Regional differences of reactivity to stimulants in the dog portal tree.

We studied the regional differences both of reactivity to various stimulants and of neurogenic responses elicited by transmural stimulation in the longitudinal and circular muscles of the truncal portal vein, mesenteric vein, splenic vein and gastric vein of the dog portal tree. Strong spontaneous activity appeared in the longitudinal muscle of the truncal portal vein (96% of preparations tested). Weak spontaneous activity sometimes appeared in the circular muscle of the truncal portal vein (41%) and rarely in the longitudinal muscle of the mesenteric vein (12%). It did not appear in other segments. The splenic vein and the gastric vein showed similar patterns in the relationship between resting tension and response to noradrenaline; that is, the responsiveness of either longitudinal or circular muscle of these two veins increased and then decreased almost parallel as resting tension increased and reached a maximum under the same resting tension. The longitudinal muscle of both the truncal portal vein and the mesenteric vein was more responsive to noradrenaline, acetylcholine, histamine and KCl than the circular muscle; for example 2.02 and 1.44 times more responsive to noradrenaline, respectively. On the other hand, the longitudinal muscle of the splenic vein and the gastric vein responded less well than the circular muscle; for example 0.36 and 0.16 times as responsive to noradrenaline, respectively. Acetylcholine and histamine caused marked contractions which were comparable to those elicited by noradrenaline in the longitudinal muscle of the truncal portal vein. Acetylcholine also elicited similar contractions in the longitudinal muscle of the mesenteric vein but the responses induced in preparations of other segments were small.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical utility of doppler ultrasonography in evaluation of early therapeutic efficacy after transcatheter arterial embolization in patients with hepatocellular carcinoma

This study was undertaken to determine the value of Doppler ultrasonography in the early evaluation of therapeutic efficacy of hepatocellular carcinoma after transcatheter arterial embolization (TAE). Fifty-two nodules in which tumor vascularity had been detected by Doppler ultrasonography before TAE were examined in 41 patients. Doppler signals were evaluated 1 week after TAE, and the results were compared with tumor vascularity as determined by dynamic magnetic resonance imaging (dynamic MRI), which was used as the gold standard. The sonographic signal disappeared in 41 (79%) of the 52 nodules and remained in 11 (21%). All nodules in which intratumor vascularity had been detected showed positive stain to dynamic MRI. Four of 41 nodules in which the sonographic signal disappeard showed positive stain on dynamic MRI. The Sensitivity of Doppler ultrasonography was 73%; specificity, 100%; and accuracy, 92%. Flow signal in deeply (≥5 cm) located small (<3 cm) nodules tended to be more difficult to detect. We conclude that Doppler ultrasonography warrants use after TAE in the early evaluation as a specific and noninvasive imaging technique.     

Functional deterioration of the liver by elevated inferior vena cava pressure: A proposed upper safety limit of pressure for maintaining liver viability in dogs

Objective Abnormally elevated central venous pressure is considered to be an etiological factor in the onset of acute hepatic failure following modified Fontan operation. This paper hypothesises that an increase in inferior vena cava pressure (IVCP) after such an operation has adverse effects on hepatic energy status.Design Various degrees of venous hypertension were produced in 10 mongrel dogs by clamping the thoracic IVC with an active veno-venous shunt and varying its flow rate from 60–2.5 ml/min/kg. Arterial ketone body ratio (KBR), reflecting the hepatic mitochondrial redox state, was measured as an index of hepatic energy status.Measurements and results: The lower the flow rates of the shunt, the higher the pressures of IVC and portal vein, while systolic blood pressure was maintained above 100 mmHg. CO significantly decreased when the pump speed was less than 30 ml/min/kg. KBR showed a negative correlation to IVCP as well as a positive correlation to portal blood flow (p<0.05).Conclusion From the simple regression line obtained between IVCP and KBR, it was determined that an upper safety limit of IVCP may lie at about 27 cmH₂O (20.5 mmHg), and that a IVCP of 35 cmH₂O (26.6 mmHg) seems to be the critical level for maintaining liver viability.Supported in part by grants from the Scientific Research Fund of the Ministry of Education and a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare, Japan     

Recent advances in biochemical diagnosis and assessment of severity in acute pancreatitis

Serum amylase is most commonly used as a biochemical marker of acute pancreatitis (AP). But it lacks specificity. The serum lipase level is more accurate and a better marker. Serum elastase -1 level is specific and remains elevated longer, but its radioimmunoassay is not routinely used. Recently, it can be rapidly measured by latex turbidometric immunoassay with automatic analyzer. Biochemically, only CRP test is available and useful to assess severity, but its sensitivity is unacceptably low in the early course of the disease. Urinary trypsinogen activation peptide (TAP) or trypsinogen-2 is an earlier marker. Increasing knowledge of the inflammatory process in AP has led to possibly useful biochemical indicators of severity, such as cytokines, nonpancreatic synovial type group II PLA2 or granulocyte elastase.     

Significance of serum ribavirin concentration in combination therapy of interferon and ribavirin for chronic hepatitis C

OBJECTIVE: The purpose of this clinical retrospective cohort study was to determine the most suitable ribavirin concentration on combination therapy of interferon (IFN)-ribavirin. METHODS: Entry criteria were serum HCV-RNA level >/=100 KIU/ml, HCV-genotype 1b, chronic hepatitis, and initial combination treatment of IFN-alpha-2b (6 million units daily for 2 weeks and then 3 times weekly for 6 weeks) and ribavirin (600-800 mg/day) for 8 weeks without stopping or decreasing the dosage of IFN and/or ribavirin. Sixty-eight consecutive patients who satisfied the above criteria were given maintenance therapy for another 16 weeks. RESULTS: A sustained virological response (SVR) rate of 25.0% (17/68) was seen in all subjects. The SVR rate was 44.0% (11/25) in the high ribavirin group with a serum ribavirin concentration of >/=3,000 ng/ml at 8 weeks after initiation of combination therapy. SVR was significantly dependent at a serum ribavirin level of >/=3,000 ng/ml (p = 0.005). The incidence of discontinuations and dose modifications for combination therapy in patients having a serum ribavirin concentration of >/=3,500 ng/ml 8 weeks after initiation of therapy was 57.1% (4/7). This value was statistically higher than that in patents with <3,500 ng/ml (p = 0.033). CONCLUSION: Our results showed that the most suitable serum ribavirin concentrations are from 3,000 to 3,500 ng/ml 8 weeks after initiation of combination therapy.     

New oral drugs for the treatment of congestive heart failure]

The crucial issues in the management of congestive heart failure (CHF) are improvement of depressed myocardial contractility and reduction of excessive load. For this purpose, positive inotropic agents and vasodilators have been developed as new oral drugs. The former include Denopamine which possesses beta 1 stimulating effect, Xamoterol which is a unique agent acting as a beta 1-partial agonist, and Ibopamine, Docarpamine and Phosphodiesterase Inhibitors which possess both inotropic and vasodilating effects and are called "Inodilators". The latter include Angiotensin Converting Enzyme Inhibitors. In addition, new vasodilators, such as, Vasopressin Antagonist have also been developed. However, careful long-term clinical trials are required with regard to the efficacy and adverse effects before these agents are widely used with safety in the management of CHF.     

Specific detection of Epstein-Barr virus in inflammatory pseudotumor of the spleen in a patient with a high serum level of soluble IL-2 receptor

A case of inflammatory pseudotumor of the spleen is described in a 63-year-old woman who presented with an intrasplenic tumor and an elevated serum level of soluble interleukin 2 receptor (sIL-2R). Microscopic examination after removal of the spleen revealed that the tumor was composed of mixed cellular infiltrates, mainly lymphocytes and plasma cells, and spindle-cell proliferation. Epstein-Barr virus (EBV) was specifically detected in the tumor by in situ hybridization for EBV RNA. The serum level of sIL-2R level was normalized after splenectomy. EBV infection may play a role in the development of splenic inflammatory pseudotumor and the elevation of sIL-2R level. Received: May 27, 1999 / Accepted: November 26, 1999     

Development of HCC in patients receiving adefovir dipivoxil for lamivudine‐resistant hepatitis B virus mutants

Aim: To identify factors for the development of hepatocellular carcinoma (HCC) in the patients who receive adefovir add‐on lamivudine for treatment of lamivudine‐resistant hepatitis B virus (HBV) mutants. Methods: A total of 247 patients who developed lamivudine‐resistant HBV mutants, with an increase of HBV DNA ≥ 1 log copies/mL, received adefovir dipivoxil 10 mg add‐on lamivudine 100 mg daily during a median of 115 weeks (range: 25–282 weeks). They were followed for the development of HCC by imaging modalities every 3?6 months. Results: HCC developed in 18 of the 247 (7.3%) patients. Eight factors were in significant association with the development of HCC by the univariate analysis. They included age, cirrhosis, platelet counts, levels of bilirubin, aspartate aminotransferase (AST), alanine aminotransferase and α‐fetoprotein, as well as YMDD mutants at the start of adefovir dipivoxil. By the multivariate analysis, AST levels, YIDD mutants, cirrhosis and age were independent factors for the development of HCC. By the Kaplan‐Meier analysis, AST levels ≥ 70 IU/L, YIDD mutants, cirrhosis and age ≥ 50 years increased the risk of HCC (P = 0.018, P = 0.035, P = 0.002 and P = 0.014, respectively). HCC developed more frequently in the patients with than without cirrhosis at the start of adefovir (10/59 [16.9%] vs. 8/188 [4.3%], P = 0.002). Conclusion: HCC can develop in cirrhotic patients receiving adefovir add‐on lamivudine. Hence, the patients with baseline AST ≥ 70 IU/L and YIDD mutants would need to be monitored closely for HCC.     

New classification of dynamic computed tomography images predictive of malignant characteristics of hepatocellular carcinoma

Aim: The aim of this study was to elucidate whether the histopathological characteristics of hepatocellular carcinoma (HCC) can be predicted from baseline dynamic computed tomography (CT) images. Methods: This retrospective study included 86 consecutive patients with HCC who underwent surgical resection between January 2000 and September 2008. The arterial‐ and portal‐phase dynamic CT images obtained preoperatively were classified into four enhancement patterns: Type‐1 and Type‐2 are homogeneous enhancement patterns without or with increased arterial blood flow, respectively; Type‐3, heterogeneous enhancement pattern with septum‐like structure; and Type‐4, heterogeneous enhancement pattern with irregular ring‐like structures. We also evaluated the predictive factors for poorly‐differentiated HCC, specific macroscopic type of HCC (simple nodular type with extranodular growth [SNEG] and confluent multinodular [CMN]) by univariate and multivariate analyses. Results: The percentages of poorly‐differentiated HCC according to the enhancement pattern were three of 51 nodules (6%) of Type‐1 and ‐2, three of 24 (13%) of Type‐3, and eight of 11 (73%) of Type‐4. The percentages of SNEG/CMN according to the enhancement pattern were 12 of 51 nodules (24%) of Type‐1 and ‐2, 13 of 24 (54%) of Type‐3, and five of 11 (45%) of Type‐4. Multivariate analysis identified Type‐4 pattern as a significant and independent predictor of poorly‐differentiated HCC (P < 0.001) while Type‐3 pattern was a significant predictor of SNEG/CMN (P = 0.017). Conclusion: Heterogeneity of dynamic CT images correlates with malignant characteristics of HCC and can be potentially used to predict the malignant potential of HCC before treatment.