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Background: Macaques are outstanding animal models for the development of new contraceptives. In women, progestin-only contraceptives often fail to block ovulation and are believed to act by altering cervix physiology. Herein, we assessed oviductal glycoprotein 1 (OVGP1) in the macaque cervix as a marker for progestogen action., Materials: Rhesus macaques were treated with estradiol (E 2 ), E 2 plus progesterone (P), and E 2 plus levonorgestrel (LNG), a contraceptive progestin. Samples consisted of archived blocks of midcervix mucosa (epithelium and lamina propria) and fresh epithelial cells collected non-invasively by cytobrush. OVGP1 was assayed by quantitative real-time PCR and localized by immunocytochemistry., Results: OVGP1 transcript was maximal after E 2 and reduced after treatment with E 2  + P (P < .05). LNG also reduced OVGP1 expression (P < .05). OVGP1-specific staining localized to epithelial cells, and transcript was quantifiable in cytobrush collected samples., Conclusions: OVGP1 expression in cytobrush samples of macaque cervix provides a non-invasive indicator of contraceptive progestin action., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Although the occurrence of pain in hospitalized children is common, assessment and treatment of pain presents unique challenges to practitioners who care for pediatric patients. Knowledge of drug mechanisms as well as metabolic differences in infants and children compared with adults is necessary for the successful treatment of acute and chronic pain syndromes. Recent reports of adverse events in children receiving both opioid and non-opioid analgesics have prompted re-examination of some long standing pain medication regimens and prescribing practices. We review advances in diagnosis and management of pain in pediatric populations.

Simulation! The deans talk about its use in medical education regularly. But how can it be used to teach the basic sciences to first- and second-year medical students? This article will help answer that question by providing information about various types of simulation activities being used in medical education and examples of their application to basic science education. The next step depends on your creativity.

Objectives: The authors sought to design an integrated theme-based hybrid simulation experience to educate and evaluate emergency medicine (EM) residents, to measure the Accreditation Council for Graduate Medical Education (ACGME) competencies using this simulation model, to measure the impact of the simulation experience on resident performance on written tests, and to measure resident satisfaction with this simulation experience., Methods: A theme-based hybrid simulation model that takes advantage of multiple simulation modalities in a concentrated session was developed and executed to both educate and evaluate EM residents. Simulation days took place at an integrated simulation center and replaced one 5-hour didactic block per quarter. Modified competency checklists were used to evaluate residents based on ACGME competencies. Written tests were administered before, during, and after simulation days. Residents were given the opportunity to evaluate the simulation days using standard residency program evaluation tools., Results: The model was proven feasible. Core competencies were measured using the model, which was executed on four occasions in 2007. Most residents met expectations based on objective checklist criteria and subjective assessment by an observing faculty member. Data from the written tests showed no overall difference in scores measured before, during, or after the simulation days. The simulation model was rated highly useful by the residents., Conclusions: With the use of a highly developed simulation center and an organized, theme-based, hybrid simulation model that takes advantage of multiple simulation modalities, the authors were able to successfully develop an educational model to both train and evaluate EM residents with a high degree of resident satisfaction.

The historical roots of simulation might be described with the broadest definition of medical simulation: "an imitation of some real thing, state of affairs, or process" for the practice of skills, problem solving, and judgment. From the first "blue box" flight simulator to the military's impetus in the transfer of modeling and simulation technology to medicine, worldwide acceptance of simulation training is growing. Large collaborative simulation centers support the expectation of increases in multidisciplinary, interprofessional, and multimodal simulation training. Virtual worlds, both immersive and Web-based, are at the frontier of innovation in medical education.

Simulation is becoming more widespread in undergraduate medical education, expanding well beyond its original application to anesthesiology. This heightened interest in simulation is being driven by advances in learning theory as well as technology developments. However, introducing simulation into a medical education curriculum presents significant challenges. This article describes the simulation initiatives at two medical schools. Both are state schools with similar enrollments; however, their approaches to developing and maintaining a simulation program differ. Regardless of these differences, both institutions have developed a variety of applications within the curriculum. The cases and applications that they have developed should be applicable to many medical schools.

Nesiritide is a recombinant formulation of B-type natriuretic peptide (BNP). Preliminary experience in the adult population has shown nesiritide to be an effective agent in the treatment of decompensated congestive heart failure (CHF) in adults. Given its physiological effects, it may be an effective agent in other clinical scenarios. We report the use of nesiritide in two infants during extracorporeal membrane oxygenation (ECMO). In one patient, nesiritide in doses up to 0.09 microg.kg(-1).min(-1) were used to control mean arterial pressure while in the other patient, doses of 0.01-0.03 microg.kg(-1).min(-1) were used to augment urine output. The potential applications of nesiritide and dosing regimens for this agent in the ECMO population are discussed.

Unlabelled: An 18-yr-old patient had a thoracic epidural placed under general anesthesia preceding an uneventful aortic valve replacement with a bioprosthetic valve. On the second postoperative day, he was anticoagulated and also received an antithrombotic medication. While ambulating, he experienced pain in his back, and there was blood in his epidural catheter. The catheter was removed, and he developed motor and sensory loss. Rapid surgical decompression resulted in recovery of his lost neurological function. Management and strategies for preventing this problem are discussed., Implications: Epidural hematoma is a rare complication of epidural anesthesia and has not been reported in pediatric patients undergoing cardiac surgery. The successful treatment of this complication requires swift recognition, diagnosis, and surgical intervention.

The use of NSAIDs has become routine for adults and children in the management of pain. NSAIDs (other than aspirin [acetylsalicylic acid]) are also enjoying greater popularity as antipyretics since the recognition of Reye's syndrome's putative association with aspirin. In neonates, NSAIDs have been used for many years in an attempt to pharmacologically close the ductus arteriosus. This review examines the various NSAIDs and their potential and real applications in the neonatal population. For completeness, acetaminophen (paracetamol), which has weak NSAID activity and is a widely used analgesic and antipyretic in this patient group, was also included. The prostaglandin system is important for healthy development, and conversely there are unique risks posed by pharmacologic interference with this system in the neonatal period. The prostanoid system in neonates has the capacity to modulate nociception, but comes at the expense of interfering with nearly every organ system. Physiologic effects of inhibition of prostaglandin synthesis applicable to neonates include disruption of the sleep cycle, increased risk of pulmonary hypertension, alterations in cerebral blood flow, decreased renal function, disrupted thermoregulation, and alterations in hemostasis balance, among others. Prostaglandins are also important for the normal development of the central nervous, cardiovascular, and renal systems, and there is evidence that the proper genesis of these systems may be adversely effected by NSAID exposure in utero and in the neonatal period. Gastrointestinal adverse effects have provided the impetus for the development and marketing of selective cyclo-oxygenase type 2 (COX-2) inhibitors. These agents' reputation for safety in adults may not be applicable to neonates. COX-2 is involved in the development of several organ systems, and its inhibition may induce a prothrombotic state. The advent of parenteral formulations of cyclo-oxygenase inhibitors, including COX-2-selective agents, increases the therapeutic flexibility of NSAIDs. However, objective data on the safety of these agents have not kept pace with their clinical availability.

Many medical disciplines participate in the acute care of hemodynamically unstable patients. At WVU we have many opportunities for multidisciplinary critical care group instruction in our simulation facility. The main educational goals of this session are the recognition and management of a pulmonary artery catheter that is coiled in the right ventricle. Recognition of waveforms and identification of catheter malposition are a priority in our critical care education programs. We present the scenario using the METI model C manikin with system 5.5 software. The target audiences for this scenario at WVU include junior house staff from assorted disciplines, masters level physician assistant students, and medical students during the second and fourth years of training. This scenario has also been included in a critical care medicine CME course for a variety of health care practitioners. We present a variety of the manufacturer's pre-packaged hemodynamic instability scenarios. Standard man awake or relaxed with the hypotension-hemorrhage scenario is described in detail. The focus is on catheter misplacement rather than on disease state. Despite prior preparation from lecture with slides, textbook review, ordemonstration without patient context, most students do not recognize a right ventricular waveform when it is simulated in the context of a patient care scenario. Debriefing occurs immediately in the simulation laboratory and includes a review of typical waveform and pressure transitions as the catheter passes from the introducer to the wedge position. Measurement of cardiac output is demonstrated. A variety of electronic resources are suggested for further self-study and more complete review of invasive monitoring principles and techniques. Students over the past 4 years have had an overwhelmingly positive response to this simulation experience.

The global approach to resuscitation has changed dramatically in the past year. The groundwork for these changes began a decade ago with the development of the Utstein guidelines for uniform reporting of critical events. Consistency in data collection was necessary to enable evidence-based review and comparison of current practice. Resuscitation protocols have been significantly altered based upon these data. Basic life support (BLS) protocols have been simplified. Early access to electrical cardioversion is the key to survival. Mobilization of AED technology in the community is essential. Several issues were identified as crucial to future improvement of resuscitation statistics. Prevention strategies should be developed for high-risk patients. There is a need to identify cases in which resuscitation should not be started. Enhancement of educational methods to improve performance and retention of skills is key. Finally, the roadblocks for performance of ethical prospective research must be minimized.

Study Objective: To determine the pharmacokinetics and preliminary efficacy of nalmefene in children in preventing epidural-induced narcotic side effects., Design: Double-blind, placebo-controlled study., Setting: University-affiliated children's hospital., Patients: Thirty-four children (aged 2-12 yrs) undergoing cardiothoracic surgery with epidural anesthesia., Interventions: Patients were randomized to receive intravenous bolus nalmefene 1 microg/kg or placebo., Measurements and Main Results: Six blood samples (one before nalmefene administration and five from 13 randomly designated time points) from each patient were assayed to determine plasma nalmefene concentrations. Patients were assessed for pain, nausea, vomiting, and urinary retention for 24 hours after administration. Concentration-time data were analyzed by a limited sampling strategy with adult pharmacokinetic parameters used as Bayesian priors. A two-compartment, first-order model was fitted to the data using ADAPT II. Pharmacokinetic parameter estimates in these patients were similar to values reported in adults. The initial disposition half-life (t(1/2alpha)) was 0.36+/-0.11 hour, the terminal elimination half-life (t(1/2beta)) 8.7+/-2.3 hours, clearance 0.729+/-0.172 L/kg/hr, and steady-state volume of distribution 7.21+/-2.49 L/kg. Ability to prevent epidural narcotic-induced side effects could not be documented at the 1-microg/kg dose. No statistically significant differences were noted between study and placebo groups with regard to pain, nausea, vomiting, or urinary retention., Conclusion: Nalmefene has similar pharmacokinetics in children as in adults. It was administered safely to these patients and did not produce unmanageable pain.

Eutectic mixture of local anesthetics (EMLA; Astra Pharmaceuticals, Wayne, PA) has been shown to reduce the pain of blood draws in children. We investigated the use of EMLA versus IV morphine for providing analgesia during chest tube removal (CTR) in children. One hundred twenty pediatric cardiothoracic surgery patients were enrolled. Patients were randomly assigned to receive either morphine (0.1 mg/kg up to 10 mg IV 30 min before CTR) or EMLA cream (5 g per chest tube cutaneously 3 h before CTR). A single, trained observer rated the patient's pain before, during, and after CTR using a 10-cm visual analog scale. The sites were evaluated for adverse effect. Methylhemoglobin levels were monitored in infants. Before CTR, the pain scores of the children who received morphine were rated lower than those who received EMLA (P < 0.01). During CTR, there was no difference in the pain score between the morphine or EMLA group. The change from baseline pain score in the morphine group was significantly larger than in the EMLA group (P < 0.01). We conclude that EMLA is safe and useful for blunting the pain of CTR.

Both theoretical and experimental work have suggested that central neurons compensate for changes in excitatory synaptic input in order to maintain a relatively constant output. We report here that inhibition of excitatory synaptic transmission in cultured spinal neurons leads to an increase in mEPSC amplitudes, accompanied by an equivalent increase in the accumulation of AMPA receptors at synapses. Conversely, increasing excitatory synaptic activity leads to a decrease in synaptic AMPA receptors and a decline in mEPSC amplitude. The time course of this synaptic remodeling is slow, similar to the metabolic half-life of neuronal AMPA receptors. Moreover, inhibiting excitatory synaptic transmission significantly prolongs the half-life of the AMPA receptor subunit GluR1, suggesting that synaptic activity modulates the size of the mEPSC by regulating the turnover of postsynaptic AMPA receptors.

Cardiopulmonary bypass (CPB) creates a myriad of pharmacological and physiological changes. Some of these changes have been studied in isolated in vitro studies. Integrating an in vitro system into an in vivo process is so complicated that many pharmacological studies simply avoid the bypass period. For the most part, the studies that do examine the bypass period deal with a single drug, reporting how it does or does not produce a predicted concentration on initiation, maintenance and termination of CPB. Based on the isolated results of these studies, this review hypothesizes a model that explains how different substances interact with the CPB system. A summary of the review's findings include the following: 1) drugs with a smaller volume of distribution are more likely to be effected; 2) the pharmacokinetic effects of lipophilic drugs undergo more alterations than hydrophilic drugs; and 3) protein binding minimizes alterations of lipophilic drugs and increase alterations of hydrophilic drugs.

Routine gynecologic care for persons with mental retardation may be difficult to provide, especially to those women who do not allow a pelvic examination to be performed. Of 275 women referred to a multidisciplinary clinic addressing the reproductive health concerns of mentally retarded women, 61 patients (22%) did not allow a gynecologic examination to be performed. The administration of ketamine alone, midazolam alone, or a combination of midazolam and ketamine allowed for the successful performance of a gynecologic examination in 81% of previously uncooperative women. No adverse effects of the medications were noted. We conclude that sedation of difficult-to-examine, mentally handicapped women can be safely performed in the outpatient setting, thus avoiding the need for general anesthesia and its inherent risks.

This retrospective study examines data from 55 patients sedated in a paediatric intensive care unit (PICU) with midazolam. Midazolam sedation was initiated with a bolus of 0.25 mg.kg-1 followed by a continuous infusion of 0.4-4 micrograms.kg-1.min-1. Physiological and metabolic parameters, infusion rates, duration, and sedation scores were monitored. Midazolam infusions were effective in sedating all the children studied during all or part of their PICU admission. The median duration of sedation was 74 h with a range of 4 to 1272 h. Haemodynamics were unchanged. Of the patients 46% were effectively alimented by the enteral route, and enteral alimentation was successful in all patients in whom it was attempted. Unassisted ventilation occurred in 44% of the patients during infusion. Oxygen consumption was 28% lower than in the control. Disadvantages of midazolam infusion have included inability to sedate during extracorporeal membrane oxygenation and development of acute tolerance.

The membrane oxygenator has replaced the bubble oxygenator in a wide variety of clinical settings. The membrane oxygenators now manufactured can be grouped into three categories based on composition and design: (1) silicone with a true membrane structure; (2) polypropylene with a microporous sheet; and (3) polypropylene with a microtubular structure. The capacity for fentanyl uptake by membrane oxygenators from these three categories was studied in vitro. Representative membrane samples were incubated in solutions containing tritiated fentanyl in Normosol-R (Abbott, North Chicago, IL) with pH adjusted to 7.4 at 37 degrees C. Fentanyl analysis was performed using liquid scintillation and radioimmunoassay techniques. The uptake of fentanyl at various concentrations (340 to 10 ng/mL) was studied. The SciMed (type 1; SciMed, Minneapolis, MN) membrane showed the greatest capacity for fentanyl uptake at all concentrations. The SciMed oxygenator was capable of binding 130 ng fentanyl/cm2 membrane. When presented with a smaller concentration (less than or equal to 20 ng/mL) of fentanyl, the membrane was able to extract all available fentanyl from solution. All of the microporous polypropylene oxygenators (types 2 and 3) absorbed significantly less fentanyl than did the SciMed brand. When exposed to 10 or 20 ng/mL, the Shiley and Omnis brands (type 2) absorbed 0.1 and 0.4 ng/cm2, respectively. Using the higher fentanyl concentrations (greater than or equal to 200 ng/mL) uptake by the Omnis membrane was 11 ng/cm2 compared with only 2 ng/cm2 by the Shiley. The Bentley BCM 7 and Terumo Capiox II 08 microtubular microporous membranes (type 3) did not show absorption of fentanyl using isolated or intact membrane models.(ABSTRACT TRUNCATED AT 250 WORDS)

The ability to deliver fluid to the pediatric patient is a function of many variables. In addition to patient-specific factors such as patient age, size, and weight, and venous size, number, and character, there exist further universal limitations inherent in the equipment which is utilized. Mechanical variables include cannula number, length, brand, and gauge; tubing length, band, style, and gauge; use of extensions; and presence and type of pressure system. This study evaluated a few of these variables. The flow rates were determined for 10 brands of 20-, 22-, and 24-gauge peripheral intravenous catheters. The catheter brands were divided into two groups, slow or faster. The differences in flow between the two categories were statistically significant. The disparities between the slowest and most rapid catheters of the same gauge were only 6.6, 5.4, and 7.7 ml/min for the 20, 22, and 24 gauges, respectively. The tubing apparatus was also a significant determinant of flow. The addition of any extensions further decreased flow. The magnitude of this slowing was a function of both the tubing and the type of extension.

The safety and efficacy of epidural morphine injected into the caudal space for control of postoperative pain following open cardiac surgery in children was studied. Thirty-two children between the ages of 2-12 yr for whom early postoperative tracheal extubation was anticipated were randomly assigned to control and study groups. Study subjects received a caudal injection of preservative free morphine sulfate (0.075 mg/kg) in preservative-free normal saline (5-10 ml) following completion of surgery, but prior to awakening and extubation of the trachea. Supplemental intravenous morphine administration and pain scores were recorded for 24 h. Patients in the study group received significantly less (P less than 0.03) morphine (0.32 mg.kg-1.24 h-1) and had significantly lower pain scores than did patients in the control group (0.71 mg.kg-1.24 h-1). The mean duration of complete analgesia in patients receiving caudally administered morphine was 6 h (range 2-12), but decreased analgesic requirements were noted for the entire 24 h. No respiratory depression was evident by clinical variables or repeated arterial blood gas values. Nausea without vomiting occurred in 4/16 patients in the study group. No patient described pruritus. The authors were unable to evaluate the occurrence of urinary retention because all patients had indwelling urinary catheters. They found caudal epidural morphine to be safe and effective in the treatment of postoperative pain in children following open heart surgery.

The anaesthetic management of children with glycogen-storage disease type IIa (Pompe's disease) presents a variety of challenges. A modification of a femoral nerve block, the inguinal paravascular block, as described by Winnie, was used in conjunction with intravenous ketamine to provide anaesthesia for a diagnostic muscle biopsy in a 5.5-month-old infant with Pompe's disease. A peripheral nerve stimulator was used to locate the femoral nerve in lieu of eliciting a paraesthesia.