The histaminergic system of the brain: its roles in arousal and autonomic regulation.
Szabadi E, Bradshaw CM, Freeman C, Scaife J, Hou RH, Langley RW.
Psychopharmacology Section, Division of Psychiatry, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.


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..

Recent advances in neuromuscular blocking agents.
Zlotos DP.
Pharmaceutical Institute, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany. zlotos@pzlc.uni-wuerzburg.de
Since the introduction of (+)-tubocurarine into anaesthetic and surgical practice (1942), a number of non-depolarizing neuromuscular blocking agents (NMBs) with improved pharmacological properties have been developed during the last sixty years. However, after withdrawal of rapacuronium from clinical use, there is still a need for an ultra-short acting non-depolarizing muscle relaxant / relaxants with rapid onset as substitution for the polarizing suxamethonium, which has several undesirable side-effects. In this paper, structure-activity relationships within four different series of NMBs (tetrahydroisoquinolinium, bistropinyl diester, aminosteroid, and amino peptide analogues) published in this millennium have been reviewed. The NMB properties of the most promising drug candidates from each series were discussed and compared to those of the already existing muscle relaxants.


Five ways to prevent nighttime leg cramps. Leg cramps can ruin a good night's sleep, but there are ways to prevent them.
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Thoracic epidural catheter insertion using the caudal approach assisted with an electrical nerve stimulator in young children.

OBJECTIVES: We evaluated whether thoracic epidural catheter placement using the caudal approach and assisted with an electrical stimulator could be performed in young children. METHODS: Ten young children (1-4 years) who underwent abdominal surgeries were studied. Under general anesthesia without muscle relaxants, caudal catheter placement was performed using an 18-gauge Crawford-type needle and a 20-gauge radiopaque epidural catheter with a stainless-steel stylet. A metal adapter and a 3-way stopcock were attached to the catheter to connect to an electrical stimulator and to inject physiological saline. Electrical stimulation was performed intermittently while advancing the catheter until it reached the target length. The catheter position was confirmed on postoperative roentgenogram. RESULTS: The mean age of the subjects was 32.2 +/- 10.1 months (13-48 months), and the height was 85.3 +/- 6.1 cm (72-93 cm). In 9 of 10 patients, an epidural catheter could be placed at the first insertion. In 1 patient, the catheter could be placed successfully at the second insertion. The electrical current required for muscle contraction at the target length was 5.8 +/- 1.5 mA. CONCLUSION: Electrical stimulation reliably indicated the location of the catheter tip. This technique for thoracic epidural catheter insertion was easy to perform and could be used in young children.

Ryanodine receptors in peritoneal mast cells: possible role in the modulation of exocytotic activity.

Previous studies have shown that ryanodine in low concentrations and caffeine increase intracellular [Ca(2+)] in the absence of external Ca(2+), suggesting Ca(2+) release from intracellular stores through ryanodine receptors (RyR). In the present study we employed amperometry to examine the effect of RyR agonists and antagonists on serotonin release elicited with compound 48/80 (10 micro g/ml). Ryanodine (1 micro M) or, similarly, 20 mM caffeine, in the absence of external Ca(2+), enhanced the amperometric response to compound 48/80 and all the individual amperometric spike parameters. Ryanodine (50 micro M), dantrolene (20 micro M) and tetracaine (50 micro M), putative antagonists of the RyR, attenuated the amperometric response significantly, decreasing the number and frequency of events as well as their amplitude. This is the first demonstration that Ca(2+) availability from RyR-operated Ca(2+) sources may contribute to the modulation of secretory activity in mast cells, affecting not only the cellular exocytotic response, but also the characteristics of single amperometric events. Immunocytochemical labelling, using a monoclonal RyR antibody, confirmed the presence of RyR in this preparation.

A randomized clinical trial comparing chiropractic adjustments to muscle relaxants / relaxant for subacute low back pain.

BACKGROUND: The adult lifetime incidence for low back pain is 75% to 85% in the United States. Investigating appropriate care has proven difficult, since, in general, acute pain subsides spontaneously and chronic pain is resistant to intervention. Subacute back pain has been rarely studied. OBJECTIVE: To compare the relative efficacy of chiropractic adjustments with muscle relaxants / relaxant and placebo/sham for subacute low back pain. DESIGN: A randomized, double-blind clinical trial. METHODS: Subjects (N = 192) experiencing low back pain of 2 to 6 weeks' duration were randomly allocated to 3 groups with interventions applied over 2 weeks. Interventions were either chiropractic adjustments with placebo medicine, muscle relaxants / relaxant with sham adjustments, or placebo medicine with sham adjustments. Visual Analog Scale for Pain, Oswestry Disability Questionnaire, and Modified Zung Depression Scale were assessed at baseline, 2 weeks, and 4 weeks. Schober's flexibility test, acetaminophen usage, and Global Impression of Severity Scale (GIS), a physician's clinical impression used as a secondary outcome, were assessed at baseline and 2 weeks. RESULTS: Baseline values, except GIS, were similar for all groups. When all subjects completing the protocol were combined (N = 146), the data revealed pain, disability, depression, and GIS decreased significantly (P <.0001); lumbar flexibility did not change. Statistical differences across groups were seen for pain, a primary outcome, (chiropractic group improved more than control group) and GIS (chiropractic group improved more than other groups). No significant differences were seen for disability, depression, flexibility, or acetaminophen usage across groups. CONCLUSION: Chiropractic was more beneficial than placebo in reducing pain and more beneficial than either placebo or muscle relaxants / relaxant in reducing GIS.

Sometimes (what seems to be) a heart attack is (really) a pain in the neck.

A 31-year-old patient complained of severe crushing chest pain that radiated to his left arm and jaw. After admission to the hospital, tests revealed a normal electrocardiogram, normal treadmill, normal coronary arteriogram, and normal cardiac enzymes. However, the patient continued to have pain, which was relieved by sublingual and intravenous nitroglycerine. He was discharged from the hospital with a diagnosis of "musculoskeletal" chest pain, taking nonsteroidal anti-inflammatory drugs, muscle relaxants, and narcotics. Two weeks later, the patient returned with worsening symptoms. Cardiac work-up was again negative. Thoracic and cervical spine radiographs were ordered for possible discogenic pain. After abnormalities were found on cervical radiographs, magnetic resonance imaging (MRI) was ordered, and the patient was referred to an orthopedic surgeon. Further work-up revealed a herniated disk at C6-C7, with radicular pain. Surgery on the suspect disk totally relieved the patient's pain.

Can first responders achieve and maintain normocapnia when sequentially ventilating with a bag-valve device and two oxygen-driven resuscitators? A controlled clinical trial in 104 patients.

BACKGROUND AND OBJECTIVE: To evaluate the capability of first responders to achieve and maintain normal ventilation of the lungs of victims employing a bag-valve device and two oxygen-driven resuscitators. METHODS: Prospective, controlled, blinded, single-centre clinical trial using a bag-valve device and one of two FR-300 devices, with 20 cmH2O working pressure, and flows of either 24 or 30 L min(-1). One hundred and four patients were analysed. Induction of anaesthesia followed by ventilation of the lungs with a bag-valve device and an Oxylator in manual and automatic modes performed by a fireman first responder. Each series was repeated for three conditions (anaesthesia; anaesthesia plus muscle relaxation, both with facemask; anaesthesia plus relaxation using an endotracheal tube). RESULTS: Patients age 49 +/- 17 yr; 47% males, 48-132 kg. Normocapnia was achieved and maintained in 66% (bag-valve device), 82% (Oxylator). CONCLUSIONS: The use of an oxygen-driven device improves the ability of first responders to achieve and maintain normocapnia even when distracted. Use of the Oxylators improves performance (P < 0.001) vs. the bag-valve device significantly.

Current diagnosis and therapy of malignant hyperthermia.
Kobayashi T.
Department of Neurology, Nakano General Hospital.
Malignant hyperthermia is an autosomal dominant disorder which results in a severe reaction to anesthetic agents in approximately 0.0005 to 0.5% of patients exposed to general anesthesia. Malignant hyperthermia is characterized by severe muscle rigidity, myoglobunuria, high fever, tachycardia, and arrhythmia precipitated by depolarizing muscle relaxants / relaxant (succinylcholine) and inhalational anesthetic agents (halothane). When MH occurs, the anesthetic agents must be discontinued immediately and dantrolene should be administered.