Side-to-side choledochoduodenostomy in the management of choledocholithiasis

Sixty patients with choledocholithiasis (either single or multiple stones of the biliary tree) were treated with lateral choledochoduodenostomy. Of these cases 83.3% were followed up for from 1 to 7 years. Only 1 patient developed cholangitis, which responded well to conservative treatment. The other cases have been asymptomatic following surgery. The diameter of the common bile duct is not an important problem in constructing a functional anastomosis.     

Do prothrombin time, transaminases, and platelet count predict the severity of fibrosis in viral liver diseases?

The goal of our study is to assess the performance of a score combining 3 serological parameters (PT, platelets and transminases) in predictive hepatic fibrosis. The study involved 54 patients, 29 of which resulted in distributing them according to the score of Metavir into 2 groupes: Group A with mild fibrosis (F1,F2) and group B with severe fibrosis (F3,F4). PT, platelets and transminase values in serum were assessed for all patients. The total score of the 3 biological parameters combined, was significantly more elabled in the severe fibrosis group than in the mild fibrosis group (P = 0.01) but it was not of much importance in 30% of cases as it did not allow to classify the patients with certainty in group A or in group B. This score does not seem to grant exemption from needle liver biopsy, but it can be improved by the association of other direct markers of fibrosis.     

Prolonged neuromuscular blockade as a result of malnutrition-induced pseudocholinesterase deficiency

Mivacurium is a short-acting neuromuscular blocking drug, ideal for short surgical procedures. The brief duration of action depends on rapid hydrolysis by plasma cholinesterase. An inherited or acquired deficiency of plasma cholinesterase can prolong the effect of mivacurium. We present an unusual case of unanticipated postoperative apnea following mivacurium administration, as a result of acquired plasma cholinesterase deficiency, in a patient with previous uneventful exposure to both mivacurium and suxamethonium (succinylcholine).     

Intracardiac thrombosis: unusual complication of Behcet's disease

Cardiac involvment is rare, and intracardiac thromboses are exceptional in Behcet's disease. We present a 29 years old male patient seen for right heart-failure, thrombophlebitis and pulmonary embolism. A right atrial thrombosis was showen at the echocardiography and confirmed by computed tomography and magnetic resonance imaging. The diagnosis of Behcet's disease was established on the finding of bipolar aphtous ulcers and skin hypersensitivity. We conclude that Behcet's disease shoud be considered as a possible cause of cardiac thrombosis in the youngs men of the Mediterranean basin.     

Relationship between anorexia and loss of serotonin uptake sites in brain of mice and rats receiving d-norfenfluramine or d-fenfluramine

Previously, we have shown that repeated administration of d-fenfluramine (D-F) to rats is associated with development of tolerance to the initial anorexia, but that in mice no such tolerance seems to occur. In the first study, we show that chronic administration of neither d-norfenfluramine (D-NF; the principal metabolite of D-F) nor the serotonin (5-HT) 2C receptor agonist m-chlorophenyl-piperazine (mCPP) is associated with the development of anorectic tolerance tested using a dessert protocol. However, compared with mice receiving these drugs for the first time, both of these chronic treatments were associated with a significant attenuation of Fos immunoreactivity (Fos-ir) in several brain regions, including bed nucleus of the stria terminalis, paraventricular hypothalamus, and central nucleus of amygdala. This attenuation is similar to that described previously in rats. Because loss of efficacy of these agents could be related to loss of 5-HT transporter (5-HTT) sites, their presumptive primary mode of action, in the final study we determined the effect of various, low-dose regimens of D-F and D-NF on 5-HT uptake in frontal cortex of mice and rats. We show in mice that D-F causes a greater loss of 5-HT uptake than D-NF, and that at the lowest dose regimen used uptake was unaffected in rats but was reduced in mice. The data are discussed in terms of the species difference in behavioral tolerance and differences in neurochemical profile of D-F and D-NF.     

Skp2 overexpression is a p27Kip1-independent predictor of poor prognosis in patients with biliary tract cancers

To better understand the pathogenesis of biliary tract carcinoma (BTC) and to increase the accuracy of predicting outcomes for patients with this disease, we performed molecular cytogenetic analyses of BTC cell lines and tumors to identify non-random amplification(s) and target gene(s) within the amplicons. Among several non random chromosomal aberrations detected in BTC cell lines by comparative genomic hybridization, gain/ampli-fication of DNA at 5p was the most frequently observed alteration. We assessed the copy number and expression status of the possible target gene SKP2 for 5p amplification in cell lines and 33 primary stage II or III tumors of BTC. SKP2 was amplified, and subsequently overexpressed in both cell lines and primary tumors of BTC. However, levels of Skp2 and p27Kip1 proteins were not correlated inversely. Heightened expression of Skp2 and reduced expression of p27Kip1 were both associated with a shorter disease-free and/or overall survival in univariate analyses. In multivariate regression analyses, Skp2 and p27Kip1 were independent predictive factors. Those results suggest that (a) overexpression of Skp2 through an amplification mechanism may contribute to the progression of BTC, (b) not only each molecule, but also the combination of Skp2 and p27Kip1, might be a useful predictor of the prognosis of BTC, and (c) molecular targets of Skp2 other than p27Kip1 may also be important factors in the pathogenesis of this disease.     

An investigation of dopaminergic metabolites in the striatum and in the substantia nigra in vivo utilising radiolabelled L-DOPA and high performance liquid chromatography: a new approach in the search for transmitter metabolites

Although the major routes of dopamine metabolism seem to be established, at least in terminal regions such as the striatum, it is important to search for previously unknown metabolites and to investigate the relevance of previously suggested minor alternative pathways. An urgent issue is to verify and quantify the transformation of dopamine to putative toxic species, another is to further explore metabolism of dopamine located in cell bodies/dendrites, e.g. in the substantia nigra. We have developed a new method in order to widen the search for alternative metabolites of dopamine. The method is based on systemic injection of tritiated L-DOPA to rats in vivo. Brain tissue was homogenised and centrifuged and the resulting supernatant fractioned following passage through a liquid chromatography system. The radioactivity of each fraction was measured using a scintillation system. By identifying fractions containing major catecholamines and metabolites, according to a standard solution, novel metabolites can be searched for in the remaining fractions. It was possible to obtain sufficient radioactivity in separate fractions of supernatant of homogenised tissue, even from such a small brain nucleus as substantia nigra. Radioactivity was obtained in those fractions that contained the major catecholamines and their metabolites, as well as in other fractions where it may represent previously unknown metabolites of L-DOPA/dopamine. The method was used to evaluate the possibility that cytochrome P450 2E1 is involved in the metabolism of dopamine in the substantia nigra. Significant changes in the radioactivity pattern were induced by inhibition of the enzyme but conclusions about whether cytochrome P450 2E1 is involved in the metabolism of dopamine or not requires further studies. The method can be used to study the metabolism of dopamine and can be extended, by using other radiolabelled precursors, also to evaluate metabolism of other transmitters, e.g. serotonin.