Risk factors for invasive aspergillosis in living donor liver transplant recipients.

Invasive aspergillosis (IA) is a severe complication of liver transplantation. Risk factors for IA after deceased donor liver transplantation (DDLT) have been presented in several reports, but are not well established for living donor liver transplant recipients. Here, a retrospective case-control study was performed. Five cases with IA were investigated after living donor liver transplantation (LDLT) between January 1999 and December 2002 at Kyoto University Hospital. For comparison, living donor liver transplant recipients without IA were taken as controls. These patients had undergone LDLT 1 month before or after each IA case and had the same survival times as the latter. We evaluated the clinical and laboratory findings for both groups up until their demise. Patients with IA after LDLT had a very poor prognosis. By univariate analysis, risk factors for IA were preoperative intensive care unit stay (P = 0.02) and preoperative steroid administration (P = 0.02). Preoperative steroid administration for fulminant hepatitis possibly predisposed to the development of IA after LDLT.     

NASOGALLBLADDER DRAINAGE FOR MIRIZZI’S SYNDROME

The authors experienced a case of Mirizzi’s syndrome successfully treated with endoscopic nasogallbladder drainage (ENGBD). The patient was a 63‐year‐old man. He was admitted with abdominal pain and jaundice. Laboratory data indicated leukocytosis and elevation of serum bilirubin level. Abdominal ultrasound showed marked swelling of gallbladder and debris in the gallbladder, therefore, the authors strongly suspected Mirizzi’s syndrome. He had past history of acute myocardial infarction and treated with anticoagulation therapy. Then, the authors couldn’t perform surgical removal or percutaneous transhepatic drainage, and tried endoscopic transpapillary drainage. Endoscopic retrograde cholangiopancreatography revealed smooth stricture in the superior portion of common bile duct and occlusion of the cystic duct, and ENGBD was then performed. After ENGBD, his complaints, laboratory data, swelling of gallbladder and stricture of common bile duct were all remarkably improved.     

A Clinical Study for the Durability of Oxygenators on Cardiopulmonary Support

Abstract: Cardiopulmonary support (CPS) requires durability of the oxygenator. The life span of the oxygenator is affected by various clinical factors, including patient condition, perfusion condition, and equipment usage. Predictors for the durability of oxygenators were evaluated clinically in this study. Thirty-two patients, who had undergone CPS during the last 3 years in our institute were assigned to this study. Fifty oxygenators had been used (Capiox SX in 19, CB Maxima in 23, and AL-6000 in 8). Significant predictors for the durability of oxygenators were evaluated by nonparametric survival analysis and proportional hazards regression analysis. Univariate regression analysis revealed 6 significant predictors for the life span of oxygenators. These were the oxygenator type, type of centrifugal pump, acidosis with blood pH less than 7.35, base excess less than -5, blood glutamic-oxaloacetic transaminase (GOT) levels greater than 1,000 IU, and blood lactate dehydrogenase (LDH) levels greater than 3,000 IU. After multivariate analysis, there remained only 2 significant predictors. An oxygenator used with a noncoated CPS system (Capiox SX with Capiox EBS) proved to have a significantly shorter life span than one used with a heparin-coated system (CB Maxima or AL-6000 with CB BP-80) (hazards ratio, 3.588, p = 0.0065). Patient conditions, which revealed acidosis with less than -5 of base excess, significantly shortened the life of the oxygenator (hazards ratio, 3.595, p = 0.0188).     

Suppressive effect of LD78 on the proliferation of human hemopoietic progenitors.

LD78 is a cDNA newly isolated from human stimulated tonsillar lymphocytes. The expression of LD78 is related to inflammatory responses and its structure has a homology with macrophage inflammatory protein 1-alpha, which is known to have an inhibitory effect on murine CFU-S. Using a colony assay technique, we examined the effects of LD78 on human hemopoietic progenitors. The addition of doses of 100 ng/ml or more of LD78 suppressed the colony formation of KMT-2, a factor-dependent myelomonocytic cell line established from cord blood cells; this suppressive activity was neutralized by the addition of antibody against LD78. The same doses of LD78 suppressed the formation of neutrophil, macrophage, and megakaryocytic colonies which were supported by human interleukin-3 and erythropoietin; however, LD78 did not affect colony formation by either non-phagocytic mononuclear cells or sorted CD34+ cells. The conditioned medium of KMT-2 cells or peripheral blood mononuclear cells cultured with LD78 suppressed colony formation by CD34+ cells. From these findings, it is suggested that LD78 affects phagocytic cells and induces factors that are inhibitory for hemopoiesis. We consider LD78 to be a new cytokine that plays an inhibitory role in hemopoiesis.     

Renal Effects of Multiple Infusion of Pyridoxalated-Hemoglobin-Polyoxyethylene Conjugate (PHP) Solution in Dogs

Abstract: Pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP), which is made from out-dated human red blood cells by two major chemical modifications, namely pyridoxalation and conjugation with polyoxyethylene (POE), is currently under development as a physiological oxygen carrier. This study assessed the effects of PHP-88 solution, which contains 8% (wt/vol) each of hemoglobin (Hb) and maltose, on renal function when it was infused 3 times every other day into the intact circulation of 8 dogs (5 dogs for the PHP group and 3 for the control group; 20 ml/kg for the first infusion, and 10 ml/kg each for the second and third infusions, at the rate of 2.5 ml/h/kg). Serial determinations of glomerular filtration rate (GFR) and renal plasma flow (RPF) were carried out pre- and postinfusion for up to 3 months along with measurements of blood and urine analyses, urine output rate, fractional excretion of sodium (FES), and free water clearance (C_H2O). The results showed that plasma colloid osmotic pressure (COP) elevated an average of 3.3 mm Hg (p = 0.0085), and GFR and RPF tended to increase by 13% (NS) and 38% (NS), respectively, immediately after the third infusion with PHP solution. Urine output rate increased during and after the infusion, and FES and C_H2O also increased for 24 h after the infusion in both groups. Blood urea nitrogen, serum creatinine, and serum Na⁺ concentrations were not affected greatly by the infusions, but hematocrit was decreased by 8% in the PHP group, indicating approximately a 42% expansion of plasma volume. These changes were observed to return to their preinfusion levels by 1 week postinfusion. Renal histology of the PHP group obtained at 2 weeks postinfusion revealed vacuole formation in the proximal tubules which was not associated with any pathologic changes indicative of cell death or regeneration. In 4 out of 5 dogs at 3 months postinfusion (necropsy), the vacuoles were not present. Though urinary N-acetyl β-glucosaminidase (NAG) activity had significantly increased after infusion, it returned to the preinfusion level by 1 month postinfusion. No detrimental effect of vacuoles on the assessed renal tubular functions was confirmed in the present study. The result demonstrated that multiple infusions of PHP solutions were well tolerated in normal dogs, and the observed effects were conceived predominantly attributable to the physiological response of the kidneys to an oncotic load into the circulation, which produced plasma volume expansion.     

Thrombopoietin in postoperative thrombocytopenia following living donor hepatectomy.

Thrombocytopenia is a frequent finding following living donor hepatectomy. It appears more pronounced in right graft donors than in left graft donors. This study analyzed postoperative thrombocytopenia in 20 living liver donors and examined the change of endogenous thrombopoietin (TPO) in its recovery. Platelet count, TPO level, fibrinogen degradation product (FDP), and D-Dimer were measured before surgery and on postoperative days (PODs) 1, 2, 3, 5, 7, and 14. Concurrently, liver and spleen volumes were calculated by computed tomography. Platelet count on POD 3 was significantly lower in right graft donors than in left graft donors (13.0 +/- 3.7 x 10(4)/microL vs. 16.8 +/- 4.0 x 10(4)/microL, P = 0.039) but recovered by POD 7 in all donors. Postoperative elevations of FDP and D-Dimer were significantly higher in right graft donors than in left graft donors. TPO level rose immediately after surgery, peaked on POD 5 in left graft donors and on POD 7 in right graft donors, and fell nearly to preoperative levels by POD 14. Postoperative TPO level per liver volume was significantly higher in right graft donors than in left graft donors. In conclusion, thrombocytopenia following living donor hepatectomy resolved within the first week regardless of graft type and was mainly associated with increasing consumption of circulating platelets, possibly due to intrahepatic and splenic congestion. With a reduced number of circulating platelets, TPO level rapidly increases. Also, with reduced consumption of platelets related to recovery from surgery, thrombocytopenia should resolve. As a consequence, TPO level would be expected to fall.     

Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line.

Epidermal growth factor (EGF) mediates many pleiotrophic biological effects, one of which is alteration of cellular morphology. In the present study, we examine the possibility that this alteration in cell morphology is caused in part by the dysfunction of cadherin-mediated cell-cell adhesion using the human oesophageal cancer cell line TE-2R, which expresses E-cadherin and EGF receptor. In the presence of EGF, TE-2R changed its shape from round to fibroblastic and its colony formation from compact to sparse. Vanadate, a tyrosine phosphatase inhibitor, further potentiated the EGF response, whereas herbimycin A, a tyrosine kinase inhibitor, interfered with it. Moreover, EGF enabled the cells to invade in organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its localisation from the lateral adhesion site to the whole cell surface. Both alpha- and beta-catenin, cadherin-binding proteins, were also expressed at the same level throughout these morphological changes. Finally, we examined tyrosine phosphorylation of E-cadherin and alpha- and beta-catenin, and observed tyrosine phosphorylation of beta-catenin induced by EGF. These results suggest that EGF counteracts E-cadherin-mediated junctional assembly through phosphorylation of beta-catenin and modulates tumour cell behaviour to a more aggressive phenotype.