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Biomedical subjects

M Coltorti

Publications and source records attributed to M Coltorti.

At least 19 recordsLinked to original sources

Last Glacial mammals in South America: a new scenario from the Tarija Basin (Bolivia).

The chronology, sedimentary history, and paleoecology of the Tarija Basin (Bolivia), one of the richest Pleistocene mammalian sites in South America, are revised here based on a multidisciplinary study, including stratigraphy, sedimentology, geomorphology, paleontology, isotope geochemistry, and (14)C geochronology. Previous studies have indicated a Middle Pleistocene age for this classic locality. We have been able to obtain a series of (14)C dates encompassing all the fossil-bearing sequences previously studied in the Tarija Basin. The dated layers range in age from about 44,000 to 21,000 radiocarbon years before present (BP), indicating that the Tarija fauna is much younger than previously thought. Glacial advances correlated to marine isotopic stages (MIS) 4 and 2 (ca. 62 and 20 ka BP, respectively) are also documented at the base and at the very top of the Tarija-Padcaya succession, respectively, indicating that the Bolivian Altiplano was not dry but sustained an ice cap during the Last Glacial Maximum. The results of this multidisciplinary study enable us to redefine the chronological limits of the Tarija sequence and of its faunal assemblage and to shift this paleontological, paleoclimatological, and paleoecological framework to the time interval from MIS 4 to MIS 2.

Animals↗

Long-term effects of Enterococcus faecium SF68 versus lactulose in the treatment of patients with cirrhosis and grade 1-2 hepatic encephalopathy.

In 40 patients with cirrhosis on a dietary protein regimen of 1 g/kg b.w., we determined the effect on chronic hepatic encephalopathy of long-term administration of Enterococcus faecium (SF68) versus lactulose. The patients received one of the two treatments for three periods of 4 weeks, each separated by drug-free 2-week intervals. The efficacy of treatment was assessed by arterial blood ammonia concentration, mental status, number connection (Reitan's part A) test and flash-evoked visual potentials. At the end of the third period the reduction in both blood ammonia concentrations and Reitan's test times was more enhanced in patients on SF68 than in patients on lactulose. Furthermore, while patients on lactulose tended to return to basal values during drug-free intervals, responders in the SF68 group maintained improvement throughout the study. In conclusion, SF68 is at least as useful as lactulose for the chronic treatment of chronic hepatic encephalopathy; it has no adverse effects, and treatment can be interrupted for 2 weeks without losing the beneficial effects.

Adult↗

Gastric endoscopic features in patients with liver cirrhosis: correlation with esophageal varices, intra-variceal pressure, and liver dysfunction.

This study was aimed at evaluating the gastric endoscopic features in patients with liver cirrhosis and at assessing whether endoscopic findings correlated with the severity of portal hypertension and of the underlying liver disease. We studied 394 cirrhotic patients and 110 controls. Prevalence of a mosaic-like pattern of the gastric mucosa was significantly higher in cirrhotics than controls (80.5 vs. 0.9%; p < 0.001). Red spots of the gastric mucosa were found in 8.1% of cirrhotic patients and in none of the control subjects. Erosions and petechiae were found in 14.5 and 5.4% of the control population, but their prevalence was significantly higher in cirrhotics (28.7 and 12.7%, respectively; p < 0.05). Severity of the mosaic-like pattern as well as the presence of red spots were closely related to the size and hemorrhagic risk of esophageal varices and to the presence of fundic varices. Also, severe mosaic-like patterns were found more frequently in patients with severe impairment of liver function, as assessed by the Child-Pugh's criteria. Furthermore, the mosaic-like pattern was more severe in cirrhotic patients with a higher degree of portal hypertension as indirectly assessed by measurement of esophageal intravariceal pressure. In conclusion, (1) a mosaic-like pattern and red spots of the gastric mucosa are the only specific signs of congestive gastropathy in liver cirrhosis, and (2) the severity of the mosaic-like pattern correlates with the severity of liver dysfunction and of portal hypertension.

Adult↗

Effect of S-adenosyl-L-methionine administration on red blood cell cysteine and glutathione levels in alcoholic patients with and without liver disease.

We measured glutathione and cysteine concentrations in erythrocytes of chronic alcohol misusers with (20 subjects) and without liver cirrhosis (20 subjects). Glutathione levels were decreased, whereas those of cysteine were increased in all patients. Parenteral treatment with S-adenosylmethionine (SAME); (2 g daily in 250 ml 0.15 M NaCl for 15 days) corrected the erythrocyte thiol alterations. We conclude that parenteral treatment with SAME affects the metabolism of SH compounds in erythrocytes of alcoholic patients.

Adult↗

[Nutritional problems in cirrhotic patients. Evaluation of dietetic aspects].

The aim of the study was to evaluate: a) the influence of the diagnosis of liver cirrhosis on the alimentary behaviour of cirrhotic patients; b) the compliance and the effect during observation-time of a personalized diet; c) the modifications, induced by the diet, of some clinical and biochemical parameters, specifically of these correlated to hepatic encephalopathy in 20 non-alcoholic cirrhotic patients. They were entered the study, in stage A-B of liver disease, according to Child-Pugh criteria. No patients received a previous specific dietetic prescription. After the collection of the alimentary intake before and after the diagnosis of liver disease, we prescribed normoprotein and hyposodium diets, reducing or increasing the caloric intake for the patients who were not at their ideal weight. From our study it stands out that the diagnosis induced all patients to reduce their caloric intake, especially of lipids. The appropriate dietetic prescription followed by short run controls led to a general improvement of the evaluated parameters, which was not kept during the following months; as a matter of fact, at the long run control all patients tended to return to their previous alimentary habits, neglecting, in the course of time, the diets they had been prescribed. We can, consequently, maintain that the cirrhotic needs a steady clinical and dietetic control since he seems to undervalue the prescribed therapies.

Analysis of Variance↗

Autonomic neuropathy in liver cirrhosis: relationship with alcoholic aetiology and severity of the disease.

Autonomic neuropathy has been frequently observed in alcohol-addicts both with and without liver disease but few data are available on non-alcoholic cirrhotics. We studied the prevalence of this disorder in 113 cirrhotics (41 alcoholics and 72 non-alcoholics) to correlate it both with residual liver efficiency and the aetiology of liver cirrhosis. We used 5 cardio-vascular tests commonly adopted to assess the parasympathetic [Valsalva manoeuvre (VR), deep breathing (DB), lying-to-standing (LS)] and sympathetic function [sustained handgrip (SH) and orthostatic hypotension (OH)]. Results obtained indicate that: a) autonomic neuropathy was observed in 60% of the patients (71% in alcoholic and 57% in non-alcoholic cirrhosis; p < 0.01); b) the alterations of the parasympathetic function are significantly more frequent than those of the sympathetic function; c) DB and SH tests seem to be influenced by the compliance of the patient; DB was the most altered test and LS was the most specific and sensitive test; d) a simplified series of three diagnostic tests (2 parasympathetic: VR and LS, plus a sympathetic one: HO) is as accurate for the diagnosis as the combination of the 5 tests.

Adult↗

[The pharmacological therapy of intrahepatic cholestasis].

Changes in liver membrane fluidity constitute one of the most important factors in the pathogenesis of experimental and human cholestasis. These alterations could partly be correlated with a defect in the methylation of membrane phospholipids and with a modification in the cholesterol/phospholipids ratio, which in turn may result from a decrease in the ademethionine hepatic levels and from a dysfunction of the enzymes involved in the ademethionine synthesis or in methylation processes, where ademethionine is a crucial factor. On the basis of these considerations, several trials have proved the protective effect of ademethionine in cholestasis and in hepatic disease with different etiology. As regard human pathology the efficacy of ademethionine was demonstrated firstly in intrahepatic cholestasis of pregnancy or estrogen-induced and later on in hepatic diseases with different etiology. These results are particularly encouraging since very few are the drugs effective in the treatment of intrahepatic cholestasis, which represents indeed a crucial element in hepatic diseases.

Animals↗

Alterations of vibratory and thermal peripheral sensitivity in liver cirrhosis.

Peripheral neurological involvement, causing distal paresthesias and/or cramps has been described in liver cirrhosis, and its symptoms are quite frequent in decompensated patients under diuretic treatment. In this paper we reported thermal (TPT) and vibratory (VPT) sensations in 100 well-defined cirrhotics (43 in group A, and 63 in B and C of Child-Pugh classification) to define the prevalence of such alterations and the role of sex, age, severity and aetiology of the cirrhosis, and diuretic treatment. The TPT and VPT values were out of the normal range in 28% and 39% of the patients, respectively. Significantly, the alteration of VPT was associated both to alcoholic aetiology and decompensated cirrhosis, whereas the only parameter significantly associated to TPT alterations was alcoholic aetiology. Multiple factors such as inappropriate nutrition, hypercatabolic status, and portal systemic shunting may play a role in inducing trophic disturbances of nervous fibres in cirrhotics.

Adult↗

Decision-making model for a non-invasive diagnosis of compensated liver cirrhosis.

Liver biopsy is used as a gold standard in the diagnosis of chronic liver disease. However, this procedure is not without risk to the patients. This study was aimed to evaluate whether clinical, ultrasonographic, and biochemical variables may discriminate between well-compensated liver cirrhosis and non-cirrhotic chronic liver disease. Logistic regression analysis was used to assess the independent predictive value of each variable. Moreover, the post-test probability of the diagnostic variables was converted into "weights" which positively correlated with the likelihood of diagnosis of liver cirrhosis. We applied a decisional rule based on the diagnostic "weight" of each variable to 412 patients, 278 with well-compensated liver cirrhosis and 134 with non-cirrhotic chronic liver disease, diagnosed by liver biopsy with/without laparoscopy. By adding the diagnostic "weights" of each variable, liver cirrhosis and non-cirrhotic chronic liver disease were correctly diagnosed in 67% and 75% of cases, respectively. This result was validated in a split sample of 100 patients (50 with compensated liver cirrhosis and 50 with non-cirrhotic chronic liver disease) randomly selected from the acquisition sample. Based on this data, diagnosis of well-compensated liver cirrhosis can be reached in over 67% of cases without using invasive procedures. However, a prospective study is needed to confirm the clinical reliability of this method.

Adult↗

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↗