Determination of plasma concentrations of propofol associated with 50% reduction in postoperative nausea

BACKGROUND: Subhypnotic doses of propofol possess direct antiemetic properties. The authors sought to determine the plasma concentration of propofol needed to effectively manage postoperative nausea and vomiting. METHODS: Patients aged 18-70 yr who were classified as American Society of Anesthesiologists physical status 1 or 2 and had surgery during general anesthesia were approached for the study. Only patients who had nausea (verbal rating score > 5 on a 0- to 10-point scale), retching, or vomiting in the postanesthetic care unit participated. Propofol was administered to these patients to achieve target plasma concentrations of 100, 200, 400, and 800 ng/ml using a computer-assisted continuous infusion device. Target concentrations were increased every 15 min until patients described at least a 50% reduction in symptoms on the verbal rating score. An arterial blood sample was obtained at each step. The measured plasma propofol concentrations were used to analyze data. Blood pressure, heart and respiratory rates, arterial blood saturation, sedation score, and overall satisfaction with treatment were recorded. RESULTS: Of the 89 patients who consented to the study, 15 patients met entry criteria and were enrolled. Five of these patients also had retching or vomiting when they entered the study. Fourteen patients responded successfully to treatment. One patient did not achieve the required response at plasma concentrations of 830 ng/ml. Hence the success rate for the treatment of postoperative nausea and vomiting was 93%. Among patients who responded, the median plasma concentration associated with an antiemetic response was 343 ng/ml. There was no difference in sedation scores from baseline and no episodes of desaturation. Hemodynamic parameters were stable during the study. CONCLUSIONS: Propofol is generally efficacious in treating postoperative nausea and vomiting at plasma concentrations that do not produce increased sedation. Simulations indicate that to achieve antiemetic plasma propofol concentrations of 343 ng/ml, a bolus dose of 10 mg followed by an infusion of approximately 10 microg x kg(-1) x min(-1) are necessary.     

Influence of timing on the dosimetric analysis of transperineal ultrasound-guided, prostatic conformal brachytherapy

Postoperative computed tomography (CT)-based dosimetric analysis of transperineal ultrasound-guided conformal prostate brachytherapy provides detailed information regarding the coverage and uniformity of the implant. However, there is no generally accepted standard for the optimal timing of the postoperative dosimetry. This report details dosimetric analysis and the effect of timing based upon CT and orthogonal film evaluation for ten unselected patients implanted with either iodine-125 (125I) or palladium-103 (103Pd). Within 2 hours after implantation, patients underwent a CT scan and the first of four sequential sets of orthogonal films. Subsequent orthogonal films were obtained on days 3, 14, and 28 postimplant. CT-based dosimetry revealed coverage of the prostate to the prescribed minimal peripheral dose (mPD) at 93.1 +/- 3.6% of the volume, the prostate volume receiving 150% of mPD was 38.2 +/- 8.7%, and the urethral and rectal doses were 114 +/- 12% and 78 +/- 19% of mPD, respectively. The implanted seeds seen on orthogonal films acted as markers for temporal changes in prostate dimensions, and the standard deviation of each dimension was used as input in an ellipsoidal volume calculation. Seed coordinates were self normalized to the center of gravity of each two-dimensional view and were measured relative to the linear regression line in the superior-inferior direction. The reproducibility of the anteroposterior (AP) film setup in terms of temporal variation in the angle of the regression line was markedly better than that of the lateral films, 1.8 degrees +/- 1.2 degrees vs. 4.3 degrees +/- 2.6 degrees, respectively. Dimensional contraction from day 0 to day 28 averaged 11.3% in the superior-inferior direction, 8.5% in the AP/PA (posteroanterior) direction, and 2.5% in the right-left lateral direction. This translated into a volume change of 20.9% (ranged 11.6-31.6%), which was determined by using the ellipsoid method. The half-life for edema resolution was 10.6 +/- 1.8 days (range 8.6-14.3 days). However, because of variability in the degree and extent of edema and its rate of resolution, we believe that it may be futile to define a single point in time as the most accurate indicator of the postoperative dose distribution. Rather, it may be preferable to accept universal standardization of timing and methodology for CT-based postoperative dosimetry, which would facilitate comparison of results between centers and maximize the information content of that single measurement. We conclude that day 0 represents the optimal time, because dosimetric evaluation at that time minimizes patient discomfort and inconvenience (a catheter is already in place), provides information about edema when it is near its maximum extent, and provides prompt closure of the learning loop and, as such, hopefully will result in improved implantation techniques and results.     

Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen

This paper examines why the law concerns itself with euthanasia. The nature of the right to life and its protection in law is explored. Such a right demands legal intervention to prohibit, or at least control, involuntary and non-voluntary euthanasia. Voluntary euthanasia is not a violation of the individual's right to life as such, so on what grounds can law limit autonomy by prohibiting such conduct? It is suggested that, while concepts of sanctity of life still play a part in the legal debate, fears of abuse in any scheme for voluntary euthanasia largely explain the reluctance of many jurisdictions to follow the example of The Netherlands. Finally, the paper asks whether reform and regulation of voluntary euthanasia are as attractive options as they are sometimes portrayed.     

Development of a new scale for measuring acculturation: the Taiwan Aboriginal Acculturation Scale (TAAS)

As part of the Taiwan Aboriginal Study Project (TASP), a new acculturation scale (the Taiwan Aboriginal Acculturation Scale, or TAAS) has been developed among the aboriginal minorities of Austronesian origin in Taiwan. The design of the original 54 items was based on Milton Gordon's concept of assimilation in association with a careful consideration of cross-cultural validity. These items were administered to 144 subjects stratified by age and sex who were randomly sampled from four major Taiwanese aboriginal groups. Item analysis and factor analysis were applied to select an 18-item scale which has three subscales (factors): cultural assimilation, social assimilation, and social attitude. Results of validity and reliability studies of the TAAS were found to be acceptable. The development of TAAS demonstrates the applicability of the concept of acculturation as a process that involves changes both in attitude, and in behaviour, to non-western societies.     

Double patch closure of ventricular septal defect with increased pulmonary vascular resistance

BACKGROUND: Closure of a large ventricular septal defect (VSD) in children with elevated pulmonary vascular resistance is associated with significant morbidity and mortality. Pulmonary hypertensive episodes continue to be a major cause of postoperative morbidity and mortality. We designed a fenestrated flap valve double VSD patch in an effort to decrease the morbidity and mortality associated with the closure of a large VSD with elevated pulmonary vascular resistance. METHODS: Eighteen children (mean age, 5.7 years) with a large VSD and elevated pulmonary vascular resistance (mean, 11.4 Wood units) underwent double patch VSD closure using moderately hypothermic cardiopulmonary bypass and cardioplegic arrest. The routine VSD patch was fenestrated (4 to 6 mm) and on the left ventricular side of the patch, a second, smaller patch was attached to the fenestration along its superior margin before closure of the VSD. RESULTS: All children survived operation and were weaned from inotropic and ventilator support within 48 hours postoperatively. Postoperative pulmonary artery pressures were significantly lower than preoperative values. One child died 9 months postoperatively. CONCLUSIONS: Closure of a large VSD in children with elevated pulmonary vascular resistance can be performed with low morbidity and mortality when a flap valve double VSD patch is used.     

Attenuation of LPA-mediated calcium signaling and inositol polyphosphate production in rat-1 fibroblasts transformed by the v-src oncogene

Alterations in cellular signaling underlie the transforming actions of many oncogenes. The vsrc oncogene tyrosine kinase, pp60vsrc, is known to alter multiple signal transduction pathways, including those involving phosphatidylinositol (PI) metabolism. In this study, we investigated the effects of vsrc-transformation on lysophosphatidic acid (LPA) receptor coupling to intracellular free calcium [Ca2+]i and PI turnover in rat-1 fibroblasts. In normal rat-1 cells, LPA rapidly elevated [Ca2+]i (EC50 = 10nM). In contrast, the ability of LPA to mobilize calcium was markedly attenuated in rat-1-vsrc cells. Further study revealed that the LPA-mediated generation of inositol (1,4,5)P3 and other inositol polyphosphates was also markedly attenuated in the vsrc-transformed cells. Although LPA caused a transient reduction in the level of PI(4,5)P2 in normal rat-1 cells, the agonist elevated the level of PI(4,5)P2 in the vsrc-transformed cells. These findings demonstrate that vsrc-transformation alters the coupling of LPA receptors to PI turnover and calcium signaling in rat-1 cells, and point to G protein-coupled receptor systems as targets for modulation by the vsrc kinase.     

Antenatal glucocorticoid therapy suppresses angiotensin-converting enzyme activity in rats with nitrofen-induced congenital diaphragmatic hernia

BACKGROUND: Carcinoma of the true vocal cord represents the earliest clinically recognizable invasive malignancy in the head and neck region and provides a unique model for studying possible prognostic genetic markers. The aim of this study was to determine whether p53 overexpression correlated with tumor recurrence in a homogenous population of patients with early stage glottic carcinoma treated with radiotherapy alone. METHODS: One hundred and fourteen patients with T1N0M0 squamous cell carcinoma of the glottis were treated with curative radiotherapy between 1976 and 1990. With a median follow-up of 6 years, actuarial local control was 80% with 23 local recurrences. Laryngeal biopsy specimens obtained prior to radiation therapy were analyzed retrospectively in 22 patients. Forty-five patients with local control were used as a control group. p53 overexpression indicating a mutated p53 gene was analyzed by immunohistochemistry using the mouse monoclonal antibody D0-7. RESULTS: Approximately 82% of carcinomas that recurred locally expressed p53 compared with only 29% of those with local control (P < 0.001). No significant relation was noted between p53 expression and histologic grade. Intensity of staining did not predict tumor recurrence. CONCLUSIONS: The authors believe that this case-controlled study demonstrated the role of p53 as an independent prognostic factor in patients with early stage glottic carcinoma.     

Partial liquid ventilation reduces pulmonary neutrophil accumulation in an experimental model of systemic endotoxemia and acute lung injury

OBJECTIVE: To determine whether pulmonary neutrophil sequestration and lung injury are affected by partial liquid ventilation with perfluorocarbon in a model of acute lung injury (ALI). DESIGN: A prospective, controlled, in vivo animal laboratory study. SETTING: An animal research facility of a health sciences university. SUBJECTS: Forty-one New Zealand White rabbits. INTERVENTIONS: Mature New Zealand White rabbits were anesthetized and instrumented with a tracheostomy and vascular catheters. Animals were assigned to receive partial liquid ventilation (PLV, n = 15) with perflubron (18 mL/kg via endotracheal tube), conventional mechanical ventilation (CMV, n = 15) or high-frequency oscillatory ventilation (HFOV, n = 5). Animals were ventilated, using an FIO2 of 1.0, and ventilatory settings were required to achieve a normal PaCO2. Animals were then given 0.9 mg/kg of Escherichia coli endotoxin intravenously over 30 mins. Partial liquid ventilation, conventional mechanical ventilation, or high-frequency oscillatory ventilation was continued for an additional 4 hrs before the animals were killed. A group of animals not challenged with endotoxin underwent conventional ventilation for 4.5 hrs, serving as the control group (control, n = 6). Lungs were removed and samples were frozen at -70 degrees C. Representative samples were stained for histology. A visual count of neutrophils per high-power field (hpf) was performed in five randomly selected fields per sample in a blinded fashion by light microscopy. Lung samples were homogenized in triplicate in phosphate buffer, ultrasonified, freeze-thawed, and clarified by centrifugation. Supernatants were analyzed for myeloperoxidase (MPO) activity by spectrophotometry with o-dianisidine dihydrochloride and hydrogen peroxide at 460 nm. MEASUREMENTS AND MAIN RESULTS: Histologic analysis of lung tissue obtained from control animals showed normal lung architecture. Specimens from the PLV and HFOV groups showed a marked decrease in alveolar proteinaceous fluid, pulmonary vascular congestion, edema, necrotic cell debris, and gross inflammatory infiltration when compared with the CMV group. Light microscopy of lung samples of animals supported with PLV and HFOV had significantly lower neutrophil counts when compared with CMV (PLV, 4 +/- 0.3 neutrophils/hpf; HFOV, 4 +/- 0.5 neutrophils/hpf; CMV, 10 +/- 0.9 neutrophils/hpf; p < .01). In addition, MPO activity from lung extracts of PLV and HFOV animals was significantly lower than that of CMV animals (PLV, 61 +/- 13.3 units of MPO activity/lung/kg; HFOV, 43.3 +/- 6.8 units of MPO activity/lung/kg; CMV, 140 +/- 28.5 units of MPO activity/lung/kg; p < .01). MPO activity from lungs of uninjured control animals was significantly lower than that of animals in the PLV, HFOV, and CMV groups (control, 2.2 +/- 2 units of MPO activity/lung/kg; p < .001). CONCLUSIONS: Partial liquid ventilation decreases pulmonary neutrophil accumulation, as shown by decreased neutrophil counts and MPO activity, in an experimental animal model of ALI induced by systemic endotoxemia. The attenuation in pulmonary leukostasis in animals treated with PLV is equivalent to that obtained by a ventilation strategy that targets lung recruitment, such as HFOV.