Cancer marker: vascular endothelial growth factor.
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Aged↗
Biomedical subjects
K Tanikawa
Publications and source records attributed to K Tanikawa.
Serum vascular endothelial growth factor levels in various liver diseases.
The clinical significance of circulating vascular endothelial growth factor (VEGF) in patients with various liver diseases was investigated. Twenty-one patients with acute hepatitis (AH), 40 with chronic hepatitis (CH), 34 with cirrhosis (LC), 16 with fulminant hepatitis (FH), 10 with primary biliary cirrhosis (PBC), 12 with autoimmune hepatitis (AIH), and 120 healthy individuals were included. Serum VEGF levels were measured by a chemiluminescence enzyme-linked immunosorbent assay. The mean values of serum VEGF levels in the patients with AH, CH, LC, FH, AIH, PBC, and control were 172.7, 58.0, 44.1, 37.3, 49.7, 74.9, and 65.0 pg/ml, respectively. The patients with AH had a level of serum VEGF significantly higher than that of the control group (P < 0.001). The serum VEGF levels in survivors of FH were significantly increased, but not in the nonsurvivors in the recovery phase compared with the levels on admission (P < 0.05). In the LC patients, serum VEGF levels were significantly lower than those of the control group (P < 0.05). These findings suggest that serum VEGF level may be associated with hepatocyte regeneration grade.
Acute Disease↗
Iodine staining for early endoscopic detection of esophageal cancer in alcoholics.
BACKGROUND AND STUDY AIMS: A retrospective epidemiological investigation has demonstrated that alcohol abuse is a major risk factor for esophageal cancer. However, prospective endoscopic screening for early detection in heavy drinkers is not available at present. PATIENTS AND METHODS: A prospective study was conducted that included 255 alcoholics (aged 52 +/- 9 years). The patients were consecutively screened using esophagoscopy with iodine staining and targeted biopsy. The study also explored whether there was a relationship between the amount of alcohol intake and the detection rate of esophageal cancer. RESULTS: Unstained lesions (larger than 5 mm) were observed on the esophageal wall in 55 patients (21.6%). Ten patients (3.9%) with 13 lesions were found to have esophageal cancer of the superficial type, with no symptoms. Cancer invasion was confined to the epithelium in three patients, to the lamina propria in seven, and to the submucosa in three. There was a direct relationship between substantial alcohol intake and the presence of esophageal cancer. CONCLUSION: Screening esophagoscopy with iodine staining is very advantageous in detecting esophageal cancer at an early stage.
Administration, Topical↗
Effect of large fundal varices on changes in gastric mucosal hemodynamics after endoscopic variceal ligation.
UNLABELLED: BACKGROUNDS AND STUDY AIMS: Effect of endoscopic variceal ligation (EVL) on gastric mucosal hemodynamics would differ in patients with and without large fundal varices. The aim of this study was to test this hypothesis. PATIENTS AND METHODS: Twenty-seven patients with cirrhosis and large sized esophageal varices were prospectively studied. There were eight patients with large fundal varices and 19 patients without large fundal varices. Before EVL, gastric mucosal hemodynamics were endoscopically assessed by laser-Doppler velocimetry and reflectance spectrophotometry in the antrum and the corpus. In the reflectance spectrophotometric measurements, gastric mucosal hemoglobin content (IHb) and gastric mucosal oxygen saturation (ISO2) were determined. The severity of portal-hypertensive gastropathy (PHG) was also recorded at the antrum and the corpus. For data analysis, PHG was scored (absent, 0; mild, 1; severe, 2; bleeding, 3). These measurements were repeated after initial (three days after initial session) and repeated (seven days after last session) EVL. RESULTS: At the antrum, neither PHG score nor gastric mucosal hemodynamic parameters were modified after initial and repeated EVL in patients with and without large fundal varices. In addition, no significant differences of the integrated changes in PHG score and gastric mucosal hemodynamic parameters were observed in the two groups. At the corpus, PHG score significantly increased after initial and repeated EVL in patients without large fundal varices. In these patients, laser-Doppler signal and ISO2 significantly decreased and IHb significantly increased after initial and repeated EVL. In contrast, PHG score, laser-Doppler signal, and ISO2 did not change significantly in patients with large fundal varices, although IHb transiently increased after initial EVL. Furthermore, the integrated changes in PHG score and gastric mucosal hemodynamic parameters were significantly lower in patients with large fundal varices than in those without. CONCLUSION: The aggravation of PHG after EVL is due to congestion of the gastric mucosal circulation. The presence of large fundal varices plays a protective role in the development of EVL-induced gastric mucosal hemodynamic derangement.
Adult↗
Ligation plus low-volume sclerotherapy for high-risk esophageal varices: comparisons with ligation therapy or sclerotherapy alone.
Endoscopic variceal ligation therapy (EVL) seems to be a more effective and safer method than endoscopic injection variceal sclerotherapy (EVS) for treating bleeding esophageal varices. However, EVL may entail a higher recurrence rate than EVS. The aim of this study was to examine whether EVL combined with low-dose EVS reduced the recurrence rate compared to treatment with EVL alone and reduced the complication rate compared to treatment with EVS alone. In this prospective study, 59 patients with cirrhosis and high-risk (F2 or F3, red color sign ++ or ) esophageal varices were enrolled. They were randomly assigned to an EVS group (n = 18), an EVL group (n = 20), and a combination EVL plus low-dose EVS group (n = 21). After the eradication of varices, follow-up endoscopic examinations were carried out for 24 months to determine the recurrence of varices. Complications, e.g., severe dysphagia, fever, renal dysfunction and pleuritis were also evaluated. The recurrence-free rate was significantly lower in the EVL group (60% at 24 months) than in either the EVS group (90%, P < 0.05) or the combination group (88%, P < 0.05). However, no significant difference was found between the EVS group and the combination group. The complication rate was significantly higher in the EVS group (50%) than in either the EVL group (5%, P < 0.01) or the combination group (10%, P < 0.01). The combination therapy seems to be useful to improve the benefits achieved with EVL alone and to reduce the harmful effects induced by EVS alone. EVL plus low-volume EVS is advisable in the treatment of high-risk esophageal varices.
Aged↗
Role of interleukin-10 in a murine model of dextran sulfate sodium-induced colitis.
BACKGROUND: Increased production of proinflammatory cytokines is characteristic of both animal models of experimental colitis and human inflammatory bowel disease. This study was designed to characterize the functional role of interleukin (IL)-10 in a murine model of experimental colitis. METHODS: Cytokine profiles were analyzed in animals with dextran sulfate sodium-induced colitis. The effect of treatment with IL-10 or anti-IL-10 antibodies on colonic cytokine production in vitro and tissue damage in vivo were evaluated. RESULTS: After the induction of colitis, there was a time-dependent increase in tissue tumor necrosis factor-alpha and IL-1beta levels, followed by a peak of the IL-10 level. The production of tumor necrosis factor-alpha and IL-1beta by cultured colonic tissues was inhibited by addition of IL-10, and conversely, it was enhanced by anti-IL-10. Treatment with IL-10 resulted in a marked improvement in intestinal inflammation. Blocking endogenous IL-10 was found to cause a modest exacerbation of inflammation. CONCLUSIONS: These results show that IL-10 has a functional role in regulating colonic inflammation during experimental colitis.
Animals↗
Detection of pro- and anti-inflammatory cytokines in stools of patients with inflammatory bowel disease.
BACKGROUND: Cytokines play a predominant role in immune and inflammatory reactions in inflammatory bowel disease. Any cytokine that is produced locally as a result of gut inflammation may leak into the bowel lumen and appear in the stools. We examined the usefulness of determining cytokine profiles in the stools of patients with ulcerative colitis or Crohn's disease. METHODS: Cytokine concentrations in stool extracts were measured in 36 patients with ulcerative colitis, 32 patients with Crohn's disease, 9 controls with inflammatory disease, and 18 normal controls by means of enzyme-linked immunosorbent assays. RESULTS: Stool concentrations of interleukin-1beta and interleukin-1 receptor antagonist in patients with active inflammatory bowel disease increased significantly and correlated with various inflammatory factors and stool concentrations of polymorphonuclear cell elastase. The ratio of interleukin-1 receptor antagonist to interleukin-1beta in active disease was reduced significantly compared with that in inactive disease or in normal controls. Paired analysis showed a decrease in tumor necrosis factor-alpha and interleukin-1beta and interleukin-1 receptor antagonist and an increase in interleukin-4 and interleukin-10 concentrations after the resolution of disease exacerbation. CONCLUSIONS: Measurement of cytokines in stools may be a useful and noninvasive means of understanding pathophysiology and clinical monitoring in inflammatory bowel disease.
Adult↗
Aortitis syndrome (Takayasu's arteritis) with cataract and elevated serum level of vascular endothelial growth factor.
The aortitis syndrome is a chronic inflammatory process that affects the aorta and its primary branches. Patients with aortitis syndrome exhibit various ocular changes. We present a patient in whom cataract was the initial objective finding. The serum concentration of vascular endothelial growth factor, a cytokine that affects neovascularization, and vasopermeability, was elevated before the initiation of prednisolone treatment. Cataract should be considered as a possible characteristic initial finding in patients with aortitis syndrome. Vascular endothelial growth factor may be involved in the progression of aortitis syndrome.
Adult↗
Vascular endothelial growth factor in patients with rheumatoid arthritis.
To examine the role of vascular endothelial growth factor (VEGF), an endothelial cell specific growth factor, in rheumatoid arthritis (RA), serum concentration of VEGF was examined in patients with RA, osteoarthritis (OA), systemic lupus erythematosus (SLE), systemic sclerosis (SS) and control subjects. Serum C-reactive protein (CRP) level, erythrocyte sedimentation rate, white blood cell count and rheumatoid factor titer were also determined in patients with RA. The serum concentration of VEGF was significantly higher in patients with RA than in controls (p < 0.01), and patients with OA (p < 0.05), SLE (p < 0.05), and SS (p < 0.05). The serum concentration of VEGF correlated with serum levels of CRP (r = 0.698, p < 0.0001). The serum concentration of VEGF before treatment was significantly higher than that after treatment in patients with RA who experienced clinical remission (p < 0.05). Our data suggest that VEGF is involved in the pathogenesis of RA and that measurement of serum concentration of VEGF is a noninvasive, useful method for monitoring the disease activity of RA.
Adolescent↗
A crossover study of oral administration of UFT in chronic liver disease: comparison of continuous and intermittent schedules.
This study was aimed at evaluating the tolerance to an intermittently administered oral UFT for hepatocellular carcinoma (HCC) with chronic liver disease (CLD). Ten patients who had received curative therapy for HCC with CLD (Child's classification A or B) were randomly assigned either an intermittent schedule (IS), oral administration of UFT (130 mg/m2/b.i.d.) with 2 days rest a week, or a continuous schedule (CS), consecutive administration of UFT with the same dose. On day 12, the serum concentration of 5-fluorouracil (5-FU) was measured. After 2 weeks rest, the patients were switched to the other schedule for 10 weeks and the concentration of 5-FU was measured on day 12. The median values of the area under the curve (AUC) and maximum concentration (Cmax) of 5-FU in IS and CS were 187.7 and 263.2 ng/ml/h, 57.1 and 93.0 ng/ml, respectively. Both the AUC and Cmax for IS were significantly lower than those for CS. One IS patient had tolerable diarrhea, while three of the CS patients had intolerable nausea and one had hemorrhagic gastritis. IS seemed to be a suitable measure for CLD.
Administration, Oral↗
Prognostic factors in cirrhotic patients receiving long-term sclerotherapy for the first bleeding from oesophageal varices.
OBJECTIVE AND DESIGN: The aim of this study was to identify prognostic factors in cirrhotic patients receiving long-term sclerotherapy for their first bleeding from oesophageal varices. METHODS: Ninety-eight patients with acute bleeding from oesophageal varices receiving long-term endoscopic injection sclerotherapy were retrospectively investigated. Thirteen variables (five qualitative and eight quantitative) related to clinical, biological, and radiographic features were collected at admission. The qualitative variables were: gender, hepatocellular carcinoma, cause of cirrhosis, ascites and degree of encephalopathy. The quantitative variables were age, bilirubin, albumin, prothrombin index, number of sessions of sclerotherapy, volume of ethanolamine oleate, time taken to reach the hospital and shock index. These variables were examined with a multivariate analysis using stepwise logistic regression procedures and a prognostic index was calculated from the Cox equation. The predictive power of the final Cox model was prospectively tested in 43 patients with cirrhosis receiving long-term sclerotherapy for their first variceal bleeding. RESULTS: Of the 13 variables studied in a multivariate analysis using a logistic regression model, four had an independent prognostic value: the presence of hepatocellular carcinoma, bilirubin, albumin and time taken to reach the hospital. When the Cox model was examined in an independent set of 43 patients, there were no statistically significant differences between the observed and expected survival. CONCLUSION: Prognosis of patients with bleeding from oesophageal varices is related to residual liver function and time taken to reach the hospital. Furthermore, the presence of hepatocellular carcinoma is an additional risk factor.
Esophageal and Gastric Varices↗
Liver-associated natural killer activity in cirrhotic rats.
An impaired host defense mechanism is well known in patients with liver cirrhosis (LC). Using a sinusoidal lavage method, lymphocytes were obtained from LC rats that were administered thioacetamide, and natural killer (NK) activity was measured by 51Cr-release assay. The NK cell count was measured by flow cytometric analysis using monoclonal antibody (Mab) 3.2.3 and/or CD 3-8+ as markers for NK cells, and by immunohistochemical staining using Mab 3.2.3. Furthermore, interferon (IFN) alpha was administered to LC rats and the subsequent changes in hepatic NK activity and NK cell count were observed. In the large granular lymphocyte (LGL)-rich fraction (Fr.1, LGLs: 60-90%), the NK activity was significantly lower in the LC rats (40.0 +/- 3.8%) compared to that in the control rats (48.4 +/- 4.3%) (P < 0.005). In addition, the number of NK cells in the liver tissues of the LC rats was significantly lower compared to that in the liver tissues of the control rats by morphometric analysis (P < 0.05). For LC rats, NK activity of the Fr.1 24 hr after IFN alpha administration (5 x 10(4) IU/100 g body weight) increased significantly (P < 0.005). Hepatic NK activity and NK cell count were reduced in the LC rats, and recovered following IFN alpha administration. The results obtained in this study may give clues to better understanding the impaired host defense mechanism in LC patients.
Animals↗
Circulating vascular endothelial growth factor in patients with colorectal cancer.
OBJECTIVE: The expression of vascular endothelial growth factor (VEGF), a glycoprotein that selectively promotes proliferation of endothelial cells, has been associated with cancer development. The aim of the present study was to determine whether serum levels of VEGF correlate with disease progression in patients with colorectal cancer. METHODS: VEGF levels were measured by a highly sensitive enzyme-linked immunosorbent assay in sera from 67 patients with colorectal cancer, 14 patients with colorectal adenomas, and 72 healthy volunteers, and in tissue homogenates from 10 patients with colorectal cancer. RESULTS: Serum VEGF levels were significantly higher in patients with colorectal cancer than in patients with colorectal adenomas or in normal controls (p < 0.01). In patients with colorectal cancer, serum VEGF levels were significantly associated with Dukes stage (p < 0.01) and with carcinoembryonic antigen levels (r = 0.725, p < 0.001). Patients with hepatic and/or lymph node metastasis had higher serum VEGF levels than those without. Surgical resection of the colorectal tumor led to a decrease in serum VEGF levels whether or not metastasis was present (p < 0.05). The tumor-bearing tissue contained significantly more VEGF than normal-appearing mucosa (p < 0.05). CONCLUSIONS: VEGF is involved in the development of colorectal cancer. Measurement of VEGF in the serum may be a useful noninvasive clinical marker for evaluating the disease status.
Adenoma↗
Two cases of adult varicella accompanied by hepatic dysfunction.
Varicella is a typical acute exanthematous viral infection caused by varicella-zoster virus (VZV). In recently years, as far as hepatic dysfunction caused by viruses other than the hepatitis virus is concerned, there have been a few reports on hepatic dysfunction accompanying varicella following organ transplantation of Europe and America and another report on an immunocompromized adult following treatment for Systemic lupus erythematosis (SLE) in Japan. Nonetheless, we searched the MEDLINE and J MEDICINE listing the publications between 1986 and 1996 and found one report on healthy adults with varicella accompanied by hepatic dysfunction in Europe and America and two reports in Japan. Only Noguchi et al. dealt with the findings of liver biopsy. We examined two healthy adults with varicella and mild-to-moderate hepatic dysfunction, and referred to the results of their liver biopsies. The present paper discusses this issue, citing some references.
Adult↗
Effect of meal induced splanchnic arterial vasodilatation on renal arterial haemodynamics in normal subjects and patients with cirrhosis.
AIMS: To investigate the relation between changes in splanchnic arterial haemodynamics and renal arterial haemodynamics in controls and patients with cirrhosis. METHODS: Superior mesenteric artery pulsatility index (SMA-PI) and renal artery pulsatility index (R-PI) were measured using Doppler ultrasonography in 24 controls and 36 patients with cirrhosis. These measurements were repeated 30 minutes after ingestion of a liquid meal or placebo. Sixteen controls and 24 patients received the meal, and eight controls and 12 patients received placebo. RESULTS: In the fasting condition, patients with cirrhosis had a lower SMA-PI (p<0.01) and a greater R-PI (p<0.01) compared with controls. Placebo ingestion had no effect on splanchnic and renal haemodynamics. In contrast, ingestion of the meal caused a notable reduction in SMA-PI (p<0.01, p<0.01) and an increase in R-PI (p<0.01, p<0.01) in controls and patients with cirrhosis. The meal induced haemodynamic change in SMA-PI was inversely correlated with that in R-PI in controls (t=-0.42, p<0.05) and in patients with cirrhosis (t=-0.29, p<0.05). CONCLUSIONS: Results support the hypothesis that renal arterial vasoconstriction seen in patients with cirrhosis is one of the kidney's homoeostatic responses to underfilling of the splanchnic arterial circulation.
Blood Pressure↗
Development of a computer program, MDGP, for population pharmacokinetic analysis written using ANSI C language on wide platforms.
MDGP, a computer program for population pharmacokinetics, has been developed. This program is based on maximum likelihood estimation with poly-dimensional normal distribution errors, and variable metric methods, direction set methods, conjugate gradient methods and the polytope method are provided as minimizations of objective function. The source codes of MDGP are described using ANSI C language. MDGP is able to run on wide platforms equipped with an ANSI C compiler. Users can use algebraic, ordinary differential and Laplace-transformed equations as descriptions of a pharmacokinetic model. Partial differential equations for each model parameter are not needed. Comparison of the estimated parameters, the iteration counts until convergence and objective function value, using MDGP and NONMEM, revealed that the calculation performance of the two programs are comparable. The MDGP is thought to be useful for the analysis of various pharmacokinetic models, including population pharmacokinetic analysis.
Humans↗
In vitro study of neutrophil apoptosis in liver cirrhosis.
Cirrhotic patients frequently manifest neutropenia and are predisposed to bacterial infections. We examined neutrophil apoptosis to determine if neutrophil survival in cirrhotic patients is shortened. Neutrophils isolated from 10 cirrhotic patients and 10 healthy volunteers were cultured for 24 hours. The time course of neutrophil viability was assessed by the trypan blue dye exclusion test and apoptosis was determined morphologically by light and electron microscopy. Apoptotic cells were also confirmed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick and labeling (TUNEL) and DNA gel electrophoresis. Fas expression of neutrophils was examined by flow cytometry. Viabilities were significantly decreased in liver cirrhosis (p<0.0001). Neutrophils from cirrhotic patients exhibited significantly greater apoptosis. Fas expression of neutrophils was significantly reduced for cirrhotic patients (p=0.0001). Neutrophils from cirrhotic patients exhibited markedly accelerated apoptosis in vitro. Shortening of neutrophil survival via apoptosis may explain in part the mechanism of neutropenia in cirrhotic patients.
Adult↗
Serum hyaluronic acid in clinical practice.
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Diagnosis, Differential↗