Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon

We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose- dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.      

Unusual Longevity Without Surgical Intervention in Complete Transposition of the Great Arteries

A case of unusual longevity to the age of 58 years is reported for a female patient with complete transposition of the great arteries. The association with a wide atrial septal defect with intact interventricular septum may have contributed to the long survival without surgery. Factors determining intercirculatory mixing and systemic oxygen saturation may be the high pulmonary flow, the location of the anatomic communication, sufficient hemoglobin concentration to allow an adequate level of systemic resistance and recirculated systemic flow, and the belated development of pulmonary vascular disease.     

Isolated hyperthermic liver perfusion with high dose tumor necrosis factor alpha in pigs: an experimental study in preparation of clinical Use

Isolated hyperthermic perfusion of the liver was performed for 45 min in 27 pigs via hepatic artery and portal vein at mean inflow temperatures between 40.7 and 41.2 degrees C. In two study groups B and C (n = 9 pigs each) 50 microg recombinant human tumor necrosis factor-alpha (rhTNFalpha) per kg body weight were added to the perfusate, whereas in a control group A liver perfusion was done without rhTNFalpha. Before reperfusion the livers were washed out with Ringer's solution in all groups followed by a protein solution in group C. At 30 and 60 min after reperfusion the maximum systemic rhTNFalpha concentrations were significantly higher in group B with 68 and 61 ng/ml compared to 14.5 and 14.9 ng/ml in group C (p < 0. 05). Mean systemic porcine TNFalpha concentration was significantly higher in group B (217 pg/ml) compared to group C (50 pg/ml) 30 min after reperfusion (p = 0.012). Survival was 7/9 in group A and C and only 2/9 in group B with 6/7 pigs dying due to severe cardiopulmonary failure within 12 h after operation. In surviving pigs of group A and C only mild and transient hepatotoxicity was registered. The presented study underlines the feasibility of high dose rhTNFalpha application in an isolated hyperthermic liver perfusion system. Washout of the liver with a protein solution before reperfusion reduces systemic TNFalpha levels as well as associated lethal cardiocirculatory and hepatotoxic side effects.     

Diagnosis and treatment of hepatic artery thrombosis after liver transplantation

The aim of this study was to examine the clinical presentation and time of hepatic artery thrombosis (HAT) after orthotopic liver transplantation (OLT), stressing the role of imaging modalities. Therapeutic options are described, such as retransplantation (Re-OLT), hepatic resections and revascularization procedures, focusing on complications and outcome in a consecutive series of 687 OLT. Over the period from 1986 to 1999, 687 OLT were carried out in 601 patients, 592 of whom were adults and 95 pediatric subjects. Of these operations 601 were primary OLT and 86 Re-OLT (71 I Re-OLT, 14 II Re-OLT and 1 III Re-OLT). In this retrospective study, we reviewed rejection episodes, time of HAT (early or late), possible cause of HAT, day of suspected diagnosis of HAT and day of confirmation of diagnosis. Clinical presentation, management, complications, outcome, survival rates and the need for Re-OLT were also recorded. The incidence of HAT was 2.47% (17/687). Early HAT (n = 9, < 30 days) was diagnosed 15.6 days after OLT (range: 3-25 days), whereas late HAT (n = 8, > 30 days) occurred 295.1 days after OLT (range: 38-1830 days). In two asymptomatic patients (2/17: 11.7%), HAT was discovered incidentally. Most of the patients (11/17: 64.7%) presented with increased liver function test values and fever. Relapsing bacteremia occurred in 7/17 cases (41.1%), whereas a biliary stricture and biliary leak were diagnosed in 3/17 (17.6%) and in 1/17 patients (5.8%), respectively. Fulminant hepatic failure was the clinical presentation in 2/17 cases (11.7%). In one case the clinical presentation was acute and chronic rejection (1/17: 5.8%). Intrahepatic abscesses were diagnosed in one case (1/17: 5.8%), as well as an intrahepatic haemorrhage (1/17: 5.8%). Doppler ultrasound (DUS) correctly revealed HAT in 9 of the 17 patients (52.9% sensitivity). In 8 of the 9 patients (88.8%) in whom HAT was diagnosed by DUS, angiography was also performed to confirm the diagnosis. Overall, angiography detected HAT in 14/17 patients (82.3% sensitivity). HAT management consisted of immediate Re-OLT in 6 patients 6.8 days (range: 3-12 days) after diagnosis. Delayed Re-OLT was performed in 6 patients 529.1 days (range: 68-1920 days) after diagnosis. The overall retransplantation rate was 70.5% (12/17). Two patients died despite undergoing intraarterial urokinase treatment. Three grafts were salvaged, but suffered biliary stricture due to ischemic cholangitis and underwent hepatico-jejunostomy. A II Re-OLT was carried out in 4 of 12 patients (33.3%). The overall mortality rate was 41.1% (7/17). One-year and 3-year overall survival rates were 58.8% (10/17) and 47.0% (8/17), respectively. Both 5- and 10-year overall survival rates were 11.7% (2/17). Although the results of OLT have improved dramatically over the past few years, HAT is still associated with substantial morbidity, a high incidence of graft failure and high mortality rates. The use of DUS to screen for HAT has permitted earlier diagnosis, but early angiographic evaluation of the hepatic arteries is still needed for accurate diagnosis of HAT and remains the gold standard. Retransplantation is the definitive solution for HAT in the majority of cases, though it is essentially the patient's clinical condition that dictates the form of management.