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Biomedical subjects

B Nordlinger

Publications and source records attributed to B Nordlinger.

At least 73 records · Page 4Linked to original sources
PubMed1996

[A good model of acute hepatic failure: 95% hepatectomy. Treatment by transplantation of hepatocytes].

The aim of this study was to develop in rats, a model of acute hepatic failure that mimics human fulminant hepatitis and to study the effect on survival of transplantation of isolated hepatocytes. This study showed that the mortality after 90% hepatectomy was reduced by the sole correction of hypoglycemia. On the other hand, 95% hepatectomy appeared as a reliable and reproductable model, associated with a period of hepatic coma, a deep disorder of coagulation, and a high mortality rate (> 80%) despite correction of hypoglycemia. In this model of acute hepatic failure, intraperitoneal transplantation of encapsulated isolated hepatocytes significantly reduced the mortality rate from 80% in the control groups to 31% in the transplanted group. A complete regeneration of the native liver was observed in all rats surviving. All animals survived after explantation of the hollow fibers. Well preserved hepatocytes were observed in hollow fibers two months after transplantation.

Animals↗
PubMed1995

Neoplastic progression of human colorectal cancer is associated with overexpression of the stromelysin-3 and BM-40/SPARC genes.

The interaction of neoplastic cells with the extracellular matrix is a critical event for the initiation of cancer invasion and metastasis. This study was designed to evaluate the potential implication of stromelysin-3 (ST3), a newly identified member of the matrix-degrading metalloproteinase family, and of BM-40/SPARC, a glycoprotein associated with the extracellular matrix, during the progression of human colorectal cancers. We analyzed the relative abundance of ST3 and BM-40/SPARC transcripts by Northern blot, and their distribution by in situ hybridization, in normal mucosa, benign adenomas, and primary colorectal adenocarcinomas and their liver metastases. The ST3 and BM-40/SPARC transcripts were overexpressed in primary colorectal cancers and their liver metastases compared to non-neoplastic mucosa. These transcripts were localized in stromal fibroblasts adjacent to the neoplastic foci. Overexpression of ST3 correlated with the progression of human colorectal tumors toward local invasion and liver metastasis. Induction of these genes also occurred in diverticulitis and digestive neoplasms such as gastric and esophageal carcinomas.

Colorectal Neoplasms↗
PubMed1995

Permeability and biocompatibility of a new hydrogel used for encapsulation of hepatocytes.

A new high-water-content (83%) and highly permeable anionic polyelectrolyte hydrogel was obtained by phase inversion of a polymer solution containing 6% polyacrylonitrile-sodium methallylsulphonate, 91% dimethylsulphoxide and 3% physiological saline solution. Hydrogel-based hollow fibres (HFs) were fabricated with a co-extrusion apparatus in collaboration with Hospal (France). HFs have an internal diameter of 800 microns and a wall thickness of 100 microns. Experimental results demonstrated that hydrogel-based HFs were permeable to albumin (mol. wt 69,000) and human immunoglobulin G (150,000), but were impermeable to immunoglobulins A (170,000) and M (900,000) after 24 h of diffusion. In vitro, the viability of isolated rat hepatocytes injected into the HFs was 64 +/- 6% after 10 d versus 30 +/- 5% for hepatocytes cultured in Petri dishes (P = 0.0001). Under these conditions, the amount of albumin released by encapsulated hepatocytes was 12 +/- 3 micrograms/24 h/10(6) cells at day 10, whereas at that time no albumin was released by hepatocytes cultured in Petri dishes. In vivo, histological study of hydrogel HFs implanted up to 6 wk in the peritoneum of rats revealed a low inflammatory tissue reaction without giant multinucleate cells in the foreign tissue, which decreased after the third week. The survival rate of encapsulated hepatocytes was over 85% 45 d after transplantation in the peritoneum of syngeneic Lewis rats. Therefore, this hydrogel demonstrates highly favourable properties for encapsulation of hepatocytes with regard to its biocompatibility, permeability and ability to maintain hepatocytes in a functional state for prolonged periods.

Analysis of Variance↗
PubMed1995

Overexpression of nm23-H1 and nm23-H2 genes in colorectal carcinomas and loss of nm23-H1 expression in advanced tumour stages.

Although a reduced expression of nm23 has been shown to correlate with a high metastatic potential in some human cancers, in colorectal cancers, conflicting data have been reported. As there are two homologous genes, nm23-H1 and nm23-H2, which encode the A and B subunits of nucleoside diphosphate kinase, efficient and simplified techniques were designed to selectively study nm23-H1 and -H2 expression in 35 colorectal cancers at both the protein and mRNA levels by immunoblotting, immunohistochemistry, and reverse transcription polymerase chain reaction (RT PCR) using specific antibodies and primers. Nm23-H1 and Nm23-H2 proteins were overexpressed in tumours compared with adjacent mucosa. This overexpression was lost, however, in some advanced cases: 89% and 81% of TNM (tumour, node, metastases) stages 0-II showed Nm23-H1 and -H2 overexpression, respectively, which significantly differed from 47% and 38% of stage III-IV tumours. Similar results were seen with nm23-H1 mRNA. Heterogenous labelling of tumoral cells was seen by immunohistological staining. This suggests a dichotomy: an overexpression of nm23-H1 and -H2 linked to early stages of cancer and a loss of nm23-H1 overexpression seen in more advanced stages. Therefore specific nm23-H1 determination should be evaluated as a prognostic factor in human colorectal carcinoma.

Adenocarcinoma↗
PubMed1995

Transplantation of allogeneic hepatocytes without immunosuppression: long-term survival.

BACKGROUND: Hepatocyte transplantation could be an alternative to whole liver transplantation. Allogeneic hepatocytes are rejected if transplanted without immunosuppression. The aim of this study was to transplant allogeneic hepatocytes in the peritoneum and to protect them from rejection by encapsulation in a new semipermeable membrane. METHODS: Rat hepatocytes were encapsulated in hydrogel-based hollow fibers, obtained from AN69 copolymer, before being transplanted into the peritoneum of rats. Outcome of allogeneic hepatocytes encapsulated in hollow fibers was compared with that of syngeneic hepatocytes encapsulated in hollow fibers, with that of free allogeneic hepatocytes, and with allogeneic hepatocytes encapsulated in hollow fibers left open. Cell viability was assessed by erythrosin exclusion, structure by electron microscopy, and function by albumin release. RESULTS: Up to 90 days, viability of allogeneic hepatocytes in hollow fibers was greater than 80%. The structure remained normal at electron microscopy. Albumin release was 16.5 +/- 0.3 micrograms/24 hr/10(6) hepatocytes (day 15), 14.2 +/- 2.0 micrograms/24 hr/10(6) hepatocytes (day 30), 8.8 +/- 0.1 micrograms/24 hr/10(6) hepatocytes (day 60), and 11.4 +/- 0.3 micrograms/24 hr/10(6) hepatocytes (day 90). Free hepatocytes and hepatocytes in hollow fibers left open did not survive at day 15. CONCLUSIONS: Viability and function of encapsulated allogeneic hepatocytes were maintained up to 90 days after transplantation, without immunosuppression.

Acrylic Resins↗
PubMed1995

Overexpression and amplification of the met/HGF receptor gene during the progression of colorectal cancer.

The c-met oncogene encodes the receptor for hepatocyte growth factor/scatter factor, a potent mitogen for epithelial cells that also promotes cell motility and invasiveness. We have studied the changes of c-met gene expression that occur during the progression of colorectal tumors. Sixteen adenomas, 123 primitive carcinomas, and 25 liver metastases were examined. In several instances it was possible to compare same-patient samples of normal colon mucosa against primary tumor and primary carcinoma against synchronous metastasis. The expression of the c-met gene was increased from 5- to 50-fold in about 50% of tumors, at any stage of progression, and in 70% of liver metastases. Overexpression was associated with amplification of the c-met gene in only 10% of carcinomas, but in 8 of 9 metastases examined. These data suggest that overexpression of the c-met oncogene contributes a selective growth advantage to neoplastic colorectal cells at any stage of tumor progression. Moreover, amplification appears to give a further selective advantage for the acquisition of metastatic potential.

Adenoma↗
PubMed1994

[Treatment of metastases of colorectal cancers].

Important advances have been made in the management of advanced colorectal cancers during the past decade, even though prognosis remains poor. Quality of life, and sometimes overall survival have been increased. Surgery is the only potentially curative treatment of liver metastases from colorectal cancer. Radiation therapy is useful as a palliative local treatment for painful bone metastases or compressive nodes. Chemotherapy, still palliative, has been shown to improve the quality of life. Although 5-fluorouracil remains the drug of reference, various routes and schedules of administration (continuous infusion, hepatic artery infusion, chronotherapy) and biomodulation, mainly by folinic acid and methotrexate have led to a significant improvement in response rates.

Colorectal Neoplasms↗
PubMed1994

Survival benefit of repeat liver resections for recurrent colorectal metastases: 143 cases. Association Francaise de Chirurgie.

PURPOSE: Resection is the only chance for cure in patients with colorectal liver metastases (LM). Five-year survival rates are close to 25%. Unfortunately, recurrences occur in most patients. Some recurrent LM are technically resectable. The aim of this study was to determine the risks and benefits of repeat resections for recurrent LM. PATIENTS AND METHODS: Data from 130 patients who received 143 repeat liver resections for recurrent LM were collected. In 116 patients, only the liver was involved, while 14 had both liver and extrahepatic recurrences. RESULTS: In the first group, the operative mortality and morbidity rates were 0.9% and 24.7%, respectively. Two- and 3-year survival rates were 57% and 33%, respectively. Recurrences were observed in 66% of patients. Twelve patients underwent a third hepatectomy for recurrence. The mortality rate was nil, and the mean survival time was 12.5 months. In the group with liver and extrahepatic metastases, the operative mortality and morbidity rates were 0% and 25%. The mean survival time was 16 months. Eleven patients died and 13 had recurrences during the follow-up period. CONCLUSION: Some hepatic recurrences after surgical excision of colorectal metastases can be resected with a low operative risk and with a long-term survival rate similar to that obtained after first resections. This emphasizes the need for a careful follow-up after hepatectomy for colorectal metastases to detect resectable recurrences.

Adult↗
PubMed1994

[Results of ileoanal anastomosis with mucosectomy and "J" pouch in hemorrhagic rectocolitis].

The aim of this study was to assess the results of ileal "J" pouch-anal anastomosis in ulcerative colitis. One hundred and fifty six patients operated on between 1983 and 1991 for ulcerative colitis were followed-up prospectively since the surgical procedure with a mean of 29 +/- 16 months (range: 6 to 92 months). There was no postoperative death. Forty-four patients (28%) presented 48 post-operative complications and 14 (9%) were reoperated. Twenty-five patients (16%) were reoperated because of a late complication. Three pouches had to be removed for untreatable fistulas which appeared to be related to a Crohn's disease in 2 cases; the reestablishment of a diverting loop ileostomy was mandatory in 2 further patients for anoperineal sepsis. The mean stool frequency at 1 year was 4.5 +/- 1.9; 40% of patients did not have nocturnal stooling. Daytime and nighttime continence were normal in 90.7% and 77.5% of cases respectively, 87% of patients considered their social life improved by the surgical cure of the disease. The results observed 5 years after the surgical procedure in 37 patients were similar to those observed at 1 year. Twenty-five patients (16%) presented one or several episodes of pouchitis, including 5 cases of chronic pouchitis. It is concluded that the treatment of ulcrerative colitis, ileal "J" pouch-anal anastomosis, is a safe and effective procedure which provides good functional results.

Adolescent↗
PubMed1994

[Transplantation of allogeneic hepatocytes without immunosuppression: long term survival].

UNLABELLED: Hepatocyte transplantation could be an alternative to whole liver transplantation. Allogeneic hepatocytes are rejected if transplanted without immunosuppression. The aim of this study was to transplant allogeneic hepatocytes in the peritoneum and to protect them from rejection by encapsulation in a new semi-permeable membrane. METHODS: Rats hepatocytes were encapsulated in hydrogel-based hollow fibers, obtained from AN69 polymer, before being transplanted into the peritoneum of rats. Outcome of allogeneic hepatocytes encapsulated in hollow fibers was compared to that of free allogeneic hepatocytes. Cell viability was assessed by erythrosine exclusion, morphology by electronic microscopy and function by albumin release. RESULTS: Up to 90 days, viability of allogenic hepatocytes in hollow fibers was above 80%. The morphology remained normal at electronic microscopy. Albumin release was 16.5 +/- 0.3 (day 15), 14.2 +/- 2.0 (day 30), 8.8 +/- 0.1 (day 60) and 11.4 +/- 0.3 micrograms/24 h/10(6) hepatocytes (day 90). Free hepatocytes did not survive at day 15. CONCLUSION: Viability and function of encapsulated allogeneic hepatocytes were maintained up to 90 days after transplantation, without immunosuppression.

Animals↗
PubMed1993

[Biliary scintigraphy. Application to the study of chronic cholestasis].

In a sample population of 49 subjects (7 normal, 42 with various liver diseases), the parameters of the activity/time curve of trimethylbromo-iminodicetic acid (TBIDA) biliary scintigraphy were compared with the clearances of bromosulfophthalein (BSP) and indocyanine green (ICG). Correlation between T1/2 and P2 BSP slope was r = 0.50 (n = 33; P < 0.01). Correlation between Tmax TBIDA and fractional ICG clearance (P ICG) was r = 0.65 (n = 44; P < 0.001). In 23 cases of chronic cholestasis correlations remained significant (T1/2-P2 BSP: r = 0.53; n = 17; P = 0.02; Tmax-P ICG: r = 0.59; n = 17; P < 0.01). A prospective study of 11 cases of chronic intrahepatic cholestasis (primary biliary cirrhosis 8, primary sclerosing cirrhosis 3) showed that these two types of tests varied concordantly. Biliary scintigraphy, therefore, seems to be an accurate method to explore hepatocellular mass (degree of hepatic insufficiency) and cholestasis. The validation of biliary TBIDA scintigraphy as hepatobiliary functional exploration method and the possibility to study intrahepatic "regions of interest" defined a priori would make it possible to obtain a functional estimate of hepatic segments or lobes, for example before wide liver excision.

Aged↗
PubMed1993

Repeat liver resection for recurrent colorectal metastases.

Sixteen patients underwent 18 repeat liver resections for recurrence of colorectal hepatic metastases that had been previously resected. Only minor liver resection had been undertaken at the first operation; three were palliative. The second operation was major hepatectomy in ten patients, minor resection in five and orthotopic liver transplantation in one. In one patient, lung metastases were resected before the second operation. One repeat hepatectomy was palliative. After partial liver resection, there were no deaths and complications were observed in six of 15 patients. One patient died 2 weeks after liver transplantation. After the second resection, 2-, 3- and 5-year survival rates were 67, 57 and 30 per cent; the mean survival time was 33 (range 8-93) months. Tumour recurrence was observed in 11 of 14 patients 4-32 (mean 13) months after a second curative liver resection; two patients received a third curative operation for recurrent liver metastases. After the second curative hepatectomy, seven patients died from disease after a mean of 36 (range 14-61) months and seven are currently alive at a mean of 33 (range 8-93) months. Four of these patients are free from disease 26-93 months after resection and three are alive with recurrence. Repeat hepatectomy for recurrent colorectal metastases can prolong survival in selected patients and has low operative risk.

Adult↗
PubMed1993

Function of ileal J pouch-anal anastomosis in patients with familial adenomatous polyposis.

Pouch function after proctocolectomy and ileal J pouch-anal anastomosis was assessed at 1 and 5 years in 41 patients with familial adenomatous polyposis. The mean(s.d.) stool frequency per 24 h decreased from 4.4(1.7) to 3.9(1.8) (P < 0.05), the mean(s.d.) nocturnal stool frequency fell from 0.6(1.0) to 0.3(0.6) (P < 0.05), and the number of patients having nocturnal bowel movements decreased from 16 to seven (P < 0.05). At 5 years, only one patient still followed a strict diet (versus ten at 1 year, P < 0.05) and only two needed antidiarrhoeal medication (versus ten at 1 year, P < 0.05). There were no episodes of pouchitis or late reservoir-related complications. The function of ileal pouch-anal anastomosis improves over time in patients with familial adenomatous polyposis.

Adenomatous Polyposis Coli↗