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Biomedical subjects

C L Hamilton

Publications and source records attributed to C L Hamilton.

At least 19 recordsLinked to original sources

Intrathecal sufentanil produces sensory changes without hypotension in male volunteers.

BACKGROUND: Intrathecally administered sufentanil is frequently associated with hypotension and sensory changes in women undergoing labor. In this study, the authors examined whether intrathecally administered sufentanil has similar effects in pain-free individuals with low concentrations of progesterone (i.e., male volunteers). METHODS: Ten male volunteers were randomly assigned to receive an intrathecal injection of either 10 microg sufentanil or saline in a double-blind fashion. Blood pressure, heart rate, oxyhemoglobin saturation, and temperatures from the body core and skin of the calf and ipsilateral great toe were recorded. Cold and pin prick sensation, motor block, and visual analogue scores for sedation, pruritus, and nausea also were assessed. Current perception thresholds using the Neurometer current perception threshold instrument (Neurotron, Inc., Baltimore, MD) were determined for three frequencies (2,000, 250, and 5 Hz, corresponding to stimulation of Abeta, Adelta, and C fibers, respectively) on the upper and lower extremities. RESULTS: Pruritus and sensory changes to pin prick and cold occurred in the sufentanil group but not the saline group. Neither group had a significant change in blood pressure, heart rate, oxyhemoglobin saturation, sedation, or core temperature. There was a clinically insignificant difference in the calf minus toe temperature index between the saline and sufentanil groups. There was a small increase in the current perception thresholds at 250 Hz in the sufentanil group. CONCLUSIONS: Intrathecally administered sufentanil did not affect blood pressure in male volunteers. The other effects of sufentanil, however, were similar to those observed in women undergoing labor. This suggests that the hypotension occurring in these women after intrathecally administered sufentanil is secondary to relief of pain, rather than to a sympathectomy.

Adolescent↗

Obstetric postanesthesia care unit stays: reevaluation of discharge criteria after regional anesthesia.

BACKGROUND: Obstetric patients may have long postanesthesia care unit (OB-PACU) stays after surgery because of residual regional block or other conditions. This study evaluated whether modified discharge criteria might allow for earlier discharge without compromising patient safety. METHODS: Data were prospectively collected for 6 months for all patients (N=358) who underwent cesarean section or tubal ligation and recovered in the OB-PACU. Regional anesthesia was used in 94% of patients. The duration of anesthesia and PACU stays, the presence and treatment of events in the PACU, and the regression of neural blockade were recorded. Discharge from the OB-PACU required a 60-min minimum stay, stable vital signs, adequate analgesia, and ability to flex the knees. After completion of prospective data collection, events that kept patients in the PACU after 60 min were reevaluated as to whether patients needed to stay in the PACU for medical reasons. "Needed to stay" events included bleeding, cardiorespiratory problems, sedation, dizziness, and pain. "Safe to leave" conditions included pruritus, nausea, and residual neural blockade. The cumulative duration of OB-PACU stays not clearly justifiable for medical reasons was calculated. RESULTS: Residual block and spinal opioid side effects accounted for the majority of "unnecessary" stays. Annually, 429 h of PACU time could have been saved using the revised criteria. Complications did not develop subsequently in any patient deemed "safe to leave." CONCLUSIONS: In many obstetric patients, the duration of PACU stays could safely be shortened by continuing observation in a lower-acuity setting. This may result in greater flexibility and more efficient use of nursing personnel.

Adult↗

Changes in the position of epidural catheters associated with patient movement.

BACKGROUND: Epidural catheter movement has been noted with change of patient position and can result in inadequate anesthesia. This study was designed to measure movement and to develop a technique that minimizes catheter displacement. METHODS: In 255 parturients requesting epidural anesthesia for labor or cesarean section, a multiorificed lumbar epidural catheter was inserted with the patient in the sitting flexed position. The distance to the epidural space, length of catheter inserted, and amount of catheter position change as the patient moved from the sitting flexed to sitting upright and then to the lateral decubitus position were measured before the catheter was secured to the skin. Adequacy of analgesia, the need for catheter manipulation, and whether the patient was considered obese were noted. Data were grouped according to body mass index (BMI): < 25, 25-30, and > 30 kg/m2. RESULTS: The groups did not differ with respect to the length of catheter initially inserted or changes in catheter position between initial taping and removal. The distance to the epidural space differed significantly among the groups, increasing with greater BMI. Catheters frequently appeared to be drawn inward with position change from the sitting flexed to lateral decubitus position, with the greatest change seen in patients with BMI > 30. Only nine catheters were associated with inadequate analgesia, four of which were replaced. No analgesic failures occurred in the BMI > 30 group. In patients judged by the anesthesiologist to be obese or to have an obese back, BMI was greater, and distance to the epidural space and the magnitude of catheter movement with position change were greater than in those who were not obese. CONCLUSIONS: Epidural catheters moved a clinically significant amount with reference to the skin in all BMI groups as patients changed position. If catheters had been secured to the skin before position change, many would have been pulled partially out of the epidural space. To minimize the risk of catheter displacement, particularly in obese patients, we recommend that multiorificed catheters be inserted at least 4 cm into the epidural space and that patients assume the sitting upright or lateral position before securing the catheter to the skin.

Anesthesia, Obstetrical↗

Intrathecal sufentanil for labor analgesia does not cause a sympathectomy.

BACKGROUND: Intrathecal sufentanil (ITS) is frequently used to provide analgesia during labor. Decreases in blood pressure and sensory changes in this circumstance suggest that ITS may have a local anesthetic effect and thus cause a sympathectomy. To determine whether ITS given to laboring women causes a sympathectomy, the authors evaluated central and lower extremity temperature changes after ITS administration. These findings were compared with those in a control group of women having spinal anesthesia with bupivacaine for elective cesarean section in whom an extensive sympathectomy was expected. METHODS: Twenty parturients classified as American Society of Anesthesiologists' physical status 1 or 2 had temperatures measured centrally, at the calf, and at the great toe at frequent intervals after receiving 10 microg ITS for labor analgesia (sufentanil group, n = 10), or hyperbaric bupivacaine 12 mg in their spinal anesthetic for cesarean section (bupivacaine group, n = 10). Calf-to-toe temperature indices (C-T) were calculated by subtracting toe temperature from calf temperature. A decrease in this index means that the toe had warmed compared with the calf and is an indication of vasodilation and a sympathectomy. RESULTS: There was no significant change in the C-T indices or central temperature in the sufentanil group, but the C-T indices and central temperature decreased significantly in the bupivacaine group. CONCLUSIONS: The decreases in the C-T index and central temperature in the bupivacaine group indicate the presence of a sympathectomy. The lack of change in the C-T indices and central temperature in the sufentanil group indicates that no significant vasodilation occurred. Therefore, the decrease in blood pressure seen after ITS administration for labor analgesia is unlikely to be the result of a sympathectomy.

Adult↗

Column-switching high-performance liquid chromatographic method for the determination of a thymidylate synthase inhibitor, LY231514, an investigational agent for the treatment of solid tumors, in human plasma.

A reversed-phase, column-switching high-performance liquid chromatographic (HPLC) method is described for the determination of a new thymidylate synthase inhibitor in human plasma. The compound and an internal standard are extracted from plasma using a Certify II solid-phase cartridge. Extracts are evaporated to dryness and the residue is reconstituted with mobile phase buffer. The analytes are separated from polar interferences and buffer salts originating from the elution step on a 4-mm YMC Basic pre-column. The fraction containing the analytes is further separated on a 25-cm YMC Basic column. The analytes are detected by their absorbance at 250 nm. The limit of quantitation is 10 ng/ml. The method is linear from 10 ng/ml to 80 micrograms/ml using three standard curve ranges. Validation studies for all three ranges show the method to be reproducible. The method has been successfully used to support pharmacokinetic studies.

Antineoplastic Agents↗

Sensitive liquid chromatographic method for the determination of a specific M1 agonist, LY246708, an investigational agent with potential for the treatment of Alzheimer's disease, in human plasma.

A reversed-phase HPLC method is reported for the determination of a new M1 agonist, LY246708, in human plasma. The compound and an internal standard were extracted from plasma with hexane at basic pH. The organic extract was evaporated to dryness and the residue was reconstituted with mobile phase [0.5% diethylamine (pH 3, adjusted with phosphoric acid)-acetonitrile (70:30, v/v)]. The analytes were separated from endogenous substances on a Zorbax CN column; the effluent was monitored by measuring its absorbance at 296 nm. The limit of quantification was determined at 1.5 ng/ml and the response was linear from 1.5 to 20 ng/ml. Validation studies showed the method to be both repeatable and reproducible. Its robustness was demonstrated by transfer between analytical laboratories and continued use in support of pharmacokinetic studies and therapeutic monitoring of the compound.

Alzheimer Disease↗

Determination of dapoxetine, an investigational agent with the potential for treating depression, and its mono- and di-desmethyl metabolites in human plasma using column-switching high-performance liquid chromatography.

A column-switching high-performance liquid chromatographic (HPLC) method is described for the determination of dapoxetine and its mono- and di-desmethyl metabolites in human plasma. The analytes, including an internal standard, were extracted from plasma at basic pH with hexane-ethyl acetate. The organic extract was evaporated to dryness and the residue reconstituted with acetonitrile. The analytes were separated from late-eluting endogenous substances on a Zorbax RX-C8 pre-column. The front-cut fraction containing the analytes was further separated on a second RX-C8 column. The analytes were detected by their native fluorescence, using excitation and emission wavelengths of 230 and 330 nm, respectively. The limit of quantitation was determined to be 20 ng/ml, and the response was linear from 20 to 200 ng/ml. The method has been successfully applied to human plasma samples in a Phase I study.

Antidepressive Agents↗

Ni(II) and Ni(I) forms of pentaalkylamide derivatives of cofactor F430 of Methanobacterium thermoautotrophicum.

A series of pentaalkylamide forms of F430 and of its 12,13-diepimer have been generated and characterized. Carbodiimide-assisted N-hydroxysulfosuccinimide activation of all five peripheral carboxylates of the F430 macrocycle allows nucleophilic attack by a number of primary amines (RNH2, R- = CH3-, CH3CH2-, CF3CH2-, CH3(CH2)3-) generating the pentaalkylamide derivatives. The identity of each derivative has been verified by fast-atom bombardment mass spectrometry (FAB-MS). The solubility of these derivatives in aprotic organic solvents varies as the amine alkyl substituent (R-) is changed. Electrochemical measurements have shown that the Ni(II/I) reduction potentials in N,N-dimethylformamide (DMF) are approximately -1 V (Ag/AgCl). Reduction by sodium amalgam in THF generates the Ni(I) form of the F430 diepimer pentabutylamide. The visible and EPR spectra of this Ni(I) species are very similar to the corresponding spectra of Ni(I) F430M (Jaun, B. and Pfaltz, A. (1986) J. Chem. Soc. Chem. Commun. 1327-1329.).

Amides↗

Racial differences in attitudes toward hospice care.

Two-hundred and fifty three adults in the Atlanta area completed a telephone survey regarding prospective personal use of hospice services. Race was found to be the only personal attribute relevant to a predisposition to use hospice care. Whites were more likely than blacks to have attitudes conducive to the choice of hospice care. Although there is evidence in the literature that black Americans are less likely to use hospice care than are white Americans, there are not yet detailed explanations of personal differences in attitudes toward using hospice care. This article suggests themes for future research on possible racial differences in attitudes toward use of hospice care.

Adult↗

Union dynamics in nursing.

Predictions of union growth among registered nurses may very well depend on hospital and nursing management's response to nurses' dissatisfaction with conditions of employment. The authors discuss federal regulations and other factors which are shaping unionization in nursing.

American Hospital Association↗

The magnetic and electronic properties of Methanobacterium thermoautotrophicum (strain delta H) methyl coenzyme M reductase and its nickel tetrapyrrole cofactor F430. A low temperature magnetic circular dichroism study.

Variable temperature magnetic circular dichroism (MCD) spectroscopy has been used to characterize the magnetic and electronic properties of the Ni(II) tetrapyrrole, F430, which is the cofactor of the S-methyl coenzyme M methylreductase enzyme from Methanobacterium thermoautotrophicum (strain delta H). 4-Coordinate forms are found to be diamagnetic (S = 0 ground state), whereas 6-coordinate forms are paramagnetic (S = 1 ground state). MCD studies, together with parallel low temperature UV-visible absorption and resonance Raman investigations, show that the equilibrium distribution of 4-coordinate square-planar and 6-coordinate bis-aquo forms of the native isomer of F430 in aqueous solution is affected by both temperature and the presence of glycerol. In the presence of 50% glycerol, the 12,13-diepimer of F430 is shown to be partially 6-coordinate in frozen solution at low temperature. Low temperature MCD magnetization data allow the determination of the axial zero-field splitting (D) of the S = 1 ground state of bis-ligand complexes of F430. The value of D is sensitive to the nature of the Ni(II) axial ligands: bis-aquo F430, D = +9 +/- 1 cm-1; bis-imidazole F430, D = -8 +/- 2 cm-1. Measurement of D = +10 +/- 1 cm-1 for F430 in the methylreductase holoenzyme argues strongly against histidine imidazole coordination to Ni(II) in the enzyme. The possible existence of alcoholic or phenolic oxygen-containing ligands (serine, threonine, tyrosine, water) to Ni(II) in the enzyme-bound cofactor is discussed.

Circular Dichroism↗

Structural and spectroscopic characterization of exogenous ligand binding to isolated factor F430 and its configurational isomers.

Binding of axial ligands to the nickel(II) of isolated factor F430 from the methyl reductase enzyme of Methanobacterium thermoautotrophicum is demonstrated. Evidence of bis-ligand coordination is obtained from the x-ray absorption, optical, and resonance Raman spectral characterization of F430 and its 12,13-diepimeric isomer in the presence of a large excess of cyanide, pyridine, or 1-methylimidazole. Significant broadening and 5-10-nm red shifts of the main 430-nm optical absorption band and shifts of up to 30 cm-1 for the high-frequency Raman lines are observed upon coordination of these axial ligands. The Raman spectra of native F430 and the diepimer with a particular axial ligand are nearly identical. Nickel x-ray absorption edge spectra of the diepimer in the absence and presence of these exogenous ligands are indicative of conversion from a square-planar to a tetragonally distorted octahedral geometry. Analyses of the nickel extended x-ray absorption fine structure data for the ligated diepimer complexes yield detailed structural information for these complexes. Implications of these data with respect to the enzymatic mechanism and the structure of the enzyme-bound factor are discussed.

Cyanides↗