with primary hyperparathyroidism. PTH stimulates the production of 1,25-dihydroxyvitamin D [1,25(OH)2D] that in turn suppresses the synthesis of PTH in parathyroid cells. OBJECTIVE: The objective of the study was to clarify whether 1,25(OH)2D indeed inhibits circulating levels of PTH and influences bone turnover, even in a patient with primary hyperparathyroidism. DESIGN, SETTING, AND PATIENT: We evaluated PTH levels in a patient with primary hyperparathyroidism and coexistent sarcoidosis whose serum 1,25(OH)2D levels were independent of PTH. INTERVENTIONS AND MAIN OUTCOME MEASURES: The present case was treated with prednisolone before and after surgical resection of parathyroid adenoma, and Ca-regulating hormones and bone markers were measured. RESULTS: Serum Ca and PTH levels significantly decreased after parathyroid surgery, whereas serum 1,25(OH)2D levels remained high. Prednisolone administration promptly decreased serum 1,25(OH)2D levels and reciprocally increased PTH levels despite consistent serum Ca levels either before or after surgery. PTH levels were negatively correlated with serum 1,25(OH)2D levels before and after surgery. Urine N-telopeptides, serum osteocalcin, and bone-type alkaline phosphatase all decreased to physiological ranges after parathyroid surgery. CONCLUSIONS: These results suggest that 1,25(OH)2D indeed inhibits the production of PTH not to exacerbate hypercalcemia in a patient with primary hyperparathyroidism. Furthermore, PTH but not 1,25(OH)2D may primarily be involved in the stimulation of bone turnover.     

Rho-kinase is an important therapeutic target in cardiovascular medicine

Rho-kinase has been identified as one of the effectors of the small GTP-binding protein Rho. Accumulating evidence has demonstrated that Rho/Rho-kinase pathway plays an important role in various cellular functions, not only in vascular smooth muscle cell (VSMC) contraction but also in actin cytoskeleton organization, cell adhesion and motility, cytokinesis, and gene expressions, all of which may be involved in the pathogenesis of cardiovascular disease. At molecular level, Rho-kinase upregulates various molecules that accelerate inflammation/oxidative stress, thrombus formation, and fibrosis, whereas it downregulates endothelial nitric oxide synthase. The expression of Rho-kinase itself is mediated by protein kinase C/NF-kappaB pathway with an inhibitory and stimulatory modulation by estrogen and nicotine, respectively. At cellular level, Rho-kinase mediates VSMC hypercontraction, stimulates VSMC proliferation and migration, and enhances inflammatory cell motility. In animal studies, Rho-kinase has been shown to be substantially involved in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke and heart failure, and to enhance central sympathetic nerve activity. Finally, in clinical studies, fasudil, a Rho-kinase inhibitor, is effective for the treatment of a wide range of cardiovascular disease, including cerebral and coronary vasospasm, angina, hypertension, pulmonary hypertension, and heart failure, with a reasonable safety. Thus, Rho-kinase is an important therapeutic target in cardiovascular medicine.     

Fas ligand expressing mononuclear cells around intrahepatic bile ducts co‐express CD68 in primary biliary cirrhosis

Abstract: Aims/Background: Apoptosis, including the Fas system, has been implicated in progressive bile duct loss in primary biliary cirrhosis (PBC). In this study, we attempted to analyze Fas ligand (FasL) expressing mononuclear cells infiltrating in the portal tracts of PBC. Methods: We immunohistochemically assessed co‐expression of leukocyte markers and FasL on infiltrating mononuclear cells in 18 patients with PBC. Twenty‐five patients with chronic hepatitis C (CH‐C) were used as controls. Results: In PBC, FasL expressing cells were scattered in the portal tracts, and some were accentuated around the damaged bile ducts. In addition, these cells co‐expressed CD68 (71%), a marker of monocytes, but not UCHL‐1, CD3 and CD57, markers of activated T cells and natural killer cells. By contrast, in CH‐C, the biliocentric pattern of FasL expression was not evident, and about half of FasL expressing cells (42–56%) co‐expressed UCHL‐1, CD3 or CD57. CD14, a receptor for bacterial products such as lipopolysaccharides, was also detected on a proportion of FasL expressing mononuclear cells around the damaged bile ducts in PBC. Conclusion: The results suggest that in PBC, FasL expressing CD68+ monocytes are at least partly involved in apoptotic bile duct loss mediated by the Fas system, and a surface molecule, CD14, participates in this process.     

Results of a survey of community-acquired-pneumonia and evaluation of old and new Japanese Respiratory Society guidelines]

We evaluated the usefulness of domestic and foreign guidelines for the diagnosis and treatment of patients with community-acquired-pneumonia at 23 institutions in 6 prefectures of the Tohoku Area, from December 2003 to November 2004. Based on the old and new Japanese Respiratory Society (JRS) guidelines, we evaluated severity, clinical efficacy and detection of atypical pneumonia. As for severity, the old guidelines led to the diagnosis of an excessive number of 'severe' cases. On the other hand, patients were appropriately diagnosed as having mild, moderate, severe, or very severe disease based on the new JRS guidelines (2005). The severity classification often correlated with the Pneumonia Severity Index (PSI) of the IDSA guidelines. The efficacy rate for patients who were prescribed the recommended drug according to the old JRS guidelines was 85.7% and for those who did not use the recommended drug it was 68.7% (p < 0.001).     

Effect of L-dopa in young patients with hypertension

The effects of L-dopa on blood pressure, heart rate, plasma renin activity, norepinephrine, epinephrine and prolactin were studied in a randomized single-blind trial in 36 patients with essential hypertension. In response to L-dopa, 250 mg administered orally, the blood pressure decreased significantly as compared with the results of placebo treatment. The heart rate and plasma norepinephrine and epinephrine were unchanged. The plasma renin activity and prolactin decreased as a result of L-dopa administration. The administration of a peripheral DA2 dopamine receptor blocker, domperidone (20 mg, orally) prevented the L-dopa-induced reduction in plasma prolactin but failed to block the fall in blood pressure and plasma renin activity. These results suggest that the blood pressure-lowering effect of L-dopa may be mediated through multiple sites involving D1 dopamine receptors, the central nervous system, and the renin-angiotensin system.