bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Role of Calcium/Calmodulin-dependent Protein Kinase II in Desflurane-induced Preconditioning and Cardioprotection by Metoprolol
Authors: Lange Markus , Smul Thorsten M. , Redel Andreas , Lotz Christopher , Jazbutyte Virginija , Schnupp Verena , Roewer Norbert , Kehl Franz 
Published: March 2009

Background
Anesthetic preconditioning is mediated by beta- adrenergic signaling. This study tested the hypotheses that desflurane-induced preconditioning is dose-dependently blocked by metoprolol and mediated by calcium/calmodulin-dependent protein kinase II (CaMK II).

Methods
Pentobarbital-anesthetized New Zealand White rabbits were instrumented for measurement of systemic hemodynamics and subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion. Rabbits were assigned to receive vehicle (control), 0.2, 1.0, 1.75, or 2.5 mg/kg metoprolol for 30 min, or the CaMK II inhibitor KN-93 in the absence or presence of 1.0 minimum alveolar concentration desflurane. Protein expression of CaMK II, phospholamban, and phospho-phospholamban was measured by Western blotting. Myocardial infarct size and area at risk were measured with triphenyltetrazolium staining and patent blue, respectively.

Results
Baseline hemodynamics were not different among groups. Infarct size was 60 +/- 3% in control and significantly (* P < 0.05) decreased to 33 +/- 2%* by desflurane. The CaMK II inhibitor KN-93 did not affect infarct size (55 +/- 4%) but blocked desflurane-induced preconditioning (57 +/- 3%). Metoprolol at 0.2 and 1.0 mg/kg had no effect on infarct size (55 +/- 3% and 53 +/-3%), whereas metoprolol at 1.75 and 2.5 mg/kg reduced infarct size to 48 +/- 4%* and 39 +/- 5%*, respectively. Desflurane-induced preconditioning was attenuated by metoprolol at 0.2 mg/kg, leading to an infarct size of 46 +/- 5%*, and was completely abolished by metoprolol at 1.0, 1.75, and 2.5 mg/kg, resulting in infarct sizes of 51 +/- 3%, 52 +/- 3%, and 55 +/- 3%, respectively.

Conclusions
Desflurane-induced preconditioning is dose-dependently blocked by metoprolol and mediated by CaMK II.
Morphine versus Mexiletine for Treatment of Postamputation Pain
Authors: Wu Christopher L. , Agarwal Shefali , Tella Prabhav K. , Klick Brendan , Clark Michael R. , Haythornthwaite Jennifer A. , Max Mitchell B. , Raja Srinivasa N. 
Published: March 2009

Background
Stump and phantom pains are debilitating sequelae of amputations that are often resistant to treatment. The efficacy of pharmacologic therapies, including opioids and sodium channel blockers, for postamputation pain is uncertain.

Methods
The authors conducted a double-blind, randomized, placebo-controlled, crossover study in adult patients with postamputation pain of 6 months or longer and greater than 3 on a 0-10 numeric pain rating scale. Each of the three treatment periods (morphine, mexiletine, or placebo) included a 1-week drug-free interval followed by 4-week titration, 2-week maintenance, and 2-week drug-taper phases. The primary outcome measure was change in average pain intensity from the drug-free baseline to the last week of maintenance.

Results
Sixty amputees were enrolled; data were analyzed from 56 subjects for one drug period, 45 subjects for two drug periods, and 35 subjects who completed all three drug periods. The mean morphine and mexiletine dosages were 112 and 933 mg, respectively. Morphine treatment provided lower pain scores compared with placebo and mexiletine (P = 0.0003). The mean percent pain relief during treatment with placebo, mexiletine, and morphine was 19, 30, and 53%, respectively (P < 0.0001, morphine vs. placebo and mexiletine). The numbers needed to treat to obtain 50% and 33% decreases in pain intensity with morphine were 5.6 and 4.5, respectively. Treatment with morphine was associated with a higher rate of side effects.

Conclusions
Therapy with morphine, but not mexiletine, resulted in a decrease in intensity of postamputation pain but was associated with a higher rate of side effects and no improvement in self-reported levels of overall functional activity and pain-related interference in daily activities.
Experimental Forearm Immobilization in Humans Induces Cold and Mechanical Hyperalgesia
Authors: Terkelsen Astrid J. , Bach Flemming W. , Jensen Troels S. 
Published: March 2009

Background
Complex regional pain syndrome is a painful condition of unknown etiology. Clinical and experimental observations suggest that limb immobilization may induce symptoms and signs characteristic of complex regional pain syndrome. This study examined the effect of forearm immobilization on regional sensory and autonomic functions in healthy subjects.

Methods
Thermal and mechanical sensitivity, skin temperature, and vasoconstrictor responses were measured in 30 healthy subjects before and 0, 3, and 28 days after scaphoid cast immobilization. Fifteen subjects served as nonimmobilized controls.

Results
At cast removal, 27 subjects experienced pain at joint movement. Cast immobilization induced cold hyperalgesia in glabrous and hairy skin on the immobilized hand and induced significant skin temperature differences between the control and the immobilized hand at cast removal and after 3 days. Immobilization also reduced pain threshold at skin fold testing at all time points after cast removal. All measures except pain threshold at skin fold testing were normalized after 28 days. Immobilization did not affect thermal detection, heat pain, and pressure pain thresholds; resting skin perfusion; or vasoconstrictor responses induced by mental stress or deep inspirations.

Conclusions
Four weeks of forearm immobilization caused transient changes in skin temperature, mechanosensitivity, and thermosensitivity, without alteration in the sympathetically mediated vascular tone.
Neural Mechanisms of Sevoflurane-induced Respiratory Depression in Newborn Rats
Authors: Kuribayashi Junya , Sakuraba Shigeki , Kashiwagi Masanori , Hatori Eiki , Tsujita Miki , Hosokawa Yuki , Takeda Junzo , Kuwana Shun-ichi 
Published: March 2009

Background
Sevoflurane-induced respiratory depression has been reported to be due to the action on medullary respiratory and phrenic motor neurons. These results were obtained from extracellular recordings of the neurons. Here, the authors made intracellular recordings of respiratory neurons and analyzed their membrane properties during sevoflurane application. Furthermore, they clarified the role of gamma-aminobutyric acid type A receptors in sevoflurane-induced respiratory depression.

Methods
In the isolated brainstem-spinal cord of newborn rat, the authors recorded the C4 nerve burst as an index of inspiratory activity. The preparation was superfused with a solution containing sevoflurane alone or sevoflurane plus the gamma-aminobutyric acid type A receptor antagonist picrotoxin or bicuculline. Neuronal activities were also recorded using patch clamp techniques.

Results
Sevoflurane decreased C4 burst rate and amplitude. Separate perfusion of sevoflurane to the medulla and to the spinal cord decreased C4 burst rate and amplitude, respectively. Both picrotoxin and bicuculline attenuated the reduction of C4 burst rate. Sevoflurane reduced both intraburst firing frequency and membrane resistance of respiratory neurons except for inspiratory neurons.

Conclusion
Under the influence of sevoflurane, the region containing inspiratory neurons, i.e., the pre-Bötzinger complex, may determine the inspiratory rhythm, because reduced C4 bursts were still synchronized with the bursts of inspiratory neurons within the pre-Bötzinger complex. In contrast, the sevoflurane-induced decrease in C4 burst amplitude is mediated through the inhibition of phrenic motor neurons. gamma-Aminobutyric acid type A receptors may be involved in the sevoflurane-induced respiratory depression within the medulla, but not within the spinal cord.
Early Packed Red Blood Cell Transfusion and Acute Respiratory Distress Syndrome after Trauma
Authors: Chaiwat Onuma , Lang John D. , Vavilala Monica S. , Wang Jin , MacKenzie Ellen J. , Jurkovich Gregory J. , Rivara Frederick P. 
Published: March 2009

Background
Transfusion of packed red blood cells (PRBCs) is a risk factor for acute respiratory distress syndrome (ARDS) in trauma patients. Yet, there is a paucity of information regarding the risk of ARDS with incremental PRBCs exposure.

Methods
For this retrospective analysis, eligible patients from National Study on Costs and Outcomes of Trauma were included. Our main exposure was defined as units of PRBCs transfused during the first 24 h after admission. The main outcome was ARDS.

Results
A total of 521 (4.6%) of 14070 patients developed ARDS, and 331 patients (63.5%) who developed ARDS received PRBCs transfusion. Injury severity, thoracic injury, polytrauma, and pneumonia receiving more than 5 units of fresh frozen plasma and 6-10 units of PRBCs were independent predictors of ARDS. Patients receiving more than 5 units of PRBCs had higher risk of developing ARDS (patients who received 6-10 units: adjusted odds ratio 2.5, 95% CI 1.12-5.3; patients who received more than 10 units: odds ratio 2.6, 95% CI 1.1-6.4). Each additional unit of PRBCs transfused conferred a 6% higher risk of ARDS (adjusted odds ratio 1.06; 95% CI 1.03-1.10).

Conclusions
Early transfusion of PRBCs is an independent predictor of ARDS in adult trauma patients. Conservative transfusion strategies that decrease PRBC exposure by even 1 unit may be warranted to reduce the risk of ARDS in injured patients.
Prevalence and Characteristics of Immunomediated Neuropathies in a Group of Patients With Autoimmune Diseases
Authors: Servioli Luisa , Pérez Cristina , Consani Sandra , Suárez Alejo , Sehabiaga Gabriel , Collazo Cecilia , Catalá Gaspar 
Published: March 2009

ABSTRACTObjective:To determine the prevalence and the clinical-neurophysiological characteristics of immunomediated peripheral neuropathies (PN) in a group of patients with systemic autoimmune diseases.Method:Fifty-nine patients with proved systemic autoimmune diseases were included. Patients underwent clinical examination and nerve conduction studies to diagnose the PN.Results:Immune PNs were detected in 18 patients (30.5%). Out of the total number of PNs (18), 39% were sensory-motor polyneuropathies, 33% mononeuritis multiplex, 11% pure sensory polyneuropathies, 11% cranial neuropathies, and 6% proximal motor neuropathies, such as the Guillain-Barré syndrome. Nine PNs (50%) appeared at the onset of the connective tissue disorders, and the rest of the cases appeared during the course of the disease. Of the total of PNs detected in this study, only 45% had a previous diagnosis. Vasculitis was the disease that presented more associated PNs. Systemic lupus erythematosus showed the widest range of PN clinical varieties.Conclusions:The first national prevalence rate of PNs in patients with systemic autoimmune diseases was provided: 30.5%. No comparative data were found in the international bibliography. Sensory-motor polyneuropathy was the most frequently observed form of PN, followed by mononeuritis multiplex. The NPs appeared with the same frequency both at the onset and during the course of the diseases under study; these predominated at the onset of vasculitis and primary Sjögren syndrome. The compromise of the peripheral nervous system is underdiagnosed.
Anatomical Localization of Motor Endplate Bands in the Human Biceps Brachii
Authors: Amirali Asif , Mu Liancai , Gracies Jean-Michel , Simpson David M 
Published: March 2009

Objectives:
Botulinum neurotoxin (BoNT) reduces disabling muscle contraction in numerous disorders with muscle overactivity. While motor endplates are the primary site of action for BoNT, their location is unknown in most human muscles. This study localized the motor endplate bands (MEB) within human biceps brachii (BB) muscles in relation to external landmarks.

Methods:
Five human BB muscles were obtained from autopsy. Three muscles were processed for Sihler's stain, a nerve staining technique, and 2 were processed by whole-mount acetylcholinesterase stain.

Results:
The major MEB in BB is an inverted V-shaped band, 1 cm in width, located 7 cm superior to the olecranon laterally, 11 cm superior to the olecranon in the middle, and 8 cm above the olecranon medially. The ratio of MEB location to total olecranon-acromion length is 0.25 at the lateral edge, 0.39 in the midline, and 0.28 at the medial edge.

Conclusions:
This study localized MEB in human BB in reference to external landmarks. This data should improve the feasibility of endplate targeting when injecting BoNT in BB, which might enhance the clinical efficacy of these injections.
Steroid-Responsive Myopathy: Immune-Mediated Necrotizing Myopathy or Polymyositis Without Inflammation?
Authors: Sadeh Menachem , Dabby Ron 
Published: March 2009

ABSTRACT

Objective:
To describe the clinical course and steroid responsiveness of a patient with subacute proximal symmetric weakness, very high serum creatine kinase activity, and myopathic pattern with fibrillations in the electromyogram, whose muscle biopsy showed necrotizing myopathy, with practically no inflammation.

Design:
Case report.

Setting:
Academic research.

Results:
Diagnosis of muscular dystrophy was suggested; nevertheless, steroid treatment was initiated, and the patient recovered and gained normal strength. However, after a few years he stopped treatment, and all symptoms recurred. He developed severe proximal weakness of all limbs. Another biopsy showed similar findings, with no inflammation; still, he responded favorably to steroids and immunosuppressive medications. Currently on a low dose of prednisone and methotrexate, he has no neurological deficit.

Conclusion:
The absence of inflammation in muscle biopsy may lead to misdiagnosis of muscular dystrophy; however, if the clinical impression is that of inflammatory myopathy, an immunomodulatory treatment should be initiated. During the past century, there has been much controversy about the diagnosis of polymyositis (PM). The debate is still ongoing. We present hereby a patient with typical course and clinical features of PM who underwent two muscle biopsies, several years apart, which showed necrotizing myopathy, practically without inflammation, leading to misdiagnosis of muscular dystrophy. This report brings up the dispute regarding the role of muscle biopsy in the diagnosis of PM.
Isolated Head Drop Triggered by Neck Surgery Following Concomitant Chemoradiotherapy
Authors: Luo Jin Jun 
Published: March 2009

ABSTRACT

Dropped head syndrome (DHS) is characterized by severe weakness of neck extension that occurs in isolation or association with a generalized neuromuscular disorder. Multietiologies may be responsible for DHS, including radiotherapy, which may cause a delayed form of DHS. However, DHS acutely triggered by neck surgery after chemoradiotherapy is rare. The author reports a case of acute onset of isolated DHS following selective neck dissection surgery after concomitant chemoradiotherapy for laryngeal cancer.
Organ Preserving Transoral Laser Microsurgery for Cancer of the Hypopharynx
Authors: Martin Alexios , Jäckel Martin C. , Christiansen Hans , Mahmoodzada Mary , Kron Martina , Steiner Wolfgang 
Published: March 2009

AbstractObjective: To assess the feasibility of transoral laser microsurgery (TLM) in the treatment of hypopharyngeal cancer, with a special focus on piriform sinus carcinomas, and to report the oncologic and functional outcomes.Study Design: Prospective case‐series study at a single institute, an academic tertiary referral center.Methods: A total of 172 patients with previously untreated squamous cell carcinoma of the hypopharynx were eligible for this study (1986–2003). The piriform sinus was the most common localization (n = 150). Patients with simultaneous second primaries, distant metastases, or N3 neck disease and cancers of the category pT4b were excluded. Fifteen percent of the patients had stages I and II (according to guidelines from the Union Internationale Contre le Cancer 2002/American Joint Commission on Cancer, 2002), and 85% had stages III and IVa. The median follow‐up period was 45 months. All patients (n = 172) were treated by TLM, mainly by selective neck dissection (93%) and/or postoperative radiotherapy (52%). Overall survival, recurrence‐free survival, organ preservation, and local control were analyzed as end points. Rate of tracheotomies, postoperative complications, and swallowing function (feeding tube dependency) were also analyzed.Results: Five‐year Kaplan‐Meier local control was 84% for pT1; 70% for pT2; 75% for pT3; and 57% for pT4a. Five‐year Kaplan‐Meier recurrence‐free survival was 73% for stages I and II, 59% for stage III, and 47% for stage IVa. The whole group of 172 hypopharyngeal cancer patients was analyzed, with an additional special focus on the homogenous group of piriform sinus carcinomas (n = 150).Conclusions: Our data support the conclusion that TLM is a valid option to standard radical surgery or standard conservation treatment. Oncologic and functional results compare favorably, while morbidity and complication rates tend to be lower.
Future Horizons in the Treatment of Enteric Neuropathies
Authors: Thapar Nikhil 
Published: March 2009

ABSTRACTEnteric neuropathies comprise a vast and disparate array of congenital and acquired disorders of the enteric nervous system (ENS), reflecting both the complexity of its neuronal composition and the many interactions that modulate its function. Although present therapeutic strategies, largely limited to surgery and the provision of artificial nutrition, have transformed the early survival and life of sufferers, levels of morbidity and mortality remain unacceptably high. This highlights the need to develop new treatments for enteric neuropathies. In the last decade, the tremendous advances in molecular biology and genetics have significantly enhanced our understanding of ENS development and function. Coupled with equivalent progress in the fields of pharmacology and stem‐cell biology, this has led to the identification of novel tools and targets for therapy, which either aim to optimise the function of the intrinsic ENS or replace/replenish components of an inadequate or dysfunctional ENS. This article reviews current work on a number of these interventions with a particular focus on the use of ENS stem cells as potential therapeutic tools for enteric neuropathies.
Treatment of Severe Malnutrition in Children: Experience in Implementing the World Health Organization Guidelines in Turbo, Colombia
Authors: Bernal Carlos , Velásquez Claudia , Alcaraz Gloria , Botero Jorge 
Published: March 2009

ABSTRACTObjective:To evaluate the implementation of the World Health Organization guidelines for the treatment of children with severe acute malnutrition in a class I hospital.Paitents and Methods:Descriptive and prospective study of 335 children under the age of 6, admitted between 2001 and 2005 for severe acute malnutrition (83%) and moderate acute malnutrition associated with illness (17%). The care of the children was provided by clinicians and medical staff trained under World Health Organization guidelines.Results:Kwashiorkor was a common result in children with severe acute malnutrition (60.8%); 58% were younger than 1 year old. Complications upon admission were diarrhea (68.4%) and anemia (51.1%), and the most common complication during hospital stay was sepsis (9%). Overall, 61.7% attained −1 standard deviation of weight for height after an average stay of 3 weeks in the hospital; 5.1% were sent to tertiary care hospitals. Overall, mortality during the 5 years was 5.7%, with sepsis the most common cause. In the first year, the mortality rate was 8.7%; it decreased to 4.0% in the last year. The mortality rate was significantly higher in children with edema. Children with moderate acute malnutrition had similar complications and mortality when compared with children with severe acute malnutrition (5.3%).Conclusions:Once the World Health Organization guidelines were implemented, low mortality rates were achieved in children with severe acute malnutrition in class I hospitals.
Percutaneous Liver Biopsy in Hemophiliac Children With Chronic Hepatitis C Virus Infection
Authors: Schwarz Kathleen B , Zellos Aglaia , Stamato Lisette , Boitnott John , Perlman Elizabeth , Chong Sonny , Casella James F 
Published: March 2009

ABSTRACTObjective:To develop a protocol for safe performance of percutaneous liver biopsies in children with deficiency of factor VIII (n = 12) or IX (n = 2) and chronic hepatitis C virus infection.Patients and Methods:Liver biopsies were performed after administration of factor VIII or IX, before and 24 weeks after cessation of antiviral therapy. To define the optimal means of providing replacement therapy, 10 children were enrolled in a randomized crossover design study of bolus versus continuous factor VIII for performance of the liver biopsy. For the crossover study, all of the patients were given a loading dose of 50 ± 5 IU recombinant factor (rF)VIII/kg; a minimum of factor VIII activity of ≥80% 30 to 60 minutes following factor VIII infusion was required for liver biopsy. For the bolus protocol, rFVIII 25 to 50 IU/kg was given 6, 14, 24, 36, 48, and 60 hours after completion of the loading dose. For the continuous protocol, rFVIII was given 3 to 4 IU/kg per hour for 48 hours, followed by a bolus of 25 IU/kg at 60 hours. In patients with factor IX deficiency, a loading dose of 100 IU/kg was followed by a bolus of 50 IU/kg at 3, 15, 27, and 48 hours after the loading dose.Results:Twenty liver biopsies were performed in children with factor VIII deficiency without major complications. One of the 3 biopsies in the patients with factor IX deficiency was complicated by a hemoperitoneum. Midazolam and fentanyl were used in the first 8 patients. However, postbiopsy pain, presumably secondary to hematoma in 2 patients and hemoperitoneum in 1, prompted us to use ultrasound to locate a suitable biopsy site and to change to propofol; this allowed us to better immobilize the liver, to minimize postbiopsy bleeding. The subsequent 15 biopsies were well tolerated without postbiopsy pain or other complication.Conclusions:Percutaneous liver biopsy in children with factor VIII deficiency can be safely performed using either bolus or continuous infusion of recombinant factor VIII. A brief general anesthetic and ultrasound guidance are recommended.
Direct Evidence of Mast Cell Participation in Acute Acid‐induced Esophageal Inflammation in Mice
Authors: Morganstern Jeffrey A , Wang Ming‐Yu , Wershil Barry K 
Published: March 2009

ABSTRACTObjectives:Mast cells have been implicated in the pathogenesis of esophagitis resulting from gastroesophageal acid reflux, but their precise role has been difficult to define. We proposed to directly examine the contribution of mast cells to neutrophil infiltration in a mouse model of acid‐induced esophageal injury.Materials and Methods:Normal and mast cell–deficient (Kit) mice underwent either a surgical procedure to induce acute acid reflux injury of the esophagus or sham surgery. Neutrophil infiltration in the esophagus was determined by morphometrical quantification. To further delineate the involvement of mast cells, acid‐induced esophageal injury was elicited in mast cell–deficient mice that had undergone mast cell reconstitution by bone marrow transplantation.Results:Normal mice exhibited significant neutrophil infiltration into the esophagus as a result of acid‐induced injury. The neutrophil accumulation was significantly diminished in mast cell–deficient mice. However, the neutrophil infiltration that resulted from acid‐induced injury in mast cell–reconstituted Kit mice was similar to that seen in normal mice.Conclusions:Our findings provide direct evidence that mast cells participate in the recruitment of neutrophils during acid‐induced esophageal injury in mice.