Acute food deprivation-induced relapse to heroin seeking after short and long punishment-imposed abstinence in male rats.

RATIONAL: Stress is a major trigger for drug relapse in humans and animal models, even after prolonged abstinence. However, animal models for stress-induced relapse were criticized for the lack of predictive and face validity. OBJECTIVES: Here we investigated the effect of acute food deprivation stress in a novel stress-induced relapse model using voluntary, punishment-imposed abstinence from heroin. We also performed a detailed characterization of the development of punishment-imposed abstinence. METHODS: Male rats were trained to self-administered heroin (0.1 mg/kg/infusion) for 2 weeks, using the seeking-taking chained schedule. Pressing the 'seeking' lever led to the insertion of the 'taking' lever and pressing the take lever resulted in heroin infusion. Following self-administration training, rats were exposed to 8 or 21 days of heroin-seeking punishment. During punishment, 30% of the completed seek links resulted in a mild escalating footshock instead of take lever presentation. Next, rats were tested for heroin seeking under extinction conditions after 24 h of food deprivation and sated conditions. RESULTS: Probabilistic punishment of seeking lever responses resulted in gradual suppression of heroin seeking and taking. Exposure to food-deprivation stress induced a robust relapse to heroin seeking after short and long punishment-imposed abstinence periods, without significant effects of time, i.e., no incubation of heroin seeking. Individual differences were observed in the development of punishment-induced abstinence and stress-induced relapse. CONCLUSIONS: These results suggest that stress is a reliable trigger to relapse even after a prolonged period of punishment-induced, voluntary abstinence.

Performance of the new biological small- and wide-angle X-ray scattering beamline 13A at the Taiwan Photon Source.

Recent developments in the instrumentation and data analysis of synchrotron small-angle X-ray scattering (SAXS) on biomolecules in solution have made biological SAXS (BioSAXS) a mature and popular tool in structural biology. This article reports on an advanced endstation developed at beamline 13A of the 3.0 GeV Taiwan Photon Source for biological small- and wide-angle X-ray scattering (SAXS-WAXS or SWAXS). The endstation features an in-vacuum SWAXS detection system comprising two mobile area detectors (Eiger X 9M/1M) and an online size-exclusion chromatography system incorporating several optical probes including a UV-Vis absorption spectrometer and refractometer. The instrumentation and automation allow simultaneous SAXS-WAXS data collection and data reduction for high-throughput biomolecular conformation and composition determinations. The performance of the endstation is illustrated with the SWAXS data collected for several model proteins in solution, covering a scattering vector magnitude q across three orders of magnitude. The crystal-model fittings to the data in the q range ∼0.005-2.0 Å-1 indicate high similarity of the solution structures of the proteins to their crystalline forms, except for some subtle hydration-dependent local details. These results open up new horizons of SWAXS in studying correlated local and global structures of biomolecules in solution.

Augmented Reality in Pediatric Septic Shock Simulation: Randomized Controlled Feasibility Trial.

BACKGROUND: Septic shock is a low-frequency but high-stakes condition in children requiring prompt resuscitation, which makes it an important target for simulation-based education. OBJECTIVE: In this study, we aimed to design and implement an augmented reality app (PediSepsisAR) for septic shock simulation, test the feasibility of measuring the timing and volume of fluid administration during septic shock simulation with and without PediSepsisAR, and describe PediSepsisAR as an educational tool. We hypothesized that we could feasibly measure our desired data during the simulation in 90% of the participants in each group. With regard to using PediSepsisAR as an educational tool, we hypothesized that the PediSepsisAR group would report that it enhanced their awareness of simulated patient blood flow and would more rapidly verbalize recognition of abnormal patient status and desired management steps. METHODS: We performed a randomized controlled feasibility trial with a convenience sample of pediatric care providers at a large tertiary care pediatric center. Participants completed a prestudy questionnaire and were randomized to either the PediSepsisAR or control (traditional simulation) arms. We measured the participants' time to administer 20, 40, and 60 cc/kg of intravenous fluids during a septic shock simulation using each modality. In addition, facilitators timed how long participants took to verbalize they had recognized tachycardia, hypotension, or septic shock and desired to initiate the sepsis pathway and administer antibiotics. Participants in the PediSepsisAR arm completed a poststudy questionnaire. We analyzed data using descriptive statistics and a Wilcoxon rank-sum test to compare the median time with event variables between groups. RESULTS: We enrolled 50 participants (n=25 in each arm). The timing and volume of fluid administration were captured in all the participants in each group. There was no statistically significant difference regarding time to administration of intravenous fluids between the two groups. Similarly, there was no statistically significant difference between the groups regarding time to verbalized recognition of patient status or desired management steps. Most participants in the PediSepsisAR group reported that PediSepsisAR enhanced their awareness of the patient's perfusion. CONCLUSIONS: We developed an augmented reality app for use in pediatric septic shock simulations and demonstrated the feasibility of measuring the volume and timing of fluid administration during simulation using this modality. In addition, our findings suggest that PediSepsisAR may enhance participants' awareness of abnormal perfusion.

Host cell protein profiling of commercial therapeutic protein drugs as a benchmark for monoclonal antibody-based therapeutic protein development.

Therapeutic proteins including monoclonal antibodies (mAbs) are usually produced in engineered host cell lines that also produce thousands of endogenous proteins at varying levels. A critical aspect of the development of biotherapeutics manufacturing processes is the removal of these host cell proteins (HCP) to appropriate levels in order to minimize risk to patient safety and drug efficacy. During the development process and associated analytical characterization, mass spectrometry (MS) has become an increasingly popular tool for HCP analysis due to its ability to provide both relative abundance and identity of individual HCP and because the method does not rely on polyclonal antibodies, which are used in enzyme-linked immunosorbent assays. In this study, HCP from 29 commercially marketed mAb and mAb-based therapeutics were profiled using liquid chromatography (LC)-MS/MS with the identification and relative quantification of 79 individual HCP in total. Excluding an outlier drug, the relative levels of individual HCP determined in the approved therapeutics were generally low, with an average of 20 ppm (µmol HCP/mol drug) measured by LC-MS/MS, and only a few (<7 in average) HCP were identified in each drug analyzed. From this analysis, we also gained knowledge about which HCP are frequently identified in mAb-based products and their typical levels relative to the drugs for the identified individual HCP. In addition, we examined HCP composition from antibodies produced in house and found our current development process brings HCP to levels that are consistent with marketed drugs. Finally, we described a specific case to demonstrate how the HCP information from commercially marketed drugs could inform future HCP analyses.

Exhaled breath condensate nitrite in premature infants with bronchopulmonary dysplasia.

BACKGROUND: Tracheal aspirate is the conventional method to measure biomarkers of inflammation and oxidation from premature infants on mechanical ventilation at risk for bronchopulmonary dysplasia (BPD), but this method is invasive. Exhaled breath condensate (EBC) is a novel, non-invasive method that has been used in older populations. Nitrite, a stable metabolite of nitric oxide (NO), is elevated in inflammatory conditions. We aim to investigate the feasibility of EBC nitrite collection from ventilated premature infants and to quantify EBC nitrite in infants with and without BPD. We hypothesize that EBC nitrite correlates with TA nitrite, and that EBC nitrite in the first week of life is higher in infants who will develop BPD than those without BPD. METHODS: In a pilot prospective cohort study, TA and EBC were collected in the first week of life from mechanically ventilated premature infants. Nitrite levels were measured using chemiluminescence. RESULTS: EBC nitrite significantly correlated with TA nitrite (r = 0.45, p = 0.025). Of 40 infants, 33 (82.5%) developed BPD. EBC and TA nitrite levels collected in the first week of life had a higher trend in infants with BPD than those without BPD (p = 0.23 and 0.38 respectively). CONCLUSIONS: Higher trend of EBC nitrite in the first week of life was associated with the development of BPD. Correlation of nitrite level in EBC with that in TA (conventional method) highlights the utility of EBC as an alternative, non-invasive method to measure inflammation. Further refinement of conditions and timing may optimize the predictive value of EBC nitrite.

SLE mortality remains disproportionately high, despite improvements over the last decade.

Despite a marked improvement in 10-year survival for systemic lupus erythematosus (SLE) patients over the past five decades, mortality rates from SLE remain high compared to those in the general population. SLE was also among the leading causes of death in young women in the United States during 2000-2015. However, it is encouraging that SLE mortality rates and the ratios of SLE mortality rates to non-SLE mortality rates have decreased every year since the late 1990s. Despite this improvement, disparities in SLE mortality persist according to sex, race, age, and place of residence. Furthermore, demographic and geographic variables seem to modify the effect of each other in influencing SLE mortality, leading to interactions between sex/race/ethnicity-associated factors and geographic differences. In other words, individuals of the same sex/race/ethnicity had differences in SLE mortality depending on where they lived. These observations highlight SLE as an important public health issue. The recognition of SLE as a leading cause of death in the general population might spur targeted public health programs and research funding to address the high lupus mortality.

Randomised clinical trial: a phase 1, dose-ranging study of the anti-matrix metalloproteinase-9 monoclonal antibody GS-5745 versus placebo for ulcerative colitis.

BACKGROUND: Matrix metalloproteinase-9 is a proteolytic enzyme whose expression is increased in ulcerative colitis. AIM: To evaluate the safety and efficacy of GS-5745, a fully humanised anti-matrix metalloproteinase-9 monoclonal antibody, in moderately-to-severely active ulcerative colitis. METHODS: We randomised 74 patients with ulcerative colitis to treatment with single or multiple ascending intravenous or subcutaneous doses of GS-5745 or placebo. Multiple-dose cohorts received either IV infusions (0.3, 1.0, 2.5 or 5.0 mg/kg GS-5745 or placebo) every 2 weeks (three total IV infusions) or five weekly SC injections (150 mg GS-5745 or placebo). The primary outcomes were the safety, tolerability and pharmacokinetics of escalating single and multiple doses of GS-5745. Exploratory analyses in the multiple-dose cohorts included clinical response (≥3 points or 30% decrease from baseline in Mayo Clinic score and ≥1 point decrease in the rectal bleeding subscore or a rectal bleeding subscore ≤1) and clinical remission (a complete Mayo Clinic score ≤2 with no subscore >1) at Day 36. Biological effects associated with a clinical response to GS-5745 were explored using histological and molecular approaches. RESULTS: Twenty-three of the 42 patients (55%) receiving multiple doses of GS-5745 had adverse events, compared with 5/8 patients (63%) receiving placebo. GS-5745 showed target-mediated drug disposition, approximately dose-proportional increases in maximum plasma concentration and more than dose-proportional increases in the area under the plasma drug concentration-time curve. Clinical response occurred in 18/42 patients (43%) receiving GS-5745 compared with 1/8 patients (13%) receiving placebo. Clinical remission occurred in 6/42 patients (14%) receiving GS-5745 and 0/8 (0%) receiving placebo. Patients with a clinical response to GS-5745 had reductions in matrix metalloproteinase-9 tissue levels (mean 48.9% decrease from baseline compared with a mean 18.5% increase in nonresponders, P = 0.008) significant improvements in histopathology scores (confirmed with three separate histological disease activity indices), as well as changes in colonic gene expression that were consistent with reduced inflammation. CONCLUSION: This phase 1 trial provides preliminary evidence for the safety and therapeutic potential of GS-5745 in the treatment of ulcerative colitis.

ESOPHAGEAL ATRESIA WITH RECURRENT TRACHEOESOPHAGEAL FISTULAS AND MICRODUPLICATION 22q11.23.

The microduplication 22q11.2 syndrome has a wide range of clinical manifestations. The phenotype ranges from normal to mental retardation and congenital anomalies. Esophageal atresia/tracheoesophageal fistula (EA/TEF) has recently been linked with the Tbx1 gene mutation located on the long arm of chromosome 22(22q11.21). We report a case with 1.4 Mb 22q11.23 duplication detected by array-CGH. The father of this infant has the same interstitial microduplication but with a normal phenotype. The phenotype seen in our case is type C (3B) esophageal atresia, tracheoesophageal fistula, and ventricular septal defect. Our patient underwent primary repair of OA/TEF malformations, which was later complicated by pneumonia and a recurrent TEF.

Elevated levels of leukotriene C4 synthase mRNA distinguish a subpopulation of eosinophilic oesophagitis patients.

BACKGROUND: Cysteinyl leukotrienes contribute to Th2-type inflammatory immune responses. Their levels in oesophageal tissue, however, do not distinguish patients with eosinophilic oesophagitis (EoE) from controls. OBJECTIVE: We asked whether mRNA levels of leukotriene C4 synthase (LTC4 S), a key regulator of leukotriene production, could serve as a marker for EoE. METHODS: Digital mRNA expression profiling (nCounter(®) Technology) was performed on proximal and distal oesophageal biopsies of 30 paediatric EoE patients and 40 non-EoE controls. Expression data were confirmed with RT-qPCR. LTC4 S mRNA levels were quantified in whole blood samples. Leukotriene E4 was measured in urine. RESULTS: LTC4 S mRNA levels were elevated in proximal (2.6-fold, P < 0.001) and distal (2.9-fold, P < 0.001) oesophageal biopsies from EoE patients. Importantly, increased LTC4 S mRNA transcripts identified a subpopulation of EoE patients (28%). This patient subgroup had higher serum IgE levels (669 U/mL vs. 106 U/mL, P = 0.01), higher mRNA transcript numbers of thymic stromal lymphopoietin (TSLP) (1.6-fold, P = 0.009) and CD4 (1.4-fold, P = 0.04) but lower IL-23 mRNA levels (0.5-fold, P = 0.04). In contrast, elevated levels of IL-23 mRNA were found in oesophageal biopsies of patients with reflux oesophagitis. LTC4 S mRNA transcripts in whole blood and urinary excretion of leukotriene E4 were similar in EoE patient subgroups and non-EoE patients. CONCLUSION & CLINICAL RELEVANCE: Elevated oesophageal expression of LTC4 S mRNA is found in a subgroup of EoE patients, concomitant with higher serum IgE levels and an oesophageal transcriptome indicative of a more-pronounced allergic phenotype. Together with TSLP and IL-23 mRNA levels, oesophageal LTC4 S mRNA may facilitate diagnosis of an EoE subpopulation for personalized therapy.

Review article: Microscopic colitis--lymphocytic, collagenous and 'mast cell' colitis.

BACKGROUND: Microscopic colitis is a relatively common cause of chronic diarrhoea in predominantly older adults, traditionally termed lymphocytic colitis and collagenous colitis. Increased mast cells found in the colonic biopsies of some patients with chronic diarrhoea may represent a distinct type of microscopic colitis. AIM: To provide an updated review of the epidemiology, diagnosis and treatment of microscopic colitis, and to discuss the role of mast cells in the gastrointestinal tract and their potential role in cases of functional diarrhoea. METHOD: A MEDLINE literature search was performed to identify pertinent articles. Relevant clinical abstracts were also reviewed. RESULTS: Incidence rates of microscopic colitis (lymphocytic and collagenous colitis) have increased over time, to levels comparable with other forms of inflammatory bowel disease. The possibility of drug-induced microscopic colitis and concomitant coeliac sprue are important considerations when evaluating these patients. There are few controlled treatment trials in microscopic colitis, with much of the data on treatment coming from retrospective studies. Mast cells have been implicated in functional bowel disorders, with increased mast cells possibly contributing to cases of otherwise unexplained chronic diarrhoea, although this concept requires further investigation. CONCLUSIONS: In patients with microscopic colitis, a systematic approach to therapy often leads to satisfactory control of symptoms. The role of mast cells in chronic diarrhoea represents an evolving field, with the potential to offer alternative treatment pathways in patients with otherwise unexplained functional diarrhoea.

First evidence of a possible association between gastric acid suppression during pregnancy and childhood asthma: a population-based register study.

BACKGROUND: Recent data in mice suggest that acid suppression during pregnancy yields offspring with type 2 T helper-dominant immunity, suggesting a predisposition for allergy. OBJECTIVE: To determine the association of in utero exposure to acid-suppressive medications and the subsequent development of allergic diseases in children. METHODS: We studied a population-based observational cohort formed by linking data from three Swedish national healthcare registers: the Medical Birth Register, the Hospital Discharge Register, and the Swedish Prescribed Drug Register. Main outcome measures included a hospital discharge diagnosis of an allergic disease or prescription for asthma medications, epinephrine auto-injectors, antihistamines or steroid ointments in children. Data were analysed using the Mantel-Haenszel procedure. RESULTS: Twenty-nine thousand four hundred and ninety (5.03%) children had a discharge diagnosis of allergy or prescriptions for allergy medications. Five thousand six hundred and forty-five (0.96%) children had been exposed to acid suppression therapy during pregnancy; of these, 405 (0.07%) were treated for allergic diseases. Exposure to acid-suppressive medications in utero was associated with an increased odds ratio (OR) for developing allergy (OR 1.43, 95% confidence interval (95% CI) 1.29-1.59). We observed this association irrespective of the type of drug, time of exposure during pregnancy, and maternal history of allergy. The use of maternal acid-suppressive medication was associated with an increased OR for the development of childhood asthma (3.7% in the population at large vs. 5.6% in exposed children, OR 1.51, 95% CI 1.35-1.69), but not for other allergic diseases. CONCLUSION: These data provide first evidence of a significant association between in utero exposure to acid-suppressive drugs and the risk of developing childhood asthma.

Profile of the dentist in the oral healthcare team in countries with developed economies.

This paper confines itself to the description of the profile of a general dentist while outlining where the boundary between specialist and generalist may lie. The profile must reflect the need to recognize that oral health is part of general health. The epidemiological trends and disease variation of a country should inform the profile of the dentist. A particular tension between the provision of oral healthcare in publicly funded and private services may result in dentists practicing dentistry in different ways. However, the curriculum should equip the practitioner for either scenario. A dentist should work to standards appropriate to the needs of the individual and the population within the country's legal and ethical framework. He/she should have communication skills appropriate to ascertain the patient's beliefs and values. A dentist should work within the principles of equity and diversity and have the knowledge and clinical competence for independent general practice, including knowledge of health promotion and prevention. He/she should participate in life-long learning, which should result in a reflective practitioner whose clinical skills reflect the current evidence base, scientific breakthroughs and needs of their patients. Within the 4-5 years of a dental degree it is not possible for a student to achieve proficiency in all areas of dentistry. He/she needs to have the ability to know their own limitations and to access appropriate specialist advice for their patients while taking responsibility for the oral healthcare they provide. The dentist has the role of leader of the oral health team and, in this capacity; he/she is responsible for diagnosis, treatment planning and the quality control of the oral treatment. The dental student on graduation must therefore understand the principles and techniques which enable the dentist to act in this role. He/she should have the abilities to communicate, delegate and collaborate both within the dental team and with other health professionals, to the benefit of the patient. The profile of a dentist should encompass the points raised but will also be based upon competency lists which are published by a variety of countries and organizations. It is important that these lists are dynamic so that they are able to change in light of new evidence and technologies.

BMPR2 mutations in pulmonary arterial hypertension with congenital heart disease.

The aim of the present study was to determine if patients with both pulmonary arterial hypertension (PAH), due to pulmonary vascular obstructive disease, and congenital heart defects (CHD), have mutations in the gene encoding bone morphogenetic protein receptor (BMPR)-2. The BMPR2 gene was screened in two cohorts: 40 adults and 66 children with PAH/CHD. CHDs were patent ductus arteriosus, atrial and ventricular septal defects, partial anomalous pulmonary venous return, transposition of the great arteries, atrioventicular canal, and rare lesions with systemic-to-pulmonary shunts. Six novel missense BMPR2 mutations were found in three out of four adults with complete type C atrioventricular canals and in three children. One child had an atrial septal defect and patent ductus arteriosus; one had an atrial septal defect, patent ductus arteriosus and partial anomalous pulmonary venous return; and one had an aortopulmonary window and a ventricular septal defect. Bone morphogenetic protein receptor 2 mutations were found in 6% of a mixed cohort of adults and children with pulmonary arterial hypertension/congenital heart defects. The current findings compliment recent reports in mouse models implicating members of the bone morphogenetic protein/transforming growth factor-beta pathway inducing cardiac anomalies analogous to human atrioventricular canals, septal defects and conotruncal congenital heart defects. The small number of patients studied and the ascertainment bias inherent in selecting for pulmonary arterial hypertension require further investigation.

Effect of strain on bone nodule formation by rat osteogenic cells in vitro.

The purpose of this study was to assess in vitro bone nodule formation by cells exposed to a range of microstrain, at a sub-optimal oscillation frequency for bone formation. Fetal rat calvarial cells experienced a Flexercell regimen within either FLEX I (deformable) or FLEX II (non-deformable) substrates. Cells in FLEX I plates were exposed to growth medium only; those in FLEX II plates were exposed to either growth medium only, or growth medium + 10(-7) M IGF-1. Cell numbers were assessed from 1 to 6 days. Other cells were exposed to the Flexercell regimen (-2 kPa, 0.05 Hz) for 1-3 (Group 1), 3-6 (Group 2), 1-9 (Group 3) or 10-15 (Group 4) days and were maintained, at other times, under standard conditions. After 21 days, nodules were counted within each well and within the compression, <999, 1000-4900, 5000-9999, 10,000-14,999 and 15,000-25,000 microstrain regions of the FLEX I membrane. Cyclic deformation inhibited cell numbers from 1 to 6 days, compared to control or IGF-1 groups (P<0.001). The number of nodules in Groups 2 and 4 were greater than Groups 1 or 3 (P<0.001), but not different from control or IGF-1 groups. Compression or tensile microstrain significantly affected nodule formation in all groups, with Group 4 producing more nodules than other groups in most microstrain regions. Thus, the number of bone nodules produced by osteogenic cell cultures exposed to cyclic deformation was significantly affected by the timing of initiation and the characteristics and magnitude of the deformation regimen.

Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members.

Studies involving the cloning and disruption of the gene for acyl-CoA:diacylglycerol acyltransferase (DGAT) have shown that alternative mechanisms exist for triglyceride synthesis. In this study, we cloned and characterized a second mammalian DGAT, DGAT2, which was identified by its homology to a DGAT in the fungus Mortierella rammaniana. DGAT2 is a member of a gene family that has no homology with DGAT1 and includes several mouse and human homologues that are candidates for additional DGAT genes. The expression of DGAT2 in insect cells stimulated triglyceride synthesis 6-fold in assays with cellular membranes, and DGAT2 activity was dependent on the presence of fatty acyl-CoA and diacylglycerol, indicating that this protein is a DGAT. Activity was not observed for acyl acceptors other than diacylglycerol. DGAT2 activity was inhibited by a high concentration (100 mm) of MgCl(2) in an in vitro assay, a characteristic that distinguishes DGAT2 from DGAT1. DGAT2 is expressed in many tissues with high expression levels in the liver and white adipose tissue, suggesting that it may play a significant role in mammalian triglyceride metabolism.

[Regional initiative on health care reform in Latin America and the Caribbean]. / Iniciativa Regional de Reforma del Sector de la Salud en América Latina y el Caribe.

Many countries throughout Latin America and the Caribbean are introducing reforms that can profoundly influence how health services are provided and who receives them. Governments in the region identified the need for a network to support health reform by building capacity in analysis and training, both at the Summit of the Americas in 1994 and at the Special Meeting on Health Sector Reform, which was convened in 1995 by an interagency committee of the Pan American Health Organization/World Health Organization, the Inter-American Development Bank, the World Bank, and other multilateral and bilateral agencies. In response, in 1997 the Pan American Health Organization and the United States Agency for the International Development launched the Latin America and Caribbean Regional Health Sector Reform Initiative. The Initiative has approximately US$ 10 million in funding through the year 2002 to support activities in Bolivia, Brazil, the Dominican Republic, Ecuador, El Salvador, Guatemala, Haiti, Honduras, Jamaica, Mexico, Nicaragua, Paraguay, and Peru. Now in its third year of implementation, the Initiative supports regional activities seeking to promote more equitable and effective delivery of basic health services.

Complications and recommended practices for electrosurgery in laparoscopy.

BACKGROUND: Electrosurgery is one of the most commonly used energy systems in laparoscopic surgery. Two major categories of potential complications related to electrosurgery in laparoscopy are mechanical trauma and electrothermal injury. The latter can result from unrecognized energy transfer in the operational field or, less commonly, to unnoticed stray current outside the laparoscopic field of view. Stray current can result from insulation failure, direct coupling, or capacitive coupling. METHODS: We reviewed the literature concerning essential biophysics of electrosurgery, including electrosurgical waveform differentiation, tissue effect, and variables that determine tissue effect. The incidence of electrosurgical injuries and possible mechanisms responsible for the injuries are discussed. Different types of injuries may result in different clinical manifestations and histopathological findings. Gross and microscopic pathological check-ups of the injury sites may distinguish between different mechanisms, and thus provide further clues postoperatively. RESULTS: Several recommended practices are proposed to avoid electrosurgical injury laparoscopically. To achieve electrosurgical safety and to prevent electrosurgical injuries, the surgical team should have a good understanding of the biophysics of electrosurgery, the basis of equipment and general tissue effects, as well as the surgeon's spatial orientation and hand-eye coordination. Some intraoperative adjuvant procedures and newly developed safety devices have become available may aid to improve electrosurgical safety. CONCLUSIONS: Knowledge of the biophysics of electrosurgery and the mechanisms of electrosurgical injury is important in recognizing potential complications of electrosurgery in laparoscopy. Procedures for prevention, intraoperative adjuvant maneuvers, early recognition of the injury with in-time salvage treatment, and alertness to postoperative warning signs can help reduce such complications.

A potential complication of laparoscopy--the surgeon's herniated cervical disk.

Almost all operations that were traditionally performed by open laparotomy operations can be done laparoscopically; however, surgeons may experience several negative health effects. A 37-year-old gynecologic laparoscopist had a herniated intervertebral disk at C5-6 level. Due to a negative trauma history, a possible explanation may be the nonergonomic posture that he held while performing laparoscopic surgery for many hours. To reduce the risk of this complication, we recommend that surgeons' spatial orientation and hand-eye coordination for laparoscopy be improved by sequential phases of training.