Masquerading neuropathies.
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Biomedical subjects
Publications and source records attributed to F W Burgess.
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This study was designed to evaluate the potential fentanyl-sparing effect of a dilute local anesthetic, bupivacaine, administered in fixed combinations with fentanyl for post-thoracotomy analgesia via a continuous thoracic epidural infusion. Forty adult patients scheduled for thoracotomy were randomly allocated in a double-blind fashion to receive an epidural infusion containing 0, 0.03, 0.06, or 0.125% bupivacaine in combination with fentanyl (4 micrograms/mL). The epidural infusions were initiated in the operating room at 10 mL/hr. During the first 24 hours, there were no between-group differences in pain scores. Total fentanyl use was significantly decreased 24% to 33% in all bupivacaine treatment groups. However, fentanyl plasma levels at 24 hours were not significantly different between groups. Arterial blood gas measurements performed on the morning after surgery revealed significant reductions in PaCO2 values, 38 +/- 4, 36 +/- 4, 37 +/- 4 mmHg for 0.03, 0.06, and 0.125% bupivacaine groups respectively, versus 44 +/- 6 for the plain fentanyl group. Arterial pH values were significantly higher in all bupivacaine treatment groups. These findings suggest that the combination of dilute bupivacaine with fentanyl for thoracic epidural analgesia for post-thoracotomy pain may have beneficial effects on pulmonary gas exchange.
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Human peripheral lymphocytes incubated with 2'-deoxycoformycin and 2'-deoxyadenosine (dAdo) reached a plateau in dATP accumulation after 4 hr that lasted for up to 24 hr. Total dATP accumulation did not exceed 15% of the control ATP concentration in the lymphocytes. In contrast, the human CCRF-CEM T lymphoblastic cell line and human erythrocytes showed a nearly linear pattern of dATP formation throughout the incubation period. By 6 hr the dATP concentration in the CCRF-CEM cells exceeded the control ATP concentration. A comparison of dATP accumulation in purified peripheral T and B lymphocytes indicated differences between these cells that favor greater dATP formation in the B lymphocytes. Incorporation studies with several adenosine analogs demonstrated that arabinosyladenine, 2-F-arabinosyladenine, tubercidin, formycin A, and 9-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)adenine form corresponding amounts of analog triphosphate in the T and B cell-enriched lymphocytes. 9-(2'-Deoxy-2'-fluoro-beta-D-arabinofuranosyl)adenine (2'-F-araA) was the only compound to show an incorporation pattern similar to that observed with dAdo by forming analog triphosphate only in the B cell-enriched lymphocyte population. Nucleoside kinase measurements showed no significant differences in dAdo, adenosine, or 2'-deoxycytidine kinase activities between the T and B lymphocytes. The inability of the T cells to incorporate dAdo or the analog 2'-F-araA into their nucleotide pools may indicate the existence of a highly specific catabolic enzyme(s).
Several B lymphoblastic cell lines are known to be relatively resistant to the combination of 2'-deoxyadenosine with an adenosine deaminase inhibitor. These cell lines are believed to have a greater capacity to dephosphorylate 2'-deoxyadenosine nucleotides, thus preventing excessive accumulation of potentially toxic metabolites. In this study, the 2'-deoxynucleoside 5'-monophosphate dephosphorylating activities of human peripheral lymphocytes were examined. Peripheral lymphocytes have at least three nucleotide 5'-monophosphate nucleotidases distinguished by different pH optimums, substrate preference, Mg2+ requirement, inhibitors, and molecular weights. Two of the enzymes appeared to be cytosolic, only one of which had significant substrate activity with dAMP. This enzyme had an acidic pH optimum (5.0), no Mg2+ requirement, was inhibited by tartrate, and demonstrated broad substrate specificity. The other cytosolic nucleotidase required Mg2+, had a pH optimum of 5.5 to 6.0, was activated by 2'-deoxyinosine, and demonstrated a substrate preference for 3'- and 5'-monophosphate 2'-deoxynucleosides of hypoxanthine, guanine, uracil, and thymine. The third enzyme, ecto 5'-nucleotidase, is associated with the cell membrane. Although the ecto 5'-nucleotidase activity was higher in the B lymphocytes, the cytosolic nucleotidases were similar in activity in the T and B lymphocytes.
The effects of the chiral isomers of erythro- and threo-9-(2-hydroxy-3-nonyl)adenines (EHNA and THNA) on purine metabolism in Sarcoma 180 cells have been determined. At concentrations of 10-80 microM [10- to 1000-fold greater than their Ki values with adenosine deaminase (ADA)], all isomers inhibited purine salvage and biosynthesis de novo. Although (+)-EHNA, the most potent ADA inhibitor, exerted the greatest effects, there was no direct correlation between the potency of ADA inhibition and the secondary effects on purine metabolism, e.g. (+)-EHNA is about 2-fold more inhibitory than (-)-EHNA in blocking purine base incorporation but about 250-fold more potent as an inhibitor of ADA (Ki of (+)-EHNA = 2 nM; Ki of (-)-EHNA = 500 nM [Bessodes et al., Biochem. Pharmac. 31, 879 (1982)]). All the isomers inhibited the incorporation of radiolabeled purine bases (adenine, guanine and hypoxanthine) and nucleosides (guanosine and inosine) into acid-soluble nucleotides and of glycine into 5'-phosphoribosyl-formylglycineamide. Unlike the results of Henderson et al. [Biochem. Pharmac. 26, 1967 (1977)] with Ehrlich ascites cells, the incorporation of adenosine into nucleotides was only slightly inhibited in Sarcoma 180 cells. (+)-EHNA did not inhibit the activities of 5-phosphoribosyl-1-pyrophosphate (PRPP) synthetase, purine phosphoribosyltransferases or nucleotide kinases in cell extracts. Accumulation of PRPP was inhibited only under conditions that fostered rapid synthesis.
BACKGROUND AND OBJECTIVES: Ropivacaine is a long-acting local anesthetic similar to bupivacaine, but with lower cardiac toxicity and intrinsic vasoconstrictive properties that may reduce the risk and extent of systemic plasma absorption. Plasma levels and risks are associated with the total dose used and the extent of absorption, with lower doses potentially representing less risk. Although both 0.5% and 0.75% ropivacaine provide adequate analgesia for wound infiltration after hernia repair, the efficacy of lower doses and the early systemic absorption have not been reported. METHODS: We studied postoperative pain and systemic plasma levels following either the injection of 30 mL of saline or 0.125%, 0.25%, or 0.5% ropivacaine into the wounds in 110 healthy patients following hernia repair under spinal anesthesia. Pain was assessed using visual analog scale (VAS) scores and algometer readings at rest and after coughing, and oral analgesic requirements were assessed in the first 5 hours after surgery and for the week after discharge. RESULTS: Both 0.25% and 0.5% ropivacaine provided pain relief following surgery when compared with saline or 0.125%. No adverse reactions to the drug were reported in any group. Plasma levels of ropivacaine peaked between 30 and 60 minutes, at 0.109, 0.249, and 0.399 mg/L for 0.125%, 0.25%, and 0.5% concentrations, respectively. Although the levels were below those producing clinical symptoms, they remained elevated for the entire 2-hour sampling period. This implies an absorption-dependent elimination which is substantially longer than reported with other routes of injection. CONCLUSIONS: Ropivacaine 0.25% and 0.5% is adequate for pain relief after outpatient hernia repair, whereas the 0.125% solution is no more effective than saline. Prolonged systemic absorption from peripheral injection may be associated with prolonged elevations of plasma concentrations, which potentially could be associated with unexpectedly high plasma levels if repeated injections are performed in the perioperative period with higher concentrations or doses.
Continuous spinal anesthesia (CSA) with hyperbaric bupivacaine (0.75% bupivacaine in 8.25% dextrose and water) was administered to 27 adult males for transurethral endoscopic surgery. Patients were randomized to receive either 3.75, 7.5 or 10 mg hyperbaric bupivacaine in a double-blind fashion. A 20-gauge nylon catheter was inserted at the L3-4 interspace, via an 18-gauge Tuohy-Schliff needle, extending only 2 cm into the subarachnoid space. All patients were placed in the lithotomy position prior to administration of the hyperbaric bupivacaine. Sensory block was assessed by pinprick and perception of a 50-Hz tetanic stimulus at 5, 10 and 20 minutes, then every 20 minutes thereafter. Peak sensory and motor block were obtained by 20 minutes for all dose ranges. Peak sensory levels were T7.1, T5.6 and T3.9 for 3.75, 7.5 and 10 mg hyperbaric bupivacaine, respectively. Linear regression analysis demonstrated a significant correlation (r = -0.68) between peak sensory level and dose of bupivacaine. Peak sensory level as estimated by pinprick and 50-Hz tetanic stimulus showed excellent correlation (r = 0.99). The role of the subarachnoid catheter in the dispersion and distribution of bupivacaine within the subarachnoid space was studied in a model spinal canal system and compared with the distribution of bupivacaine administered via a standard 25-gauge spinal needle. No significant differences were found in the distribution of bupivacaine with either method of injection. The distribution of hyperbaric bupivacaine within the subarachnoid space appears to be related to baricity but is unrelated to administration via needle or catheter.