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Biomedical subjects

S Gentile

Publications and source records attributed to S Gentile.

At least 91 records · Page 5Linked to original sources
PubMed1991

State of stupor from valproic acid during chronic treatment: case report.

We describe the case of a 26 years old woman in chronic therapy with phenobarbital, carbamazepine, valproic acid (VPA) and clonazepam who showed a hyperammonemic encephalopathy after an increase in dosage of VPA. Similar cases have been reported, but with acute-subacute onset and no correlation with the plasma levels of VPA. Our case suggests the possibility that this toxic effect occurs during chronic treatment too, when the dosage of VPA is increased.

Adult↗
PubMed1991

Collection, processing and storage of peripheral blood stem cells (PBSC).

Eight patients with hematological malignancies were treated with autologous blood stem cell transplantation (ABSCT). Hemopoietic precursor cells were mobilized into the peripheral blood (PB) by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem cell concentration. PB CFU-GM showed a 15-20 fold increase on days 15-20 after chemotherapy. Peripheral blood stem cells were collected by 5-8 continuous flow leukaphereses using a Fenwall CS 3000 blood cell separator when platelet and WBC count was rising rapidly (platelet greater than 50 x 10e9/L and WBC greater than 1 x 10e9/L). Mean CFU-GM collected per run by leukapheresis were 10.85 x 10e4/Kg (procedure 3), 10.03 x 10e4/Kg (modified procedure 1). Mononuclear cell suspension in 10% DMSO was frozen at controlled rate freezer (-1 degree C to -4 degrees C) and stored in the liquid phase of nitrogen. After thawing CFU-GM recoveries ranged from 13.8% to 81.5%; 55-70% of recovered cells excluded trypan blue dye.

Adolescent↗
PubMed1991

Treatment of malignant lymphomas with very-high-dose CVB followed by transplantation of autologous blood stem cells collected after mobilizing chemotherapy.

In 8 patients (age 25 +/- 46 years, mean 34.5), 4 with Hodgkin's disease (HD) and 4 with non-Hodgkin's lymphoma (NHL), circulating stem cells (CSC) collected at the time of rapid leukocyte and platelet recovery after intense chemotherapy were employed for autologous hematological reconstitution after very-high-dose chemotherapy (CVB combination). At the time of graft 2 patients were in 1st remission and 2 in 2nd, while the remaining 4 had persistence or progression of disease. Autografted patients received 3.4 +/- 8.3 (mean 5.2) x 10e8/Kg mononuclear cells and 2.1 +/- 40.5 (mean 22.5) x 10e4/Kg CFU-GM. All patients had prompt and sustained engraftment, though in one case platelets never reached normal levels. Recovery time was respectively 10 +/- 17 days (mean 13.2) for granulocytes 0.5 x 10e9/L, and 10 +/- 49 days (mean 20.3) for platelets greater than 50.0 x 10e9/L, with an interval of less than 4 days from greater than 0.5 to greater than 1.0 granulocytes in 7 out of the 8 patients. All patients are currently alive at 57 +/- 645 (median 262) days, and 7 in remission at 61 +/- 645 (median 297) days from autologous blood stem cell transplantation (ABSCT). Our study demonstrates that CSC collected after mobilizing chemotherapy are able to promptly restore and sustain hemopoiesis after marrow ablative chemotherapy in patients with malignant lymphoma. CSC reduce toxicity and hospitalization so impressive, that in malignant lymphomas ABSCT could rapidly be considered for first line strategy.

Adult↗
PubMed1991

Responsiveness to phenobarbital in an adult with Crigler-Najjar disease associated with neurological involvement and skin hyperextensibility.

We present the case of a 23-yr-old man who had had since birth marked and sustained unconjugated non-hemolytic hyperbilirubinemia and who had had several attacks of grand mal seizures. Analysis of serum bilirubin by diazoreactive methods showed serum levels of unconjugated bilirubin as high as 445 mumol/L that were not affected by phenobarbital administration. However, analysis of serum bile pigments by high-pressure liquid chromatography demonstrated marked decrease of unconjugated bilirubin after phenobarbital treatment (from 432.4 mumol/L to 291.0 mumol/L) associated with slight increase of bilirubin monoconjugates and disconjugates (from 0.25 mumol/L to 0.42 mumol/L). Furthermore, in the past few years the patient had exhibited striking skin hyperextensibility and diaphragm eventration. This case confirms that alkaline methanolysis-high-pressure liquid chromatography is the most reliable method for assessment of serum fraction bilirubin levels; that clinical parameters such as neurological signs do not unequivocally discriminate between type I and II Crigler-Najjar disease and that response to phenobarbital treatment remains the main diagnostic tool.

Adult↗
PubMed1990

Abnormal hepatic uptake of low doses of sulfobromophthalein in Gilbert's syndrome: the role of reduced affinity of the plasma membrane carrier of organic anions.

The plasma disappearance rate of sulfobromophthalein (VBSP; mumol/kg/min) was measured in 15 Gilbert's syndrome patients and 12 control subjects after intravenous injection of two different doses (0.59 and 5.90 mumol/kg) of the dye. Plasma disappearance rate was significantly reduced in Gilbert's syndrome patients after administration of 0.59 mumol sulfobromophthalein/kg (0.119 +/- 0.016 vs. 0.146 +/- 0.018 mumol/kg/min; mean +/- S.D.; p less than 0.001), whereas no difference was found with the higher dose (0.754 +/- 0.040 vs. 0.767 +/- 0.072 mumol/kg/min). Significant reduction was also found after administration to four Gilbert's syndrome patients and four control subjects of 0.29 and 2.95 mumol sulfobromophthalein (0.060 +/- 0.005 mumol/kg/min vs. 0.077 +/- 0.07 mumol/kg/min and 0.480 +/- 0.012 mumol/kg/min vs. 0.591 +/- 0.015 mumol/kg/min, respectively; p less than 0.01). Competition studies with combined administration of sulfobromophthalein (0.59 mumol/kg) and different doses of rifamycin SV (0.59, 1.47 and 2.95 mumol/kg) showed a significant (p less than 0.001) reduction in plasma disappearance rate in Gilbert's syndrome patients but not in controls. The rifamycin SV dose at which a 50% inhibition in plasma disappearance rate was observed was 0.8 mumol/kg. The apparent affinity (Km) of the hepatic transport was higher in Gilbert's syndrome patients than in control subjects (3.61 +/- 0.37 mumol sulfobromophthalein/kg vs. 2.76 +/- 0.29 mumol sulfobromophthalein/kg, mean +/- S.D.; p less than 0.01), whereas no difference was found in Vmax (0.95 +/- 0.11 mumol sulfobromophthalein/kg vs. 0.93 +/- 0.10 mumol sulfobromophthalein/kg/min, mean +/- S.D.; N.S.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Pulsatile glucagon has greater hyperglycaemic, lipolytic and ketogenic effects than continuous hormone delivery in man: effect of age.

The present study aimed at investigating the hyperglycaemic, lipolytic and ketogenic effects of small doses of glucagon delivered continuously or in a pulsatile manner. The study was performed in eight healthy young volunteers (24.2 +/- 1.2 years) and in eight healthy aged subjects (69.4 +/- 2.0 years). In all the subjects, endogenous pancreatic hormone secretion was inhibited by somatostatin and only glucagon was replaced. Consequently, the effects of pulsatile and continuous glucagon delivery were studied in conditions of progressive somatostatin-induced insulin deficiency. In both the young and the aged subjects, pulsatile glucagon delivery resulted in increases in plasma glucose, non-esterified fatty acid, glycerol and beta-hydroxybutyrate levels greater than those observed when the same amount of glucagon was delivered in a continuous manner. The net increases in plasma glucose, glycerol and non-esterified fatty acid levels were similar between the young and the aged subjects when glucagon was infused continuously; in contrast, the rise in plasma beta-hydroxybutyrate in the aged was only about half that observed in the young subjects. Surprisingly, when glucagon was infused in a pulsatile manner, the rises in plasma glycerol, non-esterified fatty acid and beta-hydroxybutyrate levels were all significantly smaller in the aged subjects, while no significant differences were observed in the blood glucose responses. We conclude that, in the presence of somatostatin-induced insulin deficiency, pulsatile glucagon exerts greater effects on blood glucose, plasma non-esterified fatty acid, glycerol and beta-hydroxybutyrate levels than its continuous delivery. In the elderly, the lipolytic and ketogenic, but not the hyperglycaemic, responses to pulsatile glucagon are significantly reduced.

3-Hydroxybutyric Acid↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

Dissociation between vascular and metabolic effects of nicotinic acid in Gilbert's syndrome.

The relationship between the vasodilating and the hyperbilirubinaemic effect of low and high doses (50 and 300 mg i.v.) of nicotinic acid was studied in baseline conditions and after indomethacin pretreatment in healthy controls and patients with Gilbert's syndrome (a condition characterized by fluctuating, nonhaemolytic unconjugated hyperbilirubinaemia). The hyperbilirubinaemic effect of nicotinic acid was confirmed to be more pronounced in Gilbert's syndrome patients than in controls. The magnitude of hyperbilirubinaemia in the two groups was not dependent on the dose of nicotinic acid or indomethacin pretreatment. A dose-dependent vasodilation which was inhibited by indomethacin could be demonstrated in both controls and Gilbert's syndrome subjects. Vasodilating properties of nicotinic acid were therefore found to be dissociated from the effect on bilirubin.

Adolescent↗
PubMed1989

Ageing and thymus-induced differential regulation of beta 1 and beta 2 adrenoceptors of mouse brain cortex.

Two questions have been addressed by the present paper, that is, the differential influence of age on beta 1 and beta 2 receptors and the thymus-induced recovery of such changes in receptor density and affinity have been assayed in brain cortex of Balb/c-nu mice of different ages. Results have shown a progressive decrease of beta 1 receptor density with advancing age, while no statistically significant changes were observed in beta 2 receptor density. Receptor affinity did not show any changes among the various groups examined. The influence of the thymus on receptor characteristics has been studied comparing young, old and thymus-grafted old mice. Total receptor density, which is decreased in old animals, can be up-regulated by thymus graft in old recipients. Interestingly, such a corrective effect is exerted only on the beta 1 population, the beta 2 receptor not being significantly affected. Thymic graft, therefore, acts just on the population which is found altered during ageing.

Aging↗
PubMed1989

Clinical, biochemical, and hormonal changes after a single, large-volume paracentesis in cirrhosis with ascites.

The use of paracentesis has recently been reproposed as a safe and effective alternative to diuretics for management of ascites. We have investigated the clinical and biochemical effects of large-volume paracentesis in 19 cirrhotics with tense ascites, and the relative changes in the hormones involved in sodium and water renal handling. Plasma renin activity (PRA), aldosterone (PA), and arginine vasopressin (AVP) levels and conventional liver and renal function tests were measured before and after 1, 2, and 7 days after the paracentesis. No complications were observed, but patients regained 37% of the weight lost after 1 wk. Percent weight regained was significantly and directly correlated with PA concentration measured before the paracentesis. No changes were recorded after paracentesis in biochemical and clinical data, except for a significant drop in diastolic blood pressure. No changes in AVP levels were observed. A significant increase in PA occurred after paracentesis, with a maximum peak after 48 h. The increase in PA was not accompanied by changes in PRA, but was associated with a reduction of urinary sodium excretion. A relevant fraction of body aldosterone was confined to the ascitic fluid. We conclude that the clinical results of a large-volume paracentesis can be predicted in part on the basis of PA measurement, and that removal of ascites is followed by an increase of PA of uncertain origin and effectiveness.

Aged↗
PubMed1988

Free drug levels monitoring as a detector of false metabolic refractory epilepsy.

Unbound and total plasma levels of carbamazepine (CBZ) and phenobarbital (PB) were evaluated in a group of 12 refractory patients out of 397 subjects, with normal values of total drug concentration and unbound levels below the expected ones. We established a minimal acceptable 'subtherapeutic' free drug level, i.e. less than 9.62 micrograms/ml for PB and 1.36 micrograms/ml for CBZ. PB and CBZ dosages were increased during a 3-month period. We observed a normalization of free levels, unaccompanied by a significant decrease in seizure frequency. Free drug level monitoring may prove to be an unchallenged detector of false metabolic refractory epilepsy.

Adolescent↗
PubMed1988

Advantageous metabolic effects of pulsatile insulin delivery in noninsulin-dependent diabetic patients.

This study was done to compare the actions of pulsatile and continuous insulin administration in eight noninsulin-dependent diabetic patients. Human insulin was delivered in a pulsatile manner (1.3 mU/kg.min for 2 min, followed by 11 min during which no insulin was infused) or continuously (0.2 mU/kg.min) for 325 min. Endogenous hormone secretion was inhibited by somatostatin (125 micrograms/h), and glucagon was replaced at rate of 3.5 micrograms/h. Under these conditions plasma C-peptide levels fell progressively to extremely low values at the end of the experiment. Continuous insulin infusion resulted in steady plasma insulin levels, averaging 86 pmol/L, while during intermittent insulin administration plasma insulin levels were 5.7 and 158 pmol/L before and 3 min after the start of the insulin injection, respectively. Basal plasma glucagon [mean 158 +/- 11 (+/- SE) vs. 163 +/- 21 ng/L; P = NS] levels were similar on both occasions. During replacement peripheral plasma glucagon levels were no different whatever the mode of insulin administration, nor did they differ from the basal values. The mean plasma glucose concentrations were similar before both studies and rose to 9.5 and 8.6 mmol/L in the first 65 min during continuous and pulsatile insulin administration, respectively. In contrast, during the last 65 min, plasma glucose averaged 6.2 mmol/L during both studies. The glucose infusion rate initially increased, but then rapidly fell to values close to zero at the end of the first 65 min during the continuous insulin infusion, whereas during this time it averaged 0.59 +/- 0.10 mg/kg.min (32.5 +/- 5.5 mumol/kg.min) during pulsatile insulin administration. In the last 65 min the glucose infusion rate was significantly higher during pulsatile than during continuous insulin delivery. Furthermore, pulsatile rather than continuous insulin administration significantly reduced plasma triglyceride, very low density lipoprotein triglyceride, and FFA levels and increased high density lipoprotein cholesterol and apolipoprotein-B levels. We conclude that pulsatile insulin delivery has advantageous metabolic effects compared to continuous hormone administration in patients with noninsulin-dependent diabetes mellitus.

Aged↗
PubMed1988

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↗
PubMed1988

Effect of nicotinic acid administration on serum levels of bilirubin and iron in patients with porphyria cutanea tarda.

Nicotinic acid (NA) administration in Gilbert's syndrome (GS) patients promotes an increment of bilirubin and of total iron serum levels, dependent on a defective hepatic bilitranslocase function and on a haemolytic effect of NA. In porphyria cutanea tarda (PCT): (1) the effect of nicotinic acid on bilirubinaemia is superimposable to that in controls; (2) a well documented disturbance of iron metabolism occurs; (3) but relationship between bilirubin and iron under NA load has never been investigated. The administration of 5.9 mumol/kg body weight of NA to 12 PCT patients, 10 GS subjects and nine healthy volunteers of comparable age resulted in: (1) normal behaviour of bilirubin parameters in PCT but higher bilirubinaemic values in GS subjects; (2) normal values of serum iron in GS subjects, but higher baseline values and lower sideraemic effect of nicotinic acid in PCT patients; (3) a normal NA half-life in PCT and enhanced in GS subjects. These findings confirm a defective bilirubin uptake and excretion by the liver of GS subjects with a normal iron metabolism. On the contrary, in our PCT patients a normal clearance of bilirubin occurs, but a complex disturbance of iron metabolism is well evident in baseline conditions as well as after NA administration. The latter being probably the consequence of an enhanced excretion of iron extraproduced by the haemolytic effect of NA.

Adult↗