ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb01833.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractSome monocytic cytokines are important immune regulators. We have investigated cytokine production by monocytes and the blood levels of IL‐1β, IL‐6, TNFα, and TGFβ, in patients with obstructive jaundice. The supernatant from LPS stimulated monocytes from jaundiced patients released significantly increased quantities of TNFα by both bioassay and radioimmunoassay (RIA) (12.4 ± 2.5 fmol/mL and 32.6 ± 8.3 fmol/mL, respectively, for jaundice, compared with 1.6 ± 0.3 fmol/mL and 2.4 ± 0.5 fmol/mL respectively for controls, and also of IL‐6 (54.8 ± 5.0 fmol/mL in jaundice compared with 35.6 ± 5.0 fmol/mL for controls). The production of IL‐1β and TGFβ by stimulated monocytes was unchanged. Jaundiced patients had significantly higher plasma TGFβ, but TNFα and IL‐1β were below the limits of detection. The highest monocyte TNFα and IL‐6 levels were seen in malignant disease patients, especially those with a poor immediate prognosis. We conclude that the production of some cytokines by monocytes is up‐regulated in patie

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00003.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe validity and clinical relevance of Doppler flowmetry in measuring changes in regional blood flow are uncertain. In the present study we compared changes induced by ketanserin in regional splanchnic blood flow as measured by Doppler flowmetry with changes in conventionally measured systemic and in hepatic haemodynamic indices estimated pharmacokinetically using indocyanine green. Fourteen patients with alcoholic cirrhosis and portal hypertension were evaluated. On multivariate analyses, significant associations were noted for only three indices: changes in estimated hepatic blood flow were predicted jointly by changes in flow in the main and right portal veins and hepatic artery (R2= 0.80); changes in intrahepatic shunting (indocyanine green extraction) were predicted by changes in flow in the main and right portal veins (R2= 0.55); and changes in sinusoidal perfusion (indocyanine green clearance) were significantly predicted by changes in main portal vein flow alone (R2= 0.76). These data support the validity of Doppler flowmetry in quantifying change in regional blood flow, but highlight the limitations in its clinical application and interpretation. The association of changes in main portal vein flow with changes in sinusoidal perfusion has clinical potential but requires confirmation using other modulating drugs.

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00004.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractWe retrospectively examined 154 adults to ascertain the frequency, site of and pre‐disposing factors for biliary strictures after liver transplantation, as well as their management and clinical outcome. Twenty patients (12.5%) were identified with biliary strictures; 16 were non‐anastomotic and four were anastomotic strictures. The median time from transplantation to stricture diagnosis was 17 weeks (range 3–366). Of the 16 non‐anastomotic strictures, six were intrahepatic, eight hilar and two extrahepatic (donor bile duct). A control group (n = 32) of patients transplanted immediately before and after index cases was used to examine for correlates in patients with non‐anastomotic strictures. At the time of diagnosis in the non‐anastomotic index cases, there was a higher incidence of: (i) biliary sludge (63 vs 0%; P<0.001); and (ii) clinical cholangitis (75 vs 0%; P<0.001) compared with controls. Primary sclerosing cholangitis was more often the diagnosis in index patients with non‐anastomotic strictures compared with controls (31 vs 9%; P<0.05). There were no differences between index patients and controls (non‐anastomotic group) in ABO blood group non‐identity, cold allograft ischaemia time, use of OKT3 (murine monoclonal antibody to CD3) and hepatic artery thrombosis. Of 15 patients treated with balloon dilatation, seven required stent insertion although none have required surgery. As determined by liver function tests, there was evidence of persisting graft dysfunction in index patients compared with controls (SAP 381 vs 112 U/L, P<0.001; GGT 529 vs 80 U/L, P<0.001), but there was no difference in survival during a median follow‐up time of 16 months (range: 3–48 months) from stricture diagnosis. In conclusion, biliary strictures tend to occur within 6 months of transplantation and are an important cause of ongoing graft dysfunction. Non‐anastomotic strictures were more common in patients requiring transplantation for primary

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00005.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe experimental study of possible therapies for control of the growth of liver metastases requires the availability of a model which is technically feasible and appears to exhibit growth characteristics similar to human tumours. We report on the development of an intrasplenic injection model of liver metastases, and describe the histology, growth pattern and blood flow demonstrated by light microscopy, stereology and laser Doppler flowmetry. The hepatic metastases were induced in mice by intrasplenic injection of dimethylhydrazine (DMH) induced primary colonic carcinoma cells (106cells in 1 mL). The growth and development of metastases was studied over a period of 3 weeks at predetermined time points. Tumour cells were visible in the hepatic sinusoids by day 7 by light microscopy. Macroscopically visible tumours with a diameter of 0.18 ± 0.02 cm (mean ± s.d.) were seen by day 10. By this time the tumours had derived a blood supply from the hepatic sinusoids adjacent to the tumour periphery. With further vascularization the tumours reached a diameter of 0.96 ± 0.50 cm by day 22. Metastatic growth was quantitated by stereological analysis of tumour volume in relation to non‐diseased hepatic tissue. Normal mouse liver had a mean volume of 1.13 ± 0.14 cm3. Tumour growth occurred in three phases. During the initial slow phase the volume of metastases increased from 0.03 ± 0.02 cm3at day 10 to 0.22 ± 0.24 cm3by day 16. Rapid tumour growth, occurring over the next 3 days, constituted the intermediate phase with metastatic volume reaching 1.21 ± 0.74 cm3by day 19 (P= 0.0003 compared with day 16). This growth was followed by a plateau phase when the metastatic volume was 1.40 ± 0.55 cm3at day 22. The volume of total liver and of tumour necrosis followed a similar growth pattern. A necrotic tumour volume of 0.004 ± 0.006 cm3first seen on day 10 increased to 0.05 ± 0.06 cm3by day 16, and to 0.25 ± 0.20 cm3by day 22 (P=0.0022 compared with day 16). The blood flow in metastases measured by laser Doppler flowmetry was lower compared to the non‐diseased liver. Tumour blood flow, expressed as a percentage of normal liver blood flow, was 63.31 ± 26.28% at day 10 and diminished to 27.91 ± 8.99% by day 22, with an increase in tumour size and age. The decrease in flow was significant between days 13 and 16 (P= 0.0015). This intrasplenic mouse model of metastases is reproducible and should prove useful in the study of treatment of he

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00006.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractDrug metabolism is usually impaired in malnourished patients with decompensated cirrhosis, but the separate influence of clinicopathological variables, including nutritional status, on the expression of hepatic cytochrome P450 proteins has not been well characterized. We determined the hepatic content of CYP1A2, CYP2C8/10, CYP2E1 and CYP3A proteins in 71 subjects, 21 with histologically normal livers and 50 with chronic liver disease, and then tested for potential relationships between patient variables and individual CYP proteins by multivariate linear regression analysis. Variables analysed included nutritional status (determined by experienced clinicians), serum albumin and bilirubin concentrations, prothrombin time, the grade of ascites and hepatic encephalopathy, and the Child‐Pugh score. Impaired nutrition and cachexia were associated with reductions of CYP2C8/10 levels of approximately 19 and 39%, respectively, relative to cases in which nutrition was replete. Similarly, CYP2E1 protein was reduced by approximately 13 and 26%, according to the apparent severity of nutritional impairment. In contrast, nutritional status did not contribute to variability in expression of CYP1A2 or CYP3A proteins. Of the clinicopathological variables analysed, only serum bilirubin was shown to have an independent influence on CYP protein content. Thus, elevated serum bilirubin concentrations were associated with significant declines in the contents of CYP1A2 and CYP2C8/10 but not CYP3A or CYP2E1. The mechanisms for the effects of nutritional status and serum bilirubin concentration on the levels of CYP proteins are unclear, but could be mediated by factors such as cytokines, dietary composition and alterations in the level of serum bile acids. Knowledge of the influence of clinicopathological factors and nutritional status on CYP expression should lead to more rational drug prescribing in patients with hepatic diseas

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00007.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe reproducibility of echo‐Doppler measurements of portal vein and superior mesenteric artery blood flow has not been extensively studied. In the present study, two groups of subjects were examined to test inter‐ and intra‐observer reproducibility. Each study population consisted of 15 non‐portal hypertensive and 15 portal hypertensive subjects. With a standardized technique, the cross‐sectional area and velocity of blood flow in the portal vein and superior mesenteric artery were recorded in triplicate by skilled operators. The flow volume of each vessel was calculated by multiplying the cross‐sectional area by the velocity of blood flow. The measurements were performed in a blind fashion over a 60 min period. The reproducibility of measurements was assessed by calculation of intraclass correlation coefficients and coefficients of variation. The intra‐observer intraclass correlation coefficient was 0.77 for portal vein blood flow and 0.84 for superior mesenteric artery blood flow, suggesting good reproducibility. The intra‐observer coefficient of variation was 11 and 9%, respectively. In contrast, the interobserver intraclass correlation coefficient was calculated to be 0.49 for portal blood vein blood flow and 0.57 for superior mesenteric artery blood flow, indicating fair reproducibility. In addition, the interobserver coefficients of variation were calculted to be 20 and 18%, respectively. These data suggest that intra‐observer reproducibility in echo‐Doppler measurements of portal vein and superior mesenteric artery blood flow is acceptable but inter‐observer reproducibility is not. Examination by a single operator, rather than multiple operators, is therefore advisable. Even when measurements are performed by a single investigator an approximate variance of 10% in the measurement in a single subje

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00008.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractA hospital‐based study was performed in order to examine the subsite distribution of colorectal cancer diagnosed in 1992–93 in the Zaanstreek region. The localization was compared with tumours diagnosed in the years 1972–73 and 1982–83. The number of colorectal cancers has markedly increased, and a significant rise in localization of tumours proximal to the splenic flexure has occurred (32% in 1972–73 to 43% in 1992–93). There also appears to be greater incidence of colorectal cancer in women. A trend towards an increase of proximal localization of tumours in women was noted. Possible explanations for this phenomenon are discussed. The results of this study suggest the importance of improved diagnostic accuracy in colorectal cancer and, in addition, may have consequences for screening

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00009.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractAlthough less common than oesophageal varices in portal hypertension, gastric fundal varices carry a higher mortality rate when they rupture. They are less amenable to sclerotherapy. We have developed a minimally invasive balloon‐occluded retrograde transverse obliteration (B‐RTO) procedure to treat gastric fundal varices. B‐RTO involves inserting a balloon catheter into an outflow shunt (gastric‐renal or gastric‐vena caval inferior) via the femoral or internal jugular vein. Blood flow is then blocked by inflating the balloon, and 5% ethanolamine oleate iopamidol is injected in a retrograde manner. The embolized gastric varix subsequentlyl disappears. B‐RTO was performed in 32 patients with gastric varices. Follow‐up endoscopies were performed at intervals of 2–4 months for an average observation period of 14 months. Eradication of the varices has been confirmed in 31 of 32 patients. No recurrence occurred in any patients in the follow‐up period. There were no significant changes in liver function after the procedure. We conclude that B‐RTO is a safe and effective procedure for the treatment of gas

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00010.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe prevalence of gastric ulcer and its relationship to the severity of cirrhosis and degree of portal hypertension was evaluated in 245 cirrhotic patients, and compared with 245 age‐ and sex‐matched healthy subjects. Portal and systemic haemodynamic studies were performed in cirrhotic patients. The prevalence of gastric ulcer in cirrhotic patients was 20.8%, which was significantly higher than the 4.0% found in healthy controls. Using a multivariate logistic regression model, the hepatic venous pressure gradient was found to be the only predictor of the prevalence of gastric ulcer in cirrhotic patients to present with gastric ulcer. The hepatic venous pressure gradient was significantly higher in cirrhotic patients with gastric ulcer than in those without (17.3 ± 4.4 vs 15.5 ± 5.0 mmHg, P= 0.01). Other variables, including sex, smoking, cardiac output and severity or aetiology of cirrhosis did not show significant differences between the two patient groups. The prevalence of gastric ulcer in cirrhotic patients whose hepatic venous pressure gradient was below 12 mmHg (4.5%) was similar to that observed in the healthy controls (4.0%). However, when the hepatic venous pressure gradient was>12 mmHg, the prevalence of gastric ulcer (24.4%) was significantly higher than that in control subjects. However, the incidence of gastric ulcer was not related to the degree of portal hypertension. In conclusion, the prevalence of gastric ulcer in cirrhotic patients was found to be significantly higher than in the age‐ and sex‐matched healthy subjects. Portal hypertension with a hepatic venous pressure gradient>12 mmHg may be an important factor contributing to the increased prevalence of gastric ulcer observed in patients with liver

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb00011.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY