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Biomedical subjects

G Graziani

Publications and source records attributed to G Graziani.

At least 127 records · Page 7Linked to original sources
PubMed1984

Pharmacokinetic study of the new sulfamethopyrazine-trimethoprim combination (kelfiprim) in renal insufficiency.

The combination of trimethoprim (TMP) and sulfamethopyrazine (SMP) has been successfully used to treat chronic urinary tract infections. Since parenchymal involvement associated with renal insufficiency of varying degree is not infrequent in these patients, it was considered important to study the pharmacokinetics of TMP and SMP in a fixed dose combination. Four groups of patients were studied: 1) 4 patients with endogenous creatinine clearance (CLcR) between 80 and 40 ml/min; 2) 3 patients with CLcR between 40 and 10 ml/min; 3) 3 patients on chronic peritoneal dialysis (CAPD); and 4) 3 patients on haemodialysis. A single oral dose of 250 mg TMP and 200 mg SMP was given to each patient. Multiple samples were collected over 9 days and the following pharmacokinetic parameters were calculated: total area under the plasma level curve, slow disposition rate constant beta and the corresponding t1/2 beta, plasma clearance and the apparent volume of distribution. The results show that the two moieties of the TMP-SMP combination behaved differently in uraemic patients as fas as elimination rate was concerned. TMP was eliminated more slowly both in patients with diminished renal function and in those subjected to haemo- or peritoneal dialysis. The reduction in the rate of elimination of TMP was significantly correlated with the degree of renal impairment. The elimination of SMP, however, was not significantly affected by the reduced renal function; indeed a tendency to increase was noted, at least in dialyzed patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Dopamine and frusemide in oliguric acute renal failure.

Into 24 oliguric patients with acute renal failure (ARF) for whom mannitol and high-dose frusemide had failed to promote a diuresis, dopamine (3 micrograms/kg/min) plus frusemide (10-15 mg/kg/h) were infused for 6-24 h. In 19 of the 24 patients this treatment produced significant increases in diuresis (from 11 +/- 7 to 85 +/- 51 ml/h; p less than 0.001) and natriuresis (from 45 +/- 13 to 88 +/- 22 mEq/1; p less than 0.001), without any significant modification of blood pressure, pulse rate or central venous pressure. 10 of the 24 patients required dialysis: 5 because therapy failed to promote diuresis and the other 5 because of their hypercatabolic state in spite of polyuria. 5 patients died of causes unrelated to ARF. Since all patients who responded were treated within 24 h after the onset of oliguria, it appears to be crucial to administer dopamine and frusemide early, before more severe anatomical and functional damage develops.

Acute Kidney Injury↗
PubMed1984

Pharmacological studies on the mode of action of flavoxate.

Previous studies on the mode of action of flavoxate have shown that the drug exerts a selective and direct muscle relaxant activity. In order to study the mode of action of flavoxate, the following activities were investigated: calcium blocking, inhibition of cyclic AMP phosphodiesterase (PDE), local anaesthetic activity, the effects on the synthesis and release of prostaglandins. In the K+-depolarized guinea-pig taenia coli, contracted by CaCl2, flavoxate and papaverine showed a moderate calcium antagonistic activity. Anticholinergic drugs, such as atropine and emepronium, did not exert a similar action. The antispasmodic activity of a drug can be correlated with inhibition of cyclic AMP phosphodiesterase, and since papaverine is a potent PDE inhibitor, we tested flavoxate for this activity. Flavoxate exerted a PDE inhibitory activity about three and five times greater than that of aminophylline in tissues homogenates of guinea-pig ureter and urinary bladder, respectively. It also showed the same local anaesthetic activity of lidocaine. Finally, the synthesis and release of prostaglandins by urinary bladder muscle in vitro have been investigated before and after treatment with flavoxate. Myolytic activity of papaverine and flavoxate do not involve inhibition of prostaglandins synthesis in rat urinary bladder in vitro. Therefore, the mode of action of flavoxate can be related to a superimposition of myotropic, calcium antagonistic and local anaesthetic activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

Interferon-induced changes in the susceptibility of murine and human lymphoma cells to natural cytotoxic lymphocytes.

Mouse YAC-1 and human K562 leukemic cells were treated in vitro with fibroblast interferon (IF) and tested for their susceptibility to NK effector lymphocytes. In both cases a decrease in target susceptibility was induced by the IF treatment. "Cold" competition experiments confirmed that loss or masking of NK target structures occurred in IF-pretreated cells. In fact, when radio-labeled untreated cells were used as targets, IF-pretreated leukemias produced inhibitory effects lower than those mediated by intact cells. However when IF-pretreated targets were used, cold cells either intact or preincubated with IF gave similar competitive effects. These data suggest that IF modulates differentially distinct subsets of NK target structures.

Animals↗
PubMed1984

Hemodialysis without anticoagulants: efficiency and hemostatic aspects.

In 29 patients with high risk of bleeding, 111 hemodialyses have been performed without heparin (WHD) or other anticoagulants. The same patients were switched to low dose heparin dialysis (LDHD) as soon as the bleeding risk had ceased. The dialyzer had to be changed in 11 and the drip chamber in 20 WHDs because of partial clotting. This phenomenon did not occur during LDHD. The comparative efficiencies of the two techniques were evaluated by measuring the urea and creatinine clearances of the dialyzers. No significant difference between LDHD and WHD clearances was observed. In 7 of 29 patients, hemostasis variables were studied before, during and after both modes of treatment. Fibrinogen, platelet count, antithrombin III and prothrombin time did not differ with the different dialysis procedures. During dialysis, platelet factor 4 (PF4) levels were significantly higher than baseline values (P less than 0.01), with no difference between WHD and LDHD. Plasma fibrinopeptide A (FPA) levels remained normal during LDHD, but significantly increased during WHD (P less than 0.001). Our data indicate that WHD is feasible, with a low risk of extravascular coagulation. The bleeding risk is not increased during or after dialysis, and the danger of intravascular coagulation is low as confirmed by the isolated elevation of FPA plasma levels, unaccompanied by changes in other variables.

Acute Kidney Injury↗
PubMed1984

Branched chain and aromatic free amino acids in plasma and skeletal muscle of uremic patients undergoing hemodialysis and CAPD.

Plasma and skeletal muscle free amino acids were measured in patients submitted to Hemodialysis (HD) or Continuous Ambulatory Peritoneal Dialysis (CAPD) in order to evaluate the effects of these different dialysis modalities on amino acid pools; the data were compared with those obtained in control subjects and in patients with advanced Chronic Renal Failure (CRF) not submitted to Regular Dialysis Treatment (RDT). Our findings show low intracellular concentrations of VAL, total Branched Chain Amino Acid (BCAA) and TYR in uremic patients treated with CAPD but not in those undergoing HD. The observed differences in muscle amino acid pattern could be well explained by a changed amino acid metabolism regulation in CAPD, possibly related to the sustained hyperinsulinism and to an increased rate of hepatic protein synthesis.

Adult↗
PubMed1983

Prospective controlled trial of a Y-connector and disinfectant to prevent peritonitis in continuous ambulatory peritoneal dialysis.

A controlled study in two centres compared the efficacy of the standard continuous ambulatory peritoneal dialysis (CAPD) system with that of a new method consisting of a Y-shaped set filled with sodium hypochlorite during the dwelling time. 62 new CAPD patients were randomly allocated to the standard method (group A: 30 patients; age 55.5 +/- 17.5 years) or to the Y-system (group B: 32 patients; age 55.1 +/- 14.3 years). In group A, there were 31 peritonitis episodes in 17 patients (57%) during a cumulative period of 351 months--1 episode every 11.3 patient-months. In group B, there were 11 peritonitis episodes in 10 patients (31%) during 363 months--1 episode every 33 patient-months. Life-table analysis showed a significant difference between the incidence of peritonitis in the two groups. The Y-system method is simple and economical and the frequency and the severity of side-effects appears to be acceptable.

Adolescent↗
PubMed1983

Effect of Denzimol, a new anticonvulsant drug, on rat cerebellum. Morphological and histochemical patterns of Purkinje cell layer.

The effects of Denzimol, a new anticonvulsant drug, were analyzed in the Purkinje cell layer of rat cerebellum. No modifications in the general histochemical and ultrastructural patterns were induced by chronic administration of the drug. A slight increase in the storage of lipopigments in the cytoplasm of Purkinje neurons was found. No effects on secondary fluorescence (indicative of changes in biogenic amines) were found while an increase in specific SSADH activity, a degradative enzyme in GABA metabolism was present. Some observed histological and ultrastructural alterations (presence of "balloned" Purkinje neurons showing, in particular, enlarged cisternae of the endoplasmic reticulum) may be a stress effect probably due to the gastric tube insertion by which the drug was administered.

Animals↗
PubMed1983

'Y' connector system for prevention of peritonitis in CAPD: a controlled study.

To compare the efficacy of the standard Oreopoulos CAPD system with that of a new method consisting of a Y-shaped set filled with sodium hypochlorite during the dwelling time, a randomised controlled study was performed in 62 new CAPD patients. Life table analysis showed a significantly (p less than 0.001) less frequent incidence of peritonitis in the group treated with the Y connector system. This study shows that the Y system appears to be effective in reducing the incidence of peritonitis, as compared with the standard technique, in patients on the CAPD programme. The method is simple and economical and the incidence and the severity of side effects appear to be acceptable.

Adolescent↗
PubMed1983

Acetohydroxamate in struvite stones: in vivo study.

This report describes the results obtained with a combination of acetohydroxamic acid (AHA) and antibacterial agents in 13 patients with recurrent struvite stones complicated by refractory infections with urease-producing bacteria. Intravenous antibiotic pulses plus oral AHA achieved urine sterilisation in all. Then oral chemotherapy plus AHA was given for a mean period of 10.8 +/- 5.4 months. In four patients, the urine remained sterile, but in all the patients urinary pH remained below 6.4 and urinary NH4+ below 40 mg/dl. Despite the persistence of urea-splitting bacteria, the radiographic data showed an arrest of stone growth during the first year of treatment.

Anti-Bacterial Agents↗
PubMed1983

Denzimol, a new anticonvulsant drug. I. General anticonvulsant profile.

The anticonvulsant profile of N-[beta-[4-(beta-phenylethyl)phenyl]-beta-hydroxyethyl]imidazole hydrochloride (denzimol, Rec 15-1533) has been evaluated in mice, rats and rabbits in comparison with some standard antiepileptic drugs. Denzimol suppressed electrically and chemically induced tonic seizures but did not prevent the clonic ones. In mice and rabbits the anticonvulsant activity of denzimol against maximal electroshock seizures was almost equal to that of phenytoin and phenobarbital with more rapid onset of action, whereas in rats the compound resulted in being the most potent and the less toxic one showing a longer duration of anticonvulsant activity than phenytoin. In the maximal pentetrazol seizures test in rats denzimol showed a profile similar to that of phenytoin and carbamazepine, but different from that of barbiturates and benzodiazepines so that it is suggested that its clinical application would be that of "grand mal" and psychomotor type seizures therapy.

Animals↗
PubMed1983

Denzimol, a new anticonvulsant drug. II. General pharmacological activities.

The paper reports on the pharmacological properties of N-[beta-[4-(beta-phenylethyl)phenyl]-beta-hydroxyethyl]imidazole hydrochloride (denzimol, Rec 15-1533), a compound endowed with anticonvulsant properties, and its possible side effects. Effects on the CNS, effects on vigilance and general motility are similar to those of phenytoin and occur at doses much above anticonvulsant levels. The drug has good in vitro antihistamine, anticholinergic and anti-5-HT activity which accounts for the effects on the gastrointestinal system e.g. inhibition of gastric secretion and motility and anti-ulcer properties. There was no significant effect on the cardiovascular system or respiration, except an interesting antiarrhythmic activity.

Analgesics↗
PubMed1983

Denzimol, a new anticonvulsant drug. III. Toxicological evaluation.

The toxicological characteristics of N-[beta-[4-(beta-phenylethyl)phenyl]- beta-hydroxyethyl]imidazole hydrochloride (denzimol, Rec 15-1533) a drug with a very good anti-convulsant activity in pharmacological studies carried out in different animal species, were evaluated in acute and chronic toxicity studies. The following overall results were obtained: the acute oral toxicity in mice and rats is of low order; in the chronic oral studies denzimol was generally well tolerated when given to rats for 13 and 26 weeks and to dogs for 52 weeks at different dosage levels. In particular, there was no evidence of remarkable neurological effects or lesions in any of these studies. The results of the studies in rats showed the major target organs for the toxicity of denzimol to be the liver and kidney, where mild, reversible changes were observed; instead in dogs no pathological effect was seen, at any of the dosages used (10, 30, 100 mg/kg p.o. per one year).

Administration, Oral↗
PubMed1983

Dopamine-frusemide therapy in acute renal failure.

In 16 patients with ARF and in three with hepatorenal syndrome we infused dopamine (3 micrograms/kg/min) and frusemide (10-15 mg/kg/day) for 6-24 hours. This treatment produced in all patients a significant diuresis and natriuresis without any modification of blood pressure, pulse rate, and central venous pressure. In three patients with hepatorenal syndrome diuresis was established during dopamine and frusemide infusion, but severe oliguria again reappeared when drug infusion was stopped. This experience suggests that this therapy may avoid fluid overload and hyperkalaemia in oliguric patients reducing the need for dialysis. It is also the first successful approach in the treatment of hepatorenal syndrome although its effect is transient.

Acute Kidney Injury↗