PubMed HealthSearch

Biomedical subjects

M Coltorti

Publications and source records attributed to M Coltorti.

At least 19 recordsLinked to original sources

Alteration of erythrocyte glutathione, cysteine and glutathione synthetase in alcoholic and non-alcoholic cirrhosis.

Glutathione (GSH) and cysteine were determined in the plasma and the erythrocytes of alcoholic and non-alcoholic cirrhotics as fluorescent monobromobimane derivatives by high-performance liquid chromatography (HPLC). Cirrhotic patients displayed a significant decrease of plasma GSH, as well as of plasma cysteine, that was related to the degree of liver disease but not to the nutritional conditions. On the contrary, erythrocyte cysteine was found to increase significantly in all cirrhotics, particularly in alcoholics, regardless of the severity of disease. In an attempt to find a possible explanation of these alterations, the GSH synthesizing enzymes, gamma-glutamylcysteine synthetase (GC-s) and GSH synthetase (GSH-s) activities were determined in the erythrocytes. GSH-s activity was significantly lower in cirrhotic patients, whereas GC-s activity did not differ in the three groups.

Adult

Local deterioration of the cutaneous venoarterial reflex of the hand in cirrhosis.

Cutaneous focal blood perfusion and an index of cutaneous vascular resistance were determined on the dorsum and palm of the hand of 34 patients with liver cirrhosis and of 24 healthy control subjects. Tests were performed with a laser-Doppler technique before and during stimulation of the vasoconstrictor venoarterial reflex, performed by means of venous occlusion of the forearm. The mean arterial blood pressure of the cirrhotics turned out to be lower than that of the controls. On the dorsum of their hands a normal blood perfusion and a reduced vascular resistance were verified, suggesting the intervention of a local autoregulatory phenomenon of the blood flow. The blood perfusion turned out to be higher, whereas the vascular resistance was lower than the norm on the palm of the hands of cirrhotic patients who had palmar erythema, showing the presence of an anomalous non-autoregulatory vasodilation. The extent of venoarterial reflex on the dorsum of the hand turned out to be identical in the patients and controls, whereas that on the palm turned out depressed. This anomaly was present also in patients without palmar erythema, although less marked than in those with erythema. The data obtained suggest the presence of a disturbance in the functioning of the arteriovenous anastomoses (numerous in the palm but very scarce in the dorsum), superimposed on the venoarterial reflex. It may depend on the existence, in hepatic cirrhosis, of an impairment of the specialized autonomic nervous mechanisms that control temperature loss.

Blood Pressure

Hepatitis C virus infection is an additive risk factor for development of hepatocellular carcinoma in patients with cirrhosis.

The aim of the present study was to evaluate whether hepatitis C virus plays any role in the development of hepatocellular carcinoma in cirrhotic patients. The role of age, sex, alcohol abuse, and infection by other hepatitic viruses, such as hepatitis B and Delta viruses, was also assessed. We found that mean age and male/female ratio were significantly higher in patients with HCC plus liver cirrhosis than in those with liver cirrhosis alone. Also, the prevalence of HCV infection was found to be higher in HCC patients compared to cirrhotics. Further, by means of multiple logistic regression, we evaluated the independent role of each variable in the development of HCC. Age, male sex, and to a lesser degree, HCV infection, as assessed by anti-HCV positivity, were the only risk factors which significantly correlated with the development of HCC. Moreover, when age and sex were excluded from the statistical model, HCV infection, but not HBV, HDV, and alcohol abuse, appeared to be associated with HCC. In conclusion, based on these data, age and male sex are the most important factors for the development of hepatocellular carcinoma in cirrhotic patients. Hepatitis C virus, at least in the Mediterranean area, may play a role as an additive risk factor of HCC in patients suffering from liver cirrhosis.

Age Factors

Liver cirrhosis in Italy. A multicentre study on presenting modalities and the impact on health care resources. National Project on Liver Cirrhosis Group.

A cross-sectional multicentric study was carried out over a six-month period as part of the "Progetto Nazionale Cirrosi Epatica", in order to update information about: a) the prevalence of different aetiologic factors and various nosological varieties of cirrhosis in Italy, as well as its presenting modalities; b) the currently used approach either to the diagnosis or the treatment of complications of cirrhosis; c) the impact of liver cirrhosis on medical care in terms of number of hospitalizations and length of hospital stay, instrumental procedures and management, and d) the size of patient's population referred to the participating centers, in order to help design further studies. From February 1st through July 31st 1987, 1,386 forms relative to 1,101 patients were collected. In 320 patients the diagnosis of cirrhosis was first made during the investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Alterations of glucose metabolism in chronic liver disease.

The prevalence of glucose intolerance has been studied by oral glucose tolerance test in 670 patients affected by chronic liver disease. The glycometabolic status was evaluated by criteria given by WHO in 1980. Sixty-nine subjects appeared to be affected by chronic persistent hepatitis and 140 by chronic active hepatitis. In these patients the prevalence of diabetic responses (DR) did not differ much from that of the general population in our geographic area. In contrast, a markedly higher frequency of DR appeared in a cirrhotic group of 401 patients compared to non-cirrhotic subjects. The cirrhotics, divided according to different disease stages, showed a higher DR frequency in decompensated patients than in well compensated patients, the prevalence reaching 63% in the former subgroup. The coincident presence of hepatocarcinoma - documented in 60 other cirrhotic patients - does not modify the prevalence of diabetes. Other risk factors for diabetes such as age, sex, and family history have been considered. Our results suggest that: (1) all these factors seem not to play a major role in the pathogenesis of alterations of glucose metabolism in patients suffering from chronic liver disease, and therefore (2) liver cirrhosis by itself might be a risk factor in the disturbance of glucose tolerance.

Adult

Age-associated decline of hepatic handling of cholephilic anions in humans is reverted by S-adenosylmethionine (SAMe).

Decreased fluidity of hepatocyte plasma membrane may contribute to the age-associated changes of liver function. This study aimed at investigating whether the hepatic clearance of organic anions declines with age and whether S-adenosylmethionine (SAMe), a substance proven to be effective in reversing the age-related decrease of membrane fluidity, might influence this process. Nicotinic acid (NA) half-life and serum bilirubin pharmacokinetics after NA load (5.9 mumol/kg body weight i.v.) were studied in 10 healthy young males (YM) aged 14-28 years and in 10 healthy elderly males (EM) aged 65-81 years, before and after SAMe administration (800 mg/day intravenously for 10 days). At baseline, EM showed serum total bilirubin (STB) levels significantly higher than YM. Similarly, the bilirubinaemic mean curves, STB peak and STB time curve concentration after NA load, expressed as area under the curve (AUC), were significantly higher in EM than in YM (p less than 0.01). NA half-life was also significantly prolonged in the aged group (p less than 0.001). SAMe treatment was followed by a significant decrease of basal STB, STB peak and AUC of STB after NA load in EM (p less than 0.01 vs pre-treatment values) while NA half-life was significantly shortened in both groups (p less than 0.001). As NA and bilirubin share a common carrier protein for hepatic uptake, bilitranslocase, the changes observed in EM may be attributed to the reduced lateral mobility of hepatocyte plasma membrane proteins occurring with age. SAMe, by improving membrane fluidity, may increase the diffusion coefficient of bilitranslocase restoring the hepatic handling of organic anions.

Adolescent

Effect of metoclopramide on transmural oesophageal variceal pressure and portal blood flow in cirrhotic patients.

This study was undertaken to evaluate the effect of metoclopramide on transmural oesophageal variceal pressure and portal blood flow in cirrhotic patients. Sixteen cirrhotics were randomly assigned to metoclopramide (10 mg i.v.) or saline. Metoclopramide significantly decreased transmural variceal pressure (15.7% decrease, p less than 0.05 vs. basal value). In order to evaluate if the metoclopramide-induced drop in transmural variceal pressure was due to an effect on portal haemodynamics, we also measured, by means of real time and pulsed Doppler ultrasonography, portal vein diameter, mean velocity of portal flow, and portal venous flow. No significant change was observed before and after metoclopramide. In conclusion, metoclopramide, which increases lower oesophageal sphincter pressure, significantly decreases transmural variceal pressure in cirrhotic patients. However, it does not have any effect on portal haemodynamics.

Double-Blind Method

Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis.

Recent studies have established the clinical efficacy of S-adenosyl-L-methionine (SAMe) in the treatment of cholestasis associated with hepatic diseases, pregnancy and the administration of estrogen-containing oral contraceptives. In 4 clinical trials involving a total of 639 patients with cholestasis due to acute or chronic liver disease, SAMe in an intravenous dose of 800 mg/day or an oral regimen of 1.6 g/day for 2 weeks was superior to placebo in relieving the symptom of pruritus and in restoring serum total bilirubin and serum alkaline phosphatase towards normal. The drug is also effective in intrahepatic cholestasis of pregnancy (ICP), with intravenous administration of 800 mg/day for 2 weeks producing a substantial reduction in pruritus and an improvement in abnormal liver function indices. Moreover, SAMe treatment decreases the incidence of premature labour. SAMe appears to be the first safe and effective approach to the treatment of this syndrome, and also protects against the adverse hepatic effects of small doses of estrogen in patients with a history of ICP by normalising liver biochemistry and the oversaturated biliary lipid composition of the gallbladder bile. In animal models, SAMe reverses the pathological liver changes induced by xenobiotics such as taurolithocholate and alpha-naphthyl-isothiocyanate (ANIT) and the antipsychotic chlorpromazine. Several cooperative mechanisms appear to underlie the anticholestatic action of SAMe, the most important being the restoration of normal hepatocyte membrane fluidity and Na+, K+ ATPase activity, through a reversal of the reduction in phospholipid methylation produced by hepatotoxic agents. In addition, SAMe may act by promoting trans-sulphuration pathway reactions and consequently improving the detoxifying capacity of this metabolic system.

1-Naphthylisothiocyanate

Familial clustering of hepatitis C virus infection and chronic liver disease.

The present study was undertaken to assess the prevalence of HCV antibodies (anti-HCV) and of chronic liver disease in relatives of anti-HCV positive subjects suffering from chronic active liver disease. We studied 122 subjects from 24 families. Each family had at least one positive anti-HCV component with histologically proven chronic liver disease. Anti-HCV was found in 32% of subjects; 82% of these were suffering from chronic liver disease diagnosed on the basis of physical examination and biochemical parameters. Prevalence of anti-HCV was higher in spouses, parents, and siblings of the index case as compared to the offspring. In conclusion, the transmission of HCV infection and of HCV-related chronic liver disease is contributed to by factors associated with the familial environment.

Adolescent

Decrease of total, glutathione and cysteine SH in non-alcoholic cirrhosis.

The content of plasma thiols was determined in 42 patients with non-alcoholic cirrhosis. Total thiols were evaluated by Ellman's method, glutathione and cysteine by HPLC in fluorescence. Cirrhotic patients showed a significant decrease in plasma thiol content with respect to a control group of 32 healthy subjects, as total sulphydryls as well as glutathione and cysteine. The thiol decrease does not seem to be related to nutritional status or dietetic factors. Our data indicate that liver cirrhosis, independently from alcohol abuse, produces a decrease in all plasma thiols, probably secondary to a complex alteration of the transsulfuration pathway.

Adult

Malnutrition in cirrhotic patients: anthropometric measurements as a method of assessing nutritional status.

This study was undertaken to evaluate by anthropmetric measurements the nutritional status of cirrhotic patients at different stages of the disease and to establish intra- and inter-observer variability in the determination of these parameters. In 60 healthy controls and 108 cirrhotics (63 'well compensated' and 45 'decompensated' groups A and B + C on the Child-Pugh classification respectively) two independent experienced observers measured biceps, triceps, subscapular and overiliac skinfold thicknesses and arm circumference three times. Each observer was unaware of the results obtained by the other. No significant intra- or inter-observer variability was found. The study indicates that skinfold thickness measurements are a reliable and reproducible method of assessing the nutritional status of cirrhotics. It was found that more than 50 per cent of the decompensated patients were malnourished, with skinfold values significantly lower than those of the controls. In comparison with skinfold thickness and arm circumference, parameters such as body weight and lean body mass are unreliable, and other indices such as muscle and/or fat arm area do not add any significant information to the evaluation of the nutritional status of cirrhotics.

Adult

Prevalence of HBcAg and delta-Ag in liver tissue of patients with HBsAg positive chronic hepatitis.

One hundred and twenty HBsAg positive patients with chronic liver disease, 94 with CAH and 26 with CPH, were studied in order to characterize chronic HBsAg positive hepatitis virologically. All patients came from a geographical area (Campania, Italy) with a high prevalence of HBV and HDV infection. Each patient was tested for the presence of HBsAg, HBeAg, anti-HBe and anti-delta in serum (by RIA techniques), and of HDV (by direct immunofluorescence) and HBcAg (by indirect immunofluorescence and PAP-immunoperoxidase) in liver biopsy specimens. Anti-delta serum positivity was remarkably more frequent in patients with CAH (40%) than in those with CPH (19%). Delta-Ag was found in 94.7% of the anti-delta positive patients with CAH, but in none of the five anti-delta positive patients with CPH. In contrast, the frequency of HBcAg tissue positivity was similar in CAH and CPH. Positivity for HBcAg was less frequent in CAH with cirrhosis than in CAH without cirrhosis, while there was no difference in the prevalence of delta-Ag.

Adolescent

Effect of different doses of S-adenosyl-L-methionine (SAMe) on nicotinic acid-induced hyperbilirubinaemia in Gilbert's syndrome.

S-adenosyl-L-methionine (SAMe) has been shown to increase hepatocyte membrane fluidity thereby relieving signs of oestrogen-induced cholestasis. S-adenosyl-L-methionine might therefore prove effective in improving the efficiency of the transport of organic anions such as nicotinic acid (NA) and bilirubin which is impaired in Gilbert's syndrome (GS). In this study the effects on the metabolization rate of NA and bilirubin of two dosages of SAMe were evaluated in respect to placebo in ten male inpatients (mean age 24 years, range 16-31) with GS. Each patient received both SAMe (800 and 200 mg/day, respectively) and placebo treatment i.v. over a period of 10 days. The NA test (5.9 mumol/kg b.w. i.v.) was carried out in the same volunteers after each treatment. Unconjugated bilirubin (UCB) levels were significantly lower (p less than 0.01) after 800 mg/day SAMe than after placebo while the lower dosage of SAMe did not affect UCB values. The bilirubin time curve concentration, expressed as area under the curve (AUC), was significantly reduced (p less than 0.01) after 800 mg SAMe in comparison with the values obtained after placebo and 200 mg SAMe. Also plasma NA half-life was significantly reduced (p less than 0.01) by the higher dose of SAMe in respect to placebo and not by the lower dose.

Adolescent

Effect of somatostatin on salivary secretion in man.

Intravenous infusion of pentagastrin increases salivary secretion progressively at doses from 1 to 4 micrograms/kg body weight/h. Pentagastrin also stimulates salivary secretion of amylase. Simultaneous administration of somatostatin, at the dose that inhibits gastric secretion of pentagastrin-stimulated HCl, blocks the effect of pentagastrin on salivary flow, while it does not reduce the amylase concentration. The data suggest that different mechanisms underlie the effects exerted by pentagastrin on salivary flow and on the concentration of amylase in saliva.

Adult

Comparison between ranitidine 150 mg b.d. and ranitidine 300 mg nocte in the treatment of duodenal ulcer.

A multicenter trial was undertaken to assess the clinical usefulness of a single night-time dose of ranitidine in the short-term healing of duodenal ulcer. 384 patients with endoscopically diagnosed duodenal ulcer were randomly allocated to treatment with ranitidine either 150 mg b.d. or 300 mg as a single night-time dose for four weeks. The patients not healed after four weeks were again treated for four weeks. Of the 356 patients who completed the study, according to the protocol, 148 of 176 (84.1%) recovered on ranitidine 150 mg b.d. and 147 of 180 (81.7%) recovered on 300 mg nocte after four weeks. The healing rates increased to 95.8% and 94.8% respectively after four more weeks. Ulcer symptoms were rapidly reduced with no significant differences between the two treatment groups. There were no unwanted effects in either group and no significant abnormal biochemical or hematological changes. The results of this study support the hypothesis that ranitidine 300 mg given as one night-time dose and ranitidine 150 mg b.d. are equally effective. Ranitidine 300 mg once daily in a clinical practice may be advantageous to the patient.

Adult