Pharmacokinetics, hepatic biotransformation and biliary and urinary excretion of bromosulfophthalein (BSP) in an experimental liver disease mimicking biliary cirrhosis

We studied the hepatic handling of bromosulfophthalein in healthy rabbits with hepatic coccidiosis 28 days after an experimental infection with sporulated oocysts of Eimeria stiedai, an experimental model of liver disease histopathologically resembling primary biliary cirrhosis in man. A pharmacokinetic study of the results was performed following a multicompartmental model with 7 transfer constants to describe the physiological disposition of the dye. The study showed that the plasma disappearance, distribution volume (Vi), hepatic biotransformation and the biliary and urinary elimination of conjugated (BSPc) and unconjugated (BSPu) bromosulfophthalein were markedly altered. Whereas Vi and urinary excretion of the dye were significantly increased, the hepatic clearance, biotransformation and biliary excretion of BSPc and BSPu were drastically reduced in infected rabbits. Satisfactory agreement was obtained between the experimental and estimated data, particularly those relating to biotransformation clearance and biliary and urinary excretion of the dye. These results demonstrate that severe liver disease in rabbits with histopathological liver alterations resembling several hepatic dysfunctions in man markedly reduce hepatic uptake, metabolism and biliary excretion of a xenobiotic such as BSP.     

The effect of major railway accidents on the psychological health of train drivers—I. Acute psychological responses to accident

The acute psychological reactions of 101 train drivers to on-the-track accidents were studied by means of clinical interviews and questionnaires (Impact of Event Scale, GHQ-20 and a questionnaire addressing stress symptoms, pre-accident expectancies and worries). More than half of the train drivers reported moderate to high intrusive distress (mean 11.3) within hours to days after the accident but only 1/3 reported symptoms of acute psychophysiological arousal. Intrusive symptoms related to visual impressions were most frequently reported. Avoidance was less prevalent (mean 8.8).

Clinical interviews, relationship between pre-accident worries and severity of the acute responses and positive correlation between GHQ-scores relating to the fortnight preceding the accident and IES-intrusion scores, suggest that premorbid variables may influence the stress response. Involvement in more than two previous accidents invoked a feeling of vulnerability and produced stronger acute responses. Post-accident experiences involving various personal contacts did not correlate with the stress responses in this study and only a few drivers experienced such events in a negative way. Denial of the possibility of being involved in accidents was not associated with increased risk of strong acute responses, indicating that denial does not predict poor outcome in healthy persons exposed to situations where possibility of avoiding the event is outside the control of the person.     

Growth of colorectal polyps: design of a prospective, randomized, placebo-controlled intervention study in patients with colorectal polyps.

One hundred and sixteen patients were included, during 18 months, in a double-blind placebo-controlled intervention study, with calcium, vitamins A, C, E and selenium (in a cocktail) or placebo against growth of colonic polyps. Patients were randomized within three arms, according to diameter of the largest polyp, < 5 mm, 5-9 mm or > 9 mm. Polyps > 9 mm were resected, the others were left to be measured annually before resection after 3 years. The protocol (performed in all of the patients) included registration of demographic data, family and personal history, measurement of polyps, collection of blood specimens, stools and biopsy samples. Registration of nutritional status, diet history and 5-day prospective food consumption, was performed in 108 patients. The patient compliance was registered every third month by the hospital pharmacist, with concomitant delivery of new boxes of capsules. Additionally, stool collections were performed from all of the patients for the measurement of faecal calcium, bile salts and fat. Inclusion rate of 37, 41 and 38 patients in each of the three 6-month periods was uniform. The group with the largest polyps measuring 5-9 mm comprised 44% of the material. The sex ratio corresponded to that in overall referrals for colonoscopy. The age relationship of size and multiplicity of polyps and the distribution of polyps in the large bowel corresponded to previous experience in polyp-bearing individuals of the same age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional cerebral flow velocity waveforms in the human fetus.

The purpose of this study was to determine regional cerebral flow velocity waveforms in the human fetus. Flow velocity waveforms were determined at the level of the middle cerebral artery, vertebral artery, and intracerebellar arteries in 25 fetuses between 23 and 39 weeks' gestation. The pulsatility index was used to quantify the waveforms. Technically acceptable waveforms were obtained at all three vessels in 20 fetuses. The pulsatility index was lowest for the intracerebellar artery in all the fetuses studied. The pulsatility indices of the vertebral artery and middle cerebral artery were not significantly different. These data suggest that significant fetal regional cerebral blood flow differences occur in utero, with intracerebellar arterial resistance being lower than resistance in other regions of the brain.     

Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II: ventricular arrhythmias, channelopathies and implantable defibrillators.

This consensus paper on behalf of the Study Group on Sports Cardiology of the European Society of Cardiology follows a previous one on guidelines for sports participation in competitive and recreational athletes with supraventricular arrhythmias and pacemakers. The question of imminent life-threatening arrhythmias is especially relevant when some form of ventricular rhythm disorder is documented, or when the patient is diagnosed to have inherited a pro-arrhythmogenic disorder. Frequent ventricular premature beats or nonsustained ventricular tachycardia may be a hallmark of underlying pathology and increased risk. Their finding should prompt a thorough cardiac evaluation, including both imaging modalities and electrophysiological techniques. This should allow distinguishing idiopathic rhythm disorders from underlying disease that carries a more ominous prognosis. Recommendations on sports participation in inherited arrhythmogenic conditions and asymptomatic gene carriers are also discussed: congenital and acquired long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy and other familial electrical disease of unknown origin. If an implantable cardioverter defibrillator is indicated, it is no substitute for the guidelines relating to the underlying pathology. Moreover, some particular recommendations for patients/athletes with an implantable cardioverter defibrillator are to be observed.     

Reduction in the middle cerebral artery pulsatility index after decompression of polyhydramnios in twin gestation.

Amniotic fluid decompression was performed for symptomatic polyhydramnios complicating four sets of discordant twin gestations. Doppler ultrasound waveforms of the middle cerebral artery were determined before and after the procedure in seven of the eight fetuses. After amniocentesis, the pulsatility index of the middle cerebral artery (PIMCA) was reduced in all fetuses (p < 0.01). When one considers only the larger twin in each set, the magnitude of the change in PIMCA was relatively consistent among the different sets (-0.60 +/- 0.14; p < 0.01; range, -0.45 to -0.79). The smaller twins showed a much more variable response (-0.82 +/- 0.70; range, -0.05 to -1.75). The pulsatility index of the umbilical artery (PIUA) showed no consistent trend in the five subjects in which it was determined. In principle, the cerebrovascular dilation indicated by the PIMCA measurements may in part be due to acute increases in maternal and fetal carbon dioxide tensions following relief of maternal restrictive lung dysfunction. More importantly, the acute fall in amniotic fluid pressure--the external pressure to which the fetoplacental unit is exposed--leads to pooling of blood in fetal and placental veins, and thereby reduces the effective blood volume of the fetoplacental unit. This effective hypovolemia, functionally analogous to that produced by fetal hemorrhage, elicits changes in regional vascular resistances that favor cerebrovascular perfusion. The impact of acute amniotic fluid decompression on the fetal circulation reflected in the marked changes in PIMCA suggests a role for monitoring to avoid large acute changes in pressure during therapeutic amniocentesis.