Clinical significance of vascular endothelial growth factor and hepatocyte growth factor in multiple myeloma

Angiogenesis is a crucial process in the progression of multiple myeloma (MM). Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are multifunctional cytokines that potently stimulate angiogenesis including tumour neovascularization. Serum levels of VEGF and HGF were measured in 52 patients with MM by enzyme-linked immunosorbent assay (ELISA). Serum levels of VEGF and HGF were elevated in MM patients compared with healthy controls (VEGF: mean 0.31 ng/ml and 0.08 ng/ml respectively, P < 0.01; HGF: mean 2.17 ng/ml and 0.45 ng/ml, respectively, P < 0.001). In serial samples taken after chemotherapy, serum VEGF and HGF levels were correlated with M-protein levels. Serum levels of VEGF were higher in patients with extramedullary plasmacytomas than in patients without them (P < 0.05). They were also significantly higher in a group of patients who showed poor response to chemotherapy (P < 0.01). Serum levels of HGF were higher in patients with complications such as anaemia, hypercalcaemia and amyloidosis than in patients without these complications (P < 0.01, P < 0.05, P < 0.05 respectively). Both serum VEGF and HGF levels were significant predictors of mortality (P = 0.01, P = 0.02, respectively, log-rank test). The present study demonstrated that serum levels of VEGF and HGF are significantly elevated and dependent on the severity of MM, suggesting that measurement of VEGF and HGF may be useful for assessing disease progression and for predicting the response to chemotherapy in MM patients.     

Suppression of atherosclerotic development in Watanabe heritable hyperlipidemic rabbits treated with an oral antiallergic drug, tranilast

BACKGROUND: Inflammatory and immunological responses of vascular cells have been shown to play a significant role in the progression of atheromatous formation. Tranilast [N-(3,4-dimethoxycinnamoyl) anthranillic acid] inhibits release of cytokines and chemical mediators from various cells, including macrophages, leading to suppression of inflammatory and immunological responses. This study tested whether tranilast may suppress atheromatous formation in Watanabe heritable hyperlipidemic (WHHL) rabbits. METHODS AND RESULTS: WHHL rabbits (2 months old) were given either 300 mg x kg-1 x d-1 of tranilast (Tranilast, n=12) or vehicle (Control, n=13) PO for 6 months. Tranilast treatment was found to suppress the aortic area covered with plaque. Immunohistochemical analysis showed that there was no difference in the percentage of the RAM11-positive macrophage area and the frequency of CD5-positive cells (T cells) in intimal plaques between Tranilast and Control. Major histocompatibility complex (MHC) class II expression in macrophages and interleukin-2 (IL-2) receptor expression in T cells, as markers of the immunological activation in these cells, was suppressed in atheromatous plaque by tranilast treatment. Flow cytometry analysis of isolated human and rabbit peripheral blood mononuclear cells showed that an increase in expression both of MHC class II antigen on monocytes by incubation with interferon-gamma and of IL-2 receptor on T cells by IL-2 was suppressed by the combined incubation with tranilast. CONCLUSIONS: The results indicate that tranilast suppresses atherosclerotic development partly through direct inhibition of immunological activation of monocytes/macrophages and T cells in the atheromatous plaque.     

Serovar-distribution, drug-resistance, and DNA analysis of Salmonella strains isolated from sporadic diarrhea cases or healthy cases in Tama, Tokyo (1991-2000)]

Serovar-distribution and drug-resistance of a total of 421 Salmonella strains, which were 98 stains from sporadic diarrhea cases and 323 strains from healthy cases between 1991 and 2000 in Tama, Tokyo were investigated. In serological typing tests, the strains tested were classified into 26 different kinds of serovar in diarrhea cases, 58 in food handlers, and 25 in individuals for health care. Salmonella serovar Enteritidis (S. Enteritidis) was the most predominant serovar in three cases. Following, S. Typhimurium and S. Infantis in diarrhea cases, S. Hadar, S. Montevideo and S. Thompson in food handlers, or S. Typhimurium, S. Lichfield and S. Oranienburg in healthy individuals were frequent. The drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, SXT, NA, FOM, and NFLX) showed that 57.1% of the strains from diarrhea cases and 36.8% from the healthy cases were resistant to one or the other of the drugs examined. Drug-resistance patterns of those showed 13 types in diarrhea cases and 25 types in healthy cases. Out of them, strains which showed a predominant and common pattern in both cases were SM resistant-S. Enteritidis and CP.TC.SM.ABPC resistant-S. Typhimurium. In addition, the latter strains were also resistant to sulfiso-xzole (SU). In DNA analysis by RAPD method of their strains, common DNA finger-prints were observed in both cases through out the investigation period.     

Noninvasive detection of coronary artery bypass graft patency by intravenous electron beam computed tomographic angiography

This study evaluates the usefullness of intravenous electron beam computed tomographic angiography (EBA) for the detection of coronary artery bypass graft patency in 43 patients (33 men and 10 women, mean age, 65 years) who had coronary artery bypass graft surgery. EBA was performed a few days before selective bypass graft angiography (SGA). Forty axial cross-sections of angiographic images of the heart were acquired consecutively by an electrocardiographic trigger signal at 40% of the RR interval, which corresponds to the end-systolic phase. EBA data were reconstructed as a three-dimensional shaded surface display of the heart and bypass grafts. Detectability of the patency of bypass gratis was evaluated, taking selective angiographic images of the bypass grafts as a gold standard. One hundred and nine grafts (96%) out of 114 grafts were subjected to evaluation: 37 grafts were left internal mammary artery grafts (LIMA), 7 were right internal mammary artery grafts (RIMA), 6 were gastroepiploic artery grafts (GEA), 7 were free gastroepiploic artery grafts with venous drainage (free-GEA), 7 were radial artery grafts (RAG), and 45 were saphenous vein gratis (SVG). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBA were 98%, 100%, 100%, 91%, and 98%, respectively. EBA sampled at the end-systolic period was determined to be useful for the detection of coronary artery bypass graft patency and occlusion.     

Relationship of exercise or pacing induced ST segment depression and myocardial lactate metabolism in patients with hypertrophic cardiomyopathy

To elucidate a mechanism and clinical implications of chest pain and ST segment depression during exercise in patients with hypertrophic cardiomyopathy (HCM), we investigated myocardial lactate metabolism during atrial pacing in 18 patients with HCM and 7 control subjects with normal coronary arteriograms. At an average peak pacing rate of 146 beats/min, 11 patients with HCM showed the lactate extraction ratio decreasing to less than 5%, and 6 of them produced lactate, suggesting the development of myocardial ischemia. These 11 patients with abnormal lactate metabolism demonstrated ST segment depression (82%) and chest pain (73%) during pacing and also presented abnormal results (55%) on an exercise stress test. These abnormal findings were not observed in the other 7 patients who had ratios of 5% or more at peak pacing. These observations suggest that ST segment depression and chest pain are manifestations of myocardial ischemia even in patients with HCM who have normal coronary arteriograms, and that patients with pacing induced abnormal lactate metabolism are at an increased risk of developing myocardial ischemia during exercise.     

Salt sensitivity in Goldblatt hypertensive rats--role of extracellular fluid volume and renin-angiotensin system

Effects of a high-salt diet on blood pressure, extracellular fluid volume, and the renin-angiotensin system in rats with the two types of Goldblatt hypertension were examined. Both in one-kidney, one clip (1K1C) rats and in one-kidney, sham-clipped (1K) rats, systolic blood pressures of rats which received a high-salt diet for 4 weeks were higher than those of rats of respective groups on a normal-salt diet, suggesting an increased sensitivity of blood pressure to changes in salt intake. Whereas sodium space was increased in 1K rats on the high-salt 1K1C rats receiving the high-salt did not have significantly increased sodium space. These results suggest that acceleration of 1K1C hypertension with salt load could not be explained only by changes in extracellular fluid volume. In contrast, both in two-kidney, one clip (2K1C) rats and in two-kidney, sham-clipped (2K) rats, the high-salt diet produced no change in blood pressure despite the increase in sodium space, suggesting a decreased salt sensitivity. Although on the normal-salt diet the blood pressure of 2K1C rats tended to correlate with plasma renin activity, on the high-salt diet plasma renin activity was markedly decreased, and then blood pressure highly correlated with sodium space. Accordingly, the lesser salt sensitivity in 2K1C rats is probably attributable to the counterbalance of the suppressed renin-angiotensin system against volume expansion. Evidence presented suggests, therefore, that 1K1C rats have greater salt sensitivity of blood pressure than 2K1C rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin resistance in nondiabetic patients is associated with expansive remodeling in coronary arterial lesions

OBJECTIVE: Insulin resistance has been implicated as an important initiating factor in coronary atherosclerosis. However, associations between insulin resistance and specific morphologic features of atherosclerotic coronary arteries remain unclear. We ultrasonographically evaluated the morphologic features of atherosclerotic coronary arteries in nondiabetic patients with insulin resistance. METHODS: Before intervention, 90 patients with 105 culprit lesions underwent intravascular ultrasound examination through which vessel area, lumen area and plaque area were evaluated. Expansive remodeling (lesion vessel area more than 5% greater than at the proximal reference segment) and constrictive remodeling (lesion vessel area more than 5% less than at the distal reference segment) were also evaluated. Insulin resistance was determined by homeostasis model assessment and defined as values above the 75th percentile (that is, 1.71). RESULTS: Insulin-resistant patients numbered 23, while nonresistant patients numbered 67. Culprit lesions in the insulin-resistant group showed larger vessel area (18.16 +/- 6.94 compared with 13.64 +/- 4.28 mm, P = 0.0001) and plaque area (16.64 +/- 6.78 compared with 12.05 +/- 4.12 mm, P = 0.0001) and more frequently showed expansive remodeling (56% compared with 14%, P < 0.0001) and calcific plaque (33% compared with 12%, P = 0.01). Multivariable logistic regression analysis identified only insulin resistance (odds ratio, 4.9, P = 0.008) as an independent predictor of expansive remodeling. CONCLUSIONS: Insulin resistance independently predicted expansive remodeling, underscoring the importance of insulin resistance in coronary atheroscrelosis.     

Association of primary hyperparathyroidism with myotonic dystrophy in two patients

In two patients primary hyperparathyroidism developed in association with myotonic dystrophy (MyD). Both patients had solitary adenoma, and the adenomas were surgically removed. After the operation, subjective improvement of muscle weakness was found in one patient. Because parathyroid hormone secretion is regulated by extracellular calcium concentration and because abnormalities in transmembrane calcium transport are thought to play a role in the pathogenesis of MyD, the concurrence of these rather rare disorders in two patients raises the possibility that abnormalities in transmembrane calcium transport may underlie the development of primary hyperparathyroidism in patients with MyD. Although further studies are needed to clarify the possible link between these two disorders, the present study emphasizes the importance of evaluation of parathyroid function in patients with MyD.