The Effect of Vitamin E Succinate on Ischemia Reperfusion Injury

Ischemia–reperfusion (I/R) injury is, in part, related to the burst of reactive oxygen species (ROS) generated after reperfusion. Vitamin E has been shown to exert its biological effects as an antioxidant, inhibiting the ROS. In this report, the effect of Vitamin E succinate (VES) on ischemia/reperfusion injury and NF-κB expression was studied in a rat skeletal muscle model during reperfusion following a 4-h ischemic period. The study group consisted of muscle flaps infused with 150 mg/kg of VES given intraperitoneally 1 h post-initiation of ischemia. Muscle viability based on nitroblue tetrazolium staining, edema, and Doppler blood flow was measured in a control and a study group. Muscle samples were analyzed by standard gel shift assay. The VES experimental group showed an increase in muscle viability compared to controls (average of 44.675% versus 31.925%, respectively, p = 0.0415). Blood flow, measured by Doppler 24 h after reperfusion, was increased in the VES study group compared to controls (10.3 vs. 5.1 ml/g/s p = 0.00355). Additionally, the VES group showed a trend of decreasing edema compared with the control; however, not at a level that was statistically significant (p = 0.1267). The VES-treated group showed a decreased expression of NF-κB as compared to controls (p < 0.05). These results show that vitamin E succinate has a protective effect in preventing I/R injury as measured by increased muscle viability and reperfusion blood flow. Vitamin E can exert its efforts as an antioxidant as well as other biological roles, including inhibition of NF-κB.     

Effect of fluid resuscitation on acute skeletal muscle ischemia-reperfusion injury after hemorrhagic shock in rats

BACKGROUND: Severe extremity wounds with vascular injury are common in military trauma, and tourniquets are commonly used for hemorrhage control. The complications of tourniquet use in the setting of trauma are not well studied. This study investigated the combined effect of hemorrhagic shock and fluid resuscitation with Hextend (HX; BioTime, Inc) or lactated Ringer's (LR) on skeletal muscle subjected to tourniquet-induced ischemia-reperfusion injury. STUDY DESIGN: Thirty male Sprague-Dawley rats underwent 33% arterial hemorrhage followed by 3 hours of tourniquet application. Before reperfusion, 10 animals each were resuscitated with lactated Ringer's (3 times shed volume) or HX (shed volume). Ten control animals received no resuscitation. Rats were euthanized 2 hours after tourniquet release and the tibialis anterior and medial gastrocnemius muscles were examined for edema (muscle wet weight) and viability (nitroblue tetrazolium reduction). Contralateral muscles served as controls for each animal, with results expressed as the ratio of the tourniquet limb to contralateral limb values. RESULTS: The tibialis anterior and medial gastrocnemius muscles in all groups experienced edema, with all weight ratios greater than one. Resuscitation with HX resulted in significantly (p < 0.05) greater edema than did no resuscitation in both muscles and greater edema than with lactated Ringer's in the medial gastrocnemius. All groups experienced a loss of viability as well, with nitroblue tetrazolium reduction ratios less than one. Resuscitation with HX resulted in significantly less viability loss than did no resuscitation in the medial gastrocnemius. No significant differences in viability were seen in the tibialis anterior. CONCLUSIONS: Resuscitation with HX or lactated Ringer's does not adversely affect muscle viability in ischemia-reperfusion injury. HX may be a better clinical choice when skeletal muscle ischemia-reperfusion injury is a risk, despite greater edema.     

Simvastatin pretreatment reduces the severity of limb ischemia in an experimental diabetes model

OBJECTIVE: The purpose of this study was to examine the effects of simvastatin pretreatment in the setting of acute limb ischemia-reperfusion injury in an experimental diabetes model that is associated with a high risk for limb loss. METHODS: Adult male Sprague-Dawley rats were randomized into two groups. Diabetes was induced in the first group by intravenous streptozotocin injection. The second group served as the nondiabetic group. Eight weeks after the streptozotocin injection, half of the rats in the diabetic and the nondiabetic groups were further randomized to receive either intraperitoneal simvastatin (1 mg/kg per day) or saline treatment for 6 weeks. Bilateral hind-limb ischemia was induced for 4 hours by the tourniquet method. After 24 hours of reperfusion, tissue samples were collected from the gastrocnemius and anterior tibial muscles bilaterally for measurement of muscle edema, percentage of necrosis, and malondialdehyde (MDA), glutathione, and myeloperoxidase (MPO) levels. RESULTS: Ischemic injury was more prominent in diabetic animals. The diabetic animals with limb ischemia exhibited a 7% increase in tissue edema, a 47% increase in muscle necrosis and MPO level, and a 15% reduction in glutathione levels compared with the nondiabetic animals (P < .05). Simvastatin treatment with 1 mg/kg for 6 weeks reduced the ischemic injury. Simvastatin pretreatment led to a 71% reduction in muscle necrosis in diabetic animals (P < .001). The protective effects of simvastatin pretreatment also correlated with a 23% improvement in tissue edema, a 75% reduction in tissue myeloperoxidase content, and a 71% increase in glutathione levels in diabetic animals (P < .01). Furthermore, skeletal muscle injury, characterized by tissue edema and leucosequestration, was significantly less severe with simvastatin pretreatment compared with the nondiabetic animals (P < .01). CONCLUSION: Simvastatin pretreatment reduced limb ischemia-reperfusion injury in diabetic and nondiabetic animals. We conclude that simvastatin pretreatment may be a potential therapeutic intervention for skeletal muscle ischemia-reperfusion injury in the clinical setting.     

Hyperbaric Oxygen Therapy Reduces Severity and Improves Survival in Severe Acute Pancreatitis

Severe acute pancreatitis is characterized by pancreatic necrosis, resulting in local and systemic inflammation. Hyperbaric oxygen (HBO) therapy modulates inflammation, but has not been extensively studied in pancreatitis. This study investigates the effects of HBO in a rat model of severe acute pancreatitis. Sixty-four rats were induced with severe pancreatitis using 4% sodium taurocholate and randomized to HBO treatment or control. HBO was commenced 6 h after induction (100% oxygen at 2.5 atmospheres for 90 min) and continued every 12 h for a maximum of eight treatment episodes. Surviving animals were killed at 7 days. Severity of pancreatitis was graded macroscopically and microscopically. Lung edema was calculated using wet and dry lung weights. Macroscopic and microscopic severity scores (mean ± SE) of HBO-treated animals with pancreatitis (8.3 ± 0.7; 9.6 ± 0.4) were lower than those of controls (10.5 ± 0.5; 11.1 ± 0.4) (p = 0.02 and p = 0.03, respectively). The HBO-treated group had reduced pancreatic necrosis compared to controls (40 ± 4% vs. 54 ± 4%; p = 0.003). There was no difference in pulmonary edema between the groups. Median survival in the HBO-treatment group was 51 h, compared to 26 h in controls. Day-7 survival was significantly improved in the HBO-treated animals compared to controls (40% vs. 27%; p = 0.04). HBO therapy reduces overall severity, decreases the extent of necrosis, and improves survival in severe acute pancreatitis.     

Vaginal smooth muscle cell apoptosis is increased in women with pelvic organ prolapse

To compare the smooth muscle content and apoptosis of the vagina in women with and without anterior vaginal wall prolapse. Vaginal tissues were sampled in women with (n = 6) or without (n = 6) anterior vaginal wall prolapse undergoing hysterectomy. Smooth muscle of the vagina was studied by immunohistochemistry. Digital image analysis was used to determine the fractional area of smooth muscle in the histologic cross-sections. Apoptosis was assessed by TUNEL assay. The fractional area of non-vascular smooth muscle in the vagina of women with anterior vaginal wall prolapse was significantly decreased compared to women without prolapse (0.36 ± 0.12 vs. 0.16 ± 0.12 P = 0.021) and the apoptotic index was significantly higher compared to women without prolapse (0.04 ± 0.01 vs. 0.02 ± 0.03, P = 0.041). The fraction of smooth muscle in the vagina is significantly decreased and the rate of apoptosis is higher in women with anterior vaginal wall prolapse compared to women without prolapse.     

Remote Renal Injury Following Partial Hepatic Ischemia/Reperfusion Injury in Rats

Liver ischemia/reperfusion has been shown to result in injury of remote organs such as the heart and lungs. Whether or not acute liver injury also results in kidney injury has so far not been adequately addressed. In anesthetized Wistar rats, partial (70%) normothermic hepatic ischemia was applied for 75 min. After 24 h of reperfusion, renal injury was assessed by histology, creatinine and blood urea nitrogen (BUN) serum concentrations, renal expression of proinflammatory genes [quantitative real-time polymerase chain reaction (qRT-PCR)], caspase-3 activation (Western blot), and neutrophil accumulation (myeloperoxidase assay). Twenty-four hours after hepatic ischemia, creatinine (0.57 ± 0.06 vs. 0.32 ± 0.04 mg/dL) and BUN (40.7 ± 15.3 vs. 14.3 ± 2.0 mg/dL) were increased when compared to sham. qRT-PCR revealed higher renal intercellular adhesion molecule-1 gene expression following hepatic ischemia (166 ± 45% when compared to sham) but no differences in renal monocyte chemoattractant protein-1, macrophage inflammatory protein-2, and inducible NO synthase expression. In both groups, kidneys showed no morphological damage and no increase in caspase-3 and myeloperoxidase activity. Severe hepatic ischemia results in a moderate impairment of renal function in rats but does not trigger an inflammatory response in the kidney and does not result in morphological damage of the kidney. A part of this study has been presented as a poster presentation at the 2006 Congress of the American Hepato-Pancreato-Biliary Association in Miami Beach, FL, March 9–12.     

A comparison of acute mouse hindlimb injuries between tourniquet- and femoral artery ligation-induced ischemia-reperfusion

The tourniquet or femoral artery ligation is widely used to stop extremity hemorrhage or create a bloodless operating field in the combat scenario and civilian setting. However, these procedures with subsequent reperfusion also induce ischemia-reperfusion (IR) injuries. To fully evaluate animal models of limb IR injuries, we compared tourniquet- and femoral artery ligation-induced IR injuries in the hindlimb of mice. In C57/BL6 mice, 3 h of unilateral hindlimb ischemia was induced by placement of a rubber band at the hip joint or a surgical ligation of the femoral artery. The tourniquet or femoral artery ligation was then released, allowing for 24 h of reperfusion. Compared to the femoral artery ligation/IR, the tourniquet/IR induced more severe skeletal muscle damage, including muscle necrosis and interruption of muscle fibers. There was no gastrocnemius muscle contraction in tourniquet/IR, while femoral artery ligation/IR markedly weakened gastrocnemius muscle contraction. Motor nerve terminals disappeared, and endplate potentials (EPPs) were undetectable in tourniquet/IR, whereas femoral artery ligation/IR only induced mild impairment of motor nerve terminals and decreased the amplitude of EPPs. Additionally, western blot data showed that proinflammatory cytokine levels (IL-1β and TNF-α) were higher in the tourniquet/IR than that in femoral artery ligation/IR. Moreover, tourniquet/IR caused significant tissue edema and dilation of lymphatic vessels in the hindlimb, compared to femoral artery ligation/IR. The above data demonstrated that tourniquet/IR-induced acute hindlimb injuries are more severe than those induced by femoral artery ligation/IR. This suggests that future investigators should determine which hindlimb IR model (tourniquet/IR or femoral artery ligation/IR) is optimal depending on the purpose of their study.     

Diode Laser Trabeculoplasty Versus Argon Laser Trabeculoplasty in the Control of Primary Open Angle Glaucoma

A randomised prospective study was carried out to determine whether diode laser trabeculoplasty (DLT) is as effective as argon laser trabeculoplasty (ALT) in the control of primary open angle glaucoma (POAG). Forty eyes of 40 patients with uncontrolled intraocular pressure (IOP) despite maximum topical medication were entered into the study. Twenty eyes received DLT, spot size 100 μm, exposure time 0.2 s, mean power 1034 (±56.4) mW. Twenty eyes received ALT, spot size 50 μm, exposure time 0.2 s, mean power 528 (±44.7) mW. They were reviewed at 2 h, 2 and 8 weeks, and 3, 6, 12, 18 and 24 months after laser treatment. Two eyes were withdrawn from the DLT group and four from the ALT group because of uncontrolled IOP during follow-up. Of the remaining eyes in the trial, mean IOP reductions for DLT and ALT, respectively, were: 6 months 7.42 (±2.36) mmHg and 6.36 (±2.3) mmHg; 12 months 7.02 (±2.6) mmHg and 6.28 (±2.2) mmHg; 18 months 6.86 (±2.8) mmHg, 5.98 (±2.02) mmHg; 24 months 6.50 (±2.72) mmHg, 5.92 (±2.02) mmHg. There was a significant reduction in each laser group when IOP at each stage was compared with baseline (p<0.001) (paired Student's t-test), but no significant difference between the two groups. In the ALT group peripheral anterior synechiae developed in four eyes and post laser pain in seven eyes. These complications were not noted following DLT. We conclude that DLT and ALT are equally effective in IOP control, but DLT is associated with less anterior segment inflammation. Paper received 18 February 1997; accepted after revision 14 August 1998.     

Hypothermic in situ perfusion of the porcine liver using Celsior or Ringer-lactate solution

Background  Hypothermic perfusion (HP) of the liver is applied during total vascular exclusion (TVE) to reduce ischemic injury during liver resection. No studies have been performed comparing different perfusion solutions for HP. The aim of this experimental study was to compare Ringer-lactate solution (RL) with Celsior solution (Cs) for HP in a pig model of 60-min TVE. Method  Twenty pigs underwent 60-min TVE of the liver. Groups were TVE without HP (no-HP, n = 9), TVE with HP using RL (n = 6), and TVE with HP using Cs (n = 5). Blood and liver tissue samples were taken before TVE and during 24-h reperfusion. Results  In the no-HP group, plasma aspartate aminotransferase values were significantly increased during reperfusion (p < 0.05), while liver tissue pO₂ levels (p < 0.01) were decreased when compared to the HP groups. After 24-h reperfusion, bile production and liver tissue glutathione content were significantly higher (p < 0.05) in the Cs group (42.0 ± 1.7 mL/h and 44.9 ± 2.2 nmol/mg, respectively) as compared to the RL group (31.5 ± 3.5 mL/h and 19.6 ± 1.8 nmol/mg, respectively). Conclusion  The protective effect of HP during TVE was confirmed in this study. HP with Cs was more effective in reducing ischemic injury as compared to HP with RL.     

Biomechanical comparison of different fixation methods on the tibial side in anterior cruciate ligament reconstruction: a biomechanical study in porcine tibial bone

Background The fixation strength of the hamstring tendon graft on the tibial side is considered the weak point in anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to compare the biomechanical characteristics of four types of ACL reconstruction methods on the tibial side. Methods Extensor digitorum tendons harvested from fresh bovine forelimbs were used as the graft materials in this study. Twenty-eight porcine tibias were divided into four groups based on different fixation methods. Group D was fixed using a double spike plate (DSP), group I was fixed using an interference screw, group DI-80 was fixed using both an interference screw and DSP (80 N tension was applied to DSP), and group DI-150 was fixed using both an interference screw and DSP (150 N tension was applied to DSP). Results The displacement of the grafts in response to 500 cycles of 0–150 N loading was significantly greater in groups D (10.3 ± 15 mm) and I (5.5 ± 1.7 mm) than that in groups DI-80 (2.1 ± 0.3 mm) and DI-150 (1.2 ± 0.4 mm), with no significant differences between groups DI-80 and DI-150. The ultimate failure load and stiffness were significantly higher in groups DI-80 (745 ± 156 N, 103 ± 17 N/mm) and DI-150 (801 ± 129 N, 151 ± 35 N/mm) than those in groups D (374 ± 53 N, 70 ± 13 N/mm), and I (520 ± 76 N, 78 ± 18 N/mm). The stiffness of group DI-150 was significantly greater than that of group DI-80. Conclusions Our results indicate that the initial fixation strength of the hamstring tendon can be increased by using an interference screw combined with DSP on the tibial side.     

The Effect of Deferoxamine on Ischemic Changes in Rat Skeletal Muscle: A Preliminary Study

The purpose of this study was to evaluate the effectiveness of deferoxamine in preventing detrimental microvascular changes in ischemically damaged skeletal muscle during the initial reperfusion stage. Sprague-Dawley rats were given saline or deferoxamine (25 or 50 mg/kg) intravenously just prior to release of an air tourniquet placed around one hindlimb for 4 h. The limb was allowed to reperfuse for 2 h. Vascular leakage of plasma protein was assayed by determining the amount of ¹³¹I-labeled serum albumin that was given intravenously 30 min prior to release of the tourniquet. The wet and dry weights of the gastrocnemius and tibialis anterior muscles and the ¹³¹I activity were evaluated in both ischemic and nonischemic limbs. Although vascular permeability and edema increased markedly in both muscles in the ischemic limbs, there were no significant differences between the saline or either treatment groups. The lack of effect of deferoxamine in this initial report suggests that skeletal muscle may differ from other tissues in the early reperfusion stage.     

The effect of deferoxamine on ischemic changes in rat skeletal muscle: a preliminary study.

The purpose of this study was to evaluate the effectiveness of deferoxamine in preventing detrimental microvascular changes in ischemically damaged skeletal muscle during the initial reperfusion stage. Sprague-Dawley rats were given saline or deferoxamine (25 or 50 mg/kg) intravenously just prior to release of an air tourniquet placed around one hindlimb for 4 h. The limb was allowed to reperfuse for 2 h. Vascular leakage of plasma protein was assayed by determining the amount of 131I-labeled serum albumin that was given intravenously 30 min prior to release of the tourniquet. The wet and dry weights of the gastrocnemius and tibialis anterior muscles and the 131I activity were evaluated in both ischemic and nonischemic limbs. Although vascular permeability and edema increased markedly in both muscles in the ischemic limbs, there were no significant differences between the saline or either treatment groups. The lack of effect of deferoxamine in this initial report suggests that skeletal muscle may differ from other tissues in the early reperfusion stage.     

Use of dextran sulfate in tourniquet-induced skeletal muscle reperfusion injury

Background

Lower extremity ischemia–reperfusion injury (IRI)—prolonged ischemia and the subsequent restoration of circulation—may result from thrombotic occlusion, embolism, trauma, or tourniquet application in surgery. The aim of this study was to assess the effect of low-molecular-weight dextran sulfate (DXS) on skeletal muscle IRI.

Methods

Rats were subjected to 3 h of ischemia and 2 or 24 h of reperfusion. To induce ischemia the femoral artery was clamped and a tourniquet placed under the maintenance of the venous return. DXS was injected systemically 10 min before reperfusion. Muscle and lung tissue samples were analyzed for deposition of immunoglobulin M (IgM), IgG, C1q, C3b/c, fibrin, and expression of vascular endothelial-cadherin and bradykinin receptors b1 and b2.

Results

Antibody deposition in reperfused legs was reduced by DXS after 2 h (P < 0.001, IgM and IgG) and 24 h (P < 0.001, IgM), C3b/c deposition was reduced in muscle and lung tissue (P < 0.001), whereas C1q deposition was reduced only in muscle (P < 0.05). DXS reduced fibrin deposits in contralateral legs after 24 h of reperfusion but did not reduce edema in muscle and lung tissue or improve muscle viability. Bradykinin receptor b1 and vascular endothelial-cadherin expression were increased in lung tissue after 24 h of reperfusion in DXS-treated and non-treated rats but bradykinin receptor b2 was not affected by IRI.

Conclusions

In contrast to studies in myocardial infarction, DXS did not reduce IRI in this model. Neither edema formation nor viability was improved, whereas deposition of complement and coagulation components was significantly reduced. Our data suggest that skeletal muscle IRI may not be caused by the complement or coagulation alone, but the kinin system may play an important role.     

Prevention of postoperative nausea and vomiting in children following adenotonsillectomy,using tropisetron with or without low-dose dexamethasone

Purpose Postoperative nausea and vomiting (PONV) after adenotonsillectomy in children is, in spite of the prophylactic administration of tropisetron, still a frequent event. The aim of this study was to evaluate the benefit of the additional systemic administration of low-dose dexamethasone (0.15 mg·kg⁻¹) for the prevention of PONV. Methods With hospital ethics committee approval, we investigated children undergoing adenotonsillectomy receiving tropisetron (0.1 mg·kg⁻¹; maximum dose, 2 mg) or tropisetron (0.1 mg·kg⁻¹; maximum dose, 2 mg) plus dexamethasone (0.15 mg·kg⁻¹; maximum dose, 6 mg) intraoperatively. The incidence of vomiting episodes and the need for postoperative analgesics were recorded. Patient data were analyzed using the t-test and the χ² test (significance level of P = 0.05). Data values are means ± SD. Results Ninety children (39 girls and 51 boys), aged 5.6 ± 2.8 years and weighing 21.9 ± 8.8 kg, were enrolled in the study. The overall incidence of vomiting was 38.9% within the first 24 h (67 vomiting events) and 44.4% within 48 h postoperatively (87 vomiting events). The incidence of vomiting in the tropisetron-only group was 53.3% (24/45) at 24 h and 60% (27/45) at 48 h (24 h: P < 0.001 and 48 h: P = 0.04) and 24.4% (11/45) at 24 h and 28.9% (13/45) at 48 h in the tropisetron-dexamethasone group. The need for postoperative nalbuphine was double in patients treated with tropisetron-dexamethasone (0.61 mg ± 0.36 mg·kg⁻¹·48 h⁻¹) compared to that in patients receiving only tropisetron (0.31 mg ± 0.28 mg·kg⁻¹·48 h⁻¹; P < 0.0001). Conclusion A low-dose bolus of dexamethasone (0.15 mg·kg⁻¹) in combination with tropisetron, compared to tropisetron alone, considerably reduced the incidence of vomiting in children following pediatric adenotonsillectomy.     

Hemorrhage-Induced Hepatic Injury and Hypoperfusion can be Prevented by Direct Peritoneal Resuscitation

Background  Crystalloid fluid resuscitation after hemorrhagic shock (HS) that restores/maintains central hemodynamics often culminates in multi-system organ failure and death due to persistent/progressive splanchnic hypoperfusion and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) using peritoneal dialysis solution reverses HS-induced splanchnic hypoperfusion and improves survival. We examined HS-mediated hepatic perfusion (galactose clearance), tissue injury (histopathology), and dysfunction (liver enzymes). Methods  Anesthetized rats were randomly assigned (n = 8/group): (1) sham (no HS); (2) HS (40% mean arterial pressure for 60 min) plus conventional i.v. fluid resuscitation (CR; shed blood + 2 volumes saline); (3) HS + CR + 30 mL intraperitoneal (IP) DPR; or (4) HS + CR + 30 mL IP saline. Hemodynamics and hepatic blood flow were measured for 2 h after CR completion. In duplicate animals, liver and splanchnic tissues were harvested for histopathology (blinded, graded), hepatocellular function (liver enzymes), and tissue edema (wet–dry ratio). Results  Group 2 decreased liver blood flow, caused liver injuries (focal to submassive necrosis, zones 2 and 3) and tissue edema, and elevated liver enzymes (alanine aminotransferase (ALT), 149 ± 28 μg/mL and aspartate aminotransferase (AST), 234 ± 24 μg/mL; p < 0.05) compared to group 1 (73 ± 9 and 119 ± 10 μg/mL, respectively). Minimal/no injuries were observed in group 3; enzymes were normalized (ALT 89 ± 9 μg/mL and AST 150 ± 17 μg/mL), and tissue edema was similar to sham. Conclusions  CR from HS restored and maintained central hemodynamics but did not restore or maintain liver perfusion and was associated with significant hepatocellular injury and dysfunction. DPR added to conventional resuscitation (blood and crystalloid) restored and maintained liver perfusion, prevented hepatocellular injury and edema, and preserved liver function. Presented at the Digestive Disease Week, American Association for the Study of Liver Diseases, Los Angeles, CA, USA, May 2006. No conflicts of interest exist. Grant support: This project was supported by a VA Merit Review grant and by NIH research Grant # 5R01 HL076160-03, funded by the National Heart, Lung, and Blood Institute and the United States Army Medical Resources and Material Command.     

Low-level laser therapy can reduce lipopolysaccharide-induced contractile force dysfunction and TNF-α levels in rat diaphragm muscle

Our objective was to investigate if low-level laser therapy (LLLT) could improve respiratory function and inhibit tumor necrosis factor (TNF-α) release into the diaphragm muscle of rats after an intravenous injection of lipopolysaccharide (LPS) (5 mg/kg). We randomly divided Wistar rats in a control group without LPS injection, and LPS groups receiving either (a) no therapy, (b) four sessions in 24 h with diode Ga–AsI–Al laser of 650 nm and a total dose of 5.2 J/cm², or (c) an intravenous injection (1.25 mg/kg) of the TNF-α inhibitor chlorpromazine (CPZ). LPS injection reduced maximal force by electrical stimulation of diaphragm muscle from 24.15 ± 0.87 N in controls, but the addition of LLLT partly inhibited this reduction (LPS only: 15.01 ± 1.1 N vs LPS + LLLT: 18.84 ± 0.73 N, P < 0.05). In addition, this dose of LLLT and CPZ significantly (P < 0.05 and P < 0.01, respectively) reduced TNF-α concentrations in diaphragm muscle when compared to the untreated control group.     

The Wide-Awake Approach to Dupuytren’s Disease: Fasciectomy under Local Anesthetic with Epinephrine

The Wide-Awake Approach to Dupuytren's contracture involves fasciectomy under local anesthetic with epinephrine and no tourniquet. The goal of this study is to show that the Wide-Awake Approach produces equivalent outcomes to fasciectomy under general anesthetic with a tourniquet, with fewer risks to the patient. A multicenter retrospective review was conducted on 111 patients with fasciectomies under local or general anesthetic between 2001 and 2007. Data on patient demographics, comorbidities, cost, as well as range of motion was collected and evaluated using Microsoft Excel and SAS. Of 148 fingers, 102 were treated under local and 46 under general anesthetic. The average postoperative Total Active Motion (TAM) for general anesthetic patients was 199.0 ± 29.6 (D5), 223.9 ± 29.3 (D4), 234.6 ± 14.6 (D3), and 246.7 ± 14.4 (D2). The average postoperative TAM for local anesthetic patients was 168.3 ± 62.2 (D5), 195.9 ± 67.5 (D4), 173.0 ± 72.6 (D3), and 177.5 ± 31.8 (D2). There were no significant differences between any of these individual groups (p = 0.09, 0.26, 0.12, and 0.20, respectively); however, when pooled, the overall TAM was significantly greater in the general anesthesia group (222.0 ± 29.7 vs. 186.0 ± 63.0, p = 0.002.). Complication rates and types were similar with both techniques. The Wide-Awake Approach to Dupuytren’s contracture avoids general anesthetic risks and has cost benefits to healthcare providers. Although it yields similar range of motion outcomes to fasciectomy performed under general anesthesia, total active motion may be better with fasciectomy done under general anesthesia.     

Practical Limitations of Bioresorbable Membranes in the Prevention of Intra-Abdominal Adhesions

Introduction  Intra-abdominal adhesions are a significant source of postoperative morbidity. Bioresorbable barriers composed of hyaluronic acid and carboxymethylcellulose (HA/CMC) reduce adhesion formation by physically separating injured or healing peritoneal surfaces. To assess whether the efficacy of a physical barrier can extend beyond the site of application, we evaluated the effectiveness of an HA/CMC barrier in preventing adhesions distal to the site of placement. Methods  Adhesions were induced in rats by creating peritoneal ischemic buttons on either side of a midline incision. An HA/CMC barrier (Seprafilm™ Genzyme) was intraoperatively placed either under the midline incision, unilaterally over half the ischemic buttons, or bilaterally over all ischemic buttons. Control buttons received no HA/CMC. On day 7 adhesions were scored. In similar experiments, peritoneal fluid was collected at 24 h to assess the effects of HA/CMC on tissue plasminogen activator activity. Results  Placement of HA/CMC under the midline incision did not reduce adhesion formation to distal ischemic buttons (72 ± 7%) compared to controls (80 ± 8%). Unilateral placement of HA/CMC significantly (p < 0.05) reduced adhesion formation to those ischemic buttons over which the barrier was applied (35 ± 7%) compared to both contralateral (83 ± 9%) and control (80 ± 8%) ischemic buttons. The bilateral application of HA/CMC also significantly (p < 0.05) reduced adhesion formation to all ischemic buttons compared to controls (22 ± 7% vs. 66 ± 7%, respectively). HA/CMC did not affect peritoneal tPA activity. Conclusions  Effective adhesion reduction by the physical barrier HA/CMC appears to be limited to the site of application in this rat model. Despite the presence of a bioresorbable membrane at predicted sites of adhesion formation in the peritoneal cavity, adhesions readily form to distal unprotected sites. Presented, in part, at the 49th Annual Meeting of The Society for Surgery of the Alimentary Tract, May 17–21, 2008, San Diego, CA, USA This work was supported in part, by the Smithwick Endowment Fund to the Department of Surgery at Boston University School of Medicine.     

Risk of Calcium Oxalate Nephrolithiasis after Calcium or Combined Calcium and Calcitriol Supplementation in Postmenopausal Women

Although calcium supplementation can cause hypercalciuria, the risk of nephrolithiasis has been shown to decrease rather than increase among subjects who had a higher calcium intake. Hypercalciuria is also a well-established side effect of calcitriol administration. However, the risk of nephrolithiasis is not well defined. The present study was undertaken to prospectively determine the effect of calcium with or without calcitriol on physicochemical risk factors associated with calcium oxalate nephrolithiasis in Thai postmenopausal women with osteoporosis. Subjects consisted of 53 Thai women more than 10 years postmenopausal who were randomly allocated to receive 750 mg of calcium carbonate supplement alone (n= 28) or 750 mg of calcium carbonate plus 0.5 mg calcitriol (n= 25) daily. Mean ± SEM for age was 65.3 ± 1.1 years, body weight 53.5 ± 1.3 kg. Urine samples for biochemical assays were collected at baseline and 3 months after treatment. Supersaturation for calcium oxalate stone formation was assessed from the 24 h urine constituents by the Tiselius’s index, AP(CaOx). Three months of calcium supplement alone resulted in a modest, but not significant, increase in urinary calcium (baseline, 2.90 ± 0.43 mmol/day; after treatment 3.58 ± 0.54 mmol/day) with no change in urinary oxalate, citrate or magnesium. In contrast, calcium together with calcitriol caused a significant increase in urinary calcium (baseline, 2.87 ± 0.41 mmol/day; after treatment, 4.08 ± 0.57 mmol/day; p<0.05). No significant change in other urine constituents after treatment with calcium and calcitriol was detected. Therefore, AP(CaOx) did not significantly increase either after calcium alone (baseline, 1.17 ± 0.39; after treatment, 1.36 ± 0.28) or after calcium plus calcitriol (baseline, 1.09 ± 0.17; after treatment, 1.09 ± 0.19). However, after treatments, 12 subjects (23%) – 6 receiving calcium supplement alone and 6 receiving calcium plus calcitriol supplement – had high AP(CaOx) values (greater than the upper limit of 95% CI for AP(CaOx) derived from non-stone-forming Thai women). The post-treatment/baseline ratio was 3.21 ± 0.74 for urinary calcium, 1.01 ± 0.19 for urinary oxalate, and 2.23 ± 0.42 (median 1.15) for AP(CaOx). The post-treatment/baseline ratio of calcium, but not for urinary oxalate, had a significant correlation with the post-treatment/baseline ratio of AP(CaOx). Our findings suggest that the alteration in the risk of calcium oxalate nephrolithiasis based on urinary composition is related to the alteration in urinary calcium. The risk of calcium oxalate nephrolithiasis does not increase significantly after calcium or combined calcium and calcitriol supplement in the majority of postmenopausal women with osteoporosis. Received: 10 March 1999 / Accepted: 16 November 1999     

Muscle activity during a dash shown by 18F-fluorodeoxyglucose positron emission tomography

Background ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been used to examine muscle activity during running. The dash is a basic activity in various kinds of sports but differs from running in terms of intensity and severity. The purpose of this study was to evaluate muscle activity during running at full speed using FDG PET. Methods Six healthy men were investigated during a dash for 10 min after intravenous injection of FDG (37 MBq). Another six healthy men were studied as controls. PET images were obtained 45 min after the FDG injection. Regions of interest were drawn on the anterior and posterior thighs and the anterior and posterior legs. The standardized uptake value (SUV) was calculated to examine the FDG uptake of muscle tissue per unit volume according to an equation. Results In the control group, the mean SUVs of the anterior thigh, posterior thigh, anterior leg, and posterior leg were 0.49 ± 0.04, 0.44 ± 0.02, 0.46 ± 0.05, and 0.44 ± 0.07, respectively. In the dash group, the mean SUVs of the anterior thigh, posterior thigh, anterior leg, and posterior leg were 0.74 ± 0.20, 0.79 ± 0.08, 0.61 ± 0.07, and 0.60 ± 0.08, respectively. FDG accumulation of every one of the four compartments in the dash group was significantly higher than that in the control. FDG accumulation of the posterior thigh was significantly higher than that of the anterior and the posterior leg in the dash group (P < 0.02). Conclusion Based on the results of our investigation, posterior thigh muscles were especially active during a dash.