PJ34, a poly-ADP-ribose polymerase inhibitor, modulates visceral mitochondrial activity and CD14 expression following thoracic aortic ischemia-reperfusion

Background

Visceral ischemia-reperfusion injury (VI) contributes to adverse outcomes following the repair of thoracoabdominal aneurysms. Experiments were designed to determine whether a poly-adenosine diphosphate-ribose polymerase (PARP) inhibitor modulates indexes of metabolic function (mitochondrial activity), inflammatory cell activation, and tissue inflammation (lipopolysaccharide receptor CD14 messenger ribonucleic acid) following VI.

Methods

129S1/SvImj mice were subjected to thoracic aortic occlusion followed by 48 hours of reperfusion. Normal saline was administered to 25 untreated control mice and PJ34 to 21 mice before and immediately after thoracic aortic ischemia-reperfusion. Sham mice (n = 13) underwent median sternotomy alone. At 48 hours, all animals were euthanized and tissues harvested for quantitative analysis.

Results

PJ34 improved intestinal (P < .05) but not hepatic mitochondrial activity following reperfusion. CD14 messenger ribonucleic acid levels in liver (P < .004), kidney (P < .003), and spinal cord (P < .03) tissue were less in PJ34-treated mice.

Conclusions

PJ34 preserved the metabolic function of intestinal but not hepatic tissue during reperfusion. PJ34 uniformly decreased the expression of an important marker of inflammatory cell activation and tissue inflammation in visceral tissue following VI. PARP inhibitors may serve as a therapeutic modality to abrogate the stress response to VI.     

Kaposi’s sarcoma following living donor kidney transplantation: review of 7,939 recipients

Introduction  Kaposi’s sarcoma (KS) is one of the most common tumors to occur in kidney recipients, especially in the Middle East countries. Limited data with adequate sample size exist about the development of KS in living kidney recipients. Methods  Therefore, we made a plan for a multicenter study, accounting for up to 36% (n = 7,939) of all kidney transplantation in Iran, to determine the incidence of KS after kidney transplantation between 1984 and 2007. Results  Fifty-five (0.69%) recipients who developed KS after kidney transplantation were retrospectively evaluated with a median follow-up of 24 (1–180) months. KS occurred more often in older age when compared to patients without KS (49 ± 12 vs. 38 ± 15 years, P = 0.000). KS was frequently found during the first 2 years after transplantation (72.7%). Skin involvement was universal. Furthermore, overall mortality rate was 18%, and it was higher in patients with visceral involvement compared to those with mucocutaneous lesions (P = 0.01). However, KS had no adverse affect on patient and graft survival rates compared to those without KS. Forty-four patients with limited mucocutaneous disease and four with visceral disease responded to withdrawal or reduction of immunosuppression with or without other treatment modalities. Renal function was preserved when immunosuppression was reduced instead of withdrawn in patients with and without visceral involvement (P = 0.001 and 0.008, respectively). Conclusion  The high incidence of KS in this large population studied, as compared to that reported in other transplant patient groups, suggests that genetic predisposition may play a pathogenetic role.     

Evaluation of a novel modified suture material designed to facilitate intracorporeal knot tying during laparoscopic surgery

BACKGROUND AND PURPOSE: Laparoscopic intracorporeal knot tying in minimally invasive surgery is an advanced skill. Mastering this skill is an arduous process with a long learning curve. While recent advances in instrumentation have allowed easier suturing and tying, until now, no attempts have been made to modify the suture material in order to facilitate this process. We present an evaluation of a novel modified suture material designed to allow inexperienced surgical residents to tie intracorporeal knots laparoscopically using conventional laparoscopic needle drivers. SUBJECTS AND METHODS: Surgical residents with no prior experience in laparoscopic surgery were invited to take part in this investigation. Each of the 14 participants was given a 10-minute demonstration of laparoscopic intracorporeal knot tying and then allowed a mentored practice session of 10 minutes. In the first trial, they were then randomized to tie a laparoscopic knot with either a standard or a modified dry suture. Time and accuracy scores were recorded. They then performed the same task with the other type of suture. On the second trial, wet standard and modified sutures were used, and the order of the sutures used in the first trial was reversed. RESULTS: The average time taken to tie an intracorporeal knot laparoscopically was significantly less when the modified suture was used in both dry and wet conditions (162.71 +/- 10.79 seconds v 270.86 +/- 22.76 seconds; P = 0.0039, and 123.29 +/- 4.70 seconds v 247.57 +/- 23.17 seconds; P = 0.0032, respectively). No significant difference in accuracy scores was noted with the two sutures. CONCLUSIONS: Our modified suture design allowed inexperienced surgical residents to perform intracorporeal laparoscopic knot tying on average faster than the standard suture did. The concept of modifying suture design to facilitate laparoscopic suturing and knot tying deserves further investigation and development.     

Off-pump coronary artery grafting in patients with left main coronary artery disease

BACKGROUND: Left main coronary artery disease (LMCD) is considered a relative contraindication to off-pump coronary artery bypass (OPCAB) grafting. This study evaluates the safety and feasibility of OPCAB in these patients compared to an on-pump group (cardiopulmonary bypass, CPB) with LMCD. METHODS: Between January 2000 and July 2002, 95 patients with left main coronary artery stenosis >50% underwent coronary revascularization. Seventy-three unselected patients underwent OPCAB and 22 underwent revascularization using CPB. The techniques used for OPCAB included the use of deep traction sutures in the posterior pericardium and stabilizers to expose the distal coronary targets. Intraluminal coronary shunts were routinely used during construction of the anastomoses. Variables were analyzed using a Student's paired t-test with statistical significance defined as p < 0.05. RESULTS: The mean age in the OPCAB group was 59.9 years and the CPB group 61.8 years (p = 0.54). There were 56 males (77%) in the OPCAB and 18 (82%) in the CPB groups. Mean preoperative left ventricular ejection fraction (LVEF) was 40.3% in OPCAB and 47.3% in CPB (p = 0.015). Average number of grafts was 3.1 in OPCAB and 4.1 in CPB (p = 0.0038). There were no conversions to CPB in those patients initially chosen to undergo OPCAB. There were no early deaths in OPCAB. There was one death in CPB. Mean hospital length of stay was 6.9 days for OPCAB and 9.1 for CPB (p = 0.0159). CONCLUSIONS: Patients with LMCD can undergo OPCAB grafting safely and effectively despite reduced LVEF. LMCD should no longer be seen as a contraindication to perform OPCAB grafting.     

Control of severe hemorrhage using C-clamp and arterial embolization in hemodynamically unstable patients with pelvic ring disruption

Introduction

Hemorrhage is the leading cause of death in patients with a pelvic fracture. The majority of blood loss derives from injured retroperitoneal veins and broad cancellous bone surfaces. The emergency management of multiply injured patients with pelvic ring disruption and severe hemorrhage remains controversial. Although it is well accepted that the displaced pelvic ring injury must be rapidly reduced and stabilized, the methods by which control of hemorrhagic shock is achieved remain under discussion. It has been proposed to exclusively use external pelvic ring stabilization for control of hemorrhage by producing a ‘tamponade effect’ of the pelvis. However, the frequency of clinically important arterial bleeding after external fixation of the pelvic ring remains unclear. We therefore undertook this retrospective review to attempt to answer this one important question: How frequently is arterial embolization necessary to control hemorrhage and restore hemodynamic stability after external pelvic ring fixation?

Materials and methods

We performed a retrospective review of 55 consecutive patients who presented with unstable types B and C pelvic ring fractures. Those patients designated as being in hemorrhagic shock (defined as a systolic blood pressure less than 90 mmHg after receiving 2 L of intravenous crystalloid) were treated by application of the pelvic C-clamp. Patients who remained in hemorrhagic shock, or were determined to be in severe shock (defined as mandatory catecholamines or more than 12 blood transfusions over 2 h), underwent therapeutic angiography within 24 h in order to control bleeding.

Results

Fourteen patients were identified as being hemodynamically unstable (ISS 30.1±11.3 points) and were treated with a C-clamp. In those patients with persistent hemodynamic instability, arterial embolization was performed. After C-clamp application, 5 of 14 patients required therapeutic angiography to control bleeding. Two patients died, one from multiple sources of bleeding and the other from an open pelvic fracture (total mortality 2/14, 14%).

Conclusions

Although the C-clamp is effective in controlling hemorrhage, one must be aware of the need for arterial embolization to restore hemodynamic stability in a select subgroup of patients.

     

CXC chemokine expression and synthesis in skeletal muscle during ischemia/reperfusion

BACKGROUND: The chemokines keratinocyte-Derived Cytokine (KC) and macrophage inflammatory protein (MIP)-2, murine equivalents of human interleukin 8, have been implicated in remote injury after acute hind limb ischemia/reperfusion (I/R). These studies were designed to determine whether the cytokines responsible for remote tissue injury are also synthesized and accumulate in the ischemic or reperfused hind limb. METHODS: B6, 129SF2/J mice were subjected to either 3 hours of unilateral hind limb ischemia alone (IA) or 3 hours of ischemia followed by 4 or 24 hours of reperfusion (I/R). After IA or I/R, experimental and control (nonischemic) contralateral hind limbs were harvested for analysis of protein content, messenger RNA (mRNA), tissue edema, and viability. RESULTS: IA did not increase KC or MIP-2 mRNA or protein levels. In contrast, I/R resulted in a 15- and 10-fold increase in KC mRNA after 4 and 24 hours of reperfusion, respectively. KC protein levels were increased 10-fold after 4 hours of reperfusion and 30-fold after 24 hours (vs IA or sham; P < .001). MIP-2 mRNA transiently increased 42-fold after 4 hours of reperfusion but decreased to basal levels after 24 hours of reperfusion. Despite the relative increase in MIP-2 mRNA by 4 hours of reperfusion, significantly increased (8- to 10 fold) MIP-2 protein levels were not detected until 24 hours of reperfusion only in the reperfused limbs. Tissue edema was increased significantly (P < .01) compared with sham after just 4 hours of reperfusion and remained increased at 24 hours. Tissue viability decreased 52% after 4 hours of reperfusion and did not change significantly by 24 hours. CONCLUSIONS: Skeletal muscle is a site of significant ongoing chemokine synthesis during reperfusion. The persistent increase in muscle chemokine levels at 24 hours of reperfusion was not associated with increased edema or injury. The role of these chemokines during reperfusion may be further investigated by local or oral administration of chemokines or chemokine receptor antagonists. CLINICAL RELEVANCE: I/R injury remains an important clinical problem across a variety of surgical specialties. In the critical care arena, serum levels of proinflammatory cytokines have been useful in predicting the mortality associated with acute respiratory distress syndrome and sepsis. In this article, the data presented indicate that murine skeletal muscle produces potent proinflammatory neutrophil and macrophage chemokines during reperfusion, but not during ischemia. These findings suggest that measurement of tissue and/or serum levels of chemokines during reperfusion may be an important adjunct to predicting tissue injury along with ongoing inflammation during the clinical course of reperfusion injury. Within the vascular system, severe inflammatory responses are usually associated with thrombotic events. New techniques to noninvasively image thrombin activation (by using magnetic resonance imaging) in reperfused limbs may coincide with the pattern of murine skeletal muscle chemokine expression in humans. The data suggest that reperfusion is when chemokine mRNA and protein synthesis increase. Within the time periods studied in these experiments, the chemokine component of the inflammatory response remained in the reperfused, rather than the systemic nonreperfused, tissue. This observation may underestimate the degree of the systemic response to ischemia because the single mouse hind limb represents only 7% of the mouse total body area, whereas the human limb represents nearly 18% of the adult body area. Despite this shortcoming, these data provide potential temporal and quantitative information regarding the location and magnitude of chemokine synthesis in skeletal muscle during reperfusion.     

Bilateral gluteal compartment syndrome after total hip arthroplasty under epidural anesthesia

The gluteal compartment syndrome is uncommon and is discussed in only a few published case reports. The simultaneous bilateral gluteal compartment syndrome is exceptionally rare and is tackled in only 4 case reports to date. We report a case of bilateral gluteal compartment syndrome after total hip arthroplasty under epidural anesthesia and discuss its management.     

Curative potential of multimodality therapy for locally recurrent rectal cancer

OBJECTIVE: To assess the results of multimodality therapy for patients with recurrent rectal cancer and to analyze factors predictive of curative resection and prognostic for overall survival. SUMMARY BACKGROUND DATA: Locally recurrent rectal cancer is a difficult clinical problem, and radical treatment options with curative intent are not generally accepted. METHODS: A total of 394 patients underwent surgical exploration for recurrent rectal cancer. Ninety were found to have unresectable local or extrapelvic disease and 304 underwent resection of the recurrence. The latter patients were prospectively followed to determine long-term survival and factors influencing survival. RESULTS: Overall 5-year survival was 25%. Curative, negative resection margins were obtained in 45% of patients; in these patients a 5-year survival of 37% was achieved, compared to 16% (P <.001) in patients with either microscopic or gross residual disease. In a logistic regression analysis, initial surgery with end-colostomy and symptomatic pain (both univariate) and increasing number of sites of the recurrent tumor fixation in the pelvis (multivariate) were associated with palliative surgery. Overall survival was significantly decreased for symptomatic pain (P <.001) and more than one fixation (P =.029). Survival following extended resection of adjacent organs was not different from limited resection (28% vs. 21%, P =.11). Patient demographics and factors related to the initial rectal cancer did not affect outcome. Perioperative mortality was only 0.3%, but significant morbidity occurred in 26% of patients, with pelvic abscess being the most common complication. CONCLUSIONS: This study demonstrates that many patients with locally recurrent rectal cancer can be resected with negative margins. Long-term survival can be achieved, especially for patients with no symptoms and minimal fixation of the recurrence in the pelvis, provided no gross residual disease remains.     

Content-based medical image classification using a new hierarchical merging scheme

Automatic medical image classification is a technique for assigning a medical image to a class among a number of image categories. Due to computational complexity, it is an important task in the content-based image retrieval (CBIR). In this paper, we propose a hierarchical medical image classification method including two levels using a perfect set of various shape and texture features. Furthermore, a tessellation-based spectral feature as well as a directional histogram has been proposed. In each level of the hierarchical classifier, using a new merging scheme and multilayer perceptron (MLP) classifiers (merging-based classification), homogenous (semantic) classes are created from overlapping classes in the database. The proposed merging scheme employs three measures to detect the overlapping classes: accuracy, miss-classified ratio, and dissimilarity. The first two measures realize a supervised classification method and the last one realizes an unsupervised clustering technique. In each level, the merging-based classification is applied to a merged class of the previous level and splits it to several classes. This procedure is progressive to achieve more classes. The proposed algorithm is evaluated on a database consisting of 9100 medical X-ray images of 40 classes. It provides accuracy rate of 90.83% on 25 merged classes in the first level. If the correct class is considered within the best three matches, this value will increase to 97.9%.