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Biomedical subjects

D Kahn

Publications and source records attributed to D Kahn.

At least 253 records · Page 14Linked to original sources

Liver regeneration in rats treated with the antiandrogen flutamide.

Previous studies have shown that male rat liver undergoes demasculinization during hepatic regeneration after partial hepatectomy. In the present study the effect of the antiandrogen flutamide on liver regeneration was assessed. Adult male Wistar rats were treated with flutamide (2 mg/rat/day or 5 mg/rat/day subcutaneously) or vehicle for 3 days prior to and daily after partial hepatectomy. Rates of DNA and polyamine synthesis were assessed by measuring thymidine kinase and ornithine decarboxylase activities, respectively. The rate of liver growth after partial hepatectomy in the three groups was similar at all time points examined. The increases in thymidine kinase activity and ornithine decarboxylase activity after partial hepatectomy were comparable throughout the study. Thus, administration of flutamide did not influence the regenerative response after partial hepatectomy.

Animals↗

A porcine model for the study of liver regeneration.

A technique of 65% partial hepatectomy in the pig is described. Thymidine kinase activity and mitotic index were used as indices of liver regeneration. Thymidine kinase activity increased from a baseline value of 1526 +/- 256 to a maximum of 23992 +/- 4966 dpm/mg protein on the third day after partial hepatectomy. The mitotic index also increased from 0-13.3 +/- 1.66 on the third postoperative day. The indices of regeneration remained unchanged after sham operation.

Animals↗

Effect of partial portal vein ligation on hepatic regeneration.

To evaluate the effect of portal hypertension and diminished portal venous blood flow to the liver on hepatic regeneration, male rats were subjected to partial portal vein ligation and subsequently to a two-thirds partial hepatectomy. The levels of ornithine decarboxylase activity at 6 h after partial hepatectomy were greater (p less than 0.001) in the rats with prior partial portal vein ligation than in those without portal hypertension. The rats with prior partial portal vein ligation also had greater (p less than 0.005) levels of thymidine kinase activity at 48 h after partial hepatectomy than did those without portal hypertension. Hepatic sex hormone receptor activity was not affected by prior partial portal vein ligation either before or after partial hepatectomy. The reductions in both estrogen and androgen receptor activity observed in the hepatic cytosol after partial hepatectomy were similar to those observed in control animals. These data indicate that animals with portal hypertension having a diminished hepatic portal blood flow have a normal capacity to regenerate hepatic mass following a hepatic resection.

Animals↗

Liver replacement with reduced size donor organs.

End stage liver disease in children can be treated with orthotopic liver transplantation (OLT). Nevertheless, the expansion of this therapy in Europe has been limited because of the shortage of appropriate size-matched donors. One possible technical solution is the OLT of a liver graft previously reduced in size by in situ resection preceding the harvesting procedure. To study the impact of this technique we examined two different operative procedures performed on Landrace pigs. Group 1 consisted of 20 standard donor/recipient weight matched OLT. In group 2, 15 OLT were performed using right lateral and medial lobes (55% of the original donor liver). The donor/recipient weight ratio in the group was 2:1. Cold ischemia times were 90 +/- 16 min for group 1 and 98 +/- 9 min for group 2. It is emphasized that in contrast to all the other reports using resected liver grafts for OLT, the donor resection in our study was always performed in situ under normothermic conditions, preceding the harvesting procedure. This was designed to reduce the cold ischemia time. No significant technical problems were encountered. The biochemical results of group 2 pigs compared to group 1 demonstrate an analogous, postoperative course. This might be explained by regenerative stimuli acting on the resected liver tissues and enhancing their metabolic function. These data support the conclusion that resected adult donor liver grafts may be used for pediatric transplant recipients.

Animals↗

Effect of FK506 in experimental organ transplantation.

FK506 is the most potent immunosuppressive agent known. Its toxicity is substantial in dogs, minor in rats, and unknown in subhuman primates. In small doses that are nontoxic even in dogs, it can be used in synergistic combination with cyclosporine, steroids, and presumably in other drugs.

Animals↗

The role of U tube palliative treatment in high bile duct carcinoma.

Twenty-one patients with cholangiocarcinoma at the confluence of the main right and left hepatic ducts were referred to our professorial surgical unit between 1968 and 1982. All were evaluated, treated, and documented prospectively with follow-up to mid 1986. No lesion was deemed resectable. The U tube palliative bypass developed during the course of the study was used in 14 patients, and its role in treating high bile duct carcinoma was evaluated. Histologic confirmation of the diagnosis was obtained in 71% of patients. Seven patients received additional treatment with radical radiotherapy. The 30-day overall hospital mortality rate was 19%. The 1- and 2-year survival rates were 57% and 33%, respectively. The quality of survival was usually good. The need for centralized referral and treatment of these difficult patients is stressed. The case against radical resection for this lesion is presented. It is concluded that radical resection is seldom possible, and therefore the U tube palliative procedure is advocated in most patients.

Adenoma, Bile Duct↗

Does hyperprolactinemia affect hepatic regeneration independent of sex steroids?

Prolactin, administered exogenously, has been shown to be trophic to the liver, causing increases in the liver weight-to-body weight ratio. In ornithine decarboxylase activity, and in thymidine kinase activity. To investigate the effect of endogenous hyperprolactinemia on hepatic regeneration, pituitary isografts were placed beneath the renal capsule in rats 2 weeks before the rats underwent a two-thirds partial hepatectomy. Prolactin levels 2 weeks after the transplant were greater in the animals with the pituitary isografts compared with levels in controls. The increase in the liver weight-to-body weight ratio after hepatectomy was similar in the rats with pituitary transplant and the controls. However, chronic hyperprolactinemia was associated with increased basal levels of ornithine decarboxylase activity and thymidine kinase activity. Both ornithine decarboxylase activity and thymidine kinase activity increased after partial hepatectomy, and the magnitude of the changes was similar for both groups of animals. The levels of estrogen receptor activity before the partial hepatectomy and the reduction in receptor activity that follows partial hepatectomy were similar in the two groups of animals. Moreover, the levels of androgen receptor activity within the liver before partial hepatectomy and the increase in receptor activity after hepatectomy were similar in the two groups of animals. Thus, chronic sustained hyperprolactinemia has no beneficial effect on the hepatic regenerative response, despite induction of both basal ornithine decarboxylase and thymidine kinase activities.

Animals↗

Effect of 15-deoxyspergualin on experimental organ transplantation.

DSPG had a definite but relatively feeble immunosuppressive effect in rats undergoing heterotopic heart transplantation and in dogs after renal transplantation. The drug was toxic in both species, although less so in rats. In dogs, synergistic interactions with cyclosporine and steroids were not evident.

Animals↗

Surgical technique of orthotopic liver transplantation.

Although significant strides have been made in the surgical technique of orthotopic liver transplantation, numerous problems and nuisances are still encountered. Further surgical refinements will certainly evolve. The development of better preservation techniques, the use of intraoperative flowmeters, and the availability of new technologies, such as an artificial liver, should impact and advance the techniques of liver transplantation significantly and improve the overall results even further.

Adult↗

Effect of an antiandrogenic H2 receptor antagonist on hepatic regeneration in rats.

Because biochemical "feminization" of the liver in males is observed with hepatic regeneration and because the hepatic regenerative response in females is greater than that in males, the possibility that antiandrogens might potentiate liver regeneration was investigated. Before 70% hepatectomy, adult male Wistar rats were treated with cimetidine, an antiandrogenic H2 antagonist, at doses up to 10 times greater than those used clinically. Control animals received either the saline vehicle or ranitidine, an H2 antagonist without antiandrogenic properties. Treatment with cimetidine reduced the hepatic cytosolic androgen receptor content compared with ranitidine treatment. Hepatectomy caused a further reduction in androgen receptor activity in all groups. Hepatic cytosolic estrogen receptor activity was comparable in all groups throughout the study. Moreover, the rate of liver growth and the levels of ornithine decarboxylase and thymidine kinase activity induced as part of the regenerative response were similar in all groups. Thus, cimetidine, despite its ability to bind to androgen receptors, and ranitidine, an H2 receptor antagonist without antiandrogen action, do not modulate the hepatic regenerative response to a 70% partial hepatectomy.

Animals↗

Hypertrophic ileocaecal valve simulating a malignant tumour. A case report.

A patient presented with rectal bleeding which, on investigation, was though to be due to a polyp within the caecum. The benign nature of the lesion could not be established conclusively without surgical exploration. A limited right hemicolectomy was performed and examination of the specimen revealed a prominent ileocaecal valve. The problem of diagnosing this entity pre-operatively is discussed.

Aged↗