Effect of necrosis modulator necrox-7 on hepatic ischemia-reperfusion injury in beagle dogs

Objective

The liver is susceptible to ischemia-reperfusion (IR) injury during inflow occlusion for hepatectomy. There is no effective pharmacologic agent available to prevent the release of high-mobility-group box 1 (HMGB1) or to ameliorate IR injury. This pilot study sought to develop a model in beagle dogs for the purpose of testing the efficacy of a necrosis modulator, necrox-7, to prevent hepatic IR injury in beagle dogs.

Methods

Six male beagle dogs were randomly assigned to the control group (group A; n = 3) or the treatment group (group B; n = 3). Under general anesthesia, group B received intravenous infusion of necrox-7 (13 mg/kg over 20 minutes) followed by 60 minutes of left hepatic inflow occlusion and 60 minutes of reperfusion. Both groups were tested for serum biochemicals, hematology values, liver biopsies, and plasma HMGB1 levels over a 48-hour period.

Results

The maximum alanine transferase (ALT), aspartate transferase (AST), and lactate dehydrogenase (LDH) levels among group A versus group B were: ALT 868.3 ± 337.4 IU/L vs 274.3 ± 72.6 IU/L (P = .041); AST 1,024.7 ± 246.5 IU/L vs 505.3 ± 66.7 IU/L (P = .024); and LDH 962.7 ± 226.2 IU/L vs 552.7 ± 62.4 IU/L (P = .039). Liver biopsy demonstrated marked necrosis and inflammatory infiltrates in group A, whereas group B showed little evidence of IR injury. The plasma HMGB1 concentration was significantly lower among group B versus A.

Conclusion

This pilot study developed a hepatic IR injury model, demonstrating that necrox-7 reduced hepatic necrosis secondary to IR injury in a large animal setting.     

Use of 2.0 mini plate system as reduction plate

Fracture stabilization and reduction using temporary plates during intramedullary tibial nailing was introduced as a novel concept in fracture surgery by Benirschke et al. (Orthop Trans 18:1055–1056, 1995). The concept of temporary reduction using one-third tubular plates proved useful in aiding metaphyseal and periarticular fracture fixation also. However, planning the strategic location of final plate was the main limitation with this technique using one-third tubular plates. We used 2.0 mini plates as provisional reduction plates that solved the issue of planning and placement of plates. The main advantage of our technique is that the final definitive plate can be applied directly over the mini plates. Here, we will describe our technique using relevant fracture case in metaphyseal–periarticular location.     

Prostate calculi in cancer and BPH in a cohort of Korean men：presence of calculi did not correlate with cancer risk

Prostatic calculi are common and are associated with inflammation of the prostate. Recently,it has been suggested that this inflammation may be associated with prostate carcinogenesis. The aim of this study was to investigate the relationship between prostatic calculi and prostate cancer （PCa） in prostate biopsy specimens. We retrospectively analyzed 417 consecutive patients who underwent transrectal ultrasonography （TRUS） and prostate biopsies between January 2005 and January 2008. Based on the biopsy findings,patients were divided into benign prostatic hyperplasia and PCa groups. TRUS was used to detect prostatic calculi and to measure prostate volume.The correlations between PCa risk and age,serum total PSA levels,prostate volume,and prostatic calculi were analyzed. Patient age and PSA,as well as the frequency of prostatic calculi in the biopsy specimens,differed significantly between both the groups （P〈0.05）. In the PCa group,the Gleason scores （GSs） were higher in patients with prostatic calculi than in patients without prostatic calculi （P = 0.023）. Using multivariate logistic regression analysis,we found that patient age,serum total PSA and prostate volume were risk factors for PCa （P = 0.001）,but that the presence of prostatic calculi was not associated with an increased risk of PCa （P = 0.13）. In conclusion,although the presence of prostatic calculi was not shown to be a risk factor for PCa,prostatic calculi were more common in patients with PCa and were associated with a higher GS among these men.     

The long-term outcomes of transplantation of kidneys with multiple renal arteries

Kidneys with multiple renal arteries are increasingly procured for transplantation. To compare the outcomes of kidney transplantation using allografts with multiple arteries, we studied long-term graft function and survival according to their number of arterial anastomoses during an 18-year period from July 1, 1990, through December 31, 2008, in which only the recipient's external iliac artery or internal iliac artery was used for anastomosis (n = 1186). The recipients were divided into four groups: group I, single renal artery with single anastomosis (n = 890, 75.0%); group Il, multiple renal arteries, single anastomosis (n = 26, 2.2%); group Ill, multiple renal arteries, multiple anastomoses (n = 236, 19.9%); and group IV, polar artery ligation (n = 34, 2.9%). We compared the following variables patient and graft survivals; mean creatinine levels at 1 and 6 months, as well as 1-, 3-, and 5-years posttransplant; the number of acute rejection episodes, and the rates of vascular and urologic complications. The creatinine values and incidences of acute rejection episodes did not differ significantly (P = 0.399 and P = 0.990, respectively). There were no significant differences among the four groups in graft survival (P = 0.951), patient survival (P = 0.751), incidence of vascular (P = 0.999) or urologic complications (P = 0.371). The four groups were subdivided according to the recipient arterial anastomosis to the main graft renal artery. The subdivided groups showed no significant differences in graft or patient survival, or complications rates. The results indicated that multiplicity of renal arteries in kidney transplantation did not adversely affect allograft or patient survival compared with single renal artery transplantation. Moreover, the type of the arterial anastomosis (main renal artery end-to-end anastomosed to internal iliac artery or end-to-side anastomosed to external iliac artery appeared to not affect graft or patient survival or the incidence of vascular or urologic complications.     

Altered expression of K+ -Cl- cotransporters affects fast paired-pulse inhibition during GABA receptor activation in the gerbil hippocampus

K+ -Cl- cotransporter (KCC) plays an important role in maintaining neuronal activity. However, the effect of seizure activity or pharmacological manipulation of GABAergic transmission on KCC expression remains to be clarified. Therefore, the present study was performed to investigate whether seizure activity or GABA receptor agonist treatment changes KCC expression in the gerbil hippocampus. Furthermore, the effect of blockade of KCC on inhibitory transmission in the dentate gyrus was identified following applications of GABA receptor agonists. The distribution of KCC immunoreactivity in the hippocampus was similarly detected between seizure-resistant (SR) and seizure-sensitive (SS) gerbils. Baclofen (a GABAB receptor agonist) treatment markedly increased KCC expression in the gerbil hippocampus. Baclofen treatment significantly reduced paired-pulse inhibition in the dentate gyrus. Furosemide (a KCC inhibitor) treatment amplified the effect of baclofen on paired-pulse responses. In contrast, muscimol (a GABAA receptor agonist) treatment reduced KCC expression. Enhanced paired-pulse inhibition by muscimol treatment was not affected by furosemide treatment. These findings suggest that seizure activity in the gerbil may not affect KCC expression in the hippocampus. In addition, altered KCC immunoreactivity induced by baclofen or muscimol may play an important role in maintaining or regulating inhibitory transmission during GABA receptor activation.     

Association of APOE genetic polymorphism with cognitive function and suicide history in geriatric depression

Apolipoprotein E (APOE) has been associated with a variety of late-life neuropsychiatric disorders, including geriatric depression. This study determined whether APOE genotypes affect vulnerability to geriatric depression. We also tested the effect of the presence of the APOE epsilon4 (APOE4) allele on age of onset, suicide attempt history and cognitive function in geriatric depressed patients. We genotyped APOE in 111 elderly inpatients diagnosed as having major depression and 144 normal controls. The depressed patients were evaluated at baseline using the Hamilton Rating Scale for Depression and the Mini-Mental State Examination (MMSE) after admission. Age of onset of depression and suicide attempt history in the depressed group were evaluated by interview and medical record. We found no association between APOE genotypes and geriatric depression (p = 0.342) or APOE4 status and age of onset of depression (p = 0.281). However, compared with depressed subjects lacking the APOE epsilon4 allele, depressed subjects who were also APOE4 carriers showed significantly lower MMSE scores (p = 0.021) and an increased suicide attempt history (p = 0.012). The APOE genotype may contribute to cognitive performance and suicidality in geriatric depression, rather than being a specific risk factor for the disorder.     

Effect of splenic artery embolization for splenic artery steal syndrome in liver transplant recipients: estimation at computed tomography based on changes in caliber of related arteries

Purpose

To estimate the effect of splenic artery embolization (SAE) on blood flow in orthotopic liver transplantation (OLT) recipients with splenic artery steal syndrome (SASS) based on changes in caliber of related arteries upon serial computed tomography (CT) scans.

Methods

Between 2004 and 2007, nine OLT recipients with SASS underwent SAE. They had CT scans before and after SAE: short-, mid-, and long-term, ie, approximately 1 week, 1 month, and 1 year, respectively. The diameters of the celiac axis (CA), common hepatic artery (CHA), and splenic artery (SA) were measured with arterial phase of each CT scan and the ratios of SA to CHA diameter (SA/CHA) calculated to analyze their changes during the follow-up period.

Results

The diameters of celiac axis, CHA, and SA and SA/CHA changed most rapidly during the short-term period. The CHA diameter significantly increased short-term post-SAE by CT and slightly decreased thereafter. However, the mid-term and long-term post-SAE CT values were still significantly greater than those on the pre-SAE CT. The SA diameter steadily decreased throughout the follow-up. The SA/CHA decreased until the mid-term. The SA diameter and SA/CHA were significantly smaller upon mid-term and long-term post-SAE CT compared with those at pre-SAE CT.

Conclusions

The effect of SAE to improve hepatic arterial flow in OLT recipients with SASS might be expected for at least approximately one year. The effect maximally occurred during the short-term after SAE on the basis of changes in the caliber of related arteries upon CT.     

Aggressive Surgical Approach for Patients with T4 Gastric Carcinoma: Promise or Myth?

Background

Surgical outcomes of multiorgan resection (MOR) for T4 gastric carcinoma reported in the literature are widely variable. We herein report a large surgical series of T4 gastric carcinoma.

Methods

One hundred seventy-nine patients with cT4 gastric carcinoma were recruited onto the study. Patient characteristics, surgical strategy and related complications, long-term survival, and prognostic factors of T4 gastric carcinoma were analyzed.

Results

Of 179 cT4 gastric carcinoma, there were 57 cT4 (pT3) with MOR, 91 pT4 with MOR, and 31 cT4 without MOR. pT4 with MOR were more likely to be associated with nodal metastasis, cellular dedifferentiation, and lymphoperineural infiltration compared to those of pT0–3 (P < 0.01 for all). For 91 pT4 with MOR, their surgical mortality and morbidity rates were 4.4 and 28.6%, respectively; their 1-, 3-, and 5-year overall survival rates were 55.2, 22.4, and 12.2%, respectively. The long-term survival of cT4 (pT3) with MOR was superior to pT4 with MOR (P = 0.006) and cT4 without MOR (P = 0.004). There was a striking difference between pT4 with MOR, R0 and pT4 with MOR, and R1 or R2 (P = 0.007). By means of multivariate analysis, lymph node status, liver invasion, and positive surgical margin were independent prognostic factors.

Conclusions

Aggressive surgical management of pT4 gastric carcinoma should be limited to patients without adverse prognostic factors such as advanced nodal involvement and pancreatic invasion.     

Malignant peripheral nerve sheath tumor mimicking carotid body tumor--case report and review

Malignant peripheral nerve sheath tumor is a rare neurogenic tumor that usually presents in geriatic patients. Typically, it is found in the trunk and extremities and rarely presents in the head and neck region. It may mimic a carotid body tumor when it presents in the neck. We report the first case of malignant peripheral nerve sheath tumor of the vagus nerve in an adolescent boy. He presented with an asymptomatic lateral neck lump that was thought to be a benign schwannoma on preoperative imaging. We describe the diagnostic dilemma and management difficulties in this patient and review the literature.