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R Riva

Publications and source records attributed to R Riva.

At least 91 records · Page 5Linked to original sources
PubMed1984

[Esophageal motor changes in patients with Raynaud's phenomenon and suspected scleroderma. Electromanometric and serologic evaluations].

Esophageal motor dysfunction in patients with collagen disease, although rather frequent, presents difficult etiopathogenetic arrangement. By means of esophageal manometric evaluation and immunopathologic study the Authors observed 44 patients with Raynaud's phenomenon idiopathic or joined with Scleroderma. From collected data the utility of esophageal manometry in early diagnosis is pointed out.

Adult↗
PubMed1984

Mechanism of altered drug binding to serum proteins in pregnant women: studies with valproic acid.

The mechanism underlying the impaired serum protein binding of valproic acid (VPA) in pregnancy was examined in samples collected from 24 healthy women in the last 3 weeks of gestation and 15 age-matched nonpregnant female controls. Experiments were performed in vitro using a rapid equilibrium dialysis technique free from in vitro alterations in free fatty acids (FFA). At a total drug concentration of approximately 420 mumol/L, the free VPA fraction was 10.2 +/- 2.9% (SD) in pregnant women and 4.8 +/- 1.0% in controls (p less than 0.001). Pregnancy was associated with a marked reduction in serum albumin levels but with only a slight, nonsignificant elevation in FFA. Free VPA fraction was negatively correlated with serum albumin levels. A positive correlation between free VPA fraction and FFA was observed in the pregnant group but not in the controls. The only sample collected during labour showed a striking elevation of both free VPA fraction and FFA, in spite of a normal albumin concentration. Scatchard's plots showed VPA bound to two classes of binding sites on the albumin molecule. The number of primary (n1) and secondary (n2) binding sites in pregnant women (n1 = 2.0; n2 = 10.7) was virtually identical to that observed in the controls (n1 = 1.9; n2 = 9.8). The association constants of the primary (k1) and secondary (k2) sites were lower in pregnant women (15.9 X 10(3) and 0.19 X 10(3) L/mol, respectively, vs. 22.6 X 10(3) and 0.33 X 10(3) L/mol in controls) but the difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Valproic acid binding to human serum albumin and human plasma: effects of pH variation and buffer composition in equilibrium dialysis.

The binding of valproic acid (VPA) to human serum albumin (HSA) and to pooled human plasma has been investigated by using equilibrium dialysis with three different dialysis solutions: phosphate buffer (solution I), Krebs solution (solution II), and Krebs solution without calcium (solution III). The effect of pH variation from 6.4 to 8.2 has been also investigated. VPA free fraction increased by increasing pH with all the dialysis solutions (from 4.1% at pH 6.4 to 9.4% at pH 8.2 with solution I, from 8.1% to 11.3% with solution II, and from 10.6% to 14.3% with solution III, in plasma). At each pH value, free fraction obtained with solution III was the highest and that obtained with solution I was the lowest. Data in plasma and HSA solution were similar. In a separate experiment we compared (at pH 7.4, with plasma) the three more frequently used dialysis solutions: phosphate buffer, phosphate buffer with NaCl, and Krebs solution. They gave, respectively, a mean VPA free fraction of 7.8, 10.3, and 12.7%. These findings can explain the wide range of VPA free fraction values reported in the literature. Researchers intending to determine VPA free concentration by equilibrium dialysis should take into account these methodological aspects.

Buffers↗
PubMed1984

Free and total plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide in epileptic patients: diurnal fluctuations and relationship with side effects.

The diurnal fluctuations in free and total plasma levels of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) and their relationship with intermittent side effects were examined in 10 epileptic patients stabilized on chronic CBZ therapy alone or in combination with phenobarbital (PB). With a t.i.d. or q.i.d. dosing schedule, total plasma levels of CBZ and CBZ-E fluctuated to a similar extent (average 34% and 29%, respectively). The diurnal changes in free levels of both compounds mirrored closely those of the total levels. Free fraction values ranged from 13 to 26% for CBZ and from 24 to 66% for CBZ-E. Owing to the lower protein binding of the metabolite, CBZ-E/CBZ ratios were higher in plasma water (0.49) than in whole plasma (0.22). A good correlation was found between both total and free CBZ levels and dose-related side effects (diplopia, nystagmus). On the other hand, no apparent relationship was found between side effects and either total or free plasma CBZ-E. The correlation with the presence of neurological signs of toxicity for the sum of CBZ + CBZ-E levels was no better than that observed for CBZ levels alone. These data do not support the hypothesis that CBZ-E contributes significantly to the development of dose-related side effects in CBZ-treated patients.

Adult↗
PubMed1984

Differential transplacental binding of valproic acid: influence of free fatty acids.

The unbound fraction of valproic acid (VPA) was found to be significantly lower in cord serum (6.0 +/- 0.8%) than in maternal serum collected before oxytocin (12.2 +/- 2.7%) or after delivery (9.9 +/- 2.3%). The difference was probably due to the concentration of free fatty acids (acting as displacing agents) being higher in maternal serum. The transplacental binding gradient explains the clinical observation that total VPA levels at delivery are higher in the newborn than in the mother.

Dialysis↗
PubMed1984

Stereoselective binding of propranolol enantiomers to human alpha 1-acid glycoprotein and human plasma.

The binding of propranolol enantiomers to human albumin (ALB), alpha 1-acid glycoprotein (alpha 1-AGP) and plasma was studied. (-) propranolol is more bound than (+)propranolol to alpha 1-AGP (P less than 0.001) and to plasma (P less than 0.05). In solutions containing ALB at a constant concentration (580 mumol/l) and alpha 1-AGP at increasing concentrations, the binding of both isomers increases but the stereo selectivity is evident throughout the alpha 1-AGP concentration range examined (25-100 mumol/l).

Adult↗
PubMed1984

Diurnal fluctuations in free and total steady-state plasma levels of carbamazepine and correlation with intermittent side effects.

The relationship between diurnal fluctuations in free (unbound) and total plasma carbamazepine levels and the appearance of intermittent side effects was investigated in nine epileptic patients receiving chronic therapy with carbamazepine, alone or in combination with phenobarbital. On a three-times-daily or four-times-daily dosing schedule, both total and free carbamazepine levels fluctuated considerably (on an average, 41 and 45%, respectively, around the mean). Side effects (particularly diplopia and nystagmus) were observed in five patients and showed an intermittent pattern in four. Side effects were never found at total carbamazepine levels less than 34 mumol/L but invariably appeared at levels greater than 38 mumol/L. At levels between 34 and 38 mumol/L adverse effects were inconsistently observed. The correlation between plasma carbamazepine levels and manifestations of toxicity was slightly stronger when free rather than total levels were considered. Side effects were always apparent at free levels greater than 7.2 mumol/L. These data underline the limitations of relying on a single drug level determination during the monitoring of carbamazepine therapy and emphasize the necessity of carefully adjusting the dosing schedule, to minimize the appearance of intermittent adverse effects.

Adolescent↗
PubMed1984

Hyperammonemia in asterixis induced by carbamazepine: two case reports.

Two patients developed asterixis while they were taking carbamazepine at "therapeutic" levels. The only laboratory abnormality was slight hyperammonemia. It occurred with normal hepatic function as a dose-related effect. In fact, the blood ammonia level decreased and asterixis ceased when carbamazepine was stopped or reduced in dosage. The relationship between asterixis and hyperammonemia during carbamazepine therapy is discussed.

Aged↗
PubMed1984

Plasma concentrations of propranolol and 4-hydroxy-propranolol at steady-state in neurological patients: intersubject and intrasubject correlations with dose.

Plasma concentrations of propranolol (PROP) and its active 4-hydroxymetabolite were determined in neurological patients receiving chronic therapy with relatively low PROP doses (40-240 mg/day). Plasma PROP concentrations determined before the morning dose were much lower than, but significantly correlated (r = 0.91) with the drug level two hours after dosing. 4-hydroxypropranolol (4-OH-P) was often undetectable (less than 1 ng/ml) in the early morning samples. Plasma concentrations of both parent drug and metabolite determined two hours after the morning dose correlated weakly with the prescribed daily dose. The intrapatient dose-concentration relationship, on the other hand, was strong, particularly for the parent drug. The ratio between 4-OH-P and PROP in plasma was inversely related to the PROP concentration, at least over the lower PROP concentration range (0-100 ng/ml). The usefulness of determining the concentration of the metabolite in the evaluation of the pharmacological action of low doses of PROP is discussed.

Adolescent↗
PubMed1984

External fixation in the treatment of fractures of the distal forearm.

The authors present 12 cases of fractures of the lower forearm treated by Hoffmann external fixation. They discuss the indications for this method and its advantages over internal fixation and closed treatment by manipulation and plaster. The advantages are: simplicity and rapidity of treatment, good toleration of the instrumentation, constant control of the soft tissues, almost bloodless technique, complete freedom of joints not involved in the fracture, and the ability to adjust the position of the wrist and hand as union progresses so as to gradually restore the physiological position in the later stages.

Adult↗
PubMed1983

[Relation between the distribution and orientation of collagen fibers and the inorganic phase of calcification processes in the anterior leaflet of the human mitral valve].

The collagen fibers observed in calcified valves appear randomly distributed without any preferential arrangement. In these areas also the hydroxylapatite crystals do not show any orientation. It is suggested that the disorder of the organic phase is a factor favouring the deposition of the calcium crystals.

Calcification, Physiologic↗
PubMed1983

Diurnal fluctuations in free and total plasma concentrations of valproic acid at steady state in epileptic patients.

The diurnal fluctuations in free and total plasma concentrations of valproic acid (VPA) were determined by taking serial blood samples at 2-h intervals in six epileptic patients receiving maintenance therapy with sodium valproate (9.6-24.0 mg/kg in three divided daily doses). Both the free and the total concentrations fluctuated markedly during the period examined (0800-1800 h). The fluctuation of the free drug was about twice as great as that of the total drug (79 +/- 27% versus 47 +/- 21%, p less than 0.01). There was a considerable inter- and intrapatient variability in free VPA fraction. In at least four of six patients the free fraction increased in proportion to the increase in total concentration. These findings are in line with available evidence that the binding of VPA to plasma proteins is saturable within the clinically occurring concentration range. The changing and unpredictable relationship between total and free concentration suggests that VPA therapy can be monitored more rationally by measuring the free drug.

Adolescent↗
PubMed1983

Valproic acid free fraction in epileptic children under chronic monotherapy.

The total and free (nonprotein-bound) concentration of valproic acid (VPA) was determined in plasma samples collected at two different times of the day (before the morning dose and 3 h later) in 62 epileptic children receiving maintenance single-drug therapy with sodium valproate. Both the total and the free concentrations were lower in the early than in the late morning samples (total VPA: 394.4 +/- 150.0 vs. 556.9 +/- 175.2 mumol/L; free VPA: 20.1 +/- 11.1 vs. 31.3 +/- 17.4 mumol/L). The average free fraction of the drug was also lower in the early morning (4.8 +/- 1.3 vs. 5.4 +/- 1.6%, p less than 0.001). At both sampling times, the free fraction was positively correlated (p less than 0.01) with the total concentration. Evidence is presented that, at equal total plasma VPA concentration, the free fraction of the drug is significantly (p = 0.01) higher in the early than in the late morning samples. The rise in plasma free fatty acids (acting as displacing agents) after the overnight fast is probably responsible for this difference in free fraction. The implications of these findings with respect to the monitoring of free plasma VPA levels are discussed.

Adolescent↗
PubMed1983

Free fraction of valproic acid: in vitro time-dependent increase and correlation with free fatty acid concentration in human plasma and serum.

The effect of sample incubation and storage on the protein binding of the antiepileptic drug valproic acid (VPA) and on the concentration of free fatty acids (FFA) was investigated in serum and plasma collected from four normal volunteers. Both the free fraction of VPA and the concentration of FFA increased progressively with time when samples were incubated at 4 to 37 degrees C. These effects occurred to the same extent in both serum and heparinized plasma. At 4 degrees C and at room temperature, the increase in free drug fraction was relatively small (18 and 25% respectively at 24 h), whereas at 37 degrees C it was quite considerable (24% at 8 h and 40% at 24 h). At room temperature, FFA rose on average by 22% at 4 h, 34% at 8 h, and 86% at 24 h, whereas at 37 degrees C the increases at the same incubation times were 59, 90, and 160%, respectively. There was a strong positive relationship between changes in free VPA fraction and FFA content of the samples. The time-dependent changes in VPA binding capacity described in this study may lead to overestimation of the actual free concentration in vivo, especially when this is estimated by equilibrium dialysis or ultracentrifugation techniques requiring long incubation (centrifugation) times at 37 degrees C.

Adult↗
PubMed1983

Decreased phenytoin level during antineoplastic therapy: a case report.

We report a case of interaction between anticonvulsant and antineoplastic drugs in one male patient with seizures from brain tumour. The patient was treated with phenytoin (PHT), phenobarbital (PB), and an antineoplastic protocol based on a combination regimen with carmustine (BCNU), vinblastin (VLB), methotrexate (MTX), and radiotherapy. Plasma concentrations of PHT fell from 9.4 to 5.6 micrograms/ml 24 h after VLB administration, and remained low for at least 10 days. During this period, partial seizures occurred. Plasma concentrations of PB were unchanged during the period of observation. It is suggested that impaired absorption of PHT, caused by VLB or MTX or both, is responsible for this interaction.

Antineoplastic Agents↗
PubMed1983

Phenobarbital and propranolol in essential tremor: a double-blind controlled clinical trial.

In a double-blind study with Latin square design, phenobarbital (about 1.3 mg per kilogram), propranolol (about 1.7 mg per kilogram), and placebo were given orally for 1 month to 12 patients with essential tremor. By clinical evaluation, only propranolol appeared to be significantly more effective than placebo. As judged by tests of manual skill, none of the treatments significantly improved tremor. Patients' subjective evaluation and tremor amplitude measurement (by accelerometer) showed a significantly better effect of both propranolol and phenobarbital than placebo. These data suggest that phenobarbital may be a valuable alternative to propranolol in essential tremor.

Adolescent↗