The lidocaine (MEGX) test as an index of hepatic function: its clinical usefulness in liver surgery.

BACKGROUND: The purpose of this study was to evaluate the clinical usefulness of the lidocaine test, as an index of hepatic function, in the different fields of liver surgery. METHODS: The lidocaine (MEGX [monoethylglycinexylidide]) test, which was performed in 200 patients with different liver diseases and in 23 organ donors, was compared with common laboratory tests. The MEGX value was related to postoperative complications in patients who undergo liver resection and to the survival of patients with cirrhosis who are awaiting transplantation. In organ donors, the test was related to the outcome of patients who underwent transplantation. RESULTS: The MEGX value was significantly higher in patients without cirrhosis compared to patients with cirrhosis (77.8 +/- 25 ng/mL vs 35.6 +/- 30 ng/mL; P < .05); among patients with cirrhosis, there was a significant difference between those patients classified Child A and those classified Child B and C (43.3 +/- 25 ng/mL vs 11.5 +/- 7.1 ng/mL; P < .05). The patients classified Child A who underwent liver resection with MEGX value less than 25 ng/mL had a significantly higher rate of postoperative complications compared with other patients (P < .001). Patients with cirrhosis who were awaiting liver transplantation and who had a MEGX value of less than 10 ng/mL had a life expectancy of no longer than 1 year. CONCLUSIONS: The MEGX test is a reliable index of hepatic function. Patients carrying hepatocellular carcinoma with MEGX value of less than 25 ng/mL have a high risk of liver insufficiency after hepatic resection. Patients with decompensated cirrhosis who have an MEGX value of less than 10 ng/mL should undergo transplantation as soon as possible.

Modifications of metabolic control in type 1 diabetic children and adolescents: experience over the last 20 years.

The aim of this retrospective study was to verify whether the daily number of insulin injections could have affected metabolic control in 181 unselected diabetic patients (age 0.66-14.75 yr at onset of diabetes) followed in our clinic from the 1970s to the 1990s. They were evaluated regularly since onset of disease for a mean follow-up period of 6.8 years. The factor with the greatest effect on HbA1c levels was the year of disease onset, which was negatively correlated with HbA1c independently of the daily number of injections and disease duration. Disease duration showed an effect on metabolic control only in the first 5 years of disease. Daily insulin injections affected metabolic control above all as regards 1 vs 2 or more injections. Regarding the change in insulin regimen from 2 to 3-4 injections, there was an improvement in metabolic control in patients with HbA1c > 9% and a worsening in those with HbA1c < 7%/ After the first 5 years of the disease HbA1c levels were higher in adolescent patients than in both younger and older patients. In conclusion, increasing the daily number of injections does not seem in itself capable of eliciting marked improvement in metabolic control, as in our young diabetic patients in the last decade. Multiple insulin injection therapy seems to be mostly indicated for patients with poor control and for adolescents.

Flecainide acetate: concentration-response relationships for antiarrhythmic and electrocardiographic effects.

In order to evaluate the concentration-response relationship for either antiarrhythmic or electrocardiographic effects, 13 patients with symptomatic, stable, premature ventricular contractions (> 100/hour) were selected, and flecainide was administered as a single oral dose (200 mg) and as chronic treatment (150 mg b.i.d. for 21 days). In both settings a Holter monitoring, serial electrocardiogram (ECG) tracings and serum samples for flecainide concentrations were obtained; the relationships between drug levels, antiarrhythmic efficacy, and ECG modifications were analysed. The results obtained indicated that QRS and PR intervals lengthened significantly either after acute oral administration or after chronic treatment by 21-36% (mean values), and that the QRS interval changes were significantly correlated to serum flecainide concentrations (r = 0.68, p < 0.001 after acute and r = 0.79, p < 0.001 after chronic administration). However, for any given plasma concentration of flecainide, the percentage widening of QRS intervals was smaller after chronic treatment, as shown by the different slopes of the correlation lines (7.7 +/- 4.0% ml.micrograms -1 after acute dosing versus 3.8 +/- 1.1% ml.micrograms -1 after chronic treatment, p < 0.001). This finding suggests a relative reduction of flecainide's effects on ECG intervals during chronic treatment, while the antiarrhythmic efficacy was maintained (flecainide effective in 8/13 patients in acute and in 11/13 patients in chronic) without significant differences between flecainide's minimal effective concentrations (262 +/- 119 ng/ml and 319 +/- 276 ng/ml for acute vs chronic respectively). We conclude that during chronic treatment a dissociation seems to occur between the electrocardiographic and the antiarrhythmic effects and this could limit the clinical usefulness of monitoring QRS intervals.

Flecainide: evidence of non-linear kinetics.

The pharmacokinetics of flecainide has been studied in 12 patients with ventricular arrhythmias, both after single administration and during chronic treatment. Both the half-life and the AUC were significantly increased during chronic treatment. This suggests that the kinetics of flecainide might be non-linear also in patients with normal kidney and liver function. The increase in plasma flecainide levels during chronic treatment could not be predicted, so close monitoring of its plasma levels is advisable.

[Lysine acetyl salicylate. Clinical contribution and preliminary data]. / L'acetilsalicilato di lisina per via rettale. Contributo clinico e dati preliminary.

In the general study of antipyretic products for children prone to febrile convulsions, the authors describe the results obtained administering, the rectal route, three different doses of lysine acetylsalicylate (20-30-40 mg/kg/b.w.) to 53 children with fever. The lower dose was often inadequate in these patients, who need a quick reduction of body temperature below 38 degrees C. The two higher doses were useful both in clinical and in statistical terms, without relevant differences between groups. A statistically significant inverse correlation between blood levels of salicylates and temperature was also shown. No undesirable side effects were observed. The authors conclude that ASL, by rectal route, has to be considered a drug of choice for this indication.

Relationships between iodothyronine peripheral metabolism and ketone bodies during hypocaloric dietary manipulations.

Relationships between iodothyronine and metabolic substrate metabolism during undernutrition were evaluated in four normal subjects who fasted for 48h (Group I) and in four groups (II to V) of obese patients who underwent selective dietary manipulations: 360 calories [carbohydrate (CHO) 40 g/day]; 800 calories containing respectively 19 g/day - ketogenic - (K) and 112 g/day - non ketogenic - (NK) of CHO; and a step-diet programme (during which total calories were progressively reduced from 2500 to 500). Serum T3 levels decreased significantly and constantly during fasting, 360 and 800 K studies, and transiently during the 800 NK diet. During the step-diet programme, a significant fall was found only when 1250 K or less were given. Conversely, serum reverse T3 rose significantly and constantly during 360 and 800 K diets, while a transient increase was found during the 800 NK diet. During the step-diet programme reverse T3 rose only when 750 calories were given. Ketogenesis developed in all studies but one (800 NK), and in the step-diet programme significantly below the 1000 calorie step. Other substrate modifications in each study were also evaluated. Serum T3 levels showed a significant correlation with ketone bodies (KB) in all the ketogenic studies, while no correlation was found in non ketogenic study (800 NK). During the step-diet programme ketone bodies and iodothyronine modifications appeared to be related to the amount of calories. Based on these results, we suggest a relationship between the dietary-induced modifications of iodothyronine metabolism and the development of ketogenesis.