bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose Response of Intravenous Heparin on Markers of Thrombosis during Primary Total Hip Replacement
Authors: Sharrock Nigel E. , Go George , Sculco Thomas P. , Salvati Eduardo A. , Westrich Geoffrey H. , Harpel Peter C. 
Published: November 2003

Background
Thrombogenesis in total hip replacement (THR) begins during surgery on the femur. This study assesses the effect of two doses of unfractionated intravenous heparin administered before femoral preparation during THR on circulating markers of thrombosis.

Methods
Seventy-five patients undergoing hybrid primary THR were randomly assigned to receive blinded intravenous injection of either saline or 10 or 20 U/kg of unfractionated heparin after insertion of the acetabular component. Central venous blood samples were assayed for prothrombin F1+2 (F1+2), thrombin-antithrombin complexes (TAT), fibrinopeptide A (FPA), and D-dimer.

Results
No changes in the markers of thrombosis were noted after insertion of the acetabular component. During surgery on the femur, significant increases in all markers were noted in the saline group (P < 0.0001). Heparin did not affect D-dimer or TAT. Twenty units per kilogram of heparin significantly reduced the increase of F1+2 after relocation of the hip joint (P < 0.001). Administration of both 10 and 20 U/kg significantly reduced the increase in FPA during implantation of the femoral component (P < 0.0001). A fourfold increase in FPA was noted in 6 of 25 patients receiving 10 U/kg of heparin but in none receiving 20 U/kg (P = 0.03). Intraoperative heparin did not affect intra- or postoperative blood loss, postoperative hematocrit, or surgeon's subjective assessments of bleeding. No bleeding complications were noted.

Conclusions
This study demonstrates that 20 U/kg of heparin administered before surgery on the femur suppresses fibrin formation during primary THR. This finding provides the pathophysiologic basis for the clinical use of intraoperative heparin during THR.
Pharmacokinetics of Prilocaine after Intravenous Administration in Volunteers
Authors: van der Meer Auke Dirk , Burm Anton G. L. , Stienstra Rudolf , van Kleef Jack W. , Vletter Arie A. , Olieman Wim 
Published: November 2003

Background
Prilocaine exists in two stereoisomeric configurations, the enantiomers S(+)- and R(-)-prilocaine. The drug is clinically used as the racemate. This study examined the pharmacokinetics of the enantiomers after intravenous administration of the racemate.

Methods
Ten healthy male volunteers received 200 mg racemic prilocaine as a 10-min intravenous infusion. Blood samples were collected for 8 h after the start of the infusion. Plasma concentrations were measured by stereoselective high-performance liquid chromatography (HPLC). Unbound fractions of the enantiomers in blank blood samples, spiked with racemic prilocaine, were determined using equilibrium dialysis.

Results
The unbound fraction of R(-)-prilocaine (mean +/- SD, 70%+/-8%) was smaller (P < 0.05) than that of S(+)-prilocaine (73%+/-5%). The total plasma clearance of R(-)-prilocaine (2.57+/-0.46 l/min) was larger (P < 0.0001) than that of S(+)-prilocaine (1.91+/-0.30 l/min). The steady-state volume of distribution of R(-)-prilocaine (279+/-94 l) did not differ from that of S(+)-prilocaine (291+/-93 l). The terminal half-life of R(-)-prilocaine (87+/-27 min) was shorter (P < 0.05) than that of S(+)-prilocaine (124+/-64 min), as was the mean residence time of R(-)-prilocaine (108+/-30 min) compared with S(+)-prilocaine (155+/-59 min; P < 0.005).

Conclusions
The pharmacokinetics of prilocaine are enantioselective. The difference in clearance is most likely a result of a difference in intrinsic metabolic clearance. The difference in the pharmacokinetics of the enantiomers of prilocaine does not seem to be clinically relevant.
Pharyngeal Mucosal Pressures, Airway Sealing Pressures, and Fiberoptic Position with the Intubating versus the Standard Laryngeal Mask Airway
Authors: Keller Christian , Brimacombe Joseph 
Published: November 2003

Background
The tube of the intubating laryngeal mask (ILM) is more rigid than the standard laryngeal mask airway (LMA), and the authors have tested the hypothesis that pharyngeal mucosal pressures, airway sealing pressures, and fiberoptic position are different when the two devices are compared.

Methods
Twenty anesthetized, paralyzed adults were randomly allocated to receive either the LMA or ILM for airway management. Microchip sensors were attached to the size 5 LMA or ILM at locations corresponding to the pyriform fossa, hypopharynx, base of tongue, posterior pharynx, and distal and proximal oropharynx. Mucosal pressures, airway sealing pressures, and fiberoptic positioning were recorded during inflation of the cuff from 0 to 40 ml in 10-ml increments.

Results
Airway sealing pressures were higher for the ILM (30 vs. 23 cm H2O), but epiglottic downfolding was more common (56% vs. 26%). Pharyngeal mucosal pressures were much higher for the ILM at five of six locations. Mean mucosal pressures in the distal oropharynx for the ILM were always greater than 157 cm H2O, regardless of cuff volume. There was no correlation between mucosal pressures and airway sealing pressures at any location for the LMA, but there was a correlation at three of six locations for the ILM.

Conclusions
The ILM provides a more effective seal than the LMA, but pharyngeal mucosal pressures are higher and always exceed capillary perfusion pressure. The ILM is unsuitable for use as a routine airway and should be removed after its use as an airway intubator.
Pharmacokinetic Modeling of M6G Formation after Oral Administration of Morphine in Healthy Volunteers
Authors: Lotsch Jorn , Weiss Michel , Ahne Gabi , Kobal Gerd , Geisslinger Gerd 
Published: November 2003

Background
Morphine is metabolized to two major metabolites, morphine-3-glucuronide and morphine-6-glucuronide (M6G). Under the conditions of long-term oral morphine administration, the accumulation of M6G may contribute to the analgesic effects, but it may also cause respiratory depression.

Methods
Five healthy male volunteers (ages 25-34 yr) received 90 mg MST (morphine sulfate 5H2O sustained-released tablet, equivalent to 67.8 mg oral morphine). Multiple plasma and urine samples were taken for as long as 14 and 36 h, respectively. Individual pharmacokinetics after intravenous administration of morphine and M6G were available from a previous investigation. A new model that considers the M6G-plasma profile as a sum of the input from the first-pass metabolism of morphine and the input from systemically available morphine was applied to the plasma concentration versus time curves of M6G. The concentrations of M6G at the effect site after long-term morphine administration were simulated.

Results
The fraction of morphine absorbed from the gut was 82+/-14%. Of this, 42+/-8% passed through the liver, resulting in an oral bioavailability of morphine of 34+/-9%. Of the total amount of M6G, 71+/-7% was formed during the first-pass metabolism, and 29+/-7% was formed by metabolism of systemic morphine. After 36 h, the amounts of M6G and morphine excreted in the urine were 92+/-17% and 9+/-3%, respectively. Simulation of effect-site concentrations of M6G indicated that after multiple oral dosing of morphine in patients with normal liver and renal function, M6G might reach concentrations two times greater than that of morphine.

Conclusions
M6G may contribute to the analgesic and side effects seen with long-term morphine treatment. The current model of morphine and M6G pharmacokinetics after oral administration of morphine may serve as a pharmacokinetic basis for experiments evaluating the analgesic contribution of M6G with long-term oral dosing of morphine.
Fentanyl and Morphine, but not Remifentanil, Inhibit Acetylcholine Release in Pontine Regions Modulating Arousal
Authors: Mortazavi Steven , Thompson Janel , Baghdoyan Helen A. , Lydic Ralph 
Published: November 2003

Background
Opioids inhibit the rapid eye movement (REM) phase of sleep and decrease acetylcholine (ACh) release in medial pontine reticular formation (mPRF) regions contributing to REM sleep generation. It is not known whether opioids decrease ACh release by acting on cholinergic cell bodies or on cholinergic axon terminals. This study used in vivo microdialysis to test the hypothesis that opioids decrease ACh levels at cholinergic neurons in the laterodorsal tegmental nuclei (LDT) and LDT axon terminals in the mPRF.

Methods
Nine male cats were anesthetized with halothane, and ACh levels within the mPRF or LDT were assayed using microdialysis and high-pressure liquid chromatography (HPLC). ACh levels were analyzed in response to dialysis of the mPRF and LDT with Ringer's solution (control), followed by dialysis with Ringer's solution containing morphine sulfate (MSO4) or naloxone. ACh in the mPRF also was measured during either dialysis delivery or intravenous infusion of remifentanil and during dialysis delivery of fentanyl.

Results
Compared with dialysis of Ringer's solution, microdialysis with MSO4 decreased ACh by 23% in the mPRF and by 30% in the LDT. This significant decrease in ACh was antagonized by naloxone. MSO4 and fentanyl each caused a dose-dependent decrease in mPRF ACh when delivered by dialysis. Remifentanil delivered by continuous intravenous infusion or by dialysis into the mPRF did not alter mPRF ACh.

Conclusions
Morphine inhibits ACh at the cholinergic cell body region (LDT) and the terminal field in the mPRF. ACh in the mPRF was not altered by remifentanil and was significantly decreased by fentanyl. Thus, MSO4 and fentanyl disrupt cholinergic neurotransmission in the LDT-mPRF network known to modulate REM sleep and cortical electroencephalographic activation. These data are consistent with the possibility that inhibition of pontine cholinergic neurotransmission contributes to arousal state disruption by opioids.
Mild Therapeutic Hypothermia for Postischemic Vasoconstriction in the Perfused Rat Liver
Authors: Zar Harvey A. , Tanigawa Koichi , Kim Young-Myeong , Lancaster Jack R. 
Published: November 2003

Background
Mild hypothermia, a promising therapy being evaluated for various clinical situations, may suppress the formation of reactive oxygen species during reperfusion and may ameliorate microcirculatory perfusion failure (the "no-reflow phenomenon").

Methods
Isolated rat livers underwent 30 min of perfusion, 2.5 h of ischemia, and 3 h of reperfusion. The temperature was maintained at 34 degrees C (mild hypothermia, n = 5) or 38 degrees C (normothermia, n = 6) for all three periods by perfusion of a modified Krebs Henseleit solution, air surface cooling, or both. A third group of livers was normothermic before and during ischemia and mildly hypothermic during reperfusion (reperfusion hypothermia, n = 6). Control livers had 3 h of perfusion at normothermia. Chemiluminescence (a measure of the generation of reactive oxygen species) and hepatic vascular resistance were monitored simultaneously to evaluate the effect of temperature on the formation of reactive oxygen species and the development of no reflow. Also measured were thiobarbituric acid reactive species and lactate dehydrogenase, as indicators of oxidative stress and cell injury.

Results
Mild hypothermia decreased formation of reactive oxygen species and postischemic increases in vascular resistance. Reperfusion hypothermia also decreased postischemic increases in vascular resistance, but not as effectively as did mild hypothermia. Levels of thiobarbituric acid reactive species were lower for reperfusion hypothermia than for mild hypothermia at only 0 and 30 min of reperfusion. Lactate dehydrogenase was significant only at 0 min of reperfusion for the normothermic group. Oxygen consumption did not change.

Conclusion
The prevention of hepatic vascular injury by suppression of oxidative stress may be an important protective mechanism of mild hypothermia.
Acute Lung Injury after Instillation of Human Breast Milk into Rabbits' Lungs
Authors: O'Hare Brendan , Chin Christopher , Lerman Jerrold , Endo Junko 
Published: November 2003

Background
The authors compared the lung injury in rabbits that occurred after tracheal instillation of human breast milk (HBM) acidified to pH 1.8 with hydrochloric acid (HCl), HBM at its native pH (7.0), and HBM acidified with gastric juice to pH 1.8 and 3.0.

Methods
The alveolar-to-arterial oxygen tension gradient and dynamic compliance were recorded before and hourly for 4 h after intratracheal instillation of 0.8 ml/kg HBM acidified with HCI (pH 1.8), HBM at its native pH (7.0), HBM acidified with gastric juice (pH 1.8 or 3.0), or 5% dextrose solution acidified with gastric juice (pH 1.8) as a control in 30 adult rabbits. The circulating neutrophil count and phagocyte oxidant activity were determined before and 1 and 4 h after instillation.

Results
The alveolar-to-arterial oxygen tension gradient increased and dynamic compliance decreased significantly in all groups after instillation of HBM compared with baseline values and those in the control group. The severity of the lung injury after instillation of HBM at all pH values (1.8, 3.0, and 7.0) and after acidification with gastric juice or HCl was similar. The circulating neutrophil count increased steadily for 4 h after instillation (P < 0.013), whereas spontaneous phagocyte oxidant burst activity peaked at 1 h (P < 0.007) and returned to baseline by 4 h after instillation.

Conclusions
The severity of the lung injury after tracheal instillation of 0.8 ml/kg HBM in rabbits is similar at pH values between 1.8 and 7.0 after acidification with HCl or gastric juice. Tracheal instillation of HBM increases the circulating neutrophil count and phagocyte oxidant burst activity.
Recirculatory and Compartmental Pharmacokinetic Modeling of Alfentanil in Pigs
Authors: Kuipers Jette A. , Boer Fred , Olofsen Erik , Olieman Wim , Vletter Arie A. , Burm Anton G. L. , Bovill James G. 
Published: November 2003

Background
Cardiac output (CO) is likely to influence the pharmacokinetics of anesthetic drugs and should be accounted for in pharmacokinetic models. The influence of CO on the pharmacokinetic parameters of alfentanil in pigs was evaluated using compartmental and recirculatory models.

Methods
Twenty-four premedicated pigs were evaluated during halothane (0.6-2%) anesthesia. They were assigned randomly to one of three groups. One group served as control. In the other groups, the baseline CO was decreased or increased by 40% by pharmacologic intervention (propranolol or dobutamine). Boluses of alfentanil (2 mg) and indocyanine green (25 mg) were injected into the right atrium. Blood samples were taken for 150 min from the right atrium and aortic root. Arterial concentration-time curves of indocyanine green and alfentanil were analyzed using compartmental models (two-stage and mixed-effects approach) and a recirculatory model, which can describe lung uptake and early distribution.

Results
The CO of individual pigs varied from 1.33 to 6.44 l/min. Three-compartmental modeling showed that CO is a determinant of the central compartment volume (V1, r2 = 0.54), fast peripheral compartment volume (V2, r2 = 0.29), steady state distribution volume (Vss, r2 = 0.29), fast distribution clearance (Cl12, r2 = 0.39), and elimination clearance (Cl10, r2 = 0.51). Recirculatory modeling showed that CO is a determinant of total distribution volume (r2 = 0.48), elimination clearance (r2 = 0.54), and some distribution clearances. The pulmonary distribution volume was independent of CO.

Conclusions
Cardiac output markedly influences the pharmacokinetics of alfentanil in pigs. Therefore, accounting for CO enhances the predictive value of pharmacokinetic models of alfentanil.
Epidural Analgesia during Labor and Maternal Fever
Authors: Philip John MD , Alexander James M. , Sharma Shiv K. , Leveno Kenneth J. , McIntire Donald D. , Wiley Jackie 
Published: November 2003

Background
In recent observational studies, epidural analgesia during labor at patient request has been associated with maternal fever. The authors report a secondary analysis of fever in women who were randomized to receive either epidural or patient-controlled intravenous analgesia during labor.

Methods
Maternal tympanic temperature was measured during spontaneous labor in 715 women at term who were randomized to either epidural analgesia with bupivacaine and fentanyl or to patient-controlled intravenous analgesia with meperidine. Intent-to-treat analysis of women with fever (temperature > or = 38.0 degrees C) versus those without was performed using Student t test and Fisher exact test to determine statistical significance (P < 0.05).

Results
Epidural analgesia was associated with maternal fever (odds ratio = 4.0; 95% confidence interval = 2.0-7.7), as was nulliparity (odds ratio = 4.1; 95% confidence interval = 1.8-9.1) and labor longer than 12 h (odds ratio = 5.4; 95% confidence interval = 2.9-9.9). These factors were all independent variables for maternal fever when analyzed using logistic regression.

Conclusions
Epidural analgesia is associated with maternal fever. However, nulliparity and dysfunctional labor are also significant cofactors in the fever attributed to epidural analgesia.
Spinal versus Epidural Anesthesia for Cesarean Section in Severely Preeclamptic Patients
Authors: Hood David D. , Curry Regina 
Published: November 2003

Background
Selection of spinal anesthesia for severely preeclamptic patients requiring cesarean section is controversial. Significant maternal hypotension is believed to be more likely with spinal compared with epidural anesthesia. The purpose of this study was to assess, in a large retrospective clinical series, the blood pressure effects of spinal and epidural anesthesia in severely preeclamptic patients requiring cesarean section.

Methods
The computerized medical records database was reviewed for all preeclamptic patients having cesarean section between January 1, 1989 and December 31, 1996. All nonlaboring severely preeclamptic patients receiving either spinal or epidural anesthesia for cesarean section were included for analysis. The lowest recorded blood pressures were compared for the 20-min period before induction of regional anesthesia, the period from induction of regional anesthesia to delivery, and the period from delivery to the end of operation.

Results
Study groups included 103 women receiving spinal anesthesia and 35 receiving epidural anesthesia. Changes in the lowest mean blood pressure were similar after epidural or spinal anesthesia. Intraoperative ephedrine use was similar for both groups. Intraoperative crystalloid administration was statistically greater for patients receiving spinal versus epidural anesthesia (1780 +/- 838 vs. 1359 +/- 674 ml, respectively). Neonatal Apgar scores and incidence of maternal intensive care unit admission or postoperative pulmonary edema were also similar.

Conclusion
Although we cannot exclude the possibility that the spinal and epidural anesthesia groups were dissimilar, the magnitudes of maternal blood pressure declines were similar after spinal or epidural anesthesia in this series of severely preeclamptic patients receiving cesarean section. Maternal and fetal outcomes also were similar.
ATX II, A Sodium Channel Toxin, Sensitizes Skeletal Muscle to Halothane, Caffeine, and Ryanodine
Authors: Fletcher Jeffrey E. , Adnet Pascal J. , Reyford Hugo , Wieland Steven J. , Stewart Sherri L. , Rosenberg Henry 
Published: November 2003

Background
The function or expression of subtypes of the sodium ion (Na+) channel is altered in biopsies or cultures of skeletal muscle from many persons who are susceptible to malignant hyperthermia (MH). ATX II, a specific Na+ channel toxin from a sea anemone, causes delayed inactivation of the channel similar to that seen in cell cultures of MH muscle. ATX II was added to skeletal muscle to determine whether altered Na+ channel function could increase the sensitivity of normal skeletal muscle to agents (halothane, caffeine, ryanodine) to which MH muscle is hypersensitive.

Methods
Studies were performed of fiber bundles from the vastus lateralis muscle of persons who were deemed not MH susceptible (MH-) or MH susceptible (MH+) according to the MH diagnostic test and of strips of diaphragm muscle from rats. Preparations in a tissue bath containing Krebs solution were connected to a force transducer. ATX II was introduced 5 min before halothane, caffeine, or ryanodine.

Results
ATX II increased the magnitude of contracture to halothane in preparations from most MH-, but not MH+, human participants. After ATX II treatment, preparations from 9 of 24 MH- participants generated contractures to halothane, 3%, that were of the same magnitude as those from MH+ participants. Preparations from four of six ATX II-treated healthy participants also gave responses of the same magnitude as those of MH-susceptible participants to a graded halothane challenge (0.5-3%). The contractures to bolus doses of halothane in specimens from male participants were more than three times larger than the contractures in specimens from female participants. In rat muscle, ATX II increased the magnitude of contracture to caffeine (2 mM) and decreased the time to produce a 1-g contracture to ryanodine (1 microM).

Conclusions
ATX II, which causes delayed inactivation of the Na+ channel in cell cultures similar to that reported in cultures of MH+ skeletal muscle, increased the sensitivity of normal muscle to three agents to which MH+ muscle is hypersensitive. The increased sensitivity to halothane, 3%, occurred in most (79%), but not all, MH- participants, and this effect was most evident in male participants. Therefore, abnormal function of the Na+ channel, even if it is a secondary event in MH, may contribute to a positive contracture test result for MH.
Differential Effects of Intrathecally Administered Morphine and Its Interaction with Cholecystokinin-B Antagonist on Thermal Hyperalgesia following Two Models of Experimental Mononeuropathy in the Rat
Authors: Yamamoto Tatsuo , Sakashita Yoshihiko 
Published: November 2003

Background
Cholecystokinin-B receptor activation has been reported to reduce morphine analgesia. Neuropathic pain is thought to be relatively refractory to opioids. One possible mechanisms for a reduced effect of morphine on neuropathic pain is the induction of cholecystokinin in the spinal cord by nerve injury. The authors evaluated the role of the spinal cholecystokinin-B receptor on morphine analgesia in two rat neuropathic pain models: chronic constriction injury and partial sciatic nerve injury.

Methods
A chronic constriction injury is created by placing four loosely tied ligatures around the right sciatic nerve. A partial sciatic nerve injury was created by tight ligation of one third to one half of the right sciatic nerve. All drugs were injected intrathecally 7 and 11 days after the nerve injury. The effect of the drugs was reflected in the degree of paw withdrawal latency to thermal nociceptive stimulation. The paw withdrawal latencies of injured and uninjured paws were measured 5, 15, 30, and 60 min after the drugs were injected.

Results
In the chronic constriction injury model, intrathecal morphine increased the paw withdrawal latencies of injured and uninjured paws. PD135158, a cholecystokinin-B receptor antagonist, potentiated the analgesic effect of morphine on injured and uninjured paws. In the partial sciatic nerve injury model, the effect of morphine on the injured paw was less potent than that on the uninjured paw, and PD135158 potentiated the morphine analgesia in the uninjured paw and had only a minor effect on the morphine analgesia in the injured paw.

Conclusions
The effectiveness of morphine for thermal hyperalgesia after nerve injury depends on the type of nerve injury. The role of the cholecystokinin-B receptor in morphine analgesia in thermal hyperalgesia after nerve injury also depends on the type of nerve injury.