Acute hypoxia simultaneously induces the expression of gp91phox and endothelial nitric oxide synthase in the porcine pulmonary artery

BACKGROUND: The effect of hypoxia on the formation of superoxide (O2-), the expression of gp91phox and endothelial NO synthase (eNOS) were studied in pig intact pulmonary artery (PA) segments and PA vascular smooth muscle cells (PAVSMCs) and PA endothelial cells (PAECs). METHODS: Segments and cells were incubated under hypoxic conditions for 2 hours (with or without enzyme inhibitors) and the formation of O2- measured spectrophotometrically. Protein expression was assessed using Western blotting and immunocytochemistry. RESULTS: Hypoxia promoted the formation of O2- in PA segments, PAVSMCs and PAECs, an effect inhibited by diphenylene iodonium and apocynin (NAD[P]H oxidase inhibitors). Hypoxia induced O2- formation was enhanced by inhibition of eNOS and augmented by endotoxin and cytokines and re-oxygenation. Hypoxia also promoted the expression of gp91phox and eNOS. In intact PA segments hypoxia induced the expression of nitrotyrosine and eNOS in the endothelium. CONCLUSIONS: The simultaneous upregulation of NAD[P]H oxidase and eNOS in response to hypoxia in the PA results in the simultaneous formation of O2-, NO, and ONOO-. This may represent either a protective mechanism designed to counter the pro-oxidant effect of hypoxia or a novel pathological mechanism underlying the progression of acute respiratory distress syndrome (ARDS).     

Laparoscopic repair of hiatus hernia: Does mesh type influence outcome? A meta-analysis and European survey study

Background

Synthetic mesh (SM) has been used in the laparoscopic repair of hiatus hernia but remains controversial due to reports of complications, most notably esophageal erosion. Biological mesh (BM) has been proposed as an alternative to mitigate this risk. The aim of this study is to establish the incidence of complications, recurrence and revision surgery in patients following suture (SR), SM or BM repair and undertake a survey of surgeons to establish a perspective of current practice.

Methods

An electronic search of EMBASE, MEDLINE and Cochrane database was performed. Pooled odds ratios (PORs) were calculated for discrete variables. To survey current practice an online questionnaire was sent to emails registered to the European Association for Endoscopic Surgery.

Results

Nine studies were included, comprising 676 patients (310 with SR, 214 with SM and 152 with BM). There was no significant difference in the incidence of complications with mesh compared to SR (P = 0.993). Mesh significantly reduced overall recurrence rates compared to SR [14.5 vs. 24.5 %; POR = 0.36 (95 % CI 0.17–0.77); P = 0.009]. Overall recurrence rates were reduced in the SM compared to BM groups (12.6 vs. 17.1 %), and similarly compared to the SR group, the POR for recurrence was lower in the SM group than the BM group [0.30 (95 % CI 0.12–0.73); P = 0.008 vs. 0.69 (95 % CI 0.26–1.83); P = 0.457]. Regarding surgical technique 503 survey responses were included. Mesh reinforcement of the crura was undertaken by 67 % of surgeons in all or selected cases with 67 % of these preferring synthetic mesh to absorbable mesh. One-fifth of the respondents had encountered mesh erosion in their career.

Conclusions

Both SM and BM reduce rates of recurrence compared to SR, with SM proving most effective. Surgical practice is varied, and there remains insufficient evidence regarding the optimum technique for the repair of hiatal hernia.

     

What Are the Biomechanical Effects of Half-pin and Fine-wire Configurations on Fracture Site Movement in Circular Frames?

Background

Fine-wire circular frame (Ilizarov) fixators are hypothesized to generate favorable biomechanical conditions for fracture healing, allowing axial micromotion while limiting interfragmentary shear. Use of half-pins increases fixation options and may improve patient comfort by reducing muscle irritation, but they are thought to induce interfragmentary shear, converting beam-to-cantilever loading. Little evidence exists regarding the magnitude and type of strain in such constructs during weightbearing.

Questions/purposes

This biomechanical study was designed to investigate the levels of interfragmentary strain occurring during physiologic loading of an Ilizarov frame and the effect on this of substituting half-pins for fine-wires.

Methods

The “control” construct was comprised of a four-ring all fine-wire construct with plain wires at 90°-crossing angles in an entirely unstable acrylic pipe synthetic fracture model. Various configurations, substituting half-pins for wires, were tested under levels of axial compression, cantilever bending, and rotational torque simulating loading during gait. In total three frames were tested for each of five constructs, from all fine-wire to all half-pin.

Results

Substitution of half-pins for wires was associated with increased overall construct rigidity and reduced planar interfragmentary motion, most markedly between all-wire and all-pin frames (axial: 5.9 mm ± 0.7 vs 4.2 mm ± 0.1, mean difference, 1.7 mm, 95% CI, 0.8–2.6 mm, p < 0.001; torsional: 1.4% ± 0.1 vs 1.1% ± 0.0 rotational shear, mean difference, 0.3%, 95% CI, 0.1%–0.5%, p = 0.011; bending: 7.5° ± 0.1 vs 3.4° ± 0.1, mean difference, −4.1°, 95% CI, −4.4° to −3.8°, p < 0.001). Although greater transverse shear strain was observed during axial loading (0.4% ± 0.2 vs 1.9% ± 0.1, mean difference, 1.4%, 95% CI, 1.0%–1.9%, p < 0.001), this increase is unlikely to be of clinical relevance given the current body of evidence showing bone healing under shear strains of up to 25%. The greatest transverse shear was observed under bending loads in all fine-wire frames, approaching 30% (29% ± 1.9). This was reduced to 8% (±0.2) by incorporation of sagittal plane half-pins and 7% (±0.2) in all half-pin frames (mean difference, −13.2% and −14.0%, 95% CI, −16.6% to 9.7% and −17.5% to −10.6%, both p < 0.001).

Conclusions

Appropriate use of half-pins may reduce levels of shear strain on physiologic loading of circular frames without otherwise altering the fracture site mechanical environment at levels likely to be clinically important. Given the limitations of a biomechanical study using a symmetric and uniform synthetic bone model, further clinical studies are needed to confirm these conclusions in vivo.

Clinical Relevance

The findings of this study add to the overall understanding of the mechanics of circular frame fixation and, if replicated in the clinical setting, may be applied to the preoperative planning of frame treatment, particularly in unstable fractures or bone transport where control of shear strain is a priority.     

An Assessment of Radiologically Inserted Transoral and Transgastric Gastroduodenal Stents to Treat Malignant Gastric Outlet Obstruction

Introduction

Self-expanding metallic stents (SEMS) are used to palliate malignant gastric outlet obstruction (GOO) and are useful in patients with limited life expectancy or severe medical comorbidity, which would preclude surgery. Stenting can be performed transorally or by a percutaneous transgastric technique. Our goal was to review the outcome of patients who underwent radiological SEMS insertion performed by a single consultant interventional radiologist.

Methods

Patients were identified from a prospectively collected database held by one consultant radiologist. Data were retrieved from radiological reports, multidisciplinary team meetings, and the patients’ case notes. Univariate survival analysis was performed.

Results

Between December 2000 and January 2011, 100 patients (63 males, 37 females) had 110 gastroduodenal stenting procedures. Median age was 73 (range 39–89) years. SEMS were inserted transorally (n = 66) or transgastrically (n = 44). Site of obstruction was the stomach (n = 37), duodenum (n = 50), gastric pull-up (n = 10), or gastroenterostomy (n = 13). Seven patients required biliary stents. Technical success was 86.4 %: 83.3 % for transoral insertion, 90.9 % for transgastric insertion. Eleven patients developed complications. Median GOO severity score: 1 pre-stenting, 2 post-stenting (p = 0.0001). Median survival was 54 (range 1–624) days. Post-stenting GOO severity score was predictive of survival (p = 0.0001).

Conclusions

The technical success rate for insertion of palliative SEMS is high. Insertional technique can be tailored to the individual depending on the location of the tumor and whether it is possible to access the stomach percutaneously. Patients who have successful stenting and return to eating a soft/normal diet have a statistically significant increase in survival.     

Malignant round cell tumours of bone: atypical clinical and imaging features

Objective.To describe the clinical, radiological and MRI features of six atypical cases of histologically proven appendicular Ewing sarcoma/ primitive neuroectodermal tumour (PNET). Design. Retrospective review of case notes and available imaging was carried out. Patients. Six patients (4 male, 2 female; mean age 27years, range 19–44 years), presenting over a 77-month period, were identified from the Bone Tumour Register. All had unusual clinical and imaging features for Ewing sarcoma/PNET. Results and conclusions. Four tumours were centred on the distal femoral metaphysis, one in the proximal tibial metaphysis and one in the distal tibial metaphysis. Plain radiographs were available in four cases and showed minor cortical changes. MRI demonstrated a relatively small, eccentrically located intraosseous component with a large, eccentric extraosseous component. Extension into the epiphysis was seen in three cases and into the adjacent joint in two cases. Intraosseous ”skip” metastases were present in three cases. The clinical and imaging features were atypical for conventional intraosseous Ewing sarcoma/PNET and the exact site of origin (intraosseous, periosteal or soft-tissue) was unclear. Received: 6 December 1999 Revision requested: 7 February 2000 Revision received: 20 July 2000 Accepted: 4 August 2000     

Complete worldwide operative experience in laparoscopic diaphragm pacing: results and differences in spinal cord injured patients and amyotrophic lateral sclerosis patients

Background  Diaphragm movement is essential for adequate ventilation, and when the diaphragm is adversely affected patients face lifelong positive-pressure mechanical ventilation or death. This report summarizes the complete worldwide multicenter experience with diaphragm pacing stimulation (DPS) to maintain and provide diaphragm function in ventilator-dependent spinal cord injury (SCI) patients and respiratory-compromised patients with amyotrophic lateral sclerosis (ALS). It will highlight the surgical experiences and the differences in diaphragm function in these two groups of patients. Methods  In prospective Food and Drug Administration (FDA) trials, patients underwent laparoscopic diaphragm motor point mapping with intramuscular electrode implantation. Stimulation of the electrodes ensued to condition and strengthen the diaphragm. Results   From March of 2000 to September of 2007, a total of 88 patients (50 SCI and 38 ALS) were implanted with DPS at five sites. Patient age ranged from 18 to 74 years. Time from SCI to implantation ranged from 3 months to 27 years. In 87 patients the diaphragm motor point was mapped with successful implantation of electrodes with the only failure the second SCI patient who had a false-positive phrenic nerve study. Patients with ALS had much weaker diaphragms identified surgically, requiring trains of stimulation during mapping to identify the motor point at times. There was no perioperative mortality even in ALS patients with forced vital capacity (FVC) below 50% predicted. There was no cardiac involvement from diaphragm pacing even when analyzed in ten patients who had pre-existing cardiac pacemakers. No infections occurred even with simultaneous gastrostomy tube placements for ALS patients. In the SCI patients 96% were able to use DPS to provide ventilation replacing their mechanical ventilators and in the ALS studies patients have been able to delay the need for mechanical ventilation up to 24 months. Conclusion   This multicenter experience has shown that laparoscopic diaphragm motor point mapping, electrode implantation, and pacing can be safely performed both in SCI and in ALS. In SCI patients it allows freedom from ventilator and in ALS patients it delays the need for ventilators, increasing survival. Presented as an oral presentation at the Plenary Session of SAGES 2008 Scientific Session, Philadephia.     

Home glucometer monitoring markedly improves diagnosis of post renal transplant diabetes mellitus in renal transplant recipients

BACKGROUND: Definitions of de novo posttransplant diabetes mellitus (PTDM) have varied widely in the renal transplant literature, and most have not used the American Diabetes Association (ADA) definition of diabetes (fasting plasma glucose [FPG] > or = 126 mg/dl on two occasions, or a casual plasma glucose level >200 mg/dl). Most patients are monitored for PTDM by 12-hour FPG levels drawn for clinic visits. In contrast, we describe the diagnosis of PTDM by home glucometer monitoring METHODS: We screened 89 consecutive nondiabetic renal transplant recipients for PTDM by ADA criteria and home glucometer monitoring during the first 3 months posttransplant RESULTS: Of 23 patients with impaired fasting glucose levels of 111-126 mg/dl, 14 (61%) met ADA criteria for diabetes mellitus of based on home glucometer monitoring. The incidence of de novo PTDM was 31% during this period. Predictors of PTDM in a Cox proportional hazards model were race and acute rejection, with a trend towards BMI. Clinic visit FPG levels did not differ between PTDM and non-PTDM patients. All diagnoses were made based on prelunch or supper FPG >200 mg/dl. CONCLUSIONS: Overnight FPG are inadequate for diagnosis of PTDM. All renal transplant recipients with impaired FPG should, at minimum, have home FPG testing.     

Longitudinal analysis of chronic allograft nephropathy: clinicopathologic correlations

BACKGROUND: Loss of the allograft from chronic allograft nephropathy and death of the patient from vascular, malignant, or infective disease are the major problems in renal transplantation today. Protocol biopsy of the long-term kidney has provided new data with which to develop strategies for prevention and treatment of chronic allograft nephropathy. METHODS: Two series of long-term protocol biopsies are reviewed. In the first, renal biopsies were obtained at time 0, and at 3 months and 12 months, and the recipients of the renal allografts were followed up for up to 15 years. In the second, the kidneys of recipients of simultaneous pancreas kidney transplants were biopsied annually for 10 years, and the results correlated with clinical events. RESULTS: Chronic allograft nephropathy is caused by acute and chronic immune-mediated damage, as well as by chronic calcineurin inhibitor nephrotoxicity. Both immune and nonimmune mechanisms exacerbate pre-existing donor disease and ischemia-reperfusion injury. Established interstitial fibrosis and arteriolar hyalinosis lead to progressive glomerular sclerosis and eventual loss of the graft. CONCLUSION: Protocol biopsies have shown that clinical parameters of renal function underestimate the severity of chronic graft damage. Strategies for preventing or treating chronic renal allograft dysfunction and subsequent graft loss must better control rejection and simultaneously avoid nephrotoxicity.     

Laparoscopic cholecystectomy in a patient with a biventricular cardiac assist device.

Evaluation and management of abdominal pathology in patients with ventricular assist devices is likely to become increasingly important as the utilization of these devices expands. Ventricular assist devices represent a class of intracorporeal or paracorporeal mechanical devices that augment cardiac output in patients with congestive heart failure. Patients with ventricular assist devices supporting both right and left ventricles (biventricular assist devices) are uniquely challenging to the general surgeon because these devices restrict direct access to the abdominal cavity and because of the perioperative implications of biventricular heart failure. We describe herein the first reported successful laparoscopic cholecystectomy in a patient with a paracorporeal biventricular assist device. Cholecystectomy was performed in this patient for acute cholecystitis that occurred while the patient was awaiting heart transplantation. Our results add weight to the small body of evidence that laparoscopy is well tolerated in ventricular assist devices patients. The unique aspects of the biventricular assist device patient make laparoscopic abdominal intervention particularly suitable in this patient population.