In utero allotransplantation of fetal hepatocytes into a preimmune fetus could be used in early treatment of many inherited hepatic metabolic diseases. This study was designed to assess the tolerance to hepatocyte transplantation and to test the feasability and toxicity of such an injection in a primate model. Fetal hepatocytes were obtained from two 120-day-old Macaca mulatta fetuses and cryopreserved. They were thawed, cultured in vitro, and transduced with a recombinant retrovirus expressing beta-galactosidase. Transduction efficiency was 75-85%. Three unrelated fetuses (90, 100, and 104 days old) were each given 1-2 x 10(7) transduced cells via the umbilical vein. This caused vasospasm and severe bradycardia. Two fetuses died in the 48 hours after transplantation; the third survived and was killed at the end of gestation. No evidence of the infused cells was found. Three fetuses (90 days old) were, therefore, given 3-4 10(7) hepatocytes by direct intrahepatic injection. All the fetuses survived without side effect. Donor cells were not apparent from histochemical staining and PCR reactions. There was no evidence of inflammatory reaction. These findings indicate that the protocole could be improved by increasing the number of transplanted cells and using specific hepatic promoters in the retroviral vectors to achieve an effective postnatal chimerism.

Animals↗

PubMedDate not supplied

Effect of the oral administration of branched chain amino acids on hepatic encephalopathy in the rat.

The aim of this study was to investigate the effect of oral administration of branched-chain amino acid (BCAA)-enriched diets after portacaval shunt (PCS) in rats. Fifty-one Sprague-Dawley male rats (200 gm) underwent PCS and 55 a sham operation. Half of the animals received BCAA 142 mg per day through a gastric tube; the other half underwent a sham procedure. Sleep disturbances were evaluated at 7, 14, and 28 days postoperatively by measurement of the excitability of the reticular brain-stem formation during the slow-wave sleep and paradoxical sleep. Animals were killed at the same intervals and liver/body weight ratio, plasma, and brain amino acids, brain norepinephrine, brain serotonin, 5-hydroxyindolacetic acid and histamine were measured. Each group of animals was matched with a similar group of sham-operated rats, i.e., receiving or not receiving BCAA. After PCS (as compared to sham-operated animals) a significant hyperexcitability of the reticular brain-stem formation was found during the slow-wave sleep. The liver/body weight ratio was significantly lower. Tryptophan (free tryptophan in the plasma), phenylalanine, tyrosine, and histidine increased in the plasma and the brain. Leucine and isoleucine were decreased in the plasma. After PCS, an initial decrease at 7 days postoperatively of brain norepinephrine and blockade of the intracerebral metabolism of tryptophan were observed. These changes were transient and progressively disappeared at 14 and 28 days postoperatively. Brain histamine remained at a very high level through the experiment. A good correlation was demonstrated between modification of the sleep disturbance and tryptophan (or 5- hydroxyindolacetic acid) and histamine brain levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMedDate not supplied

Role of surgical therapy in management of intractable ascites.

Almost 10% of patients with cirrhosis and ascites develop intractable ascites. When large-volume paracentesis fails to relieve ascites, patients may be submitted to one of the three following surgical options: portosystemic shunting, peritoneovenous shunting, or liver transplantation. Portosystemic shunting is efficient in clearing ascites, but it is associated with a high rate of encephalopathy and liver failure. The indications for portosystemic shunting are therefore limited for treatment of intractable ascites and should be performed only in patients with good liver function in whom all other treatments failed. Peritoneovenous shunting has been associated with a high rate of early complications and valve obstruction. Improvements in perioperative care and in the material used have greatly reduced the operative risks and increased the patency rate. Mortality remains high in patients with severe liver failure or with a history of spontaneous bacterial peritonitis or variceal bleeding. Peritoneovenous shunting should not be done when these risk factors are present. In the absence of such risk factors, peritoneovenous shunting is a good procedure and may provide definitive relief of ascites and long-term survival in more than 50% of the operated patients. In patients with poor risk factors liver transplantation may be preferable, and the onset of intractable ascites in a patient with a severely compromised liver should trigger the indication of liver replacement.

Ascites↗

PubMedDate not supplied

Anomalous origin of the left coronary artery from the pulmonary trunk and its relationship with the morphology of the cardiac semilunar valves in Syrian hamsters.

The conditions of the aortic and pulmonary valves and the arrangement in the origin of the coronary arteries were studied in 247 Syrian hamsters belonging to a single family subjected to high endogamous pressure. Most specimens (n = 216) were examined using a stereomicroscope. The remaining 31 were studied histologically. In 110 specimens both cardiac semilunar valves were normal. The aortic valve was bicuspid and the pulmonary valve was normal in 79 animals, while a normal aortic valve and a bicuspid pulmonary valve occurred in 37. In the remaining 21 specimens both semilunar valves were bicuspid. In 34 cases, the left coronary artery originated from the pulmonary trunk. Statistical analyses indicate that there is no significant relationship between the bicuspid condition of the pulmonary valve and the fact that a coronary artery arises from the pulmonary trunk. On the other hand, they substantiate that the frequency of this coronary artery anomaly significantly increases when the aortic valve is bicuspid. The present findings agree with the hypothesis that abnormal migration of the neural crest cells may be responsible for the combined occurrence of bicuspid aortic valve and anomalous origin of the left coronary artery from the pulmonary trunk. In addition, they suggest that the neural crest cells involved in the formation of the pulmonary valve diverge from those migrating into the aortic valve and those imposing spatial order upon the development of the proximal coronary arteries.

Animals↗

PubMedDate not supplied

Neoomphaloplasty: An old and new technique.

The authors review several proposed approaches to neoomphaloplasty, with emphasis on the use of three flaps anchored to the fascia, allowing the exposed central area to heal unaided. The procedure is straightforward and can be performed singly or during abdominoplasty. Results are both cosmetic and natural-looking.

Bladder Exstrophy↗

PubMedDate not supplied

[Detection of alcohol-related problems in primary care].

The results of a survey of primary health care physicians in order to know which factors are associated with the efficacy in the detection and treatment of patients with alcohol-related problems are analyzed in this article. The number of diagnosed patients is related with previous formal education on alcohol-related problems of primary health care physicians. Primary health care physicians are very interested in this issue, but they don't feel satisfied nor gratified with their work with this type of patients. Gratifying feelings are directly related to previous formal education, and those who feel gratified diagnose more patients. Needs for formal education must be accompanied by profound organizational changes in the coordination of actions between primary health care, specialized services and social care.

Alcoholism↗

PubMedDate not supplied

Resection of hepatocellular carcinoma.

The majority of hepatocellular carcinoma occurs in patients with liver cirrhosis. Although the tumors are often discovered at an early stage during surveillance of these patients, the underlying cirrhosis renders the surgery more difficult and exposes the patients to higher rates of postoperative morbidity and mortality than occurs in other types of liver surgery. Over the past 20 years surgeons have developed new surgical procedures and techniques to firstly reduce the unnecessary resection of liver parenchyma and to decrease intraoperative blood loss. Better patient selection and understanding of prognostic factors will hopefully result in a further decrease in operative risk and postoperative recurrence. Adjuvant chemotherapy may prove effective in reducing the postoperative recurrence but at this stage surgery still remains as the best treatment for patients with recurrent tumor which is accessible to resection.

Carcinoma, Hepatocellular↗