ABSTRACT
The ongoing important debate about the relative benefits/risks of COX-1 or COX-2 NSAIDs is hampered by the use of a measure of 'selectivity' that is inherently flawed. An alternative measure provides more meaningful and clinically relevant information.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Confounding Factors, Epidemiologic , Cyclooxygenase 1/metabolism , Cyclooxygenase 2 Inhibitors/metabolism , Cyclooxygenase Inhibitors/metabolism , Humans , Inhibitory Concentration 50ABSTRACT
The tryptophan (TRP) depletion paradigm has been employed to investigate mood and behavioral effects of acutely lowering plasma TRP, and presumably brain serotonin (5-hydroxytryptamine [5-HT]) levels through administration of a special diet and/or amino acid drink. Our goal was to test the assumption that a corresponding fall in central levels of TRP and 5-HT (measured by its major metabolite, 5-hydroxyindoleacetic acid [5-HIAA]) occurs during the standard execution of this method in healthy adult subjects. Three males and two females completed the protocol, which included a one-day low-TRP diet and a TRP-free amino acid drink. Lumbar puncture was performed, with placement of an indwelling catheter connected to a peristaltic pump and fraction collector. Cerebrospinal fluid (CSF) was sampled continuously for a 13.5-hour period (before, during, and after the drink), with fractions removed every 15 minutes. Plasma samples were simultaneously obtained. CSF TRP levels and plasma TRP levels were highly correlated, falling a mean of 92% and 85% from baseline, respectively. CSF nadirs were reached several hours after plasma nadirs. CSF 5-HIAA decreased modestly (24% to 40%, mean 31% change from baseline), with lowest concentrations observed 8-12 hours after the amino acid drink. These data suggest that TRP depletion results in substantial declines in central 5-HT turnover.
Subject(s)
Tryptophan/cerebrospinal fluid , Tryptophan/deficiency , Adult , Affect/drug effects , Brain/metabolism , Catheters, Indwelling , Diet , Drinking , Female , Humans , Hydroxyindoleacetic Acid/cerebrospinal fluid , Male , Serotonin/metabolism , Tryptophan/administration & dosage , Tryptophan/blood , Tyrosine/administration & dosage , Tyrosine/blood , Tyrosine/cerebrospinal fluidABSTRACT
Spinal anesthesia continues to be one of the major techniques in the arsenal of the modern anesthesiologist. Inadequate anesthesia may follow a spinal anesthetic for a variety of reasons. We report a case in which entry of a spinal needle into a subcutaneous cyst mimicked the free flow of cerebrospinal fluid seen with dural puncture. This was confirmed by microscopic examination of the fluid, which was consistent with the contents of a subcutaneous cyst. This represents an unusual cause for failure of spinal anesthesia. Such a possibility should be borne in mind, especially when "clear fluid" return occurs through a spinal needle placed at a relatively superficial depth.
