bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin
Authors: Nikitas Georgios , Deschamps Chantal , Disson Olivier , Niault Théodora , Cossart Pascale , Lecuit Marc
Published: October 2011

Listeria monocytogenes (Lm) is a foodborne pathogen that crosses the intestinal barrier upon interaction between its surface protein InlA and its species-specific host receptor E-cadherin (Ecad). Ecad, the key constituent of adherens junctions, is typically situated below tight junctions and therefore considered inaccessible from the intestinal lumen. In this study, we investigated how Lm specifically targets its receptor on intestinal villi and crosses the intestinal epithelium to disseminate systemically. We demonstrate that Ecad is luminally accessible around mucus-expelling goblet cells (GCs), around extruding enterocytes at the tip and lateral sides of villi, and in villus epithelial folds. We show that upon preferential adherence to accessible Ecad on GCs, Lm is internalized, rapidly transcytosed across the intestinal epithelium, and released in the lamina propria by exocytosis from where it disseminates systemically. Together, these results show that Lm exploits intrinsic tissue heterogeneity to access its receptor and reveal transcytosis as a novel and unanticipated pathway that is hijacked by Lm to breach the intestinal epithelium and cause systemic infection.
Deleterious Impact of a γ-Aminobutyric Acid Type A Receptor Preferring General Anesthetic When Used in the Presence of Persistent Inflammation
Authors: Boegel Kevin , Gyulai Ferenc E. , Moore Kerry K. , Gold Michael S.
Published: October 2011

Background

Experimental data suggest general anesthetics preferring γ-aminobutyric acid receptor type A may increase postoperative pain in patients with persistent inflammation. The current study was designed to begin to test this hypothesis.

Methods

Groups of rats were defined by the presence of inflammation, surgical intervention, and/or the type of general anesthetic used for a 3-h period of anesthesia. Persistent inflammation was induced with complete Freund adjuvant. The surgical intervention was a plantar incision. Three mechanistically distinct general anesthetics were used: pentobarbital, ketamine/xylazine, and isoflurane. Ongoing pain and hypersensitivity were assessed with guarding behavior analysis and the von Frey test, respectively.

Results

There was no influence of general anesthetic type on the magnitude or time course of recovery from postoperative hypersensitivity in the absence of persistent inflammation. However, in the presence of persistent inflammation, recovery from hypersensitivity was significantly slower in the pentobarbital group than in the ketamine/xylazine or isoflurane groups. The pentobarbital effect was significant within 3 days of surgery and persisted through the remainder of the testing period. A comparable delay in recovery was observed in pentobarbital-anesthetized inflamed rats not subjected to hind paw incision. The time to 50% recovery in the pentobarbital-treated inflamed groups was almost double that in the other groups. No differences were observed between ketamine/xylazine and isoflurane. Pentobarbital exposure did not increase guarding scores.

Conclusions

These results suggest that general anesthetics preferring γ-aminobutyric acid receptor type A may have deleterious consequences when used in the presence of persistent inflammation.
Perioperative Stroke in Noncardiac, Nonneurosurgical Surgery
Authors: Ng Julie L. W. , Chan Matthew T. V. , Gelb Adrian W. , Warner David S.
Published: October 2011

Perioperative stroke after noncardiac, nonneurosurgical procedures is more common than generally acknowledged. It is reported to have an incidence of 0.05-7% of patients. Most are thrombotic in origin and are noted after discharge from the postanesthetic care unit. Common predisposing factors include age, a previous stroke, atrial fibrillation, and vascular and metabolic diseases. The mortality is more than two times greater than in strokes occurring outside the hospital. Delayed diagnosis and a synergistic interaction between the inflammatory changes normally associated with stroke, and those normally occurring after surgery, may explain this increase. Intraoperative hypotension is an infrequent direct cause of stroke. Hypotension will augment the injury produced by embolism or other causes, and this may be especially important in the postoperative period, during which monitoring is not nearly as attentive as in the operating room. Increased awareness and management of predisposing risk factors with early detection should result in improved outcomes.
Autopsy Utilization in Medicolegal Defense of Anesthesiologists
Authors: Lee Lorri A. , Stephens Linda S. , Fligner Corinne L. , Posner Karen L. , Cheney Frederick W. , Caplan Robert A. , Domino Karen B.
Published: October 2011

Background

The rate of autopsy in hospital deaths has declined from more than 50% to 2.4% over the past 50 yr. To understand the role of autopsies in anesthesia malpractice claims, we examined 980 closed claims for deaths that occurred in 1990 or later in the American Society of Anesthesiologists Closed Claims Project Database.

Methods

Deaths with autopsy were compared with deaths without autopsy. Deaths with autopsy were evaluated to answer the following four questions: Did autopsy findings establish a cause of death? Did autopsy provide new information? Did autopsy identify a significant nonanesthetic contribution to death? Did autopsy help or hurt the defense of the anesthesiologist? Reliability was assessed by κ scores. Differences between groups were compared with chi-square analysis and Kolmogorov-Smirnov test with P < 0.05 for statistical significance.

Results

Autopsies were performed in 551 (56%) of 980 claims for death. Evaluable autopsy information was available in 288 (52%) of 551 claims with autopsy. Patients in these 288 claims were younger and healthier than those in claims for death without autopsy (P < 0.01). Autopsy provided pathologic diagnoses and an unequivocal cause of death in 21% of these 288 claims (κ= 0.71). An unexpected pathologic diagnosis was found in 50% of claims with evaluable autopsy information (κ = 0.59). Autopsy identified a significant nonanesthetic contribution in 61% (κ = 0.64) of these 288 claims. Autopsy helped in the defense of the anesthesiologist in 55% of claims and harmed the defense in 27% (κ = 0.58) of claims with evaluable autopsy information.

Conclusions

Autopsy findings were more often helpful than harmful in the medicolegal defense of anesthesiologists. Autopsy identified a significant nonanesthetic contribution to death in two thirds of claims with evaluable autopsy information.
ARA290, a Peptide Derived from the Tertiary Structure of Erythropoietin, Produces Long-term Relief of Neuropathic Pain
Authors: Swartjes Maarten , Morariu Aurora , Niesters Marieke , Brines Michael , Cerami Anthony , Aarts Leon , Dahan Albert
Published: October 2011

Background

Exogenous erythropoietin inhibits development of allodynia in experimental painful neuropathy because of its antiinflammatory and neuroprotective properties at spinal, supraspinal, and possibly peripheral sites. The authors assess the effect of a nonhematopoietic erythropoietin analog, ARA290, on tactile and cold allodynia in a model of neuropathic pain (spared nerve injury) in rats and mice lacking the β-common receptor (βcR mice), a component of the receptor complex mediating tissue protection.

Methods

Twenty-four hours after peripheral nerve injury, rats and mice were injected with ARA290 or vehicle (five 30-μg/kg intraperitoneal injections at 2-day intervals, followed by once/week, n = 8/group). In a separate group of eight rats, ARA290 treatment was restricted to five doses during the initial 2 weeks after surgery.

Results

In rats, irrespective of treatment paradigm, ARA290 produced effective, long-term (as long as 15 weeks) relief of tactile and cold allodynia (P < 0.001 vs. vehicle-treated animals). ARA290 was effective in wild-type mice, producing significant relief of allodynia. In contrast, in βcR mice no effect of ARA290 was observed.

Conclusions

ARA290 produces long-term relief of allodynia because of activation of the β-common receptor. It is argued that relief of neuropathic pain attributable to ARA290 treatment is related to its antiinflammatory properties, possibly within the central nervous system. Because ARA290, in contrast to erythropoietin, is devoid of hematopoietic and cardiovascular side effects, ARA290 is a promising new drug in the prevention of peripheral nerve injury-induced neuropathic pain in humans.
Offset Analgesia in Neuropathic Pain Patients and Effect of Treatment with Morphine and Ketamine
Authors: Niesters Marieke , Hoitsma Elske , Sarton Elise , Aarts Leon , Dahan Albert
Published: October 2011

Background

Offset analgesia, in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation, has not been described previously in patients with chronic pain.

Methods

Offset analgesia responses in 10 patients with neuropathic pain (in both legs) were compared with 10 matched healthy controls and volunteers from a convenience sample (n = 110) with an age range of 6-80 yr. Offset analgesia was defined by the reduction in electronic pain score upon the 1°C decrease in noxious heat stimulus relative to the peak pain score where pain was administered at the volar side of the arm.

Results

Offset analgesia was present in healthy volunteers irrespective of age and sex (pain score decrease = 97 ± 1% [mean ± SEM]). In contrast, a reduced or absent offset analgesia response was observed in patients with neuropathic pain (pain score decrease = 56 ± 9% vs. controls 98 ± 1%, P < 0.001). Intravenous treatment with ketamine, morphine, and placebo had no effect on offset analgesia in patients, despite sharp reductions in spontaneous pain scores.

Conclusions

These data indicate that offset analgesia is fully developed at the age of 6 yr and does not undergo additional maturation. The reduced or absent responses observed in patients with chronic neuropathic pain indicate the inability to modulate changes in pain stimulation, with perseverance of pain perception in situations in which healthy subjects display signs of strong analgesia. Both central and peripheral sites may be involved in the altered offset analgesia responses in these patients.
Structural Studies of the Actions of Anesthetic Drugs on the γ-Aminobutyric Acid Type A Receptor
Authors: Akk Gustav , Steinbach Joe Henry
Published: October 2011

The γ-aminobutyric acid type A receptor is the major transmitter-gated inhibitory channel in the central nervous system. The receptor is a target for anesthetics, anticonvulsants, anxiolytics, and sedatives whose actions facilitate the flow of chloride ions through the channel and enhance the inhibitory tone in the brain. Both the kinetic and structural aspects of the actions of modulators of the γ-aminobutyric acid type A receptor are of great importance to understanding the molecular mechanisms of general anesthesia. In this review, the structural rearrangements that take place in the γ-aminobutyric acid type A receptor during channel activation and modulation are described, focusing on data obtained using voltage-clamp fluorometry. Voltage-clamp fluorometry entails the binding of an environmentally sensitive fluorophore molecule to a site of interest in the receptor, and measurement of changes in the fluorescence signal resulting from activation- or modulation-elicited structural changes. Detailed investigations can provide a map of structural changes that underlie or accompany the functional effects of modulators.
Genetic Variation, β-blockers, and Perioperative Myocardial Infarction
Authors: Nagele Peter , Liggett Stephen B. , Warner David S.
Published: October 2011

Perioperative myocardial infarction is a common and potentially fatal complication after noncardiac surgery, particular among patients with cardiovascular risk factors. β-blockers have been considered a mainstay in prevention and treatment of perioperative myocardial infarction, yet recent evidence suggests that β-blockers may have an unfavorable risk profile in this setting, and the use has become controversial. What seems conspicuously absent from the current discussion is the appreciation of how much interindividual genetic variation influences the clinical response to β-blocker therapy. Genetic variation in the adrenergic signaling pathway is common, and has a major impact on adrenergic receptor function and β-blocker efficacy in other cardiovascular diseases, such as heart failure and hypertension. Genetic variation in the cytochrome P450 2D6, or CYP2D6, enzyme, which is responsible for the metabolism of most β-blockers, is also important and can lead to poor metabolizing of β-blockers (potential toxicity) or their ultra-rapid degradation (decreased efficacy). Here, we review the molecular, cellular, and physiologic consequences of polymorphisms in the adrenergic signaling pathway and CYP2D6 gene, and show that these are likely relevant factors influencing efficacy, safety, and toxicity of β-blocker therapy in prevention and treatment of perioperative myocardial infarction.
Perioperative Nerve Injury after Total Hip Arthroplasty
Authors: Jacob Adam K. , Mantilla Carlos B. , Sviggum Hans P. , Schroeder Darrell R. , Pagnano Mark W. , Hebl James R.
Published: October 2011

Background

Perioperative nerve injury (PNI) is a recognized complication of total hip arthroplasty (THA). Regional anesthesia (RA) techniques may increase the risk of neurologic injury. Using a retrospective cohort study, the authors tested the hypothesis that use of RA increases the risk for PNI after elective THA.

Methods

All adult patients who underwent elective THA at Mayo Clinic during a 20-yr period were included. The primary outcome was the presence of a new PNI within 3 months of surgery. Multivariable logistic regression was used to evaluate patient, surgical, and anesthetic risk factors for PNI.

Results

Of 12,998 patients undergoing THA, 93 experienced PNI (incidence = 0.72%; 95% CI 0.58-0.88%). PNI was not associated with type of anesthesia (OR = 0.72 for neuraxial-combined vs. general; 95% CI 0.46-1.14) or peripheral nerve blockade (OR = 0.65; 95% CI 0.34-1.21). The risk for PNI was associated with younger age (OR = 0.79 per 10-yr increase; 95% CI 0.69-0.90), female gender (OR = 1.72; 95% CI 1.12-2.64), longer operations (OR = 1.10 per 30-min increase; 95% CI 1.03-1.18) or posterior surgical approach (OR = 1.91 vs. anterior approach; 95% CI 1.22-2.99). Neurologic recovery was not influenced by the use of RA techniques in patients with PNI.

Conclusions

The risk for PNI after THA was not increased with the use of neuraxial anesthesia or peripheral nerve blockade. Neurologic recovery in patients who experienced PNI was not affected by the use of RA. These results support the use of RA techniques in patients undergoing elective THA given their known functional and clinical benefits.
Influence of Patient Comorbidities on the Risk of Near-miss Maternal Morbidity or Mortality
Authors: Mhyre Jill M. , Bateman Brian T. , Leffert Lisa R.
Published: October 2011

Background

Maternal morbidity and mortality are increased in the United States compared with that of other developed countries. The objective of this investigation is to determine the extent to which it is possible to predict which patients will experience near-miss morbidity or mortality.

Methods

The authors defined near-miss morbidity as end-organ injury associated with length of stay greater than the 99 percentile or discharge to a second medical facility, and identified all cases of near-miss morbidity or death from admissions for delivery in the 2003-2006 Nationwide Inpatient Sample. Logistic regression was used to examine the effect of maternal characteristics on rates of near-miss morbidity/mortality.

Results

Approximately 1.3 per 1,000 hospitalizations for delivery was complicated by near-miss morbidity/mortality as defined in this study (95% CI 1.3-1.4). Most of these events (58.3%) occurred in 11.8% of the delivering population-in those women with important medical comorbidities or obstetric complications identified before admission for delivery. The highest rates were noted among women with pulmonary hypertension (98.0 cases per 1,000 deliveries), malignancy (23.4 per 1,000), and systemic lupus erythematosus (21.1 per 1,000).

Conclusions

Risk for near-miss morbidity or mortality is substantially increased among an identifiable subset of pregnant women. To the extent that antepartum multidisciplinary coordination and high-quality intrapartum care improve delivery outcomes for women with significant antepartum medical and obstetric disease, then public health investments to reduce the national burden of delivery-related near-miss morbidity and mortality will have the greatest effect by focusing resources on identifying and serving these high-risk groups.
Use of Concatemers of Ligand-Gated Ion Channel Subunits to Study Mechanisms of Steroid Potentiation
Authors: Steinbach Joe Henry , Akk Gustav
Published: October 2011

Synaptic receptors of the nicotinic receptor gene family are pentamers of subunits. This modular structure creates problems in studies of drug actions, related to the number of copies of a subunit that are present and their position. A separate issue concerns the mechanism of action of many anesthetics, which involves potentiation of responses to neurotransmitters. Potentiation requires an interaction between a transmitter and a potentiator, mediated through the target receptor. We have studied the mechanism by which neurosteroids potentiate transmitter responses, using concatemers of covalently linked subunits to control the number and position of subunits in the assembled receptor and to selectively introduce mutations into positionally defined copies of a subunit. We found that the steroid needs to interact with only one site to produce potentiation, that the native sites for steroid interaction have indistinguishable properties, and that steroid potentiation appears to result from a global effect on receptor function.
Prolonged Central Venous Desaturation Measured by Continuous Oximetry Is Associated with Adverse Outcomes in Pediatric Cardiac Surgery
Authors: Crowley Ryan , Sanchez Elizabeth , Ho Jonathan K. , Lee Kate J. , Schwarzenberger Johanna , Marijic Jure , Sopher Michael , Mahajan Aman
Published: October 2011

Background

The role of continuous central venous oxygen saturation (ScvO₂) oximetry during pediatric cardiac surgery for predicting adverse outcomes is not known. Using a recently available continuous ScvO₂ oximetry catheter, we examined the association between venous oxygen desaturations and patient outcomes. We hypothesized that central venous oxygen desaturations are associated with adverse clinical outcomes.

Methods

Fifty-four pediatric patients undergoing cardiac surgery were prospectively enrolled in an unblinded observational study. ScvO₂ was measured continuously in the operating room and for up to 24 h post-Intensive Care Unit admission. The relationships between ScvO₂ desaturations, clinical outcomes, and major adverse events were determined.

Results

More than 18 min of venous saturations less than 40% were associated with major adverse events with 100% sensitivity and 97.6% specificity. Significant correlations resulted between the ScvO₂ area under the curve less than 40% and creatinine clearance at 12 h in the Intensive Care Unit (r = -0.58), Intensive Care Unit length of stay (r = 0.56), max inotrope use (r = 0.52), inotrope use at 24 h (r = 0.40), inotrope index score (r = 0.39), hospital length of stay (r = 0.36), and length of intubation (r = 0.32).

Conclusions

We demonstrate that ScvO₂ desaturations by continuous oximetry are associated with major adverse events in pediatric patients undergoing cardiac surgery. The most significant associations with major adverse events are seen in patients with greater than 18 min of central venous saturations less than 40%. Our results support the further investigation of ScvO₂ as a potential target parameter in high-risk pediatric patients to minimize the risk of major adverse events.
Protective and Detrimental Effects of Sodium Sulfide and Hydrogen Sulfide in Murine Ventilator-induced Lung Injury
Authors: Francis Roland C. , Vaporidi Katerina , Bloch Kenneth D. , Ichinose Fumito , Zapol Warren M.
Published: October 2011

Background

The antiinflammatory effects of hydrogen sulfide (H2S) and sodium sulfide (Na2S) treatment may prevent acute lung injury induced by high tidal volume (HVT) ventilation. However, lung protection may be limited by direct pulmonary toxicity associated with H2S inhalation. Therefore, the authors tested whether the inhalation of H2S or intravascular Na2S treatment can protect against ventilator-induced lung injury in mice.

Methods

Anesthetized mice continuously inhaled 0, 1, 5, or 60 ppm H2S or received a single bolus infusion of Na2S (0.55 mg/kg) or vehicle and were then subjected to HVT (40 ml/kg) ventilation lasting 4 h (n = 4-8 per group).

Results

HVT ventilation increased the concentrations of protein and interleukin-6 in bronchoalveolar lavage fluid, contributing to reduced respiratory compliance and impaired arterial oxygenation, and caused death from lung injury and pulmonary edema. Inhalation of 1 or 5 ppm H2S during HVT ventilation did not alter lung injury, but inhalation of 60 ppm H2S accelerated the development of ventilator-induced lung injury and enhanced the pulmonary expression of the chemoattractant CXCL-2 and the leukocyte adhesion molecules CD11b and L-selectin. In contrast, pretreatment with Na2S attenuated the expression of CXCL-2 and CD11b during HVT ventilation and reduced pulmonary edema. Moreover, Na2S enhanced the pulmonary expression of Nrf2-dependent antioxidant genes (NQO1, GPX2, and GST-A4) and prevented oxidative stress-induced depletion of glutathione in lung tissue.

Conclusions

The data suggest that systemic intravascular treatment with Na2S represents a novel therapeutic strategy to prevent both ventilator-induced lung injury and pulmonary glutathione depletion by activating Nrf2-dependent antioxidant gene transcription.
Neuroprotective Effect of Curcumin in an Experimental Rat Model of Subarachnoid Hemorrhage
Authors: Kuo Chang-Po , Lu Chueng-He , Wen Li-Li , Cherng Chen-Hwan , Wong Chih-Shung , Borel Cecil O. , Ju Da-Tong , Chen Chun-Mei , Wu Ching-Tang
Published: October 2011

Background

Subarachnoid hemorrhage (SAH) causes a high mortality rate and morbidity. It was suggested that oxidant stress plays an important role in neuronal injury after SAH. Therefore, we assessed the effect of curcumin on reducing cerebral vasospasm and neurologic injury in a SAH model in rat.

Methods

A double-hemorrhage model was used to induce SAH in rats. Groups of animals were treated with intraperitoneal injection of 20 mg/kg curcumin (curcumin group, n = 24) or dimethyl sulfoxide (vehicle group, n = 33), normal saline (SAH group, n = 34) or normal saline (sham group, n = 22), 3 h after SAH induction and daily for 6 days. Glutamate was measured before SAH induction and once daily for 7 days. Glutamate transporter-1, wall thickness and the perimeter of the basilar artery, neurologic scores, neuronal degeneration, malondialdehyde, superoxide dismutase, and catalase activities were assessed.

Results

Changes of glutamate levels were lower in the curcumin group versus the SAH and vehicle groups, especially on day 1 (56 folds attenuation vs. vehicle). Correspondingly, glutamate transporter-1 was preserved after SAH in curcumin-treated rats. In the hippocampus and the cortex, malondialdehyde was attenuated (30% and 50%, respectively). Superoxide dismutase (35% and 64%) and catalase (34% and 38%) activities were increased in the curcumin rats compared with the SAH rats. Mortality rate (relative risk: 0.59), wall thickness (30%) and perimeter (31%) of the basilar artery, neuron degeneration scores (39%), and neurologic scores (31%) were improved in curcumin-treated rats.

Conclusions

Curcumin in multiple doses is effective against glutamate neurotoxicity and oxidative stress and improves the mortality rate in rats with SAH.
Neonatal Desflurane Exposure Induces More Robust Neuroapoptosis than Do Isoflurane and Sevoflurane and Impairs Working Memory
Authors: Kodama Mitsuyoshi , Satoh Yasushi , Otsubo Yukiko , Araki Yoshiyuki , Yonamine Ryuji , Masui Kenichi , Kazama Tomiei
Published: October 2011

Background

In animal models, neonatal exposure to volatile anesthetics induces neuroapoptosis, leading to memory deficits in adulthood. However, effects of neonatal exposure to desflurane are largely unknown.

Methods

Six-day-old C57BL/6 mice were exposed to equivalent doses of desflurane, sevoflurane, or isoflurane for 3 or 6 h. Minimum alveolar concentration was determined by the tail-clamp method as a function of anesthesia duration. Apoptosis was evaluated by immunohistochemical staining for activated caspase-3, and by TUNEL. Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was performed to examine apoptosis comparatively. The open-field, elevated plus-maze, Y-maze, and fear conditioning tests were performed to evaluate general activity, anxiety-related behavior, working memory, and long-term memory, respectively.

Results

Minimum alveolar concentrations at 1 h were determined to be 11.5% for desflurane, 3.8% for sevoflurane, and 2.7% for isoflurane in 6-day-old mice. Neonatal exposure to desflurane (8%) induced neuroapoptosis with an anatomic pattern similar to that of sevoflurane or isoflurane; however, desflurane induced significantly greater levels of neuroapoptosis than almost equivalent doses of sevoflurane (3%) or isoflurane (2%). In adulthood, mice treated with these anesthetics had impaired long-term memory, whereas no significant anomalies were detected in the open-field and the elevated plus-maze tests. Although performance in a working memory task was normal in mice exposed neonatally to sevoflurane or isoflurane, mice exposed to desflurane had significantly impaired working memory.

Conclusions

In an animal model, neonatal desflurane exposure induced more neuroapoptosis than did sevoflurane or isoflurane and impaired working memory, suggesting that desflurane is more neurotoxic than sevoflurane or isoflurane.
Evolution of the Inflammatory and Fibroproliferative Responses during Resolution and Repair after Ventilator-induced Lung Injury in the Rat
Authors: Curley Gerard F. , Contreras Maya , Higgins Brendan , O'Kane Cecilia , McAuley Daniel F. , O'Toole Daniel , Laffey John G.
Published: October 2011

Background

The time course and mechanisms of resolution and repair, and the potential for fibrosis following ventilation-induced lung injury (VILI), are unclear. We sought to examine the pattern of inflammation, injury, repair, and fibrosis following VILI.

Methods

Sixty anesthetized rats were subject to high-stretch; low-stretch, or sham ventilation, and randomly allocated to undergo periods of recovery of 6, 24, 48, and 96 h, and 7 and 14 days. Animals were then reanesthetized, and the extent of lung injury, inflammation, and repair determined.

Results

No injury was seen following low-stretch or sham ventilation. VILI caused severe lung injury, maximal at 24 h, but largely resolved by 96 h. Arterial oxygen tension decreased from a mean (SD) of 144.8 (4.1) mmHg to 96.2 (10.3) mmHg 6 h after VILI, before gradually recovering to 131.2 (14.3) mmHg at 96 h. VILI induced an early neutrophilic alveolitis and a later lymphocytic alveolitis, followed by a monocyte/macrophage infiltration. Alveolar tumor necrosis factor-α, interleukin-1β, and transforming growth factor-β1 concentrations peaked at 6 h and returned to baseline within 24 h, while interleukin-10 remained increased for 48 h. VILI generated a marked but transient fibroproliferative response, which restored normal lung architecture. There was no evidence of fibrosis at 7 and 14 days.

Conclusions

High-stretch ventilation caused severe lung injury, activating a transient inflammatory and fibroproliferative repair response, which restored normal lung architecture without evidence of fibrosis.
Advances in the Management of Sepsis and the Understanding of Key Immunologic Defects
Authors: Skrupky Lee P. , Kerby Paul W. , Hotchkiss Richard S.
Published: October 2011

Anesthesiologists are increasingly confronting the difficult problem of caring for patients with sepsis in the operating room and in the intensive care unit. Sepsis occurs in more than 750,000 patients in the United States annually and is responsible for more than 210,000 deaths. Approximately 40% of all intensive care unit patients have sepsis on admission to the intensive care unit or experience sepsis during their stay in the intensive care unit. There have been significant advances in the understanding of the pathophysiology of the disorder and its treatment. Although deaths attributable to sepsis remain stubbornly high, new treatment algorithms have led to a reduction in overall mortality. Thus, it is important for anesthesiologists and critical care practitioners to be aware of these new therapeutic regimens. The goal of this review is to include practical points on important advances in the treatment of sepsis and provide a vision of future immunotherapeutic approaches.
Intraoperative Acceleromyography Monitoring Reduces Symptoms of Muscle Weakness and Improves Quality of Recovery in the Early Postoperative Period
Authors: Murphy Glenn S. , Szokol Joseph W. , Avram Michael J. , Greenberg Steven B. , Marymont Jesse H. , Vender Jeffery S. , Gray Jayla , Landry Elizabeth , Gupta Dhanesh K.
Published: October 2011

Background

The subjective experience of residual neuromuscular blockade after emergence from anesthesia has not been examined systematically during postanesthesia care unit (PACU) stays. The authors hypothesized that acceleromyography monitoring would diminish unpleasant symptoms of residual paresis during recovery from anesthesia by reducing the percentage of patients with train-of-four ratios less than 0.9.

Methods

One hundred fifty-five patients were randomized to receive intraoperative acceleromyography monitoring (acceleromyography group) or conventional qualitative train-of-four monitoring (control group). Neuromuscular management was standardized, and extubation was performed when defined criteria were achieved. Immediately upon a patient's arrival to the PACU, the patient's train-of-four ratios were measured using acceleromyography, and a standardized examination was used to assess 16 symptoms and 11 signs of residual paresis. This examination was repeated 20, 40, and 60 min after PACU admission.

Results

The incidence of residual blockade (train-of-four ratios less than 0.9) was reduced in the acceleromyography group (14.5% vs. 50.0% control group, with the 99% confidence interval for this 35.5% difference being 16.4-52.6%, P < 0.0001). Generalized linear models revealed the acceleromyography group had less overall weakness (graded on a 0-10 scale) and fewer symptoms of muscle weakness across all time points (P < 0.0001 for both analyses), but the number of signs of muscle weakness was small from the time of arrival in the PACU and did not differ between the groups at any time.

Conclusion

Acceleromyography monitoring reduces the incidence of residual blockade and associated unpleasant symptoms of muscle weakness in the PACU and improves the overall quality of recovery.
Clinical and Radiological Mid-Term Outcomes of Lumbar Single-Level Total Disc Replacement
Authors: Scott-Young Matthew N. , Lee Matthew J. , Nielsen David E. A. , Magno Carly L. , Kimlin Kristy R. , Mitchell Evan O.
Published: October 2011

Study Design.

Prospective single-center case cohort study.

Objective.

Evaluation of clinical and radiographic outcomes of a consecutive 122-patient cohort with discogenic back pain, at 2- to 10-year follow-up periods, treated by a single surgeon, with CHARITÉ Artificial Disc (DePuy Spine, Raynham, MA).

Summary of Background Data.

Minimum 2-year clinical and radiographic level 1 data for the first lumbar artificial disc, the CHARITÉ Artificial Disc (DePuy Spine), have recently been published, demonstrating sustained clinical benefit of the device for the treatment of degenerative disc disease.

Methods.

Patients were assessed preoperatively using clinical outcome measures, including visual analog scale (VAS) score back and leg, Oswestry Disability Index (ODI), 36-Item Short Form Health Survey (SF-36), and Roland-Morris Questionnaires (RMDQ), and further assessed postoperatively, 3-, 6-, 12-months, and yearly thereafter.

Results.

Average follow-up was 44.9 ± 23.3 months (n = 122). The median age at surgery was 43.0 ± 9.0 years. Preoperative diagnosis included degenerative disc disease in 118 (96.7%) and internal disc disruption in 4 (3.3%). Surgery was performed at L5–S1 in 96 (77.9%) patients and at L4–L5 in 27 (22.1%). Statistically significant clinical improvements from baseline were observed on VAS (back and leg), ODI, SF-36 PCS, SF-36 MCS, and RMDQ 3 months onward. Back VAS scores decreased from 78.2 ± 21.3 preoperatively to 21.9 ± 27.8 by final follow-up. ODI scores decreased from 51.1 ± 17.3 to 16.2 ± 17.9 at last follow-up. The RMDQ scores also decreased from 16.7 ± 4.7 to 4.2 ± 5.8. SF-36 PCS and MCS increased from 25.7 ± 11.0 to 46.4 ± 10.3 for PCS and from 35.5 ± 17.4 to 51.6 ± 10.8 for MCS. Patient satisfaction surveys indicated that 90.56% patients rated their satisfaction with the surgery as “excellent” or “good” at 2 years. Range of motion averaged 8.6 ± 3.5 (median = 8.0°) at the last follow-up time point.

Conclusion.

Outcomes verify the clinical efficacy of total disc replacement for treatment of discogenic back pain with or without radiculopathy. The outcomes instruments demonstrated statistically significant improvements 3 months onward.

Level of Evidence: N/A
The Charcot Joint: A Modern Neurologic Perspective
Authors: Chisholm Kara A , Gilchrist James M
Published: October 2011

The Charcot joint, or Charcot neuroarthropathy, is a syndrome that was described over 140 years ago but one with very little exposure in the neurologic literature. We present a case recently seen and then discuss the history, epidemiology, pathophysiology, clinical features, and diagnosis of acute and chronic Charcot joint disease with particular emphasis on the value and limitations of imaging. A diagnostic algorithm is proposed. We also review the therapeutic strategies available for acute and chronic Charcot joints with a treatment algorithm. This review is aimed at enhancing the awareness of neurologists regarding Charcot neuroarthropathy, because they are often the principal caregivers for patients with peripheral neuropathy. We hope to promote early detection of acute Charcot neuroarthropathy, thereby reducing or preventing the bony deformation of chronic Charcot neuroarthropathy.
Neuromuscular Diseases Associated With Chronic Hepatitis C Virus Infection
Authors: Stübgen Joerg-Patrick
Published: October 2011

Hepatitis C virus (HCV) infection is a growing international health problem, and more than 170 million people are chronic carriers. Up to 50% of HCV-positive patients develop at least one extrahepatic manifestation during the course of disease. To varying degrees of certainty, there is evidence of an association between chronic HCV infection and a variety of neuromuscular diseases. The pathogenesis of most extrahepatic diseases remains unclear but possibly includes HCV lymphotropism and/or HCV-induced autoantibodies. The therapeutic approach to HCV-associated autoimmune disorders entails eradication of HCV with one of the recombinant interferon-alpha preparations with or without additional immunosuppressive drugs.
Ocular Myasthenia Gravis in an Academic Neuro-Ophthalmology Clinic: Clinical Features and Therapeutic Response
Authors: Mittal Manoj Kumar , Barohn Richard J , Pasnoor Mamatha , McVey April , Herbelin Laura , Whittaker Thomas , Dimachkie Mazen
Published: October 2011

Objective:

The frequency of ocular myasthenia gravis (OMG) in patients referred to an academic neuro-ophthalmology clinic for suspected myasthenia gravis is not known. Our objective was to determine the frequency of ocular OMG in patients referred to an academic neuro-ophthalmologist and determine alternate diagnoses and response to therapy.

Methods:

We performed a retrospective chart review of patients presenting to the University of Kansas Neuro-Ophthalmology Clinic with suspected OMG over 9 years. We defined OMG as isolated ptosis/diplopia at initial presentation supported by at least one of the following abnormal tests: edrophonium test, ice test, Cogan lid twitch, fatigability on sustained upgaze, acetylcholine receptor binding antibody, greater than 10% decrement on repetitive stimulation, or abnormal single-fiber jitter. We also determined the cause of ptosis/diplopia if it was not the result of OMG. Patients who progressed from OMG to generalized disease were termed transformed myasthenia gravis (TMG).

Results:

One hundred thirty-eight patients were referred with mean age at presentation 58 ± 19 years. Myasthenia gravis was diagnosed in 101 patients; 95 had OMG; six had generalized MG. Diagnosis in the other 37 was cranial nerve palsies (nine), levator dehiscence (five), multiple sclerosis (two), blepharospasm (two), decompensated phorias (three), accommodation spasm (four), exophoria (three), skew deviation (two), Graves disease (one), hypertropia (one), myopathy (one), neurosarcoidosis (one), progressive supranuclear palsy (one), Miller Fisher variant of Guillain-Barre syndrome (one), and obstructive sleep apnea (one). Mean follow-up was 3.0 ± 2.8 years. Test sensitivity/specificity in OMG was fatigability on sustained upgaze 0.80/0.63; ice pack 0.80/0.25; Cogan lid twitch 0.59/1.00; edrophonium 0.88/0.50; acetylcholine receptor binding antibody 0.38/1.00; repetitive nerve stimulation 0.24/1.00; and single-fiber electromyography 0.90/1.00. Pyridostigmine was used without prednisone in 59 of 97 patients with OMG and 12 of 59 developed TMG. Prednisone was used in 38 patients; 21 of 38 (55%) met Myasthenia Gravis Foundation of America improvement status and none had TMG.

Conclusion:

The diagnosis of myasthenia gravis was confirmed in the majority of patients referred to our academic neuro-ophthalmology clinic, but 27% did not have myasthenia gravis. It is possible that prednisone treatment of OMG may prevent progression to TMG, but further study is required.
Increasing Mitral Valve Repair Rates with Nonresectional Techniques
Authors: Rankin J. Scott , Gaca Jeffrey G , Brunsting Louis A. , Daneshmand Mani A. , Milano Carmelo A. , Glower Donald D. , Smith Peter K.
Published: October 2011

In every common mitral pathology studied to date, repairing the patient's own diseased valve to adequate function has yielded superior long-term results as compared with prosthetic valve replacement with either tissue or mechanical devices. Thus, increasing rates of mitral repair across all valve pathologies would seem to be a logical clinical goal. Techniques for mitral valve repair have undergone continual evolution over the past 50 years. Recently, emphasis has been placed on preserving leaflet surface area and avoiding tissue resection, by combining the methods of Gore-Tex artificial chordal replacement, autologous pericardial leaflet augmentation, and full ring annuloplasty. Using combinations of these three techniques appropriate to the given valve pathology, acute mitral repair rates now are approximating 98% for all common mitral disease etiologies. Simultaneously, operative mortalities for mitral repair have fallen significantly and now are negligible, whereas long-term outcomes using these methods have been increasingly more stable. As a result of innovations from multiple sources, mitral valve surgery has been converted from a higher risk procedure to one of the safest operations in most centers. This review will detail the technical application of “nonresectional” mitral repair approaches to a broad range of mitral disease pathologies.
Handheld Office-Based Spirometry versus Laboratory Spirometry in Low-Risk Patients Undergoing Lung Resection
Authors: Puri Varun , Zoole Jennifer B. , Musick Joanne , Krupnick Alexander S. , Kreisel Daniel , Crabtree Traves D. , Patterson G. Alexander , Meyers Bryan F.
Published: October 2011

Objective

To compare handheld office spirometry with laboratory spirometry in evaluation of low-risk patients undergoing pulmonary resection.

Methods

Low-risk patients evaluated for lung resection were enrolled in a prospective study and underwent office and laboratory spirometry. Standard laboratory spirometry values were considered the gold standard. Values of forced expiratory volume in 1 second (FEV1) <1.5 L or FEV1% <60% were determined in advance to signal high risk.

Results

Thirty patients with mean age 64 ± 12 years and median Karnofsky performance status 100 (80–100) were evaluated. The mean FEV1-office spirometry and mean FEV1-laboratory spirometry were comparable (2.14 L vs 2.36 L) as were the mean FEV1%-office spirometry and FEV1%-laboratory spirometry (78% vs 85%). The differences were within limits established a priori. Laboratory spirometry identified 3 of 30 (10%) patients as high risk and office spirometry identified 5 of 30 (16%) patients as high risk, including the 3 patients identified by laboratory spirometry. The sensitivity of office spirometry for detecting high risk was 100% (3/3) and specificity was 93% (25/27). The negative predictive value of office spirometry was 100% (25/25). Office spirometry added a median of 1 minute to the office visit, whereas laboratory spirometry added 42 minutes. Eventually, 25 of 30 (83%) patients underwent lung resection. There were 12 lobar and 13 sublobar resections. One patient developed postoperative respiratory morbidity. This patient was high risk by office spirometry but not by laboratory spirometry. This patient was discharged on home oxygen.

Conclusions

Office spirometry FEV1 and FEV1% are clinically comparable to formal laboratory spirometry values. Office Spirometry saves time and possibly expense in the preoperative workup of patients evaluated for lung resection.
Safety of Percutaneous Endoscopic Gastrostomy in Medically Complicated Infants
Authors: Minar Philip , Garland Jeffery , Martinez Alfonso , Werlin Steven
Published: October 2011

Background and Objective:

Percutaneous endoscopic gastrostomy (PEG) tubes have been placed in children for more than 2 decades to provide nutrition to those unable to adequately and safely feed orally. Despite the well‐documented success of PEG placement in older children, there is only 1 published article documenting the safety of PEG placement in small infants. In all children, PEG studies demonstrate the major complication rate to vary from 0.5% to 17%. The objective of this study was to evaluate the incidence of acute complications of PEG placement in medically complicated infants with a weight of less than 6 kg.

Patients and Methods:

We reviewed the charts of all infants cared for in the neonatal intensive care unit of Wheaton Franciscan Health Care‐St Joseph's Regional Hospital, Milwaukee, WI, who received a PEG tube between January 2001 and June 30, 2008.

Results:

Forty infants with a mean gestational age of 29 weeks (range 23–41 weeks) with a mean weight of 3250 g (range 2100–5600 g) at time of PEG placement were included. The primary indication for most infants was dysphagia or inability to orally feed safely. A PEG was successfully placed in 38 of 40 (95%) infants. There was 1 major complication: a 38‐week infant with Prader‐Willi syndrome developed a pneumomediastinum caused by a tear at the upper esophageal sphincter. In a second infant the PEG bumper could not be passed beyond the upper esophageal sphincter. Sixteen infants had other surgical procedures performed at the time of PEG placement. For those infants only having a PEG placed, the mean procedure time was 10 minutes.

Conclusions:

PEG placement is both feasible and safe in small, medically complicated infants.
Long‐term Efficacy of Low‐dose Tricyclic Antidepressants for Children With Functional Gastrointestinal Disorders
Authors: Teitelbaum Jonathan E. , Arora Ruchi
Published: October 2011

Objective:

The aim of the study was to determine the long‐term efficacy of the tricyclic antidepressant (TCA) drugs amitriptyline or imipramine in treating functional gastrointestinal disorders (FGIDs) in pediatric patients.

Materials and Methods:

A retrospective chart review of children with a diagnosis of irritable bowel syndrome, functional dyspepsia, and functional abdominal pain diagnosed on the basis of the Rome III criteria was performed. Charts were analyzed for response to the medication and the duration of the response.

Results:

A total of 98 patients took a TCA for an FGID. Of the 98 patients, 77 patients (78.6%) responded to the treatment for an average of 10.73 (range 1–45) months.

Conclusions:

TCAs are effective in treating FGIDs in pediatric patients for a long duration.
Results of Extremely‐low‐birth‐weight Infants Randomized to Receive Extra Enteral Calcium Supply
Authors: Carroll William F. , Fabres Jorge , Nagy Tim R. , Frazier Marcela , Roane Claire , Pohlandt Frank , Carlo Waldemar A. , Thome Ulrich H.
Published: October 2011

Background and Objective:

Bone mineral deficiency continues to occur in extremely‐low‐birth‐weight (ELBW) infants despite formulas enriched in calcium (Ca) and phosphorus (P). This study tested whether extra enteral Ca supplementation increases bone mineral content (BMC) and prevents dolichocephalic head flattening and myopia in ELBW infants.

Study Design:

Infants 401 to 1000 birth weight receiving enteral feeds were randomized to receive feeds supplemented with Ca‐gluconate powder or pure standard feeds. The main outcome measures were the excretion of Ca and P by weekly spot urine measurements, the degree of dolichocephalic deformation (fronto‐occipital diameter to biparietal diameter ratio, FOD/BPD) at 36 weeks postmenstrual age, and the BMC (by dual‐energy x‐ray absorptiometry) at discharge. Cycloplegic refraction was measured at 18 to 22 months corrected age.

Patients and Results:

Ninety‐nine ELBW infants with a gestational age of 26 weeks (23–31) (median [minimum‐maximum]) were randomized at a postnatal age of 12 days (5–23) weighing 790 g (440–1700). Urinary Ca excretion increased and P excretion decreased in the Ca‐supplemented group. Total BMC was 89.9 ± 2.4 g (mean ± SE) in the supplemented group and 85.2 ± 2.6 g in the control group (P = 0.19). The FOD/BPD was 1.50 (1.13–1.69, mean ± SD [standard deviation]) and 1.47 (1.18–1.64) in the supplemented and control groups, and the refraction 0.98 ± 1.23 and 1.40 ± 1.33 dpt (P = 0.68), respectively in 64 ELBW infants (79% of survivors) at 2‐year follow‐up.

Conclusions:

Extra enteral Ca supplementation did not change BMC, head shape, or refraction. The decreased P excretion may reflect P deficiency in infants receiving extra Ca, preventing improved bone mineral accretion.