Improved survival outcome for hepatoblastoma based on an optimal chemotherapeutic regimen--a report from the study group for pediatric solid malignant tumors in the Kyushu area

Background/purpose

The survival outcome for patients with hepatoblastoma normally depends on the resectability of the tumor. In Japan, the pre and/or postoperative chemotherapy protocol using a combination of cisplatin (CDDP) and tetrahydropyranyl-Adriamycin (THP-ADR) has been the standard treatment since 1991. This study aims to assess exactly what influence the establishment of this chemotherapy protocol has had on both the tumor resectability and the outcome of patients with hepatoblastoma.

Methods

From 1982 to 1997, 60 patients with hepatoblatoma were treated in the Kyushu area, Japan. Based on the pretreatment extent of disease (PRETEXT), the outcome and tumor resectability were compared between group A (1982 to 1990, n = 27, PRETEXT I:5, II:8, III:6, IV:8) and group B (1991 to 1997, n = 33, PRETEXT I:9, II:9, III:5, IV:10).

Results

The 5-year survival rates (group A and group B) were 33% and 73% for all cases (P < .01), 100% and 89% for PRETEXT I, 38% and 89% for II (P < .05), 17% and 80% for III (P < .01), and 0% and 40% for IV (P < .01), respectively. The 5-year survival rates for patients with metastases were 0% for group A (n = 5) and 57% for group B (n = 7; P < .01). The rates of a complete resection of primary tumor were 48% for group A and 67% for group B. In particular, a significant difference was found regarding the complete resection rate between groups A and B in the patients with PRETEXT III (17% for group A and 80% for group B; P < .01). In the patients with an incomplete tumor resection (14 for group A, 11 for group B), the 5-year survival rates were 0% for group A and 45% for group B (P < .01).

Conclusions

The optimal chemotherapeutic regimen of CDDP and THP-ADR was thus found to greatly contribute to the improved survival rate of hepatoblastoma patients. Preoperative chemotherapy resulted in an increased resectability of the tumor, whereas postoperative chemotherapy played an important role in the increased cure rate of cases with either an incomplete tumor resection or metastasis. However, refractory cases with PRETEXT IV or metastasis may still require the development of an even more effective treatment modality, including the use of blood stem cell transplantation.     

Peritoneal Infusion with Cold Saline Decreased Postoperative Intra-Abdominal Adhesion Formation

Background

Postoperative intra-abdominal adhesion is a common morbidity after laparotomy. We try to determine whether peritoneal infusion with cold saline may decrease postoperative intra-abdominal adhesion formation.

Methods

Ninety-six male BALB/c mice weighing 25-30 g were randomized into four groups: (I) adhesion model with infusion of 4°C cold saline, (II) adhesion model with infusion of room temperature saline, (III) adhesion model without infusion of saline, and (IV) sham operation without infusion of saline. Adhesion scores, incidence of adhesion, and serum cytokines were measured at postoperative days 1, 3, 7, and 14.

Results

Group I had lower adhesion scores than groups II and III (P < 0.0001). IL-6, IL-10, and TNF-α were significantly increased in the groups I, II, and III compared to group IV (P < 0.0001). IL-6 in group I was significantly decreased compared to that in group III (P < 0.0004). IL-10 in group I was significantly increased compared to that in groups II (P < 0.0001) and III (P < 0.05). TNF-α in group I was significantly decreased compared to that in groups II (P < 0.0004), and III (P < 0.05).

Conclusion

Peritoneal infusion with cold saline may decrease the degree of postoperative intra-abdominal adhesion formation.     

Lisinopril inhibits endothelin-1 in the early period of hepatic reperfusion injury in a partial hepatectomy model

Background

Ischemia-reperfusion (I/R) injury is a major problem during liver surgery. We investigated the effects of lisinopril, an angiotensin-converting enzyme inhibitor, in the early postoperative period of reperfusion injury after Pringle's maneuver during an 80% partial hepatectomy (PH) in rats.

Methods

Four groups of male Sprague-Dawley rats were studied: Group 1 (n = 10), sham laparotomy; group 2 (n = 10), PH without portal occlusion; group 3 (n = 10), PH with portal pedicle clamping; group 4 (n = 15), same as group 3 with additional intravenous lisinopril preconditioning (1 mg/kg⁻¹). We analyzed superoxide radical (O₂⁻), nitric oxide (NO), peroxynitrite (ONOO⁻) levels in the liver tissue and blood levels of alanine aminotransferase (ALT) and endothelin-1 (ET-1).

Results

ALT and ET-1 levels were progressively increased in group 2 (P > .05) versus group 3 (P < .001 and P < .05), showing hepatocellular damage due to I/R injury in the remnant liver, although histopathologic changes were unremarkable at this early stage. The levels of ALT and ET-1 decreased with lisinopril precontioning in group 4 compared with group 2 (P > .05 and P < .01) or group 3 (P < .05 and P < .001). O₂⁻ levels were increased significantly in groups 2 and 3 (P < .01 for both). O₂⁻ level in Group 4 was remarkably decreased albeit not significant compared with the other groups. NO and ONOO⁻ levels were also significantly greater in groups 2 (P < .01 and P < .05) and 3 (P < .001 and P < .01). These levels were decreased significantly among group 4 compared with group 3 (P < .05), a decline almost to the level of group 1 (P > .05).

Conclusion

In the early postoperative period of an extended hepatectomy model, Pringle's maneuver causes I/R increasing the insult to the remnant liver. Lisinopril preconditioning alleviated I/R injury by decreasing the O₂⁻, NO, ONOO⁻, ET-1, and ALT levels, thereby exerting a protective role on the remaining liver.     

The effects of gabexate mesilate on the microsurgical reconstruction of the hepatic artery in living donor liver transplantation

Objectives

Microsurgical reconstruction of hepatic artery is essential but require challenging techniques especially for living donor liver transplantation (LDLT), because the recipient artery is short, located deep, and usable vessel grafts are limited. Furthermore, hepatic artery thrombosis (HAT) can be a lethal complication. Therefore, we began the systemic administration of gabexate mesilate, a strong serine protease inhibitor. It has often been effective to treat disseminated intravascular coagulation. The purpose of this study was to examine the effects of gabexate mesilate on the microvascular reconstruction.

Methods

From 1991 to 2009, we performed 134 microsurgical reconstructions of LDLT. This retrospective investigation of those cases divided them into four groups: group I, anticoagulation with heparin (n = 3); group II, heparin and gabexate mesilate (20 mg/kg/d; n = 26); group III, heparin and full-dose gabexate mesilate (40 mg/kg/d; n = 72); and group IV, full-dose gabexate mesilate alone (n = 33). Groups I and II were mainly pediatric cases (left lobe grafts only); groups III and IV, adult cases (left: right = 57:48). Using ultrasonography to 14 days, we investigated HAT by examining pulsatile index, resistive index, and acceleration time.

Results

HAT occurred in groups I, II, III, and IV at 33.3% (1/3), 11.5% (3/26), 6.9% (5/72), and 0% (0/33), respectively. The 5-year survival rates of groups III + IV versus groups I + II were 82.4% and 71.1%, respectively (P < .05). In HAT cases, even before the event the acceleration times were delayed to over 100 milliseconds.

Conclusion

Gabexate mesilate administration was safe for and protective of microvascular reconstructions in LDLT.     

The role of monocyte chemoattractant protein-1 in biliary atresia

Background

The aim of this study was to explain the role of monocyte chemoattractant protein-1 (MCP-1) in biliary atresia (BA).

Methods

Concentrations of serum MCP-1 and collagen type IV were measured in 38 patients with BA by using commercially available kits. MCP-1 was also assessed in liver biopsy specimens by using immunohistochemistry. Subjects were classified into groups. Group 1 comprised BA patients with normal liver function (n = 13), group II comprised BA patients with moderate liver dysfunction (n = 18), group III comprised BA patients older than 20 years awaiting liver transplantation (n = 7), and the control group comprised age-matched patients without evidence of liver disease (n = 23).

Results

Serum MCP-1 levels were significantly increased in group II compared with group I (P < .0001) and the control group (P < .0001). Serum MCP-1 levels in group III were lower than in the control group (P < .0001). There was a significant linear correlation between serum MCP-1 levels and type IV collagen levels in group II. Group II subjects with portal hypertension (PH) had higher MCP-1 levels than those without PH (P = .0009). Biopsy specimens showed MCP-1 was expressed mainly on biliary epithelial cells, vascular endothelial cells, and hepatocytes in group II.

Conclusions

These findings suggest that MCP-1 probably plays a significant role in the development of progressive liver fibrosis in BA.     

The Effect of Vasopressin on Organ Blood Flow in an Endotoxin-Induced Rabbit Shock Model

The effects of vasopressin on the vasculature differ from those of other vasopressors, and its effects on the coronary artery remain debatable. This study was undertaken to examine the effects of vasopressin in a rabbit endotoxin-induced shock model and to compare these effects with those of norepinephrine. Thirty rabbits were divided into four study groups: a normal control group (group I, n = 5), a shock control group (group II, n = 5), a vasopressin group (group III, n = 10), and a norepinephrine group (group IV, n = 10). Shock was induced by intravenously infusing lipopolysaccharide (Escherichia coli O111:B4) in groups II, III, and IV. In groups III and IV, systemic blood pressure was maintained to the level of group I by adjusting vasopressin and norepinephrine doses. Left ventricle, right ventricle, ventricular septum, kidney, liver, spleen, and skeletal muscle blood flows were measured using radioisotope tagged microspheres at baseline and 2 h after initial blood flow measurement. No difference in organ blood flows were observed between groups I and II, and coronary blood flow in the left ventricle, right ventricle, and ventricular septum was similar in all study groups. However, renal blood flow was significantly lower in group IV than in group III (p <. 05) and hepatic arterial blood flow was significantly lower in group III than in group IV (p <. 05). Thus, effect of vasopressin on organ blood flow is organ dependent. Vasopressin increased renal blood flow and decreased hepatic arterial blood flow in this endotoxin-induced shock model, whereas norepinephrine did not. However, coronary blood flow was not changed by shock status or vasopressor type.     

Hypothermia decreases postoperative intra-abdominal adhesion formation

Background

Hypothermia may decrease postoperative intra-abdominal adhesion. We sought to determine the most suitable temperature for hypothermia for decreasing postoperative adhesion formation.

Methods

One hundred and twenty male BALB/c mice weighing 25 to 30 g were randomized into 5 groups: adhesion model with infusion of cold saline at (I) 15°C; (II) 10°C; or (III) 4°C; (IV) adhesion model without infusion of saline; and (V) sham operation without infusion of saline. Adhesion scores, incidence of adhesion, and serum cytokine levels were measured at postoperative days 1, 3, 7, and 14.

Results

Adhesion scores among groups I, II, and III did not differ significantly. Interleukin-6 was significantly decreased in groups I, II, and III, compared to the levels in groups IV and V (P < .05). Tumor necrosis factor-α levels in groups I and II were significantly decreased compared to those in groups III, IV, and V (P < .05).

Conclusion

We suggest that 15°C is the appropriate temperature for induction of hypothermia to decrease postoperative intra-abdominal adhesion formation.     

The Protective Effect of Aprotinin and α-Tocopherol on Ischemia-Reperfusion Injury of the Rat Liver

Background

Liver injury caused by ischemia-reperfusion (I/R) processes is a complication of hepatic resection surgery and transplantation, particularly using grafts from marginal donors. Despite improvements in organ preservation and advances in surgical techniques, I/R injury remains a significant clinical problem. In this study, we investigated whether aprotinin provided protection against the adverse effects of I/R injury in liver tissue.

Methods

Forty rats were randomized into four groups (n = 10): group I: (control group) I/R + no medication; group II: sham-operated group + no medication or I/R; group III: I/R + aprotinin; group IV: I/R + α-tocopherol. Malondialdehyde (MDA) was measured in the liver tissue and superoxide dismutase (SOD), catalase (CAT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), as well as lactate dehydrogenase (LDH) in rat serum.

Results

Administration of aprotinin and α-tocopherol before I/R resulted in significant reductions of MDA levels compared to the I/R alone group (group I; P = .01 and P < .01, respectively). Administration of aprotinin or α-tocopherol prior to I/R resulted in significant increases in SOD and CAT levels compared with the I/R group (P < .05 each). Compared to the I/R group, significant decreases in plasma AST, ALT, and LDH levels were observed both in the aprotinin and in the α-tocopherol group (P < .05). Histological evaluation revealed the injury grade to be relatively lower among groups III and IV compared to group I.

Discussion

In conclusion, rat hepatic structures in aprotinin and α-tocopherol administered groups were well protected. Therefore, aprotinin may provide protection against the adverse effects of I/R injury in liver transplantation.     

Effect analysis of 1-year posttransplant body mass index on chronic allograft nephropathy in renal recipients

Objective

We sought to evaluate the effects of body mass index (BMI) at 1 year after transplantation on chronic allograft nephropathy (CAN).

Methods

We grouped 564 kidney transplanted patients between June 1997 and March 2005 according to BMI at 1 year after transplantation: group I showed a BMI more than 18.5 and less than or equal to 25 (normal weight); group II, BMI greater than 25 and less than or equal to 30 (overweight); and group III, BMI greater than 30 (obese). We retrospectively studied all patients. All donors were living donors, none of whom were prisoners.

Results

One-year posttransplant BMI was greater than preoperative values in groups II and III (P < .05 and P < .01 respectively). The CAN incidences among the three groups were 34.9% (128/367), 38.4% (48/125), and 43.1% (31/72), respectively (group I vs III; P < .05). With the increase in 1-year posttransplant BMI the rates of hypertension, diabetes mellitus, and hyperlipidemia increased, but there was no difference in acute rejection episodes among the three groups. Multivariate analysis revealed BMI at the first postoperative year to show a significant influence on CAN.

Conclusions

One-year BMI after kidney transplantation has a strong association with CAN. Thus diet control, exercise, and decreased immunosuppressive agent exposure may control BMI and decrease the incidence of CAN.     

Effect of prenatal glucocorticoids and postnatal nitric oxide inhalation on survival of newborn rats with nitrofen-induced congenital diaphragmatic hernia

Background/Purpose: Pulmonary hypertension and pulmonary hypoplasia account for the high mortality rate associated with congenital diaphragmatic hernia (CDH). In animal models of CDH, postnatal nitric oxide (NO) inhalation resulted in significantly better survival rates and antenatal glucocorticoid administration in improved lung compliance. The objective of this study was to evaluate the combined effect of prenatal glucocorticoid administration and postnatal NO inhalation on the survival rate of newborn rats with nitrofen-induced CDH. Methods: Right-sided CDH was induced by maternal administration of a single oral dose (100 mg, intraperitoneally) of nitrofen on day 11.5 of pregnancy. Dexamethasone (DEX, 0.25 mg/kg) was given in groups III and IV by maternal intraperitoneal injection on day 18.5 and 19.5 of pregnancy. Control animals (groups I and II) received vehicle alone. After spontaneous delivery, the newborn animals were exposed to either NO (80 ppm; groups II and IV) or room air (groups I and III). Vitality (Rat-Score), sO₂ and survival were monitored continuously for 12 hours until animals were killed. Hernia size was estimated as percentage of total thoracic content. Results: Right-sided CDH was observed in 392 of 491 newborn rats (81%). Animals with large hernias ([gt ]50%) died within 4 hours after birth, irrespective of treatment. Hernias with less than 50% of the thoracic volume were considered clinically relevant hernias. In this category, 12.5% of animals without treatment (group I) survived compared with 63.6% after NO treatment alone (group II; P [lt ] .01). Survival rate after DEX treatment alone (group III) was 69.4% (group III v I; P [lt ] .01). In group IV (DEX and NO) 95.2% of the animals survived (group IV v I; P [lt ] .001). In contrast to DEX alone, NO administration resulted in significantly better sO₂(group II and IV) compared with group I (P [lt ] .05). Conclusion: Combination of prenatal maternal glucocorticoids and postnatal NO inhalation significantly improved survival rate of newborn rats with nitrofen-induced CDH.     

Outcomes in Patients Receiving HeartMate II Versus HVAD Left Ventricular Assist Device as a Bridge to Transplantation

Objective

Ventricular assist devices have become a standard treatment for patients with advanced heart failure. We present data comparing results after implantation of HeartMate II (HM II) versus HVAD (HW) left ventricular assist devices (LVADs) for the past 7 years at our institution.

Methods

From July 2006 to August 2012, 121 consecutive patients underwent LVAD implantation: 70 (57.9%) received HM II and 51 (42.1%) HW. Patient demographics, perioperative characteristics, and laboratory parameters as well as postoperative outcome were compared retrospectively.

Results

Patients in the HM II group were significantly younger (P < .01), with more deranged liver function (higher bilirubin [P = .02] and alanine aminotransferase [P = .01] levels), and had a significantly higher rate of preoperative infections requiring antibiotic treatment (P = .02) and a higher body core temperature (P < .01). Other demographic and preoperative parameters did not show statistical differences. Most postoperative characteristics were also similar between the two groups. HM II patients had a significantly higher transfusion rate, but there were no differences in incidence of resternotomy (P = .156). Recovery and VAD explantation were more likely in the HM II group (P = .02). Although there was no significant difference in survival (log rank test: P = .986; Breslow test: P = .827), HM II patients were more likely to develop a percutaneous site infection (P = .01).

Conclusions

Both HM II and HW provide similar early postoperative outcome and good long-term survival. The differences observed between the groups may be related to demographic and preoperative factors rather than the type of the device used.     

Effects of Radiation on Protein Oxidation and Lipid Peroxidation in the Brain Tissue

Radiation produces reactive oxygen species that modify macromolecules such as protein and lipid by oxidation and act in many pathological processes, causing serious damage to the brain. This study sought to evaluate the effects of radiation and the protective effect of N-acetylcysteine (NAC) on the brain tissue of guinea pigs based on the levels of lipid peroxidation and protein oxidation. Thirty-two guinea pigs were divided into groups of eight animals each: control group (group I); radiation group (group II); NAC group (group III), and NAC administered before radiation exposure group; (group IV). Guinea pigs in groups II and IV were exposed to Co⁶⁰ radiotherapy using the Source-Axis-Distance = 80 technique. The levels of protein carbonyl content and malondialdehyde (MDA), which is a marker for lipid peroxidation, were investigated by the Evans-Levine and Uchiyama-Mihara methods, respectively. The protein carbonyl and MDA levels of group II were significantly greater than those of group I (P < .01). The protein carbonyl and MDA levels of group IV were lower than those of group II. The difference between the MDA levels of group IV and group II was significant (P < .01); however, the difference in protein carbonyl levels between the two groups was not significant. The results indicated that radiation increased protein oxidation and lipid peroxidation in the brain, and NAC administration before radiation exposure may aid in the treatment by decreasing protein and lipid oxidation.     

Randomized controlled pilot trial of nifedipine as oral therapy vs topical application in the treatment of fissure-in-ano

Background

Fissure-in-ano is a common condition that leads to pain and affects quality of life. Sphincterotomy remains the gold standard, but it may lead to troublesome incontinence in some patients. To overcome this problem, numerous pharmacologic therapies have been tested with varying outcomes. The investigators compared the effect of the addition of oral and topical nifedipine to conservative measures in the treatment of patients with fissure-in-ano.

Methods

Ninety patients with fissure-in-ano, randomized into 3 groups of 30 each, were included in the study. Group I received conventional treatment, group II received oral nifedipine and conventional treatment, and group III received topical nifedipine along with conventional treatment. Patients were followed for 8 weeks for pain relief (assessed using a visual analogue scale) and healing to evaluate the effect of treatment.

Results

Pain relief was significantly better in the group III at 3 weeks and 2 months compared with group I (P < .05). Groups II and III were comparable in terms of pain relief. Healing rates were significantly better in group II (P = .03) and group III (P = .00) compared with group I, but groups II and III were found to be comparable. Adverse effects were most commonly reported by group II patients, but these were not significantly higher than in other 2 groups.

Conclusions

We recommend the addition of either oral or topical nifedipine to conservative measures to significantly improve pain relief and healing rates in patients with fissure-in-ano.     

Downregulation of the expression of bone morphogenetic protein 7 in experimental pyelonephritis

Bone morphogenetic protein 7 (BMP 7) is a member of the transforming growth factor (TGF) beta superfamily and is involved in regeneration, repair, and development of specific tissues, for example kidney, gut, lens, and skeleton. BMP 7 has emerged as a renotrophic factor and experimental studies have shown its protective role against fibrotic processes. Tubulointerstitial changes are present in the pyelonephritic kidney which progresses to fibrosis. Renal fibrosis may lead to significant morbidity in the form of hypertension, proteinuria, and loss of renal function. The objective of this study was to investigate BMP 7 expression in experimental acute and chronic pyelonephritis models. Eighteen Wistar rats were injected with 0.1 mL solution containing E. coli ATCC 25922 10¹⁰ cfu mL^–1 into left renal medullae. Six rats were used as a sham group and were given 0.1 mL 0.9% NaCl. Pyelonephritic rats were sacrificed 24 h (group I, n=6), 1 week (group II, n=6), and 6 weeks (group III, n=6) after E. coli injection. Serum creatinine levels were analyzed. Renal tissues were studied histopathologically by use of hematoxylin and eosin and scored for diagnosis of pyelonephritis. BMP 7 expression was studied semiquantitatively by immunohistochemical staining. Acute (group I) and chronic (group II and group III) pyelonephritic histopathological changes were observed in experimental pyelonephritic groups. A gradual decrease in BMP 7 expression was observed in the tubulointerstitial and tubular area of the pyelonephritic kidneys, mildest in the acute pyelonephritic group and most severe in the chronic pyelonephritic 6th week group. A statistically significant difference was observed between tubulointerstitial BMP 7 expression by groups I and III (P=0.017) and by groups III and IV (P=0.000). Tubular BMP 7 expression was statistically significantly different between groups II and IV (P=0.009) and between groups III and IV (P=0.002). The data imply that BMP 7 has a major role in chronic pyelonephritis. Tubulointerstitial and tubular BMP 7 expression also had a significant negative correlation with fibrosis, tubular, atrophy, and vascular changes. Serum creatinine levels of the study group were all normal. We conclude that the decrease in renal BMP 7 expression in experimental chronic pyelonephritis is one of the factors responsible for fibrotic changes in persistent renal damage.     

Curcumin Nutrition for the Prevention of Mesenteric Ischemia-Reperfusion Injury: An Experimental Rodent Model

Background

Curcumin is an anti-oxidant molecule known to be a potent inhibitor of nuclear factor-κB (NF-κB). It has been shown to attenuate ischemia/reperfusion (I/R) injury in several organ systems. In this study, we sought to investigate the effects of curcumin on the prevention of superior mesenteric artery I/R injury in rats.

Methods

Wistar albino rats were randomly allocated to 3 groups: group I, sham operated (n = 10); group II, I/R injury only (n = 10); group III, curcumin-treated I/R cohort (n = 10). Group I animals underwent laparotomy without I/R injury. After group II animals underwent laparotomy, 60 minutes of superior mesenteric artery ligation were followed by 3 hours of reperfusion. In the curcumin group, 15 days before I/R, curcumin (40 mg/kg) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion. Intestinal tissue samples were obtained to investigate intestinal mucosal injury; in addition we estimated levels of myeloperoxidase (MPO) activity, malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), interleukin (IL)-6, and tumor necrosis factor (TNF)-α.

Results

There were statistically significant decreases in GSH levels, along with an increase in intestinal mucosal injury scores, MPO activity, MDA levels, NO, IL-6, and TNF-α in group I when compared with groups II and III (P = .01). Curcumin treatment in group III produced a significant increase in GSH levels, as well as a decrease in intestinal mucosal injury scores, MPO activity, MDA, and NO levels when compared with group II (P < .05).

Conclusion

This study showed that curcumin treatment significantly attenuated reperfusion injury in a superior mesenteric artery I/R model in rats.     

Effects of pretreatment with a small dose of dexmedetomidine on sufentanil-induced cough during anesthetic induction

Purpose

We aimed to investigate the effects of pretreatment with a small dose of dexmedetomidine on the cough caused by sufentanil during anesthetic induction.

Methods

Two hundred and forty patients undergoing elective gynecological surgery under general anesthesia were randomly allocated to 4 groups (n = 60, each group). Dexmedetomidine 0, 0.1, 0.25, and 0.5 μg/kg was administered in 5 min to groups I, II, III, and IV, respectively, followed by the induction of general anesthesia with intravenous propofol, at a target concentration of 5 μg/ml, and sufentanil 0.5 μg/kg. The incidences and severity of cough that occurred within 1 min after the injection of sufentanil were recorded, and the incidences of cardiovascular adverse events that occurred between the administration of the dexmedetomidine infusion and 1 min after tracheal intubation were recorded.

Results

The incidences of cough in group II, group III, and group IV were lower than that in group I (6.7, 5.0, and 6.7 vs. 26.7 %, P < 0.01), while there were no significant differences between group II, group III, and group IV. The incidences of severe sinus bradycardia in group III and group IV were higher than that in group I (18.3 and 23.3 vs. 0.0 %, P < 0.01), while there was no significant difference between group I and group II. There was no significant difference in the incidence of low blood pressure among the four groups.

Conclusion

Dexmedetomidine at 0.10, 0.25, and 0.50 μg/kg significantly reduced the incidence of sufentanil-induced cough during anesthetic induction, with the effect being most marked for 0.10 μg/kg dexmedetomidine.     

Factors associated with sustained virological response in liver transplant recipients with recurrent hepatitis C

Background

Antiviral therapy has achieved sustained virological response (SVR) in less than one third of orthotopic liver transplantation (OLT) patients with recurrent hepatitis C.

Aim

The aim of this study was to identify predictors of SVR in OLT patients treated with pegylated interferon and ribavirin (PEG+RBV) for recurrent hepatitis C virus (HCV).

Methods

We analyzed data from our transplantation database for 62 subjects treated with PEG+RBV between August 2001 and September 2008. After univariate examination for factors known to be associated with SVR, significant associations (P < .05) were probed using multivariate logistic regression. Kaplan-Meier patient and graft survival analyses were compared between patients with (n = 19; 30.6%) versus without SVR.

Results

On univariate analysis, longer duration of therapy, low pretreatment HCV RNA (<1 million IU/mL), and early virological response (EVR) were associated with SVR. On multivariate analysis, only low pretreatment HCV RNA predicted SVR. Patient survival was significantly higher in the SVR group.

Conclusions

Covariates associated with SVR among OLT patients with recurrent HCV were similar to the pretransplantation group. Potentially modifiable risk factors, such as obesity, diabetes mellitus, and metabolic syndrome, were not significant predictors of treatment response. Patient survival was associated with SVR, highlighting the impact of successful HCV therapy on long-term post-OLT outcomes.     

Parthenolide inhibits polyethylene particle–induced mouse calvarial osteolysis in vivo

Background

Periprosthetic osteolysis and aseptic loosening (AL) after joint arthroplasty are serious problems encountered after an implant surgery. AL is possibly caused by osteolysis or local bone resorption induced by implant-derived wear particles. However, effective treatments for osteoclastic bone resorption and AL mediated by wear particles have not been developed except surgical revision. Therefore, a new strategy should be developed to improve osteolysis associated with AL via pharmacologic intervention.

Materials and methods

The effects of parthenolide (PTN), a nuclear factor-kappa B inhibitor and sesquiterpene lactone, on polyethylene particle–induced osteolysis in vivo were investigated using a mouse calvarial model. Bone volume/tissue volume (BV/TV, %), bone surface/bone volume (BS/BV, 1/mm), osteoclast number per bone perimeter (N.Oc/B.Pm, /mm), and eroded surface per bone surface (ES/BS, %) were determined by micro-computed tomography and histologic analyses.

Results

Severe bone resorption and rapid osteoclast formation were found in the cranium of the subjects after polyethylene particles were implanted. ES/BS (P < 0.001), N.Oc/B.Pm (group III, P < 0.05; group IV, P < 0.001), and BS/BV (P < 0.001) increased compared with those in group II; BS/BV (P < 0.001) decreased in group II but was improved in groups III and IV, which were treated with PTN. No significant difference in these parameters was observed among groups I, III, and IV.

Conclusions

PTN possibly elicited therapeutic effects on osteolysis induced by wear particles, indicating that PTN could be used as a therapeutic agent of AL induced by wear particles.     

Antirejection Effect of Herba Asari Extract in Rats After Cardiac Allograft Implantation

Objective

We studied the antirejection effect of asarinin, the extract of Herba Asari, in rats that underwent cardiac allograft implantation.

Methods

Rats received either olive oil (as a placebo control) or cyclosporine, with various amounts of asarinin or a combination of asarinin and cyclosporine daily through oral administration. 102 recipient SD rats were divided randomly into 7 groups: 1) group A, treated with 8 ml/kg olive oil per day; 2) group B, treated with 2.5 mg/kg cyclosporin A (CsA) each day; 3) group C, treated with 5 mg/kg cyclosporin A (CsA) each day; 4) group D1, treated with 12.5 mg/kg asarinin each day; 5) group D2, treated with 25 mg/kg asarinin each day; 6) group D3, treated with 50 mg/kg asarinin each day; 7) group E, treated with 12.5 mg/kg asarinin and 2.5 mg/kg CsA each day. Allograft survival was observed in each group of rats. On the seventh day posttransplantation; we analyzed weights, pathological lesions, and the levels of interleukin (IL)-2, interferon (IFN)-γ, IL-4, and IL-10 in peripheral blood.

Results

The survival time of donor hearts in the asarinin groups was significantly prolonged (P < .01) when compared with the control group (7.8 ± 0.7 days). The weights of rats increased in group C, group D2, group D3, and group E at 7 days after operation. Pathological lesions were significantly less severe. The levels of IL-2 and IFN-γ decreased remarkably (P < .01), while those of IL-4 and IL-10 were not affected (P > .05) in the asarinin groups (D2 and D3).

Conclusions

Asarinin decreased peripheral blood concentrations of IL-2 and IFN-γ with prolongation of allograft heart survival.     

Volumetric hemodynamic changes and postoperative complications in hypothermic liver transplanted patients

Introduction

Hepatic diseases decrease the liver's involvement in thermoregulation. Removal of the liver during transplantation increases the incidence of hypothermia during the surgery. The aims of the present study were to analyze the hemodynamic changes among hypothermic liver transplantations and to determine its relationship to postoperative complications.

Methods

Conventional and volumetric hemodynamic monitoring and intramucosal pH measurements were performed during 54 liver transplantations. According to the core temperature until graft reperfusion, patients were classified into group A, hypothermic patients (temperature < 35°C; n = 25) versus group B, normothermic patients (temperature > 36°C; n = 29). We examined the relationships between central venous pressure (CVP), intrathoracic blood volume index, cardiac index (CI), and oxygen delivery index, oxygen consumption index, as well as the fluctuation of the mean arterial pressure (MAP) and gastric intramucosal pH and activated clotting time. We recorded prolonged ventilation time, vasopressor and hemodialysis requirements, occurrence of infections, and intensive care days.

Results

There were no significant differences in the MELD scores. More Child-Pugh class C patients (P < .01) showed significantly higher APACHE II scores (P < .02) among group A. During hepatectomy and at the same intrathoracic blood volumes, the hypothermic group showed significantly higher CVP levels (P < .02). During the anhepatic and postreperfusion phases, the decreased CI levels (P < .05) were associated with increased MAP values (P < .05). Without differences in oxygen delivery, the oxygen consumption was lower in group A (P < .05). The intramucosal pH levels were the same in the both groups during the whole examination period. More instances of infection, intensive care, and hemodialysis treatment days, were observed as well as significantly longer vasopressor requirements and coagulopathy among the hypothermic group (P < .007).