Cyclosporine and partial liver allotransplants in a simplified rat model

We designed a simplified rat model to assess the effects of cyclosporine (CsA) on liver transplants. Auxiliary liver grafts consisting of 20 per cent of the whole liver were supplied with portal inflow and the bile was drained into the stomach. The cuff technique was used routinely for both end-to-end and end-to-side venous anastomoses. The host liver was totally deprived of portal inflow. Two inbred strains of rats, LEW and F344, were used for isograft (LEW----LEW) and allograft (F344----LEW). All survivors were killed at the end of the fourth week after transplantation. During four weeks, the isografts increased by 108 per cent in wet liver weight. Animals with allograft were treated with CsA given i.m., in a daily dose of 20 and 40 mg/kg for the first ten days post transplantation. The CsA-treated rats were free from parenchymal destruction of the allograft, as was characteristic of the allograft controls. The rats given CsA in the dose of 40 mg/kg showed a 173 per cent increase in the wet liver weight of the transplant, such being greater than allografts in rats on 20 mg/kg of CsA (100 per cent) and even than isografts. These results indicate that auxiliary partial liver grafts benefit from the use of CsA not only through suppression of allorejection but through a potential "hepatotrophic effect" of the agent.     

Preservation of pancreas in the University of Wisconsin solution supplemented with AP39 reduces reactive oxygen species production and improves islet graft function

Ischemia-reperfusion injury (IRI) results in increased rates of delayed graft function and early graft loss. It has recently been reported that hydrogen sulfide (H₂S) protects organ grafts against prolonged IRI. Here, we investigated whether the preservation of pancreas in University of Wisconsin (UW) solution supplemented with AP39, which is a mitochondrial-targeted H₂S donor, protected pancreatic islets against IRI and improved islet function. Porcine pancreata were preserved in the UW solution with AP39 (UW + AP39) or the vehicle (UW) for 18 h, followed by islet isolation. The islet yields before and after purification were significantly higher in the UW + AP39 group than in the UW group. The islets isolated from the pancreas preserved in UW + AP39 exhibited significantly decreased levels of reactive oxygen species (ROS) production and a significantly increased mitochondrial membrane potential as compared to the islets isolated from the pancreas preserved in the vehicle. We found that the pancreas preserved in UW + AP39 improved the outcome of islet transplantation in streptozotocin-induced diabetic mice. These results suggest that the preservation of pancreas in UW + AP39 protects the islet grafts against IRI and could thus serve as a novel clinical strategy for improving islet transplantation outcomes.     

Functional transition: Inconsistently parallel to the increase in future liver remnant volume after preoperative portal vein embolization

BACKGROUNDPreoperative portal vein embolization (PVE) is a widely used strategy to enable major hepatectomy in patients with insufficient liver remnant. PVE induces hypertrophy of the future liver remnant (FLR) and a shift of the functional reserve to the FLR. However, whether the increase of the FLR volume (FLRV) corresponds to the functional transition after PVE remains unclear.AIMTo investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional (3D) computed tomography (CT) and ^99mTc-galactosyl-human serum albumin (^99mTc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODSThirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I, Hokkaido University Hospital between October 2013 and March 2018 were enrolled. Three-phase dynamic multidetector CT and ^99mTc-GSA SPECT scintigraphy were performed at pre-PVE, and at 1 and 2 wk after PVE; 3D ^99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis system. Functional FLRV (FFLRV) was defined as the total liver volume × (FLR volume counts/total liver volume counts) on the 3D ^99mTc-GSA SPECT CT-fused images. The calculated FFLRV was compared with FLRV.RESULTSFFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE (P < 0.01). The increase in FFLRV and FLRV was 55.1% ± 41.6% and 26.7% ± 17.8% (P < 0.001), respectively, at 1 wk after PVE, and 64.2% ± 33.3% and 36.8% ± 18.9% (P < 0.001), respectively, at 2 wk after PVE. In 3 of the 33 patients, FFLRV levels decreased below FLRV at 2 wk. One of the three patients showed rapidly progressive fatty changes in FLR. The biopsy at 4 wk after PVE showed macro- and micro-vesicular steatosis of more than 40%, which improved to 10%. Radical resection was performed at 13 wk after PVE. The patient recovered uneventfully without any symptoms of pos-toperative liver failure.CONCLUSIONThe functional transition lagged behind the increase in FLRV after PVE in some cases. Evaluating both volume and function is needed to determine the optimal timing of hepatectomy after PVE.     

Airway occlusion pressure (P0.1) — A useful predictor for the weaning outcome in patients with acute respiratory failure —

Twenty-five patients who required mechanical ventilatory support (MVS) after major surgery or severe burns were studied to determine whether airway occlusion pressure (P_0.1) is a clinically useful indicator to predict the success or failure of the weaning trial. A total of 33 weaning trials were attempted on these patients. Of the 33 trials, 24 were followed by successful weaning and 9 by failure. Although the success group, when compared with the failure group, had a lower respiratory rate (P 0.001), a lower minute ventilation (P 0.001), a higher maximal voluntary ventilation to minute ventilation ratio (P 0.01) and a higher forced vital capacity (P 0.05), no threshold values separated the success from the failure group. The alveolar-arterial P_{O 2} gradient, with an Fi _{O 2} of 1.0, in weaning success and failure showed no statistical difference. In contrast, all patients in the success group had a P_0.1 of less than 3.5cmH₂O and those in the failure group had a P_0.1 of greater than 3.5cmH₂O (P 0.001). We conclude that P_0.1 is a clinically superior indicator for discontinuing MVS in patients with acute respiratory failure.(Okamoto K, Sato T, Morioka T: Airway occlusion pressure (P_0.1)—A useful predictor for the weaning outcome in patients with acute respiratory failure—. J Anesth 4: 95–101, 1990)     

Evaluation of conventional weaning criteria in patients with acute respiratory failure

We evaluated the reliability of conventional weaning criteria from a ventilator during 33 weaning trials on 25 patients with acute respiratory failure (ARF). Of 13 criteria, a ratio of maximal voluntary ventilation to minute ventilation (MV) 2, a vital capacity 12ml·kg^–1, a spontaneous respiratory rate 25 breaths·min^–1, and a MV 10l·min^–1 appeared to be useful for predicting successful weaning outcome. However, even using those criteria, there were many falsely-negative cases. The alveolar-arterial P_{O 2} gradient 350mmHg at an Fi _{O 2} 1.0 was not useful as a predictor of weaning outcome. The present study demonstrates that conventional criteria are frequently inaccurate for predicting weaning outcomes and suggests that the use of some of these criteria may unnecessarily prolong the length of ventilator support. Since ventilation of most patients with poor oxygenation can be successfully discontinued by placing them on a continuous positive airway pressure system, these results suggest that the improvement of oxygenation is not an indispensable prerequisite for weaning from mechanical ventilators.(Okamoto K, Iwamasa H, Dogomori H, et al.: Evaluation of conventional weaning criteria in patients with acute respiratory failure. J Anesth 4: 213–218, 1990)     

Effect of irradiation on transforming growth factor-β secretion by malignant glioma cells

Glioblastoma cells secrete transforming growth factor- (TGF-), whichhas a variety of immunosuppressive properties. We investigatedthe effect of irradiation TGF- secretion by malignantglioma cells. Three malignant glioma cell lines (T98G,A172, KG-1-C) were cultured and irradiated using 10and 50 Gy Linac radiation. After further culturefor 36 hours in serum-free culture medium, thesupernatants were collected. The TGF- activity in theculture supernatants was determined using a specific bioassay.The levels of the active form and totalTGF- in the supernatants from irradiated malignant gliomacells decreased compared to those from un-irradiated cells.However, since irradiation inhibited the growth of tumorcells, the amount of TGF- secretion per cellin irradiated cells tended to increase after irradiation.These results suggest that malignant glioma cells canstill secrete TGF- and activate latent TGF- evenafter large dose irradiation, despite the inhibition oftumor growth.     

Calcified convexity dura mater and acute epidural haematoma mimicking calcified chronic subdural haematoma

We report a patient with calcification of the convexity dura mater and an acute epidural haematoma. CT revealed a calcified layer between the haematoma and brain parenchyma, which mimicked acute bleeding into a calcified chronic subdural haematoma. The appearance of a calcified haematoma does not always mean a chronic lesion, and that emergency operation should not be foregone, when there is a history of acute head trauma and progressive impairment of consciousness.     

Primary anorectal malignant melanoma: Report of a case

(Received for publication on Aug. 18, 1997; accepted on May 15, 1998)     

Effect of intracarotid bradykinin infusion on cerebral blood flow in dogs

We examined whether intracarotid infusion of bradykinin altered circulation in the normal canine brain. Twenty-four anesthetized dogs were divided into four groups receiving different doses of bradykinin (1, 2.5, 5, and 10 micrograms kg-1 min-1). Regional cerebral blood flow (rCBF) was measured continuously using laser Doppler flowmetry through a burr hole in the frontal bone. Systemic blood pressure (SBP) and heart rate (HR) were monitored simultaneously. Higher doses of bradykinin significantly but temporarily decreased rCBF and SBP immediately after the start of infusion; these parameters rapidly recovered and then were stable through the rest of the infusion. During this period, percent change in rCBF and SBP was small, and differences between groups were not significant. On the other hand, HR increased during infusion and remained high. SBP, rCBF, and HR returned to pre-infusion levels after bradykinin was stopped. The results suggest that intracarotid infusion of bradykinin for treatment of brain tumors would be safe in terms of circulation to the uninvolved brain.