Stellate ganglion block improved loss of visual acuity caused by retrobulbar optic neuritis after herpes zoster.
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Biomedical subjects
Publications and source records attributed to A Asada.
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BACKGROUND: The finding that i.v. lidocaine suppresses cardiac sympathetic nerve activity during 1 MAC halothane, but not during 2 MAC or 3 MAC halothane, suggests that the neurally mediated circulatory effects of i.v. local anesthetics may vary with background autonomic activity. This study aimed to compare the effects of i.v. lidocaine and bupivacaine on cardiac sympathetic nerve activity (CSNA) during normal and high levels of CSNA. METHODS: Cats were anesthetized with halothane and allocated to three groups. In groups I-L and I-B, sympathetic hyperactivity was induced by electrical stimulation of the posterior hypothalamus. CSNA, heart rate and mean arterial pressure were then measured before and after administration of lidocaine 2 mg.kg BW-1 i.v. (Group I-L, n = 7) or bupivacaine 0.5 mg.kg BW-1 i.v. (Group I-B, n = 7) during 1% halothane anesthesia. In Group II (n = 7), following administration of bupivacaine 0.5 mg.kg BW-1 i.v., CSNA, sinus cycle length (SCL), and subintervals of atrioventricular conduction time (A-H, H-V, and H-S) at pacing were measured during 0.8%, 1.6% and 2.4% halothane anesthesia without sympathetic hyperactivity. RESULTS: Lidocaine suppressed CSNA hyperactivity and tachycardia significantly in Group I-L, but bupivacaine did not do so in Group I-B. In Group II, bupivacaine did not affect CSNA at any concentrations of halothane, but lengthened SCL, A-H, H-V and H-S intervals significantly at each concentration of halothane. CONCLUSIONS: We conclude that i.v. bupivacaine, unlike i.v. lidocaine, does not suppress CSNA during either normal or high CSNA under halothane anesthesia although i.v. bupivacaine has stronger depressive effects on cardiac conduction than does i.v. lidocaine during deep halothane anesthesia.
We studied the effects of ATP and epinephrine on distribution of ischemic hepatic tissue flow in the isolated perfused rat liver. Five minutes after clamping both the portal vein and hepatic artery, perfusion was started. Lidocaine was infused into the portal vein, and the concentration of lidocaine in hepatic outflow was measured with FPIA. The oxygen extraction ratio was also measured. Tissue surface blood flow was measured with laser-Doppler flowmetry. We measured the tissue flow at 2 points: one where flow was more than 10 ml.min-1.100 gm liver weight-1 (R), and the other where flow was less than 10 ml.min-1.100 gm liver weight-1 (P). After perfusion pressure had become stable, ATP or epinephrine was infused for 15 minutes. Perfusion pressure increased, and tissue flow of R decreased significantly, while that of P increased (not significantly). The extraction ratio of lidocaine decreased significantly by epinephrine, and that of oxygen decreased (not significantly). We conclude that in the ischemic liver, vasoconstriction results in changes in the distribution of tissue blood flow and alters drug metabolism.
In a randomized double-blind study, the use of continuous epidural lidocaine during surgery combined with preoperative epidural morphine was compared with that of preoperative epidural morphine alone for postoperative analgesia in 20 patients undergoing hepatectomy. Morphine 2 mg was administered through a catheter inserted epidurally at T10-11 before surgery, followed by continuous epidural administration of 1% lidocaine 5ml.h-1 in group Lid (n = 10) or normal saline 5ml.h-1 in group NS (n = 10) during surgery. Anesthesia was maintained with N2O-O2-isoflurane in both groups. On admission to the ICU, the visual analog scale score (VAS; mm) was 20 +/- 7 (mean +/- SE) in group Lid and 38 +/- 10 in group NS, and the number of patient with VAS < or = 30 was 9 in group Lid and 4 in group NS; these differences were significant (P < 0.05). Pain score during mobilization in group Lid was significantly lower than that in group NS (P < 0.05). All patients in both groups had adequate analgesia for the remainder of their stay in the ICU. No patient had any serious adverse effect. We conclude that continuous epidural administration of lidocaine during hepatectomy combined with administration of epidural morphine just before surgery results in better pain relief during the early postoperative period than that obtained with epidural morphine alone, and is without serious side effects.
We describe two patients (a 21-year-old woman and a 26-year-old man) with crush syndrome who were injured by being buried under collapsed buildings in the Kobe-Awaji Earthquake, and thereafter developed severe pain in the affected limbs. On arrival at our ICU 3 days after the injury, sensation and muscular power were completely absent in both patients. Emergent fasciotomy was performed for the woman. In both patients, burning pain and allodynia occurred in the affected legs between 1 and 3 weeks following the injury while sensation and muscular power partially recovered over the same time period. Pain was not effectively controlled by oral or intramuscular analgesics. Continuous epidural analgesia with 0.25% bupivacaine at a rate of 2 ml.h-1 was effective for relieving pain in the woman, but was not effective in the man, for whom supplemental analgesics, transcutaneous nerve stimulation and near infrared radiation were required to relieve pain. We conclude that persistent pain is one of the important complications of crush syndrome, and that early treatment of pain including epidural analgesia is necessary and may improve functional prognosis of affected patients.
A 28-year-old primipara with pulmonary embolism due to deep venous thrombosis was scheduled for cesarean section under general anesthesia. Her Swan-Ganz catheter and blood gas data revealed pulmonary hypertension and hypoxemia, respectively. Heparin was discontinued 6 hours before operation. A transesophageal echocardiogram (TEE) probe and an inferior vena cava filter were inserted before surgery. Anesthesia was maintained with nitrous oxide and isoflurane in oxygen before delivery, and after delivery with nitrous oxide in oxygen, fentanyl and midazolam. Nitroglycerin and prostaglandin E1 were administered before and after delivery, respectively, to control pulmonary artery pressure, although they were not effective. The anesthetic course was uneventful and her baby's Apgar scores were satisfactory. Mean pulmonary artery pressure (MPAP) gradually decreased after surgery. The inferior vena cava filter may be effective in preventing new pulmonary embolism, and MPAP and TEE monitoring are useful for early detection of pulmonary emboli.
Less than 5% of immature CD4/CD8 double-positive (DP) thymocytes are positively selected to survive and differentiate into single-positive CD4 and CD8 T cells, while self-reactive DP thymocytes undergo apoptosis (negative selection). Both positive and negative selection events are active processes that involve signaling through the T cell receptors (TCRs) and through some accessory molecules. The two events differ quantitatively in the strength of the interaction between TCR and peptide/major histocompatibility complex molecules. We established an in vitro model of positive selection that can be analyzed quantitatively. Positive selection is likely to inhibit glucocorticoid-induced apoptosis in DP thymocytes. Proper crosslinking of TCR together with CD4, CD8, or LFA-1 inhibits the death, and its inhibitory activity is mimicked by proper combinations of ionomycin, a calcium ionophore, and phorbol myristate acetate (PMA), a protein kinase C (PKC) activator. The drug concentrations are within narrow ranges, and are lower than those which are required for the proliferation of mature T cells. Transient stimulation with the combinations of ionomycin and PMA induces differentiation and commitment of isolated DP thymocytes to the CD4 or CD8 T cell lineage in suspension cultures. The level of PKC activity appears to determine the lineage to commit. Functional mature T cells are induced from the committed cells upon secondary stimulation. Activation of calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, also appears to be essential for positive selection as well as for the inhibition of glucocorticoid-induced apoptosis. Negative selection and the regulation of mature T cell apoptosis through TCR and steroid receptors are also discussed.
We determined the early postoperative analgesia using intraoperative continuous epidural infusion of lidocaine during general anesthesia in patients undergoing upper abdominal surgery in a prospective double-blind manner. After insertion of an epidural catheter at the T10-T11 interspace, general anesthesia was induced. Thirty patients were randomly allocated to receive continuous epidural infusion of either 0.5% (n = 15) or 1% (n = 15) plain lidocaine at 10 ml/hr. The infusion was continued from 10 to 15 minutes before surgery until the end of surgery. Visual analog pain scale (0-10) within 30 minutes after the end of surgery was significantly lower in the 1% lidocaine group (5.6 +/- 0.9, mean +/-SE) than in the 0.5% lidocaine group (8.2 +/- 0.8), however, it was unsatisfactory in both groups. Plasma concentrations of lidocaine and its principal metabolite, monoethylglycinexylidide, gradually increased through epidural infusion, but remained below the toxic range in both groups. We conclude that continuous epidural lidocaine during general anesthesia offered limited analgesia in the early postoperative period.
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BACKGROUND: Ropivacaine is a local anesthetic with a long duration of action. Although it is less toxic than bupivacaine, local anesthetic toxicity is possible when the plasma concentration is increased. Because ropivacaine is an amide-type local anesthetic, it is metabolized by cytochrome P450 (P450) in the liver, and its elimination and plasma concentration can be dependent on the level of P450. The purpose of this investigation was to elucidate the metabolism of ropivacaine by human hepatic P450. METHODS: The metabolism of ropivacaine was compared using recombinant human and purified rat hepatic P450 isozymes. An inhibition study using antibodies against rat P450 was performed using hepatic microsomes from human and rat to identify which P450s are involved in ropivacaine metabolism. RESULTS: Ropivacaine was metabolized to 2',6'-pipecoloxylidide (PPX), 3'-hydroxyropivacaine (3'-OH Rop), and 4'-hydroxyropivacaine (4'-OH Rop) by hepatic microsomes from human and rat. PPX was a major metabolite of both human and rat hepatic microsomes. In a reconstituted system with rat P450. PPX was produced by CYP2C11 and 3A2, 4'-OH Rop by CYP1A2, and 3'-OH Rop by CYP1A2 and 2D1. Formation of PPX in rat hepatic microsomes was inhibited by anti CYP3A2, but not by CYP2C11 antibody, and formation of 3'-OH Rop was inhibited by CYP1A2 and 2D1 antibodies. Anti CYP3A2 and 1A2 antibodies inhibited the formation of PPX and 3'-OH Rop in human hepatic microsomes, respectively. Recombinant human P450s expressed in lymphoblast cells were used for further study. CYP3A4 and 1A2 formed the most PPX and 3'-OH Rop, respectively. Ropivacaine N-dealkylation and 3'-hydroxylation activities correlated well with the level of CYP3A4 and 1A2 in human hepatic microsomes, respectively. CONCLUSIONS: Ropivacaine was metabolized to PPX, 3'-OH Rop, and 4'-OH Rop by hepatic P450. PPX was a major metabolite in human hepatic microsomes. CYP3A4 was involved in producing PPX. CYP1A2 was involved in the formation of 3'-OH Rop in human hepatic microsomes.
Lidocaine was used for evaluation of hepatic function in a patient undergoing hepatic resection. Preoperatively, half-life of indocyanine green (ICG) was 33 min after intravenous administration. Plasma concentration of the N-dealkylated metabolite of lidocaine, monoethylglycinexylidide (MEGX), was quantitatively determined to evaluate hepatic function. The patient's rate of formation of MEGX at 15 min after administration of lidocaine was within normal limits, at 56 micrograms/L. These findings suggest that in this patient, hepatic cytochrome P-450IIIA activity was not impaired, but selective impairment of uptake of ICG into hepatocytes or excretion into the bile ducts was present. The rate of formation of MEGX was decreased, and plasma concentration of bilirubin was elevated postsurgically; this could have been the result of decreased cytochrome P-450IIIA activity or decreased hepatic blood flow after hepatic resection. We conclude that the rate of formation of MEGX is a better index of hepatic function than is ICG half-life.
The metabolism of lidocaine was studied using microsomes from extrahepatic tissues of rats, including lung, kidney and brain, or using a reconstituted system with purified CYP2B1 and CYP4B. Rat pulmonary microsomes metabolized lidocaine to an N-deethylated metabolite, monoethylglycinexylidide (MEGX). Renal microsomes produced MEGX and 3-hydroxylidocaine (3-OH LID), although the rate of MEGX formation was much lower in renal than in pulmonary microsomes. Other metabolites were not detected. Lidocaine was not metabolized by brain microsomes. In extrahepatic tissues, pulmonary microsomes had the highest activity. Hence, two major forms of cytochrome P450 isozymes, CYP2B1 and CYP4B1, in rat pulmonary microsomes were used for further study. The study with a reconstituted system using purified cytochrome P450 isozymes revealed that only CYP2B1 showed lidocaine deethylation activity; the other form of cytochrome P450 in the lung, CYP4B1, did not. The Michaelis-Menten constant for lidocaine N-deethylation by rat pulmonary microsomes was 0.27 mM. Antibody against CYP2B1 completely inhibited the formation of MEGX by pulmonary microsomes. These results suggest that lidocaine is metabolized by rat lung, including CYP2B1.
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Tumor necrosis factor alpha inhibitor (TNF-INH) was purified from human urine and it was composed of 161 amino acid residues. The complete amino acid sequence of TNF-INH found by sequence analysis agreed with that predicted from the cDNA structure for the extracellular domain (1-161 portion) of 55-kDa TNF receptor and its processing site at the C-terminal was Asn-161.
A strong fibrinolytic enzyme (nattokinase) was purified from the vegetable cheese natto. Nattokinase was extracted from natto with saline and isolated by sequential use of hydrophobic chromatography on Butyl-Toyopearl, ion-exchange chromatography on CM-Toyopearl, and gel-filtration on Sephadex G-50. The isolated protein gave a single sharp band on SDS-PAGE either before or after reduction. The sequence, as determined by automated Edman degradation of the uncleaved molecule and its enzymatically derived peptide, consisted of a total 275 amino acid residues (M.W = 27,728) and exhibited a high homology with the subtilisins. The purified nattokinase digested not only fibrin but also several synthetic substrates. Among the synthetic substrates, the most sensitive substrate was Suc-Ala-Ala-Pro-Phe-pNA for subtilisin. PMSF inhibited both the fibrinolytic activity and the amidolytic activity. The results indicate that nattokinase is a subtilisin-like serine protease.
It has been suggested that the two acidic regions around residue 70 and residue 170 in yeast cytochrome c1, a subunit of ubiquinol-cytochrome c reductase (complex III), interact with cytochrome c in the electron transfer reaction and that the QCR6 protein, the acidic subunit of yeast complex III, enhances this interaction. In order to determine the roles of the acidic regions of cytochrome c1 more precisely, we introduced several mutations in the two acidic regions and examined their effects on the ability of modified cytochrome c1 to complement the respiration deficiency of yeast cells lacking only cytochrome c1 or both cytochrome c1 and the QCR6 protein. The mutant cytochrome c1 with the deletion of the first acidic region (delta 68-80) was still functional in the cytochrome c1-deficient strain. Mutant cytochrome c1 with the deletion of the second acidic region (delta 168-179) caused a decrease in the complementing ability, but this is probably due to failure in its proteolytic maturation and/or correct assembly into complex III. Mutant cytochrome c1 with altered charge distribution in the acidic regions (Asp170Asp171-->Asn170Asn171 or Asp170Asp171-->Asn170Lys171) made the cytochrome c1-deficient cells respiration-competent. On the other hand, mutant cytochrome c1 with the deletion of the first acidic region (delta 68-80) or altered charge distribution in the second region (Asp170Asp171-->Asn170Lys171) did not restore the respiration deficiency of the cells lacking not only cytochrome c1 but also the QCR6 protein.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To evaluate the effect of high-dose pentobarbital therapy on phenytoin pharmacokinetics. DESIGN: A prospective, clinical study. SETTING: The intensive care unit of a university hospital. PATIENTS: Ten adult patients with cerebral lesions requiring anticonvulsants and control of intracranial pressure. INTERVENTIONS: Each patient received phenytoin sufficient to maintain a plasma concentration at 15 micrograms/mL (60 mumol/L) both before and after barbiturate therapy. Plasma concentrations of total phenytoin, unbound phenytoin, and the major metabolite of phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin, were measured, and pharmacokinetic variables obtained before and after barbiturate therapy were compared. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of total phenytoin remained within the therapeutic range during the 12-hr period preceding barbiturate therapy. After barbiturate therapy, plasma concentrations of both total and unbound phenytoin were significantly less than those concentrations before barbiturate therapy. For total phenytoin, maximum metabolic velocity was increased by 62% (1.09 +/- 0.62 to 1.77 +/- 0.52 mg/L/hr, 1.20 +/- 0.68 to 1.95 +/- 0.57 nmol/L/sec, p < .05), and area under the plasma concentration-time curve (0 to infinity) and mean residence time were each decreased by 73% (32.5 +/- 20.0 to 8.7 +/- 3.1 min.mg/mL, 2.14 +/- 1.25 to 0.57 +/- 0.19 sec.mmol/L, p < .01, and 135,000 +/- 69,000 to 37,000 +/- 11,000 secs, p < .005, respectively) after barbiturate therapy. The plasma concentration of the principal metabolite of phenytoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin, was significantly increased after barbiturate therapy. CONCLUSIONS: Phenytoin metabolism is increased by barbiturate therapy, and supplemental doses of phenytoin and frequent drug monitoring may be required after barbiturate therapy.