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Biomedical subjects

R L James

Publications and source records attributed to R L James.

At least 37 records · Page 2Linked to original sources

Small-dose propofol by continuous infusion does not prevent postoperative vomiting in females undergoing outpatient laparoscopy.

This study was designed to test the hypothesis that there is a direct prophylactic antiemetic effect of small-dose propofol given by continuous infusion. Sixty female patients undergoing outpatient laparoscopy under general anesthesia were randomized to receive, in a double-blind fashion, either a bolus of 0.1 mg/kg followed by a constant infusion of 1 mg.kg-1.h-1 of propofol or an equivalent volume of 10% Intralipid (placebo) beginning 30 min before induction of anesthesia and continuing until discharge from Stage I postanesthesia care unit (PACU). Anesthesia was induced and maintained in a standard fashion in all patients. The number of emetic episodes before and after discharge from PACU, nausea scores (11-point numerical scale), and time to discharge were evaluated. No significant differences between Intralipid and propofol were found for any of the outcome variables tested. While small-dose propofol is an effective adjuvant in reducing chemotherapy-induced emesis, we were unable to demonstrate any beneficial effect of propofol in reducing postoperative nausea and vomiting when used as the sole prophylactic medication in this patient population. Propofol may have a synergistic effect when administered with other antiemetics, or the specific antiemetic effect of propofol, if it exists, may be dose-dependent and the dose used in this study was below the efficacy threshold.

Adolescent↗

Structure-affinity relationships and stereospecificity of several homologous series of local anesthetics for the beta2-adrenergic receptor.

UNLABELLED: Local anesthetics inhibit binding of ligands to beta2-adrenergic receptors (beta2ARs), and, as a consequence, inhibit intracellular cAMP production. We hypothesized that among homologous local anesthetics, their avidity at inhibiting binding of tritiated dihydroalprenolol (3H-DHA) to beta2ARs would increase with increasing length of alkyl substituents and would demonstrate stereospecificity. Specific binding of 3H-DHA to human beta2ARs was assayed in the presence of six different members of the 1-alkyl-2,6-pipecoloxylidide class of local anesthetics (including mepivacaine, ropivacaine, and bupivacaine), the R(+) and S(-) bupivacaine enantiomers, lidocaine, prilocaine, etidocaine, procaine, and tetracaine. Avidity of binding to beta2ARs increased with increasing length of the alkyl chain (pKi values = 2.4, 3.6, 4.3, 4.1, 4.1, 5.9 for the methyl [mepivacaine], ethyl, S(-)propyl [ropivacaine], butyl [bupivacaine], pentyl, and octyl derivatives, respectively). We found no evidence for bupivacaine stereospecificity (pKi values = 4.3 and 4.9 for the S(-) and R(+) isomers, respectively). Other amide and ester local anesthetics also showed increasing potency with increasing length of alkyl substituents (pKi values = 3.6, 3.8, and 4.3 for lidocaine, prilocaine, and etidocaine; 4.2 and 5.6 for procaine and tetracaine, respectively). The correlation between increased inhibition of beta2AR binding and alkyl chain length resembles the correlation between local anesthetic potency at nerve block and increased alkyl chain length. The lack of clear stereospecificity is consistent with the relatively low potency these agents demonstrate at inhibition of beta2AR binding. Finally, the relatively potent inhibition of beta2ARs by etidocaine, tetracaine, and bupivacaine suggests that their propensity for cardiovascular depression after accidental intravenous overdose could result from beta2AR or beta1AR blockade and inhibition of cAMP production. IMPLICATIONS: Local anesthetics demonstrate a rank order of avidity for displacing ligands from beta2-adrenergic receptors such that larger molecules displace ligands at lower concentrations than smaller local anesthetic molecules. This relationship between molecular size and receptor avidity could explain the greater propensity for cardiovascular toxicity of relatively large local anesthetics such as bupivacaine.

Adrenergic beta-2 Receptor Antagonists↗

Enhancement of analgesia from systemic opioid in humans by spinal cholinesterase inhibition.

Intravenous opioids cause analgesia and increase release of ACh in spinal cord dorsal horn in animals, and these effects are enhanced by intrathecal neostigmine injection. The purpose of the current study was to test whether intrathecal neostigmine enhanced analgesia and increased cerebrospinal fluid concentrations of ACh over those induced by i.v. alfentanil in volunteers, and also to test whether neostigmine enhanced alfentanil-induced side effects. After human studies committee approval, 40 healthy volunteers received an intrathecal injection of saline or neostigmine (50, 100 or 200 microg) followed in 60 min by a computer-controlled, stepped i.v. infusion of alfentanil to escalating targeted plasma concentrations. Pain report to hand and foot immersion in ice water, sedation, nausea, weakness, vital signs, end-tidal CO2 and oxyhemoglobin saturation were measured 60 min after spinal injection and at the end of each 20-min alfentanil infusion. Cerebrospinal fluid was sampled once after drug administration. Intrathecal neostigmine alone caused analgesia in the foot but not in the hand, and was accompanied by leg weakness, whereas IV alfentanil alone caused equivalent analgesia in both the hand and the foot and was accompanied by nausea, sedation, increased end-tidal CO2 and decreased oxyhemoglobin saturation. Neostigmine enhanced analgesia but not respiratory effects induced by i.v. alfentanil; it also enhanced nausea and sedation. Intravenous alfentanil increased cerebrospinal fluid ACh concentration, and neostigmine enhanced this change. These data in humans are consistent with a spinal cholinergic mechanism of i.v. opioid analgesia. Because neostigmine enhances both analgesia and side effects induced by i.v. alfentanil, the clinical utility of their use in combination will depend on the relative strength of these interactions.

Acetylcholine↗

Oxygen administration during transport and recovery after outpatient surgery does not prevent episodic arterial desaturation.

STUDY OBJECTIVE: To compare the efficacy of two different oxygen (O2) delivery systems in preventing episodic arterial desaturation in the immediate postoperative period. STUDY DESIGN: Randomized, prospective, nonblinded comparison in patients. SETTING: Operating room and postanesthesia care unit (PACU) of a university outpatient surgery center. PATIENTS: 100 ASA status I and II adults, male and female, age greater than 18 years, undergoing outpatient surgical procedures not involving the upper airway. INTERVENTIONS: Group I received supplemental O2 administered by bag-valve-mask during transport, followed by 40% face shield in the PACU. Group 2 received supplemental O2 by nasal cannula at 4 L/min both during transport and during PACU stay. MEASUREMENTS AND MAIN RESULTS: Arterial O2 saturation (SpO2) was collected by computer from a recording pulse oximeter at 15-second intervals beginning before extubation and continuing until O2 administration was discontinued in PACU. Neither mode of therapy was successful in completely eliminating arterial desaturation defined as SpO2 less than 90%, nor was there any difference in efficacy between the two treatment groups. Group 1 had 8 patients desaturate on 9 different occasions (5 times during transport, 4 times in PACU). Group 2 had 5 patients desaturate on 9 different occasions (4 times during transport, 5 times in PACU). CONCLUSION: Routine O2 administration during transport and PACU stay did not abolish episodic desaturation, even in healthy patients undergoing minor surgical procedures. Given the marked difference in acquisition cost, it would appear that O2 administration by nasal cannula is a more cost-effective alternative for routine postoperative O2 administration in certain groups of patients undergoing general anesthesia for outpatient surgery.

Adult↗

Relative efficacy and potency of beta-adrenoceptor agonists for generating cAMP in human lymphocytes.

BACKGROUND: Dopexamine and dobutamine are traditionally described as having primarily beta 2-adrenergic agonist properties; norepinephrine is generally classified as beta 1-selective; and epinephrine, isoproterenol, and dopamine are considered mixed beta 1- and beta 2-receptor agonists. Much of this selectivity is designated from studies conducted with intact cardiovascular systems in which indirect actions (eg, norepinephrine release from presynaptic nerve terminals) are not separated from direct agonist-receptor interactions. OBJECTIVE: To assess the relative efficacy and potency of dopamine, dobutamine, dopexamine, epinephrine, isoproterenol, and norepinephrine for directly stimulating cyclic adenosine monophosphate (cAMP) production in human lymphocytes, a model of beta 2-adrenoceptor function. DESIGN: Open-label, prospective paired studies of lymphocytes from nine healthy human volunteers (seven men). SETTING: Experimental laboratory of a large, university-affiliated medical center. INTERVENTIONS: Concentration-response curves were generated for each adrenergic agonist; maximal cAMP production was used to compare efficacy. For the agonists that more than doubled basal cAMP concentrations, EC50 calculations were used to compare potency. MEASUREMENTS AND MAIN RESULTS: Isoproterenol and epinephrine produced the greatest concentrations of cAMP of the agonists tested. cAMP production was increased by isoproterenol at concentrations 1/10 to 1/10,000 that of the other agonists. Norepinephrine stimulated cAMP production only one third as much as epinephrine and isoproterenol, but more than double the level of dopamine, dobutamine, and dopexamine. EC50 concentrations for norepinephrine were 10-fold higher than epinephrine and 50-fold higher than isoproterenol. CONCLUSIONS: Epinephrine and isoproterenol are the most efficacious and potent direct-acting beta 2-adrenergic receptor agonists using this lymphocyte cAMP model. Norepinephrine exhibits significant effects on the beta-receptors on lymphocytes, suggesting beta 2-adrenoceptor effects with high concentrations of this drug. The very low cAMP levels generated by dopamine, dobutamine, and dopexamine (even in high concentrations) support other evidence that these agents have little direct effect on the beta 2-adrenoceptor.

Adrenergic beta-Agonists↗

A pharmacokinetic and pharmacodynamic evaluation of milrinone in adults undergoing cardiac surgery.

Milrinone can reverse acute postischemic myocardial dysfunction after cardiopulmonary bypass, although neither the appropriate bolus dose nor its pharmacokinetics has been established for cardiac surgical patients. Consenting patients undergoing cardiac surgery received milrinone (25, 50, or 75 micrograms/kg) in an open-label, dose-escalating study if their cardiac index was < 3 L.min-1.m-2 after separation from bypass. Heart rate, mean arterial blood pressure, pulmonary capillary wedge pressure, and cardiac index were determined before and after the administration of milrinone. Timed blood samples were obtained for measurement of milrinone plasma concentrations and pharmacokinetic analysis. Twenty-nine of 60 consenting patients had cardiac indices < 3 L.min-1.m-2 after separation from bypass, received milrinone, and completed the protocol. All three bolus doses of milrinone significantly increased cardiac index. The 50- and 75-micrograms/kg doses produced significantly larger increases in cardiac index than the 25-micrograms/kg dose; however, the 75-micrograms/kg dose did not produce a significantly larger increase in cardiac index than did the 50-micrograms/kg dose. Two of 10 patients receiving milrinone 25 micrograms/kg, but no patient receiving either 50 or 75 micrograms/kg, required early epinephrine rescue when the cardiac index failed to increase by > 15%. The 75-micrograms/kg dose was associated with a case of ventricular tachycardia. The three-compartment model better described milrinone drug disposition than the two-compartment model by both visual inspection and Schwartz-Bayesian criterion. There was only limited evidence of dose-dependence, so data from all three doses are reported together (and normalized to the 50-micrograms/kg dose). Data from one patient was discarded (samples mislabeled). Using mixed-effects nonlinear regression (for n = 28), the following volumes were determined for the three compartments: V1 = 11.1 L, V2 = 16.9 L, and V3 = 363 L. Similarly, the following clearances were estimated for the three compartments: Cl1 = 0.067 L/min, Cl2 = 1.05 L/min, and Cl3 = 0.31 L/min. The 50-micrograms/kg loading dose appeared more potent than the 25-micrograms/kg dose, and, as potent, but with possibly fewer side-effects than the 75-micrograms/kg dose. The short context-sensitive half-times of 6.7 or 10.2 min after 1- or 10-min bolus infusions underscore the need for prompt institution of a maintenance infusion when milrinone concentrations must be maintained.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Predictive value of blood clotting tests in cardiac surgical patients.

This study prospectively evaluated numerous tests of clotting function in 897 consecutive adult cardiac surgical patients over 18 months. This included coronary operation, valve replacement, and reoperative patients. The tests included activated clotting time, activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen, fibrin/fibrinogen degradation products, platelet count, and Duke's earlobe bleeding time. Other variables such as age, sex, and cardiopulmonary bypass duration were included in the multivariate analysis. Statistically significant correlations were found between 16-hour mediastinal drainage and activated partial thromboplastin time, fibrinogen, activated clotting time, fibrin/fibrinogen degradation products, platelet count, and prothrombin time. Scatter plots indicate that these relationships, although statistically significant, had little predictive value and were largely significant as a result of the large number of patients in each group, which permitted weak correlations to reach statistical significance. The best multivariate model constructed could explain only 12% of the observed variation in postoperative blood loss. Because the predictive values of the tests are so low, it does not appear sensible to screen patients routinely using these clotting tests shortly after cardiopulmonary bypass.

Adult↗

A laboratory comparison of three pulmonary artery oximetry catheters.

BACKGROUND: Measurement of mixed venous hemoglobin oxygen saturation via catheters employing reflectance spectrophotometry has been available for more than 10 yr. Despite numerous clinical reports that have presented data showing the poor accuracy of these devices when used clinically, they are still widely used in clinical care. The reason for lack of agreement with measurements made using bench spectrophotometry is unclear. The purpose of this study is to define the performance limitations of three hemoglobin oxygen saturation catheters (Oximetrix 3, SAT-2, and HEMOPRO2) in a controlled laboratory environment using a blood flow loop primed with fresh whole human blood as a model. Our hypothesis is that the performance limitations of these devices represent inherent limitations in the technology, not error introduced by patient anatomy and physiology. METHODS: Blood was equilibrated in a flow loop to four analytic gas mixtures designed to achieve oxygen saturation of approximately 50%, 60%, 70%, and 80%, respectively, with carbon dioxide tension, pH, and temperature held constant. Saturation readings from the catheters were collected on-line by microcomputer. Periodic blood samples were withdrawn from the flow loop for analysis on a bench spectrophotometer and subsequent comparison with catheter-derived values. RESULTS: By all measures, performances of the Oximetrix 3 and SAT-2 systems were comparable (all data are presented as percent saturation unless otherwise noted); bias +/- precision was 3.20 +/- 2.47 and -1.25 +/- 3.36, respectively, versus -9.97 +/- 7.05 for the HEMOPRO2. The 95% confidence limits based on intracatheter variability were +/- 3.49, +/- 2.90, and +/- 9.13 for the Oximetrix 3, SAT-2, and HEMOPRO2, respectively. The 95% confidence limits based on total variability, although similar for Oximetrix 3 (+/- 4.83) and SAT-2 (+/- 6.59), were larger for the HEMOPRO2 (+/- 13.82). The 95% confidence intervals for agreement between catheter brands were -2.14, 11.04 (Oximetrix 3 - SAT-2); -0.18, 26.52 (Oximetrix 3 - HEMOPRO2) and -5.24, 22.68 (SAT-2 - HEMOPRO2). CONCLUSIONS: While the Oximetrix 3 and SAT-2 may be acceptable as continuous monitors used to detect changes or trends, none of the three systems is equivalent to conventional bench oximetry for the measurement of hemoglobin oxygen saturation.

Catheters, Indwelling↗

Performance characteristics and interanalyzer variability of PO2 measurements using tonometered human blood.

We performed a side-by-side comparison of the ability of four blood gas analyzers (IL-1312, Corning-178, AVL-995, and ABL-330) to measure PO2 across a wide range under controlled laboratory conditions. Samples of fresh whole human blood, tonometered with analytic quality gas, were prepared with partial pressures of oxygen from 0 to 283 mm Hg. Fifteen determinations were made at 16 levels of tonometric PO2 (tPO2) on each of the four blood gas analyzers. The bias, precision, and root mean squared error (RMSE) of the PO2 measurement relative to tPO2 were determined for each analyzer at each tPO2 level. Mean bias and precision across the range tested were 2.78 +/- 1.29 mm Hg (IL), -0.35 +/- 1.91 (Corning), 2.14 +/- 1.43 (AVL), and 3.00 +/- 1.47 (ABL). RMSE was 3.28, 2.61, 3.57, and 2.41 for IL, AVL, ABL, and Corning, respectively. Percent RMSE (RMSE/tPO2 x 100%), ranged from 0.9% (AVL at 75 mm Hg PO2 and IL at 283 mm Hg tPO2) to 9.1% (IL at 29 mm Hg tPO2). Three analyzers (AVL, ABL, and Corning) showed a statistically significant (p < 0.0001) correlation between RMSE and tPO2, and no correlation between percent RMSE and tPO2. This demonstrates that, for these instruments, accuracy is a function of the magnitude of the tPO2 value. IL did not show a significant correlation between RMSE and tPO2 but did demonstrate a significant negative correlation (r = -0.78, p > 0.001) between percent RMSE and tPO2, indicating that, for this analyzer, accuracy is not a function of tPO2. The differences in PO2 measurements between pairs of analyzers were also examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗

Significance of gaseous microemboli in the cerebral circulation during cardiopulmonary bypass in dogs.

BACKGROUND: Gaseous microemboli during cardiac surgery may damage the brain by reducing cerebral blood flow (CBF). We examined whether the incidence of gaseous microemboli during 150-minute hypothermic (28 degrees C) cardiopulmonary bypass (CPB) adversely affects CBF (radioactive microspheres). METHODS AND RESULTS: Thirty anesthetized dogs were placed on CPB using bubble oxygenators with 50% O2 (n = 10) or 100% O2 (n = 10) to produce a wide range in the number of gaseous microemboli or membrane oxygenators with 50% O2 (n = 10) to avoid microemboli. The number of carotid artery microemboli occurring in a 1-minute interval was counted using a 5-MHz Doppler probe every 15 minutes for the duration of CPB, which lasted 258 +/- 5 minutes. With bubbled 100% O2, the number of microemboli averaged 4.1 +/- 1.7 emboli per minute on normothermic bypass and increased with cooling to 18.3 +/- 4.9 emboli per minute (P < .001). With bubbled 50% O2, the microemboli number was greater on normothermic bypass (19.8 +/- 9.8 emboli per minute, P = .0653 compared with bubbled 100% O2) and increased with cooling (100.3 +/- 18.7 emboli per minute, P < .001) to a greater extent than with bubbled 100% O2 (P < .001). In contrast, with membrane 50% O2, the emboli number was small (0.6 +/- 0.1 emboli per minute) and did not change with CPB temperature. CBF values were not reduced after termination of CPB, even when compared with prebypass values, being 48.3 +/- 7.5 mL/min per 100 g (bubbled 50% O2), 49.6 +/- 4.1 mL/min per 100 g (bubble 100% O2), and 44.5 +/- 2.8 mL/min per 100 g (membrane 50% O2, P = .7581). Similarly, regional perfusion to the cerebellum, hippocampus, and caudal brainstem was not adversely affected by microemboli. After CPB, cortical biopsies demonstrated no difference among groups with respect to lactate (P = .1753), energy charge (P = .5179), and brain water content (P = .939). Retinal histopathology indicated no differences among groups. CONCLUSIONS: These results indicate that: (1) the incidence of gaseous microemboli during hypothermia increases when a bubble oxygenator is used, and (2) global CBF and regional brain perfusion are not adversely affected by numerous gaseous microemboli.

Animals↗

Maturational changes in F waves in growing chickens.

The F waves evoked by supramaximal stimulation of distal tibial nerve were evaluated in chickens aged 2 to 15 weeks. Latency of these potentials increased from mean +/- SD 11.4 +/- 0.12 ms at week 2 to mean 12.88 +/- 0.65 ms at week 15. The F-wave latency increased linearly with age. When this latency was corrected for a standard distance to compensate for the increasing limb length with age, latency decreased with maturity.

Aging↗

Age-related effects on motor nerve conduction velocity in chickens.

Compound motor-nerve action potentials evoked by supramaximal stimulation of the proximal and distal aspects of the tibial nerve were evaluated in chickens 1 to 15 weeks old. Motor-nerve conduction velocity increased from a mean of 22.6 m/s at week 1 to a mean of 52.7 m/s at week 15. The increase in conduction velocity was greatest for the first few weeks, and reached a plateau at 10 weeks. Subcutaneous limb temperature, limb length, and proximal latency measurements also increased with age; however, distal latency measurements were not significantly influenced by age. A quadratic equation was calculated to predict mean motor-nerve conduction velocity for maturing chickens.

Action Potentials↗

Efficacy of chloramphenicol, enrofloxacin, and tetracycline for treatment of experimental Rocky Mountain spotted fever in dogs.

Dogs were experimentally inoculated with Rickettsia rickettsii to characterize the comparative efficacies of chloramphenicol, enrofloxacin, and tetracycline for the treatment of Rocky Mountain spotted fever (RMSF). All three antibiotics were equally effective in abrogating the clinical, hematologic, and vascular indicators of rickettsial infection. Antibiotic treatment for 24 h was sufficient to decrease the rickettsemia to levels below detection by Vero cell culture. Early treatment with all three antibiotics resulted in a similar decrease in antibody titer, but acute and convalescent serum samples taken at appropriate times would have still facilitated an accurate diagnosis of RMSF in all but one dog, which did not seroconvert. We conclude that chloramphenicol, enrofloxacin, and tetracycline are equally efficacious for treating experimental canine RMSF.

Animals↗

Human islet cell induced T cell lines and clones from diabetic children.

T cell lines and clones were derived by coculturing peripheral blood mononuclear cells from young children with newly diagnosed insulin dependent diabetes mellitus (IDDM) with sonicates of HLA-DR haploidentical human islet cells. These cells proliferated in response to human islet cell sonicates but failed to do so when stimulated with sonicates of human exocrine pancreas or thyroid gland. Preparations of islet cells obtained by repeated freezing and thawing also stimulated proliferation of the lines but purified membrane or protein preparations of the islet failed to induce proliferation, suggesting that determinants recognized by T cells were lost on further purification. This method of deriving T cell lines and clones appears to be significantly easier and quicker than non-antigen cloning using anti CD3.

Antigens, Differentiation↗

Traumatic spondylolisthesis of the axis in a patient presenting with torticollis. A case report.

In a 34-year-old man with an acute traumatic spondylolisthesis (ATS) of the axis, the presenting physical sign was severe torticollis associated with reactive spasm of the right sternomastoid muscle. Computed axial tomography (CAT) was useful both in assessing the nature of ATS (which involved more displacement of the axis fracture and adjacent soft-tissues on the right side of the neck) and in ascertaining reduction, realignment, and healing. The reduction was sustained by halo-vest immobilization.

Adult↗

Atraumatic removal of a well-fixed porous ingrowth hip prosthesis.

The authors describe their experience in the removal of a firmly fixed porous coated femoral component of a bipolar hip prosthesis in a 36-year-old man on a methadone maintenance program. The uncemented prosthesis had been implanted for 15 months when the patient complained of hip pain. A methicillin-resistant Staphylococcus aureus infection was found in the hip joint. It was decided to remove the femoral component when the infection failed to respond to irrigation, debridement, and several weeks of intravenous antibiotic therapy and because the patient developed early signs of impending renal compromise and a deterioration of his general nutritional status. The technique for separating and removing the well-fixed porous ingrowth component from its intramedullary environment without damaging the cortical tube of the proximal femur is described.

Adult↗