Albumin improves the response to diuretics in patients with cirrhosis and ascites: results of a randomized, controlled trial.

BACKGROUND/AIMS: Diuretic treatment of ascites could result in intravascular volume depletion, electrolyte imbalance and renal impairment. We investigated whether intravascular volume expansion with albumin exert beneficial effects in cirrhosis with ascites. METHODS: In protocol 1, 126 cirrhotic inpatients in whom ascites was not relieved following bed rest and a low-sodium diet, were randomly assigned to receive diuretics (group A) or diuretics plus albumin, 12.5 g/day (group B). In protocol 2, group A patients continued to receive diuretics and group B diuretics plus albumin (25 g/week) as outpatients and were followed up for 3 years. End points were: disappearance of ascites, duration of hospital stay (protocol 1), recurrence of ascites, hospital readmission and survival (protocol 2). RESULTS: The cumulative rate of response to diuretic treatment of ascites was higher (p < 0.05) and hospital stay was shorter (20 +/- 1 versus 24 +/- 2 days, p < 0.05) in group B than in group A patients. After discharge, group B patients had a lower cumulative probability of developing ascites (19%, 56%, 69% versus 30%, 79% and 82% at 12, 24 and 36 months, p < 0.02) and a lower probability of readmission to the hospital (15%, 56%, 69% versus 27%, 74% and 79%, respectively, p < 0.02). Survival was similar in the two groups. CONCLUSIONS: Albumin is effective in improving the rate of response and preventing recurrence of ascites in cirrhotic patients with ascites receiving diuretics. However, the cost/benefit ratio was favorable to albumin in protocol 1 but not in protocol 2.

Interferon and thymosin combination therapy in naive patients with chronic hepatitis C: preliminary results.

AIMS/BACKGROUND: This randomized study was performed to compare the efficacy of interferon-alpha (IFN-alpha) + thymosin alpha 1 (Talpha1) treatment to that of IFN-alpha alone in light of biochemical and virological response of naive patients with chronic hepatitis C. METHODS: Seventeen patients were treated with IFN alpha-2b (3 million units MU three times a week) + Talpha1 (1 mg twice weekly); the other 17 patients received only IFN alpha-2b at the same dose. All patients were treated for 6 months and followed up for 12 months. Biochemical (ALT values) and virological (HCV-RNA) responses to treatment were determined. RESULTS: Combination therapy showed significantly higher efficacy than monotherapy in achieving biochemical and virologic end-of-treatment response (p<0.05). At 12 month follow-up, the sustained biochemical response was slightly greater in patients treated with combination therapy than in those treated with monotherapy. No significant difference in response by HCV-1b subtype was observed between the two treatment groups; however, HCV-2c subtype showed a trend to responding better to IFN-alpha+Talpha1 than to IFN-alpha alone. CONCLUSIONS: These data suggest that the immune modulator Talpha1 may be additive or synergistic with IFN-alpha in normalizing end-treatment biochemical and virological responses in patients with chronic hepatitis C. Higher doses and/or more prolonged courses may improve the sustained response rates to this treatment.

[Clinical-epidemiological study of the efficacy of thermal therapy in gastroenterologic diseases]. / Indagine clinico-epidemiologica sulla efficacia della terapia termale nella patologia gastroenterologica.

PURPOSE: To evaluate the therapeutic effects of drinking mineral water, its influence on gastrointestinal drug consumption as well as on working days missed in patients with dyspeptic syndrome or chronic constipation due to irritable bowel syndrome. MATERIALS AND METHODS: A questionnaire was sent to 1500 physicians and 965 forms were available concerning patients who had mineral water treatment at Montecatini. RESULTS: Mineral water therapy determined a striking short- and medium-term improvement on clinical symptoms. Furthermore, this treatment reduced gastrointestinal drug consumption per year, as well as the number of working days missed. CONCLUSIONS: This epidemiological study confirms the utility of drinking mineral water in the treatment of some gastrointestinal syndromes either in the short and in the medium run.

Cardiac autonomic modulation and incidence of late potentials in essential hypertension: role of age, sex, ventricular mass and remodeling.

The influence of age, sex, left ventricular hypertrophy (LVH) and geometry on the autonomic activity to the heart was investigated in 96 hypertensive out-patients (53 men, mean age 53 +/- 9 years) and 39 healthy subjects (19 men, mean age 43 +/- 1 years). Using 24-h Holter recordings, time [the standard deviation of all RR intervals (SDNN) and the square root of the mean of the squared differences between adjacent normal RR intervals (RMSSD)] and power spectral analysis of RR intervals [Fast Fourier algorithm, low/high frequency (LF/HF) ratio] were calculated over 24 h, daytime (D) and nighttime (N) periods in all subjects. Signal averaged electrocardiogram was recorded in 50 patients to detect late potentials. Stepwise multiple linear regression analysis showed that the 24-h LF/HF ratio was influenced by age and sex, D-LF/HF by age and N-LF/HF by sex, a higher LF/HF ratio being found in younger patients and in men. These data suggest a more prominent sympathetic modulation of cardiac activity in these groups. No differences in RR period variations were observed between patients with or without LVH. Late potentials were observed in 10 patients, and did not correlate with any of the measured parameters.

[Role of the liver in the regulation of glucose metabolism in diabetes and chronic liver disease]. / Ruolo del fegato nella regolazione del metabolismo glucidico in corso di diabete e di epatopatia cronica.

The liver plays a major role in the regulation of glucose metabolism: plasma glucose concentration is the result of peripheral glucose utilization and liver production. Several hormones, including insulin, glucagon, growth hormone, cortisol, and catecholamines contribute to the regulation of glucose metabolism by the liver. In this review, we examine hepatic glucose metabolism, in particular the actions of insulin and contrainsular hormones on glucose hepatic uptake and production in patients with diabetes or chronic liver disease. The most frequent patterns of hepatic involvement that take place during diabetes, i.e. nuclear glycogenesis, steatosis, portal fibrosis, and diabetic steatonecrosis, are discussed. Also considered are anomalies of glucose homeostasis observed in chronic liver disease, including glucose intolerance, diabetes, and hypoglycemias. There is a strong correlation between diabetes mellitus and the liver: diabetic patients have typical histological lesions, while several glucose metabolism alterations are commonly found in subjects with chronic liver disease. The pathogenesis of impaired glucose metabolism during chronic liver disease has not yet been fully understood: further clinical and experimental studies should clarify this issue.

Relevance of inapparent coinfection by hepatitis B virus in alpha interferon-treated patients with hepatitis C virus chronic hepatitis.

The aim of the study was to investigate whether an "inapparent" coinfection by hepatitis B virus (HBV) in anti-HCV-positive chronic liver disease patients may influence interferon (IFN) response. Fourteen anti-HCV-positive, hepatitis B surface antigen (HBsAg)-negative but serum HBV-DNA-positive patients and 111 anti-HCV-positive, HBsAg-negative, and HBV-DNA-negative patients with chronic hepatitis were treated with 3 MU of recombinant alpha-2a IFN 3/week for 1.2 months. Serum HBV-DNA and HCV-RNA were determined before treatment, after 6-12 months, and at the time of alanine aminotransferase (ALT) flare-up by HBV polymerase chain reaction (PCR) and HCV PCR, respectively. IgM anti-HBc were tested using the IMx Core-M assay (Abbott Laboratories, North Chicago, IL). By the end of treatment, ALT values had become normal in 4/14 HBV-DNA-positive patients (28%), but all "responders" (4/4) relapsed. IgM anti-HBc was detected both before treatment and during ALT elevation in three patients and only during ALT relapse in another three. In the remaining 111 patients, a biochemical response to IFN treatment was observed in 54% and relapse of ALT values in 47%. "Inapparent" HBV/HCV coinfection may be implicated in cases of resistance to IFN. HBV replication and HBV-related liver damage may persist in patients in whom HCV replication was inhibited by current doses of IFN, as suggested also by the presence of IgM anti-HBc in some cases. Further studies will show the effect of different treatment schedules. HBV-DNA and/or IgM anti-HBc detection with very sensitive methods may be important both as a prognostic factor and as a tool for better understanding of intervirus relationships and mechanisms involved in multiple hepatitis virus infections.

Chronic viral hepatitis induced by hepatitis C but not hepatitis B virus infection correlates with increased liver angiogenesis.

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections lead to cirrhosis and increase the risk for the development of hepatocellular carcinoma (HCC). Angiogenesis is an essential step in oncogenesis and contributes to tumor progression in adult organs; however, to what extent angiogenesis occurs in the liver during chronic viral hepatitis has not been studied. Ninety-nine matched patients affected by chronic hepatitis due to either HBV or HCV were studied together with 13 controls (5 patients were affected by familial hyperbilirubinemia with normal liver histology; 6 patients with stage II primary biliary cirrhosis; and 2 patients with pseudo inflammatory tumor). Microvessel density was assessed in liver biopsies by immunostaining using two different antibodies against endothelial cell antigens, QB-END/10 and Factor VIII. In addition, the liver homogenates and sera of HCV- or HBV-positive patients and controls were tested for their capacity to stimulate the migration and proliferation of freshly isolated human endothelial cells in vitro. Evidence of angiogenesis was significantly more frequent in HCV-positive patients compared with HBV-infected subjects or controls (74% vs. 39% vs. 8%) (chi2 = 20.78; P < .0001) (HCV+ vs. HBV+ vs. controls). The degree of microvessel density was also higher in HCV- than in HBV-positive patients or controls (chi2 = 12.28; P < .005). In addition, HCV-positive sera and liver homogenates stimulated a higher migration and proliferation of human endothelial cells in vitro compared with HBV-positive or control sera and liver homogenates. These observations indicate that angiogenesis is particularly linked to HCV infection, suggesting a possible contribution to HCV-related liver oncogenesis.

Impaired response to alpha interferon in patients with an inapparent hepatitis B and hepatitis C virus coinfection.

The possibility of hepatitis B virus (HBV) infection in HBsAg-negative patients has been shown. However, an "inapparent" coinfection by HBV in hepatitis C virus (HCV)-positive patients generally is not taken into account in clinical practice. Mechanisms responsible for resistance to interferon (IFN) have not been completely clarified. The aim of this study was to investigate whether an "inapparent" coinfection by HBV in anti-HCV-positive chronic liver disease patients may influence IFN response. Fourteen anti-HCV positive, HBsAg-negative but serum HBV DNA-positive patients by PCR and 111 anti-HCV-positive, HBsAg-negative and HBV DNA (PCR)-negative patients with chronic hepatitis were treated with 3 MU of recombinant alpha-2a IFN 3 times weekly for 12 months. Serum HBV DNA and HCV RNA were determined before treatment, after 6-12 months and in coincidence with ALT flare-up by PCR. HBV PCR was performed using primers specific for the S region of the HBV genome and HCV PCR with primers localised in the 5'NC region of HCV genome. IgM anti-HBc was tested using IMx Core-M Abbott assay. By the end of treatment, ALT values had become normal in 4/14 HBV DNA-positive patients (28%), but all "responders" (4/4) relapsed between 2 and 5 months after therapy. All but one patient were HCV RNA-positive before treatment, 6 were also both HBV DNA and HCV RNA-positive during ALT flare-ups. In 5 patients, only HBV DNA and in 3 patients, only HCV RNA was detected when transaminase values increased. All patients remained HBsAg-negative and anti-HCV-positive. IgM anti-HBc was detected both before treatment and during ALT elevation in 3 patients and only during ALT relapse in 3 others. Of the 111 anti-HCV positive, HBsAg-negative and HBV DNA (PCR)-negative patients with chronic hepatitis, a biochemical response to IFN treatment was observed in 54% of the cases. Relapse of ALT values was observed in 47% of the cases during a follow-up of 1 year after treatment. "Inapparent" HBV/HCV coinfection may be implicated in cases of resistance to IFN treatment. In addition, HBV replication may persist in patients in whom HCV replication was inhibited by IFN treatment. The pathogenic role of HBV in liver disease was confirmed by detection of IgM anti-HBc in some cases; the appearance of these antibodies only after IFN treatment suggests that IFN may exert a selective role in favour of HBV. Further studies will show the effect of different treatment schedules. HBV DNA and/or IgM anti-HBc detection with very sensitive methods may be important both as a prognostic factor and as a tool for better understanding interviral relationships and mechanisms involved in multiple hepatitis virus infections.

Long course and prognostic factors of virus-induced cirrhosis of the liver.

OBJECTIVE: Chronic infection by hepatitis B virus (HBV) and hepatitis C virus (HCV) is now recognized as a major cause of liver cirrhosis. This study was aimed at evaluating the natural history of the disease in a large series of Italian patients with HBV- and HCV-related cirrhosis without portal hypertension at entry. METHODS: The clinical records of 405 patients (233 males, mean age 54 +/- 9 yr) with histologically proven cirrhosis (321 with HCV-related and 84 with HBV-related cirrhosis) and no clinical evidence of portal hypertension at entry were retrospectively examined to evaluate the occurrence of complications and the cumulative mortality rate during follow-up. RESULTS: Patients had a mean follow-up of 8 +/- 3 yr. The cumulative survival rate was 99.1% at 5 yr, 76.8% at 10 yr, and 49.4% at 15 yr. The age-adjusted death rate was 3.14 and 2.84 times higher than in the general Italian population in men and women, respectively. Only the bilirubin level was an independent indicator of survival. Esophageal varices, ascites, jaundice, hemorrhage, hepatic encephalopathy, and hepatocellular carcinoma significantly reduced the survival rate (major complications), whereas thrombocytopenia, diabetes, and cholelithiasis did not affect survival (minor complications). The incidence of hepatocellular carcinoma was similar in patients with either HBV- or HCV-related disease and was quite frequent, especially in males. CONCLUSIONS: This study demonstrates that the course of virus-induced liver cirrhosis is not influenced by the etiology of the disease and that the occurrence of complications significantly shortens life expectancy. The longer survival rate observed in this study is probably due to the fact that cirrhosis was here recognized by liver biopsy in the absence of clinical evidence of portal hypertension.

Pharmacokinetics and pharmacodynamics of torasemide and furosemide in patients with diuretic resistant ascites.

BACKGROUND/AIM: To evaluate the pharmacokinetics and pharmacodynamics of furosemide and torasemide in patients with cirrhosis and diuretic resistant ascites. METHODS: Eighteen patients were randomly allocated to receive intravenous torasemide (40 mg) or furosemide (80 mg). The renal response to these drugs was assessed in baseline conditions and in the 24 h following drug administration together with plasma and urinary concentrations of furosemide, torasemide and its metabolites. RESULTS: Torasemide induced significantly greater diuretic and natriuretic effects than furosemide in the first hour after drug administration. No other significant differences between the two drugs were observed with respect to the renal response to these drugs. Torasemide reached a lower maximum plasma concentration than furosemide, but the former drug had a longer apparent terminal half-life and lower renal and non-renal clearances. Comparing these results with those previously reported in healthy subjects, both drugs showed a reduced elimination rate through renal and non-renal routes, and a larger distribution to body fluids. As a consequence, the half-life of both drugs was longer than in healthy subjects. Urinary excretion of pharmacologically active species, however, was quantitatively unchanged after torasemide administration, whereas it was reduced after furosemide. Finally, the natriuretic potency of both drugs was markedly reduced in these patients. CONCLUSIONS: The pharmacokinetics and pharmacodynamics of torasemide and furosemide are markedly altered in patients with diuretic resistant ascites.

[Viral liver cirrhosis: natural course, pathogenesis and clinical implications of the complications]. / La cirrosi epatica virus-correlata: storia naturale, patogenesi e implicazioni cliniche delle complicanze.

The role of hepatitis B virus (HBV) and hepatitis C virus (HCV) as a major cause of chronic liver disease is now accepted worldwide. This study was aimed at evaluating the natural history of the disease in patients with virus-induced chronic active hepatitis or cirrhosis, and the influence played by age, sex and etiology, liver function tests and by the occurrence of different complications. We retrospectively examined the clinical records of 506 inpatients: 194 were affected by chronic active hepatitis (125 males, 69 females, mean age 45 +/- 11 years, 146 HCV- and 48 HBV-related), and 312 by cirrhosis without clinical evidence of portal hypertension (178 males, 134 females, mean age 53 +/- 9 years, 249 HCV- and 63 HBV-related). The occurrence of cirrhosis in the chronic active hepatitis group was then calculated, together with the occurrence of complications and the cumulative mortality rate of established cirrhosis. During follow-up 93 patients with chronic hepatitis developed cirrhosis. The cumulative probability of developing cirrhosis in this group was 6.64% at 5 years, 56.1% at 10 years and 86.8% at 15 years. These patients were therefore included in the cirrhosis group for the final analysis, so that a total of 405 cirrhotic patients were evaluated: these patients had a cumulative survival rate of 99.1% at 5, 76.8% at 10 and 49.4% at 15 years. Comparing the age-adjusted death rate of our patients with the general Italian population, we observed that in patients with liver cirrhosis it was 3.14 and 2.84 times higher in men and women, respectively. Bilirubin was an independent indicator of survival. Several complications, such as esophageal varices, ascites, jaundice, hemorrhage, hepatic encephalopathy and hepatocellular carcinoma significantly reduced the survival rate and were indicated as major complications, while thrombocytopenia, cholelithiasis and diabetes did not affect survival and thus were called minor complications. Incidence of hepatocellular carcinoma was very high especially in males, without correlation with etiology. In conclusion, the progression of virus-induced chronic active hepatitis to cirrhosis is not influenced by sex and etiology. Similarly, the different etiology does not modify the natural history of cirrhosis while the occurrence of one or more major complications significantly shortens survival. The longer survival rate observed in patients with cirrhosis included in this study is probably due to the selective inclusion of patients with early disease and no evidence of portal hypertension.

Thyroxine-binding globulin in elderly patients with hepatocellular carcinoma.

In order to evaluate the possible relevance of the increased serum levels of thyroxine binding globulin (TBG) in elderly patients with cirrhosis and hepatocellular carcinoma (HCC), TBG and alpha-fetoprotein (AFP) levels were measured in 3 groups: (i) 14 healthy subjects (mean age: 74 +/- 2 years); (ii) 15 patients with cirrhosis of the liver (mean age: 70 +/- 1 years); (iii) 17 patients with cirrhosis and HCC (mean age: 71 +/- 1 years). Both TBG and AFP levels were significantly higher (p < 0.01) in the patients with HCC, as compared to the healthy subjects or to the cirrhotic ones without HCC. The increased plasma TBG levels in cirrhotic patients with HCC is probably due to a derepression of the TBG gene in hepatocytes undergoing neoplastic transformation. The results suggest that TBG together with AFP may be of diagnostic value for the presence of HCC in aging patients with liver cirrhosis.

"Inapparent" hepatitis B virus infection and hepatitis C virus replication in alcoholic subjects with and without liver disease.

We evaluated hepatitis B virus DNA and hepatitis C virus RNA in sera from 110 HBsAg and IgM HBc antibody-negative heavy drinkers (50 cirrhosis, 13 chronic active hepatitis, 25 fatty liver with or without mild to moderate fibrosis, alcoholic hepatitis or both and 22 healthy alcoholic subjects) with polymerase chain reaction. Results of hepatitis C virus polymerase chain reaction were compared with those obtained with two tests (second generation recombinant immunoblot assay and enzyme-linked immunosorbent assay) used to detect hepatitis C virus antibodies. Hepatitis B virus DNA was found in three (2.7%) patients. Hepatitis C virus RNA was detected in 29 (29.8%) of the 97 subjects whose sera were well preserved for RNA extraction (42.5% cirrhosis, 83.3% chronic active hepatitis, 8% fatty liver and 0% healthy alcoholic subjects). Results obtained with second-generation recombinant immunoblot assay and enzyme-linked immunosorbent assay had a high degree of agreement with polymerase chain reaction as expected, the kappa indexes being 0.76 and 0.61, respectively. Nevertheless, five hepatitis C virus RNA-positive patients had negative recombinant immunoblot assay results, whereas all hepatitis C virus RNA-positive patients had positive or borderline enzyme-linked immunosorbent assay results. We conclude that, in Italian HBsAg-negative alcoholic patients, "inapparent" hepatitis B virus infection is rare. On the contrary, hepatitis C virus infection, as detected on hepatitis C virus polymerase chain reaction, is quite frequent, especially in patients who have cirrhosis and chronic active hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating growth hormone and insulin-like growth factor-I in nonalcoholic liver cirrhosis with or without superimposed hepatocarcinoma: evidence of an altered circadian rhythm.

Adult liver is considered the major source of circulating insulin-like growth factor-I (IGF-I). Growth hormone (GH) exerts its effects by stimulating IGF-I release from the liver, which then mediates the somatogenic actions in target tissues. In turn, circulating IGF-I levels operate a negative feedback mechanism on GH release. In cirrhotic patients, single daily determinations, performed after an overnight fast, indicated that serum IGF-I are decreased, whereas GH levels are increased. To verify whether this phenomenon occurs through the 24-h period, we have studied the profiles of GH and IGF-I in cirrhotic patients with or without superimposed hepatocellular carcinoma (HCC) and in a group of control subjects. The results of the present studies suggest that in cirrhotic patients, the above changes are constantly present through the 24-h period, and are associated with a loss of circadian rhythm for both GH and IGF-I. These data are consistent with a failure of the liver to synthesize and release IGF-I in response to GH. In addition, the presence of constantly higher IGF-I levels in cirrhotic patients with superimposed HCC, compared with cirrhotic patients without HCC, raises the hypothesis of a causal relationship between IGF-I and the development of HCC.

A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis.

In order to assess the liver protective activity and the antioxidant properties of a new silybin complex (IdB1016), we carried out a short-term pilot study on 20 patients with chronic active hepatitis (CAH), randomly assigned to 240 mg of silybin b.i.d. (10 patients, 4 m/6 f, mean age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood samples were collected before and after 7 days of treatment for liver function tests (LFTs), malonaldehyde (MDA) as an index of lipid peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in protecting cells against free radical-mediated lipid peroxidation. In the treated group, there was a statistically significant reduction of mean (+/- SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0 (+/- 13.3) to 65.9 (+/- 7.5) u/l, (p < 0.01), of alanine aminotransferase (ALT) from 115.9 (+/- 12.9) to 82.5 (+/- 10.6) u/l (p < 0.01), of gamma-glutamyltranspeptidase (gamma-GT) from 51.4 (+/- 9.3) to 41.3 (+/- 4.2) u/l (p < 0.02) and of total bilirubin (TB) from 0.76 (+/- 0.08) to 0.53 (+/- 0.04) mg/dl (p < 0.05). Alkaline phosphatase (AP) fell slightly from 143.4 (+/- 6.4) to 137.5 (+/- 7.8) u/l. There were no significant changes in MDA, Cu or Zn serum concentrations. These results show that IdB1016 may improve LFTs related to hepatocellular necrosis and/or increases membrane permeability in patients affected by CAH.

[Ursodeoxycholic hemisuccinate in the treatment of chronic active hepatitis. A controlled clinico-therapeutic study]. / L'emisuccinato dell'acido ursodesossicolico nel trattamento dell'epatite cronica attiva. Studio clinico-terapeutico controllato.

This controlled study was performed on 36 patients affected by HBV and/or HCV correlated chronic hepatitis (CAH). Eighteen of them received 300 mg of UDCA-hemisuccinate orally twice a day for six months; the other 18 received 200 mg of S-adenosyl-methionine (SAMe) twice a day for six months. The two groups were determined randomly. Treatment with UDCA-hemi-succinate produced a statistically significant reduction in ALT (from 167 +/- 17 to 119 +/- 15 U/l; p < 0.0001), AST (from 122 +/- 14 to 86 +/- 11 U/l; p < 0.0001) and y-GT (from 81 +/- 10 to 53 +/- 6 U/l, p < 0.0001). The results obtained suggest that UDCA-hemi-succinate may be useful in the long-term treatment of chronic liver diseases of viral aetiology because it improves the biochemical parameters of hepatocellular necrosis and/or increased liver cell permeability.

Comparison of the effects of torasemide and furosemide in nonazotemic cirrhotic patients with ascites: a randomized, double-blind study.

In a randomized double-blind trial we compared the effects of torasemide, a new loop diuretic, and furosemide in nonazotemic cirrhotic patients with ascites during a 3-day period in association with potassium canrenoate (200 mg/day) administration. Doses of loop diuretics administered in this trial (10 and 25 mg/day of torasemide and furosemide, respectively) had been shown to be equipotent in healthy subjects. Torasemide induced significantly greater natriuresis than furosemide (p less than 0.02), with a twofold greater percentage increase in basal values (day 1: 130% vs. 50%; day 2: 104% vs. 42%; and day 3: 65% vs. 26%, respectively). Body weight loss was significantly higher during torasemide (p less than 0.02) administration, and the overall decrease at the end of the treatment was twice as high for furosemide (2.5 +/- 0.6 kg vs. 1.3 +/- 0.4 kg, respectively). Diuresis was also higher during torasemide administration, but the difference was not significant (p = 0.08). The extent of kaliuresis observed during the two treatments was almost identical despite the striking differences in the natriuretic response. The effects of the two treatments on plasma electrolytes, creatinine clearance, blood urea nitrogen, mean arterial pressure, heart rate and plasma arginine vasopressin concentration were similar. Both drugs caused increases in plasma renin activity at the end of the treatment, whereas plasma aldosterone concentration slightly increased only after torasemide administration. Despite the presence of a trend toward a more pronounced effect on these parameters after torasemide administration, no significant difference between the two treatments was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic antipyrine metabolism in athletes.

The aim of the present study was to investigate the influence of prolonged physical exercise on hepatic metabolism. An oral antipyrine loading test (15 mg/kg body weight) was carried out on 24 healthy male subjects: 8 controls, 8 sprinters (anaerobic activity), 8 long distance runners (aerobic activity). Antipyrine clearance resulted to be significantly higher in athletes vs. controls, without a significant difference between the two groups of athletes. These results put forward the importance of the degree of physical activity (1) for the evaluation of antipyrine-loading-test results as expression of liver function and (2) whenever drugs with a low therapeutic index are used in athletes.

[Quick freezing in the preparation of special hospital diets]. / Utilizzazione della congelazione rapida nella preparazione di diete speciali ospedaliere.

The study has been undertaken to test the usefulness of the freezing-method on foods in the dietary formulations of the Hospital Food Service. Thirty-six recipes of specific diets (blended, liquid diets and diets of normal texture with high and low protein content) have been tested. These recipes were precooked and frozed within 2 hours. They were tested for taste, texture, aspect and colour by the same staff of the Dietetic Service (2 Dietitians and 2 Cooks). Twenty-eight recipes, after being reheated, have shown satisfactory results for all the characteristics tested. The time from freezing (test 15, 30, 45 days after freezing) does not influence the results. The freezing method is then useful for the most part of the specific Hospital Diets. A stock of frozen preparations can be used at any moment even by not qualified personnel and let a better work organization of the Dietetic Service Kitchen.

Estimate of prevalence of glucose intolerance in chronic liver disease. Degree of agreement among some diagnostic criteria.

In patients with chronic liver disease, the reliability of various criteria generally used to diagnose impaired glucose tolerance and diabetes was evaluated. Twenty-one patients with chronic persistent hepatitis, 68 patients with chronic active hepatitis and 57 patients with liver cirrhosis were studied. All subjects underwent an oral glucose tolerance test (75 g). Impaired glucose tolerance and diabetes were diagnosed according to the criteria established by: the National Diabetes Study Group; Fajans and Conn; the European Diabetes Study Group; Deutsche Diabetes Gesellschaft; Kobberling & Creutzfeld criteria 1 and 2; Wilkerson; and the University Group Diabetes Program. The results obtained are in partial agreement with other reported data, showing a high prevalence of both impaired glucose tolerance and diabetes in chronic liver disease, with a positive correlation to the severity of hepatic involvement. However, our results show that the agreement among the criteria most frequently used for diagnosing impaired glucose tolerance and diabetes is still far from satisfactory.