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Biomedical subjects

J M Metreau

Publications and source records attributed to J M Metreau.

At least 19 recordsLinked to original sources

Reverse seroconversion of hepatitis B after allogeneic bone marrow transplantation: a retrospective study of 37 patients with pretransplant anti-HBs and anti-HBc.

BACKGROUND: Reverse seroconversion to hepatitis B virus (HBV), i.e., HBV reactivation in patients with pretransplant antibodies to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc), is rarely re-ported after allogeneic bone marrow transplantation. METHODS: To determine this risk, we studied clinical outcome and serological changes in 37 patients with pretransplant anti-HBs and anti-HBc. RESULTS: In 33 cases, no change in HBV markers was observed in the posttransplant period. In four cases, anti-HBs and anti-HBc were lost, and hepatitis B surface antigen, hepatitis B e antigen, and HBV DNA emerged together with acute hepatitis, after cessation of immunosuppression. The actuarial risk of reactivation in the 37 patients was 20.5% (median follow-up 20 months). No reactivation occurred in patients with anti-HBs-positive donors. CONCLUSION: Although few cases of postallogeneic bone marrow transplantation reverse seroconversion to HBV have been reported, this study demonstrates that the actuarial risk is relatively high and suggests that donor vaccination might be proposed prophylactically or that HBs-specific immunoglobulin infusions might be warranted.

Adolescent↗

On the use of ion-pair chromatography to elucidate doxorubicin release mechanism from polyalkylcyanoacrylate nanoparticles at the cellular level.

The major hypothesis underlying the remarkable efficiency of polyalkylcyanoacrylate particles loaded with doxorubicin against multidrug resistant tumor cells in vitro, is based on the ion-pair association of doxorubicin with soluble hydrolysis products of polyalkylcyanoacrylate. In an attempt to demonstrate the validity of this hypothesis, we have used ion-pair reversed-phase high-performance liquid chromatography and a laboratory-synthetized compound, i.e., the 2-cyano-2-butylhexanoic acid, as a model for polyalkylcyanoacrylate highly polydispersed degradation products. It is shown that, compared to a counter-ion, like heptane sulfonic acid, 2-cyano-2-butylhexanoic acid exhibits an effective ion-pairing effect at different pH values and organic mobile phase conditions. Moreover, at pH close to physiological conditions and at low mobile phase organic modifier percentage, this effect is experimentally observed, which strongly supports the initial hypothesis.

Antibiotics, Antineoplastic↗

Sedimentation field-flow fractionation of cellular species.

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.

Cell Fractionation↗

Terbinafine-induced prolonged cholestasis with reduction of interlobular bile ducts.

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.

Aged↗

Serial quantitative determination of hepatitis C virus RNA levels after liver transplantation. A useful test for diagnosis of hepatitis C virus reinfection.

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.

Adult↗

Multiple nuclear dots antinuclear antibodies are not specific for primary biliary cirrhosis.

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.

Adult↗

Idiopathic biliary ductopenia in adults: a report of five cases.

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.

Adolescent↗

[Ultrasonographic and x-ray computed tomographic aspects of Mirizzi's syndrome].

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.

Adult↗

An unusual case of Crigler-Najjar disease in the adult. Classification into types I and II revisited.

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.

Adult↗

Ascitic fluid pH in alcoholic cirrhosis: a reevaluation of its use in the diagnosis of spontaneous bacterial peritonitis.

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.

Adult↗

Computer-aided selection of diagnostic tests in jaundiced patients.

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.

Adolescent↗

Possible role of a defect in hepatic bilirubin glucuronidation in the initiation of cholesterol gallstones.

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.

Adolescent↗

Role of bilirubin overproduction in revealing Gilbert's syndrome: is dyserythropoiesis an important factor?

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.

Adolescent↗