Dragutin Ivanović

Dopamine antagonists induce gastric lesions in rats

Gastric lesions were provoked in all rats that had received intraperitoneally a single dose of the dopamine antagonists haloperidol, metoclopramide or domperidone 24 h before. Dose-dependence was demonstrated for haloperidol. This drug induced gastric lesions as early as 90 min after its application. The ulcerogenic effect of haloperidol was completely prevented or markedly reduced by simultaneous applications of dopamine agonists bromocriptine or L-dopa. We conclude that the model of gastric lesions induced by dopamine antagonists could be successfully applied in further investigations of the role of dopamine in the pathogenesis of ulcer disease.

Poisoning with 2,4-dichlorophenoxyacetic acid treated by hemodialysis

In this paper four patients are presented who had been poisoned by 2,4-dichlorophenoxyacetic acid (2,4-D). The first patient, aged 51 years, had attempted to commit suicide by taking orally 400 ml of a 40% solution of 2,4-D. He was admitted in a coma, 6.5 h after poisoning. Extracorporal hemodialysis was performed and the course of the illness was satisfactory. The second patient, aged 80 years, had accidentally drunk 100 ml of a 40% solution of 2,4-D. He was admitted in a coma a few hours after poisoning. Hemodialysis and resin hemoperfusion were performed and the course of the illness was satisfactory. Prior to the above therapy the patient had a 2,4-D serum concentration of 177 mg/100 ml. 2,4-D clearance was 56,3 ml/min during this therapy. The third patient, aged 24 years, had drunk 200 ml of a 40% solution of 2,4-D in a suicide attempt, and paraquat poisoning was also suspected. He was admitted 10 h after poisoning and immediately hemodialysis and hemoperfusion were carried out: the course of the illness was satisfactory. On admittance the concentration of 2,4-D in serum was 122.5 mg/100 ml, and clearance was 72.9 ml/min during treatment.The fourth patient, aged 50 years, had accidentally drunk 100–200 ml of a 40% solution of 2,4-D. He was admitted in a coma 3 h after poisoning. Hemodialysis was performed and the course of the illness was satisfactory. On admittance the concentration of 2,4-D in serum was 37 mg/100 ml and clearance was 68.7 ml/min. On the fourth day after admittance clinical signs of 2,4-D poisoning appeared again, with a serum concentration of 43.9 ml/100 ml. The patients condition improved after further hemodialysis. In the first two patients there was a prolonged corrected Q-T interval during coma.

The influence of dopamine receptor agonists and an antagonist on acute pancreatitis in rats.

The influence of the dopamine receptor-stimulating agent, bromocriptine, the dopamine-releasing drug, amantadine, and the dopamine antagonist, domperidone, on acute pancreatitis was studied in rats. Acute pancreatitis was induced by ligation of the bile duct at its point of entry into the duodenum. Each drug was applied intraperitoneally 1 h before induction of acute pancreatitis and all the surviving animals were killed 24 h thereafter. The control, saline-pretreated animals exhibited the mortality rate, macroscopical and histological changes, as well as increase of serum amylase levels that were consistent with acute pancreatitis. Domperidone induced a large increase in serum amylase which was significantly reduced by the simultaneous administration of bromocriptine. However, both bromocriptine and amantadine, when given separately did not prevent the increase of serum amylase levels to the control levels. Statistical analysis showed that the difference between the mortality rate in the control and treated groups did not reach the level of significance probably due to the rather limited number of animals used. On the other hand, application of bromocriptine as well as amantadine successfully reduced the onset of acute pancreatitis whereas domperidone, a rather specific peripheral dopamine receptor blocker, had the opposite effect. Both bromocriptine and amantadine significantly reduced the mortality rate from acute pancreatitis in domperidone-pretreated rats. Since the aggravating effect of domperidone was successfully reduced by simultaneous application of bromocriptine, we think that these effects are mediated by peripheral dopamine receptors. However, the mechanisms whereby dopamine receptor-stimulating and dopamine-releasing drugs produce their beneficial effects remain to be elucidated.

DIGOXIN-LIKE SUBSTANCE IN THE SERUM OF UREMIC PATIENTS BEFORE AND AFTER HEMODIALYSIS

SummaryDigoxin concentrations in serum samples were measured before and after hemodialysis of 31 uremic patients (pts) who either never took digoxin or who had not taken digoxin for at least 1 year. False positive digoxin was found in 22 of 31 patients (71%) before hemodialysis and in 14 of 31 patients (45%) after hemodialysis. The concentrations ranged from 0.1 to 0.5 nmol/L, mean value was 0.20 ± 0.16 before hemodialysis and after hemodialysis ranged 0.1 to 0.4 nmol/L mean value was 0.11 ± 0.14 nmol/L. The difference before and after hemodialysis is statistically significant. Some of the patients had a constant value before and after hemodialysis. None had a higher value after hemodialysis than they did before. Eight patients, who had positive serum digoxin before hemodialysis with concentrations up to 0.5 nmol/L, became negative after hemodialysis. Our results indicate that a digoxinlike substance in uremic serum could be at least partly dialyzable.

Aetiology and outcome of acute renal failure secondary to war related trauma and infectious disease in Croatia

Summary: The aim of our study was to explore the aetiology and the outcome of acute renal failure (ARF) during the war in Croatia. of the 2132 patients admitted to our hospital between April 1990 and November 1992 due to war related trauma, 11 (0.5%) developed ARF. We believe that the development of ARF in these patients was secondary to an overwhelming septic process. Most of our patients suffered from multiple organ failure. of the 11 patients suffering from ARF due to war related trauma only four recovered (63.6% had died). We attribute the lethal outcome to the progression of the septic process. Patients who developed ARF due to infectious diseases unrelated to trauma had a different prognosis. Acute renal failure caused by the Hantan virus ran a benign course, in both its oliguric and non‐oliguric form. Patients who developed ARF as a complication of leptospirosis also had a good prognosis. Although ARF is usually of a multifactorial genesis, our study aimed to emphasize the importance of disseminated septic processes as a cause of ARF.

PLACE AND ROLE OF NEW MEMBRANES IN MULTIPLE ORGAN FAILURE: AN ADVANCE OR RUMORS

Acute renal failure is a clinical syndrome characterized by high mortality. There have been numerous attempts to improve survival in this condition, such as the use of drugs, vasoactive medication, biocompatible membranes, high flux, etc. Nevertheless, mortality remains high (1–4). Some promising preliminary results in this field have already been published by our team (5,6). ARF is on the one side mostly a part of MOF and rare independent clinical event. As has been previously documented, the greater the number of organ systems involved in MOF the higher the mortality rate. In a randomized prospective study we tried to answer whether biocompatibility, or high flux, or both, have any effect on survival of dialysis dependent patients with multiple organ failure.