F-18 fluorodeoxyglucose positron emission tomographic imaging in a patient with persistent hiccups.

Department of Nuclear Medicine, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.

Pharmacological alternatives for the alleviation of back pain.

Drugs constitute a convenient option for low back pain and are commonly used. However, evidence for their efficacy is meagre. Many drugs used for back pain are no more, or only slightly more, effective than placebos. Others have side effects that outweigh their usefulness in relieving pain. On the basis of the evidence, no drug regimen can be legitimately recommended for back pain. The management of back pain requires measures other than drugs. One exception is the use of willow (Salix) bark for acute exacerbation of pain. Ironically, for chronic low back pain, the most effective and long-lasting outcomes have been documented for normal saline by injection into tender points in the lumbar spine.

Protective effects of dantrolene against myocardial injury induced by isoproterenol in rats: biochemical and histological findings.
Acikel M, Buyukokuroglu ME, Erdogan F, Aksoy H, Bozkurt E, Senocak H.
Department of Cardiology, Faculty of Medicine, Ataturk University, 25240 Erzurum, Turkey. macikel@atauni.edu.tr
PURPOSE: We investigated whether dantrolene might protect the heart against myocardial injury (MI) induced by isoproterenol (ISO), using an experimental model in rats. METHODS: Twenty-eight rats were randomized to treatment with saline only (control group, n=8), ISO only (ISO group, n=8), low-dose dantrolene (LDD)+ISO (LDD group, n=6) and high-dose dantrolene (HDD)+ISO (HDD group, n=6). ISO (150 mg/kg/day, s.c.), LDD (5 mg/kg/day, i.p.) and HDD (10 mg/kg/day, i.p.) were given once a day for two consecutive days. At the end of the second day, blood samples were taken from abdominal aorta shortly after the rats were anesthetised for cardiac troponins T (cTnT) and I (cTnI) assay, and the hearts were removed and observed microscopically. RESULTS: cTnT and cTnI levels were increased in the ISO group when compared with the control group (p<0.001). LDD and HDD significantly reduced cTnT and cTnI levels when compared with the ISO group. Elevations of cTnT and cTnI appeared to relate to the severity of histological changes. The rate of animals that exhibited marked MI was higher in the ISO group than in the control group (p<0.001). The rats in both LDD and HDD groups showed less histological changes when compared to the ISO group (p<0.01). There was no significant difference between the control group and both LDD and HDD groups. CONCLUSIONS: This study shows that dantrolene has a significant effect in the protection of the heart against MI induced by ISO. We believe that pretreatment with dantrolene may contribute to developing novel strategies in the cardiotoxicity animal models and in the prevention of the cardiotoxic effects of elevated levels of catecholamines.

Steroidal nondepolarizing muscle relaxants / relaxant do not simulate the effects of glucocorticoids on glucocorticoid receptor-mediated transcription in cultured skeletal muscle cells.

Harvard Medical School, and Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114, USA..

Steroid-induced myopathy in patients intubated due to exacerbation of chronic obstructive pulmonary disease.
Amaya-Villar R, Garnacho-Montero J, Garcia-Garmendia JL, Madrazo-Osuna J, Garnacho-Montero MC, Luque R, Ortiz-Leyba C.
Intensive Care Unit, University Hospital Virgen del Rocio, Avenida Manuel Siurot s/n, 41013 Seville, Spain. ramaya@supercable.es
OBJECTIVE: To determine incidence, risk factors and impact on various outcome parameters of the development of acute quadriplegic myopathy in a selected population of critically ill patients. SETTING: A prospective cohort study carried out in the intensive care unit of a tertiary-level university hospital. PATIENTS: All patients admitted due to acute exacerbation of chronic obstructive pulmonary disease who required intubation and mechanical ventilation, and received high doses of intravenous corticosteroids. INTERVENTIONS: A neurophysiological study was performed in all cases at the onset of weaning. Muscular biopsy was taken when the neurophysiological study revealed a myopathic pattern. MEASUREMENTS AND RESULTS: Twenty-six patients were enrolled in the study. Nine patients (34.6%) developed myopathy. Only seven patients were treated with muscle relaxants. Histology confirmed the diagnosis in the three patients who underwent muscle biopsy. APACHE II score at admission, the rate of sepsis and the total doses of corticosteroids were significantly higher in patients with myopathy compared with those patients that did not develop it. Myopathy is associated with an increase in the duration of mechanical ventilation [15.4 (9.2) versus 5.7 (3.9) days; p<0.006], the length of ICU stay [23.6 (10.7) versus 11.4 (7.05) days; p<0.003] and hospital stay [33.3 (19.2) versus 21.2 (16.1) days; p<0.034)]. Myopathy was not associated with increased mortality. CONCLUSIONS: In the population under study, severity of illness at admission, the development of sepsis and the total dose of corticosteroids are factors associated with the occurrence of myopathy after the administration of corticosteroids. Myopathy was associated with prolonged mechanical ventilation and in-hospital stay.

Genetic testing for enzymes of drug metabolism

STUDY DESIGN: This is a structured review of genomic (genetic) testing for enzymes of drug metabolism. OBJECTIVES: Recently, industry began offering genomic testing for enzymes of drug metabolism. As such, the objective of this review was to determine if genomic testing for enzymes of drug metabolism has any imminent clinical relevance for the practice of pain medicine. METHODS: Relevant references relating to pharmacogenetics, pharmacogenomics, and the metabolizing of drugs used in pain medicine by cytochrome P-450 enzymes were located and reviewed in detail. The P-450 enzymes that metabolize each drug and whether that drug had been identified as being subject to a clinical consequence of a genetic polymorphism of the P-450 enzyme involved in its metabolism were placed into tabular form. RESULTS OF DATA SYNTHESIS: 1) For a large number of drugs, we do not yet know which cytochrome P-450 enzymes are involved in their metabolism; 2) For a large number of drugs, the consequences of a P-450 genetic polymorphism have yet to be determined; 3) Genetic polymorphism can lead to important potential clinical consequences for some opioids, anticonvulsants (phenytoin), benzodiazepines (diazepam), muscle relaxants / relaxant (succinylcholine), antidepressants (imipramine, nortriptyline, venlafaxine), typical neuroleptics, alcohol, antihypertensives (propranolol, timolol), local anesthetics (procainamide), L-dopa, nicotine, and warfarin. Based on these results, factors for and against using genomic testing were reviewed. CONCLUSIONS/RECOMMENDATIONS: It was concluded that genomic testing for enzymes of drug metabolism has significant potential for improving the efficacy of drug treatment and reducing adverse drug reactions. Recommendations for when such testing would be useful are outlined. Copyright American Academy of Pain Medicine

Hip status in cerebral palsy after one year of continuous intrathecal baclofen infusion.

The purpose of this study was to assess whether reduction of muscle tone by continuous intrathecal baclofen infusion affects the progression of hip subluxation in persons with cerebral palsy. This prospective, open-label, case series was conducted at multiple specialty referral centers. There were 33 subjects, ages 4 to 31 years. All had a pretreatment lower extremity Ashworth score of >/=3; all subjects had a significant reduction in tone after a bolus injection of intrathecal baclofen and received an implanted pump for continuous delivery of intrathecal baclofen. Subjects had hip x-rays before and 1 year after pump implantation. The primary outcome measure was change in absolute hip migration percentage. One third of the hips had an increase of absolute migration percentage of 5% or more; 12% of the hips had a decrease of migration percentage of 5% or more. Change of migration percentage class was used as a second outcome criterion. 90.9% of hips manifested no deterioration or had improvement of their migration percentage class during the year of intrathecal baclofen therapy. The observed changes were not associated with the subject's age or the severity of cerebral palsy.

Dantrolene stabilizes domain interactions within the ryanodine receptor.
Kobayashi S, Bannister ML, Gangopadhyay JP, Hamada T, Parness J, Ikemoto N.
Boston Biomedical Research Institute, Watertown, Massachusetts 02472, USA.
Interdomain interactions between N-terminal and central domains serving as a "domain switch" are believed to be essential to the functional regulation of the skeletal muscle ryanodine receptor-1 Ca(2+) channel. Mutational destabilization of the domain switch in malignant hyperthermia (MH), a genetic sensitivity to volatile anesthetics, causes functional instability of the channel. Dantrolene, a drug used to treat MH, binds to a region within this proposed domain switch. To explore its mechanism of action, the effect of dantrolene on MH-like channel activation by the synthetic domain peptide DP4 or anti-DP4 antibody was examined. A fluorescence probe, methylcoumarin acetate, was covalently attached to the domain switch using DP4 as a delivery vehicle. The magnitude of domain unzipping was determined from the accessibility of methylcoumarin acetate to a macromolecular fluorescence quencher. The Stern-Volmer quenching constant (K(Q)) increased with the addition of DP4 or anti-DP4 antibody. This increase was reversed by dantrolene at both 37 and 22 degrees C and was unaffected by calmodulin. [(3)H]Ryanodine binding to the sarcoplasmic reticulum and activation of sarcoplasmic reticulum Ca(2+) release, both measures of channel activation, were enhanced by DP4. These activities were inhibited by dantrolene at 37 degrees C, yet required the presence of calmodulin at 22 degrees C. These results suggest that the mechanism of action of dantrolene involves stabilization of domain-domain interactions within the domain switch, preventing domain unzipping-induced channel dysfunction. We suggest that temperature and calmodulin primarily affect the coupling between the domain switch and the downstream mechanism of regulation of Ca(2+) channel opening rather than the domain switch itself.

Treatment of fibromyalgia with Cyclobenzaprine, Flexeril: A meta-analysis.

OBJECTIVE: To systematically review the effectiveness of Cyclobenzaprine, Flexeril in the treatment of fibromyalgia. METHODS: Articles describing randomized, placebo-controlled trials of Cyclobenzaprine, Flexeril in people with fibromyalgia were obtained from Medline, EMBase, Psyclit, the Cochrane Library, and Federal Research in Progress Database. Unpublished literature and bibliographies were also reviewed. Outcomes, including global improvement, treatment effects on pain, fatigue, sleep, and tender points over time, were abstracted. RESULTS: Five randomized, placebo-controlled trials were identified. The odds ratio for global improvement with therapy was 3.0 (95% confidence interval [95% CI] 1.6-5.6) with a pooled risk difference of 0.21 (95% CI 0.09-0.34), which calculates to 4.8 (95% CI 3.0-11) individuals needing treatment for 1 patient to experience symptom improvement. Pain improved early on, but there was no improvement in fatigue or tender points at any time. CONCLUSION: Cyclobenzaprine, Flexeril-treated patients were 3 times as likely to report overall improvement and to report moderate reductions in individual symptoms, particularly sleep.

Skin sensitivity to rocuronium and vecuronium: a randomized controlled prick-testing study in healthy volunteers.

Prick tests are frequently used for the authentication of neuromuscular blocking drugs (NMBDs) as causative drugs for anaphylactic reactions during anesthesia. Unfortunately, the actual threshold concentration for skin testing remains debatable for most NMBDs. We studied the flare and wheal responses to prick tests with rocuronium and vecuronium. Thirty healthy, nonatopic, anesthesia-naive male and female volunteers (14 men and 16 women) from 18 to 40 yr of age were assigned randomly to receive a total of 10 prick tests-4 ascending dilutions (1:1000, 1:100, 1:10, and 1) of rocuronium and vecuronium and 2 controls-on both forearms. An assessor blinded to the assignment monitored systemic and skin responses to NMBDs and measured wheal and flare surfaces immediately after and 15 min after prick tests. None of the volunteers experienced any immediate systemic or cutaneous responses to rocuronium or vecuronium. Although a dilution of 1:1000 of both NMBDs failed to promote any skin response at 15 min, 50% and 40% of the subjects had a positive skin reaction to undiluted rocuronium and vecuronium, respectively. We demonstrated a sex effect related to smaller threshold concentration-induced cutaneous reactions in female volunteers to both muscle relaxants. Our observation questions the reliability of prick testing with undiluted solutions of rocuronium and vecuronium for the diagnosis of allergy. IMPLICATIONS: Building concentration-skin response curves to prick tests with rocuronium and vecuronium in healthy, nonatopic, anesthesia-naive male and female volunteers demonstrated that the nonreactive concentration for both muscle relaxants / relaxant is the 1:1000 dilution of the stock solutions. Our observation calls into question the past practice of prick-testing skin for sensitivity to neuromuscular blocking drugs by using undiluted solutions.