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Biomedical subjects

T C Lee

Publications and source records attributed to T C Lee.

At least 91 records · Page 5Linked to original sources
PubMed1999

Medroxyprogesterone acetate and dexamethasone are competitive inhibitors of different human steroidogenic enzymes.

Medroxyprogesterone acetate (MPA), a widely used progestin, can suppress the hypothalamic-pituitary-gonadal axis but can also directly inhibit gonadal steroidogenesis; the success of MPA as a treatment for gonadotropin-independent sexual precocity derives from its direct action on steroidogenic tissues. Dexamethasone, a widely used glucocorticoid, can suppress the hypothalamic-pituitary-adrenal axis, but its potential effect directly on the adrenal is unclear. Previous reports suggested that these two drugs may act on the initial steps in the rodent steroidogenic pathway; therefore, we investigated their abilities to inhibit the first three human enzymes in steroidogenesis: the cholesterol side-chain cleavage enzyme (P450scc), the 17alpha-hydroxylase/17,20-lyase (P450c17), and type II 3beta-hydroxysteroid dehydrogenase/isomerase (3betaHSDII). We found no effect of either drug on P450scc in intact human choriocarcinoma JEG-3 cells. Using microsomes from yeast expressing human P450c17 or microsomes from human adrenals, we found that dexamethasone inhibited P450c17 with a Ki of 87 micromol/L, which is about 1000 times higher than typical therapeutic concentrations, but that MPA has no detectable action on P450c17. Using microsomes from yeast expressing human 3betaHSDII, we found that this enzyme has indistinguishable apparent Km values of 5.2-5.5 micromol/L and similar maximum velocities of 0.34-0.56 pmol steroid/min x microg microsomal protein for the three principal endogenous substrates, pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone. In this system, MPA inhibited 3betaHSDII with a Ki of 3.0 micromol/L, which is near concentrations achieved by high therapeutic doses of 5-20 mg MPA/kg x day. These data establish the mechanism of action of MPA as an inhibitor of human steroidogenesis, and are in contrast with the results of earlier studies indicating that MPA inhibited both P450c17 and 3betaHSD in rat Leydig cells. These studies establish the "humanized yeast" system as a model for studying the actions of drugs on human steroidogenic enzymes and suggest that 3betaHSDII may be an appropriate target for pharmacological interventions in human disorders characterized by androgen excess or sex steroid dependency.

Animals↗
PubMed1999

Transpedicular instrumentation as an adjunct in the treatment of thoracolumbar and lumbar spine tuberculosis with early stage bone destruction.

OBJECT: Because modern imaging techniques now allow for early diagnosis of spinal tuberculosis, more conservative management options are possible. The authors evaluated the effectiveness of transpedicular instrumentation for treatment of thoracolumbar and lumbar spinal tuberculosis in patients with mild bone destruction and the main symptom of "instability catch" (a sudden painful "snap" that occurs when one extends from a forward bent to an upright position). METHODS: Eighteen patients (nine men and nine women, age range 49-71 years) with spinal tuberculosis were treated with transpedicular instrumentation that was supplemented with posterolateral fusion and chemotherapy. All patients were wheelchair dependent or bed-ridden due to severe instability catch, with a mean symptom duration of 2.5 months (range 1-6 months). Two contiguous vertebrae were involved in 17 patients, and a single vertebrae was involved in one. In five patients mild neurological deficits (Frankel Grade D) were present. During surgery, the screws were implanted into the two nonaffected pedicles nearest the lesion to stabilize the involved segments. No attempt at radical debridement or neural decompression was undertaken. The follow-up period ranged from 21 to 40 months. Postoperatively the instability catch was relieved within 10 days (excellent outcome) and within 1 month (good outcome) in seven and eight patients, respectively, and within 3 months (fair outcome) in two; in the remaining patient, the symptom did not resolve (poor outcome). A short duration of symptoms (generally < 3 months) and bone destruction of less than 50% in the involved vertebral bodies were observed in patients who made a good or excellent outcome. During the follow-up period, good maintenance of spinal alignment, stabilization of the involved segment, and resolution of the inflammatory process were shown; however, there was no strong evidence that fusion had occurred at the bony defect. Patients in whom a fair outcome was achieved experienced a longer duration of symptoms, and in each, one vertebral body with greater than 50% bone destruction was demonstrated. However, good maintenance of spinal alignment was also shown during the follow-up period. The patient whose outcome was poor had the longest history (6 months) of symptoms and the most extensive involvement of the spine (> 50% destruction of two adjacent lumbar vertebral bodies). Postoperatively, implant failure occurred and the patient developed a wound infection. CONCLUSIONS: Transpedicular instrumentation provides rapid relief of instability catch and prevents late angular deformity in patients with thoracolumbar and lumbar spinal tuberculosis in whom limited (< 50%) bone destruction of the involved vertebral bodies has been shown and whose main symptom is instability catch.

Aged↗
PubMed1999

Failure of screening to detect HIV in a foreign laborer who died of toxoplasmosis of the central nervous system.

The most common neurologic complication in patients with acquired immunodeficiency syndrome (AIDS) is cerebral toxoplasmosis. Patients with cerebral toxoplasmosis have characteristic findings on clinical examination and neuroimaging. They require prolonged treatment and have a considerable mortality rate. We report a case of cerebral toxoplasmosis in a foreign laborer with AIDS, in whom a human immunodeficiency virus (HIV) screening test failed to detect-HIV infection. The patient, a 23-year-old man from Thailand, presented in a confused state 2 weeks after his arrival in Taiwan. Computed tomography showed a mass effect, and magnetic resonance imaging showed multiple ring-enhanced lesions in the cerebrum. Serologic tests were positive for anti-HIV antibody and also showed high anti-Toxoplasma immunoglobulin G titers. Although symptomatic treatment was initiated, the patient's condition deteriorated rapidly and he died of multiple organ failure due to brain stem herniation a few days after admission. As the number of foreign laborers working in Taiwan has increased dramatically in recent years, the issues raised by this case are the efficacy of our screening protocols for foreign laborers and the increased occupational hazards encountered by medical personnel in Taiwan.

AIDS Serodiagnosis↗
PubMed1999

Food processing on a space station: feasibility and opportunities.

An alternative strategy for processing plants into food on a space or other isolated station including an Advanced Life Support (ALS) system is proposed. Regular gravity (1 G) or hypogravity (< 1 G) has been considered. A key feature of this strategy is to include not only kitchen-scale preparation and processing but small-scale advanced food processing such as thermoplastic extrusion, homogenization, centrifugation, fermentation, etc. These processes are flexible and multifunctional and could significantly increase the variety, palatability, nutritional value, and shelf stability of foods, and the number of menu items based on ALS crops. The processes would minimize the time to process the food items and provide psychological support for the crew. The periodic processing of various crop harvests into shelf-stable foods for long-term storage can be performed. Unit operations as illustrated by various processing flow sheets on the manufacturing of individual products will be discussed in association with the equipment.

Equipment Design↗
PubMed1999

Development of expanded extrusion food products for an Advanced Life Support system.

Extrusion processing was proposed to provide texture and to expand the variety of cereal food products in an isolated Advanced Life Support (ALS) system. Rice, wheat, and soy are the baseline crops selected for growing during long-term manned space missions. A Brabender single-screw laboratory extruder (model 2003, L/D 20:1), equipped with round nozzles of various lengths, was used as a prototype of a small-size extruder. Several concepts were tested to extend the variety and improve the quality of the products, to decrease environmental loads, and to promote processing stability. These concepts include: the blending of wheat and soybean flour, the extrusion of a coarser rice flour, separation of wheat bran, and optimization of the extruder nozzle design. An optimal nozzle length has been established for the extrusion of rice flour. Bran separating was necessary to improve the quality of wheat extrudates.

Ecological Systems, Closed↗
PubMed1999

On a wing and a prayer: the biomechanics of the Rev. Dr. Samuel Haughton (1821-1897).

In 1873, Samuel Haughton published Principles of Animal Mechanics. Based on research begun in 1862, it was a response to Darwin's The Origin of Species by Means of Natural Selection published three years earlier. In this article, the nature of Haughton's biomechanical researches is described by reviewing and re-analysing some of his original work. He showed how muscles could be seen as designed to carry out the maximum amount of work with the least expenditure of energy. Haughton used the results to argue against Darwin's theory of natural selection, the "unproved hypothesis" as Haughton called it. Despite correspondence with Darwin, Haughton received no scientific rebuttal of his arguements. To this day, it would seem, there is a lack of concordance between the biomechanical view of organic life as "optimised" and the evolutionary view of life under continual transformation as organic forms descended "from a supposed common ancestor."

Biological Evolution↗
PubMed1998

Induction of pulmonary fibrosis in organ-cultured rat lung by cadmium chloride and transforming growth factor-beta1.

Cadmium chloride (CdCl2) exposure has been reported to induce pulmonary fibrosis in rats. Accumulating evidence has shown that cytokines play a pivotal role in the excessive production of connective tissue components in pulmonary fibrosis. In this report, rat lung slice cultures were used to study the synergistic involvement of transforming growth factor-beta1 (TGF-beta1) in CdCl2-induced alveolar fibrosis. Rat lung slices were maintained at the interphase of air and medium on a polyester mesh stretched on a plastic scaffold. Treatment of lung slices with 2.5, 5 or 10 microM CdCl2 for 7 days resulted in 85, 40 and 6% respectively for relative survival. Under these culture conditions, CdCl2 alone did not induce alveolar fibrosis in rat lung slices. However, in the presence of 0.5 ng/ml TGF-beta1, CdCl2 at a dose ranging from 1 to 5 microM increased the thickness of alveolar septa. Furthermore, the thickness of alveolar septa in lung slices treated with CdCl2 was dose-dependently increased by the presence of TGF-beta1. The thickened alveolar septa were apparently due to the deposition of excessive extracellular matrix, as revealed by trichrome stain and ultrastructural examination. Our results also show that fibrogenic activity induced by the combined treatment with CdCl2 and TGF-beta1 can be reduced by co-treatment with 200 microg/ml lambda-carrageenan, a TGF-beta1 inhibitor. Therefore, the present results indicate that TGF-beta1 can synergistically stimulate the fibrogenic activity in lung tissue subsequent to CdCl2 injury.

Animals↗
PubMed1998

Induction of sister chromatid exchanges and micronuclei by titanium dioxide in Chinese hamster ovary-K1 cells.

Titanium dioxide (TiO2) has color properties of extreme whiteness and brightness, is relatively inexpensive, and is extensively used as a white pigment in a variety of materials. TiO2, an effective blocker of ultraviolet light, is frequently added to sunscreens and cosmetic creams. However, the genotoxicity of TiO2 remains to be controversial. In this report, we have demonstrated that TiO2 can be transported into Chinese hamster ovary-K1 (CHO-K1) cells. The effects of TiO2 on induction of sister chromatid exchanges (SCE) and micronuclei (MN) were then studied in these cells. The SCE frequency in CHO-K1 cells treated with TiO2 at a nonlethal dose range (0 to 5 microM) for 24 h was significantly and dose-dependently increased. By the conventional MN assay, TiO2 at the dose ranged from 0 to 20 microM slightly increased the MN frequency in CHO-K1 cells. However, in the cytokinesis-block MN assay, the number of MN per 1000 binucleated cells was significantly and dose-dependently enhanced in CHO-K1 cells treated TiO2 at the same dose range for 24 h. These results suggest that TiO2 is a potential genotoxic agent.

Animals↗
PubMed1998

Effect of patient position and hypotensive anesthesia on inferior vena caval pressure.

STUDY DESIGN: This is a prospective study to measure the inferior vena caval pressure of 20 patients in different positions and different states of blood pressure. OBJECTIVES: Because the inferior vena caval pressure could affect the vertebral venous pressure, which in turn may influence blood loss during lumbar spinal surgery, this study was designed to provide the quantitative data necessary to stress the importance of patient positioning and to assess the effect of controlled hypotension on inferior vena caval pressure. SUMMARY OF BACKGROUND DATA: Positioning patients with a pendulous abdomen and controlled hypotension has been practiced widely during lumbar spinal surgery. It is generally believed that the former will help reduce vertebral venous engorgement and the latter will produce a bloodless surgical wound. However, there have been no complete studies in which quantitative changes of inferior vena caval pressure resulting from different positions was examined. In addition, it would be interesting to know what happens to inferior vena caval pressure during induced hypotension. Could there be an adverse effect on the inferior vena caval pressure during the hypotensive state? METHODS: An intravenous catheter was introduced into the inferior vena cava in each of 20 patients undergoing spinal surgery. In each patient, the inferior vena caval pressure was measured when the patient was supine, prone on a conventional pad, and prone on a Relton-Hall frame. It was followed by isoflurane-induced hypotension with reduction of mean arterial pressure by 20 mm Hg. RESULTS: In this series, the inferior vena caval pressure ranged from 8.2 to 23.4 mm Hg (with a mean of 15.3 mm Hg) when patients were positioned prone on a conventional pad. However, when they were subsequently positioned prone on a Relton-Hall frame, the inferior vena caval pressure decreased dramatically to a range of 4.6 to 13.6 mm Hg (with a mean of 8.2 mm Hg). In each patient the measured inferior vena caval pressure when positioned prone on a conventional pad was 1.5 times greater than that measured with the patient positioned on a Relton-Hall frame. There was a statistically significant difference between these two positions (F = 75.996; P < 0.05). The patients' mean arterial pressure ranged from 92 to 105 mm Hg before induced hypotension. During this time, the inferior vena caval pressure ranged from 4.1 to 13.1 mm Hg (mean, 8.2 mm Hg). During the hypotensive state, the patients' inferior vena caval pressure was found to range from 4.2 to 13.6 mm Hg (mean, 8.1 mm Hg). In each patient the hypotensive interior vena caval pressure may be slightly higher or lower than the baseline pressure. However, the variation never exceeded 1.7 mm Hg. Statistically, there was no significant difference between these two periods (t = 0.956; P > 0.05). CONCLUSIONS: A device allowing the patient's abdominaL viscera to hang freely while the patient is in a prone position significantly reduces their inferior vena caval pressure. The patients also has a constant inferior vena caval pressure during isoflurane-induced hypotension.

Adult↗
PubMed1998

Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without direct electron transfer.

In the biosynthesis of steroid hormones, P450c17 is the single enzyme that catalyzes both the 17alpha-hydroxylation of 21-carbon steroids and the 17,20-lyase activity that cleaves the C17-C20 bond to produce C19 sex steroids. Cytochrome b5 augments the 17,20-lyase activity of cytochrome P450c17 in vitro, but this has not been demonstrated in membranes, and the mechanism of this action is unknown. We expressed human P450c17, human P450-oxidoreductase (OR), and/or human cytochrome b5 in Saccharomyces cerevisiae and analyzed the 17alpha-hydroxylase and 17,20-lyase activities of the resulting yeast microsomes. Yeast expressing only P450c17 have 17alpha-hydroxylase and trace 17,20-lyase activities toward both Delta4 and Delta5 steroids. Coexpression of human OR with P450c17 increases the Vmax of both the 17alpha-hydroxylase and 17,20-lyase reactions 5-fold; coexpression of human b5 with P450c17 also increases the Vmax of the 17,20-lyase reactions but not of the 17alpha-hydroxylase reactions. Simultaneous expression of human b5 with P450c17 and OR, or addition of purified human b5 to microsomes from yeast coexpressing human P450c17 and OR, further increases the Vmax of the 17,20-lyase reaction without altering 17alpha-hydroxylase activity. Genetically engineered yeast and mixing experiments demonstrate that OR is both necessary and sufficient for microsomal 17,20-lyase activity. Addition of purified human holo-b5, apo-b5, or cytochrome c to microsomes containing both human P450c17 and OR demonstrate that the stimulatory action of b5 does not require electron transfer from b5 to P450c17. These data suggest that human b5 acts principally as an allosteric effector that interacts primarily with the P450c17.OR complex to stimulate 17, 20-lyase activity.

Catalysis↗
PubMed1998

Closed reduction of bilateral locked facets of the cervical spine under general anaesthesia.

BACKGROUND: Bilateral facet interlocking of the cervical spine is a relatively uncommon type of cervical spinal injury. It is frequently associated with devastating neurological symptoms and signs. Early reduction of the locked facets is thought to be critical in preventing progressive secondary spinal cord injury. Whereas skull tong traction remains our primary option for closed reduction of bilateral locked facets of the cervical spine, it is not always successful, even with heavy traction weights. Other more aggressive measures may occasionally be required. The authors report their experience in reducing bilateral locked facets of the cervical spine by manual closed reduction. METHODS: This small series consists of six cases of cervical spinal injury with bilateral locked facets in which manual closed reduction under general anaethesia and muscle relaxation was used. Three of them presented with complete quadriplegia (Frankel class A). One case presented with incomplete but severe neurological deficits (Frankel class B). After unsuccessful closed reduction with skull traction, these patients were treated by manual closed reduction under general anaesthesia and muscle relaxation, followed by anterior discectomy, interbody fusion and stabilization. RESULTS: All cases made neurological improvement after the procedures. Even in cases with initial severe neurological deficits, the recovery was remarkable. The recovery was dramatic in two cases. Case 1 improved from Frankel class B to E; and Case 5 from Frankel class A to D. No case deteriorated neurologically after the procedures. Pneumonia occurred in Case 3; and stress ulcer accompanied by haemorrhage was noted in Case 4. None of these complications was directly related to the procedures. CONCLUSION: The potential for improvement of neurological function following early and successful reduction and fixation of the dislocated spine is emphasized. With meticulous techniques, manual closed reduction may be an effective alternative to skull tong traction when the latter fails.

Adult↗
PubMed1998

Measuring the shape and size of microcracks in bone.

Microcracks in bone are normally measured from two-dimensional, transverse sections but this provides incomplete information about their three-dimensional shape and size. The methods of stereology can usefully be applied in such a case. This problem has been addressed using a theoretical model and a numerical simulation. Results show that the data are consistent with a crack shape which is elliptical, with axis ratio approximately 4.5:1 and with size variation (expressed as the ratio of standard deviation to mean length) of at least 0.1. Measured lengths will, on average, be smaller and have more scatter than true lengths. Errors caused by omitting small cracks are relatively unimportant. Knowledge of the true crack dimensions, and their variability, is important for the analysis of damage, stress fracture, remodelling and adaptation.

Adaptation, Physiological↗
PubMed1998

Types of purinoceptors and phospholipase A2 involved in the activation of the platelet-activating factor-dependent transacetylase activity and arachidonate release by ATP in endothelial cells.

Acyl analogs of PAF are the major products synthesized during agonist stimulation of endothelial cells. We have previously shown that PAF: 1-acyl-2-lyso-sn-glycero-3-phosphocholine transacetylase in calf pulmonary artery endothelial cells is activated by ATP through protein phosphorylation, and the increase in transacetylase activity by ATP contributes to the biosynthesis of acyl analogs of PAF (J. Biol. Chem. 272, 17431-17437, 1997). To understand the mechanisms(s) by which ATP stimulates acyl analogs of PAF production, we have identified the subtypes of the purinergic receptor that are linked to the activation of two enzymes involved in the generation of acyl analogs of PAF, namely, transacetylase and phospholipase A2. Experiments with transient transfection of the cells with antisense and sense thio-oligonucleotide to cytosolic phospholipase A2 (cPLA2) were also performed to evaluate whether downstream activation of cPLA2 is involved in ATP-receptor mediated induction of arachidonate release and synthesis of radylacetyl-GPC. We found that the P2u/P2Y2 receptor, which recognizes a pyrimidine nucleotide, UTP, as well as purine nucleotides, shows a potency profile of UTP > ATP = ATP gamma S > 2-methylthio-ATP in mediating the activation of PAF: lysophospholipid transacetylase. On the other hand, ADP beta S and 2-methylthio-ATP have similar potencies as ATP but have lower potencies than UTP and ATP gamma S in stimulating the release of arachidonate. These results suggest that both P2u/P2Y2 and P2y/P2Y1 receptor subtypes promote arachidonate release. In addition, transient transfection of endothelial cells with cPLA2 antisense but not the sense thio-oligonucleotide inhibited the stimulation of arachidonate release and [3H]acetate incorporation into radyl[3H]acetyl-GPC. Thus, our data suggest that a receptor-mediated process is involved in the activation of transacetylase for the induced synthesis of acyl analogs of PAF in endothelial cells. Furthermore, it is likely that cPLA2 supplies the lysophospholipids as substrates for the transacetylation reaction.

Acetylesterase↗
PubMed1998

Chemical hypoxia triggers apoptosis of cultured neonatal rat cardiac myocytes: modulation by calcium-regulated proteases and protein kinases.

Myocardial infarctions and stroke arise primarily as a result of hypoxia/ischemia-induced cell injury. However, the molecular mechanism of cardiac cell death due to hypoxia has not been elucidated. We showed here that chemical hypoxia induced by 1 mM azide triggered apoptosis of isolated neonatal rat ventricular cardiac myocytes but had no effect on cardiac fibroblasts. The azide-induced cardiomyocyte apoptosis could be characterized by a reversible initiation phase (0-46 h after azide exposure) during which cytosolic ATP levels remained little affected. This was followed by an irreversible execution phase (12-18 h) exhibiting prominent internucleosomal DNA fragmentation, cell membrane leakage, mitochondrial dysfunction, and increased calpain messenger RNA. Blocking extracellular calcium influx or intracellular calcium release was each effective in suppressing myocyte apoptosis. Cell death was also found to be mediated by calcium sensitive signal transduction events based on the use of specific antagonists. Consistent with the induction of calpain expression during apoptosis, blocking de novo protein synthesis and calpain activity inhibited cell death. These regulatory features coupled with the ease of the cell system suggest that the myocyte apoptosis model described here should be useful in the study of events leading to the demise of the myocardium.

Animals↗
PubMed1998

Fluorescence-aided detection of microdamage in compact bone.

En bloc staining with basic fuchsin is an established method for demonstrating microdamage in bone. Using transmitted light microscopy, variations in light intensity, depth of focus and magnification are necessary to distinguish fully-stained microcracks generated in vivo, from partially-stained or unstained artefactual cracks due to cutting and machining. This process is both difficult and time-consuming. In this study, 2 methods were used to examine fuchsin-stained microcracks in human rib sections, transmitted light and epifluorescence microscopy. No differences were found in crack number, density or length between the 2 methods indicating comparable accuracy. Using green epifluorescence, only microcracks containing fuchsin fluoresced orange against the darkfield background, enabling unstained, artefactual cracks to be screened out. Under UV epifluorescence, microcracks stained through the full 100 microm depth of the section fluoresced purple. Partially-stained artefactual cracks failed to fluoresce and were screened out. Epifluorescence is a simple, rapid and accurate screening method for differentiating fully-stained from artefactual microcracks in bone.

Aged↗
PubMed1998

Arsenite inhibits mitotic division and perturbs spindle dynamics in HeLa S3 cells.

Arsenical compounds, known to be human carcinogens, were shown to disturb cell cycle progression and induce cytogenetic alterations in a variety of cell systems. We report here that a 24 h treatment of arsenite induced mitotic accumulation in human cell lines. HeLa S3 and KB cells were most susceptible: 35% of the total cell population was arrested at the mitotic stage after treatment with 5 microM sodium arsenite in HeLa S3 cells and after 10 microM in KB cells. Under a microscope, we observed abnormal mitotic figures in arsenite-arrested mitotic cells, including deranged chromosome congression, elongated polar distance of mitotic spindle, and enhanced microtubule immunofluorescence. The spindle microtubules of arsenite-arrested mitotic cells were more resistant to nocodazole-induced dissolution than those of control mitotic cells. According to turbidity assay, arsenite at concentrations below 100 microM significantly enhanced polymerization of tubulins. Since spindle dynamics play a crucial role in mitotic progression, our results suggest that arsenite-induced mitotic arrest may be due to arsenite's effects on attenuation of spindle dynamics.

Animals↗
PubMed1998

Lidocaine concentrations in plasma and cerebrospinal fluid after systemic bolus administration in humans.

UNLABELLED: Preclinical studies suggest that systemic lidocaine acts at the level of the spinal dorsal horn to inhibit hyperalgesia resulting from nerve injury, yet no clinical data are available to support this view. Therefore, we sought to characterize the time course of lidocaine in the plasma and cerebrospinal fluid (CSF) after an IV bolus injection of lidocaine 2 mg/kg in patients scheduled for surgery involving spinal anesthesia. Sixty-five patients were randomly allocated to one of five study groups (n = 13 per group) receiving IV lidocaine before CSF/ plasma sampling at 5, 10, 15, 30, or 60 min. Gas chromatographic analysis of these samples revealed a fast but transient peak (5-15 min) in lidocaine plasma levels (1.7+/-0.16 microg/mL), which declined rapidly thereafter. Only small concentrations of IV lidocaine were found in the CSF (6%- 8% of plasma concentration), but this fraction remained stable from 15 min until termination of the experiment. No statistical correlation was observed between plasma and CSF lidocaine levels. These data suggest that because of the prolonged availability of lidocaine at the spinal dorsal horn level, systemic administration of lidocaine suppresses central sensitization within the spinal cord after nerve injury in humans. IMPLICATIONS: Cerebrospinal fluid concentrations of lidocaine after its systemic bolus delivery in humans indicate that the spinal cord may be the major site of antinociceptive action by this route of drug administration.

Adolescent↗