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A model has been developed for ordering diagnostic tests in jaundiced patients. The system proceeds in two steps: (i) diagnostic hypotheses are calculated for each patient from the results of physical examination and routine biological investigations; (ii) given these hypotheses, the most efficient test (out of 22) for reaching the final diagnosis is selected using four criteria: diagnostic value, risk, financial cost, and time in obtaining the result. This model was tested in 62 patients. In 43 of them (69%), the selected test was sufficient for reaching a diagnostic accuracy of 100%. In this group of patients, a mean of 3.7 (range 1-6) tests per patient was ordered by physicians. In the 19 remaining patients, the selected test was not sufficient for the final diagnosis, thus requiring a multiple choice process. It is suggested that such a system could help physicians to improve the care of patients by more efficient ordering of diagnostic tests. [ABSTRACT FROM PUBLISHER]

An ascitic fluid pH less than or equal to 7.31 has been advanced as being the best index in the early diagnosis of spontaneous bacterial peritonitis in cirrhotic patients. In order to test the validity of this criteria, 55 patients with alcoholic cirrhosis and ascites were studied. In each patient, arterial blood and ascitic fluid samples were analysed for pH, PCO2, total CO2 and PO2, and the pH gradient between blood and ascites was calculated. White blood cell and polymorphonuclear cell counts were determined in ascitic fluid, and cultures of ascites were done under aerobic and anaerobic conditions. Twelve patients had a culture proven spontaneous bacterial peritonitis. Their mean ascitic fluid pH (+/- SD) was 7.38 +/- 0.09 (range 7.21-7.49) and differed significantly (p less than 0.05) from that found in patients without spontaneous bacterial peritonitis: 7.44 +/- 0.06 (range 7.34-7.6.3). A marked overlap was observed, however, between the two groups, and only three out of the 12 patients with spontaneous bacterial peritonitis had an ascitic fluid pH less than or equal to 7.31. The pH gradient was 0.10 +/- 0.08 (range -0.01 to +0.28) in the spontaneous bacterial peritonitis group, as compared with 0.02 +/- 0.04 (range -0.09 to +0.12) in the sterile group (p less than 0.01), but a marked overlap was also noted between the two groups. In the spontaneous bacterial peritonitis group, the polymorphonuclear count was 3588 +/- 3849/microliter (range 60-11 776) versus 41 +/- 138/microliter (range 0-813) in the sterile group (p less than 0.0001). All but one patient in the spontaneous bacterial peritonitis group and only two patients in the sterile group had over 250 polymorphonuclear/ microliter. Thus, in our experience, neither the ascitic fluid pH nor the pH gradient values accurately discriminated the individual patients with and without spontaneous bacterial peritonitis. A polymorphonuclear count less than 250/ microliter remained the best criteria for the diagnosis of spontaneous bacterial peritonitis in cirrhotic patients, before having the results of ascitic fluid cultures. [ABSTRACT FROM PUBLISHER]

Abnormally low activity of hepatic bilirubin UDP-glucuronosyltransferase was found in 25% of 81 unselected patients with gallstones, as compared with only 3% in 35 controls. At the time of cholecystectomy, the stones were taken for analysis in 48 of 81 patients, and a bile sample was obtained in 42 of them. Among the stones, 75% were cholesterol stones, 15% pigment stones, and 10% 'intermediate' stones. Low hepatic conjugating activity was not preferentially associated with a given type of stone. No relation was found between the enzymic deficiency and the biliary cholesterol saturation index. A high proportion of biliary bilirubin monoglucuronide (over 40%) was found in four of seven patients with low transferase activity, as was earlier demonstrated in patients with overt Gilbert's syndrome. Raised biliary bilirubin monoglucuronide was also found in three patients, out of 46, who had normal transferase but raised biliary beta-glucuronidase activity. There was no evidence that deficient bilirubin conjugation could be a consequence of gallstones: the activity of another hepatic microsomal enzyme, glucose 6-phosphatase, taken as a reference, was measured in 12 patients and was always normal. Taking into account the very high frequency of a bilirubin centre in the cholesterol stones (87% of the cases in the present series), it is suggested that the increased proportion in poorly soluble biliary bilirubin monoglucuronide, which was associated with defective conjugation, could act as a trigger for gallstone initiation, regardless of the final composition of the stone. [ABSTRACT FROM PUBLISHER]

Gilbert's syndrome was diagnosed in 37 patients with unconjugated hyperbilirubinaemia without overt haemolysis or structural liver abnormality, who had a marked reduction in hepatic bilirubin UDP-glucuronosyltransferase activity (B-GTA) (as compared with that of 23 normal subjects). No significant correlation existed in these patients between serum bilirubin level and the values of B-GTA, thus suggesting that factors other than a low B-GTA must influence the degree of hyperbilirubinaemia in Gilbert's syndrome. Studies of 51Cr erythrocyte survival and 59Fe kinetics in 10 unselected patients demonstrated slight haemolysis in eight, whereas mild ineffective erythropoiesis was suggested in all from a low 24-hour incorporation of radioactive iron into circulating red cells. This overproduction of bilirubin resulting from mild haemolysis and perhaps dyserythropoiesis might reflect only an extreme degree of the normal situation. It certainly contributes to the hyperbilirubinaemia of Gilbert's syndrome and may play a major role in the manifestation of this condition. [ABSTRACT FROM PUBLISHER]

Presents letters to the editor on topics related to internal medicine. Description of three cases of pentazocine-related agranulocytosis; Interaction of lithium and methyldopa; Incidence of jaundice after administration of troleandomycin and oral contraceptives.

The antifungal drug terbinafine has infrequently been incriminated in the occurrence of acute liver injury. We report a case of prolonged cholestasis that occurred in a 75-year-old woman, following terbinafine administration. Jaundice followed by pruritus appeared after four weeks of therapy and was associated with mixed hepatocellular and cholestatic liver tests abnormalities. Following drug withdrawal, serum bilirubin returned to normal values within three months, but anicteric cholestasis persisted for over six months. A liver biopsy performed after six months showed centrilobular cholestasis, discrete portal fibrosis, and a reduction in the number of interlobular biliary ducts. Terbinafine should be added to the list of drugs that can cause reduction in interlobular bile ducts. [ABSTRACT FROM AUTHOR]

Objective: WWOX is an autosomal recessive cause of early infantile developmental and epileptic encephalopathy (WWOX-DEE), also known as WOREE (WWOX-related epileptic encephalopathy). We analyzed the epileptology and imaging features of WWOX-DEE, and investigated genotype-phenotype correlations, particularly with regard to survival., Methods: We studied 13 patients from 12 families with WWOX-DEE. Information regarding seizure semiology, comorbidities, facial dysmorphisms, and disease outcome were collected. Electroencephalographic (EEG) and brain magnetic resonance imaging (MRI) data were analyzed. Pathogenic WWOX variants from our cohort and the literature were coded as either null or missense, allowing individuals to be classified into one of three genotype classes: (1) null/null, (2) null/missense, (3) missense/missense. Differences in survival outcome were estimated using the Kaplan-Meier method., Results: All patients experienced multiple seizure types (median onset = 5 weeks, range = 1 day-10 months), the most frequent being focal (85%), epileptic spasms (77%), and tonic seizures (69%). Ictal EEG recordings in six of 13 patients showed tonic (n = 5), myoclonic (n = 2), epileptic spasms (n = 2), focal (n = 1), and migrating focal (n = 1) seizures. Interictal EEGs demonstrated slow background activity with multifocal discharges, predominantly over frontal or temporo-occipital regions. Eleven of 13 patients had a movement disorder, most frequently dystonia. Brain MRIs revealed severe frontotemporal, hippocampal, and optic atrophy, thin corpus callosum, and white matter signal abnormalities. Pathogenic variants were located throughout WWOX and comprised both missense and null changes including five copy number variants (four deletions, one duplication). Survival analyses showed that patients with two null variants are at higher mortality risk (p-value = .0085, log-rank test)., Significance: Biallelic WWOX pathogenic variants cause an early infantile developmental and epileptic encephalopathy syndrome. The most common seizure types are focal seizures and epileptic spasms. Mortality risk is associated with mutation type; patients with biallelic null WWOX pathogenic variants have significantly lower survival probability compared to those carrying at least one presumed hypomorphic missense pathogenic variant., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

TCF4 haploinsufficiency by deletions, truncating variants or loss-of-function missense variants within the DNA-binding and protein interacting bHLH domain causes Pitt-Hopkins syndrome (PTHS). This neurodevelopmental disorder (NDD) is characterized by severe intellectual disability (ID), epilepsy, hyperbreathing and a typical facial gestalt. Only few aberrations of the N-terminus of TCF4 were associated with milder or atypical phenotypes. By personal communication and searching databases we assembled six cases with the novel, recurrent, de novo missense variant c.1165C > T, p.(Arg389Cys) in TCF4. This variant was identified by diagnostic exome or panel sequencing and is located upstream of the bHLH domain. All six individuals presented with moderate to severe ID with language impairment. Microcephaly occurred in two individuals, epilepsy only in one, and no breathing anomalies or myopia were reported. Facial gestalt showed some aspects of PTHS but was rather non-specific in most individuals. Interestingly, the variant is located within the AD2 activation domain next to a highly conserved coactivator-recruitment motif and might alter interaction with coactivator proteins independently from the bHLH domain. Our findings of a recurrent missense variant outside the bHLH domain in six individuals with an ID phenotype overlapping with but not typical for PTHS delineate a novel genotype-phenotype correlation for TCF4-related NDDs., (© 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

Purpose: DYRK1A syndrome is among the most frequent monogenic forms of intellectual disability (ID). We refined the molecular and clinical description of this disorder and developed tools to improve interpretation of missense variants, which remains a major challenge in human genetics., Methods: We reported clinical and molecular data for 50 individuals with ID harboring DYRK1A variants and developed (1) a specific DYRK1A clinical score; (2) amino acid conservation data generated from 100 DYRK1A sequences across different taxa; (3) in vitro overexpression assays to study level, cellular localization, and kinase activity of DYRK1A mutant proteins; and (4) a specific blood DNA methylation signature., Results: This integrative approach was successful to reclassify several variants as pathogenic. However, we questioned the involvement of some others, such as p.Thr588Asn, still reported as likely pathogenic, and showed it does not cause an obvious phenotype in mice., Conclusion: Our study demonstrated the need for caution when interpreting variants in DYRK1A, even those occurring de novo. The tools developed will be useful to interpret accurately the variants identified in the future in this gene., (© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)

Cause of complex dyskinesia remains elusive in some patients. A homozygous missense variant leading to drastic decrease of PDE2A enzymatic activity was reported in one patient with childhood-onset choreodystonia preceded by paroxysmal dyskinesia and associated with cognitive impairment and interictal EEG abnormalities. Here, we report three new cases with biallelic PDE2A variants identified by trio whole-exome sequencing. Mitochondria network was analyzed after Mitotracker™ Red staining in control and mutated primary fibroblasts. Analysis of retrospective video of patients' movement disorder and refinement of phenotype was carried out. We identified a homozygous gain of stop codon variant c.1180C>T; p.(Gln394*) in PDE2A in siblings and compound heterozygous variants in young adult: a missense c.446C>T; p.(Pro149Leu) and splice-site variant c.1922+5G>A predicted and shown to produce an out of frame transcript lacking exon 22. All three patients had cognitive impairment or developmental delay. The phenotype of the two oldest patients, aged 9 and 26, was characterized by childhood-onset refractory paroxysmal dyskinesia initially misdiagnosed as epilepsy due to interictal EEG abnormalities. The youngest patient showed a proven epilepsy at the age of 4 months and no paroxysmal dyskinesia at 15 months. Interestingly, analysis of the fibroblasts with the biallelic variants in PDE2A variants revealed mitochondria network morphology changes. Together with previously reported case, our three patients confirm that biallelic PDE2A variants are a cause of childhood-onset refractory paroxysmal dyskinesia with cognitive impairment, sometimes associated with choreodystonia and interictal baseline EEG abnormalities or epilepsy.

TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands.

Autosomal recessive microcephaly or microcephaly primary hereditary (MCPH) is a genetically heterogeneous neurodevelopmental disorder characterized by a reduction in brain volume, indirectly measured by an occipitofrontal circumference (OFC) 2 standard deviations or more below the age- and sex-matched mean (-2SD) at birth and -3SD after 6 months, and leading to intellectual disability of variable severity. The abnormal spindle-like microcephaly gene (ASPM), the human ortholog of the Drosophila melanogaster "abnormal spindle" gene (asp), encodes ASPM, a protein localized at the centrosome of apical neuroprogenitor cells and involved in spindle pole positioning during neurogenesis. Loss-of-function mutations in ASPM cause MCPH5, which affects the majority of all MCPH patients worldwide. Here, we report 47 unpublished patients from 39 families carrying 28 new ASPM mutations, and conduct an exhaustive review of the molecular, clinical, neuroradiological, and neuropsychological features of the 282 families previously reported (with 161 distinct ASPM mutations). Furthermore, we show that ASPM-related microcephaly is not systematically associated with intellectual deficiency and discuss the association between the structural brain defects (strong reduction in cortical volume and surface area) that modify the cortical map of these patients and their cognitive abilities., (© 2017 Wiley Periodicals, Inc.)

Objective: Mutations in the syntaxin binding protein 1 gene (STXBP1) have been associated mostly with early onset epileptic encephalopathies (EOEEs) and Ohtahara syndrome, with a mutation detection rate of approximately 10%, depending on the criteria of selection of patients. The aim of this study was to retrospectively describe clinical and electroencephalography (EEG) features associated with STXBP1-related epilepsies to orient molecular screening., Methods: We screened STXBP1 in a cohort of 284 patients with epilepsy associated with a developmental delay/intellectual disability and brain magnetic resonance imaging (MRI) without any obvious structural abnormality. We reported on patients with a mutation and a microdeletion involving STXBP1 found using array comparative genomic hybridization (CGH)., Results: We found a mutation of STXBP1 in 22 patients and included 2 additional patients with a deletion including STXBP1. In 22 of them, epilepsy onset was before 3 months of age. EEG at onset was abnormal in all patients, suppression-burst and multifocal abnormalities being the most common patterns. The rate of patients carrying a mutation ranged from 25% in Ohtahara syndrome to <5% in patients with an epilepsy beginning after 3 months of age. Epilepsy improved over time for most patients, with an evolution to West syndrome in half. Patients had moderate to severe developmental delay with normal head growth. Cerebellar syndrome with ataxic gait and/or tremor was present in 60%., Significance: Our data confirm that STXBP1 mutations are associated with neonatal-infantile epileptic encephalopathies. The initial key features highlighted in the cohort of early epileptic patients are motor seizures either focal or generalized, abnormal initial interictal EEG, and normal head growth. In addition, we constantly found an ongoing moderate to severe developmental delay with normal head growth. Patients often had ongoing ataxic gait with trembling gestures. Altogether these features should help the clinician to consider STXBP1 molecular screening., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) have been predominantly described in epileptic encephalopathies of female, including infantile spasms with Rett-like features. Up to now, detection of mutations in this gene was made by laborious, expensive and/or time consuming methods. Here, we decided to validate high-resolution melting analysis (HRMA) for mutation scanning of the CDKL5 gene. Firstly, using a large DNA bank consisting to 34 samples carrying different mutations and polymorphisms, we validated our analytical conditions to analyse the different exons and flanking intronic sequences of the CDKL5 gene by HRMA. Secondly, we screened CDKL5 by both HRMA and denaturing high performance liquid chromatography (dHPLC) in a cohort of 135 patients with early-onset seizures. Our results showed that point mutations and small insertions and deletions can be reliably detected by HRMA. Compared to dHPLC, HRMA profiles are more discriminated, thereby decreasing unnecessary sequencing. In this study, we identified eleven novel sequence variations including four pathogenic mutations (2.96% prevalence). HRMA appears cost-effective, easy to set up, highly sensitive, non-toxic and rapid for mutation screening, ideally suited for large genes with heterogeneous mutations located along the whole coding sequence, such as the CDKL5 gene., (Copyright © 2012 Elsevier B.V. All rights reserved.)

More than 15 years ago a pioneering report on the separation of cellular material using sedimentation field-flow fractionation (SdFFF) was published. Surprisingly, only a few reports on SdFFF applications to cell separations are available as yet. The major limitations which seemed to slow the development of SdFFF applications in biology appeared to be related to the development of specific instrumentation. Therefore, guidelines are given for setting up a biocompatible SdFFF apparatus. SdFFF elution of cells with different characteristics was performed to demonstrate the efficiency, completeness, and rapidity of cell separations by this method. Retention data describing the effect of lifting forces on nucleated cells are compared to those for red blood cells (RBC). The effects of flow rates, field intensity, and injection protocol were studied using normal human RBC eluted in isotonic medium as a probe for retention conditions. When possible, data were also compared to previously published reports. Guidelines for elution and separation optimization are given. Using mixtures of nucleated and living red blood cells, viability studies showed a surprisingly high recovery of each type of material., (Copyright 1997 Academic Press.)

After liver transplantation for hepatitis C virus (HCV)-related cirrhosis, recurrent viral infection is almost constant, resulting in acute graft dysfunction in 30-75% of cases. Acute graft dysfunction in the post-transplant period may also be the result of various causes (such as rejection, CMV infection, sepsis, or technical problems). Therefore, the role of HCV reinfection is often difficult to document. The aim of this study was to assess the diagnostic value of serial HCV RNA quantitation in this setting. Fourteen patients transplanted with follow-up greater than 6 months were studied. HCV RNA was quantitated before and serially after transplantation, using branched DNA technology. In cases of acute graft dysfunction, usual investigations and additional HCV RNA quantitation were conducted. There were 15 episodes of acute graft dysfunction in 12 patients. Six episodes had a hepatitic biochemical pattern, and 5 of them were associated with a concomitant HCV RNA peak. Nine episodes had a mixed, hepatitic, and cholestatic biochemical pattern, and 5 of them were associated with a concomitant peak of HCV RNA. Overall, 10 of 15 (66%) episodes of acute graft dysfunction were associated with HCV RNA peak, which strongly suggests that HCV was the etiologic factor. In 9 of these 10 episodes, no other cause of dysfunction was found, and one had associated CMV disease. In 5 cases, no peak of HCV RNA was observed and the causes of dysfunction were CMV (in 2 cases) and rejection, granulomatosis, and unknown (in 1 case each). Serial quantitations of HCV RNA levels after liver transplantation for cirrhosis C provide a useful tool in the diagnosis of HCV reinfection of the graft.

Multiple nuclear dots antinuclear antibodies display a specific immunofluorescence pattern on HEp-2 cells. They have been reported to be strongly associated with primary biliary cirrhosis, especially when sicca syndrome was present. To determine whether multiple nuclear dots antinuclear antibodies are specific for primary biliary cirrhosis, we studied the clinical, biochemical, immunological and morphological features of 38 patients between December 1983 and September 1990 who had serum multiple nuclear dots antinuclear antibodies detected in an immunology laboratory of a large medical center. Sufficient information was reliable in 36 patients; the group included 31 women and 5 men (mean age = 57.6 +/- 14.5, range = 30 to 87). Fifteen patients (42%) had primary biliary cirrhosis, 5 patients (14%) had type 1 autoimmune chronic active hepatitis, 4 patients (11%) had liver disease of unknown cause and 12 patients (33%) had various immunological disorders but no liver disease. Two of the patients with primary biliary cirrhosis (13%) had clinical sicca syndrome. Our study demonstrates the following: (a) serum multiple nuclear dots antinuclear antibodies are not specific for liver disease because they can be observed in one third of patients with various immunological disorders without liver involvement, and (b) serum multiple nuclear dots antinuclear antibodies are not specific for PBC because they can also be observed in type 1 autoimmune chronic active hepatitis. Our results also suggest that patent sicca syndrome is abnormally present in patients with primary biliary cirrhosis and multiple nuclear dots antinuclear antibodies.

The clinical and pathological findings of five adult cases of idiopathic nonsyndromatic paucity of interlobular bile ducts are reported. Patients were 18-32 years old at the onset of the disease; four presented with pruritus and/or jaundice and one with bleeding of the esophageal varices. Two patients were siblings. Serum alkaline phosphatase counts ranged from 1 to 16 times the upper normal value, and total bilirubin counts ranged from 0.6 to 8.8 mg/dL (10 to 150 mumol/L). Initial liver biopsy showed portal and periportal fibrosis with cholangiolar proliferation and reduction in the number of interlobular bile ducts. Antimitochondrial antibodies were absent, and bile ducts were normal after opacification. The patients were observed for 3-11 years. Repeated liver biopsies in the five patients showed progression of the lesions, with development of biliary type cirrhosis in four. Two of the four patients with cirrhosis died of hepatic failure 3 and 11 years after onset of the disease. In the two other cases, liver transplantation was performed successfully. These cases suggest that chronic cholestasis with marked ductopenia resembling the nonsyndromatic paucity described in infancy and childhood may reveal itself at an adult age. This disorder, possibly familial, may rapidly progress to severe and even fatal liver disease and could be a new indication for liver transplantation.

We present the case of a 25-year-old man with Crigler-Najjar disease who had since birth a marked unconjugated hyperbilirubinemia without bilirubin overproduction, without any neurological involvement and in whom phenobarbital administration failed to produce any effect. Analysis of his biliary bile pigments on two occasions showed (i) a decrease excretion of bilirubin, as indirectly suggested by a high ratio of biliary bile acids over total bilirubin; (ii) an increase in unconjugated bilirubin IX alpha quantitated by thin-layer chromatography (TLC) following alkaline methanolysis and by direct extraction and TLC of the tetrapyrroles; (iii) a high proportion of bilirubin monoconjugates whereas the excretion of diconjugates was very low. Classification of the present patient into Crigler-Najjar disease type I or II was not possible. The most striking and practical difference among the various cases of Crigler-Najjar disease remains the response to phenobarbital. Among cases of Crigler-Najjar disease which respond to enzyme induction and Gilbert's syndrome, the continuous spectrum suggests a common defect.

Gallbladder bile collected by duodenal intubation or during surgery was examined microscopically in patients who were free of stones and in patients with proven stones. None of the 16 patients free of stones had cholesterol monohydrate crystals or calcium bilirubinate granules in bile. Among the 17 patients with proven cholelithiasis, 13 with cholesterol stones had cholesterol monohydrate crystals in their bile, but only 2 of the 4 patients with pigment stones had calcium bilirubinate granules. These data confirm that cholesterol monohydrate crystals are sensitive and specific for cholesterol stones, whereas calcium bilirubinate granules lack sensitivity for the diagnosis of pigment stones. From these results, the diagnostic usefulness of microscopic examination of bile collected from the duodenum was studied prospectively in 46 patients with symptoms suggestive of cholelithiasis but in whom stones had not been visualized at cholecystography and ultrasonography. In 15 of them, bile was found to be abnormal: cholesterol monohydrate crystals were seen in 11, cholesterol crystals + calcium bilirubinate granules in 2 and calcium bilirubinate granules in 2. To date, nine of these patients have been operated on: 6 (all with cholesterol monohydrate crystals) had small cholesterol gallstones and 3 (2 with cholesterol monohydrate crystals and 1 with calcium bilirubinate granules) had signs strongly suggestive of the recent migration of gallstones. One patient refused operation, but minute pigment stones were found to be associated with calcium bilirubinate granules at duodenal intubation. In the other 31 patients, bile contained neither cholesterol monohydrate crystals nor calcium bilirubinate granules. They were not operated on and were followed up with repeated investigations for 12 to 24 months.(ABSTRACT TRUNCATED AT 250 WORDS)

The Mirizzi syndrome is due to common hepatic duct obstruction secondary to the impaction of a large gallstone in the neck of the gallbladder or the cystic duct. The sonographic and computed tomography features in 3 cases of Mirizzi syndrome are described and compared with percutaneous transhepatic cholangiography or endoscopic retrograde cholangiography findings. The Mirizzi syndrome was diagnosed preoperatively on sonography in 2 out of 3 cases and on plain computed tomography scans in all 3 cases. However pre or intraoperative visualization of the biliary tract is mandatory in suspected Mirizzi syndrome to detect the presence or absence of cholecystobiliary fistula, in order to adapt the operative strategy.

Phenobarbital was administered to a patient with extrahepatic biliary obstruction who was initially thought to have cholestatic hepatitis. On two occasions, administration of the drug was associated with a decrease of jaundice, pruritus, and serum bile acid levels. This strongly suggests that phenobarbital may be effective not only in intrahepatic cholestasis, as reported earlier, but also in extrahepatic obstruction, and therefore cannot be used for the differention of these two types of cholestasis.