New therapies for the treatment of chronic hepatitis C.

Treatment of chronic hepatitis C (HCV) was based on Interferon alpha IFNalpha administration three times a week (tiw), but the efficacy of this schedule (evaluated as virological sustained response) was limited to less than 20% of patients. The combination of Ribavirin and IFN is known to be significantly more effective than IFN monotherapy in naive and relapser patients but it induces a sustained response only in 41% of patients and in less than 30% of patients infected with genotype 1. Several studies on IFN and viral kinetics suggested that daily administration of IFN may increase the sustained response rate. The development of pegylated IFNs, characterized by a long half life and weekly administrability, seems to induce a significant improvement in the treatment of chronic hepatitis particularly in combination with Ribavirin. In order to further improve the efficacy of treatment in chronic hepatitis C (HCV) many controlled clinical trials evaluating Amantadine, Micophenolate, alpha1 Thymosin, Maxamine (in combination with IFN or pegylated IFN), Protease, Helicase, Polymerase inhibitors, Ribozymes and anti-sense olygonucleotides, and Interleukin 10 are in progress. Finally anti-HCV vaccine development seems to be very promising.

Urinary D-glucaric acid excretion in the Seveso area, polluted by tetrachloro-dibenzo-p-dioxin (TCDD): five years of experience.

On July 10, 1976, an explosion in a factory in Seveso, Italy, located 30 km north of Milan, producing trichlorophenol caused the release of TCDD-containing compounds in the surrounding area. Since extremely small doses of TCDD have been shown to induce hepatic microsomal enzymes in animals, urinary D-glucaric acid excretion (a measurable index of enzyme induction), has been investigated in Seveso in adults and children 6 to 8 years old, in order to clarify whether levels of environmental exposure to TCDD were sufficient to produce an induction in man. Urine samples were collected from 1976 to 1981. As a control group, people living in Cannero (a nonindustrialized village on lake Magiore), in Busto Arsizio (a small industrial town near Milan) and in Lentate (a noncontaminated zone near Seveso) were chosen. In the first period of collection, children with chloracne (which is considered to be a characteristic manifestation of intoxication with chlorinated products) showed significantly increased levels of D-glucaric acid excretion compared to children without chloracne living in the same zone. As far as chronic exposure is concerned, up to 3 years after the accident both adults and children living in the Seveso area showed a statistically significant enhancement of D-glucaric acid elimination compared to the control groups. This study demonstrates that adults and children living in the polluted zones had an increased activity of hepatic microsomal enzymes for some years, since, although the urinary excretion of D-glucaric acid is only an indirect measure of enzyme activity, studies in man have indicated that it is, however, sensitive and quantitative.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of IgM antibody to hepatitis B core antigen in the diagnosis of hepatitis B exacerbations.

IgM anti-HBc levels were measured by the IMx Core-M Abbott assay in 939 serum samples in order to define a specific and sensitive cut-off value for diagnosis of chronic hepatitis B. The sera used were obtained from 52 chronic HBV patients and 10 HBV carriers with HCV or HDV co-infections and 155 asymptomatic subjects without evidence of liver disease. A Youden index value of 95.4% with 98% sensitivity and 97.4% specificity was obtained for an IMx Index value of 0.204 as cut-off. A one-year follow-up study with monthly tests has shown that quantitative analysis of IgM anti-HBc can serve as a noninvasive tool for monitoring HBV infection, and provides an accurate diagnosis of hepatitis B exacerbations. Significant elevations of IgM anti-HBc levels were associated with hepatitis B exacerbations in 96.2% of the cases but with none of the ALT flare-ups observed in HCV or HDV infected individuals. These results suggest that quantitative analysis of IgM anti-HBc provides the highest degree of confidence in definition of spontaneous and therapy-induced exacerbations or remissions of hepatitis B.

The role of transplantation in small hepatocellular carcinoma complicating cirrhosis of the liver.

Of 176 hepatic transplants performed from 1986 to December 1992, 27 patients had small hepatocellular carcinoma (< or = 5 centimeters) complicating cirrhosis of the liver. All patients were asymptomatic for the hepatic malignancy and the diagnosis was established in each instance preoperatively by means of serial sonographic scans and alpha-fetoprotein levels. Cirrhosis was classified as Child's A in eight instances, as Child's B in 16 and Child C's in three. The cause was alcoholic in three patients, posthepatitic in 21 patients (eight hepatitis B virus [HBV] positive and 13 hepatitis C virus [HCV] positive) and undetermined in three. The in-hospital mortality rate was 11 percent (three of 27). Additionally, five patients died at different intervals after transplantation: only two died of neoplastic recurrence at 12 and 32 months, respectively (7.4 percent rate). Actuarial survival rates were 82 percent at one year and 71 percent at three years, with a mean follow-up period of 32 months (range six to 78 months). Morbidity related to the procedure was a relevant problem: 21 percent of the patients had prompt resumption of normal life while 37 percent required repeated hospitalization and 42 percent required strict control on an outpatient basis. The most frequent problem was HBV or HCV reinfection of the grafted liver, which occurred in 42 percent. Based on this experience, transplantation of the liver has shown an excellent oncologic accuracy for small hepatocellular carcinoma in cirrhosis of the liver, thus representing the most rational surgical procedure for patients with Child's B and Child's C cirrhosis classification. The relevant mortality and morbidity rates, strictly related to this procedure, suggest other options as more appropriate in those with Child A cirrhosis at this time.

gamma-Glutamyl-transpeptidase in diabetics: a case control study.

Several investigators have reported high levels of gamma-glutamyl-transpeptidase (GGT) in the diabetic population. Therefore, we undertook a study to see the prevalence of 'isolated' high GGT in a large population of diabetics without chronic liver disease (CLD), as compared to an age- and sex-matched control group of non-diabetic subjects without CLD, and the role of extrahepatic factors in 'isolated' high GGT, as possible etiopathogenetic causes. We selected 351 diabetics with normal hepatologic screening, without echographic abnormalities of the hepatic parenchyma or the biliary tract. Age, duration and therapy of diabetes, body mass index (BMI), alcohol consumption, glycosylated hemoglobin (HbA1), and the presence of hepatitis B virus (HBV) were studied to see if they are related to high GGT. The control group included 260 age- and sex-matched non-diabetic subjects. We did not find any significant difference between diabetics and the control group in the prevalence of high GGT (mean: 17.5% vs. 23%; women: 16% vs. 14.5%). Multiple regression analysis showed that alcohol consumption plays the major role in the high GGT of both men and women.

Increased urinary D-glucaric acid excretion by children living in an area polluted with tetrachlorodibenzoparadioxin (TCDD).

Extremely small doses of TCDD have been shown to induce hepatic microsomal enzymes in animals. Whether levels of environmental exposure to TCDD were sufficient to produce enzyme induction in man, has been investigated in Seveso, where in July 1976 explosion in a factory spread toxic substances, one of which was TCDD, to the surrounding area. The hepatic microsomal enzyme activity was assessed by estimating urinary d-glucaric acid (UGA) excretion in children 6-8 years old. In 31 children, urine samples were collected between August and December 1976; in 67 other children in February 1979. As a control group 60 children living in Busto Arsizio (a small industrial town near Milan) and 26 living Cannero (a non-industrialized village on Lake Maggiore) were chosen. In the first period of collection, children with chloracne (which is considered to be a characteristic manifestation of intoxication with chlorinated products), showed significantly increased levels of UGA compared with children without chloracne. In 1979, children living in the Seveso area showed a statistically significant enhancement of d-glucaric acid excretion compared to the control groups. In conclusion, this study demonstrates that many children living in the Seveso area have an increased activity of hepatic microsomal enzymes, since, although the urinary excretion of d-glucaric acid is only an indirect measure of enzyme activity, studies in man have indicated that it is both sensitive and quantitative. As far as the cause of this increase is concerned, since it is possible to exclude the influence of alcohol, contraceptives, phenobarbitone or other drugs, it is reasonable to conclude that TCDD, a potent inducer agent, could be responsible for this phenomenon.

Alpha interferon treatment in chronic hepatitis C.

INTRODUCTION: Alpha interferon (alpha IFN) treatment normalizes serum ALT levels in at least half of all patients affected by chronic hepatitis C, but a reactivation of the disease is frequently observed after the end of therapy. Different regimens of alpha IFN therapy have been proposed but the optimal schedule is still controversial. Recently at least 6 different types of HCV have been identified and the HCV genotype has been proposed as an important factor influencing the response to alpha IFN therapy. OBJECTIVE: The aim of this study was to evaluate the efficacy of different regimens of alpha IFN in chronic hepatitis C, and to study the relationship between the response to treatment and HCV genotypes. METHODS: 160 consecutive patients affected by biopsy-proven chronic hepatitis C were randomly treated with different doses of lymphoblastoid alpha IFN [adjusted to the body surface area (m2)] and different durations of therapy, as follows: 2 MU/m2/t.i.w. for 6 or 12 months or 4 MU/m2/t.i.w. for 6 or 12 months. Biochemical and virological responses were studied: ALT levels were monitored monthly during and for at least 6 months after the end of treatment, and serum HCV RNA was assessed before and at the end of therapy, using nested RT-PCR. Biochemical responses were defined in advance as follows: non-response as maintenance of abnormal ALT levels during treatment; complete response as the normalization of ALT by the 4th month and lasting until the end of treatment; sustained response as a complete response lasting for at least 6 months after the end of therapy. The clearance of serum HCV RNA at the end of therapy was considered a virological response. In pre-treatment sera stored at-80 degrees, HCV genotyping was performed according to the method of Okamoto. The Chi square test and multiple stepwise logistic regression were used for the statistical analysis. RESULTS: A sustained biochemical response was significantly more frequent in patients treated for 12 than in patients treated for 6 months, independently of the dosage (45% vs 24% in patients treated with 2 MU/m2/tiw, and 55.5% vs 30% in those treated with 4 MU/m2/tiw). The distribution of HCV genotypes (according to the classification of Okamoto) was 9.8% type I, 45.5% type II, 37.1% type III and 7.6% type V. Both the biochemical and virological responses were significantly correlated to the HCV genotype, being significantly more frequent in patients infected with type III or V (71-60% biochemical and 48-50% virological response, respectively) than in patients with type I or II (15% biochemical and 18-21% virological response, respectively). CONCLUSIONS: 12 months of alpha IFN treatment seemed to be significantly more efficacious than 6 months of therapy, and a significant relationship between the HCV genotype and the biochemical and virological response to alpha IFN was found.

Prospective comparison of four lymphoblastoid interferon alpha schedules for chronic hepatitis C. A multivariate analysis of factors predictive of sustained response to treatment.

OBJECTIVE: Interferon alpha (IFN-alpha) provides effective treatment in some patients with chronic hepatitis C. Since this drug is costly and causes potentially severe side effects, there is a need for clarification of the optimal dose regimen and treatment duration and of the predictive factors of long-term response to this therapy. DESIGN: Prospective, randomized study in patients with chronic hepatitis C. SETTING: 'Crespi' Division of Medicine and Centre for Liver Diseases, Niguarda Hospital, Milan, Italy. PATIENTS AND METHODS: One hundred and forty-two patients with chronic hepatitis C were randomized to receive IFN-alpha at a dosage of 2-4 mega units/square metre of body surface area thrice weekly for 6-12 months. Eleven baseline variables that might predict sustained response to IFN-alpha were evaluated in this series. Sustained response was defined as normalization of transaminase levels observed by the fourth month of therapy and lasting for at least 6 months after treatment withdrawal. RESULTS: According to univariate analysis, variables significantly associated with sustained response to treatment were: hepatitis C virus (HCV) genotype, treatment duration, serum HCV-RNA level and duration of hepatitis. On multivariate analysis only two of these variables were found to be independently associated with sustained response to IFN-alpha: HCV genotype (P < 0.0001) and treatment duration (P = 0.0015). In the patients infected with genotype 1b, IFN-alpha was effective only when administered at the higher dosage and for the longer period. CONCLUSION: Viral genotype and treatment duration are independently related to sustained response to IFN-alpha in patients with chronic hepatitis C. The patients infected with HCV genotype 1b should receive IFN-alpha at the higher dosage and for the longer period.

Antioxidant drugs combined with alpha-interferon in chronic hepatitis C not responsive to alpha-interferon alone: a randomized, multicentre study.

OBJECTIVE: After non-response to the initial course of therapy, retreatment with alpha-interferon is not effective. The aim of this study was to ascertain whether the administration of N-acetyl cysteine and vitamin E could increase the response rate to retreatment with alpha-interferon. DESIGN: Prospective, multicentre clinical trial. SETTING: Twelve hospitals in Lombardy, Italy. PARTICIPANTS: 120 consecutive patients affected by biopsy-proven chronic hepatitis C who had been non-responders to a previous course of alpha-interferon, administered at the dosage of 3-6 million units (MU) three times a week (tiw) for 6 months. INTERVENTIONS: The patients were randomly assigned to one of two groups of treatment: group A, natural interferon-alphaN3, 6 or 9 MU tiw, when the body weight was < 60 kg or > or = 60 kg, respectively; group B, the same dosage of natural interferon-alphaN3 in association with oral administration of N-acetyl cysteine 1200 mg/day and vitamin E 600 mg/day. The period of treatment was 6 months in both groups. RESULTS: Neither end-therapy biochemical response nor sustained biochemical response rates were improved by the combination treatment, and in no case was clearance of the virus from serum observed. CONCLUSIONS: In this randomized study carried out on 120 patients with chronic hepatitis C not responsive to alpha-interferon, oral supplementation with N-acetyl cysteine and vitamin E did not improve the poor efficacy of retreatment with alpha-interferon alone.

The rational use of albumin in patients with cirrhosis and ascites. A Delphi study for the attainment of a consensus on prescribing standards.

BACKGROUND: Ascites is one of the most frequent severe complications in patients with liver cirrhosis. The treatment of this chronic disease usually requires the prolonged use of albumin, frequently continued even after patients' discharge from the hospital. AIMS: Aim of the study was to define a consensus among Italian physicians with regard to the use of albumin in patients with decompensated cirrhosis and ascites. METHODS: The study adopted the Delphi technique to conduct the consensus activities. All controversial issues related to the use of albumin were identified by the experts' board and proposed to the 68 participating hepatology centres through two subsequent questionnaires. The questionnaires, returned by the specialists involved, were collected and the answers classified to verify the elements on which a consensus was reached. RESULTS: The home use of albumin can help to improve the patient's general conditions and well-being. About 77% of the experts involved considered likely that albumin administration could shorten hospital stays or could reduce the number of hospital admissions. The results of the study, along with a socioeconomic analysis, were presented to the Italian Drug Commission, which subsequently removed the specific hypoalbuminemia level as a prerequisite for having the drug reimbursed by the National Health Service. CONCLUSIONS: For an outpatient prescription, the hypoalbuminemia limit of 2.5 g/dl or less is not sufficient, while the decision whether to administer the drug requires the evaluation of patient's overall clinical conditions as an essential criterion for the prescription of a home treatment with albumin.

Abstinence-induced oxidative stress in moderate drinkers is improved by bionormalizer.

BACKGROUND/AIMS: The aim of this investigation was to study the oxidative phenomena which take place in the early recovery phase after alcohol withdrawal. Furthermore, the effects of a novel natural antioxidant, Bionormalizer (BN), in such a clinical setting was studied. METHODOLOGY: Forty-six alcoholics with moderate drinking habits (daily ethanol intake: > 80g to < 120g) were enrolled in the study, divided into two groups and given either a placebo or 9g of BN by mouth every night for one week. The patients agreed to stop drinking alcohol, and daily blood sampling was obtained for routine tests and to check plasma and erythrocyte levels of MDA, SOD, GPX and the hydroperoxide level. The groups were comparable in terms of initial biochemical parameters. RESULTS: BN prevented the early increase of plasma TBARS observed in the placebo group, enabling a near-to-normal level of plasma and erythrocyte MDA by the fourth day. BN also prevented the significant drop of erythrocyte GPX and the transient decrease of plasma SOD observed in the placebo group. Despite alcohol withdrawal, plasma lipid hydroperoxide remained significantly elevated in the placebo group, but this phenomenon was rapidly improved by BN. CONCLUSIONS: To a significant extent, BN is able to prevent the free radical-mediated lipoperoxidative changes that occur soon after alcohol withdrawal, while fastening the recovery mechanisms.

Cyanocobalamin absorption abnormality in alcoholics is improved by oral supplementation with a fermented papaya-derived antioxidant.

BACKGROUND/AIMS: Thirty alcoholic patients and 24 teetotaler dyspeptic patients were considered and underwent baseline blood chemical evaluation and the Schilling test. METHODOLOGY: During gastroscopy, biopsy samples were taken to assay: routine histology, malonyldialdehyde, vitamin E and glutathione concentration and for testing vitamin B12-Intrinsic Factor binding. Examinations were repeated after 1-week supplementation with Bionormalizer. RESULTS: Plasma malonyldialdehyde level and lipid hydroperoxides concentration as well as either malonyldialdehyde and xanthine oxidase concentration in the gastric mucosa in alcoholics were significantly higher than in controls and despite unchanged alcohol consumption, significantly decreased after Bionormalizer supplementation. Gastric mucosal glutathione was markedly depressed in alcoholics and partly recovered after Bionormalizer supplementation. Although the alcoholics showed a normal intrinsic factor secretion in the gastric juice, they exhibited a markedly depressed intrinsic factor-cobalamin binding on the "ex vivo" study. Moreover, nearly 23% of them had an abnormal Schilling test. Both these impairments reverted to normal after Bio-normalizer supplementation. CONCLUSIONS: It can be postulated that the antioxidative action played by Bionormalizer, possibly due to its availability substrates for glutathione synthesis as well as to its effects on local oxidative burst from neutrophil, is able to recover a normal cobalamin absorption.

Improvement of hemorheological abnormalities in alcoholics by an oral antioxidant.

BACKGROUND/AIMS: It has been shown that alcohol impairs erythrocyte (red blood cell) membrane fluidity and lipid composition. The aim of this study was to test the effect of a novel acid-resistant antioxidant on the hemorrheology in alcoholics. METHODOLOGY: Thirty alcoholics (25 males, 5 females; mean age: 42 years; range: 31-54; 150 g ethanol/day for 3-5 years) were enrolled into the study. Patients were randomly and double-blindly allocated into 2 groups which were given, for a 2 week period, 18 g/day of Bionormalizer (obtained from biofermentation of carica papaya, pennisetum purpureum, sechium edule, Osato Res. Foundation, Gifu, Japan) dissolved in 5 mL of water at bedtime and 3 hours prior to examination. Placebo consisted of flavored sugar. Healthy teetotalers served as control. On the examination day, blood samples were taken for testing: routine tests, plasma glutathione, ascorbic acid, selenium, plasma lipid hydroperoxides and alpha-tocopherol. Erythrocytes were separated and tested for red blood cell malonyldialdehyde and glutathione content. The hemorheological studies were as follows: blood and plasma viscosity, whole blood filterability, red blood cell membrane fluidity by electron spin resonance, red blood cell aggregation index by photometric rheoscopy and red blood cell deformability by ektacytometry. RESULTS: As compared to healthy controls, alcoholics on placebo treatment showed no change of plasma viscosity but a significantly higher red blood cell malonyldialdehyde, blood viscosity (P < 0.05) and lower plasma glutathione, whole blood filterability and red blood cell fluidity (P < 0.01). No relationship appeared between biochemical tests and red blood cell membrane fluidity. Bionormalizer group showed a significant recovery to control values of either blood viscosity and whole blood filterability (P < 0.01) and a partial, although significant, improvement of red blood cell membrane fluidity, red blood cell malonyldialdehyde and plasma glutathione (P < 0.05). As compared to healthy control, red blood cell aggregation decreased in alcoholics (P < 0.05) and was not affected by Bionormalizer. However, Bionormalizer significantly improved the reduced red blood cell deformability (P < 0.05 vs. alcoholics) and this parameter correlated with red blood cell malonyldialdehyde (r: 0.62. P < 0.05). CONCLUSIONS: These preliminary data suggest that an effective antioxidant supplementation is able to improve the hemorrheology in alcoholics either by directly affecting the ethanol-related lipoperoxidation and xanthine oxidase system activation and/or by modifying red blood cell membrane characteristics.

Tauroursodeoxycholic acid for the treatment of HCV-related chronic hepatitis: a multicenter placebo-controlled study.

BACKGROUND/AIMS: Tauroursodeoxycholic acid is a promising drug for the treatment of chronic cholestatic liver diseases since it has more favourable physicochemical and metabolic properties than ursodeoxycholic acid. Tauroursodeoxycholic acid may be of benefit also for necroinflammatory liver disease, especially for HCV-related chronic hepatitis in which bile duct damage and some degree of cholestasis are frequently seen at histology. METHODOLOGY: One hundred and fifty patients with chronic hepatitis were randomly assigned to receive tauroursodeoxycholic acid at daily doses of 500 mg or 750 mg, or a placebo for 6 months. RESULTS: A consistent decrease in aminotransferase serum levels was observed in patients treated with tauroursodeoxycholic acid compared with placebo (p<0.001) and a progressive improvement with time was also found (p<0.05; linear time effect). CONCLUSIONS: Tauroursodeoxycholic acid improves the biochemical expression of chronic hepatitis. Long-term studies with clinically relevant end-points are warranted.

[S-Adenosylmethionine: plasma levels in hepatic cirrhosis and preliminary results of its clinical use in hepatology. Double-blind study]. / S-adenosilmetionina: livelli plasmatici nella cirrosi epatica e primi risultati sul suo impiego clinico in epatologia. Studio in doppio cieco

Since S-adenosylmethionine (SAMe) plasma levels are highly reduced in cirrhotic patients, this, showing that a more or less overt deficiency of SAMe-dependent biological transmethylations does exist in the hepatocyte pathology, mostley affecting the albuminopoyesis. Treatment with 15 mg SAMe i.v. or i.m. administered four times a day for 30 days' period, induced in 15 patients with hepatic cirrhosis a statistically significant improvement of the afore mentioned livel cell function, albuminopoyesis: a significant improvement was also observed in the other biohumoral parameters considered to test hepatic function. Administration of equimolecular (with respect to SAMe) doses of L-methionine and ATP to a group of 15 cirrhotic patients under clinical conditions similar to those of the group previously studied, induced none of the modifications observed in the latter. This proved that the therapeutic effects are due only to S-adenosylmethionine.

[A new therapeutic approach in hepatic hydrothorax]. / Un nuovo approccio terapeutico nell'idrotorace epatico.

Hepatic hydrothorax is a complication of hepatic cirrhosis which frequently conditions respiratory insufficiency. Traditional therapy is almost always inefficacious. The paper reports four cases which were successfully treated using pleurodesis with sterile talc. Treatment was simple with no major complications. At the 6-month check-up no cases of recurrent pleural effusion were observed.

[Controlled clinical trial of 2-mercapto-propionyl-glycine in chronic hepatopathies]. / Sperimentazione clinica controllata della 2-mercapto-propionil-glicina nelle epatopatie croniche

A controlled clinical trial comparing 2-Mercapto-Priopionyl-Glycine (2-MPG) plus B12 vitamin with B12 vitamin alone in chronic liver disease has been conducted in seven hospitals in Italy. Patients were divided into two groups on the basis of liver histology; group I included 26 patients showing histological evidence for chronic persistent hepatitis (C.P.H.) (according to De Groote et al.) whereas group II consisted of 54 patients with chronic aggressive hepatitis (C.A.H.) or compensated liver cirrhosis. Patients of each group were randomly allocated to 2-MPG plus B12 vitamin, or to placebo plus B12 vitamin, in a double-blind way. The drug (or placebo) was diluted in 500 ml of 10% Levulose, and administered intravenously; 1000 gamma of B12 vitamin were added to each bottle. Patients in the 2-MPG group received 2.5 gms of the drug daily; the treatment lasted for 30 days. The following parameters were checked in all patients on admission, and repeated at the end of treatment: Serum bilirubin, serum Cholesterol, A.P., BSP retention, Prothrombin time, S-GOT, S-GPT, Gamma-GT, Total serum Protein, serum electrophoresis, Immunoglobulins. Patients given 2-MPG showed significant decreases of serum transaminases, and improvement of BSP retention.

[Double-blind polycentric study of the action of S-adenosylmethionine in hepatic cirrhosis]. / Studio policentrico in doppio cieco sull'azione della solfoadenosilmetionina nella cirrosi epatica

Two comparable groups of patients with hepatic cirrhosis of different genesis in a compensation phase have been treated for 30 days with S-adenosylmethionine and vitamine B-12 (28 cases) or with vitamine B-12 alone (25 cases). The drugs were given by slow intravenous route at the daily dose of 150 mg of SAMe and 2000 gamma of vit. B-12 or of 2000 gamma of vit. B-12 alone, in two adminstrations. An evaluation of the results was carried out mostly on the laboratory data testing the liver function. Only the group of patients who had received SAMe showed significant modifications of all the parameters considered. This is confirming SAMe ability to restore hepatocyte activity bringing also to normal the protein synthesis.

[Effect of tiropramide chlorhydrate on intestinal transit time in patients with irritable colon syndrome]. / Azione della tiropramide cloridrato sul tempo di transito intestinale in pazienti affetti da sindrome del colon irritabile.

The effect of tiropramide hydrochloride--a new spasmolytic drug with calmodulin-independent activity--in correcting alterations of intestinal transit, has been investigated in 40 IBS patients (20 with accelerated and 20 with delayed transit time). Intestinal transit has been evaluated by means of radioopaque markers. Tiropramide hydrochloride, at a dose of 100 mg t.i.d. for 4 weeks, was found significantly more effective than placebo both in normalizing intestinal transit time and in inducing symptomatic relief.

Comparison of once-daily bedtime administration of famotidine and ranitidine in the short-term treatment of duodenal ulcer. A multicenter, double-blind, controlled study.

A multicenter, double-blind, randomized, controlled study was conducted in 234 duodenal ulcer patients to compare the efficacy and safety of the H2-receptor antagonists famotidine and ranitidine in the treatment of duodenal ulcer. Patients received 40 mg famotidine (119 patients) or 300 mg ranitidine (115 patients) once daily at bedtime for 4 weeks. If ulcer lesions persisted, treatment was extended to 6 weeks. Efficacy was assessed by relief of symptoms and endoscopic findings of ulcer healing. Safety was determined on the basis of reports of side effects, results of laboratory tests, and, in selected patients, changes in plasma levels of hormones. The 4- and 6-week healing rates achieved with famotidine were 76% and 91%, respectively, and with ranitidine they were 76% and 87%, respectively; the differences in healing rates for the two drugs were not statistically significant. Similarly, both drugs provided satisfactory relief of pain and dyspeptic symptoms. However, famotidine produced significantly (P less than 0.05) greater relief of postprandial fullness and heartburn. The incidence of untoward effects was low in both treatment groups, and abnormal results in laboratory tests were observed in only one patient, a chronic alcoholic receiving famotidine, who withdrew from the study because of a slight elevation in serum transaminase levels. One patient in the ranitidine treatment group dropped out of the study because of a generalized urticarial rash; however, a causal relationship between drug and effect could not be established. The authors conclude that famotidine may be regarded as the best alternative to ranitidine in the treatment of duodenal ulcer.