Should sagittal osteotomy line be parallel to tibial posterior slope in high tibial osteotomy?

BACKGROUND: The reason why the osteotomy line in the sagittal view should be parallel to the medial tibial posterior slope in open wedge high tibial osteotomy (OWHTO) remains unclear. In addition, previous study reported that a posterolateral hinge position led to an increase in tibial posterior slope (TPS) after OWHTO. Our aims were to examine the relationships between angles among the tibial plateau and osteotomy planes or the hinge point and the change in TPS, and the location of the hinge position after OWHTO using three-dimensional computed tomography (3DCT). We hypothesized that the sagittal angle between the tibial plateau and osteotomy planes with an anterior-widening proximal tibial fragment resulted in increased TPS, and the hinge position located posterolaterally. METHODS: Preoperative planning anticipated a weight-bearing line ratio of 62% on the radiograph. The anterior gap was 67% of the posterior gap in OWHTO. We identified the tibial plateau and upper and lower osteotomy planes on 3DCT of 82 patients with symptomatic medial osteoarthritic knee after OWHTO. The osteotomy plane angles between the tibial plateau and upper osteotomy planes, and opening gap angles between both osteotomy planes in the coronal and sagittal views were measured. The anteroposterior (AP) and lateral hinge position was displayed as a percentage on the upper osteotomy plane. We assessed the relationships among them. RESULTS: The TPS significantly increased after OWHTO (p = 0.002). There was no significant difference between the sagittal osteotomy plane angle and the change in TPS. The sagittal opening gap angle and the AP hinge position ratio were significantly correlated with the change in the TPS (r = 0.477 p < 0.001 and r = - 0.342, p = 0.002, respectively). The hinge position was located a mean of 16.0% from the lateral and 48.6% from the posterior tibial edge in the upper osteotomy plane. CONCLUSIONS: Contrary to our expectation, the osteotomy plane did not need to be parallel to the tibial plateau plane in the sagittal view. However, the osteotomy gap should be rectangular in the sagittal view. The hinge position located nearly in the center of the sagittal view.

Predictive factors for the progression of spontaneous osteonecrosis of the knee.

PURPOSE: To assess potentially predictive factors that were evaluated 1 year after the onset of symptoms in patients with spontaneous osteonecrosis of the knee (SONK) and to determine receiver operating characteristic (ROC) curve cut-off values. METHODS: Within 1 year of symptom onset, patients with SONK-selected treatment options, mainly based on severity of pain, chose either conservative treatment (n = 27 knees) or operative treatment (n = 27 knees). Knee and whole-leg radiographs, knee MRIs and bone mineral density scans of the lumbar spine, femoral neck and femoral condyles were obtained. The parameters measured were: (1) anatomical angle on whole-leg radiograph and (2) lesion size and medial meniscus extrusion on MRI. RESULTS: The anatomical angle and lesion size in the sagittal section (depth) on MRI were markedly larger in the operative treatment group than those in the conservative treatment group. The anatomical angle and depth on MRI of SONK at Stages 1-3 were significantly different between groups, with odds ratios (95 % confidence intervals) of 1.16 (1.18-2.34) and 1.11 (1.01-1.23). One year after symptom onset, ROC curve cut-off value for anatomical angle was 180° and depth on MRI was 20 mm. CONCLUSION: An anatomical angle >180° and depth >20 mm on MRI were predictive factors for a poorer prognosis 1 year after symptom onset in patients with SONK. Our results on radiographs and MRI provided a predictive prognosis for patients with SONK at the initial visit to their orthopaedic surgeons. LEVEL OF EVIDENCE: III.

Usefulness of long tibial axis to measure medial tibial slope for opening wedge high tibial osteotomy.

PURPOSE: To assess which tibial slope measurements on knee, whole leg radiographs and three-dimensional reconstructed computed tomography (CT) were useful in clinical practice before and after opening wedge high tibial osteotomy. METHODS: Medial and lateral tibial slopes on knee, whole leg radiographs and three-dimensional reconstructed CT were measured in 50 patients with knee osteoarthritis. To investigate the intraobserver reproducibility and interobserver reliability for each medial and lateral tibial slope on knee, whole leg radiographs and CT, the measurements were repeated twice by two observers. The statistical differences between the medial and lateral tibial slopes obtained by the three methods, and the differences and correlation coefficients for the medial and lateral tibial slopes between knee or whole leg radiographs and CT were calculated. RESULTS: The reproducibility and reliability of medial and lateral tibial slopes on CT were superior to those on whole leg or knee radiographs. The medial and lateral tibial slopes on whole leg radiographs had better reproducibility and reliability than those on knee radiographs. The mean medial tibial slopes on knee, whole leg radiographs and CT were 9.3 ± 3.4°, 12.3 ± 4.3° and 11.0 ± 3.9°, respectively. The mean lateral tibial slopes were 7.9 ± 3.1°, 9.6 ± 3.6° and 9.3 ± 2.9°, respectively. The medial tibial slopes on knee, whole leg radiographs and CT were significantly higher than the lateral tibial slopes (p < 0.01 for all). CONCLUSIONS: Tibial slope measurements using CT required time and specialized software. Therefore, measurements of the medial tibial slope using the long tibial axis on whole leg radiographs were more reproducible and reliable and could be an alternative to CT in clinical practice. LEVEL OF EVIDENCE: III.

Impairment of host resistance to helminthes with age in murine small intestine.

Age-associated alterations of Th2 immune responses against nematode parasites are largely unknown. We investigated primary and memory responses against two types of gastrointestinal nematode parasites, Heligmosomoides polygyrus (Hp) and Nippostrongylus brasiliensis (Nb), in aged mice. The small intestinal gene expression of Th2 cytokines was almost unchanged after primary (Nb and Hp) and secondary infection (Hp) in aged mice in contrast to strongly increased small intestinal gene expression of Th2 cytokines in young (3-month-old) mice. Mucus production decreased (Nb), and worm expulsion was impaired (Nb and Hp) compared with the young mice. Immunofluorescent staining revealed that after Hp infection, the number of alternatively activated macrophages, which are induced by Th2 cytokines, was lower in the aged mice. On the other hand, the number of CD4(+) T cells recruited to the worm cysts was normal compared with the young mice. These results suggest that migration of CD4(+) T cells to the host-parasite interface is not affected by ageing. Alterations in Th2 immune responses in aged mice might be due to inappropriate or insufficient activation of CD4(+) T cells in the submucosa.

The extent of degeneration of cruciate ligament is associated with chondrogenic differentiation in patients with osteoarthritis of the knee.

OBJECTIVE: Degeneration in cruciate ligaments results from abnormal biomechanical stress and the aging process. Such degeneration is a common outcome in patients with osteoarthritis (OA) of the knee and contributes to the progression of OA. However, to date, there are no specific markers that can predict the extent of ligament degeneration. We hypothesized that the extent of degeneration has correlations to increased chondrogenic potential. METHODS: Twenty anterior cruciate ligaments (ACLs) and 30 posterior cruciate ligaments (PCLs) from 30 knees of 28 adult patients with OA at the time of total knee arthroplasty were used for the study. Degeneration was histologically assessed using a grading system. Expressions of Scleraxis (as a ligament cell marker) and Sry-type HMG box 9 (SOX9) (as a chondrogenic marker) were immunohistochemically assessed in each grade. RESULTS: We found the opposite expression pattern between Scleraxis and SOX9 according to the grade. The percentage of Scleraxis-positive cells decreased significantly by grade (60.9±23.7 in grade 1, 39.7±30.5 in grade 2, and 13.9±27.1 in grade 3, P<0.0001). In contrast, the percentage of SOX9-positive cells increased significantly by grade (2.5±4.9 in grade 1, 17.5±13.4 in grade 2, and 50.9±27.1 in grade 3, P<0.0001). Furthermore, co-localized expression of both Scleraxis and SOX9 was demonstrated in chondrocyte-like cells. CONCLUSIONS: This study indicates that chondrogenic differentiation is associated with the progression of degeneration in human ligaments. Our results suggest that the expression of SOX9 as a chondrogenic marker could be an indicator for the extent of degeneration in human ligaments. It remains to be elucidated whether suppression of chondrogenic differentiation can prevent progression of the degenerative process of cruciate ligaments in patients with OA.

Navigated opening wedge high tibial osteotomy improves intraoperative correction angle compared with conventional method.

PURPOSE: The correction angle after high tibial osteotomy (HTO) depends on an accurate preoperative planning and an accurate intraoperative technique. We hypothesized that the use of a navigation system in opening wedge HTO would improve the intraoperative target angles in the coronal and sagittal planes. METHODS: Postoperative femoro-tibial angle (FTA) and tibial posterior slope (TPS) in 28 knees with navigated opening wedge HTO were compared to those in 31 knees with the conventional method. Intraoperative correction angle was determined by the predicted medial opening width in the conventional group, and by the change of hip-knee-ankle angle in the navigated group. We defined lateral unstable knee as the knees with lateral cortex breakage or lateral tibial plateau fracture. RESULTS: Mean postoperative FTA was higher in the conventional group than in the navigated group (P < 0.037). In the conventional group, 4 lateral unstable knees were corrected to 174.6°. In the navigated group, 5 lateral unstable knees were corrected to 170.3° and no knees showed FTA > 173°. Mean change in TPS was greater in the conventional group than in the navigated group (P = 0.001). CONCLUSION: The navigation system in opening wedge HTO might reduce undercorrection in the knees with lateral cortex breakage or lateral tibial plateau fracture, and provide the better intraoperative FTA and TPS. LEVEL OF EVIDENCE: III.

Effects of mechanical stress on cytokine production in mandible-derived osteoblasts.

OBJECTIVE: Mechanical stress is known to be an important factor in the regulation of bone remodeling, and mandibular bone is continuously exposed to mechanical stressors such as occlusal force. Therefore, in this study, we investigated the effects of mechanical stress approaching occlusal force, to which mandible-derived osteoblasts (MDOB) are exposed, on cytokine expression and production using an original hydrostatic pressure apparatus. MATERIALS AND METHODS: The levels of cytokine in MDOB were examined by real-time RT-PCR, ELISA, and western blotting. In addition, mitogen-activated protein kinase inhibitor for ERK1/2, JNK, and p-38 pathways was used to identify the signal transduction pathway. RESULTS: Hydrostatic pressure increased the expression of IL-6 and TNF-α mRNA in a magnitude- and time-dependent manner and also enhanced IL-6 and TNF-α protein production. Furthermore, hydrostatic pressure changed the RANKL/OPG ratio in favor of RANKL for both mRNA and protein levels. Specific inhibitor of p-38 pathway but not that of the ERK1/2 and JNK pathways suppressed the up-regulation of RANKL production induced by hydrostatic pressure loading. CONCLUSION: These results suggest that MDOB play a role in cytokine production in response to mechanical stress and that occlusal force may support the maintenance of mandible bone homeostasis by activating bone remodeling through osteoclastogenesis.

Implications of the Collar Sign in Incompletely Occluded Aneurysms after Pipeline Embolization Device Implantation: A Follow-Up Study.

BACKGROUND AND PURPOSE: The angiographic collar sign has been recently described in patients with incompletely occluded aneurysms after Pipeline Embolization Device implantation. The long-term implications of this sign are unknown. We report angiographic outcomes of patients with the collar sign with follow-up of up to 45 months and the implications of this angiographic finding. MATERIALS AND METHODS: We performed a retrospective review of a prospectively maintained data base of patients who underwent Pipeline Embolization Device implantation for an intracranial aneurysm at our institution between January 2014 and December 2016. We included patients with a collar sign at the initial follow-up angiogram after Pipeline Embolization Device implantation. RESULTS: A total of 198 patients with 285 aneurysms were screened for the collar sign on initial and subsequent follow-up angiograms. There were 226 aneurysms (79.3%) with complete occlusion at the first follow-up. Of 59 incompletely occluded aneurysms, 19 (32.2%) aneurysms in 17 patients were found to have a collar sign on the first angiographic follow-up (median, 6 months; range, 4.2-7.2). Ten (52.6%) aneurysms underwent retreatment with a second Pipeline Embolization Device, which resulted in aneurysm occlusion in 1 (10%) patient. There were only 3 (15.8%) aneurysms with complete occlusion at the last follow-up, 2 (10.5%) of which had a single Pipeline Embolization Device implantation and another single (5.3%) aneurysm with a second Pipeline Embolization Device implantation. CONCLUSIONS: A collar sign on the initial angiogram after Pipeline Embolization Device placement is a predictor of poor aneurysm occlusion. Because the occlusion rates remain equally low regardless of retreatment in patients with a collar sign, radiologic follow-up may be more appropriate than retreatment.

Signaling pathway on the effect of oxygenated warm perfusion prior to cold preservation of the liver grafts from non-heart-beating donors, and the additive effect of edaravone.

We have previously reported that oxygenated warm perfusion prior to cold preservation (preperfusion) improved the function and viability of liver grafts from non-heart-beating donors (NHBD) using an ex vivo perfusion model. In this study, we evaluated the signaling pathway underlying these effects as well as the additive effect of preperfusion administration of edaravone, a free radical scavenger. Preperfusion treatment suppressed activation of JNK, p38 MAPK, and ERK. The addition of edaravone provided an insignificant increase in bile production and a trend to a decrease in TUNEL-positive cells. Oxygenated perfusion prior to cold preservation improved the function and viability of the grafts from NHBD, which accompanied impairment of MAPK activation. Moreover, the addition of edaravone significantly enhanced the effects of preperfusion.

Quality of life and problems affecting recipients more than 10 years after living donor liver transplantation.

BACKGROUND: We initiated living donor liver transplantation (LDLT) in 1991, allowing us to examine issues related to long-term survival. The aim of this study was to review the long-term outcomes of LDLT in children. PATIENTS AND METHODS: We performed 116 LDLT from 1991 to present, including 17 recipients who survived >10 years. They were evaluated for growth, immunosuppressive therapy, complications, and quality of life (QOL). RESULTS: The average age at LDLT was 5.4 years (range, 6 months to 17 years), with a present average age of 17.2 years (range, 11-28 years). At the time of LDLT, 6 recipients had growth retardation with body weights low for age by 2 standard deviations (SD). However, 4 of 6 recipients who underwent LDLT before age of 2 years caught up, reaching average heights and body weights for their ages. Among 6 recipients who were diagnosed with acute rejections by biopsy >5 years after LDLT, 5 improved after steroid pulse therapy. One recipient with a steroid-resistant acute rejection was administered deoxyspergualin after steroids. Chronic rejection was not observed in this series. One recipient has not required immunosuppressive therapy for >4 years with a good present condition. CONCLUSION: The majority of LDLT recipients achieved a good QOL during long-term survival; they are pursuing normal studies.

Management of living donor liver transplant patients using twice-daily 4-hour intravenous cyclosporine therapy.

Oral administration of cyclosporine (CsA) is the currently favored route in most liver transplant centers. From October 1998 to January 2008, 86 living donor liver transplantations (LDLTs) were performed in 85 patients (46 adults and 39 children) at our institution. Seventy-three patients received tacrolimus (Tac), and 12 intravenous CsA twice daily at a dose of 3 mg/kg/d as a 4-hour continuous infusion. Thirteen of 73 Tac-based patients were switched to CsA because of side effects. Five were switched to intravenous CsA because they were unable to take the drug orally because of severe Tac-related complications. The remaining eight patients switched to oral CsA. We evaluated patients (11 adults and three children), including 12 with induction therapy and two with conversion therapy within 2 weeks of LDLT. The patients were given a 4-hour intravenous infusion of CsA at an initial dose of 3 mg/kg/d. Stable and adequate blood CsA concentrations were achieved by 4-hour intravenous CsA administration. Among several factors, only graft-to-recipient weight ratio (r = .743, P < .0001) showed significant correlations with initial blood CsA concentration. No adverse effects were observed after intravenous CsA. No patients developed biopsy-proven acute cellular rejection (ACR) during intravenous CsA administration, whereas two patients had histopathologically diagnosed episodes of ACR after conversion from intravenous to oral CsA. Our findings suggest that immediate administration of a 4-hour intravenous infusion of CsA at an initial dose of 3 mg/kg/d is practical and effective for routine clinical use.

Cortical stroke affects activity and stability of theta/delta states in remote hippocampal regions.

Cognitive impairment is a common outcome of ischemic stroke. Our previous work has shown that an experimental stroke in the cortex reduces activity in remote hippocampal layers in rats. This study seeks to uncover the underlying functional connections between these areas by analyzing changes to oscillatory activity, signal power, and communication. We induced an ischemic stroke in the left somatosensory cortex of rats and used linear micro-electrode arrays to simultaneously record from cortex and hippocampus under urethane anesthesia at two weeks and one month after stroke. We found significant increase in signal power, as well as an increase in the number of brain state changes in response to stroke. Our results suggest that the cortex modulates the activity and stability of hippocampal oscillations, which is disrupted following cortical stroke that can lead to cognitive impairment.

A free radical scavenger, edaravone, prevents ischemia-reperfusion injury in liver grafts from non-heart-beating donors.

BACKGROUND: Due to the increase in liver transplantation, the donor shortage has become a serious problem, requiring marginal, non-heart-beating donors (NHBDs). The aims of this study were to evaluate the cytoprotective effect of edaravone, a free radical scavenger, on warm ischemia-reperfusion (I/R) injury of liver grafts from NHBDs. METHODS: Rat livers were harvested from heart-beating donors (HB group) or from NHBDs undergoing cardiac arrest for 30 minutes led by thoracotomy (NHB group), and reperfused for 60 minutes with Krebs-Henseleit bicarbonate buffer after cold preservation for 6 hours. In another group (ED group), warm ischemic livers from NHBDs were reperfused with buffer containing edaravone (1 mg/L) after cold preservation. RESULTS: In the ED group, portal flow volume, bile production, and energy charge were significantly ameliorated. Lipid peroxidation, elevation of hepatic enzymes, and release of tumor necrosis factor-alpha and interleukin-1 beta were significantly alleviated, compared with the NHB group. CONCLUSIONS: These results suggested that edaravone has suppressive effects on warm I/R injury in liver grafts from NHBDs.

Parkinsonism during cyclosporine treatment in liver transplantation: an unusual case report.

OBJECTIVES: Cyclosporine (CyA) has been associated with various neurological reactions but parkinsonism is not generally recognized as a nervous system side effect. We describe herein a rare case, in that the patient developed parkinsonism with rest tremor after receiving CyA following orthotopic liver transplantation (OLT). METHODS: The patient was a 42-year-old man who had liver cirrhosis with hepatitis C. We performed OLT because of liver failure and started immunosuppressive therapy with CyA + methylprednisolone + CD25 antibody. Ten days after OLT, he developed parkinsonism with a rest tremor. The patient did not have a pre-existent neurological disorder, and had not received significant amounts of dopamine-blocking drugs. RESULTS: We administered levodopa with marked improvement. Three days after that event, the neurologist suggested the possibility of drug-induced parkinsonism. We converted the immunosuppressive drug from CyA to tacrolimus. After that, the symptom disappeared. At 75 days after OLT, he was discharged with no neurological medication and now he is completely recovered. CONCLUSION: We think that parkinsonism may be an occasional consequence of CyA because of its relation to withdrawal of the drug and the lack of another evident cause.

Distinct roles of RAG1 and RAG2 in binding the V(D)J recombination signal sequences.

The RAG1 and RAG2 proteins initiate V(D)J recombination by introducing double-strand breaks at the border between a recombination signal sequence (RSS) and a coding segment. To understand the distinct functions of RAG1 and RAG2 in signal recognition, we have compared the DNA binding activities of RAG1 alone and RAG1 plus RAG2 by gel retardation and footprinting analyses. RAG1 exhibits only a three- to fivefold preference for binding DNA containing an RSS over random sequence DNA. Although direct binding of RAG2 by itself was not detected, the presence of both RAG1 and RAG2 results in the formation of a RAG1-RAG2-DNA complex which is more stable and more specific than the RAG1-DNA complex and is active in V(D)J cleavage. These results suggest that biologically effective discrimination between an RSS and nonspecific sequences requires both RAG1 and RAG2. Unlike the binding of RAG1 plus RAG2, RAG1 can bind to DNA in the absence of a divalent metal ion and does not require the presence of coding flank sequence. Footprinting of the RAG1-RAG2 complex with 1, 10-phenanthroline-copper and dimethyl sulfate protection reveal that both the heptamer and the nonamer are involved. The nonamer is protected, with extensive protein contacts within the minor groove. Conversely, the heptamer is rendered more accessible to chemical attack, suggesting that binding of RAG1 plus RAG2 distorts the DNA near the coding/signal border.

Influence of coronal bowing on the lower alignment and the positioning of component in navigation and conventional total knee arthroplasty.

BACKGROUND: Coronal alignment is an important factor for the function and longevity of total knee arthroplasty (TKA). Coronal bowing of the lower extremity is common among Asians and it may pose a risk for malalignment of the lower leg and malposition of component. HYPOTHESIS: We hypothesized that coronal bowing itself has a risk for malalignment of the lower leg and malposition of femoral/tibial components and that navigation TKA is beneficial for patients with coronal bowing. We investigated the incidence of femoral/tibial bowing in patients treated with TKA and compared the radiographic parameters between the navigation group and the conventional group. Additionally, the influence of coronal bowing on these radiographic parameters was investigated. MATERIALS AND METHODS: We enrolled 35 patients with knee osteoarthritis and 70 bilateral simultaneous TKAs. The patients underwent TKA with the use of a computer tomography-free navigation in one knee and conventional TKA in the contralateral knee. Preoperative coronal bowing were measured, and the subjects were divided into 2 subgroups, i.e. the bowing group and the non-bowing group. Lateral bowing was expressed as plus (+) and medial bowing was expressed as minus (-). Various radiographic parameters, including coronal bowing, lower leg alignment, component position, and outliers were compared between the navigation group and the conventional group. RESULTS: Femoral bowing varied from -7.4° to 10.9° with an average of 3.0°. Tibial bowing varied from -4.1° to 4.6° with an average of 0.4°. The femoral component was placed more properly in the navigation group. Number of outlier regarding to the coronal femoral component angle to the femoral mechanical axis was 14 cases (37.8%) in the bowing group and 6 cases (18.2%) in the non-bowing group (P=0.04). DISCUSSION: In conclusion, coronal femoral bowing has an important effect on femoral bone cut in TKA. The navigated TKA was more consistent than conventional TKA in aiding proper alignments of femoral component. LEVEL OF EVIDENCE: Level II, comparative prospective study.

Edoxaban is effective in reducing the incidence of asymptomatic phlebographic events following closed-wedge high tibial osteotomy.

INTRODUCTION: The purpose of this study was twofold: to investigate whether edoxaban significantly decreases the rate of venous thromboembolism (VTE) following closed-wedge high tibial osteotomy (CWHTO), in terms of phlebographic event, and to determine whether edoxaban is safe or increases the rate of hemorrhagic complications. We hypothesized that edoxaban would decrease the incidence of VTE and would not increase the rate of hemorrhagic complications. MATERIALS AND METHODS: We randomly enrolled 60 patients undergoing CWHTO. The patients were divided into two groups: one group receiving edoxaban (15mg in 5 patients, 30mg in 23 patients) and a non-edoxaban group. All patients underwent computed tomography venography on day 7to diagnose postoperative VTE. Blood samples were obtained on the day before CWHTO and on postoperative days 1, 3, 7 and 14. The incidence of VTE and hemorrhagic events in both groups was compared using unpaired Student t-test or chi-square test. RESULTS: The incidence of VTE was significantly greater in the non-edoxaban group (31.3% versus 7.1%; P=0.02). The incidence of deep vein thrombosis (DVT) was also significantly greater in the non-edoxaban group (28.1% versus 3.6%; P=0.01). A single patient from the edoxaban group experienced major bleeding. On days 3 and 7, D-dimer levels were significantly lower in the edoxaban group (P=0.03 and 0.003, respectively). On days 3, 7 and 14, activated partial thromboplastin time was significantly greater in the edoxaban group (P=0.02, 0.01 and 0.006, respectively). CONCLUSION: Patients undergoing CWHTO are at risk of postoperative VTE. Edoxaban helps prevent asymptomatic phlebographic VTE and DVT following CWHTO; however, the risk of major bleeding must be considered. LEVEL OF EVIDENCE: II.

The effect of perfusion prior to cold preservation and addition of biliverdin on the liver graft from non-heart-beating donors.

AIM: Our aim was to improve the energy status and viability of a liver graft from a non-heart-beating donor (NHBD), we investigated the effects of perfusion prior to cold preservation and the addition of an antioxidant, biliverdin. METHODS: Rats were divided into five groups: group 1: without 30 minutes warm ischemia (WI) and cold preservation (control group); group 2 without WI and with 6 hours of cold preservation in UW solution (HBD group); group 3 with WI and cold preservation (NHBD group); group 4 with 30 minutes perfusion prior to cold preservation (PRE group); and group 5 with addition of biliverdin to precold preservation perfusion (BV group). Oxygenated Klebs-Henseleit solution was used as the perfusate prior to and after preservation. Portal flow and bile production during reperfusion, energy charge (EC), ATP level, GOT, and TNF-alpha were measured as well as a histological evaluation. RESULTS: Portal flow of the PRE and BV groups during 1 hour of reperfusion was higher than of that the NHBD group. Bile production of the PRE group was also higher than that of the NHBD group, but bile production in the BV group was comparable to the NHBD group. EC of the PRE group was higher than that of the NHBD group prior to and after reperfusion. The EC and ATP levels of the BV group after reperfusion were higher than those of the NHBD and PRE groups. The GOT and TNF-alpha were reduced in the BV group. CONCLUSIONS: Precold preservation perfusion improves the viability of grafts from NHBDs. Furthermore, biliverdin exerted an additive effect to ameliorate energy status.

Continuous low-dose human atrial natriuretic peptide promotes diuresis in oliguric patients after living donor liver transplantation.

Human atrial natriuretic peptide (ANP) is beneficial for the prophylaxis of acute renal failure (ARF) after liver transplantation (OLT). We evaluated renal function in OLT patients with or without ARF, describing cases unresponsive to loop diuretics successfully treated with continuous low-dose ANP infusion without hemodialysis. Twenty-seven consecutive adult-to-adult living donor liver transplantations (LDLTs) were performed in 26 patients. One case was excluded due to the need for continuous hemodialysis (HD) during the operation. Of the 26 cases, 6 (23%, group 2) developed ARF in the first 30 days after LDLT; the other 20 were ARF-free (group 1). The median follow-up was 24 months. No patient required either continuous or intermittent HD. Only one patient died due to multiple liver abscesses. Mean preoperative serum creatinine (sCr) value and intraoperative blood loss in group 2 were significantly higher than those in group 1. Three cases in group 2 failed to improve on high-dose loop diuretics with low-dose dopamine, exhibiting fluid overload. The remaining three cases in group 2 responded to conventional diuretic treatments. Continuous low-dose ANP was started 2, 4, or 5 days after LDLT, and urine output significantly increased after ANP administration. The serum creatinine values were 1.1, 1.2, and 1.1 at 1 month and 1.0, 0.9, and 0.6 mg/dL at 6 months after LDLT. Massive blood loss during the operation caused ARF, but did not affect renal function after LDLT. Continuous low-dose ANP improved renal function and diuresis for oliguric ARF patients, preventing the need for HD or continuous venovenous hemodialysis.

Casein and 3-methylcholanthrene carcinogenesis in inbred C57BL/6Os female mice.

Groups of inbred C57BL/6Os female mice were subjected to one of the following -reatments: 1) subamyloidogenic administration of sodium caseinate (C group); 2) four intragastric intubations of 0.25 mg 3-methylcholanthrene (MCA) (MCA group); 3) a sodium caseinate injection followed by MCA (C-MCA group); or 4) MCA followed by a soidum caseinate injection (MCA-C group). During their life-spans, mice of the C group developed a significantly high incidence of neoplasms, especially histiocytic lymphomas, No myelogenous leukemia was observed in the C group, but it was seen in the MCA, C-MCA, and MCA-C groups. The occurrence rate of other neoplasms was significantly high in the C, MCA, and MCA-C groups, but it was not significantly high in the C-MCA group compared with the untreated group. Results suggested that sodium caseinate treatment shifts target organs in MCA carcinogenesis. In all treated groups, amyloidosis of a secondary type was observed at a significantly high rate in the following order of severity by treatment group: MCA, MCA-C, C-MCA, and C groups, MCA was obviously amyloidogenic with or without sodium caseinate adjuvant treatment; although the sodium caseinate treatment was subamyloidogenic, it elicited neoplasms, including neoplasms of lymphoreticular tissue.