Lectin staining of neoplastic and normal background colorectal mucosa in nonpolyposis and polyposis patients

A lectin histochemistry approach was adopted for comparative assessment of a colon cancer risk. Binding of Ulex europaeus agglutinin-I (UEA-I), peanut agglutinin (PNA), Griffonia simplicifolia agglutinin-II (GSA-II), and Dolichos biflorus agglutinin (DBA) was investigated in tumor and background tissue from a total of 34 adenoma and 44 cancer patients and compared with reaction patterns in control and familial adenomatous pplyposis (FAP) patients. Adenoma patients with UEA-I positive rectal mucosa were found to have a 33.3 percent familial history of large bowel cancer, which was significantly higher (P <0.05) than the respective 4.0 percent figure for patients with negative rectal mucosa. In the cancer patients, an even stronger correlation was noted, with a 63.2 percent UEA-I positive family history association being recorded, as opposed to 4.0 percent in the negative rectal mucosa patients (P <0.01). Thus, the results suggest that, apparently, normal rectal background mucosa of individuals genetically at high risk for colon and rectal cancer demonstrates a specific lectin binding ability similar to that of FAP patients and that the simple method using UEA-I staining of rectal biopsy specimens can be of practical use in identification of high-risk colorectal cancer.     

Results of distal splenorenal shunt with versus without splenopancreatic disconnection

From December 1973 to December 1987, we performed a distal splenorenal shunt (DSRS) in 112 cases of portal hypertension, including 107 with postnecrotic liver cirrhosis and 5 with idiopathic portal hypertension (IPH). They comprised about 50% of our surgical cases with esophageal varices. In 1981, we modified our operative procedure towards a more extended splenopancreatic disconnection (SPD) in order to prevent the "stealing" of the shunt through the pancreatic vein. In one group of 69 patients who underwent DSRS alone, the operative mortality was 2.9%; postoperative encephalopathy was seen in 17.4%, late hepatic failure in 40.6%, and recurrence of varices in 4.3%. In the other group, 43 patients who underwent DSRS with SPD, there were no operative deaths, no encephalopathy (better than DSRS alone at p less than 0.05), and late hepatic failure was seen in only 9.3% (better than DSRS alone at p less than 0.025), while the recurrence rate of 7% was the only statistical increase. These data show that DSRS + SPD can improve chances of survival.     

Vipoma of the Pancreas Complicating Ulcerative Colitis

We report a case of vipoma of the pancreas in conjunction with ulcerative colitis in a 20-yr-old woman. Twenty months after the onset of ulcerative colitis, the patient complained of watery diarrhea and was found to have an electrolyte disorder. A pancreatic tumor was detected by ultrasonography and computed tomography, along with an elevation of serum vasoactive intestinal polypeptide (VIP). The secretory diarrhea diminished dramatically, and the serum VIP level decreased into the normal range immediately after resection of the pancreatic tumor. Immunohistochemical staining revealed a pancreatic vipoma. Despite removal of the vipoma, she underwent restorative proctocolectomy and ileal J-pouch anal anastomosis 2 yr later due to progression of the ulcerative colitis. Postoperative course was uneventful, with excellent functional results. Knowledge of this rare condition accompanying ulcerative colitis may help in the management of the patient with an atypical clinical course.     

Can signal intensity of the continuous wave Doppler regurgitant jet estimate severity of mitral regurgitation?

Visual estimates of the intensity of the continuous wave (CW) Doppler regurgitant jet signal have been used to estimate the severity of valvular regurgitation. Theoretically, the strength of the reflected Doppler signal is a function of the number of scatterers. To test this approach quantitatively, free jets were produced in 27 experiments using a power injector and cornstarch suspension varying in concentration from 1% to 3%. Flow volume was varied from 5 to 15 ml, and orifice diameter varied from 2.5 to 10 mm. Machine settings were kept constant. Also, 22 patients with mitral regurgitation (MR)--5 mild, 11 moderate, and 6 severe by angiography--were studied. Average signal intensity under the CW Doppler flow curve was calculated using a computer image processor. In MR patients, average regurgitant flow (RF) intensity was compared with average mitral forward flow (FF) signal intensity. (1) The intensity under the CW flow signal in the free jet experiments correlated well with injection volume (r greater than 0.98). (2) RF average signal intensity did not correlate with angiographic MR severity (r = 0.21), but the ratio of RF to FF average signal intensity did correlate with MR severity (r = 0.73). (3) The sensitivity and the specificity of an RF/FF ratio greater than 0.65 for angiographically severe mitral regurgitation were both 83%. (4) The sensitivity and specificity of an RF/FF ratio less than 0.50 for angiographic mild mitral regurgitation were both 80%. The ratio of regurgitant to forward mitral flow CW Doppler signal intensity appears to be an accurate and clinically applicable method for estimating the severity of mitral regurgitation.     

Lysophosphatidic acid transactivates both c-Met and epidermal growth factor receptor, and induces cyclooxygenase-2 expression in human colon cancer LoVo cells

AIM: To examine whether lysophosphatidic acid (LPA) induces phosphorylation of c-Met and epidermal growth factor receptor (EGFR), both of which have been proposed as prognostic markers of colorectal cancer, and whether LPA induces cyclooxygenase-2 (COX-2) expression in human colon cancer cells. METHODS: Using a human colon cancer cell line, LoVo cells, we performed immunoprecipitation analysis, followed by Western blot analysis. We also examined whether LPA induced COX-2 expression, by Western blot analysis. RESULTS: Immunoprecipitation analysis revealed that 10 umol/L LPA induced tyrosine phosphorylation of c-Met and EGFR in LoVo cells within a few minutes. We found that c-Met tyrosine phosphorylation induced by LPA was not attenuated by pertussis toxin or a matrix metalloproteinase inhibitor, in marked contrast to the results for EGFR. In addition, 0.2-40 umol/L LPA induced COX-2 expression in a dose-dependent manner. CONCLUSION: Our results suggest that LPA acts upstream of various receptor tyrosine kinases (RTKs) and COX-2, and thus may act as a potent stimulator of colorectal cancer.     

Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease

AIM: Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD), and progresses to the end stage of liver disease. Biochemical markers of liver fibrosis are strongly associated with the degree of histological liver fibrosis in patients with chronic liver disease. However, data are few on the usefulness of markers in NAFLD patients. The aim of this study was to identify better noninvasive predictors of hepatic fibrosis, with special focus on markers of liver fibrosis, type VI collagen 7S domain and hyaluronic acid. METHODS: One hundred and twelve patients with histologically proven NAFLD were studied. RESULTS: The histological stage of NAFLD correlated with several clinical and biochemical variables, the extent of hepatic fibrosis and the markers of liver fibrosis were relatively strong associated. The best cutoff values to detect NASH were assessed by using receiver operating characteristic analysis: type VI collagen 75 domain ≥5.0 ng/mL, hyaluronic acid ≥43 ng/mL. Both markers had a high positive predictive value: type VI collagen 7S domain, 86% and hyaluronic acid, 92%. Diagnostic accuracies of these markers were evaluated to detect severe fibrosis. Both markers showed high negative predictive values: type VI collagen 7S domain (≥5.0 ng/mL), 84% and hyaluronic acid (≥50 ng/mL), 78%, and were significantly and independently associated with the presence of NASH or severe fibrosis by logistic regression analysis. CONCLUSION: Both markers of liver fibrosis are useful in discriminating NASH from fatty liver alone or patients with severe fibrosis from patients with non-severe fibrosis.     

An alpha-adrenergic blocker titrated by self-measured blood pressure recordings lowered blood pressure and microalbuminuria in patients with morning hypertension: the Japan Morning Surge-1 Study

BACKGROUND: The impact on microalbuminuria of strict treatment aimed at lowering of self-measured morning blood pressure using an adrenergic blockade is unclear. METHODS: We conducted an open-label multicenter trial, the Japan Morning Surge-1 Study, that enrolled 611 hypertensive patients, whose self-measured morning systolic blood pressure levels were more than 135 mmHg while taking antihypertensive drugs. These were randomly allocated to an experimental group, whose members received bedtime administration of 1-4 mg doxazosin (doxazosin group) or a control group whose members continued without any add-on medication (control group). The urinary albumin/creatinine ratio was investigated at the baseline and 6 months after the randomization. RESULTS: Both the morning and evening blood pressures and urinary albumin/creatinine ratio (-3.4 vs. 0.0 mg/gCr for urinary albumin/creatinine ratio; P < 0.001) were more markedly reduced in the doxazosin group than in the control group. This difference in the urinary albumin/creatinine ratio between the two groups was more marked in the patients with microalbuminuria (n = 238, -27.9 vs. -8.1 mg/gCr, P < 0.001). The reduction of urinary albumin/creatinine ratio was significantly associated with the use of doxazosin, and the change in all self-measured blood pressures (morning, evening, the average morning-evening), and these associations were independent of each other (P < 0.001). CONCLUSION: Adding a bedtime dose of an alpha-adrenergic blocker titrated by self-measured morning blood pressure in treated hypertensive patients with uncontrolled morning hypertension significantly reduced blood pressure and urinary albumin excretion rate, particularly in those with microalbuminuria.     

Morning blood pressure surge and hypertensive cerebrovascular disease: role of the alpha adrenergic sympathetic nervous system

BACKGROUND: The morning surge of blood pressure (BP) is associated with alpha-adrenergic activity. We studied the association between the alpha-adrenergic morning surge in BP and silent cerebrovascular disease in elderly patients with hypertension. METHODS: We conducted ambulatory BP monitoring three times (twice at baseline and after nighttime dosing of the alpha1-blocker doxazosin) in 98 elderly hypertensive patients in whom the presence of silent cerebral infarcts (SCI) was assessed by brain magnetic resonance imaging. The morning BP surge (MBPS) was calculated as the mean systolic BP during the 2 h after waking minus the mean systolic BP during 1 h that included the lowest sleep BP. The alpha-adrenergic MBPS was calculated as the reduction of MBPS by doxazosin. RESULTS: The prevalence of multiple SCI was higher in the Surge group (top quartile: MBPS > or = 45 mm Hg, n = 24) than in the Nonsurge group (MBPS < 45 mm Hg, n = 74) (54% v 31%, P = .04), and in the higher alpha-adrenergic surge group (top quartile: alpha-adrenergic MBPS > or = 28 mm Hg, n = 25) than in the lower alpha-adrenergic surge group (< 28 mm Hg, n = 73) (68% v 26%, P < .0001). In the Surge group, subjects with higher alpha-adrenergic surge (n = 17) had a markedly higher frequency of multiple SCI, whereas none in the lower alpha-adrenergic surge group had multiple SCI (n = 7) (77% v 0%, P = .001). The alpha-adrenergic MBPS was closely associated with multiple SCI (10 mm Hg increase: OR = 1.96, P = .006), independently of age, MBPS, 24-h systolic BP, and other confounding factors. CONCLUSION: The morning BP surge, particularly that dependent on alpha-adrenergic activity, is closely associated with advanced silent hypertensive cerebrovascular disease in elderly individuals.     

Hemodialysis improves myocardial interstitial edema and left ventricular diastolic function in patients with end-stage renal disease: noninvasive assessment by ultrasonic tissue characterization

Congestive heart failure is the most common cause of mortality in patients with end-stage renal disease (ESRD). Ultrasonic tissue characterization with integrated backscatter offers a promising method for the noninvasive assessment of regional myocardial contractile performance and fibrosis. The aim of this study was to investigate the effect of hemodialysis (HD) on myocardial tissue characterization and left ventricular function in ESRD patients. We examined 26 patients with ESRD undergoing routine HD (age 63 ± 12 years, duration of HD 9.2 ± 3.2 years) and 30 patients with essential hypertension (HT; 60 ± 10 years). Routine echocardiographic parameters and the cyclic variation of ultrasonic integrated backscatter of the ventricular septum (CV-IBS) were measured. Left ventricular mass index was significantly larger in patients with ESRD than in those with HT (217 ± 56 vs 146 ± 45 g/m², P < 0.05). The indices for left ventricular diastolic function (E/A, the ratio of left ventricular peak early to late diastolic filling velocity; DT, the deceleration time of the early diastolic filling) and CV-IBS had deteriorated significantly in patients with ESRD before HD compared with those with HT (E/A, 0.6 ± 0.2 vs 0.9 ± 0.3, P < 0.05; DT, 228 ± 23 vs 184 ± 19 ms, P < 0.05; CV-IBS, 9.0 ± 1.3 vs 12.4 ± 0.9 dB, P < 0.05), possibly reflecting interstitial fibrosis. In patients with ESRD, HD reduced calculated left ventricular mass index by 19% (before HD, 217 ± 56 vs immediately after HD, 176 ± 45 g/m², P < 0.05) and CV-IBS by 19% (9.0 ± 1.3 vs 7.3 ± 1.1 dB, P < 0.05), that possibly reflected improvement of interstitial edema. HD also significantly improved indices for left ventricular diastolic function (E/A, 0.6 ± 0.2 vs 0.9 ± 0.2, P < 0.05; DT, 228 ± 23 vs 188 ± 21 ms, P < 0.05). HD improves myocardial interstitial edema and left ventricular diastolic function in patients with ESRD. Noninvasive assessment of ultrasonic tissue characterization is useful in defining the pathophysiological changes of ventricular myocardium in patients with ESRD. Received: December 17, 2001 / Accepted: April 19, 2002 Correspondence to O. Hirono