Biomedical subjects

E Pisi

Publications and source records attributed to E Pisi.

At least 37 records · Page 2Linked to original sources

PubMed1993

Low frequency of allelic loss in the cyclin A gene in human hepatocellular carcinomas: a study based on PCR.

The cyclin A gene was first identified at a site of hepatitis B virus DNA integration in a primary liver cancer (PLC). It has now been mapped to 4q27, in the proximity of a chromosomal locus (4q32) which is frequently rearranged and deleted in PLC. We took advantage of the TaqI polymorphism recently described in the cyclin A gene to search for allelic loss in this gene by means of PCR. Tumorous and non-tumorous tissue from 50 patients with PLC was analyzed: 27 samples (54%) were homozygous for the A1 type allele (i.e. the allele bearing the TaqI restriction site), three (6%) were homozygous for the A2 type allele (without the TaqI site) and 20 (40%) were heterozygous. Comparison of tumorous and non-tumorous patterns showed that only one (5%) tumorous tissue out of 20 heterozygous patients was homozygous, indicating the loss of an allele at this locus. We conclude that allelic loss in the cyclin A gene is a rare event in patients with PLC, and that PCR is rapid and reliable for the detection of allelic loss in the cyclin A gene when only small amounts of DNA are available.

Alleles↗

PubMed1993

Abdominal lymphadenopathy detected by ultrasonography in HIV-1 infection: prevalence and significance.

By using abdominal ultrasonography (UlS), deep nodes were detected in 41 of 85 (48%) HIV-1 positive subjects, most of them heroin addicts, but in none of 85 healthy HIV-negative controls. Computerized tomography, performed in 10 cases of lymphadenopathy, invariably confirmed the UlS findings. Prevalence [asymptomatic carriers: 8/15 (53%); PGL patients: 8/18 (44%); ARC: 13/27 (48%); AIDS: 12/25 (48%)], number, size, and site of deep nodes were comparable among the different CDC groups. No correlation was found between abdominal and superficial lymphadenopathy. Median serum concentrations of gammaglobulins (g/dl) and IgG (mg/dl) were higher in patients with than without deep nodes (2.25 vs 1.87 and 2540 vs 1900, respectively) (p < 0.01) as well as in cases with than without superficial nodes (2.15 vs 1.80 and 2340 vs 1941, respectively) (p < 0.05). Abdominal lymphadenopathy occurred during all stages of HIV infection even in asymptomatic carriers: this should be considered in the differential diagnosis of UlS-detected deep nodes. Enlargement of either deep or superficial nodes seems to reflect a state of polyclonal B cell activation.

Abdomen↗

PubMed1993

Unresponsiveness of hepatic nitrogen metabolism to glucagon infusion in patients with cirrhosis: dependence on liver cell failure.

Glucagon exerts an up-regulatory effect on hepatic nitrogen metabolism in healthy subjects, but its potential role in the presence of liver failure is uncertain. The effects of glucagon on urea synthesis and hepatic nitrogen clearance during alanine infusion were studied in five control subjects and six cirrhotic patients in paired experiments at spontaneous glucagon concentrations and at high physiological glucagon levels (approximately 300 to 500 pmol.L-1) induced by a 7.5-hr continuous glucagon infusion. In all experiments the urea nitrogen synthesis rate increased linearly with increasing alpha-amino-nitrogen concentrations. At spontaneous glucagon concentrations the dynamics of alpha-amino nitrogen to urea nitrogen conversion (functional hepatic nitrogen clearance) were significantly reduced in cirrhosis (23.2 +/- 6.7 L.hr-1 vs. 35.3 +/- 8.0 L.hr-1, p < 0.05) in relation to decreased liver function. Glucagon superinfusion caused a 63% increase in the dynamics of the process in controls (57.7 +/- 11.0 L.hr-1; p vs. spontaneous glucagon, p < 0.01), whereas in cirrhosis it increased on average by only 15% (26.7 +/- 10.7; p = NS). The glucagon-induced change in functional hepatic nitrogen clearance significantly correlated with galactose elimination capacity and antipyrine clearance (r = 0.905 and 0.964, respectively). Glucagon, in high physiological concentrations achieved with glucagon infusion, does not produce significant effects on hepatic nitrogen metabolism in cirrhosis. The reduced sensitivity of the cirrhotic liver to glucagon seems to be dependent on decreased hepatocellular function. These data do not support the role of glucagon as a "catabolic" hormone in cirrhosis.

Adult↗

PubMed1993

Persistence of hepatitis B and hepatitis C viral genomes in primary liver cancers from HBsAg-negative patients: a study of a low-endemic area.

The role of HBV and HCV in the course of primary liver cancer in patients who are negative for HBsAg has been debated. Using a combination of serological and polymerase chain reaction assays, we investigated the association between HCV and HBV infections and primary liver cancer in 24 HBsAg-negative patients living in France. The presence of HCV RNA and HBV DNA sequences was tested for in serum and in tumorous and nontumorous liver samples. Twelve patients had anti-HCV, and 11 patients had anti-HBs and/or anti-HBc. HCV RNA sequences were found in the serum samples of all anti-HCV-positive patients and none of the patients who were negative. Patients with HCV viremia had HCV RNA genomic sequences and presumed replicative intermediates in both tumorous and nontumorous specimens. Sequence analysis of a hypervariable region in the E2/NS1 gene of HCV showed significant variations between the viral molecules isolated from the nontumorous, tumorous and serum samples. This eliminated the hypothesis of the contamination of the tumor by nontumorous cells and serum particles and assessed that liver tumor cells did contain HCV RNA genomes. Eleven of 22 patients tested had HBV DNA in the serum; 5 patients were anti-HBc positive and anti-HBs positive. Patients with HBV viremia had HBV DNA sequences in both tumorous and nontumorous liver specimens. Selective loss of part of the HBV genome in the tumorous tissue of two of these patients suggested HBV DNA persistence in clonally expanded malignant cells. Only 4 of the 22 patients were negative for both viruses. Our results show that HBsAg-negative hepatocellular cancer in France is associated with chronic HBV or HCV infection and, in some cases, both; these findings are consistent with an etiological role for HBV and HCV in HCC that develops in cirrhotic patients living in areas of low prevalence.

Base Sequence↗

PubMed1992

Defective methionine metabolism in cirrhosis: relation to severity of liver disease.

A block in the transsulfuration pathway has previously been suggested in cirrhosis on the basis of increased fasting methionine concentrations, decreased methionine elimination and low levels of methionine end products. To date, methionine elimination has never been studied under controlled steady-state conditions, and the relation of the severity of liver disease to impaired methionine metabolism has not been clarified. We measured methionine plasma clearance in 6 control subjects and in 12 patients with cirrhosis during steady-state conditions obtained by a primed, continuous methionine infusion. In the presence of high-normal fasting methionine concentrations (range = 14 to 69 mumol.L-1 in controls and 26 to 151 mumol.L-1 in cirrhotic patients), methionine plasma clearance was reduced in cirrhotic patients (2.25 +/- S.D. 0.43 ml.sec-1 vs. 2.86 +/- S.D. 0.43 ml.sec-1 in controls; p less than 0.05), whereas methionine half-life was increased (282 +/- 90 min vs. 187 +/- 25 min in controls; p less than 0.05). Fasting methionine significantly correlated with methionine clearance. The infused methionine was not degraded to urea to any significant extent in cirrhotic patients, whereas a threefold increase in urinary urea nitrogen excretion rate was observed in controls. Similarly, taurine concentrations significantly increased both in plasma and in the urine in controls but not in cirrhotic patients. In cirrhotic patients methionine plasma clearance significantly correlated with galactose elimination capacity (r = 0.818) and with the Child-Pugh score (rs = -0.795). The study supports a major role of impaired liver cell function in the reduced metabolism of methionine and decreased formation of methionine end products that occur in cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Effect of S-adenosyl-L-methionine administration on plasma levels of sulphur-containing amino acids in patients with liver cirrhosis.

An impaired transsulphuration pathway has been described in patients with liver cirrhosis. The defective metabolic step is located at the site of S-adenosyl-L-methionine (SAMe) formation from methionine. In a placebo-controlled study, we measured the fasting plasma levels of sulphur-containing amino-acids in cirrhotic patients with hypermethioninemia and/or severe hepatocellular failure, during treatment with exogenous SAMe (1.2 g i.v. for 3 days, followed by an oral administration of 1.2 g for an additional 30 days; 8 cases) or saline and placebo tablets (8 cases). All subjects were initially treated during hospital admission, and completed the oral study as out-patients. In patients given SAMe, long-term treatment doubled the plasma concentration of the secondary sulphur-containing amino acid cystine (from 36 [SD 18] mumol.l(-1) to 67 [36]) and taurine (from 42 [13] mumol.l(-1) to 89 [33]), which were on average low-normal at baseline, without any change in the concentration of methionine, of neutral amino acids, and of polyamines. No changes in plasma amino acids were observed in the control group. Two-factor, repeated measures of analysis of variance revealed differences between SAMe- and placebo-treated patients, consistent with an effect of long-term SAMe administration on secondary sulphur-containing amino acids. The potential therapeutic advantage of such treatment remains to be determined in clinical studies.

Journal Article↗

PubMed1992

Polyamine plasma levels and liver regeneration following partial hepatic resection in man.

Polyamines (putrescine, spermidine, and spermine) are widely distributed in animal and vegetal tissues, where their intracellular concentration strictly correlates with normal and pathological cell growth and protein synthesis. By means of a sensitive HPLC technique, the fasting plasma concentrations of polyamines were measured serially in 11 patients who underwent partial hepatic resection because of focal liver lesions. Samples were obtained before surgery and over the next 6 months, during hepatic regeneration. Liver volume was also measured by ultrasound on the basis of the 3 maximum diameters of the liver. From 2 to 4 weeks after surgery, plasma putrescine increased by a maximum of 78%, and spermidine by approximately 50%. No changes were observed in spermine levels. The spermidine/spermine ratio nearly doubled during liver regeneration. The volume of the liver decrease from 1505 [SD 236] ml to 743 [151] ml after resection, and returned to nearly normal values after 6 months (1231 [100] ml, p < 0.05 vs. basal values). The liver regeneration rate was highest 2-4 weeks after resection, and declined thereafter, when prevailing polyamine concentrations returned to normal. These data show that liver regeneration is accompanied by a significant increase in fasting putrescine and spermidine concentrations, which might be biochemical signals of active liver cell regeneration.

Adult↗

PubMed1992

Anthropometric assessment of the nutritional status of patients with liver cirrhosis in an Italian population.

A poor nutritional status has repeatedly been described in advanced liver cirrhosis, but the exact prevalence of the defect and its relation to the aetiology and severity of liver disease in the Italian population are only partly known. Anthropometric measurements were carried out in 200 patients with cirrhosis (135 M, 65 F). Liver disease was related to alcohol abuse in 77 cases, but most patients had stopped alcohol for at least 6 months before study. In comparison to a normal elderly Italian and to an age-matched North-American population, 5 to 45% of male patients with cirrhosis and 10 to 30% of females had signs of malnutrition, the proportion being variable according to the test used. Male patients showed a remarkable reduction in muscle mass (30-45% of patients, mainly in the presence of moderate-to-severe or severe liver failure), whereas female patients showed a more remarkable reduction of fat stores (15-30% of cases), with advancing liver failure, and a less severe reduction in muscle mass. No direct effect of alcohol was demonstrated in this selected population.

Adipose Tissue↗

PubMed1992

Oral BCAA supplementation in cirrhosis with chronic encephalopathy: effects on prolactin and estradiol levels.

The effects of oral BCAA supplementation on fasting levels of prolactin and estradiol were retrospectively analyzed in frozen plasma samples of patients with cirrhosis and chronic hepatic encephalopathy, taking part in a 3-month randomized, double-blind trial. Twenty-five patients had received 0.24g of BCAA per kg body weight, 24 had received an equinitrogenous amount of casein, in addition to a diet providing 0.7-1.0 g/kg of protein. Thirty-eight were males, 11 post-menopausal women. Fasting prolactin did not show any change in the BCAA group, where mental state significantly improved. In the casein group plasma prolactin increased by nearly 50% during the 3-month period. Similarly, estradiol concentrations were unchanged during BCAA supplementation, and increased during casein treatment. The analysis of variance demonstrated significant differences between the 2 treatments. Liver function tests and nutritional parameters (albumin, transferrin, urinary creatinine) supported a superiority of BCAA over casein. These data suggest that the favorable effects of BCAA on mental state are not mediated by changes in cerebral neurotransmission, but are due mainly to maintained liver function, possibly related to improved nutrition.

Administration, Oral↗

PubMed1991

Elimination of infused branched-chain amino-acids from plasma of patients with non-obese type 2 diabetes mellitus.

Increased plasma levels of branched-chain amino-acids (BCAA) have been demonstrated in poorly controlled diabetes mellitus, and related to absolute or relative insulin deficiency. To study the pathogenesis of this alteration, the elimination of BCAA from plasma was measured in 8 patients with non-obese type 2 diabetes mellitus and in 8 age-matched control subjects during steady-state BCAA concentrations induced by a primed-continuous infusion. Fasting BCAA levels were increased by 40-50% in patients with diabetes. The plasma clearances of valine, isoleucine, and leucine, calculated as infusion rate divided by steady-state concentration, were reduced by 20% in diabetics, despite 50% hyperinsulinemia (P < 0.01). Basal BCAA levels and BCAA clearance were negatively correlated (r(2) = 0.46 - 0.56). The endogenous basal appearance rates of BCAA, estimated by the basal concentrations multiplied by the plasma clearances, were normal in diabetics, and there was no difference in the apparent volumes of distribution of BCAA. The increased basal concentration of BCAA in poorly controlled type 2 diabetics (693 [SD 114; n = 8] mumol/l vs 479 [88; n = 8] in controls (P < 0.005) is attributable to changes in plasma clearances, without any change in the efflux of BCAA into plasma. This may be due to insulin resistance.

Journal Article↗

PubMed1991

Thyroid gland size and function in patients with cirrhosis of the liver.

Thyroid dysfunction has long been reported in patients with liver disease, but limited information is available on thyroid gland size in cirrhosis. Most studies were carried out on small, selected series of patients, and no study has measured thyroid volume in relation to the etiology of liver disease. Thyroid volume was measured at ultrasound in 118 consecutive patients with cirrhosis of different etiology and 48 healthy subjects matched for age and sex. No subjects had evidence of overt thyroid disease. The mean volume was increased by 17% (from 16.0 [SD 5.2] ml in controls to 18.8 [7.6] in cirrhosis; P less than 0.025), and thyroid enlargement (antero-posterior diameter greater than 20 mm) was present in 38% of cases, in the presence of hormone values indicative of low-T3 syndrome. No significant differences in thyroid gland size were observed in relation to the extent of liver dysfunction or to the etiology of liver disease. The prevalence of thyroid nodules was similar in controls and in patients with cirrhosis. In only 8% of cases were laboratory values indicative of hypothyroidism, with low free triiodothyronine and raised thyroid-stimulating hormone levels; in these patients thyroid volume was decreased on average by 26%. This was mainly the case with patients with primary biliary and alcoholic cirrhosis. The largest mean thyroid volume was observed in patients with HBsAg + ve postnecrotic cirrhosis, whose thyroid volume was increased on average by 37%, and 53% of subjects had thyroid enlargement. This finding raises the question of a possible direct involvement of the thyroid in hepatitis B virus infection.

Female↗

PubMed1991

Prognostic indicators in compensated cirrhosis.

In an attempt to identify variables predicting prognosis, 100 consecutive patients with compensated cirrhosis of the liver were followed for a mean of 4.9 (SD 0.7) yr. Fifty-one patients belonged to Child-Pugh class A, 49 to class B. At entry, five laboratory parameters were considered, together with sex, the grade of esophageal varices, and seven variables measured by ultrasonography (liver and spleen volume and the calibers of the splanchnic vessels). In a subgroup of 56 patients, the galactose elimination capacity also was determined. Forty-six patients were alive at the end of follow-up. Survival was analyzed according to Cox's model. Six parameters were able to predict survival (albumin, bilirubin, liver volume, prothrombin activity, cholesterol, varices). However, step-wise Cox regression analysis identified only four variables that independently correlated with survival: albumin, bilirubin, cholesterol, and liver volume. Galactose elimination failed to add any significance to routine liver function tests. This prospective study confirms the ability of routine liver function tests in predicting survival in compensated cirrhosis. The measurement of liver volume, easily obtained by ultrasonography, is also significant for prognosis, and may be introduced into clinical practice.

Actuarial Analysis↗

PubMed1991

Hepatic amino-nitrogen clearance to urea-nitrogen in control subjects and in patients with cirrhosis: a simplified method.

The functional hepatic nitrogen clearance during amino acid infusion is a measure of liver cell mass. The clinical feasibility of the test has so far been limited by methodological problems. A simplified procedure was used to measure the urea-nitrogen synthesis rate and functional hepatic nitrogen clearance in nine subjects with normal liver function and in nine patients with cirrhosis. The method was based on only four consecutive 2-hr urine collections and five blood samples. Total body water was calculated from a nomogram based on age and anthropometric data, whereas the gut urea hydrolysis was assigned one fixed fraction of synthesis (0.17 in control subjects and 0.26 in patients with cirrhosis). Finally, a solution of a single amino acid, alanine, was infused as substrate for urea synthesis. Urea-nitrogen synthesis rate increased linearly with increasing alpha-amino-nitrogen concentration, and the slope of the regression (functional hepatic nitrogen clearance) was reduced in cirrhosis from 37.5 +/- 7.0 L/hr to 18.4 +/- 6.7 L/hr; p less than 0.005. The hepatic nitrogen clearance was linearly related to the clinical status (Child-Pugh score), to routine liver function tests and to galactose elimination capacity (r = 0.869), a well-established, quantitative, liver function measure. The simplified method makes the measurement of hepatic nitrogen clearance suitable for routine clinical use. The test might prove useful to study the alterations of nitrogen metabolism in cirrhosis, with special reference to hepatic encephalopathy.

Adult↗

PubMed1990

Ultrasonographic follow-up of liver cirrhosis.

Ultrasonography and upper gastrointestinal endoscopy were prospectively used to study 100 consecutive patients with liver cirrhosis. After a period of 20 months to 55 months, 21 patients had died, 23 were lost at follow-up, and 56 patients were reevaluated. In the patients who died during follow-up, the entry liver volume, measured by means of the hepatic volumetric index, was lower as compared to the 56 cirrhotics who survived. During the study period, liver volume significantly decreased to values similar to those observed, at entry, in patients who died. Moreover, esophageal varices increased in size, and the splanchnic veins enlarged. Abdominal ultrasonography provides data regarding the natural history of liver cirrhosis, which might be used, in addition to tests of liver function and endoscopy, as prognostic factors in cirrhotic patients.

Adult↗

PubMed1990

Synthesis of urea after a protein-rich meal in normal man in relation to ageing.

An age-related decline in the functional capacity of the liver has been repeatedly demonstrated by means of dynamic tests. We measured the urea-N synthesis rate in response to a protein-rich meal in 24 healthy subjects divided into three age-groups (less than or equal to 55 years, 56-70 years; greater than or equal to 71 years). No differences were observed in the basal state. The peak urea synthesis and the mean urea synthesis in the 5 hours after the meal were blunted with increasing age, and a negative correlation was present between mean or peak urea synthesis and age (r = -0.572 and r = -0.541, respectively). No differences in basal and post-meal total alpha-amino-nitrogen or individual plasma amino acids were observed. Hormone responses were similar. Galactose elimination capacity was also reduced with increasing age, and correlated with mean and peak urea synthesis after a protein mean (r = 0.640 and r = 0.591, respectively). These data suggest that the capacity of the liver to produce urea in response to a protein-rich meal is reduced in the elderly in relation to a decreased functional liver cell mass.

Age Factors↗

PubMed1990

Prevalence and significance of abdominal lymphadenopathy in patients with chronic liver disease: an ultrasound study.

Enlarged abdominal, mainly periportal, lymph nodes were detected by real time ultrasonography in 19% (42 of 227) of patients with chronic liver disease who had no evidence of tumor, upper gastrointestinal carcinoma, or lymphoproliferative disorder. Computed tomography, performed in 15 cases, always confirmed the sonographic findings. Lymph node biopsies from two patients showed reactive hyperplasia. Lymphadenopathy occurred more frequently in autoimmune (primary biliary cirrhosis, autoimmune, and liver-kidney microsomal antibody-positive chronic hepatitis: 33, 25, and 22% of cases, respectively) than nonautoimmune disease (cryptogenic, alcoholic, and hepatitis B virus-related chronic hepatitis: 16, 12, and 10% of cases, respectively) (p less than 0.005). Four of five patients with mixed polyclonal cryoglobulinemia or monoclonal gammopathy had lymphadenopathy. In 125 patients, including 25 with lymphadenopathy, who were monitored for a median period of 25 months, the ultrasonographic pattern remained unchanged. Abdominal, presumably benign, lymphadenopathy may accompany chronic liver disease, especially when prominent immunological features coexist. This should be kept in mind for the correct interpretation of such an ultrasound finding.

Abdomen↗

PubMed1990

Analysis of the deterioration rates of liver function in cirrhosis, based on galactose elimination capacity.

The prognosis of cirrhotic patients may depend on their liver function, but very few data are available to predict life expectancy in individual subjects on the basis of their liver function tests. The yearly changes in liver function, based on galactose elimination capacity (GEC), were retrospectively analyzed in 76 cirrhotic patients. The first GEC measurement had always been performed at the time of diagnosis. From that time on, mean GEC changes (in mmol/min per year) were +0.13 [SD 0.60] in the 1st year (range: +1.42/-1.35), and -0.03 [0.30] in the 2nd year (P = ns). Only after 36 months could a significant deterioration in liver function be demonstrated, but GEC changes still ranged from +0.14 to -0.35. The trend in liver function was similar in patients with alcoholic and non-alcoholic cirrhosis, but in alcoholics a favourable effect of abstinence was proved. In individual subjects, 2 consecutive GEC measurements, at least 6 months apart, failed to predict the following GEC values. The coefficients of determination between expected and measured GEC or delta GEC were 0.13 and 0.36, respectively (n = 58). When forecasting was limited to 2 years (n = 38), still only 31% and 55% of GEC values and delta GEC variance was predictable on the basis of preceding GEC values. The study shows that no definite trends in liver function deterioration rates can be observed in cirrhosis. This limits the usefulness of liver function tests in predicting prognosis in cirrhotic patients.

Adult↗

PubMed1990

Mechanisms and consequences of the impaired trans-sulphuration pathway in liver disease: Part II. Clinical consequences and potential for pharmacological intervention in cirrhosis.

The liver is actively involved in the metabolism of the sulphur-containing essential amino acid, methionine. Methionine is transformed into S-adenosyl-L-methionine (SAMe) and then into sulphur-containing metabolites (cysteine, taurine and glutathione) via the trans-sulphuration pathway. Liver disease may affect the trans-sulphuration pathway and decrease the clearance of methionine, which leads to increased fasting methionine concentrations in blood and reduced formation of cysteine and glutathione. There is evidence that this defect, located at the level of SAMe-synthetase, may cause nutritional defects and contribute to negative nitrogen balance whenever non-essential sulphur-containing amino acids are not supplied in adequate amounts. In addition, cirrhotic patients may be at increased risk of hepatotoxicity after treatment with substances which are detoxified via glutathione. The SAMe-synthetase block may be overcome by administration of oral or intravenous SAMe, which improves the fasting amino acid profile and increases the hepatic glutathione concentration. Controlled studies on long term SAMe treatment in patients with cirrhosis are needed to confirm this possible beneficial effect.

Amino Acids↗