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1.
Anesth Analg ; 106(1): 294-300, table of contents, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18165593

ABSTRACT

BACKGROUND: Cyclooxygenase 2 inhibition has proven analgesic efficacy in a variety of surgical procedures. We postulated that perioperative cyclooxygenase 2 inhibition significantly reduces postoperative morphine requirements after major thoracic surgery and investigated the site of this potential analgesic effect. METHODS: Ninety-two patients participated in this single-center, double-blind, randomized, placebo-controlled, parallel-group trial. Patients between the ages of 18 and 80 yr undergoing a thoracotomy or median sternotomy were randomized to receive either nimesulide or placebo in combination with a standard analgesic regimen perioperatively. Nimesulide was administered orally the evening before surgery and at 12-h intervals for 5 days postoperatively. The primary efficacy variables were morphine consumption and pain scores for the first 48 h postoperatively. The secondary efficacy variable was the effect of nimesulide on cyclooxygenase activity in cerebrospinal fluid (CSF). RESULTS: Pain scores at rest or with movement, and total morphine consumption for the first 48 h postoperatively, were not statistically different between the groups. The mean difference in total morphine consumption up to 48 h postoperatively between the nimesulide and placebo group was a 9.0 mg reduction (95% CI: -28.9 to 10.9 mg) (P = 0.37). Adjusted mean (se) CSF 6-keto-PGF1alpha (6-keto-PGF1alpha) concentrations increased by 54.7 (25.7) pg/mL from preoperatively to Day + 2 postoperatively in the placebo group, whereas adjusted mean (se) CSF 6-keto-PGF1alpha concentration decreased by 0.6 pg/mL (18.2 pg/mL) in the nimesulide group. These changes were not statistically different between the groups (P = 0.095). CONCLUSION: Nimesulide, at a dose of 90 mg twice daily in combination with a standard analgesic regimen, does not influence pain scores, morphine requirements, or CSF prostaglandin levels after major thoracic surgery.


Subject(s)
Analgesics, Opioid/therapeutic use , Cyclooxygenase 2 Inhibitors/therapeutic use , Morphine/therapeutic use , Pain, Postoperative/prevention & control , Sternum/surgery , Sulfonamides/therapeutic use , Thoracotomy , 6-Ketoprostaglandin F1 alpha/cerebrospinal fluid , Administration, Oral , Aged , Cyclooxygenase 2 Inhibitors/administration & dosage , Double-Blind Method , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Pain Measurement , Prospective Studies , Prostaglandin-Endoperoxide Synthases/cerebrospinal fluid , Sulfonamides/administration & dosage , Time Factors , Treatment Outcome
2.
Pain Med ; 8(8): 669-77, 2007.
Article in English | MEDLINE | ID: mdl-18028045

ABSTRACT

Meralgia paresthetica (MP), coined from the Greek words meros (thigh and algos), meaning pain, is a neurological disorder characterized by a localized area of paresthesia and numbness on the anterolateral aspect of the thigh. The incidence of MP is more common than often reported in the literature. The etiology of MP includes mechanical factors such as obesity, pregnancy, and other conditions associated with increased intrabdominal pressure, surgery of the spine, and pelvic osteotomy. A coherent history and pertinent physical examination is essential in making the diagnosis; however, red flags such as tumor and lumbar disk herniations must be recognized and appropriately treated. While the diagnosis of MP is essentially a clinical diagnosis, sensory nerve conduction velocity studies are a useful adjunctive diagnostic tool. The management of MP includes treating the underlying cause (if any) and conservative management. Surgery should only be adopted when all nonoperative therapies have failed to manage the condition in an effective manner.


Subject(s)
Paresthesia/diagnosis , Paresthesia/therapy , Humans , Paresthesia/epidemiology , Paresthesia/etiology , Paresthesia/physiopathology , Paresthesia/surgery
3.
Methods Mol Biol ; 357: 313-8, 2007.
Article in English | MEDLINE | ID: mdl-17172697

ABSTRACT

Proteomics offers the opportunity to comprehensively investigate the anucleate platelet. Here, we present a detailed procedure for enrichment by immunoprecipitation, using the monoclonal antibody 4G10, of the dynamic phosphotyrosine proteome of human platelets. Such an approach offers the possibility of capturing the dynamic tyrosine phosphorylation events that occur upon platelet activation and aggregation, with an aim to identify novel signaling proteins.


Subject(s)
Blood Platelets/metabolism , Immunoprecipitation/methods , Phosphotyrosine/metabolism , Proteome/analysis , Electrophoresis, Gel, Two-Dimensional , Humans , Phosphorylation , Proteome/metabolism , Proteomics/methods
4.
Reg Anesth Pain Med ; 31(2): 152-67, 2006.
Article in English | MEDLINE | ID: mdl-16543102

ABSTRACT

Cervical radicular pain affects 83 per 100,000 adults annually. Diagnosis by means of physical examination, imaging, and electrophysiological studies is characterized by high specificity but low sensitivity. In this review, we focus on the role of the dorsal root ganglion and those treatment modalities that aim at pathophysiological mechanisms occurring after injury to the dorsal root ganglion. Cervical nerve injury initiates multiple events that lead to changes in nerve function and result in spontaneous firing at the dorsal root ganglion. Among these, inflammation and changes in ion-channel function play a pivotal role. Although many treatment modalities are described in the literature, the available evidence for efficacy does not allow us to formulate definitive conclusions on the optimal therapy. A lack of evidence is reported for cervical spine surgery. Interlaminar epidural steroid administration and radiofrequency techniques adjacent to the cervical dorsal root ganglion have the highest, but still weak recommendations.


Subject(s)
Ganglia, Spinal/physiology , Pain , Radiculopathy/diagnosis , Radiculopathy/therapy , Animals , Disease Management , Humans , Pain/diagnosis , Pain/physiopathology , Pain Management , Radiculopathy/physiopathology
5.
Anesth Analg ; 101(4): 1221-1225, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16192549

ABSTRACT

UNLABELLED: It may be required to ensure patency of the airway in the lateral position in certain circumstances. We performed a prospective randomized clinical trial investigating the effects of left lateral patient positioning on airway anatomy and subsequent airway management. Laryngoscopic airway examination was performed in anesthetized patients, in the supine and left lateral positions, and in the presence and absence of cricoid pressure. Patients were randomized to airway management via an endotracheal tube or laryngeal mask airway (LMA). The left lateral position resulted in a deterioration of laryngoscopic view in 35% of patients and improvement in none. In the lateral position, failure of airway management occurred in more patients with the endotracheal tube versus LMA (8 of 39 versus 1 of 30; P = 0.03), and the mean time to successful completion of airway management was longer with tracheal intubation compared with the LMA (39 +/- 19 s versus 26 +/- 12 s; P = 0.002). LMA use results in more reliable airway control compared to tracheal intubation in the lateral position. The LMA should be considered as the primary airway device when instituting airway management in this position. IMPLICATIONS: Inadequate airway management may be fatal. There are recommendations for airway difficulties, but the evidence favoring any specific strategy is limited. This study suggests that, in the lateral position, a laryngeal mask airway more rapidly and reliably establishes airway control than attempts at endotracheal intubation. It further suggests that placing a patient with an inadequate airway into the lateral position will hinder, not help, airway management.


Subject(s)
Intubation, Intratracheal/methods , Laryngeal Masks , Female , Humans , Laryngoscopy , Male , Posture , Prospective Studies
7.
Reg Anesth Pain Med ; 29(6): 606-9, 2004.
Article in English | MEDLINE | ID: mdl-15635521

ABSTRACT

OBJECTIVE: This case report describes the diagnosis and subsequent management of a very unusual complication of intrathecal pump insertion, namely that of traumatic syrinx secondary to the presence of an intrathecal catheter within the substance of the spinal canal. CASE REPORT: A woman with a 10-year history of chronic pain after a fall was scheduled to have an intrathecal pump inserted to deliver morphine as a continuous infusion. The intrathecal space was entered at L(1)/L(2). Under fluoroscopic imaging, the catheter was threaded to the T6 level. The catheter was then secured and tunneled subcutaneously and implanted in the anterior abdominal wall. After implantation, the patient complained of difficulty in moving her left leg with loss of spinothalamic sensation on her left side from T(6) to L(5). Magnetic resonance imaging (MRI) showed a traumatic syrinx secondary to the presence of an intrathecal catheter within the substance of the canal. The catheter was removed, and serial MRI revealed the syrinx had not increased in size. The patient underwent reinsertion of an intrathecal catheter for control of her pain. Her postoperative course thereafter was uneventful. CONCLUSION: Insertion of an intrathecal catheter may be associated with spinal cord trauma in patients receiving general anesthesia. Serial neurologic examinations and MRI are helpful in guiding treatment.


Subject(s)
Catheters, Indwelling/adverse effects , Infusion Pumps, Implantable/adverse effects , Syringomyelia/etiology , Female , Humans , Injections, Spinal , Magnetic Resonance Imaging , Syringomyelia/diagnosis
8.
Proteomics ; 2(6): 642-8, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12112843

ABSTRACT

Signalling cascades are regulated both positively and negatively by tyrosine phosphorylation. Integrin mediated platelet adhesion triggers signal transduction cascades involving translocation of proteins and tyrosine phosphorylation events, ultimately causing large signalling complexes to be assembled. In resting platelets, a small number of phosphorylated proteins are evident with molecular mass of 50-62 kDa and 120-130 kDa. In thrombin activated human platelets, however, there is a large increase in the number of tyrosine phosphorylated signalling proteins detected. These proteins include pCas (130 kDa), FAK (125 kDa), PI(3)k (85 kDa) and src (85 kDa). However, it is unlikely that this list of proteins represents all the dynamic changes that occur after platelet activation and it is understood that more proteins remain unidentified. In this study, we propose a method for the isolation of the phosphotyrosine proteome from both resting and thrombin activated human platelets. All the dynamic phosphotyrosine events that occur in the platelet after thrombin activation were isolated by immunoprecipitation, using the monoclonal antibody 4G10, allowing us to obtain higher concentrations of relatively low abundant proteins. The resulting phosphotyrosine proteomes were separated by two-dimensional gel electrophoresis. Sixty-seven proteins were reproducibly found to be unique in the thrombin activated platelet proteome when compared to resting platelets. We have positively identified ten of these proteins by Western blotting and matrix-assisted laser desorption/ionisation-time of flight mass spectrometry and these include FAK, Syk, ALK-4, P2X6 and MAPK kinase kinase. This proteomics approach to understanding the signalling events following platelet activation may elucidate potential drug targets for the treatment of coronary thrombosis.


Subject(s)
Blood Platelets/metabolism , Phosphotyrosine/chemistry , Proteome/chemistry , Thrombin/metabolism , Databases as Topic , Electrophoresis, Gel, Two-Dimensional , Enzyme Precursors/metabolism , Focal Adhesion Kinase 1 , Focal Adhesion Protein-Tyrosine Kinases , Humans , Immunoblotting , Integrins/metabolism , Intracellular Signaling Peptides and Proteins , Platelet Activation , Precipitin Tests , Protein-Tyrosine Kinases/metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Syk Kinase , Tyrosine/metabolism
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