TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons.

Increased activity and excitability (sensitisation) of a series of molecules including the transient receptor potential ion channel, vanilloid subfamily, member 1 (TRPV1) in pain-sensing (nociceptive) primary sensory neurons are pivotal for developing pathological pain experiences in tissue injuries. TRPV1 sensitisation is induced and maintained by two major mechanisms; post-translational and transcriptional changes in TRPV1 induced by inflammatory mediators produced and accumulated in injured tissues, and TRPV1 activation-induced feed-forward signalling. The latter mechanism includes synthesis of TRPV1 agonists within minutes, and upregulation of various receptors functionally linked to TRPV1 within a few hours, in nociceptive primary sensory neurons. Here, we report that a novel mechanism, which contributes to TRPV1 activation-induced TRPV1-sensitisation within ~ 30 min in at least ~ 30% of TRPV1-expressing cultured murine primary sensory neurons, is mediated through upregulation in cyclooxygenase 2 (COX2) expression and increased synthesis of a series of COX2 products. These findings highlight the importance of feed-forward signalling in sensitisation, and the value of inhibiting COX2 activity to control pain, in nociceptive primary sensory neurons in tissue injuries.

A Suggested Approach of Managing Excessive Maxillary Gingival Display in Terminal Dentition.

The aim of this paper is to report a suggested approach for the management of excessive maxillary gingival display with terminal dentition. A segmental osteotomy of the maxillary process was performed, and the latter used as grafting material for lateral sinus augmentation that was performed simultaneously. Following the graft maturation period, implants were inserted and rehabilitated with a fixed dentogingival prosthesis. Consequently, the mandible was prosthetically restored following the new occlusal plane dictated by the rehabilitated maxilla. Clinically, the procedure showed a drastic improvement in the patient's appearance, eliminating the excessive gingival display. Radiologically, it led to a vertical translation of the maxillary process level in an apical direction. Nevertheless, the resected process used as grafting material was noticed to have a suboptimal behavior as long as it showed increased intrasinusal resorption, barely sufficient for a regular implant accommodation. The described therapy concept seems to be a plausible approach when it comes to manage excessive maxillary gingival displays in edentulous patients or those presenting a terminal dentition. However, at the time of sinus augmentation, authors recommend to graft a mixture of resected maxillary process and a bone substitute material, in order to get more stable results.

Visual function with bilateral implantation of monofocal and multifocal intraocular lenses: a prospective, randomized, controlled clinical trial.

PURPOSE: To evaluate visual function of three types of multifocal intraocular lenses (IOLs) and one monofocal IOL (as the control group) after cataract surgery. METHODS: One hundred fourteen patients participated in a prospective, randomized, controlled clinical study and received monofocal Tecnis Z9000 (AMO) (n = 24, 48 eyes); symmetric diffractive multifocal Tecnis ZM900 (AMO) (n = 26, 52 eyes); zonal refractive multifocal ReZoom (AMO) (n = 32, 64 eyes); and asymmetric diffractive multifocal TwinSet (Acri.Tec) (n = 32, 64 eyes) IOLs. RESULTS: Mean binocular distance best spectacle-corrected visual acuity (BSCVA) (logMAR) was 0.05 for controls, 0.08 for ZM900, 0.07 for ReZoom, and 0.11 for TwinSet, with mean binocular distance BSCVA at near of 0.49, 0.06, 0.22, and 0.11, respectively. Mean contrast sensitivity was better for the monofocal IOL group than for the multifocal IOLs. Patients assigned to TwinSet had less favorable contrast sensitivity scores. Patients with monofocal IOLs had more frequently recommended near addition (74%) than those with multifocal IOLs. Patients with refractive ReZoom had also recommended near addition more frequently than the two diffractive groups. The percentage of dysphotopsia phenomena was 81% in patients with diffractive multifocal ZM900 compared with 48% in patients with monofocal IOLs, 53% with refractive ReZoom, and 47% with diffractive TwinSet. CONCLUSIONS: The monofocal IOL showed better visual function and lesser photic phenomena than multifocal IOLs but patients were spectacle dependent. ReZoom provided better distance BSCVA than the TwinSet diffractive model. Patients with Tecnis and TwinSet diffractive multifocal IOLs were more spectacle independent than patients with ReZoom. Patients with TwinSet had the worst visual function. Patients implanted with the Tecnis diffractive ZM900 were those reporting more photic phenomena.

Report of a jaw osteonecrosis possibly causedby denosumab.

PURPOSE: To report a case of osteonecrosis of the jaw (ONJ) occurring in an implant area possibly related to denosumab, a relatively new antiosteoporotic agent. MATERIALS AND METHODS: Two months following the extraction of both maxillary first molars, a bilateral maxillary sinus floor elevation was performed on a 64-year-old female patient under a biannual 60 mg denosumab antiosteoporotic treatment. Seven months later, two implants were inserted in a single-stage procedure in each of the grafted sinuses. After 3 months, the implants underwent prosthetic rehabilitation at one side, and a series of failures that led to an ONJ instalment at the other side. RESULTS: The ONJ persisted over 7 months and was only resolved by a surgical approach consisting of a piezoelectric osteotomy and platelet-rich fibrin with a tension-free wound closure. CONCLUSIONS: A cumulative effect of denosumab is likely to be associated with a jaw osteonecrosis, which in this case was manageable using a surgical approach with no need to interrupt the appropriate drug treatment course. Conflict of interest statement: The authors certify that they are not affiliated with, or involved in any organisation or entity with any financial or non-financial interest in the subject matter or materials discussed in this manuscript.

Left-sided gastroschisis.

Gastroschisis is a periumbilical, abdominal wall defect arising to the right of the umbilicus. We describe the clinical course of a left-sided gastroschisis in a term female born at 39 weeks' gestation. To our knowledge, there have been only 14 left-sided abdominal wall defects reported in the literature. We discuss our case and review the literature to try to determine if there is any clinic difference between right- versus left-sided lesions to make recommendations as to management.

Protection from lethal endotoxic shock after testosterone depletion is linked to chromosome X.

Men are considered more susceptible to sepsis after severe injury than are women, which has been attributed to a suppressing effect of male sex steroids on the inflammatory response. Moreover, the effect of sex steroids on the inflammatory process depends on the genetic background. The present study examined the genetic contribution to survival after endotoxic shock in mice depleted of testosterone by surgical castration. Six-week-old male mice, from strains A/J, AKR/J, C57BL/6J (B6), BALBc/J, DBA/2J, and C3H/HeN, were castrated (CX) or nonoperated (NoOp). Two weeks after surgery, mice were injected intraperitoneally with Escherichia coli lipopolysaccharide (15 mg/kg) and the frequency of mortality was monitored. CX A/J mice showed a significantly higher survival rate than NoOp mice, but this protective effect was not observed in the other strains. Administration of 5-alpha-dihydrotestosterone to CX A/J mice reverted the protection by CX. The protective effect of CX was also observed in crosses of female A/J and male B6 (AXB), but not female B6 and male A/J (BXA), suggesting that protection is linked to the A/J X chromosome. This possibility was corroborated by using consomic mice containing A/J chromosome X and the remaining chromosomes from B6. These results suggest that testosterone is a negative factor in the recovery from endotoxic shock, depending on the genetic background.

Phacoemulsification and lens-iris diaphragm retropulsion syndrome.

Lens-iris diaphragm retropulsion syndrome is mainly caused by a reverse pupillary block as a result of a defect or laxity in the zonular apparatus. It is characterized by a posterior displacement of the lens-iris diaphragm with posterior iris bowing, pupil dilation, and pain. The authors describe a new management technique using an iris hook retractor to lift the iris to relieve the pupillary block.

Minimally invasive thoracoscopic ultrasound for localization of pulmonary nodules in children.

PURPOSE: Children with cancer may develop lesions in the lung that may represent metastatic disease. Thoracotomy is considered the standard approach for resection of pulmonary nodules. Recently, thoracoscopic techniques have been applied in these situations. However, nodules that are deep in the lung parenchyma may not be visible. A technique has been developed whereby minimally invasive thoracoscopic ultrasound (MITUS) may be used to guide resection of deep pulmonary nodules. METHODS: We conducted a retrospective review of children undergoing MITUS at our institution. Only patients with single isolated lesions were chosen to have this diagnostic procedure performed. Patients undergo single lung ventilation. Two 5-mm ports are inserted, one for the grasper and the other for the camera. One 12-mm port is inserted for the flexible 10-mm ultrasound probe and the endoscopic stapler. The patient has CO(2) insufflation to create a 5-mm Hg pneumothorax. Twenty mL/kg of normal saline is introduced into the chest cavity for acoustic coupling. The ultrasound probe is used to isolate the nodule(s), guide resection, and check margins. The specimen is removed and placed in a removable specimen bag to reduce the chance of port site recurrence. After the lung has been inspected, irrigation is removed, and a chest tube inserted. RESULTS: Eight procedures were performed on 7 patients (5 males, 2 females) with a median age of 15.2 years (range, 4-18 years). Patients had primary diagnoses of osteosarcoma (n = 4), Wilms' (n = 2), and lymphoma (n = 1). The median size of the lesions that were being isolated was 0.6 cm (range, 0.3-2.9 cm). None of the nodules removed were visible on the surface of the lung. Of the 8 procedures, 7 led to the removal of a pulmonary nodule. Of the 7 nodules isolated, 5 were removed thoracoscopically, with two requiring minithoracotomy because of anatomical limitations. The histologic evaluation on these specimens included osteosarcoma (n = 4), abscesses (n = 2), fibrosis (n = 1), and lymph node (n = 1). The median hospitalization was 2.5 days (range, 2-39 days). One patient had a prolonged hospitalization because of air leak and sepsis. CONCLUSION: Minimally invasive thoracoscopic ultrasound is a real time imaging tool that helps isolate small pulmonary lesions that may otherwise be difficult to see intraoperatively. We would advocate this technique for those patients having video-assisted thoracoscopy to assist clarifying whether focal lesions are malignant, thereby guiding therapy.

Laparoscopic Tenckhoff catheter placement in children using a securing suture in the pelvis: comparison to the open approach.

BACKGROUND/PURPOSE: Secure placement of peritoneal dialysis (PD) catheters in the pelvis has been described by various techniques. We describe minimally invasive placement using an Endo Close device, securing the catheter in the pelvis, and compare this method with standard open technique in children. METHODS: A retrospective institutional review was conducted for children requiring PD access from 2001 to 2007. Patients were grouped into laparoscopic with secure placement (SP) and open placement (OP) groups. Groups were cohort-matched based on age, paying particular attention to the number of catheter migrations. RESULTS: Twenty-seven patients underwent 36 procedures in SP, whereas 23 patients in OP had 32 catheter-related procedures. Exit site infections were decreased in SP (0.57 vs 1.33 episodes per patient-year). There was no difference in the number of catheter migrations (3 vs 5); however, time to migration was statistically longer in the SP group (9 vs. 2.4 months, P < .05). CONCLUSIONS: Laparoscopic placement of PD catheters using a securing suture in the pelvis is a more durable technique when compared to open placement. Extending the catheter migration time is important in children when PD is used as a bridge to renal transplantation.

Laparoscopic adrenalectomy for neuroblastoma in children: a report of 6 cases.

Neuroblastoma, a neoplasm of the sympathetic nervous system, is the most common solid extracranial tumor of childhood. Complete tumor resection has been shown to improve outcomes in both low- and high-risk neuroblastoma. The efficacy of laparoscopic adrenalectomy (LA) for metastatic lesions, benign tumors, and small neuroblastomas (<20 mm in diameter) is well established. However, the role of LA for large neuroblastomas is unclear. The authors describe the technical aspects of LA in 6 children with adrenal neuroblastomas greater than 2 cm and summarize their outcomes. All 6 patients underwent successful LA with removal of their tumors and surrounding lymph nodes. The specimens were placed in a laparoscopic specimen retrieval bag and morsulated in situ. The pathologic specimens were adequate for biologic factor analysis and histology. Mean operative time for all cases was 146 minutes. The average size of the adrenal tumors resected was 3.3 x 3.7 x 3.3 cm, and there were no intraoperative or perioperative deaths. All children, except the fifth patient who stayed for chemotherapy, were discharged home within 48 hours after surgery and are well. Our preliminary data suggest LA is a safe treatment option for neuroblastoma tumors greater than 2 cm in the select children.

Laparoscopic cystogastrostomy for the treatment of pancreatic pseudocysts in children.

Pancreatic pseudocysts (PPSs) are common sequelae of pancreatitis and pancreatic trauma. The management is based upon the pseudocyst size and presence of symptoms. Those requiring intervention are often drained using several available options. The use of laparoscopic cystogastrostomy for large and recurrent PPSs has been described in adult patients as a less morbid alternative to open drainage procedures. This technique is considered a novel approach in children. We describe 2 children who had PPSs amenable to laparoscopic cystogastrostomy. The first was an 11-year-old girl who had blunt abdominal trauma from a bicycle handlebar. The second patient was a 7-year-old girl who developed idiopathic pancreatitis. Briefly, 2 ports were placed through the anterior abdominal and gastric walls, and into the lumen of the stomach. This intraluminal placement provided access to the posterior gastric wall. Using electrocautery diathermy, an incision was made through the posterior gastric wall and into the adjacent pseudocyst to obtain complete and unobstructed drainage. Both children tolerated the procedures well with resolution of their PPSs. The patients were each discharged on the fourth postoperative day and have been asymptomatic on 2 years follow-up. Laparoscopic cystogastrostomy is a safe and effective alternative to open cystogastrostomy for the minimally invasive management of PPSs in the pediatric population.

Renal artery pseudoaneurysm secondary to blunt trauma treated with microcoil embolization.

BACKGROUND: Renal artery pseudoaneurysms are rarely described sequelae of blunt abdominal trauma. Interventional radiological advances have allowed such lesions to be managed nonoperatively. METHODS: The authors review the presentation, diagnostic evaluation, and hospital course of an 11-year-old girl who developed a right renal artery pseudoaneurysm 14 days after blunt abdominal trauma. RESULTS: An 11-year-old girl fell off a horse onto her right flank. She sustained multiple right hepatic lobe lacerations and a complex fracture of the upper pole of the right kidney. Her initial hospital course was uncomplicated, and she was discharged after an uneventful 6-day course. The child did well for 2 weeks, until she developed right back pain and gross hematuria. A computed tomography scan revealed a right renal artery pseudoaneurysm. Angiography confirmed the presence of a pseudoaneurysm, which was fed by a single segmental branch originating from the renal artery. The artery was successfully occluded with a single platinum microcoil, which was demonstrated by the absence of contrast flow into the pseudoaneurysm. The patient recovered and was discharged shortly after the procedure. She initially had intermittent pain and hematuria, which resolved. Follow-up computed tomography scans have shown resolution of both the renal and hepatic lesions. CONCLUSIONS: Renal artery pseudoaneurysms that arise after blunt abdominal trauma in the pediatric population may be safely and effectively managed with arterial embolization, thereby avoiding extensive surgical interventions.

IL-10 plasma levels are elevated after LPS injection in splenectomized A/J mice.

BACKGROUND: Splenectomy is clinically indicated in certain cases of hypersplenism and splenic trauma. However, it is associated with serious complications, in particular, reduced clearance of encapsulated organisms and a high incidence of sepsis, which has been coined overwhelming post-splenectomy sepsis (OPSS). In addition to the role of the spleen in the clearance of microorganisms, this organ may be involved in regulation of the inflammatory response. We investigated the effect of splenectomy on the inflammatory process induced by LPS in a murine model that resembles, in part, the pathophysiological aspects of sepsis. MATERIALS AND METHODS: Male mice (8-weeks-old) from different inbred strains were randomized into three groups: splenectomized (SPX), sham operated (SHAM), and non-operated controls (NoOp). After 9 days of recovery, mice were injected with LPS (15 mg/kg) and cytokine plasma levels were measured by ELISA at 1.5 or 6 h after injection. Peritoneal macrophages (PMphi) were isolated from the three groups, and cytokine production was evaluated after incubation with LPS in culture conditions. RESULTS: IL-10 plasma levels were elevated in SPX A/J mice (6.7 +/- 0.4 mug/ml) after injection of LPS (15 mg/kg) compared to NoOp A/J mice (4.2 +/- 0.2 mug/ml, P < 0.05). Similar elevation in IL-10 plasma levels was detected in SPX DBA/2J mice as compared to NoOp DBA/2J mice, but not in C57BL/6J and BALB/cJ mice. In contrast, SPX AKR mice displayed lower IL-10 levels than NoOp mice. PMphis from SPX A/J mice produced elevated levels of IL-10 compared to PMphis from SHAM or NoOp A/J mice, mimicking the in vivo observations. CONCLUSION: Our data suggest that the spleen plays an important role in modulating the inflammatory process induced by LPS, extending beyond passive clearance of encapsulated organisms. In addition, the contribution of the spleen to the inflammatory process may be influenced by the genetic background.