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B Frémond

Publications and source records attributed to B Frémond.

18 recordsLinked to original sources
PubMed1999

Detoxifying activity in pig livers and hepatocytes intended for xenotherapy.

BACKGROUND: Both livers and hepatocytes from pigs have been proposed for the treatment of end-stage liver diseases, as an alternative to allogeneic liver transplants. However, little is known of the capability of porcine hepatocytes to fulfill the biotransformation pathways of toxic compounds, including those released from livers in acute failure. We have studied the activity and expression of detoxifying enzymes in porcine livers and in cultured hepatocytes and their induction by phenobarbital. METHODS: Cytochromes P450 (CYP) 1A, 2B, and 3A and GST-like activities were tested with the following specific substrates: 7-ethoxyresorufin, 7-pentoxyresorufin, nifedipine, testosterone, 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene, and ethacrinic acid. CYP 1A1/2-, 2B1/2-, 2E1- and 3A4-related and GSTalpha proteins were analyzed by Western blotting and CYP 1A1/2, 2B1/2, 2C6, 2E1, and 3A4, aldehyde dehydrogenase, epoxide hydrolase, and GSTalpha-like RNA by Northern blotting. RESULTS: Enzymatic activities reflecting the expression of CYP 1A-, CYP 2B-, CYP 2E1-, and CYP 3A-like genes, that is, ethoxyresorufin-O-deethylase, pentoxyresorufin-O-deethylase, nifedipine oxidase and testosterone 6beta-hydroxylase, and chlorzoxazone 6-hydroxylase, were identified in pig livers. CYP 1A and CYP 2E1, GSTalpha-like proteins, CYP 1A, 2C, and 2E, epoxide hydrolase, aldehyde dehydrogenase, and GST like RNA were expressed in vivo and in vitro. CYP 2B and CYP 3A RNA and proteins, and their associated activities were induced by phenobarbital. CONCLUSIONS: Porcine hepatocytes express the most important biotransformation enzymes and their corresponding activities and RNA. Thus, livers and hepatocytes from pigs can detoxify a large spectrum of exogenous and endogenous compounds, which makes them a convenient substitute for allogeneic transplants for patients with liver failure.

Aldehyde Dehydrogenase↗
PubMed1998

[Hepatocytes in cell therapy].

Cell-based therapy could represent an alternative treatment to orthotopic liver transplantation in acute liver failures and for the correction of genetic defects of various enzymatic functions. Several recent studies indicate that hepatocytes injected either in the spleen or in portal vein can restore liver-specific function(s) in animal model systems. Alternatively, an extracorporal hybrid bioartificial liver might provide liver-specific functions, maintain the patient alive and allow spontaneous recovery of the patient's own liver, or act as a bridge toward liver transplantation in acute liver failures. Various drawbacks of devices such as flat culture substrates, hollow-fiber bioreactors or microcarriers led us to develop a reliable extracorporeal bioartificial liver based on alginate-entrapped hepatocytes. This system was used successfully for the correction of the Gunn rat genetic defect which results in the lack of bilirubin conjugation. The development of this system for clinical purposes requires large yields of functional hepatocytes. We isolated porcine hepatocytes by collagenase perfusion of the liver and cells were immobilized within alginate beads which were subsequently inoculated in a bioreactor. Porcine hepatocytes expressed liver-functions at high levels, particularly those involved in detoxification and biotransformation processes; they were immunoisolated from immunoglobins and could be cryopreserved. This system represents a promising tool for the design of an extracorporeal bioartificial liver in human beings.

Animals↗
PubMed1997

Intestinal vascular anomalies in children.

Vascular anomalies are an uncommon cause of gastrointestinal bleeding in childhood. Confusing nomenclature has made objective comparisons of published cases difficult and has interfered with an established consensus regarding diagnosis and therapeutic modalities. The purpose of this study was to clarify the situation by reviewing the records of all children who had intestinal vascular anomalies who were referred to our institution from 1975 to 1995. Thirteen lesions were identified in nine children (five boys and four girls). The median age at clinical onset was 8 years. Only two patients presented with a complex syndrome (Klippel-Trenaunay, 1; Osler-Rendu-Weber, 1). Diagnosis, location, and extension of these anomalies was only possible by angiography, which indicated that seven patients had isolated venous malformations and two had arteriovenous malformations. Because the lesions did not involve the serosa, intraoperative localization was a major problem. The main findings were a few slightly dilated mesenteric veins. Treatment was conservative in four children and surgical in five. Pathological findings on resected bowel demonstrated dilated and abnormal veins in the mucosa and submucosa. Selective angiography should not be delayed in patients with gastrointestinal bleeding if results of all other investigations are negative. Because these lesions are rarely recognizable on operative inspection, precise preoperative angiographic localization of intestinal vascular anomalies is essential to allow for a safe and limited resection of the involved bowel segment. Based on a better understanding of the natural history of these lesions, a classification of vascular anomalies of intestines in children is proposed.

Adolescent↗
PubMed1997

Mesenteric adenitis caused by Yersinia pseudotuberculosis presenting as an abdominal mass.

Infection by Yersinia pseudotuberculosis has become of increasing pathological importance. Patients normally present with symptoms similar to those of appendicitis, due to mesenteric adenitis. We present the case of 3 patients infected by Yersinia pseudotuberculosis who in addition to fever and abdominal pain had a palpable abdominal mass, so great was the enlargement of the mesenteric nodes. In 2 patients a laparotomy was carried out, followed by biopsy of a mesenteric lymph node. The diagnosis of Yersinia infection was confirmed by bacterial culture of the biopsied material and also by serology. In the third patient, serological studies and ultrasonic imaging of the abdomen led to early diagnosis and surgery was avoided. We suggest that a diagnosis of mesenteric adenitis due to Yersinia pseudotuberculosis should now be considered in all patients presenting with an abdominal mass, and in whom there is an appropriate clinical and epidemiological history. The diagnosis should be confirmed by abdominal ultrasound (alternatively Computerised Axial Tomography or Magnetic Resonance Imaging) and serological studies. In this way, unnecessary surgery can be avoided.

Adolescent↗
PubMed1996

Cell-based therapy of acute liver failure: the extracorporeal bioartificial liver.

The need for an alternative treatment to orthotopic liver transplantation for acute liver failure is a major issue, and systems capable of temporarily providing liver functions are being actively tested. Liver assist devices based on detoxication by dialysis or hemoperfusion through various membranes or cartridges proved to be inefficient because of their lack of metabolic function. An extracorporeal hybrid bioartificial liver might be an appropriate treatment, since it can provide liver-specific functions, maintain the patient alive, and allow spontaneous recovery of the patient's own liver or act as a bridge toward liver transplantation. Many devices have been proposed, including flat culture substrates, hollow-fiber bioreactors, or microcarriers, using xenogenic hepatocytes or hepatoma cell lines. Various drawbacks of these devices led us to attempt to develop a reliable extracorporeal bioartificial liver based on alginate bead-entrapped hepatocytes. This system was used successfully for the correction of the Gunn rat genetic defect, which results in lack of bilirubin conjugation. The development of this system for clinical purposes requires large yields of functional hepatocytes. We have isolated normal porcine hepatocytes by collagenase perfusion of the liver. Cells were immobilized in membrane-coated alginate gel beads, which were subsequently inoculated into a bioreactor. Porcine hepatocytes expressed liver-specific functions at high levels, particularly protein neosynthesis and enzymatic activities involved in detoxication and biotransformation processes. In addition, hepatocytes entrapped in coated alginate beads were isolated from immunoglobulins. This system represents a promising tool for the design of an extracorporeal bioartificial liver in human beings.

Animals↗
PubMed1996

[A step towards a bioartificial liver: temporary extracorporeal replacement using isolated hepatocytes].

The mortality rate of fulminant hepatic failure is about 80%. Besides orthotopic liver transplantation, specific therapies are not currently available. Indeed, not only removal of toxins is required, by means of dialysis or hemoperfusion, but specific hepatic functions must be provided to allow spontaneous liver regeneration or as a bridge before liver transplantation. Treatment with an extracorporeal bioartificial liver is an attractive approach. This system was successfully used for the correction of the Gunn rat genetic defect which results in the lack of bilirubin conjugation. The development of this system for clinical purpose requires both a large yield of functional hepatocytes and their immunoprotection in an appropriate device. We have isolated normal porcine hepatocytes by collagenase perfusion of the liver; cells are subsequently entrapped within membrane-coated alginate beads which are inoculated in a bioreactor. Plasma from an animal undergoing fulminant hepatic failure by end-to-site portocaval shunt and whole porta hepatic tightening circulates within the bioreactor. Porcine hepatocytes express liver-specific functions at high levels, particularly secretion of plasma proteins and several enzyme activities involved in the detoxication and biotransformation of xenobiotics. In addition, hepatocytes are immunoseparated from circulating immunoglobulins. Ethical concerns are discussed in the field of physiopathology, immunopathology and public health, as a prerequisite to create departments of Cell Therapy, in the near future.

Animals↗
PubMed1995

Late presenting Bochdalek hernia containing colon: misdiagnosis risk.

The case of an eleven-months-old girl is reported: she entered the intensive care unit for fever, vomiting and left pleural effusion. Abdominal echography, CT scan and colonic opacification led to the diagnosis of a colonic Bochdalek hernia. A review of the literature showed that colonic hernias are rare, with only five previous reported cases in which colon was found in the thorax. The authors emphasise that there is a high risk of misdiagnosis due to the fact that small intestine contrast studies are normal; only colonic contrasting may lead to the right diagnosis. The roles of echography and CT scan are discussed.

Colon↗
PubMed1993

Viability and function in primary culture of adult hepatocytes from various animal species and human beings after cryopreservation.

Cryopreserved hepatocytes from various animal species and human beings were tested for their ability to survive and function in primary culture. The freeze/thaw protocol primarily designed for rat hepatocytes was used with slight modifications for the cells of all other species; it consisted of suspending parenchymal cells in the Leibovitz L15 medium containing 10% fetal calf serum and 10% to 16% dimethyl sulfoxide. After transient storage at 4 degrees C cell suspensions were transferred to -20 degrees C and then to -70 degrees C before being plunged in liquid nitrogen. Hepatocytes were stored for a few weeks to 4 yr. Prolonged storage did not augment loss of cell viability and function. Cell viability after thawing was estimated by the trypan blue exclusion test, and attachment efficiency to plastic was estimated by measuring intracellular lactate dehydrogenase content. Similar values were obtained for most species tested; after cryopreservation cell viability and attachment were decreased by 10% to 25% and by 40% to 50%, respectively. A lower attachment rate was found with dog hepatocytes. Total cytochrome P-450 and protein synthesis were compared in fresh and cryopreserved cells from four species after 4, 24, 48 or 72 hr of culture. Similar values were found in both cells after 24 or 48 hr of culture. In addition, drug-metabolizing activities were measured in human hepatocytes from five donors. In most cases phenacetin deethylation activity was decreased whereas procainamide N-acetylation and paracetamol sulfoconjugation and glucuronidation were increased in cryopreserved cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Congenital intrahepatic arterio-portal fistula: diagnostic and therapeutic aspects].

The authors report the case of a 4 month old child presenting with a congenital arteriovenous fistula of the left hepatic lobe, revealed by a melaena. Doppler ultrasonography and angiography showed a voluminous vascular malformation fed by a left hepatic artery and fistulized in the portal vein. The therapeutical approach was first palliative, by ligature of the left hepatic artery which proved unsuccessful and resulted in re-permeation of the malformation through a right hepatic artery. Two embolization procedures were then attempted, without success. A left hepatectomy was then performed to remove the malformation. The main event of outcome was the secondary occurrence of a portal cavernoma, with persistent splenic segmentary portal hypertension, and oesophageal varicosity. This case report is the occasion for a literature review on congenital arteriovenous fistulae in the portal region, and for a discussion on therapeutical modalities.

Arteriovenous Fistula↗
PubMed1990

[Anterior rectal duplication. Value of ultrasonic diagnosis].

A case of neonatal anterior rectal duplication is reported. Abdominal ultrasonography revealed a prerectal cystic mass. The different types of rectal duplications and the main differential diagnosis are described. Mechanical obstruction and neoplastic risk make early surgery necessary.

Cysts↗
PubMed1988

Primary megaureter in the neonate with prenatal or postnatal diagnosis.

Twenty-nine cases of primary megaureter diagnosed before the age of 3 months are grouped in this diagnostic and therapeutic study. Seventy-five per cent were discovered by antenatal sonography due to the presence of pelvicalyceal dilatation without localising precisely the position of obstruction, twenty-five per cent were detected by the occurrence of early urinary tract infection. Four patients were operated during the first few months. 2 diversions and 2 reimplantations. Fifteen including the 2 with early diversion were submitted to later reimplantation at the average age of 15 months. 12 patients were treated conservatively by antibiotics and regular supervision. The respective results of the operated and non-operated patients were evaluated comparing the initial dilatation and the last IVU using the classification of Beurton. Regardless of the marked initial dilatation, significant spontaneous regression or complete resolution were often seen during the first year of follow-up. Thus surgery should be deferred initially even for the severely dilated forms, except in a few critical cases where a diversion is indicated. Reimplantation should be deferred for some months unless deterioration is noted, or performed only after one year or 18 months if regression is insufficient, thus optimising operative conditions.

Child, Preschool↗
PubMed1987

[Tumors of the liver secondary to androgen therapy. Apropos of 2 cases in children].

The authors report 2 cases of hepatocellular tumour in children treated with anabolic androgens for aplastic anemia. In both cases, the presentation was by a picture of acute abdomen due to hemoperitoneum caused by tumour rupture. In the first case, there was multiple hepatic adenomas necessitating right hepatic lobectomy. The second infant had a single tumour of segment IV treated by simple excision of the tumour. It was a hepatocellular-carcinoma. Follow-up for one year after the initial operation showed no signs of recurrence in both infants. The review of the literature permitted us to find 48 other cases of hepatocellular tumour secondary to androgen therapy. In order of frequency, the hepatocellular-carcinoma is the most frequent and it is usually single; followed by the adenoma which is usually multiple. The other types of tumours are rare: focal nodular hyperplasia, angiosarcoma and cholangiocarcinoma. The hepatocellular-carcinoma and adenoma have some characteristic features: spontaneous regression may occur after withdrawing of androgens; the risk of rupture is important; their evolution is almost always favorable despite of a severe histopathological picture; the alpha-foeto-protein is nearly always negative; and the metastasis are exceptional. The hepatocellular-carcinomas associated with androgen therapy are probably just adenomas with marked dysplasia, but their long term malignant potential remain unknown. Except in case of rupture, surgical intervention should be postponed until the effect of discontinuing the hormonal therapy is assessed, because of the potential for spontaneous regression. The administration of antineoplastic chemotherapeutic agents should be reserved for the tumours showing evidence of malignancy.

Adenoma↗
PubMed1986

[Prenatal diagnosis of ovarian cysts].

The authors report 10 cases of ante-natally diagnosed ovarian cysts. Ultrasonography greatly contributed to the diagnosis of this condition rarely described before. These cysts are usually follicular cysts. Physiopathological explanation still remain unclear: excessive fetal gonadotrope activity, enzymatic abnormality of the theca interna, abnormal stimulation by the mother's HCG are the main hypothesis. Ultrasonographic prenatal diagnosis is based on the discovery of an intra-abdominal round liquid area in a female fetus with normal kidneys and bladder. Obstetrical management is very simple: observation and vaginal delivery. After birth, diagnosis is assessed by clinical examination and ultrasonography which may be able to recognize a possible torsion (intracystic fluid septation). Treatment is conditioned by two facts: first these cysts are usually follicular benign lesions, second there is a high risk of complications, mainly torsion or rupture. Non-operative treatment and observation can be justified for very small cysts which have low risk of torsion. Laparotomy confirms the diagnosis: regarding non complicated cysts, surgery must be as conservative as possible: cystectomy is often feasible, leaving a laminated but functional ovary. Percutaneous puncture under ultrasonography could be considered.

Female↗
PubMed1985

[Primary perirenal suppurations in children: surgical or percutaneous drainage?].

Renal and perirenal staphylococcal suppurative processes are rare since antibiotic era. Three cases are reported. Gram negative organisms are nowadays the most prevalent bacterial species: a urinary tract disease must then be suspected. Early diagnosis is easier with recent event of new imaging techniques. (Ultrasonography and computerized tomography). Percutaneous drainage with the help of antibiotics is the treatment of choice: it is actually a very safe and efficient procedure.

Adolescent↗
PubMed1985

[Traumatic rupture of the aortic isthmus in a child, revealed by paraplegia].

After a severe polytraumatism, a 14 year-old boy presents paraplegia without vertebral lesion. Angiocardiography showed rupture of aortic isthmus. Surgical treatment resulted in successful outcome. The authors insist on the rarity of traumatic rupture of aorta in children and or the particularity of the diagnosis revealed by paraplegia.

Adolescent↗