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Biomedical subjects

S Gentile

Publications and source records attributed to S Gentile.

At least 109 records · Page 6Linked to original sources
PubMed1987

Clinical and hormonal conditions associated with sodium retention in cirrhotic patients with ascites. Evaluation by univariate and multivariate analyses.

Using multiple regression analysis, we have evaluated the clinical and hormonal conditions associated with impaired urinary sodium excretion in normoazotemic patients with cirrhosis and ascites. We retrospectively identified 13 patients with a urinary sodium excretion lower than 15 mmol/day and 13 patients with a sodium excretion higher than 15 mmol/day. Using univariate analysis, all the patients with poor sodium excretion had abnormally high levels of plasma renin activity, plasma aldosterone, and arginine vasopressin. In addition, they had a diastolic blood pressure lower than patients with high urinary sodium excretion, although otherwise were comparable as regards clinical and biochemical data. The consistency of the above associations was then tested by multiple-regression analysis in an attempt to control for potentially confounding factors and to identify only true, independent associations. After a discriminant stepwise procedure, we found that low diastolic blood pressure (P less than 0.01) and high plasma aldosterone levels (P less than 0.05) were the only two conditions independently associated with abnormally low urinary sodium excretion. These findings are consistent with the view that sodium retention in decompensated cirrhosis results from a concomitant severe contraction in the effective blood volume and an increased production and/or retention of aldosterone. The concordance between our results and several pathophysiological findings supports the validity of this statistical approach to confirm physiological and/or clinical predictions.

Adult↗
PubMed1987

Hypersideremic and hyperbilirubinemic effect of nicotinic acid in patients with Gilbert's syndrome.

Nicotinic acid test (NA) administration is followed by a rise in unconjugated bilirubin and serum total iron in healthy man. A similar concomitant effect has never been investigated in Gilbert's syndrome (GS) patients, who by definition have a hyperbilirubinemia higher than that of controls. The aim of this study was to verify whether, in addition to the hyperbilirubinemic action, NA could induce parallel hypersideremia in GS subjects. The data we obtained confirm in GS patients: 1. the well-known hyperbilirubinemia; 2. a delayed NA plasma concentration curve, and document that in GS the hypersideremic effect is comparable to that of controls. Previous investigators reported that NA produces an equimolar rise of bilirubin and iron levels in healthy man. In our study the extent of the sideremic response to NA occurring in GS patients is comparable to that seen in controls, and appears unrelated to the bilirubinemic values. If the NA effects are based on the documented hemolytic properties of NA, a disturbance in bilirubin handling by the liver of GS subjects appears to be plausible in the presence of almost normal behavior of NA-induced hypersideremia.

Adolescent↗
PubMed1986

Noninvasive evaluation of left-to-right shunts by pulsed Doppler echocardiography.

The systemic and pulmonary blood flows and the ratio of pulmonary to systemic flow were noninvasively evaluated by pulsed Doppler echocardiography in 25 children with left-to-right shunts. Fourteen patients had atrial septal defect and 11 had ventricular septal defect. In patients with atrial septal defect, right ventricular stroke volume was obtained from the recordings of mean velocity flow and the diameter at the level of pulmonary valve in short-axis view. The left ventricular stroke volume was evaluated from the suprasternal approach by positioning the sample volume within the ascending aorta just above the valvar leaflets. In children with ventricular septal defect, the pulmonary blood flow was determined at the level of the mitral orifice, whereas the systemic blood flow was estimated from the ascending aorta. The systemic and pulmonary blood flows and their ratio determined by pulsed Doppler echocardiography in the 25 patients examined, were compared using simple linear regression analysis with the results obtained by cardiac catheterization. The ratio of pulmonary-to-systemic flow showed an excellent correlation in patients with atrial septal defect (r = 0.82) and in those with ventricular septal defect (r = 0.79). Our study validates the accuracy of cross-sectional Doppler echocardiography, especially for minimizing some possibility of errors in the presence of left-to-right shunts by employing new approaches.

Blood Circulation↗
PubMed1986

[Post-necrotic endoventricular thrombosis. Comparative evaluation of the diagnostic reliability of 2-dimensional echocardiography and cineventriculography].

The purpose of this study was to assess the relative diagnostic value of two-dimensional echocardiography (2D-Echo) and biplane left ventricular cineangiography (CV) for detecting the presence of left ventricular mural thrombi (LVT) in selected patients (pts) with left ventricular aneurysm (LVA). The Echocardiographic and Angiographic data of 19 pts selected from a group of 58 pts with coronary artery disease who underwent surgery for aorto-coronary bypass and/or aneurismectomy, were retrospectively examined. The presence of LVA was shown at surgery in all patients, located near the cardiac apex in 10 pts, at the level of the antero-septal wall of left ventricle in 7 pts and of the antero-lateral wall in 2 pts. In 11 of the 19 pts (57.9%) a LVT was identified at surgery. The thrombus was large (greater than 2 cmq) in 6 pts and small (greater than 2 cmq) in 5 pts. In 10 of the 11 pts with LVT 2D-Echo showed the thrombus prior surgery (sensitivity = 91.6%) whereas CV identified the thrombus only in 7 pts (sensitivity = 73.3%). No false positive diagnosis of LVT was made by the two techniques (specificity = 100%). Six large and 4 small thrombi (1 false negative) were identified by 2D-Echo; 6 large and 1 small thrombi (4 false negative) were identified by CV. In conclusion, 2D-Echo showed a significantly higher sensitivity for LVT than CV in patients with prior Acute Myocardial infarction, especially for small thrombi.

Adult↗
PubMed1986

Plasma lipid lipoproteins and biliary lipid composition in female gallstone patients.

The relationships between biliary lipid composition and cholesterol or triglyceride concentration in plasma lipoprotein fractions (i.e., very-low density, low-density, high-density, HDL2 and HDL3) have been studied in normolipaemic female gallstone patients. Univariate and multivariate stepwise statistical analyses were used to correlate biliary-tested variables against lipid lipoprotein concentration. Cholesterol saturation index was found to be positively and independently associated with total triglycerides, very-low-density lipoprotein triglycerides, very-low-density lipoprotein cholesterol and furthermore, negatively, with HDL3-cholesterol. Percent biliary deoxycholate was positively correlated with both cholesterol saturation index and plasma very-low-density cholesterol or triglycerides. Neither cholesterol saturation index nor percent biliary deoxycholate showed any correlation with total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, HDL2-cholesterol. The present findings suggest a linkage between biliary deoxycholate, biliary cholesterol saturation and plasma very-low-density lipoprotein levels in gallstone patients. Furthermore, since the lipoprotein risk factors for coronary heart disease showed no correlation with cholesterol saturation index, these results were considered a biochemical proof against the supposed association between coronary heart disease and gallstone disease.

Adult↗
PubMed1986

Familial clustering of heterogeneous chronic unconjugated hyperbilirubinemia.

This study concerns the family of a girl affected by type 2 Crigler-Najjar syndrome; a brother and a sister died of kernicterus a few months after birth. The father and two living siblings had moderate unconjugated hyperbilirubinemia. The patient's liver uridine-diphospho-glucuronyl-transferase activity (UDPGT) was markedly reduced. All the family members underwent nicotinic acid (NA) load to test hepatic uptake capacity. This test, and NA half-life were normal in the patient and in her mother, and altered in the other relatives. The extent of the hyperbilirubinemic response to NA load, and of the NA half-life, together with physical examination over a one-year period were in good agreement with the diagnosis of Gilbert's syndrome in the patient's father and siblings. Our conclusion is that different impairments of hepatic handling of organic anions may be present in members of families with non-hemolytic bilirubinemia.

Adult↗
PubMed1986

Dose dependence of nicotinic acid-induced hyperbilirubinemia and its dissociation from hemolysis in Gilbert's syndrome.

The serum increments in unconjugated bilirubin and total iron were determined after intravenous administration of 5.90 mumol/kg body weight of nicotinic acid (NA) in 26 patients with Gilbert's syndrome (GS), seven patients with hemolytic anemia, and 13 healthy volunteers. The hyperbilirubinemic response, expressed as the area under time concentration curve of unconjugated bilirubin (AUCBR, milligrams per deciliter per 240 minutes) was significantly higher (P less than 0.01) in patients with GS than in controls and patients with hemolytic anemia, in whom no difference was observed. In contrast, comparable values of the hypersideremic effect (AUCFe, milligrams per deciliter per 240 minutes) were noticed among the three groups. In seven consecutive patients with GS, seven with hemolytic anemia, and four healthy volunteers, AUCBR, AUCFe, and the NA plasma half-life of the first fast slope of the curve were determined at three different doses of the drug (1.18, 2.95, and 5.90 mumol NA per kilogram body weight). A significant, dose-dependent increase in AUCBR was present in patients with GS, whereas it remained constant both in controls and in patients with hemolytic anemia. The NA plasma half-life was also significantly prolonged in GS with each of the three doses, but remained unchanged in the other two groups. In patients with GS, a linear correlation (r = 0.891, P less than 0.001) was present between AUCBR and NA plasma half-life. In contrast, the AUCFe value remained constant at the different doses used in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Measurement of the association of cholephylic organic anions with different binding proteins.

The binding of the colored cholephylic anions tetrabromosulfonphthalein (BSP), di-bromosulfonphthalein (DBSP), indocyanine green (ICG) and thymol blue (ThB) to a number of protein preparations including bovine serum albumin, human serum, rat hepatic cytosol and purified rat liver bilitranslocase has been studied by a direct spectrophotometric method. The experimentation provides extinction coefficients, dissociation constants and number of binding sites for the different complexes between dyes and the various proteins. Data obtained by this technique were in excellent agreement with those obtained on the same samples by ultrafiltration. The data presented indicate that the direct spectrophotometry applied to these dyes is simple, rapid and reproducible, making this the approach of choice during the purification of binding proteins when the binding capacity is the only useful criterion to follow the progress of the procedure.

Animals↗
PubMed1985

[Tardive dyskinesia].

Neuroleptic drug treatment can produce tardive dyskinesia of which the incidence, risk factors, clinical characteristics and problems of differential diagnosis are described. Possible therapeutic approaches are then considered in the light of the hypothesis that the condition may derive from a physiopathological hypersensitivity of the dopamine receptors.

Antipsychotic Agents↗
PubMed1985

Thymic regulation of brain cortex beta-adrenoceptors during development and aging.

The influence of the thymus on beta-adrenoceptors has been studied in the brain cortex of mice during developing and aging. Affinity of beta-adrenoceptors shows no statistically significant changes in the various animal models investigated. Receptor density shows a fall in both athymic nude mice and in old normal mice. Receptor density, in particular, decreases progressively with advancing age. It has been demonstrated that thymus exerts a regulatory role in both development and aging, as a neonatal thymic graft is capable of reversing the receptor impairments found in young athymic nude mice and in old normal mice.

Aging↗
PubMed1985

Comparison of nicotinic acid- and caloric restriction-induced hyperbilirubinaemia in the diagnosis of Gilbert's syndrome.

The diagnostic value of the nicotinic acid (NA)-induced hyperbilirubinaemia was compared with that resulting from caloric restriction in 40 patients with Gilbert's syndrome (GS) and 20 controls. Both tests resulted in a significant higher level of serum bilirubin in GS than in controls (P less than 0.001). When the serum bilirubin level 240 min after NA administration (5.9 mumol/kg i.v.) was higher than 18 mumoles/l, this test had a specificity and sensitivity of 100%, both in males and females with the syndrome. The discriminatory value of the test was lower when either the area under the time concentration curve or the maximal increment of serum unconjugated bilirubin were used. Reduction in caloric intake (400 calories/day) showed a lower specificity and sensitivity than the NA test, particularly in females. An increment of bilirubin at 24 h greater than 15 mumoles/l was more diagnostic than an increase by 100% or more over the pre-diet value. The efficacy was not improved by prolonging the test for additional 24 h. From these data we conclude that NA-induced hyperbilirubinaemia and, in particular the concentration of the pigment 240 min after drug administration, is more efficient than fasting-induced hyperbilirubinaemia in the diagnosis of the Gilbert's syndrome both in males and in females.

Adult↗
PubMed1985

Sex differences of nicotinate-induced hyperbilirubinemia in Gilbert's syndrome. Implication of bilitranslocase function.

Intravenous administration of nicotinic acid (NA) is followed by an increase in serum unconjugated bilirubin level. This effect is higher in Gilbert's syndrome (GS) and this test has been used in the diagnosis of the syndrome. After administration of 5.9 mumol NA/kg body weight, the maximal increment of serum unconjugated bilirubin and the area under the bilirubin concentration time curve (AUC) were significantly higher (P less than 0.01) in GS males than in GS females. The half-life of the first fast slope of plasma disappearance curve of the drug was also significantly prolonged in GS males as compared to GS females (15.91 +/- 1.12 vs 9.13 +/- 1.25 min, mean +/- SEM, P less than 0.005). The maximal bilirubin increment and AUC were linearly correlated (P less than 0.01) with NA plasma half-life. Purified preparations of bilitranslocase, a liver plasma-membrane protein involved in bilirubin and sulfobromophthalein (BSP) transport, specifically bound NA and the drug competitively inhibited BSP uptake in rat liver plasma membrane vesicles (Ki = 50 nM). These data suggest that, in addition to the hemolytic effect of the drug, NA-induced hyperbilirubinaemia could be also due to a competition between the two anions at the sinusoidal plasma membrane level. A possible implication of bilitranslocase in GS is considered.

Adolescent↗
PubMed1985

The implication of bilitranslocase function in the impaired rifamycin SV metabolism in Gilbert's syndrome.

1. The plasma disappearance rate and the increment in plasma unconjugated bilirubin after intravenous administration of 5.9 mumol of rifamycin SV (RSV)/kg body wt. were investigated in 51 subjects with Gilbert's syndrome and 35 control subjects of both sexes. 2. Both the plasma disappearance rate and the unconjugated hyperbilirubinaemia after RSV administration were higher (P < 0.001) in Gilbert's syndrome. Females, both normal and with the syndrome, showed a significantly shorter t1/2 and a lower hyperbilirubinaemic response as compared with males. A linear correlation (P < 0.001) was present between RSV plasma half-life and the hyperbilirubinaemic response. 3. In vitro, RSV was shown to inhibit sulphobromophthalein (BSP) uptake in rat liver plasma-membrane vesicles with a Ki of 20 mumol/l. Evidence that this effect was due to competition for bilitranslocase was sought on preparations of the purified protein. Under these experimental conditions, RSV inhibited BSP binding with a Ki of 17 mumol/l. 4. Since RSV competes with BSP for binding to bilitranslocase in vitro, the data are interpreted as suggesting that reduced bilitranslocase function might underlie the delayed RSV plasma clearance and the exacerbated unconjugated hyperbilirubinaemia present in Gilbert's syndrome.

Adolescent↗
PubMed1985

Impaired plasma clearance of nicotinic acid and rifamycin-SV in Gilbert's syndrome: evidence of a functional heterogeneity.

Patients with Gilbert's syndrome (GS) have impaired clearance by the liver of some organic anions. We looked for possible differences in hepatic clearance of nicotinic acid (NA) and rifamycin-SV (R-SV) among GS patients, and examined the effect produced by these anions on the plasma levels of unconjugated bilirubin (UCB). Two subgroups of GS patients, GS1 and GS2, were differentiated according to their ability to handle R-SV and NA. Compared with a control group, the alteration of the half-life both of NA and R-SV was less marked in GS1 than in GS2. UCB plasma concentration after NA and R-SV loading was more greatly increased in GS2 than in GS1 patients. In addition, a striking correlation was found in all subjects studied between UCB and the half-life of NA and R-SV. These related alterations of plasma UCB and plasma half-life or organic anions suggests a common defect of hepatic uptake. It is hypothesized that this defect is located at the level of a hepatic plasma membrane carrier.

Adolescent↗
PubMed1985

Improvement of the nicotinic acid test in the diagnosis of Gilbert's syndrome by pretreatment with indomethacin.

The hyperbilirubinemia induced by nicotinic acid (NA) is well correlated to 14C-bilirubin clearance, and is utilized to diagnose Gilbert's syndrome (GS). However, NA produces a number of vascular prostaglandin-mediated side effects. In an attempt to improve the NA test we evaluated the influence of pretreatment with Indomethacin, a PG-synthetase inhibitor, both on side effects and hyperbilirubinemia. NA (5.9 mumoles/kg of body weight i.v.) was administered on two separate occasions, before and one hour after i.m. injection of 100 mg Indomethacin in 11 GS males and 11 controls matched for sex and age (age range 18.34 years). The hyperbilirubinemic effect of NA was not modified by Indomethacin in any subject; the side effects were either significantly reduced or completely abolished. We suggest that patients undergoing the NA test for the diagnosis of GS be pretreated with Indomethacin.

Adolescent↗