[Hyponatremia in cirrhosis with ascites]. / L'iponatremia nel cirrotico con ascite.

Hyponatremia complicates ascitic hepatic cirrhosis with frequency and gravity related to the gravity of the cirrhosis itself. When hyponatremia develops, it worsens the already present secondary hyperaldosteronism and makes therapy with spironolactone inefficacious. From a pathophysiologic viewpoint a pathogenetic role in determining hyponatremia is attributable to the reduced plasmatic renal perfusion; in several patients a syndrome of inappropriate ADH secretion develops. Other neurohormonal systems (catecholamines, prostaglandins, natriuretic hormones) are probably very important in modifying renal hemodynamics and renal tubular function. In some patients a causative role for hyponatremia is attributable to iatrogenic factors (e.g.: diuretics). From a therapeutic viewpoint, we examine some schedules, pharmacologic or not, that, however, are far from being useful for all patients. We discuss, mainly, water restriction, osmotic diuretics with or without loop diuretics, loop diuretics followed by sodium reintegration and concentration-reinfusion of ascites or application of peritoneovenous shunt.

[Use of citiolone in chronic hepatitides. Results of a research with clinical and laboratory controls]. / Impiego del citiolone nelle epatiti croniche. Risultato di una ricerca con controlli clinici e laboratoristici.

The therapeutic possibilities offered by the use of a new substance, 3-acetamido-2-oxo-tetrahydro-thiophene or citiolone, in two groups of patients, the first suffering from persistent chronic hepatitis, the second from aggressive chronic hepatitis and-or compensated cirrhosis diagnosed on the basis of clinical, laboratory, and bioptic findings have been studied. The experiment was of "between patients" pattern and findings were obtained with the double-blind method. Tests were compared with a placebo and all patients were treated with a basic therapy consisting of a polyvitaminic complex. In both groups, the results confirmed the therapeutic effectiveness of the new substance and this was demonstrable, including statistically, in an improvement in the clinical picture and, above all, in certain liver function exploration tests. At termination of the treatment cycle, liver biopsies were carried out in certain patients and these showed an improvement in the liver cell picture.

Pirenzepine in the treatment of benign gastroduodenal diseases. A double-blind controlled clinical trial.

Pirenzepine (PRZ, 75 mg/day for 10 days followed by 50 mg/day for 20 days) was compared with placebo (PL) in the treatment of endoscopically confirmed active gastroduodenitis or duodenal ulcer and with carbenoxolone (CB, 300 mg/day followed by 200 mg/day) in the treatment of gastric ulcer in a 30-day double-blind clinical trial. Ninety-seven of 112 outpatients completed the trial. The results can be summarized as follows: a) Gastroduodenitis. Complete normalization of the endoscopic picture was observed in 61% of the 28 patients on PRZ and in 30% of the 27 on PL. b) Duodenal ulcer. Complete endoscopic healing was observed in 75% of the 12 patients on PRZ and in 44% of the 9 on PL. In both studied PRZ induced improvement in clinical symptoms in more patients than PL. c) Gastric ulcer. PRZ and CB induced complete healing in a similar percentage of patients (64% of 11 and 70% of 10 patients). Better results in dyspepsia were observed in the PRZ group than the CB group. No major side-effects and no pathological changes in blood and urine analyses were observed in PRZ-treated patients.

"Low T3 syndrome" in cirrhosis: effect of beta-blockade.

The so-called "low T3 syndrome" has frequently been reported in patients with cirrhosis. In this study, we aimed to determine whether administration of propranolol to such patients leads to further changes in plasma thyroid hormones, since it can affect their peripheral metabolism. Twenty cirrhotics (11 with ascites) whom we investigated showed no clinical evidence of thyroid dysfunction. The free fractions of plasma T3 and T4 (FT3, FT4) were determined by radioimmunoassay before and after the achievement of an effective beta-blockade by propranolol. The activity of the sympathetic nervous system also was evaluated by measuring plasma norepinephrine concentration. Under basal conditions, cirrhotics showed a reduced FT3 (2.45 +/- 0.11 SEM vs 3.55 +/- 0.16 pg/ml; p less than 0.001) and comparable FT4 (7.62 +/- 0.79 vs 9.2 +/- 0.42 pg/ml) and FT3/FT4 ratio (0.38 +/- 0.04 vs 0.42 +/- 0.013) with respect to healthy controls. When patients with ascites were considered apart, a reduction of FT4 was also found (6.78 +/- 0.74 pg/ml; p less than 0.01). In these patients, many of whom showed an increased plasma norepinephrine concentration, an inverse correlation between log FT3/FT4 and log plasma norepinephrine concentration was found (r = -0.79; p less than 0.01). The effective beta-blockade did not lead to significant changes in either FT3 or FT4 or FT3/FT4, whether the patients were considered as a whole (2.52 +/- 0.19 pg/ml, 9.3 +/- 1.41 pg/ml, and 0.36 +/- 0.04, respectively), or were split into groups according to the presence of ascites. When administered to cirrhotics, propranolol did not worsen thyroid hormone abnormalities, thus appearing to be safe in this respect. This may result from an impaired influence of the sympathoadrenergic system on thyroid hormone metabolism.

Renal function and effective beta-blockade in cirrhosis with ascites. Relationship with baseline sympathoadrenergic tone.

Renal function, plasma norepinephrine, renin activity (PRA) and aldosterone were determined in 17 cirrhotics with ascites, before and after effective beta-blockade (resting heart rate reduction greater than or equal to 20%) induced by oral propranolol. The drug lowered PRA (from 2.86 +/- 0.96 (S.E.) to 1.86 +/- 0.7 ng/ml/h; P less than 0.005) and plasma aldosterone (from 309.0 +/- 59.2 to 202.6 +/- 26.7 pg/ml; P less than 0.005). As expected, plasma norepinephrine (PNC) increased from 90.7 +/- 12.2 to 176.8 +/- 43 ng/l (P less than 0.01) in the 10 patients with normal basal values ('normal-PNC' group), but it decreased in 6 of the 7 patients with basal sympathoadrenergic hypertone ('high-PNC' group; mean value from 352.6 +/- 37.8 to 273 +/- 39.3 ng/ml (P = 0.06). Glomerular filtration rate and filtered sodium load did not change in the group as a whole and in 'normal-PNC' cirrhotics (from 83.2 +/- 7.1 to 81.4 +/- 7.8 ml/min, and from 11.63 +/- 0.96 to 11.45 +/- 1.14 mmol/min), but rose in 'high-PNC' patients (from 60.7 +/- 9.1 to 109.3 +/- 27.2 ml/min, and from 8.39 +/- 1.31 to 15.47 +/- 3.95 mmol/min; P less than 0.05). Renal sodium excretion increased from 2.45 +/- 0.75 to 3.16 +/- 1.01 mmol/h (P less than 0.01) in the group as a whole. Such an increase, however, was confined to 'high-PNC' cirrhotics. In this group, the tubular rejection fraction did not change and post-beta-blockade sodium excretion was correlated with the filtered sodium load (Rs = 0.83; P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)