Dermatotoxicity of agricultural chemicals in the dorsal skin of hairless dogs

BACKGROUND: Standard treatment of inoperable hepatocellular carcinoma has not been established. Somatostatin has been shown to possess antimitotic activity against a variety of non-endocrine tumours. AIMS: To assess the presence of somatostatin receptors in human liver and to treat advanced hepatocellular carcinoma with the somatostatin analogue, octreotide. METHODS: Somatostatin receptors were measured in liver tissue homogenates from patients with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Fifty eight patients with advanced hepatocellular carcinoma were randomised to receive either subcutaneous octreotide 250 micrograms twice daily, or no treatment. Groups were comparable with respect to age, sex, Okuda classification, presence of cirrhosis, and liver biochemistry and virology. RESULTS: Various amounts of somatostatin receptors were identified in liver tissue of all patients including those with hepatocellular carcinoma. Treated patients had an increased median survival (13 months versus four months, p = 0.002, log rank test) and an increased cumulative survival rate at six and 12 months (75% versus 37%, and 56% versus 13% respectively). Octreotide administration significantly reduced alpha fetoprotein levels at six months. When a multivariable Cox's proportional hazards model was fitted, variables associated with increased survival were: treatment administration, absence of cirrhosis, increased serum albumin, and small tumours. Treated patients clearly had a lower hazard (0.383) in the multivariate analysis. CONCLUSIONS: Octreotide administration significantly improves survival and is a valuable alternative in the treatment of inoperable hepatocellular carcinoma.     

Virus-associated hemophagocytic syndrome after hepatic resection: a case report

Virus-associated hemophagocytic syndrome (VAHS) is associated with a systemic viral infection and is mainly observed in immunosuppressed adult patients. This rare disease is characterized by symptoms which include a high fever, pancytopenia, and splenomegaly and sometimes results in a fatal outcome. However, thus far, little has been reported on VAHS in general surgical patients. We herein report this rare complication which occurred in a patient with hepatocellular carcinoma, as well as chronic hepatitis C, after a hepatic resection. A 66-year-old man with chronic hepatitis C and recurrent hepatocellular carcinoma underwent a repeat hepatic resection without any blood transfusions. In the early postoperative period, he recovered uneventfully. However, he suddenly began to suffer from a high fever (38.4 degrees C) and severe pancytopenia 8 days after surgery. Activated macrophages, which phagocytosed erythrocytes, were identified by a cytological study of the bone marrow. The patient was therefore treated with methylprednisolone pulse therapy 13 days after surgery. On the day following the initial administration of methylprednisolone, his clinical condition drastically improved. Fortunately, with methylprednisolone therapy, our patient recovered from acute, severe pancytopenia. In general surgery, it is often difficult for surgeons to use steroids due to their negative side effects. However, when symptoms such as fever, general fatigue and pancytopenia are observed, even in posthepatectomy patients with hepatocellular carcinoma and hepatitis, a bone marrow aspiration should be performed as soon as possible, and when VAHS is suspected, steroid pulse therapy should be the first treatment of choice. This rare but sometimes fatal complication should thus be taken into consideration in the postoperative management of hepatectomized patients with chronic hepatitis C.     

Serial changes in serum alpha-fetoprotein prior to detection of hepatocellular carcinoma in liver cirrhosis

In 49 liver cirrhosis patients with hepatocellular carcinoma in which the hepatocellular carcinoma nodule was smaller than 30 mm in size, serial changes in serum alpha-fetoprotein levels prior to the detection of the hepatocellular carcinoma were studied retrospectively, and compared with those of 70 cirrhotic patients with no hepatocellular carcinoma. The changes in alpha-fetoprotein levels were classified into the 4 types normal, low plateau, high plateau and spiky type. The spiky type (spiky elevation during a short period) was more frequently noted in the patients with hepatocellular carcinoma than in those with liver cirrhosis. In a prospective analysis of 39 patients with liver cirrhosis, hepatocellular carcinoma was detected in 6, and was also more frequently noted in the spiky type than the other types. Moreover, in the hepatocellular carcinoma patients with the spiky type of alpha-fetoprotein, hepatocellular carcinoma was suspected, on the basis of the tumor doubling time, to exist at the time of the first elevation of alpha-fetoprotein. These results suggest that the liver cirrhotics with the spiky type of alpha-fetoprotein may be considered to be a high-risk group of hepatocellular carcinoma.     

Abnormal regulation of plasma pyridoxal 5'-phosphate in patients with liver disease

Pyridoxal 5'-phosphate (PLP), the coenzyme form of vitamin B6, is essential for many biochemical reactions in the body. Studies in experimental animals have suggested that the liver is a primary site for the formation of PLP circulating in the plasma, and that it may also participate in its degradation. This study evaluates, for the first time, the effects of liver disease in man on the regulation of plasma PLP. The plasma PLP level was measured before and sequentially after the rapid intravenous administration of 50 mg of pyridoxine to patients with alcoholic cirrhosis, acute hepatitis, and extrahepatic obstruction, and to normal control subjects. The base line plasma PLP concentration was significantly lower in cirrhotic patients than in normal persons (P less than 0.025), and there was a tendency for it to be reduced in patients with extrahepatic obstruction. After administration of pyridoxine there was a significant increase in the plasma PLP level over a 2- to 12-hr period, after which the concentration returned gradually toward the initial value. The area under the concentration/time curve was from 2 to 8 times smaller (P less than 0.002) in the patients with liver disease. To assess possible mechanisms of this change, 5 mg of PLP were intravenously administered to the various patient groups and the pharmacokinetics of the disposition were assessed. The initial and steady state volumes of distribution of PLP were comparable in cirrhotics and controls (P greater than 0.05), but the clearance of plasma PLP in cirrhotics was much faster (63.0 +/- 7.4 versus 31.7 +/- 2.7 ml per min, P less than 0.004). Similar findings were obtained in the other liver disease subjects. The in vitro plasma binding of PLP at supracirculatory concentrations was comparable in cirrhotics and controls (99.4 versus 99.5%, P greater than 0.05). In conclusion: (1) plasma PLP regulation in patients with liver disease is abnormal, (2) a significant factor in the decrease in plasma PLP after intravenous pyridoxine administration in these patients appears to be an increase in the total plasma clearance of the coenzyme, and (3) it is postulated that this may be due to increased degradation of PLP by the diseased liver.     

Impact of hepatitis C virus infection on schistosomal liver disease

BACKGROUND/AIMS: This study was conducted to determine whether Hepatitis C virus infection has a role in patients with schistosomal liver disease. METHODOLOGY: Sixty patients with hepatosplenic schistosomiasis and evidence of portal hypertension were seen at the Armed Forces Hospital Riyadh, Saudi Arabia over 5 years. The impact of Hepatitis C virus infection on chronic schistosomal liver disease was studied in 30 of these patients (group one) who were Hepatitis C virus positive and compared with the other 30 patients (group two) who were Hepatitis C virus negative (control group). RESULTS: Hepatitis C virus may be an important factor contributing to deterioration of liver function for patients with hepatosplenic schistosomiasis. Liver functions showed elevated ALT in 83.3% in group one compared to 23.4% in group two. Liver biopsy in 19 patients (group one) and 16 patients (group two) showed evidence of schistosomiasis and in patients of group one, liver biopsy also showed chronic active hepatitis together with Schistosoma in 57.9%, and cirrhosis in 31.6%. None of group two patients had cirrhosis. Alpha-fetoprotein levels were elevated in 16 patients (group one) and 3 of these patients had hepatocellular carcinoma. None of the control group had radiological or histological evidence of hepatocellular carcinoma. CONCLUSION: The mean age of HCV positive patients was less than the HCV negative patients, which may indicate that Hepatitis C virus infection leads to decompensation of liver function earlier in patients with Schistosoma and severe liver disease may be promoted at a younger age in Schistosoma patients with hepatitis C.     

HCV genotypes in patients with liver disease of different stages and severity

AIMS/MATERIAL: Hepatitis C virus (HCV) genotyping was performed in 213 anti-HCV-positive patients with chronic liver disease ranging from minimal histological changes to hepatocellular carcinoma. One hundred and twenty-two patients had non-cirrhotic chronic active or persistent hepatitis (including 29 who were asymptomatic with persistently normal ALT levels) (chronic liver disease group). The other 91 had hepatocellular carcinoma and, in all but three cases, cirrhosis (hepatocellular carcinoma group). RESULTS: The overall prevalence of HCV variants was: 54.9% type 1b, 37.8% type 2, 2.5% type 1a, 2.0% type 3a, 2.0% type 4a. The genotype distribution showed no relation to the stage (chronic liver disease vs. hepatocellular carcinoma) or severity (chronic active vs. chronic persistent hepatitis) of the liver disease, or to the duration of the disease (<10 years vs. >10 years). Within the hepatocellular carcinoma group, the duration of type-1b disease was similar to that of type-2 infections. Ages at the time of infection and genotype were both independently associated with progression to cirrhosis and hepatocellular carcinoma, but multivariate analysis revealed that the effect of age was much stronger than that of genotype 1b. CONCLUSIONS: The predominance of HCV type 1b in this study reflects the higher frequency of this variant in our area. Our findings indicate that infections caused by each HCV genotype are capable of progressing to hepatocellular carcinoma.     

Wound botulism associated with black tar heroin

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is thought to play an important role in cellular immunological reactions. Expression can be induced by inflammatory cytokines in a wide variety of cells, including hepatocytes. OBJECTIVE: To compare the behaviour of ICAM-1 in liver diseases. PATIENTS AND METHODS: We assayed serum ICAM-1 (sICAM-1) in patients with hepatocellular carcinoma-associated liver cirrhosis, and compared them with a group of cirrhotic patients and controls. sICAM-1 values were also correlated with some biochemical parameters of liver function. Moreover, immunohistochemical localization of ICAM-1 was performed on liver tissue sections of patients with hepatocellular carcinoma, liver cirrhosis and a sample of normal liver. RESULTS: sICAM-1 levels were significantly higher in the hepatocellular carcinoma patients than in controls (P < 0.0001) and the cirrhosis group (P < 0.001). sICAM-1 values directly correlated with alanine aminotransferase, total bilirubin, alkaline phosphatase and gamma-glutamyltranspeptidase serum values (P < 0.05), with an inverse correlation with albuminaemia values (P < 0.05). There was no correlation with alpha-fetoprotein values, but sICAM-1 values were higher in hepatocellular carcinoma patients with large tumours (> 3 cm) than in those with small tumours (< 3 cm) (P < 0.04). Immunohistochemical localization of ICAM-1 was negative in normal liver tissue; positive staining for endothelial cells was found in chronic liver disease, while in hepatocellular carcinoma tissues, positive membrane staining was observed in hepatocytes and, to a lesser extent, at the cytoplasmic level. CONCLUSION: These results suggest that high serum levels of sICAM-1 are associated with severe liver disease, such as liver cirrhosis and hepatocellular carcinoma, and that they tend to increase with deteriorating hepatic function and tumour size.     

Pharmacokinetics of high dose methylprednisolone and use in hematological malignancies

The pharmacokinetics of oral and intravenous high dose methylprednisolone (Solu-medrone, Upjohn) were compared in patients with hematological malignancies. The aim of the study was to determine the oral bioavailability of high dose methylprednisolone and to establish whether this is a feasible and more convenient route of administration. The plasma pharmacokinetics were described by a one-compartment open model with peak plasma levels of 6.9 +/- 2.5 micrograms/ml. Total area under the plasma concentration versus time curve was similar by either route. Mean relative oral bioavailability was generally high (91 +/- 27 per cent). Retrospective analysis of 34 patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's and Hodgkin's lymphoma treated with high dose methylprednisolone showed 11 responses including two complete remissions among nine patients with CLL. There was significant improvement in platelet counts in thrombocytopenic patients and treatment was well tolerated and toxicity was relatively low. High dose methylprednisolone may therefore be a useful palliative treatment for hematological malignancies, particularly where marrow suppression is a problem.     

Circulating platelet-derived endothelial cell growth factor increases in hepatocellular carcinoma patients

BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic factor that is expressed in various cancer tissues. Little is known regarding plasma PD-ECGF levels in patients with chronic liver disease such as chronic hepatitis (CH), cirrhosis, and hepatocellular carcinoma (HCC) with cirrhosis. The expression of PD-ECGF in HCC tissues also remains to be clarified. METHODS: Plasma PD-ECGF levels in patients with chronic liver disease were determined with an enzyme-linked immunoadsorbent assay system using the mouse monoclonal antibodies specific to PD-ECGF. These were cross-sectionally compared among groups of normal persons, CH, cirrhosis, and HCC patients. The HCC patients were classified into two groups based on TNM stage: early and advanced stage disease groups. PD-ECGF expressions in HCC tissues were immunohistologically examined. RESULTS: The plasma PD-ECGF levels from the normal individuals and those with CH, cirrhosis, and HCC specimens were 4.2+/-0.5, 4.3+/-0.6, 4.6+/-1.1, and 6.0 +/-2.5 U/mL, respectively. The plasma PD-ECGF concentration was highest in HCC (P < 0.05). No significant difference was found among the normal subjects, CH, and cirrhosis specimens. Plasma PD-ECGF concentrations were significantly higher in the advanced stage disease HCC group compared with the early stage disease group (6.75+/-2.62 U/mL vs. 4.19+/-0.34 U/mL) (P < 0.05). Immunohistochemical expression of PD-ECGF in HCC cells increased significantly compared with normal liver cells (P < 0.05). CONCLUSIONS: Circulating PD-ECGF plasma level might be a new tumor marker for progression in patients with HCC. Immunohistological findings correspond to elevation of the plasma PD-ECGF in HCC patients. It is possible that increased production of PD-ECGF in HCC cells causes abundant neovascularization.     

Enhanced glycosylation and sulfation of secretory proteoglycans is coupled to the expression of a basic secretory protein

BACKGROUND: Because the prognosis of patients with hepatocellular carcinoma is not fully understood, particularly regarding therapy, we have evaluated it in a series of patients with a homogeneous diagnostic and therapeutic work-up. METHODS: From 1985 to 1996, 42 variables were recorded prospectively in 178 constructive patients who had a diagnosis of hepatocellular carcinoma. Treatment consisted of liver transplantation ( n = 22), partial hepatectomy (n = 11), arterial, chemoembolization ( n = 52), systemic or regional chemotherapy (n = 51), and other therapies (n = 5); 37 patients received no specific therapy. Statistical analysis was performed according to a Cox model. RESULTS: There were no differences between the survival of patients receiving chemotherapy, other therapies, or no treatment (control group n = 93). survival rates a 1,3, and 5 years were 81%, 74%, and 74% for liver transplantation, 72%, 58%, and 58% for hepatectomy, 55%, 26%, and 13% for chemoembolization, and 13%, 3%, and 0% for the control group. Cirrhosis, systemic syndrome, bilobar involvement, Child's stage C disease, and treatment were independent predictors of survival. CONCLUSIONS: This series shows that certain easily accessible parameters may help establish individual prognosis and stratify patients in clinical trials and indicates that chemoembolization, partial resection, and liver transplantation can prolong life expectancy of patients with hepatocellular carcinoma.     

Impaired reactivity of rat aorta to phenylephrine and KCl after prolonged hypoxia: role of the endothelium

PURPOSE: The aim of the study was to evaluate the efficacy of antiandrogen therapy on overall survival and response in unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 244 patients with unresectable HCC were included in this multicentric double-blind trial. According to a two-by-two factorial design, patients were randomly assigned to receive one of the following treatments: pure antiandrogen plus placebo (A+P group, 60 patients); luteinizing hormone-releasing hormone (LHRH) agonist plus placebo (LHRH+P group, 62 patients); pure antiandrogen plus LHRH agonist (A+LHRH group, 62 patients); or placebo plus placebo (P+P group, 60 patients). Pure antiandrogen consisted of Anandron (Roussel-Uclaf Laboratory, Romainville, France) administered orally (300 mg daily for 1 month, then 150 mg daily). LHRH consisted of goseriline acetate (3.6 mg) or triptoreline (3.75 mg) administered monthly by subcutaneous injection. Treatment was given until death. Response was evaluated every 8 weeks according to World Health Organization (WHO) criteria. RESULTS: Six patients were considered ineligible. One patient had a complete response (A+P arm) and three had a partial response (two in the LHRH+P arm and one in the A+LHRH arm). An overall log-rank test did not demonstrate any significant difference in survival among the four arms. Taking the factorial design into account, comparison of survival showed no significant difference between Anandron-containing regimens and others, or between LHRH-containing regimens and others. No serious side effects occurred for any regimen. CONCLUSION: This controlled study shows clearly the lack of efficacy of androgen treatment in unresectable HCC.     

Iron increases ethanol toxicity in rat liver

Clinical evidence indicates that patients with iron overload are more susceptible to liver cell damage from alcohol than persons with normal iron stores. Iron may act as a co-factor to catalyze the lipid peroxidation induced by hepatotoxic compounds such as alcohol. To elucidate the role of iron in ethanol-induced hepatocellular damage, we developed a new experimental model in the rat. Following dietary carbonyl iron feeding for 8 weeks, animals were pair-fed a liquid ethanol diet for 4 weeks. In iron-fed animals the liver iron content was 6.4 vs. 0.5 micrograms Fe/mg protein in the controls. Blood alcohol concentrations were similar in all ethanol-fed animals. Serum alanine aminotransferase (ALT) levels were elevated to 269 +/- 49 U/l in the iron+alcohol group compared to 52 +/- 6 U/l in the other groups. There was a strong correlation between ALT levels and hepatic iron content in the ethanol-fed animals. Morphologically, the alcohol-fed rats displayed hepatic steatosis, whereas occasional inflammation and iron in Kupffer cells was seen in the iron+alcohol animals. Ultrastructurally, necrotic hepatocytes and cells phagocytosed by Kupffer cells were only encountered in the iron+alcohol group. Compared to controls, the liver content of hydroxyproline was significantly increased in the iron+alcohol group. No morphological evidence of fibrosis was noted. The present study demonstrates biochemical and morphological evidence of increased hepatocellular damage following the combination of iron and ethanol.     

Immediate implantation into the posterior maxilla after antroplasty: the Cranin-Russell Operation

KW-2149 is a new derivative of mitomycin C (MMC). The plasma concentrations, distribution, metabolism, and excretion of [3H]-KW-2149 in normal and tumor-bearing mice after i.v. administration of 16.6 mg/kg were investigated. The plasma radioactivity decreased biexponentially after i.v. administration in normal mice. However, the unchanged drug disappeared rapidly, showing a half-life (t1/2) of 9.7 min, which was shorter than MMC's (18 min). The radioactivity was excreted in mouse urine (33%) and feces (58%) within 144 h. High radioactivity was distributed in the gallbladder, liver, kidney, pancreas, and lung at 1 h after i.v. administration to normal mice. The tumor concentration was lower than the plasma or blood concentration. The lowest radioactivity was observed in the brain. The metabolic rate of KW-2149 was very rapid. The methyl sulfide form (M-16), the symmetrical disulfide dimer (M-18), and the albumin conjugate were detected in plasma, which possessed anticellular activity. The specific anticellular activity of these compounds against uterine carcinoma (HeLa S3) was 1/100, 1, and 1/20 respectively, as compared with that of KW-2149.     

Methylprednisolone and cortisol metabolism during the early post-renal transplant period

Despite the widespread use of methylprednisolone and the well-appreciated effects of this drug on HPA suppression, little data is available which describes individual patient exposure to both methylprednisolone and cortisol following renal allograft placement. The clinical utilization of methylprednisolone during the early post-transplant period is based upon standardized dosing protocols that do not consider factors which may influence the pharmacokinetics of this drug during the post-transplant period. Therefore, this study was designed to examine the pharmacokinetics of methylprednisolone (mean dose: 28 mg) and cortisol pharmacodynamics in 9 renal transplant recipients (4 females; 5 males) who were studied during the early post-transplant period (5 to 12 days after surgery). All patients (mean serum creatinine: 1.4 +/- 0.3 mg/dl) had serial blood samples collected over a 12- to 24-hour period (depending upon the dosing schedule) which were analyzed concurrently for methylprednisolone and cortisol. A three-fold variation in drug clearance ranging from 174 to 638 ml/h/kg with a range in the volume of distribution of 0.83 to 2.24 l/kg and resultant half-lives ranging from 1.20 to 3.02 hours was noted. The cortisol response was quantitated by a 12-hour cortisol area under the curve (C-AUC12) to examine the interpatient cortisol patterns during the early post-transplant period. C-AUC12 ranged from 44.0 to 636 ng.h/ml. Significant correlations were noted between the cortisol plasma concentration at 12 hours and methylprednisolone clearance and area under the concentration versus time curve (AUC). Interpatient variability in the disposition of methylprednisolone and cortisol response noted during the early post-transplant period contradict the clinical assumptions which underlie the fixed dosing protocols currently utilized for methylprednisolone.     

Recommendations for image prefetch or film digitization strategy based on an analysis of an historic radiology image database

BACKGROUND: The effect of interferon therapy on the incidence of hepatocellular carcinoma in chronic hepatitis C is poorly defined. OBJECTIVE: To compare the incidence of hepatocellular carcinoma in interferon-treated patients with chronic hepatitis C to that of historical controls and to examine whether response to therapy is related to incidence of hepatocellular carcinoma in patients with chronic hepatitis C. DESIGN: Retrospective cohort study. SETTING: One university hospital and seven university-affiliated hospitals. PATIENTS: 419 consecutive patients with chronic hepatitis C who started interferon therapy between January 1992 and December 1993 (interferon group) and 144 patients with chronic hepatitis C who had liver biopsy between January 1986 and December 1989 and did not receive interferon (controls). INTERVENTION: Patients in the interferon group received human lymphoblastoid interferon, recombinant interferon-alpha2a, or recombinant interferon-alpha2b for 6 months. MEASUREMENTS: The end point was development of hepatocellular carcinoma on abdominal ultrasonography or computed tomography. Sustained response was defined as persistent normalization of alanine aminotransferase (ALT) levels during interferon therapy and follow-up. Relapse was defined as a normal serum ALT level at the end of treatment with an increase to an abnormal level after cessation of treatment. Nonresponse included all other ALT patterns. RESULTS: Median follow-up in the interferon and control groups was 47.6 and 46.8 months, respectively. During follow-up, hepatocellular carcinoma was found in 28 interferon-treated patients and 19 controls. Cox proportional hazards regression analysis that included all patients revealed that interferon therapy (P=0.041), older age (P=0.003), greater histologic activity (P=0.029), and higher histologic stage (P=0.049) were independent factors associated with the development of hepatocellular carcinoma. The risk ratios for development of hepatocellular carcinoma in patients with sustained response, relapse, and nonresponse were 0.06 (95% CI, 0.01 to 0.46), 0.51 (CI, 0.20 to 1.27), and 0.95 (CI, 0.48 to 1.84), respectively, compared with controls. CONCLUSIONS: The incidence of hepatocellular carcinoma was lower in patients with sustained response to interferon therapy than historical controls and nonresponders. Interferon therapy may decrease the risk for hepatocellular carcinoma in patients with chronic hepatitis C.     

Methylprednisolone pharmacokinetics, cortisol response, and adverse effects in black and white renal transplant recipients

It is generally assumed that chronic glucocorticoid therapy is similar pharmacologically when administered to either black or white renal transplant recipients, resulting in adrenal suppression, low circulating plasma cortisol concentrations, and a similar degree of drug exposure and toxicity. To examine this theory and to investigate the relationship of glucocorticoid metabolism to steroid-induced adverse effects among specific ethnic groups of renal transplant recipients, 9 black and 9 white male patients chronically receiving methylprednisolone were enrolled. All patients had stable renal function and were matched for age, weight, and time since transplant. Standard pharmacokinetic parameters for methylprednisolone were determined and cortisol responses were characterized by total cortisol area under the concentration curve (AUC), return cortisol AUC, and cortisol suppression half-life. All patients received their daily oral dose of methylprednisolone (mean daily dose = 11 mg for blacks and 11 mg for whites) as an intravenous infusion with serial plasma samples obtained over 24 h. The patients were assessed for the presence of specific cushingoid manifestations (buffalo hump, moon facies) and steroid-associated diabetes. Methylprednisolone and cortisol were analyzed via HPLC. In the black patients, the mean clearance of methylprednisolone (206 +/- 70 ml/hr/kg) was significantly slower with a smaller volume of distribution (0.95 +/- 0.32 L/kg) when compared with the white group (327 +/- 129 ml/hr/kg, P = 0.03; volume of distribution = 1.33 +/- 0.27 L/kg, P = 0.015). Despite chronic methylprednisolone therapy, a definite 24-hr cortisol response pattern was noted in 15 of the 18 patients with a mean total cortisol AUC of 732 +/- 443 ng.hr/ml in blacks and 539 +/- 361 ng.hr/ml in whites (P = 0.17, black vs. white). The mean cortisol suppression half-life was 4.31 +/- 1.54 hr in black recipients and 4.11 +/- 1.49 hr in whites (P = 0.48). The mean return cortisol AUC for the black patients was 327 +/- 279 ng.hr/ml and 370 +/- 207 ng.hr/ml for white patients (P = 0.28). The serum cortisol nadir for black patients was 12.3 +/- 7.2 ng/ml, which was significantly higher than the cortisol nadir in white patients (6.4 +/- 4.4 ng/ml; P = 0.03). A majority (94%) of patients (9 black, 8 white) had moon facies and 27% of patients (3 black, 1 white) had a buffalo hump. While 5 of 9 black patients had steroid-associated diabetes, no white patients manifested this adverse effect. The black patients with diabetes had higher cortisol AUCs with lower methylprednisolone clearances than the white group.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chemolipiodolization and prostaglandin E1 administration with use of hepatic arterial infusion port for the treatment of hepatocellular carcinoma and liver cirrhosis

Frequent chemolipiodolization and prostaglandin E1 (PGE1) administered through a hepatic arterial infusion port were used for treatment in 2 cases of hepatocellular carcinoma (HCC) with liver cirrhosis. Chemolipiodolization was performed every 4 weeks with 6 ml lipiodol, 3 ml Optilay and 30 mg Epirubicin or 10 mg Mytomycin C. PGE1 (10 ug) was administrated to the hepatic artery once every week after the first 7 days administration. The treatment resulted in a decrease of the AFP level, an arrest of HCC growth and a reduction in ascites with an improvement of clinical and biochemical parameters in both cases. These encouraging preliminary results show that frequent lipiodolization is effective for unresectable HCC and frequent PGE1 administration via the hepatic artery is a safe and efficient treatment for liver cirrhosis.     

Phase I study of a weekly 1 h infusion of paclitaxel in patients with unresectable hepatocellular carcinoma

The majority of patients with hepatocellular carcinoma will develop either unresectable or metastatic disease and, therefore, are candidates for systemic chemotherapy. Only a few chemotherapeutic agents have shown documented activity in the treatment of advanced hepatocellular carcinoma and there is clearly a need for the evaluation of new active drugs. Therefore, we performed a phase I trial with a weekly schedule of paclitaxel in patients with advanced hepatocellular carcinoma. 16 patients with documented progression of unresectable hepatocellular carcinoma were included. After premedication, paclitaxel was given as a 1 h infusion on days 1, 8, 15, 22, 29 and 36 representing one treatment cycle. The cycle was repeated every 50 days. The starting dose was 70 mg/m2 and the doses were escalated in steps of 10 mg/m2/week. A minimum of 3 patients were treated at each dose level. All treatment was given on an out-patient basis. Dose-limiting toxicity was reached at a dose of 100 mg/m2/week with 2 of 6 patients treated at that dose level having WHO grade 4 neutropenia. Other toxic side-effects were only mild. 1 partial response and 9 cases with disease stabilisation were observed in 16 patients with initially progressive disease. We, therefore, conclude that the recommended dose for a further phase II trial in patients with hepatocellular carcinoma is 90 mg/m2/week. These data indicate that paclitaxel given at this dose and schedule might have activity in hepatocellular carcinoma and further investigation in phase II trials is warranted.     

Double blind trial of pulse methylprednisolone versus conventional oral prednisolone in lupus nephritis

A double blinded clinical trial was conducted in which the efficacy and safety of pulse methylprednisolone (400 mg/day) was compared with oral prednisolone (50 mg/day), a control drug for a period of 3 months. One-hundred and two (102) patients were enrolled in the study, of which 91 patients were determined as eligible for analysis of efficacy. Patients on pulse methylprednisolone had more favorable response to therapy with regard to laboratory value changes from baseline such as CH50 and anti-DNA antibody titers. In terms of anti-DNA antibodies, a significant difference was detected at one week after treatment. With regard to time course changes in laboratory values, CH50 at one and two weeks after treatment showed a significantly higher elevation in the pulse methylprednisolone group than in the control group. There was no significant difference noted in incidence of adverse reactions between both treatment groups. No serious adverse reaction was encountered in the pulse methylprednisolone group. The physician's assessment of final global improvement significantly favored the pulse methylprednisolone-treated group. The above results suggest that the pulse therapy with methylprednisolone leads to more rapid onset of drug effect than the conventional oral prednisolone in the treatment of lupus nephritis.     

Enhancement of HBsAg detection in serum of patients with chronic liver disease following removal of circulating immune complexes

Patients with chronic liver disease and hepatocellular carcinoma may lack serological evidence of previous hepatitis B virus infection. The purpose of the present study was to test the hypothesis that circulating immune complexes may interfere with the detection of low levels of HBsAg in such patients. Sera from 190 patients were initially screened for the presence of circulating immune complexes. Patients belonged to three clinical categories: asymptomatic HBsAg carriers (50 patients), chronic liver disease (30 patients) and hepatocellular carcinoma (110 patients). Forty-one of the group of 190 patients (21%) were positive for circulating immune complexes. Sera from 21 patients were selected for further evaluation. The sera of 13 chronic liver disease or hepatocellular carcinoma patients (HBsAg negative, hepatitis B virus-DNA negative, with or without evidence of previous hepatitis B virus infection) and eight HBsAg positive carriers (four asymptomatic, three with chronic liver disease and one with hepatocellular carcinoma) were passed through a Clq affinity column (first column) to remove circulating immune complexes. Unbound material was then passed through a monoclonal IgG2a anti-HBs affinity column (second column). Unbound material (following both columns) contained free HBsAg, as determined by monocolonal radio-immunoassay, in eight patients in whom HBsAg had been undetectable in the original serum. Removal of circulating immune complexes from the serum of the three HBsAg positive patients with chronic liver disease also caused a significant increase in measurable circulating HBsAg compared with the original serum.(ABSTRACT TRUNCATED AT 250 WORDS)