Effect of an antiandrogenic H<inf>2</inf> 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 posibility that antiandrogens might potentiate liver regeneration was investigated. Before 70% hepatectomy, adult male Wistar rats were treated with cimetidine, and 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

Orthotopic liver transplantation for massive hepatic lymphangiomatosis

Lymphangiomatosis is a rare malformation of the lymphatic system that causes severe symptoms secondary to progressive growth into or close to vital structures. A case report of liver failure related to this space-occupying intrahepatic mechanism is taken as a starting point for a discussion of the problems of liver transplantation related to large hepatomegalies. © 1988

Liver transplantation for arteriohepatic dysplasia (Alagille's syndrome)

Thirteen out of 268 children (<18 years old) underwent hepatic transplantation (OLT) for end-stage liver disease (ESLD) associated with arteriohepatic dysplasia (AHD). Seven children are alive and well with normal liver function. Six children died, four within 11 days of the operation and the other two at 4 and 10 months after the OLT. Vascular complications with associated septicemia were responsible for the deaths of three children. Two died of heart failure and circulatory collapse, secondary to pulmonary hypertension and congenital heart disease. The remaining patient died of overwhelming sepsis not associated with technical complications. Seven patients had a portoenterostomy or portocholecystostomy early in life; five of these died after the OLT. Severe cardiovascular abnormalities in some of our patients suggest that complete hemodynamic monitoring with invasive studies should be performed in all patients with AHD, especially in cases of documented hypertrophy of the right ventricle. The improved quality of life in our surviving patients confirms the validity of OLT as a treatment of choice in cases of ESLD due to AHD. © 1992 Springer-Verlag

Amelioration of normothermic canine liver ischemia with prostacyclin.

A model of hepatic ischemia was developed in dogs using a pump-driven splanchnic-to-jugular vein bypass during crossclamping of the portal triad. An LD50 was established with three hours of ischemia. PGI2 given for one hour before the ischemic insult ameliorated the ischemic injury and increased survival

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

Orthotopic liver transplantation in dogs receiving FK-506.

Ten dogs that survived the perioperative events of liver transplantation were treated with 1 mg/kg/d oral FK. Eight of the recipients lived for at least 1 month postoperatively, and seven are still alive with normal hepatic function after 35 to 65 days. The consistency and good quality of results with this difficult transplant preparation using FK, in spite of its rumored great toxicity in dogs, have highlighted the importance of further developing the drug

Improved method of porcine renal allografting for transplantation Research

This study presents a refined, reproducible, and clinically appropriate animal model of renal transplantation. A pair of kidneys are harvested from a donor pig and preserved in Euro-Collins' solution (4°C). After a set period of preservation, the allografts are transplanted to two recipient pigs. The abdomen is entered through a midline incision. The right common iliac artery and vein are dissected and bilateral native nephrectomy is performed. Each allograft is then randomly assigned and transplanted to the recipients. Three minutes before un- clamping, 100 mg offurosemide and 10 g of mannitol are given IV. Immediately after reperfusion, urine output is measured for 1 h. The allograft is biopsied and ureteroneocyslostomy is created. Cystostomy is then placed using a 16F Foley catheter. The bladder neck is ligated to secure complete diversion of urine, and the abdomen is closed in layers. This kidney transplant model allows an absolutely paired study of the kidney allograft function from the same donor and also collection of pure urine at any time postoperatively, obviating the need for metabolic cages or sedation for urinary collection. This model and its unique modifications allow various transplant studies, including organ preservation, immunosuppressive protocol, and the prevention of reperfusion injury from oxygen free radicals © 1991 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Does hyperprolactinemia affect hepatic regeneration independent of sex steroids?

Prolactin, administered exogeneously, 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

Progress towards early detection services for infants with hearing loss in developing countries

BACKGROUND: Early detection of infants with permanent hearing loss through infant hearing screening is recognised and routinely offered as a vital component of early childhood care in developed countries. This article investigates the initiatives and progress towards early detection of infants with hearing loss in developing countries against the backdrop of the dearth of epidemiological data from this region. METHODS: A cross-sectional, descriptive study based on responses to a structured questionnaire eliciting information on the nature and scope of early hearing detection services; strategies for financing services; parental and professional attitudes towards screening; and the performance of screening programmes. Responses were complemented with relevant data from the internet and PubMed/Medline. RESULTS: Pilot projects using objective screening tests are on-going in a growing number of countries. Screening services are provided at public/private hospitals and/or community health centres and at no charge only in a few countries. Attitudes amongst parents and health care workers are typically positive towards such programmes. Screening efficiency, as measured by referral rate at discharge, was generally found to be lower than desired but several programmes achieved other international benchmarks. Coverage is generally above 90% but poor follow-up rates remain a challenge in some countries. The mean age of diagnosis is usually less than six months, even for community-based programmes. CONCLUSION: Lack of adequate resources by many governments may limit rapid nationwide introduction of services for early hearing detection and intervention, but may not deter such services altogether. Parents may be required to pay for services in some settings in line with the existing practice where healthcare services are predominantly financed by out-of-pocket spending rather than public funding. However, governments and their international development partners need to complement current voluntary initiatives through systematic scaling-up of public awareness and requisite manpower development towards sustainable service capacities at all levels of healthcare delivery