Early effects of vasectomy on testicular structure and on germ cell and macrophage apoptosis in the hamster

Some patients with early-stage cirrhosis preserve hepatic function, whereas others have little hepatic reserve and rapidly deteriorate. The aim of this study was to use quantitative tests of liver function (QLFTs) to define the degree of functional hepatic impairment in patients with early-stage cirrhosis (Child-Pugh score 5-7) and to determine whether the tests predicted subsequent hepatic decompensation. We recruited 10 cirrhotic (Cr) patients and 10 healthy controls (NI), who were well matched for race, age, weight, and gender. Clearances of caffeine (CF) and antipyrine (AP) after oral administration were measured from timed samples of saliva. The clearance of cholate (CA) was measured from serum samples obtained after simultaneous oral ([2,2,4,4-2H]CA) and intravenous ([24-13C]CA) administration. CA shunt was calculated as (Cl i.v./Clo x 100%). CF elimination rate (Cr v NI, mean +/- SD: 0.03 +/- 0.02 v 0.075 +/- 0.018 h-1, P < .0005) and AP clearance (24 +/- 16 v 40 +/- 7 mL/minute, P < .02) were reduced in Cr patients. CA shunt was increased in Cr patients (43 +/- 18 v 18 +/- 7%, P < .002). Five Cr patients decompensated during follow-up and had the worst CA shunts (76%, 66%, 51%, 48%, and 45%). Three subsequently received successful orthotopic liver transplantation, 1 died of hepatoma, and 1 is on the waiting list for transplantation. In conclusion, QLFTs define the degree of functional impairment in early cirrhosis and may identify Cr patients at greatest risk of decompensation who may require transplantation for survival.     

The pharmacokinetics of the glycyrrhizin and glycyrrhetic acid after intravenous administration of glycyrrhizin for the patients with chronic liver disease caused by type C hepatitis virus

Glycyrrhizin had been used widely for the patients with chronic liver disease. We examined the pharmacokinetics of the glycyrrhizin and glycyrrhetic acid in the blood stream after intra-venous administration of glycyrrhizin. The stream concentration of glycyrrhizin in the patients of liver cirrhosis tend to be kept higher than that of chronic hepatitis but there were no significant difference between them except for after a half hour from the administration. There was negative correlation between ICG R15 and the speed of excretion of glycyrrhizin from the serum. On the other hand, the concentration of the glycyrrhetic acid was kept higher in the patients with liver cirrhosis than that of chronic hepatitis, but there were no significant difference between them except for after a half hour from the administration. These findings suggested that the accumulation of glycyrrhizin and glycyrrhetic acid in the patients of liver cirrhosis can be seen by long term administration.     

Caffeine clearance by two point analysis: a measure of liver function in chronic liver disease

This study attempted to compare the pharmacokinetic parameters of caffeine in patients with chronic liver disease and in normal subjects and to define the two sampling times which are suitable for determining caffeine clearance in these patients. Ten decompensated and eight compensated cirrhotic patients, and nine patients with chronic hepatitis were given a 3.5 mg/kg single oral dose of caffeine, followed by measurement of serum caffeine concentrations at 0, 30, 60, 90 minutes and 3, 5, 10, 24 and 36 hours using the HPLC technique. Caffeine clearance and its elimination rate constant in the decompensated cirrhotic patients were significantly lower than those in the compensated cirrhotic patients and much lower than in normal subjects (p > 0.01). Caffeine clearance in chronic hepatitis patients was also significantly lower than in normal subjects. The volumes of distribution of caffeine in compensated and decompensated cirrhotic patients and normal subjects were significantly different. There was also a significant difference between normal subjects and the chronic hepatitis group. Serum caffeine clearance showed a good correlation with Child Pugh's score at r = -0.788. Two sampling times within 10 to 24 hours after oral dose of caffeine served as the best sampling points for determination of caffeine clearance by the simple equation; Cl = kel approximately Vd (Vd is a fixed value in each group). It was clearly shown that caffeine clearance, calculated by two point analysis, would be a simple and useful method for measuring liver function in chronic liver disease.     

Post-prandial serum hyaluronan concentration in patients with chronic liver disease

Serum hyaluronan measurement is an option for diagnosing cirrhosis and assessing liver fibrosis, but it is of little use in the diagnosis of chronic hepatitis and compensated liver cirrhosis. It is generally known that intake of food results in elevation of the serum hyaluronan concentration. This work was designed to determine whether a change in the serum hyaluronan concentration after eating might reflect the hepatic sinusoidal endothelial cell impairment in chronic liver diseases. The chronological measurement of serum hyaluronan concentration after eating was performed after an overnight fast in 31 patients with chronic hepatitis, 31 cirrhotic patients, and 8 healthy subjects. The hyaluronan concentration in the loading test increased with the severity of the liver disease in the patients with chronic hepatitis, being significantly higher in the patients with moderate or a higher grade of necroinflammation than in those with a minimal grade, and also significantly higher in patients with stage 3 fibrosis than in those with stage 2 or less. The elevation of the concentration after eating in patients with liver cirrhosis was marked and the range did not overlap with that in patients with chronic hepatitis. Even in 14 patients with compensated liver cirrhosis whose hyaluronan concentration pre-prandially was less than 200 ng/ml, the range of the post-prandial peak concentration did not overlap with that in the chronic hepatitis patients. These results suggest that the evaluation of post-prandial serum hyaluronan concentration is potentially useful for assessing the grading of necroinflammation and staging of fibrosis in patients with chronic hepatitis, as well as for diagnosing compensated liver cirrhosis.     

Pharmacokinetics and safety of propiverine in patients with fatty liver disease

OBJECTIVE: The present study was designed to assess the pharmacokinetics of propiverine after single and multiple dosing in patients with and without fatty liver disease. METHODS: The serum concentration-time curves of propiverine and its main metabolite propiverine-N-oxide were investigated in 12 patients with mild to moderate impairment of liver function (mean antipyrine clearance 26.0 ml x min(-1)) and in 12 controls (antipyrine clearance 42.8 ml x min(-1)). Subjects were treated orally with propiverine hydrochloride (Mictonorm) for 5 days (15 mg t. i. d.) to reach steady state. RESULTS: No significant differences were observed for propiverine and its main metabolite with regard to peak serum concentration (Cmax), area under the serum concentration-time curve (AUC) and elimination half-life (t1/2). Adverse events were reported by 12 patients. Five patients with fatty liver disease and seven patients with normal liver function complained of dry mouth and/or blurred vision. All adverse events reported were transient and mild. CONCLUSION: No pharmacokinetic differences relevant for safety were observed, comparing patients with and without fatty liver disease following repeated oral administration of propiverine. Thus there seems to be no need to adjust the dose in patients with mild to moderate impairment of liver function.     

Cytokine-induced accumulation of very long-chain fatty acids in rat C6 glial cells: implication for X-adrenoleukodystrophy

Simplified pharmacokinetic methods have been used to estimate caffeine clearance in subjects with liver disease. There is a need to have a reliable, easy to implement method for research and possible clinical use. This study evaluates the use of Bayesian pharmacokinetic forecasting techniques to estimate caffeine clearance and compares its performance to other published methods. Commonly used published methods include the two-concentration overnight salivary clearance method (Jost method) and a method that samples caffeine concentrations over a 4-hour time period (Nagel method). Both have been used in studies incorporating serial measurements of caffeine clearance to predict clinical outcomes in subjects with liver disease, but these approaches have not been proven useful. However, neither method has been formally evaluated for accuracy in estimating caffeine clearance in subjects with cirrhosis. The performance of the Jost, Nagel, and Bayesian methods was compared to a Gold Standard method that accurately measured caffeine clearance in healthy subjects and subjects with cirrhosis using an intravenous infusion of stable isotope-labeled caffeine. The Bayesian method, even when only one measured concentration of caffeine was used, was more accurate, better correlated to the Gold Standard method, and had less intraindividual variation than the two previously published methods. Before the idea of using serial measurements of caffeine clearance for clinical usefulness is rejected, a reevaluation using methods of estimating caffeine clearance that are more accurate than previous paradigms is needed.     

Survival of Vibrio vulnificus in whole blood from patients with chronic liver diseases: association with phagocytosis by neutrophils and serum ferritin levels

Vibrio vulnificus causes severe wound infections and sepsis, mostly in persons with chronic liver diseases. Survival of this organism in the whole blood collected from healthy volunteers and patients with chronic hepatitis, liver cirrhosis, and hepatoma was analyzed as an indication of susceptibility. The bacterial numbers in the blood after 5 h of incubation tended to increase with the severity of the liver disease and differed significantly between hepatoma patients and healthy volunteers (P<.05). Survival of V. vulnificus in the whole blood correlated positively with serum ferritin concentration (r=.266; P<.05) and percentage of transferrin iron saturation (r=. 200; P<.05) and correlated negatively with serum C4 concentration (r=-.198; P<.05) and phagocytosis by neutrophils (r=-.204; P<.05). Among these parameters, low phagocytosis activity (P<.01) and high ferritin level (P<.01) in the blood were the independent predictors.     

Distribution of vitronectin in plasma and liver tissue: relationship to chronic liver disease

To clarify the clinical significance of vitronectin, we compared the concentration of plasma vitronectin with serum fibrous markers and liver function test values in patients with chronic liver diseases. We also evaluated the vitronectin content in the liver by means of enzyme-linked immunosorbent assay and the localization of vitronectin in liver tissue with enzyme immunohistochemistry. In chronic liver disease, the concentration of plasma vitronectin was significantly lower than that in healthy controls, being related to the severity of liver disease. The plasma levels of vitronectin showed no correlation to fibrous markers but a significant correlation with those of serum albumin and prothrombin time. On the other hand, the content of vitronectin in liver tissue was significantly increased in chronic liver disease compared with that in normal controls. In the normal liver, vitronectin was observed in the portal area by light microscopy. In chronic hepatitis and cirrhosis, vitronectin was found in the connective tissue around the portal and central veins and in the areas of piecemeal and focal necrosis. These findings suggested that vitronectin is deposited in injured tissue through the process of repair and fibrosis and plays an important role as an adhesive protein. Moreover, the lower levels of plasma vitronectin in chronic liver disease may be due to its decreased synthesis, deposition or both in injured tissue.     

Ocular levels of azithromycin

OBJECTIVE: To assess azithromycin levels in human serum, aqueous humor, tear fluid, and conjunctival tissue specimens after administration of a single 1-g oral dose of azithromycin. METHODS: Sixty patients undergoing cataract surgery were included in this analysis. Serum, aqueous, and tear specimens were collected 3, 6, and 12 hours and 1, 2, 3, and 4 days after azithromycin administration. Conjunctival tissue biopsy specimens were collected 1, 2, 3, 4, 6, 8, 10, 12, and 14 days after azithromycin administration. All specimens were subjected to analysis by high-performance liquid chromatography-mass spectrometry. RESULTS: Azithromycin concentration ranges during the specified sampling times were as follows: serum, 21 to 974 ng/mL; tear, 82 to 2892 ng/mL; aqueous, 10 to 69 ng/mL; and conjunctival, 0.7 to 32 micrograms/g. Levels above the 90% minimal inhibitory concentration (MIC90) for Chlamydia trachomatis were detected after 4 days in all tear samples and after 14 days in all conjunctival tissue specimens following oral azithromycin administration. CONCLUSION: We demonstrated prolonged high levels of azithromycin in drug-targeted ocular tissue. Prolonged high concentrations of azithromycin in conjunctival tissue make this drug suitable for treatment of conjunctivitis caused by chlamydiae and other susceptible organisms.     

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.     

Thermographic assessment of root canal obturation using thermomechanical compaction

The potential interaction is described between caffeine and antipyrine, two drugs with a high probability of being concomitantly administered for the evaluation of liver metabolism. In order to determine the influence of antipyrine on the elimination of caffeine, salivary caffeine clearance was measured in six healthy volunteers prior to and 2 and 5 days after the administration of a single oral dose of 1000 mg of antipyrine. Total caffeine clearance increased on average by 24% (from 1.65 to 2.05 ml/min, P = 0.1) 2 days after antipyrine dosing, and 25% (from 1.65 to 2.06 ml/min, P < 0.01) 5 days after the administration of antipyrine, whereas the half-life decreased by around 24% (from 5.3 to 4 h, P = 0.09) after 2 days and 26% (from 5.3 to 3.9 h, P = 0.05) after 5 days. The apparent volume of distribution did not change. These results suggest that antipyrine is able to increase the elimination of caffeine, probably by means of inducing its hepatic metabolism. When both drugs are used sequentially in the same patient to assess the drug metabolizing activity of the liver, the caffeine test should be performed first.     

Follow-up study of auditory brainstem responses in hyperbilirubinemic newborns treated with exchange transfusion

Tumor markers have been used for the evaluation of various malignancies though the existence of false positive results in some benign diseases is known. In this study, several established markers including carcinoembryonic antigen, alpha fetoprotein, beta human chorionic gonadotropin, ferritin, CA 19-9 and CA 125 were measured in 60 patients with chronic active hepatitis, 70 patients with cirrhosis and 40 normal subjects in order to evaluate the rate of false elevation of tumor markers in chronic liver disease. Prostate specific antigen and prostatic acid phosphatase levels were also measured in male patients and controls. Serum alpha fetoprotein levels were found elevated in 20% of patients with cirrhosis. The serum CA 19-9 level showed significant elevation in chronic active hepatitis (32%) and cirrhosis (44%). Increase in CA 125 concentration was also remarkable in chronic active hepatitis (23%) and especially in cirrhosis (74%). These results indicate that it is necessary to consider the presence of high false positivity rate of CA 19-9 and CA 125 during clinical interpretation of tumor markers in patients with chronic liver disease.     

Angiosarcoma of the bladder: a review

BACKGROUND/AIMS: Correlations between serum levels of soluble tumor necrosis factor receptors p55 (TNFsRp55) and Child Pugh index have previously been reported in alcoholic patients with cirrhosis. We have undertaken this study to improve understanding of the role of tumor necrosis factor soluble receptors (TNFsRs) in alcoholic liver disease. METHODS: One hundred and two patients with alcoholic liver disease of various severity (23 pure steatosis, 22 fibrosis, seven acute alcoholic hepatitis without cirrhosis, 12 cirrhosis without acute alcoholic hepatitis, 14 cirrhosis with mild acute alcoholic hepatitis and 24 cirrhosis with severe acute alcoholic hepatitis) were studied. Blood was collected on EDTA and plasma was tested for TNFsR concentrations using ELISA assays. RESULTS: Plasma levels of TNFsRp55 and p75 increased progressively with the severity of liver disease, reaching a maximum in cirrhotic patients with severe acute alcoholic hepatitis. Plasma levels of TNFsRp55 in patients with fibrosis and of TNFsRp75 in patients with acute alcoholic hepatitis without cirrhosis were already higher than in healthy controls. In cirrhotic patients with or without acute alcoholic hepatitis TNFsRp55 and p75 were significantly increased compared with controls. In cirrhotic patients, plasma levels of TNFsRp55 correlated positively with all parameters of liver injury, whereas the TNFsRp75/ TNFsRp55 ratio correlated negatively. In cirrhotic patients with severe acute alcoholic hepatitis, the TNFsRp75/TNFsRp55 ratio was significantly lower than in all other groups. In cirrhotic patients with severe acute alcoholic hepatitis treated by prednisolone, the decrease in TNFsRp55 plasma levels between day 1 and day 15 was significantly more important in patients still alive at 2 months than in patients who died within 2 months. CONCLUSIONS: These results show that the expression of TNF-soluble receptors (TNFsRs) participates in the early phases of the alcoholic liver disease and that the TNFsRp75/TNFsRp55 ratio and plasma levels of TNFsRp55 may help to determine the diagnosis and the prognosis of severe acute alcoholic hepatitis in cirrhotics.     

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.     

Serum 27-hydroxycholesterol in patients with primary biliary cirrhosis suggests alteration of cholesterol catabolism to bile acids via the acidic pathway

Reduced cholesterol synthesis has been reported in patients with primary biliary cirrhosis but no data are available on changes in cholesterol catabolism induced by the disease. Serum levels of 7alpha-hydroxycholesterol and 27-hydroxycholesterol have been measured in 25 patients (either normocholesterolemic or hypercholesterolemic) with primary biliary cirrhosis and in control subjects. To evaluate cholesterol synthesis, serum levels of lathosterol were measured, and campesterol and sitosterol were considered to reflect intestinal absorption and biliary elimination of sterols. In normocholesterolemic patients with primary biliary cirrhosis, lathosterol was significantly lower than in normocholesterolemic controls (P < 0.05) whereas no difference was found between hypercholesterolemic patients and hypercholesterolemic controls. Serum concentrations of sitosterol were significantly higher in both normocholesterolemic and hypercholesterolemic patients with primary biliary cirrhosis as compared with the respective controls (P < 0.01). In patients with primary biliary cirrhosis, serum 7alpha-hydroxycholesterol was slightly higher than in controls. 27-Hydroxycholesterol was significantly higher in hypercholesterolemic compared to normocholesterolemic controls (P < 0.05) and a significant linear correlation (r = 0.771; P < 0.001) was found between 27-hydroxycholesterol and cholesterol. In contrast, in patients with primary biliary cirrhosis, high cholesterol concentrations were not associated with increased serum levels of 27-hydroxycholesterol. Our data confirm that in patients with primary biliary cirrhosis, cholesterol synthesis and biliary elimination of sterols are impaired and also suggest that both the feedback regulation of retained bile acids on cholesterol 7alpha-hydroxylase and the scavenger effect on elevated serum cholesterol by cholesterol 27-hydroxylase are deficient in these patients. acids via the acidic pathway.     

Gadobenate dimeglumine (BOPTA) enhanced MR imaging: patterns of enhancement in normal liver and cirrhosis

To determine whether gadobenate dimeglumine (BOPTA) will adequately enhance cirrhotic liver parenchyma, and to document the enhancement patterns in cirrhosis, 14 cirrhotic and 20 non-cirrhotic patients were evaluated before and 60-120 minutes after gadolinium-BOPTA. Proof of liver cirrhosis was biopsy (6), surgical resection (3), and clinical follow-up (5). Enhancement effects were compared quantitatively by determining the liver signal-to-noise ratio (SNR) and signal enhancement in both populations. Qualitatively assessment of the liver enhancement was performed and classified as homogeneous or heterogeneous. Quantitative analysis: cirrhotic liver parenchyma presented a higher increase in SNR values, relative to non-cirrhotic liver parenchyma, on postcontrast images. Likewise the signal enhancement of cirrhotic liver parenchyma was superior to non-cirrhotic liver on T1-weighted SE images (P = .02) and in-phase GRE images (P < .001). There was no statistical difference on out-of-phase GRE images. Qualitative analysis: on T1-weighted SE postcontrast images, cirrhotic liver parenchyma showed a homogeneous enhancement in 7 patients and heterogeneous in 7. Whereas on GRE images, cirrhotic parenchyma showed heterogeneous enhancement in 9 patients and homogeneous in 5 patients. The heterogeneous enhancement was due to the presence of hypointense nodules in 7 patients and hyperintense nodules in 2 patients. In conclusion, our study has shown that the hepatobiliary contrast agent Gd-BOPTA is effective in the cirrhotic liver, demonstrating an increased liver enhancement compared with non-cirrhotic patients.     

Detection of retroviral antibodies in primary biliary cirrhosis and other idiopathic biliary disorders

BACKGROUND: Retroviruses have been implicated in the aetiology of various autoimmune diseases. We used immunoblots as a surrogate test to find out whether retroviruses play a part in the development of primary biliary cirrhosis. METHODS: We did western blot tests for HIV-1 and the human intracisternal A-type particle (HIAP), on serum samples from 77 patients with primary biliary cirrhosis, 126 patients with chronic liver disease, 48 patients with systemic lupus erythematosus, and 25 healthy volunteers. FINDINGS: HIV-1 p24 gag seroreactivity was found in 27 (35%) of 77 patients with primary biliary cirrhosis, 14 (29%) of 48 patients with systemic lupus erythematosus, 14 (50%) of 28 patients with chronic viral hepatitis, and nine (39%) of 23 patients with either primary sclerosing cholangitis or biliary atresia, compared with only one (4%) of 24 patients with alcohol-related liver disease or alpha1-antitrypsin-deficiency liver disease, and only one (4%) of 25 healthy volunteers (p=0.003). Western blot reactivity to more than two HIAP proteins was found in 37 (51%) of patients with primary biliary cirrhosis, in 28 (58%) of patients with systemic lupus erythematosus, in 15 (20%) of patients with chronic viral hepatitis, and in four (17%) of those with other biliary diseases. None of the 23 patients with either alcohol-related liver disease or alpha1-antitrypsin deficiency, and only one of the healthy controls showed the same reactivity to HIAP proteins (p<0.0001). Our results showed a strong association between HIAP seroreactivity and the detection of autoantibodies to double-stranded DNA. HIAP seroreactivity was also strongly associated with the detection of mitochondrial, nuclear, and extractable nuclear antigens. INTERPRETATION: The HIV-1 and HIAP antibody reactivity found in patients with primary biliary cirrhosis and other biliary disorders may be attributable either to an autoimmune response to antigenically related cellular proteins or to an immune response to uncharacterised viral proteins that share antigenic determinants with these retroviruses.     

Phase II study of mitoxantrone by 14-day continuous infusion with granulocyte colony-stimulating factor (GCSF) support in patients with metastatic breast cancer and limited prior therapy

The study aim was to compare the ratio of vitamin E to serum cholesterol with the serum vitamin E level alone as a measure of vitamin E status in patients with different degrees of liver dysfunction. Assessment of serum vitamin E and total serum cholesterol was performed in 85 patients with liver cirrhosis at Child's stage A (n = 26), B (n = 26), and C (n = 33) and 50 patients with noncirrhotic liver disease. As surrogate markers of liver function, 7alpha-hydroxycholesterol and prealbumin concentrations and the plasma prothrombin time were determined. Mean serum vitamin E concentrations in Child A, B, and C patients were 27.4%, 36.9%, and 37.3% lower, respectively, than in healthy controls (P<.01). Twelve of 26 Child A, 14 of 26 Child B, and 14 of 33 Child C patients had vitamin E deficiency with respect to the absolute values, i.e., serum levels less than 13.76 micromol/L (5% percentile of healthy controls). In contrast, only two of 26 Child A, five of 26 Child B, and five of 33 Child C patients (P<.01 for Child A/B and P<.05 for Child C) were vitamin E-deficient according to the serum vitamin E to cholesterol ratio, i.e., less than 2.86 micromol/mmol. Serum vitamin E was correlated significantly with prealbumin, 7alpha-hydroxycholesterol, and the plasma prothrombin time, but the vitamin E to cholesterol ratio was not. Correcting serum vitamin E for total serum cholesterol in patients with liver cirrhosis leads to the phenomenon of reduced serum vitamin E levels inadvertently shifted toward normal values. In patients with liver cirrhosis, the absolute vitamin E concentration correlates better with the typical clinical and biochemical findings of the disease than the vitamin E to cholesterol ratio. Therefore, a considerable number of patients with advanced liver cirrhosis might actually be vitamin E-deficient.     

Effects of alcohol and liver cirrhosis on the GH-IGF-I axis

Decreased serum insulin-like growth factor (IGF-I) levels have been shown in malnutrition and liver diseases. To analyse which of them is the main cause of GH-IGF-I axis alterations, serum levels of growth hormone (GH), growth-hormone releasing factor (GHRH), IGF-I and its binding protein IGFBP-3 were measured in 85 hospitalized alcoholics (51 without cirrhosis, 15 with compensated cirrhosis and 19 with cirrhosis with ascites) and in 25 healthy controls. Liver function tests and objective nutritional assessment were also performed. Serum IGF-I and IGFBP-3 levels were lower in alcoholics, particularly in those with liver cirrhosis. Serum GH was raised in cirrhotics with ascites but GHRH levels were not significantly altered. Although these patients were frequently malnourished there was no relationship between data derived from GH-IGF-I axis and nutritional parameters. However, there was a significant positive correlation between serum GH concentrations and impaired liver function and a significant negative correlation between serum IGF-I and IGFBP-3 and impaired liver function. This suggests that, in this population, serum IGF-I and IGFBP-3 levels reflect liver dysfunction rather than malnutrition.