RESUMEN
Since there are now several ways to treat symptomatic gallstone disease, one is able to select treatment on the basis of the patient's comfort, the practicability, effectiveness, and side effects of the technique, and the relative costs. In order to assess the present status of contact dissolution with methyl tert-butyl ether with regard to these aspects, the present enquiry reports the data of 21 European hospitals. Eight hundred three patients were selected for contact litholysis of cholesterol gallbladder stones using methyl tert-butyl ether. Percutaneous transhepatic puncture of the gallbladder was performed under x-ray or ultrasound guidance. Dissolution rate, side effects, and treatment times of 268 patients from one single center were compared to those of 535 patients from the other 20 centers. Two hundred sixty-four patients were followed for five years to assess stone recurrence. Physicians were asked how they assessed the expenditure of the method, the discomfort to the patients, and the staffing situation. Patients were asked to indicate their acceptance on an analog scale. Puncture was successful in 761 (94.8%) patients. Prophylactic administration of antibiotics was not necessary. Stones were dissolved in 724 (95.1%) patients. In 315 (43.5%) sludge remained in the gallbladder. The most severe complication was bile leakage, which led 12 (1.6%) patients to have elective cholecystectomy. Toxic injuries due to the ether were not reported. Method-related lethality amounted to 0%, 30-day-lethality to 0.4%. Stone recurrence rate was about 40% in solitary stones and about 70% in multiple stones over five years. Patients with multiple stones developed recurrent stones almost twice as often as those with solitary stones. The probability of stone recurrence in patients with sludge in the gallbladder after catheter removal was not statistically significantly different from those without sludge. Seventy to 90% of the centers found the puncture to be simple and not distressing for patients and the relation between expenditure and therapeutic success to be acceptable. The acceptance of contact litholysis by the patients was excellent. Contact litholysis when applied by an experienced team provides real advantages in the treatment of gallstone disease. The method is technically simple, well accepted by the patients, and can be easily applied in community hospitals. Contact litholysis may be of particular value in patients who are not suitable for anesthesia or surgery.
Asunto(s)
Colelitiasis/tratamiento farmacológico , Éteres Metílicos/uso terapéutico , Solventes/uso terapéutico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , RecurrenciaRESUMEN
1. Pharmacokinetic parameters of trapidil (an antagonist of platelet derived growth factor) were evaluated in 12 healthy male subjects (study I) and in a group of 10 patients with liver cirrhosis (Child B) and five control subjects, respectively (study II). 2. Investigations were carried out after a single dose trapidil (200 mg) and at steady state after application of 200 mg trapidil three times daily for 5 days (study 1) or 4 days (study II). 3. Study I: The concentration-time curves of the terminal elimination phase of trapidil exhibited a slight convexity which might reflect nonlinear kinetics. The AUC of trapidil obtained after the first dose (20.5 [+/- 7.0 s.d.] micrograms ml-1 h) was markedly higher than the AUC determined at steady state (13.2 [+/- 3.8 s.d.] micrograms ml-1 h), the non-parametric 90% confidence intervals of the ratio day 5/day 1 was 0.58-0.73 (point estimator 0.64). 4. Study II: AUC averaged (21.4 [+/- 9.1 s.d.] micrograms ml-1 h) in controls and (34.4 [+/- 14.9 s.d.] micrograms ml-1 h) in cirrhotic patients. The 90% confidence intervals for the difference group 1 vs group 2 was 0.95-2.97 (point estimator 1.48, P = 0.066). At steady state, AUC averaged (13.7 [+/- 5.7 s.d.] micrograms ml-1 h) in controls and (20.8 [+/- 6.8 s.d.] micrograms ml-1 h) in cirrhotic patients (90% confidence intervals group 1 vs group 2: 0.88-2.20 [point estimator 1.45, P = 0.05]). As seen in study I, the AUC of trapidil obtained after the first dose was markedly higher than the AUC determined at steady state, the non-parametric 90% confidence intervals of the ratio day 5/day 1 was 0.48-0.84 (point estimator 0.66) in control subjects and 0.54-0.72 (point estimator 0.64) in cirrhotic patients, respectively. 5. An inverse correlation was seen between the results of the monoethylglycinxilidid (MEGX)-test and the AUC of trapidil (single dose: r = -0.516, P = 0.048; steady state: r = -0.548, P = 0.042). 6. Results of study I and study II indicate an autoinduction of trapidil metabolism after repeated oral doses. Although trapidil elimination is decreased in patients with liver cirrhosis (study II), the elimination half-life at steady state is relatively short (2.4 [+/- 1.1 s.d.] h) and therefore should prevent cumulation of trapidil even in cirrhotic patients.
Asunto(s)
Cirrosis Hepática/metabolismo , Inhibidores de Agregación Plaquetaria/farmacocinética , Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Trapidil/farmacocinética , Adulto , Área Bajo la Curva , Semivida , Humanos , Cirrosis Hepática/fisiopatología , Masculino , Inhibidores de Agregación Plaquetaria/efectos adversos , Trapidil/efectos adversosRESUMEN
Twenty-two patients with primary biliary cirrhosis were treated with ursodeoxycholic acid, 10 mg/kg per day. Fourteen patients with stages I/II were treated for 4-12 years (mean 7.5), and eight patients with stages III/IV for 5-12 years (mean 6.5). Twelve of 13 patients with early stages became asymptomatic. Aminotransferases, cholestasis-indicating enzymes and IgM improved (p < 0.01) and remained low during the whole treatment period. Ursodeoxycholic acid was the predominant serum bile acid, and lithocholic acid did not increase in the serum but did increase in the stool. Of eight patients with stages III/IV, seven were symptomatic, and four became asymptomatic. In all eight patients, laboratory data improved. Of these eight patients three experienced haemorrhage from oesophageal varices, two had to be transplanted, and one of them died. In one patient splenic rupture occurred, and in three liver function tests deteriorated. Although the number of patients was small, this is the longest treatment period so far reported. Ursodeoxycholic acid had no side effects for up to 12 years, and in patients with early stages it seemed to have a beneficial effect on symptoms and the progression of the disease. However, even with up to 12 years of therapy, ursodeoxycholic acid did not cause antimitochondrial antibodies to disappear either in the early or in the late stages, it was unable to prevent rebound effects during therapy intermission even after more than 5 years of continuous therapy, there was no decisive influence on liver histology and it did not cure the disease. Finally, although ursodeoxycholic acid improved life quality and laboratory data in all patients with late stages of the disease, it did not prevent complications due to cirrhosis.