Anandamide absorption by direct hemoperfusion with polymixin B-immobilized fiber improves the prognosis and organ failure assessment score in patients with sepsis.

PURPOSE: Direct hemoperfusion (DHP) with polymixin B-immobilized fiber (PMX) has been reported to be effective for patients with septic shock. The aim of this study was to clarify the mechanism of PMX-DHP effect on septic shock. METHODS: The following parameters were measured in septic shock patients who were treated with PMX-DHP: survival rate, sepsis-related organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE-II) score, and plasma concentrations of cannabinoids [anandamide (ANA) and 2-arachidonyl glyceride (2-AG)], cytokines [interleukin (IL)-6, IL-8, IL-10], transforming growth factor beta (TGF-beta), and calcitonin gene-related peptide (CGRP)]. The primary end point was mortality from all causes at day 28 after intensive care unit (ICU) admission or discharge. RESULTS: The survival rate of all patients at 28 days after ICU admission was 37.5% (9/24). The survival group showed significantly lower SOFA and APACHE-II scores than the nonsurvival group after PMX-DHP treatment (P = 0.008 and 0.028, respectively). The improved SOFA score group showed a better survival rate than the nonimproved SOFA score group (71.4% versus 23.5%, P = 0.028). Plasma ANA level significantly decreased after PMX-DHP treatment both in the improved SOFA score group and in the survival group. The level of 2-AG, however, showed no significant change in either group. CONCLUSION: ANA, an intrinsic cannabinoid that induces hypotension in septic shock, is inferred to be the main mechanism of the PMX-DHP effect. Removal of ANA by PMX-DHP could be key to successful septic shock treatment.

[Evaluation by undergraduate medical students of clinical clerkships in the department of anesthesiology--comparison with the evaluation in previous fiscal year].

BACKGROUND: Clinical Clerkships in the Department of Anesthesiology were evaluated by undergraduate medical students and compared with other clinical departments and those of previous fiscal year 2003. METHODS: Questionnaire surveys by 5 step Likert measure were conducted to ask the students for the evaluation of each department or division, and formative evaluation was performed after the all clerkships. The questionnaire consisted of 12 questions on 1) orientation, 2) learning chances and provision of teaching materials, 3) feedback, learning promotion and teaching attitude, 4) coordination of human relationship between medical staff and students, and 5) overall evaluation of teacher's physician. RESULTS: The average score of our department was 4.40 (mean, 5 th grade of all 26 departments/divisions), and the score of the question on provision of medical practice (4.71) was the best among the all departments/divisions. The evaluation grading was rather low for the question on chance for physical examinations (3.80). CONCLUSIONS: Reevaluation of the educational program in our department based on the results of the survey is essential for improvement of the program, and further provision of chances, especially for physical examinations, is also needed for undergraduate students in the program by including palliative medical care program.

[A trial of introduction of portfolio to elective clinical clerkship in anesthesiology].

BACKGROUND: Portfolio as one of the educational techniques was introduced to elective clinical clerkship (CC) of Anesthesiology in Sapporo Medical University School of Medicine in the 2003 fiscal year. METHODS: Fourteen medical students who elected Anesthesiology CC for 3 weeks had a duty to study and feed back their CC everyday by writing portfolio, and the attending checked and fed back their portfolio every week. At the end of the CC, questionnaire surveys by 5 step Likert measure and group discussion were conducted to determine the evaluation by students of the portfolio in Anesthesiology CC. RESULTS: The average score of the questionnaire surveys was high(4.78). However, the scores of usefulness of the portfolio for feedback to student's attitude and to good relationship among medical staff were relatively low (4.6 and 4.4, respectively). CONCLUSIONS: The use of a portfolio as a educational technique in elective CC seems to be useful, and further education to chief/senior medical staff for feedback to student's attitude and other kinds of educational techniques for feedback to good relationship among medical staff are needed.

Protein kinase C inhibitors produce mitochondrial flavoprotein oxidation in cardiac myocytes.

Inhibition of protein kinase C (PKC) antagonizes ischemic preconditioning of myocardium. Opening of mitochondrial adenosine triphosphate (ATP)-dependent potassium (mitoK(ATP)) channels and subsequent oxidation of mitochondria are known to contribute to ischemic preconditioning. We therefore tested the effects of PKC inhibitors on flavoprotein oxidation, measured by flavoprotein fluorescence, as an index of mitoK(ATP) activity in ventricular myocytes from guinea pigs. The PKC inhibitors chelerythrine (1 and 5 microM) and bisindolylmaleimide (100 and 400 nM) strongly increased flavoprotein oxidation in a dose-dependent manner. Specific inhibition of PKC-delta by rottlerin produced persistent flavoprotein oxidation. Inhibition of the production of inositol (1,4,5)-triphosphate by neomycin (0.5 mM) abolished chelerythrine- but not rottlerin-induced flavoprotein oxidation. Inhibition of PKC promotes flavoprotein oxidation via production of inositol (1,4,5)-triphosphate, possibly through the PKC-delta isoform. We speculate that although a certain degree of mitochondrial flavoprotein oxidation causes cardioprotective effects, excessive and/or persistent oxidation abolishes any beneficial actions. Instead of a simple mediator, PKC may act as a regulator of the mitoK(ATP) channel to prevent excessive mitochondrial oxidation.

Intracellular mechanism of mitochondrial adenosine triphosphate-sensitive potassium channel activation with isoflurane.

UNLABELLED: The precise mechanism of isoflurane and mitochondrial adenosine triphosphate-sensitive potassium channel (mitoK(ATP)) interaction is still unclear, although the mitoK(ATP) is involved in isoflurane-induced preconditioning. We examined the role of various intracellular signaling systems in mitoK(ATP) activation with isoflurane. Mitochondrial flavoprotein fluorescence (MFF) was measured to quantify mitoK(ATP) activity in guinea pig cardiomyocytes. To confirm isoflurane-induced MFF, cells were exposed to Tyrode's solution containing either isoflurane (1.0 +/- 0.1 mM) or diazoxide and then both drugs together (n = 10 each). In other studies, the following drugs were each added during isoflurane administration: adenosine or the adenosine receptor antagonist 8-(p-sulfophenyl)-theophylline (SPT); the protein kinase C (PKC) activators phorbol-12-myristate-13-acetate (PMA) and phorbol-12,13-dibutyrate (PDBu); the PKC inhibitors polymyxin B and staurosporine; the tyrosine kinase inhibitor lavendustin A; or the mitogen-activated protein kinase inhibitor SB203580 (n = 10 each). Isoflurane potentiated MFF induced by diazoxide (100 micro M), and diazoxide also increased isoflurane-induced MFF. PMA (0.2 micro M), PDBu (1 micro M), and adenosine (100 micro M) induced MFF. However, SPT (100 micro M), polymyxin B (50 micro M), staurosporine (200 nM), lavendustin A (0.5 micro M), and SB203580 (10 micro M) all failed to inhibit the effect of isoflurane. Our results show that isoflurane, adenosine, and PKC activate mitoK(ATP). However, our data do not support an action of isoflurane through pathways involving adenosine, PKC, tyrosine kinase, or mitogen-activated protein kinase. These results suggest that isoflurane may directly activate mitoK(ATP). IMPLICATIONS: Our results show that isoflurane activates mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channels, but not through pathways involving adenosine, protein kinase C, tyrosine kinase, or p38 mitogen-activated protein kinase. Isoflurane may directly activate mitoK(ATP) channels.

[A case of suspected pulmonary thrombosis in a patient with reactive thrombocytemia who underwent liver subsegmentectomy].

A 68-year-old man with reactive thrombocytemia (platelet count: 97.2 x 10(4).mm-3) underwent liver subsegmentectomy for hepatocellular carcinoma. Thoracic epidural combined with general anesthesia was carried out for the surgery. Platelet aggregability was monitored during the operation. At the beginning of the operation, platelet aggregability to aggregating factor ADP showed an abnormal pattern without dose dependency. In spite of continuous administration of gabexate mesilate for inhibition of thrombosis, the patient developed hypercapnia with low end tidal CO2 pressure (PETCO2) and hypoxia, suggesting pulmonary embolism. PETCO2 and SPO2 recovered soon after heparin administration. The patient recovered without any neurologic complications. This case demonstrated that hyperaggregability is possible in patients with thrombocytemia and suggests that monitoring of platelet function in patients with thrombocytemia is difficult.

Intermittent pneumatic compression prevents venous stasis in the lower extremities in the lithotomy position.

PURPOSE: To investigate the interactions of a new lithotomy positioning device (LPD) with two intermittent pneumatic compression (IPC) devices by measuring femoral venous flow velocity. METHODS: Subjects were divided into three groups: 1) supine position as a control, 2) lithotomy position using a conventional LPD, and 3) lithotomy position using a new LPD, Levitator(TM). These three groups were further divided in two according to the type of IPC device used: AV-impulse(TM) (rapid IPC) and SeQuel(TM) (standard IPC). Peak femoral venous flow velocity was measured by using an ultrasonic echo diagnostic device. Data were analyzed by one-way ANOVA with Fisher's test or by the unpaired two-tailed t test. RESULTS: Moving to the conventional lithotomy position from the supine position, venous flow velocity was decreased by 38% in both IPC device groups. Even when the new LPD was used to support the lithotomy position, the flow velocity was decreased by 24%, but the velocity was significantly higher than in the conventional lithotomy position. Both rapid and standard IPC devices increased flow velocity to 77% and 107% (first compression) and to 71% and 84% (fifth compression) of the control values during compression, respectively. In the lithotomy position group using the new LPD, similar increases in flow were seen with the use of IPC devices. CONCLUSION: Both rapid and standard IPC devices are useful for maintaining venous flow of the lower extremities in the lithotomy position.

Effects of lumbar puncture position on arterial blood gases.

We observed the changes in partial pressure of arterial oxygen (PaO 2) and carbon dioxide (PaCO 2) before and during assumption of the lateral position prior to lumbar puncture in 81 patients to investigate whether lung volume decreased and ventilation was suppressed. PaO 2 significantly decreased while the patients were in the lateral position, while PaCO 2 remained unchanged. There was a negative correlation between the change in PaO 2 and age [change in PaO 2 (mmHg)=-0.13×age (years)+4.28,P<0.01]. The fact that closing volume increases with age implies that the decrease in functional residual capacity in the lateral position could have caused the decrease in PaO 2. It is therefore advisable to continuously monitor arterial oxygenation using a noninvasive monitor, such as a pulse oximeter, while performing spinal or epidural block, especially in elderly patients.