bluuebunny/crossref_metadata_2025 huggingface dataset:
Return-to-duty Rates among Coalition Forces Treated in a Forward-deployed Pain Treatment Center
Authors: White Ron L. , Cohen Steven P.
Published: March 2009

Background

Non-battle-related injuries and the recurrence of chronic pain are major causes of medical evacuation in wartime. Because a pain medicine specialist may or may not be assigned to a forward-deployed medical unit, the treatment of pain from non-battle-related injuries in war zones is a serendipitous endeavor. Previous studies have demonstrated that the return-to-unit rate for soldiers evacuated to a tertiary care facility for pain management is abysmally low.

Methods

This is a prospective, observational study measuring return-to-duty rates in the first forward-deployed pain treatment center.

Results

Over a 6-month period, 132 patients were treated, the large majority (n = 113) of whom were coalition forces. In descending order, the four most common diagnoses among coalition forces were lumbar radiculopathy (n = 63), thoracic pain (n = 13), cervical radiculopathy (n = 8), and groin pain (n = 8). Epidural steroid injections (n = 125) were by far the most frequently performed procedure, followed by trigger point injections (n = 21), lumbar facet blocks (n = 16), and groin blocks (n = 9). Nonsteroidal antiinflammatory drugs were prescribed to 70% of patients, and 24% were referred to physical therapy. The return-to-duty rate for coalition forces was 94.7%. The primary complaint of all 7 patients who required medical evacuation outside the theaters of operation was groin pain.

Conclusions

These results demonstrate the feasibility of obtaining high return-to-duty rates when aggressive pain management strategies are used in forward-deployed areas.
A Facilitated Survey Instrument Captures Significantly More Anesthesia Events Than Does Traditional Voluntary Event Reporting
Authors: Oken Andrew , Rasmussen Mark D. , Slagle Jason M. , Jain Sonia , Kuykendall Tod , Ordonez Nelda , Weinger Matthew B.
Published: March 2009

Background

This study sought to evaluate the effectiveness of an active survey method for detecting anesthesia nonroutine events (NREs). An NRE is any aspect of clinical care perceived by clinicians or observers as a deviation from optimal care based on the context of the clinical situation.

Methods

A Comprehensive Open-ended Nonroutine Event Survey (CONES) was developed to elicit NREs. CONES, which consisted of multiple brief open-ended questions, was administered to anesthesia providers in the postanesthesia care unit. CONES data were compared with those from the same hospital's anesthesia quality assurance (QA) process, which relied on self-reporting of predefined adverse events.

Results

CONES interviews were conducted after 183 cases of varying patient, anesthesia, and surgical complexity. Fifty-five cases had at least one NRE (30.4% incidence). During the same 30-month period, the QA process captured 159 cases with 96.8% containing at least one NRE among the 8,303 anesthetic procedures conducted (1.9% overall incidence). The CONES data were more representative of the overall surgical population. There were significant differences in NRE incidence (P < 0.001), patient impact (74.5% vs. 96.2%; P < 0.001), and injury (23.6% vs. 60.3%) between CONES and QA data. Outcomes were more severe in the QA group (P < 0.001). Extrapolation of the CONES data suggested a significantly higher overall incidence of anesthesia-related patient injury (7.7% vs. only 1.0% with the QA method).

Conclusions

An active surveillance tool using the NRE construct identified a large number of clinical cases with potential patient safety concerns. This approach may be a useful complement to more traditional QA methods of self-reporting.
Comparison of Catheter-related Infection and Tip Colonization between Internal Jugular and Subclavian Central Venous Catheters in Surgical Neonates
Authors: Breschan Christian , Platzer Manuela , Jost Robert , Schaumberger Florian , Stettner Haro , Likar Rudolf
Published: March 2009

Background

The primary aim of this study was to compare catheter-associated infections and tip contaminations between percutaneously placed central venous catheters in the internal jugular and subclavian veins in surgical neonates undergoing major noncardiac surgery.

Methods

The prospectively computerized protocols of 295 procedures were analyzed retrospectively.

Results

One hundred twenty-nine internal jugular venous (group I) and 107 subclavian venous catheters (group S) were included. The median postconceptual age was 37 weeks in group I and 38 in group S. The weight ranged from 580 g to 4.5 kg in group I and from 820 g to 4.5 kg in group S at the time of insertion. Significantly more catheter-associated infections were observed in group I (15.5 vs. 4.7%; chi-square analysis: P < 0.01). The internal jugular venous catheters were also associated with a significantly increased probability of an earlier onset of a catheter-associated infection compared with the subclavian venous catheters (log rank test: P < 0.01; Cox model: P < 0.01). This probability was only slightly increased by a lower weight (Cox model: P = 0.075), and it was not increased by a lower age (Cox model: P = 0.93). Significantly more catheter tips were contaminated by pathogens in group I (55.8 vs. 33.6%; chi-square analysis: P < 0.01).

Conclusion

The internal jugular venous catheters were associated with a higher infection rate as well as earlier onset of catheter-associated infection compared with the subclavian venous catheters.
Isoflurane Preconditioning Improves Long-term Neurologic Outcome after Hypoxic–Ischemic Brain Injury in Neonatal Rats
Authors: Zhao Ping , Peng Longyun , Li Liaoliao , Xu Xuebing , Zuo Zhiyi
Published: March 2009

Background

Preconditioning the brain with relatively safe drugs seems to be a viable option to reduce ischemic brain injury. The authors and others have shown that the volatile anesthetic isoflurane can precondition the brain against ischemia. Here, the authors determine whether isoflurane preconditioning improves long-term neurologic outcome after brain ischemia.

Methods

Six-day-old rats were exposed to 1.5% isoflurane for 30 min at 24 h before the brain hypoxia-ischemia that was induced by left common carotid arterial ligation and then exposure to 8% oxygen for 2 h. The neuropathology, motor coordination, and learning and memory functions were assayed 1 month after the brain ischemia. Western analysis was performed to quantify the expression of the heat shock protein 70, Bcl-2, and survivin 24 h after isoflurane exposure.

Results

The mortality was 45% after brain hypoxia-ischemia. Isoflurane preconditioning did not affect this mortality. However, isoflurane preconditioning attenuated ischemia-induced loss of neurons and brain tissues, such as cerebral cortex and hippocampus in the survivors. Isoflurane also improved the motor coordination of rats at 1 month after ischemia. The learning and memory functions as measured by performance of Y-maze and social recognition tasks in the survivors were not affected by the brain hypoxia-ischemia or isoflurane preconditioning. The expression of Bcl-2, a well-known antiapoptotic protein, in the hippocampus is increased after isoflurane exposure. This increase was reduced by the inhibitors of inducible nitric oxide synthase. Inducible nitric oxide synthase inhibition also abolished isoflurane preconditioning-induced neuroprotection.

Conclusions

Isoflurane preconditioning improved the long-term neurologic outcome after brain ischemia. Inducible nitric oxide synthase may be involved in this neuroprotection.
Sevoflurane Directly Excites Locus Coeruleus Neurons of Rats
Authors: Yasui Yutaka , Masaki Eiji , Kato Fusao
Published: March 2009

Background

Sevoflurane, an anesthetic showing high incidence of emergence agitation in human patients, especially in children, increases noradrenaline release in the preoptic area in the rat brain. The clinically observed frequency of emergence agitation with sevoflurane is significantly reduced by drugs activating alpha2 adrenoceptors. The locus coeruleus (LC) is a source nucleus of widely spreading noradrenergic projections in the central nervous system and is also known as one of the principal targets of some alpha2-adrenoceptor agonists, such as dexmedetomidine. The authors analyzed the effects of sevoflurane and other anesthetics on the membrane current of the LC neurons to study the mechanism of the paradoxical "excitatory" effects of the anesthetics.

Methods

Effects of volatile and nonvolatile anesthetics on the membrane potential and currents of LC neurons in pontine slices of the rat were evaluated. Action potential-dependent transmission was suppressed with tetrodotoxin.

Results

Sevoflurane at 5% (measured concentration in the recording chamber, 0.5 mm) induced an early-phase inward current in most of LC neurons in a robust manner, which significantly increased the firing frequency in the absence of tetrodotoxin under current clamp recording. Preadministration of dexmedetomidine (1-3 nm) occluded this increase in firing frequency with sevoflurane. This inward current was inhibited by a gap junction inhibitor carbenoxolone and was not observed with nonvolatile general anesthetics and in non-LC neurons examined.

Conclusions

The excitatory current activated by sevoflurane in LC neurons, likely to be mediated by gap junction-related mechanisms, might be one of the potential cellular mechanisms underlying paradoxical excitatory effect of sevoflurane.
Neurokinin-1 Receptor Antagonists Inhibit the Recruitment of Opioid-containing Leukocytes and Impair Peripheral Antinociception
Authors: Rittner Heike L. , Lux Christian , Labuz Dominika , Mousa Shaaban A. , Schäfer Michael , Stein Christoph , Brack Alexander
Published: March 2009

Background

Neurokinins (e.g., substance P) contribute to pain transmission in the central nervous system, peripheral neurogenic inflammation, and leukocyte recruitment in inflammation. Leukocyte recruitment involves (1) up-regulation of adhesion molecule expression through neurokinin-1 (NK1) receptors on endothelial cells, (2) augmented chemokine production, or (3) chemotaxis through NK1 receptors on leukocytes. In inflammation, leukocytes can trigger endogenous antinociception through release of opioid peptides and activation of opioid receptors on peripheral sensory neurons. The authors hypothesized that NK1 receptor antagonists impair recruitment of opioid-containing leukocytes and stress-induced antinociception.

Methods

Rats were treated intraperitoneally and intrathecally with peripherally restricted (SR140333) or blood-brain barrier-penetrating (L-733,060) NK1 receptor antagonists and were evaluated for paw pressure thresholds, numbers of infiltrating opioid-containing leukocytes and leukocyte subpopulations, expression of adhesion molecules, NK1 receptors, and chemokines 24-48 h after complete Freund adjuvant-induced hind paw inflammation.

Results

Systemic and peripherally selective, but not intrathecal, NK1 receptor blockade reduced stress-induced antinociception (control: 177 +/- 9 g, L-733,060: 117 +/- 8 g, and control: 166 +/- 30 g, SR140333: 89 +/- 3 g; both P < 0.05, t test) without affecting baseline hyperalgesia. In parallel, local recruitment of opioid-containing leukocytes was decreased (L-733,060 and SR140333: 56.0 +/- 4.3 and 59.1 +/- 7.9% of control; both P < 0.05, t test). NK1 receptors were expressed on peripheral neurons, infiltrating leukocytes and endothelial cells. Peripheral NK1 receptor blockade did not alter endothelial expression of intercellular adhesion molecule-1 or local chemokine and cytokine production, but decreased polymorphonuclear cell and macrophage recruitment.

Conclusions

Endogenous inhibition of inflammatory pain is dependent on NK1 receptor-mediated recruitment of opioid-containing leukocytes.
Craniocervical Motion during Direct Laryngoscopy and Orotracheal Intubation with the Macintosh and Miller Blades
Authors: LeGrand Scott A. , Hindman Bradley J. , Dexter Franklin , Weeks Julie B. , Todd Michael M.
Published: March 2009

Background

Previous studies have characterized segmental craniocervical motion that occurs during direct laryngoscopy and intubation with a Macintosh laryngoscope blade. Comparable studies with the Miller blade have not been performed. The aim of this study was to compare maximal segmental craniocervical motion occurring during direct laryngoscopy and orotracheal intubation with Macintosh and Miller blades.

Methods

Eleven anesthetized and pharmacologically paralyzed patients underwent two sequential orotracheal intubations, one with a Macintosh blade and another with a Miller in random order. During each intubation, segmental craniocervical motion from the occiput to the fifth cervical vertebra (C5) was recorded using continuous lateral cinefluoroscopy. Single-frame images corresponding to the point of maximal cervical motion for both blade types were compared with a preintubation image. Using image analysis software, angular change in the sagittal plane at each of five intervertebral segments was compared between the Macintosh and Miller blades.

Results

Extension at occiput-C1 was greater with the Macintosh blade compared with the Miller (12.1 degrees +/- 4.9 degrees vs. 9.5 degrees +/- 3.8 degrees, respectively; mean difference = 2.7 degrees +/- 3.0 degrees; P = 0.012). Total craniocervical extension (occiput-C5) was also greater with the Macintosh blade compared with the Miller (28.1 degrees +/- 9.5 degrees vs. 23.2 degrees +/- 8.4 degrees, respectively; mean difference = 4.8 degrees +/- 4.4 degrees; P = 0.008).

Conclusions

Compared with the Macintosh, the Miller blade was associated with a statistically significant, but quantitatively small, decrease in cervical extension. This difference is likely too small to be important in routine practice.
Extensive and Partial Protein Hydrolysate Preterm Formulas
Authors: Szajewska Hania
Published: March 2009

Protein hydrolysate formulas for preterm infants recently have been developed. However, the indications for the use of such formulas are unclear. The aim of this article is to systematically evaluate the effect of protein hydrolysate formulas in the feeding of preterm infants through searching the MEDLINE (1966–August 2006) and Cochrane Library (Issue 4, 2006) databases. There is little evidence to support the use of extensive and partial protein hydrolysate formulas for preterm infants. High quality, long‐term trials are required before these formulas should be offered routinely in preference to other types of formula for preterm infants.
Evaluation and Management of Persistent Problems After Surgery for Hirschsprung Disease in a Child
Authors: Dasgupta Roshni , Langer Jacob C
Published: March 2009

Hirschsprung disease occurs approximately once in every 5000 live‐born infants. It is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. Once the diagnosis of Hirschprung disease has been made, most patients are now treated with a transanal approach to resection. We review the early and late postoperative complications. Late complications include persistent mechanical obstruction, recurrent or acquired aganglionosis, disordered motility in the proximal colon or small bowel, internal sphincter achalasia, or functional megacolon caused by stool‐holding behavior. These children require complex interdisciplinary care to ensure an adequate quality of life.
Intestinal Permeability and Effects of Lactobacillus rhamnosus Therapy in Children With Short Bowel Syndrome
Authors: Sentongo Timothy A , Cohran Valeria , Korff Simona , Sullivan Chris , Iyer Kishore , Zheng Xiaotian
Published: March 2009

Background:

The present study was conducted to investigate the effects of Lactobacillus rhamnosus (also known as LGG) on intestinal permeability (IP) in children with short bowel syndrome (SBS).

Patients and Methods:

In a double‐blind, placebo‐controlled crossover clinical trial, baseline IP (ie, lactulose‐to‐mannitol ratio) was measured in subjects with SBS and healthy control subjects. Subjects with SBS received LGG or placebo for 4 weeks, followed by a 3‐week washout before therapy was crossed over for another 4 weeks. IP, quantitative fecal cultures for Lactobacillus species (in colony‐forming units [cfu] per gram of stool) and hydrogen breath test (HBT) were performed during LGG and placebo phases of therapy.

Results:

Twenty‐one children (SBS, n = 9; control, n = 12) with a median age of 4.5 years (range 1.6–16.4 years) enrolled. Baseline IP measurements were similar in patients with SBS and control subjects: 0.08 ± 0.06 (mean ± SD) versus 0.07 ± 0.05 (P = 1.0). IP was correlated with age in control subjects (r = −0.83, P = 0.001) but not among patients with SBS (r = −0.55, P = 0.16). Fecal colonization with Lactobacillus species did not differ during LGG versus placebo therapy (median 1.4 × 109 cfu/g [range 4.0 × 105 to 4.0 × 109 cfu/g] vs 6.0 × 109 cfu/g [1.0 × 103 to 1.0 × 1010 cfu/g], respectively; P = 0.83). LGG therapy had no consistent effects on IP (P = 0.58) or its relationship with age (r = −0.40, P = 0.29), and was associated with conversion to positive HBT results in 1 subject.

Conclusions:

In this sample of children with SBS, the IP was within normal limits but did not correlate with age. LGG therapy had no consistent effects on IP. These findings do not support empiric LGG therapy to enhance IP in children with SBS.
Family Medicine Education in Brazil: Challenges, Opportunities, and Innovations
Authors: Blasco Pablo González , Levites Marcelo Rozenfeld , Janaudis Marco Aurélio , Moreto Graziela , Roncoletta Adriana Fernanda Tamassia , de Benedetto Maria Auxiliadora Craice , Pinheiro Thais Raquel
Published: March 2009

Since 1988, Brazil’s public health system has tried to build a national health system that responds to the needs and expectations of Brazil’s population. In 1994, the government created the Family Health Program to help carry out that goal. However, the dearth of family physicians in Brazil—the central figures in that program—limits the program’s effectiveness. The lack of family physicians can be traced primarily to the medical schools, which at that time were not training such physicians. This, in turn, can be traced to a number of conditions in Brazil (e.g., the bias toward specialization in both medical education and care) that favor specialists and discourage generalists.

In 1992, a group of physicians founded an academic society in São Paulo to promote the humanistic dimensions of doctoring and “establish the proper basis and scientific methodology for family medicine.” The society’s board eventually began teaching humanistic medicine to medical students, who became interested in family medicine. The board realized that its mission should expand to find ways to introduce and integrate family medicine into the medical schools of Brazil, to establish family medicine’s academic credentials, help attract students to family medicine as a career, and secure family medicine’s credibility in the marketplace. Since that time, the society has developed a variety of initiatives involving students, faculty, and medical schools to pursue these goals. The authors describe these initiatives, the progress made, and the challenges ahead.
Perspective: Medical Students’ Perceptions of the Poor: What Impact Can Medical Education Have?
Authors: Wear Delese , Kuczewski Mark G.
Published: March 2009

There is currently little knowledge or understanding of medical students’ knowledge and attitudes toward the poor. Teaching hospitals bring students face-to-face with poor and uninsured patients on a regular basis. However, an overview of the research available suggests that this contact does not result in students’ greater understanding and empathy for the plight of the poor and may, in fact, lead to an erosion of positive attitudes toward the poor. A basic understanding of justice suggests that as the poor are disproportionately the subjects of medical training, this population should enjoy a proportionate benefit for this service. Furthermore, medicine’s social contract with the public is often thought to include an ideal of service to the underserved and a duty to help educate the general public regarding the health needs of our nation.

In their discussion, the authors situate medical students’ attitudes toward the poor within larger cultural perspectives, including attitudes toward the poor and attributions for poverty. They provide three suggestions for improving trainees’ knowledge of and attitudes toward the poor—namely, increasing the socioeconomic diversity of students, promoting empathy through curricular efforts, and focusing more directly on role modeling. The authors argue that service learning, especially efforts that include gaining detailed knowledge of a particular person or persons, coupled with critical reflection, presents a very promising direction toward achieving these goals. Finally, they posit an agenda for future educational research that might contribute to the increased efficacy of medical education in this important formative domain.
On Outcomes and Humility
Authors: Wear Delese
Published: March 2009

The competency movement in medical education asserts itself in every corner of students’ experiences from matriculation through residency. Such a focus on making sure trainees achieve desired levels of skills, knowledge, and technique is highly desired by the patients they will be servicing, but educators’ need to turn nearly every dimension of medical education into a competency is an ill-advised leap that transforms a complex educational mission into a bottom-line venture. This commentary provides a critical examination of the wholesale use of competency measures in academic medicine, using the concurrent articles by Murray-García and García about multiculturalism and by Kumagai about narrative medicine as thoughtful examples of educational efforts that turn away from this narrow orientation, focusing instead on the ongoing reflective processes and humility that mark the lifelong development of skilled, empathic physicianhood.
Airway Changes during Labor and Delivery
Authors: Kodali Bhavani-Shankar , Chandrasekhar Sobhana , Bulich Linda N. , Topulos George P. , Datta Sanjay
Published: March 2009

Background

There are no prospective studies that evaluated airway changes during labor. The purpose of this study was to evaluate airway changes in women undergoing labor and delivery.

Methods

Two studies were undertaken to evaluate airway changes during labor. The first study used the conventional Samsoon modification of the Mallampati airway class. The airway was photographed at the onset and the end of labor. Women with class 4 airways were excluded from initial participation. In the second study, upper airway volumes were measured using acoustic reflectometry at the onset and the conclusion of labor. Acoustic reflectometry software computed the values for the components of upper airway, oral volume, and pharyngeal volume.

Results

In study 1 (n = 61), there was a significant increase in airway class from prelabor to postlabor (P < 0.001). The airway increased one grade higher in 20 (33%) and two grades higher in 3 (5%) after labor. At the end of labor, there were 8 parturients with airway class 4 (P < 0.01) and 30 parturients with airway class 3 or class 4 (P < 0.001). In study 2 (n = 21), there were significant decreases in oral volume (n = 21; P < 0.05), and pharyngeal area (P < 0.05) and volume (P < 0.001) after labor and delivery. No correlation was observed between airway changes during labor and duration of labor, or fluids administered during labor in either study.

Conclusion

Airways can change during labor. Therefore, a careful airway evaluation is essential just before administering anesthesia during labor rather than obtaining this information from prelabor data.
Dexmedetomidine Increases Hippocampal Phosphorylated Extracellular Signal–regulated Protein Kinase 1 and 2 Content by an α2-Adrenoceptor–independent Mechanism
Authors: Dahmani Souhayl , Paris Andrea , Jannier Virginie , Hein Lutz , Rouelle Danielle , Scholz Jens , Gressens Pierre , Mantz Jean
Published: March 2009

Background

Dexmedetomidine is a potent and selective alpha2-adrenoceptor (alpha2AR) agonist that exhibits a broad pattern of actions, including sedation, analgesia, and neuroprotection. Recent studies have emphasized the role of phosphorylated extracellular signal-regulated protein kinases (pERK1 and 2) in coupling rapid events such as neurotransmitter release and receptor stimulation long-lasting changes in synaptic plasticity and cell survival. Here, the authors hypothesized that dexmedetomidine increases pERK1 and 2 content and examined the mechanisms involved in this effect.

Methods

The effects of dexmedetomidine and their sensitivity to various pharmacologic agents on expression of pERK1 and 2 were studied by Western blots in hippocampal slices obtained from rats, wild-type mice, and mice carrying targeted deletions of the alpha2AR subtypes.

Results

Dexmedetomidine induced a concentration-related increase in the expression of pERK1 and 2 in rat hippocampal slices (EC50 [95% confidence interval] for pERK1, 0.97 [0.68-1.37] microm; for pERK2, 1.15 [0.62-2.14] microm). This effect was insensitive to the inhibitors of the alpha2AR-mediated signaling pathway, to prazosin, and to PP2, an inhibitor of the focal adhesion kinase-Src kinases. In contrast, it was still present in mice deleted for each of the alpha2AR subtypes and was markedly decreased by the antagonist of the I1-imidazoline receptors efaroxan, by phospholipase C and protein kinase C inhibitors, and by PD 098059, a direct inhibitor of ERK1 and 2 phosphorylation.

Conclusion

Dexmedetomidine increases the expression of pERK1 and 2 via mechanisms independent of alpha2AR activation. The I1-imidazoline receptors likely contribute to these effects. The results may be relevant to some long-term effects (e.g., neuroprotective) of dexmedetomidine in the brain.
Gabapentin Prevents Delayed and Long-lasting Hyperalgesia Induced by Fentanyl in Rats
Authors: Van Elstraete Alain C. , Sitbon Philippe , Mazoit Jean-Xavier , Benhamou Dan
Published: March 2009

Background

Opioid-induced hyperalgesia can develop rapidly after opioid exposure. Neuropathic pain and opioid-induced hyperalgesia share common pathophysiologic mechanisms. Gabapentin is effective for the management of neuropathic pain and may therefore prevent opioid-induced hyperalgesia. This study tested the effectiveness of gabapentin for prevention of long-lasting hyperalgesia induced by acute systemic fentanyl in uninjured rats. Involvement of the alpha2delta auxiliary subunits of voltage-gated calcium channels in the prevention of opioid-induced hyperalgesia by gabapentin also was assessed.

Methods

Hyperalgesia was induced in male Sprague-Dawley rats with subcutaneous fentanyl (four injections, 20, 60, or 100 microg/kg per injection at 15-min intervals). Intraperitoneal (30, 75, 150, or 300 mg/kg) or intrathecal (300 microg) gabapentin was administered 30 min before or 300 min after (intraperitoneal 150 mg/kg) the first fentanyl injection. Sensitivity to nociceptive stimuli (paw-pressure test) was assessed on the day of the experiment and for several days after injections. The effects combining gabapentin with intrathecal ruthenium red (20 ng) also were assessed.

Results

Fentanyl administration was followed by an early increase (analgesia) and by a later and sustained decrease (hyperalgesia) in nociceptive thresholds. Gabapentin did not significantly modify the early analgesic component but dose-dependently prevented the delayed decrease in nociceptive threshold. Ruthenium red partially, but significantly, opposed the prevention of opioid-induced hyperalgesia by gabapentin.

Conclusions

Intraperitoneal and intrathecal gabapentin prevents the development of hyperalgesia induced by acute systemic exposure to opioids. This prevention may result, at least in part, from binding of gabapentin to the alpha2delta auxiliary subunits of voltage-gated calcium channels.
Volatile Anesthetic Preconditioning Present in the Invertebrate Caenorhabditis elegans
Authors: Jia Baosen , Crowder C Michael
Published: March 2009

Background

Volatile anesthetics (VAs) have been found to induce a delayed protective response called preconditioning to subsequent hypoxic/ischemic injury. VA preconditioning has been primarily studied in canine and rodent heart. A more genetically tractable model of VA preconditioning would be extremely useful. Here, the authors report the development of the nematode Caenorhabditis elegans as a model of VA preconditioning.

Methods

Wild-type and mutant C. elegans were exposed to isoflurane, halothane, or air under otherwise identical conditions. After varying recovery periods, the animals were challenged with hypoxic, azide, or hyperthermic incubations. After recovery from these incubations, mortality was scored.

Results

Isoflurane- and halothane-preconditioned animals had significantly reduced mortality to all three types of injuries compared with air controls. Concentrations as low as 1 vol% isoflurane (0.64 mm) and halothane (0.71 mm) induced significant protection. The onset and duration of protection after anesthetic were 6 and 9 h, respectively. A mutation that blocks inhibition of neurotransmitter release by isoflurane did not attenuate the preconditioning effect. A loss-of-function mutation of the Apaf-1 homolog CED-4 blocked the preconditioning effect of isoflurane, but mutation of the downstream caspase CED-3 did not.

Conclusions

Volatile anesthetic preconditioning extends beyond the vertebrate subphylum. This markedly broadens the scope of VA preconditioning and suggests that its mechanisms are widespread across species and is a fundamental and evolutionarily conserved cellular response. C. elegans offers a means to dissect genetically the mechanism for VA preconditioning as illustrated by the novel finding of the requirement for the Apaf-1 homolog CED-4.
Vascular Remodeling Protects against Ventilator-induced Lung Injury in the In Vivo Rat
Authors: Kornecki Alik , Engelberts Doreen , McNamara Patrick , Jankov Robert P. , McCaul Conán , Ackerley Cameron , Post Martin , Kavanagh Brian P.
Published: March 2009

Background

The role of the pulmonary vasculature in the pathogenesis of ventilator-induced lung injury is not well established. In this study, the authors investigated the effect of vascular remodeling due to chronic pulmonary hypertension on susceptibility to ventilator-induced lung injury. The authors hypothesized that the enhanced vascular tensile strength associated with pulmonary vascular remodeling would protect against ventilator-induced lung injury.

Methods

Chronic pulmonary arterial hypertension was induced in rats by exposure to hypoxia for 28 days and was confirmed by demonstration of right ventricular hypertrophy. Normotensive and hypertensive groups of rats (as well as a group in which pulmonary hypertension was acutely reversed with a Rho-kinase inhibitor, Y-27632) were exposed to injurious ventilation (respiratory rate 30 min, 30/0 cm H2O) for 90 min. Lung injury was assessed by change in lung mechanics, oxygenation, edema development, and cytokine levels. Electron microscopy was used to examine vascular structure in additional animals.

Results

Injurious ventilation caused significant lung injury (lung compliance, oxygenation, pulmonary edema) in the normotensive controls, but not in the presence of pulmonary hypertension; acute reversal of pulmonary hypertension did not alter the lessened susceptibility to ventilator-induced lung injury. Electron microscopy demonstrated capillary endothelial and epithelial breaks in injuriously ventilated normotensive controls that were not seen with pulmonary hypertension, whether or not the pulmonary hypertension was acutely reversed.

Conclusions

Vascular remodeling induced by chronic pulmonary hypertension confers protection against the effects of injurious mechanical ventilation in vivo by a mechanism that may involve structural alterations rather than increased pulmonary artery pressure.
Lung Injury and Recovery in a Murine Model of Unilateral Acid Aspiration
Authors: Amigoni Maria , Bellani Giacomo , Scanziani Margherita , Masson Serge , Bertoli Elisa , Radaelli Enrico , Patroniti Nicolò , Di Lelio Alessandro , Pesenti Antonio , Latini Roberto
Published: March 2009

Background

Acid aspiration is a complication of general anesthesia. Most animal models developed to define its pathophysiology have focused on the acute (< or =24 h) phase of the injury. The authors describe a model of acid aspiration allowing the study of this type of lung injury over time.

Methods

The authors instilled hydrochloric acid (0.1 m, 1.5 ml/kg) or normal saline in the right bronchus of mice. Lung injury was evaluated at 6 h, 12 h, 24 h, and 2 weeks by assessing arterial blood gases, respiratory system compliance, lung wet weight normalized by body weight, lung myeloperoxidase activity, and histology. Twelve hours and 2 weeks after injury, a computed tomography scan was obtained.

Results

In the hydrochloric acid group, arterial oxygen tension decreased (P < 0.05) at 12 and 24 h, whereas it recovered at 2 weeks; respiratory system compliance was lower both at 24 h and 2 weeks (P < 0.05). Lung weight increased at 12 and 24 h (P < 0.05). Myeloperoxidase activity peaked between 6 and 12 h. Computed tomography at 12 h showed that almost 30% of the injured lung was abnormally aerated. Although reduced, the abnormalities were still present at 2 weeks as confirmed by a fibrotic scar well evident at histologic examination.

Conclusion

The authors characterized a murine model of regional acid aspiration allowing long-term survival. Despite a partial recovery, at 2 weeks the injury persisted, with evidence of fibrosis and lung compliance reduction. This long-term, low-mortality model seems suitable for assessment of the effects of different therapies on lung injury and repair.
Randomized Prospective Study Comparing the Laryngeal Tube Suction II with the ProSeal ™ Laryngeal Mask Airway in Anesthetized and Paralyzed Patients
Authors: Kikuchi Tatsuaki , Kamiya Yoshinori , Ohtsuka Tsuyoshi , Miki Tomoko , Goto Takahisa
Published: March 2009

Background

The Laryngeal Tube Suction II (LTSII; VBM, Medizintechnik, Sulz, Germany) is a recent revision of the Laryngeal Tube Suction. This study compared insertion and ventilation profiles of the LTSII and the ProSeal Laryngeal Mask Airway (PLMA; Laryngeal Mask Company, Henley-on-Thames, United Kingdom) in anesthetized and paralyzed patients.

Methods

One hundred adult male patients were randomly allocated to an LTSII or PLMArade mark group. The rate of successful insertion, insertion time, airway leak pressure at a cuff pressure of 60 cm H2O, tidal volume during pressure-controlled ventilation, incidence of gas leakage with cuff pressure reduced and with the shaft inclined, position of LTSII under fluoroscopic observation, and postoperative airway morbidity were determined.

Results

Insertion was successful in 37 and 48 of 50 patients with LTSII and PLMA, respectively (P = 0.002), with similar insertion times. Tidal volume was lower with LTSII than with PLMA. Median airway leak pressures of LTSII and PLMA were 16 and 21 cm H2O, respectively (P = 0.006). Gas leakage around the cuff was observed more frequently with LTSII than with PLMA when the cuff pressure was reduced or the shaft of the device inclined. The position of LTSII varied significantly and did not statistically correlate with patient height. Postoperative airway-related morbidity was not significantly different. Finally, tracheal misplacement of LTSII occurred in 5 of 50 patients (10%), but ventilation was possible in 4 of them, and misplacement was identified only after fluoroscopic examination was performed.

Conclusion

Airway management with LTSII is inferior to that with PLMA.
Temporal Effects of Topical Morphine Application on Cutaneous Wound Healing
Authors: Rook Jerri M. , Hasan Wohaib , McCarson Kenneth E.
Published: March 2009

Background

Studies have shown that topical administration of exogenous opioid drugs impairs wound healing by inhibiting the peripheral release of neuropeptides, thereby inhibiting neurogenic inflammation. This delay is immediate and peaks during the first days of wound closure. This study examined the effects of topical morphine treatment in a cutaneous wound healing model in the rat.

Methods

Full-thickness 4-mm-diameter wounds were placed on the periscapular region of rats that subsequently received twice-daily topical applications of IntraSite Gel (Smith+Nephew, Hull, United Kingdom) alone or gel infused with 5 mm morphine sulfate on days 0-3 or 4-10 postwounding or throughout the time course. Wound tissue was taken on days 1, 3, 5, 8, and 18 postwounding and immunostained for myofibroblast and macrophage markers or stained with hematoxylin and eosin.

Results

Delays in wound closure observed during morphine application on days 0-3 postwounding mimicked those seen in wounds treated with morphine throughout the entire healing process. However, no significant delays in closure were seen in wounds treated with morphine beginning on day 4 postwounding. Treatment of wounds with morphine significantly reduced the number of myofibroblasts and macrophages in the closing wound. In addition, morphine application resulted in decreases in skin thickness and an increase in residual scar tissue in healed skin.

Conclusions

These findings demonstrate the time-dependent and persistent nature of the detrimental effects of topical morphine on cutaneous wound healing. The data identify specific limitations that could be ameliorated to optimize topical opioid administration as an analgesic therapeutic strategy in the treatment of painful cutaneous wounds.
Total Intravenous Anesthesia Including Ketamine versus Volatile Gas Anesthesia for Combat-related Operative Traumatic Brain Injury
Authors: Grathwohl Kurt W. , Black Ian H. , Spinella Phillip C. , Sweeney Jason , Robalino Joffre , Helminiak Joseph , Grimes Jamie , Gullick Richard , Wade Charles E.
Published: March 2009

Background

Traumatic brain injury is a leading cause of death and severe neurologic disability. The effect of anesthesia techniques on neurologic outcomes in traumatic brain injury and potential benefits of total intravenous anesthesia (TIVA) compared with volatile gas anesthesia (VGA), although proposed, has not been well evaluated. The purpose of this study was to compare TIVA versus VGA in patients with combat-related traumatic brain injury.

Methods

The authors retrospectively reviewed 252 patients who had traumatic brain injury and underwent operative neurosurgical intervention. Statistical analyses, including propensity score and matched analyses, were performed to assess differences between treatment groups (TIVA vs. VGA) and good neurologic outcome.

Results

Two hundred fourteen patients met inclusion criteria and were analyzed; 120 received VGA and 94 received TIVA. Good neurologic outcome (Glasgow Outcome Score 4-5) and decreased mortality were associated with TIVA compared with VGA (75% vs. 54%; P = 0.002 and 5% vs. 16%; P = 0.02, respectively). Multivariate logistic regression found admission Glasgow Coma Scale score of 8 or greater (odds ratio, 13.3; P < 0.001) and TIVA use (odds ratio, 2.3; P = 0.05) to be associated with good neurologic outcomes. After controlling for confounding factors using propensity analysis and repeated one-to-one matching of patients receiving TIVA with those receiving VGA with regard to Injury Severity Score, Glasgow Coma Scale score, base deficit, Head Abbreviated Injury Score, and craniectomy or craniotomy, the authors could not find an association between treatment and neurologic outcome.

Conclusion

Total intravenous anesthesia often including ketamine was not associated with improved neurologic outcome compared with VGA. Multiple confounders limit conclusions that can be drawn from this retrospective study.
Cholinesterase Inhibitor Donepezil Dilates Cerebral Parenchymal Arterioles via the Activation of Neuronal Nitric Oxide Synthase
Authors: Nakahata Katsutoshi , Kinoshita Hiroyuki , Hama-Tomioka Keiko , Ishida Yuko , Matsuda Naoyuki , Hatakeyama Noboru , Haba Masanori , Kondo Toshikazu , Hatano Yoshio
Published: March 2009

Background

An acetylcholinesterase inhibitor donepezil currently is used to treat patients with Alzheimer disease. However, its direct effect on cerebral blood vessels has not been evaluated. The present study was designed to examine whether donepezil induces acute cerebral arteriolar dilation and whether neuronal nitric oxide synthase contributes to this vasodilator response.

Methods

Brain slices were obtained from neuronal nitric oxide synthase knock-out or C57BL/6J strain (control) mice as well as Wistar rats. Parenchymal arterioles were monitored using videomicroscopy. During constriction to prostaglandin F2alpha (5 x 10 m), donepezil (10-10 m) or acetylcholine (10-10 m) was added. In some experiments, brain slices were treated with a nonselective or a selective nitric oxide synthase inhibitor (N-nitro-L-arginine methyl ester [10 m] and S-methyl-L-thiocitrulline [10 m], respectively). An immunohistochemical analysis was performed using antibodies for neuronal nitric oxide synthase and acetylcholinesterase.

Results

Acetylcholine concentration-dependently dilated rat parenchymal arterioles, while S-methyl-L-thiocitrulline as well as N-nitro-L-arginine methyl ester completely abolished this response. Donepezil produced arteriolar dilation, which was inhibited by S-methyl-L-thiocitrulline or N-nitro-L-arginine methyl ester. Donepezil failed to induce arteriolar dilation in the brain slice from the neuronal nitric oxide synthase knock-out mice. Immunohistochemical analysis revealed spatial relationship between neuronal nitric oxide synthase and acetylcholinesterase in the arteriolar wall.

Conclusions

Donepezil produces acute vasodilation induced by a selective activation of neuronal nitric oxide synthase in the cerebral parenchymal arterioles. This agent may be capable of enhancing this enzymatic activity directly or via acetylcholinesterase existing on the arteriolar wall.
Greater Incidence of Emergence Agitation in Children after Sevoflurane Anesthesia as Compared with Halothane
Authors: Kuratani Norifumi , Oi Yumiko
Published: March 2009

Background

Sevoflurane is a popular inhalational anesthetic for general anesthesia in children. The higher incidence of emergence agitation has been suspected after sevoflurane anesthesia as compared with halothane, whereas some controlled studies showed conflicting results. In this report, the authors performed a meta-analysis of randomized controlled trials to compare the incidence of emergence agitation in children after sevoflurane or halothane anesthesia.

Methods

A comprehensive literature search was conducted to identify clinical trials that compared the incidence of emergence agitation in children anesthetized with sevoflurane versus halothane. Two reviewers independently assessed each report to meet the authors inclusion criteria and extracted data. The data from each trial were combined using the Mantel-Haenszel fixed-effect model to calculate the pooled odds ratio and 95% confidence interval. Funnel plots were used to assess publication bias. Subgroup analysis was used to clarify the effects of age, surgical procedure, pain treatment, and premedication on the incidence of emergence agitation.

Results

The authors identified 23 studies that met their inclusion criteria. Overall, 1,252 patients received sevoflurane and 1,111 had halothane. Heterogeneity of data was statistically refuted. The pooled odds ratio for all studies was 2.21, with a 95% confidence interval of 1.77-2.77 (P < 0.0001). Publication bias was not apparent in a funnel plot. All subgroup analyses showed a higher incidence of agitation after sevoflurane anesthesia.

Conclusions

This meta-analysis revealed that emergence agitation occurred more frequently with sevoflurane than with halothane anesthesia in children.
Inhalational Anesthetics Induce Cell Damage by Disruption of Intracellular Calcium Homeostasis with Different Potencies
Authors: Yang Hui , Liang Ge , Hawkins Brian J. , Madesh Muniswamy , Pierwola Andrew , Wei Huafeng
Published: March 2009

Background

The authors hypothesized that inhalational anesthetics induced cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of inositol 1,4,5-trisphosphate (IP3) receptors, with isoflurane having greater potency than sevoflurane or desflurane.

Methods

The authors treated DT40 chicken B lymphocytes with total IP3 receptor knockout or their corresponding wild-type control cells with equipotent exposure to isoflurane, sevoflurane, and desflurane. The authors then determined the degree of cell damage by counting the percentage of annexin V- or propidium iodide-positively stained cells or measuring caspase-3 activity. They also studied the changes of calcium concentrations in the endoplasmic reticulum, cytosol, and mitochondria evoked by equipotent concentrations of isoflurane, sevoflurane, and desflurane in both types of DT40 cells.

Results

Prolonged use of 2 minimal alveolar concentration sevoflurane or desflurane (24 h) induced significant cell damage only in DT40 wild-type and not in IP3 receptor total knockout cells, but with significantly less potency than isoflurane. In accord, all three inhalational anesthetics induced significant decrease of calcium concentrations in the endoplasmic reticulum, accompanied by a subsequent significant increase in the cytosol and mitochondrial calcium concentrations only in DT40 wild-type and not in IP3 receptor total knockout cells. Isoflurane treatment showed significantly greater potency of effect than sevoflurane or desflurane.

Conclusion

Inhalational anesthetics may induce cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of IP3 receptors. Isoflurane has greater potency than sevoflurane or desflurane to cause calcium release from the endoplasmic reticulum and to induce cell damage.
Hyperestrogenemia Simulating Kennedy Disease
Authors: Luo Jin Jun
Published: March 2009

A 71-year-old man developed clinical signs of Kennedy disease including dysarthria, dysphagia, palatal and oral mandibular fasciculations, lower-extremity weakness, gynecomastia, and testicular atrophy. Electrophysiologic studies showed sensory axonal polyneuropathy and chronic neurogenic changes of large-motor unit action potentials with decreased recruitment. Genetic analysis showed a normal 17-CAG repeat sequence. Laboratory studies showed an increased estrogen level of 180 to 220 pg/mL, probably related to his alcoholic fatty liver disease. Splenomegaly was present by ultrasound. The increased level of estrogen adversely affected estrogen-sensitive cells in breast, testicular, neuronal, and muscle cells, leading to the clinical phenotype.