Paraoxonase-1 gene Q192R polymorphism and reactive oxygen metabolites.

OBJECTIVE: Paraoxonase-1 (PON1) is a high-density lipoprotein-associated antioxidant enzyme. The Q192R polymorphism of the PON1 gene can protect against oxidative conditions, but the relationship between Q192R polymorphism and oxidative stress-related markers remains controversial. In this study, the diacron reactive oxygen metabolites (d-ROMs) test was used to investigate the relationship between Q192R polymorphism and oxidative stress-related markers in Japanese subjects. METHODS: Patients without a history of overt cardiovascular disease who were not receiving antioxidant medication were enrolled in a cross-sectional clinic-based study. An allele-specific polymerase chain reaction method was used to assess the PON1 Q192R polymorphism and compare the level of d-ROMs between genotypes. RESULTS: A total of 103 subjects were analysed. The RR genotype was associated with a significantly lower level of d-ROMs than the RQ and QQ genotypes. After multivariate analysis the relationship between the genotypes and level of d-ROMs remained independently significant. CONCLUSIONS: The RR genotype may be protective against oxidative stress in cardiovascular diseasefree Japanese subjects. In addition, the d-ROMs test can be useful for examining the role of the PON1 Q192R polymorphism under oxidative conditions.

A gene polymorphism in acetyl-coenzyme A carboxylase beta may be associated with the C-reactive protein level in a prediabetic and diabetic population.

A recent study reported a significant association between the T-allele in intron 18 of the acetyl-coenzyme A carboxylase beta (ACACB) gene (C>T polymorphism) and nephropathy caused by diabetes mellitus (DM). Considering the involvement of chronic inflammation in the pathophysiology of DM, the present study investigated an association between the ACACB gene polymorphism and high-sensitivity C-reactive protein (hsCRP) in a prediabetic and diabetic population. Anthropometric and biochemical variables including hsCRP were measured among 91 Japanese subjects (mean age: 69 years) with a hemoglobin A1c level of ≥5.6% and no history of cardiovascular disease. All subjects were genotyped by an allele-specific DNA assay. The subjects with the T-allele (n=32) showed significantly higher hsCRP levels than those without the T-allele (median level: 0.17 vs. 0.14 mg/dL, P≤0.05). Similarly, the hsCRP levels continued to differ significantly, independently of the other variables, between the subjects with and without the T-allele after adjusting for multiple variables. The present data suggest that the ACACB gene C>T polymorphism may therefore be associated with chronic inflammation in this population.

UCP1 genetic polymorphism (-3826 A/G) diminishes resting energy expenditure and thermoregulatory sympathetic nervous system activity in young females.

BACKGROUND: Recent findings regarding the existence of functional brown adipose tissue (BAT) in adult humans suggest a physiological role of BAT and uncoupling protein 1 (UCP1)-linked thermogenesis in energy balance. OBJECTIVE: To investigate whether UCP1 polymorphism was associated with resting energy expenditure (REE) and thermoregulatory sympathetic nervous system (SNS) activity in humans. METHODS: A total of 82 healthy females (20-22 years) were genotyped for the -3826 A/G polymorphism of the UCP1 gene using a fluorescent allele-specific DNA primer assay system. REE was measured by indirect calorimetry. The thermoregulatory SNS activity was assessed by heart rate variability power spectral analysis according to our previously reported method. Each subject was studied in the morning, after an overnight fast. Nutritional values were calculated on the basis of 2-day food records. RESULTS: The frequencies of A/A, A/G and G/G genotypes were 0.27, 0.45 and 0.28, respectively. No significant difference was found in anthropometric indexes among the three groups. However, in the G/G group, the percentage of energy consumed as fat was lower (A/A: 30.7 ± 1.1%, A/G: 31.3 ± 1.0%, G/G: 26.0 ± 1.2%, P<0.01), and energy intake tended to be lower (A/A: 7209 ± 310 kJ d(-1), A/G: 7075 ± 280 kJ d(-1), G/G: 6414 ± 264 kJ d(-1), P=0.16). With regard to metabolic parameters, group differences were observed in REE (A/A: 5599 ± 170 kJ d(-1), A/G: 5054 ± 115 kJ d(-1), G/G: 4919 ± 182 kJ d(-1), P<0.01) and in thermoregulatory SNS activity (A/A: 313 ± 47 ms(2), A/G: 333 ± 42 ms(2), G/G: 185 ± 23 ms(2), P<0.05). CONCLUSION: Diminished REE in G-allele carriers as well as reduced thermoregulatory SNS activity for the G/G genotype, suggest that attenuated UCP1-linked thermogenesis has an adverse effect on the regulation of energy balance.

Adiponectin gene single-nucleotide polymorphisms and treatment response to obesity.

BACKGROUND: In the adiponectin gene polymorphisms, single-nucleotide polymorphism (SNP)-45 and SNP276 have reportedly been associated with obesity, Type 2 diabetes, and other features of metabolic syndrome. AIM: Whether these adiponectin SNP affect obesity-related parameters during caloric restriction in obese subjects. SUBJECTS AND METHODS: Thirty- two obese Japanese women were treated by meal replacement with a low calorie diet for 8 weeks and asked to maintain their habitual lifestyle. Obesity-related parameters were measured before and after the treatment period. We determined four SNP (T45G, I164T, G276T, and C-11377G) using a fluorescent allele-specific DNA primer assay systemand FRET probe assay system. RESULTS: After the treatment, the extent of decrease in waist circumference was greater in the subjects with the G/G or G/T genotype of SNP276 than in those with the T/T genotype (p=0.026). As for SNP45, the extent of decrease in triglyceride levels was greater in the subjects with the T/T genotype than in those with the T/G genotype (p=0.003). For SNP-11377, the extent of decrease in systolic blood pressure and fasting plasma glucose was greater in the subjects with the C/G or G/G genotype than in those with the C/C genotype (p=0.044). CONCLUSION: Our findings indicate that each SNP in the adiponectin gene might modify the change in obesity-related parameters during meal replacement with a low calorie diet.

Anesthesia-related mortality and morbidity over a 5-year period in 2,363,038 patients in Japan.

BACKGROUND: Statistical data of mortality and morbidity related to anesthesia have not been reported in Japan since World War II. The need to comprehensively examine the events of cardiac arrest as well as mortality prompted the first national study in Japan. METHODS: Confidential questionnaires were sent to all Japan Society of Anesthesiologists Certified Training Hospitals every year from 1994 through 1998. Collected data were analyzed for incidence of cardiac arrest and other critical events during anesthesia and surgery, and their outcomes within 7 postoperative days. The principal causes of the critical incidents were also analyzed. RESULTS: With an average response rate of 39.9%, a total of 2,363,038 cases were documented over 5 years. The average incidence per year of cardiac arrest during surgery due to all etiologies and that totally attributable to anesthesia was 7.12 [95%CI: 6.30,7.94] and 1.00 [0.88, 1.12]) per 10,000 cases, respectively. The average mortality per year in the operating room or within 7 postoperative days due to all etiologies and that totally attributable to anesthesia was 7.18 [6.22, 8.13] and 0.21 [0.15, 0.27] per 10,000 cases, respectively. The two principal causes of cardiac arrest during anesthesia and surgery due to all etiologies were massive hemorrhage (31.9%) and surgery (30.2%), and those totally attributable to anesthesia were drug overdose or selection error (15.3%) and serious arrhythmia (13.9%). Preventable human errors caused 53.2% of cardiac arrest and 22.2% of deaths in the operating room totally attributable to anesthesia. CONCLUSIONS: The rates in Japan of cardiac arrest and death during anesthesia and surgery due to all etiologies as well as those totally attributable to anesthesia are comparable to those of other developed countries.

[Perioperative mortality and morbidity for the year 1999 in 466 Japanese certified anesthesia-training hospitals: with special reference to operative regions--report of Committee on Operating Room Safety of Japanese Society of Anesthesiologists].

Perioperative mortality and morbidity in Japan for the year 1999 were analyzed retrospectively with special reference to operative regions. The total number of analyzed cases was 701,940. The percentages for each operative region were as follows, craniotomy 4.5%, thoracotomy 3.3%, heart and great-vessels 3.9%, thoracotomy with laparotomy 0.8%, laparotomy except caeserian-section 31.7%, ceserian-section 3.2%, head-neck and otolarynx 14.5%, chest-abdomen-perineum 11.1%, spine 3.5%, extremity including peripheral-vessel 16.5%, and others 6.9%. The incidence of serious events, including cardiac arrest and severe hypotension and hypoxemia suggesting impending cardiac arrest was 34.58 per 10,000 cases in all operative regions. The events were observed more frequently in heart and great-vessels 247.26, thoracotomy with laparotomy 128.91 and thoracotomy 61.55, and less frequently in chest-abdomen-perineum 13.52 and extremity including peripheral-vessel 16.99. Regarding the prognosis of events, the cases with no sequela were 69.9% in all operative regions. While there were fewer cases with no sequela in craniotomy 50.4%, thoracotomy with laparotomy 54.3% and heart and great-vessels 58.6%, there were more cases in head-neck and oto-larynx 95.2% and chest-abdomen-perineum 90.5%. The incidence of serious events totally attributable to anesthetic management was 7.79 per 10,000 cases in all operative regions. The events were observed more frequently in thoracotomy 12.82, heart and great-vessels 12.29 and spine 11.06, and less frequently in extremity including peripheral-vessel 5.17 and chest-abdomen-perineum 6.05. Regarding the prognosis of events, the cases with no sequela were 93.1% in all operative regions. There were fewer cases with no sequela in thoracotomy with laparotomy 80.0% and craniotomy 81.8%. The main cause of events in thoracotomy and spine was the inadequate airway management, and in heart and great-vessels was the overdose or miss-selection of drugs. Although the incidence of serious events totally attributable to anesthetic management was one fourth of all events, most of them resulted from human factors. Thus, the more efforts are necessary to improve the outcomes. While the total deaths from 701,940 cases, including death on the operation day or within 7 days after it, were 528 cases (7.52 per 10,000 cases), the deaths totally attributable to anesthesia were 7 cases (0.10 per 10,000 cases).

[Annual report of perioperative mortality and morbidity for the year 1999 with a special reference to anesthetic methods at Certificated Training Hospitals of Japanese Society of Anesthesiologists].

The Committee on Operating Room Safety of Japanese Society of Anesthesiologists (JSA) sends annually confidential questionnaires of perioperative mortality and morbidity to Certificated Training Hospitals of JSA. This report is on perioperative mortality and morbidity in 1999 with a special reference to anesthetic methods. Four hundred and sixty-seven hospitals reported the number of cases referred to anesthetic methods and total numbers of cases were 727,723. The incidences of cardiac arrest per 10,000 cases due to all etiology are estimated to be 6.77 cases in average, 5.33 cases in inhalation anesthesia, 34.26 cases in total intravenous anesthesia (TIVA), 5.26 cases in inhalation anesthesia plus epidural or spinal or conduction block, 5.29 cases in TIVA plus epidural or spinal or conduction block, 0.73 cases in spinal with continuous epidural block (CSEA), 2.85 cases in epidural anesthesia, 1.63 cases in spinal anesthesia, 2.53 cases in conduction block and 46.51 cases in other methods. However, the incidences of cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated to be 0.78 case in average, 0.51 case in inhalation anesthesia, 1.35 cases in TIVA, 0.97 case in inhalation anesthesia plus epidural or spinal or conduction block, 1.51 cases in TIVA plus epidural or spinal or conduction block, 0.73 case in CSEA, 1.71 cases in epidural anesthesia, 0.54 case in spinal anesthesia, 2.52 cases in conduction block and 1.08 cases in other methods. The incidences of severe hypotension per 10,000 cases due to all etiology are estimated to be 16.64 cases in average, 13.61 cases in inhalation anesthesia, 100.36 cases in TIVA, 13.32 cases in inhalation anesthesia plus epidural or spinal or conduction block, 9.07 cases in TIVA plus epidural or spinal or conduction block, 3.65 cases in CSEA, 6.26 cases in epidural anesthesia, 7.31 cases in spinal anesthesia, 2.52 cases in conduction block and 28.12 cases in other methods. On the other hand, the incidences of cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated to be 2.40 cases in average, 1.65 cases in inhalation anesthesia, 0.81 cases in TIVA, 3.92 cases in inhalation anesthesia plus epidural or spinal or conduction block, 2.77 cases in TIVA plus epidural or spinal or conduction block, 2.56 cases in CSEA, 3.42 cases in epidural anesthesia, 2.71 cases in spinal anesthesia, zero case in conduction block and zero case in other methods. The incidences of severe hypoxia per 10,000 cases due to all etiology are estimated to be 5.32 cases in average, 6.7 cases in inhalation anesthesia, 9.17 cases in TIVA, 5.16 cases in inhalation anesthesia plus epidural or spinal or conduction block, 4.53 cases in TIVA plus epidural or spinal or conduction block, 2.56 cases in CSEA, zero case in epidural anesthesia, 1.08 cases in spinal anesthesia, zero case in conduction block and 1.08 cases in other methods. On the other hand, the incidences of severe hypoxia per 10,000 cases totally attributable to anesthesia are estimated to be 2.39 cases in average, 3.22 cases in inhalation anesthesia, 2.43 cases in TIVA, 2.26 cases in inhalation anesthesia plus epidural or spinal or conduction block, 2.77 cases in TIVA plus epidural or spinal or conduction block, zero case in CSEA, zero case in epidural anesthesia, 0.54 cases in spinal anesthesia, zero case in conduction block and 1.08 cases in other methods. The mortality rates of cardiac arrest per 10,000 cases due to all etiology are estimated to be 3.56 cases in average, 2.82 cases in inhalation anesthesia, 24.55 cases in TIVA, 1.4 cases in inhalation anesthesia plus epidural or spinal or conduction block, 1.51 cases in TIVA plus epidural or spinal or conduction block, zero cases in CSEA, 0.57 cases in epidural anesthesia, 0.27 cases in spinal anesthesia, zero case in conduction block and 42.18 cases in other methods. On the other hand, the mortality rates of cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated to be 0.08 case in average, 0.09 case in inhalation anesthesia, 0.27 case in TIVA, 0.05 case in inhalation anesthesia plus epidural or spinal or conduction block, zero case in TIVA plus epidural or spinal or conduction block, zero case in CSEA, 0.57 case in epidural anesthesia, zero case in spinal anesthesia, conduction block and other methods. The outcomes of cardiac arrest totally attributable to anesthesia are 70.2% of full recovery without any sequelae, 10.5% of death within 7 days, 1.8% of vegetative state and 17.5% of unknown results while the outcome of critical events including severe hypotension and severe hypoxia totally attributable to anesthesia is 94.9% of full recovery without any sequelae, 0.4% of death within 7 days, 0.2% of vegetative state and 4.5% of unknown results. These results indicate that there are no differences in mortality and morbidity totally attributable to anesthesia among anesthetic methods in 1999 at Certificated Training Hospitals of Japan Society of Anesthesiologists.

[Perioperative mortality and morbidity in 1999 with a special reference to age in 466 certified training hospitals of Japanese Society of Anesthesiologists--report of Committee on Operating Room Safety of Japanese Society of Anesthesiologists].

Perioperative mortality and morbidity in Japan from Jan. 1 to Dec. 31, were studied retrospectively. Committee on Operating Room Safety of Japanese Society of Anesthesiologists (JSA) sent confidential questionnaires to 774 Certified Training Hospitals of JSA and received answers from 60.2% of the hospitals. We analyzed their answers with a special reference to the age group. The total number of anesthetics available for this analysis was 732,788. All cases were divided in to 7 groups; group A(< 1 months), group B(< 12 months), group C(< 5 years), group D(< 18 years), group E (< 65 years), group F(< 85 years), and group G(> 85 years). The incidences of all critical events including cardiac arrest, severe hypotension, and severe hypoxemia were 168.14, 47.86, 24.63, 14.65, 28.43, 50.4, and 43.68 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The overall mortality rate (death during anesthesia and within 7th postoperative day) were 74.10, 6.63, 3.30, 3.07, 4.82, 13.74, and 11.84 per 10,000 anesthetics in patients with group A, B, C, D, E, F, and G, respectively. The incidences of cardiac arrest were 54.15, 8.84, 5.08, 2.56, 4.84, 11.02, and 6.66 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The mortality rates after cardiac arrest were 42.75, 2.95, 2.54, 1.70, 2.00, 6.56, and 5.18 in patients with group A, B, C, D, E, F, and G, respectively. The incidences of all critical events, the incidence of cardiac arrest, and the overall mortality rate were much higher in group A than other groups and lower in group D. Mortality and morbidity due to all kinds of causes including anesthetic management, intraoperative events, co-existing diseases, and operation were as follows. The incidence of all critical events attributable to co-existing disease were the highest in these four groups, and 94.04, 15.46, 7.87, 6.13, 7.26, 17.38, and 16.29 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The incidences of all critical events attributable to anesthetic management were 31.35, 16.94, 4.60, 6.09, 10.77, and 14.07 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The incidence of cardiac arrest in group A was much more attributable to co-existing disease and operation than other causes. The incidences of cardiac arrest attributable to anesthetic management were 0.00, 1.47, 0.25, 0.34, 0.83, 0.92, and 0.22 per 10,000 in patients with group A, B, C, D, E, F, and G, respectively. The mortality rates in these groups were 0.00, 0.00, 0.00, 0.17, 0.07, 0.05, and 1.48, and no death was found in cases under 5 years of age. The two cases of death in G group were due to too high anesthesia levels in spinal anesthesia. Other causes including overdose of anesthetics, toxic effect of local anesthetic, improper management of airway, and incompatible blood transfusion were preventable with the anesthesiologists' effort in protocol development and skilled assistance.

[Perioperative mortality and morbidity for the year of 1999 in 466 Japanese Certified Anesthesia-training Hospitals: with special reference to ASA-physical status--report of Committee on Operating Room Safety of Japan Society of Anesthesiologists].

Perioperative mortality and morbidity in Japan for the year 1999 were studied retrospectively. Committee on Operating Room Safety of the Japan Society of Anesthesiologists (JSA) sent confidential questionnaires to 774 Certified Training Hospitals of JSA and received answers from 60.2% of the hospitals. We analyzed their answers with special reference to ASA physical status (ASA-PS). The total number of anesthetics analyzed was 655, 644. Mortality and morbidity due to all kinds of causes including anesthetic management, intraoperative events, co-existing diseases, and operation were as follows. The incidence of cardiac arrest (per 10,000 anesthetics) was 0.68, 3.76, 14.37, 67.03, 0.36, 4.68, 27.96, 206.30 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The incidences of critical events including cardiac arrest, severe hypotension, and severe hypoxemia were 8.93, 26.99, 71.30, 188.52, 8.68, 31.27, 136.16, and 790.92 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The mortality rates (death during anesthesia and within 7th postoperative day) after cardiac arrest were 0.16, 0.94, 5.71, 33.51, 0.00, 1.46, 16.41 and 167.76 per 10,000 anesthetics in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The overall mortality rates were 0.24, 1.66, 12.16, 67.03, 0.00, 3.51, 34.65 and 417.14 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. Overall mortality and morbidity were higher in emergency anesthetics than in elective anesthetics. ASA-PS correlated well with overall mortality and with morbidity, regardless of etiology. The incidences of cardiac arrest totally attributable to anesthesia were 0.24, 0.45, 1.47, 8.38, 0.36, 1.75, 2.43 and 11.34 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The incidences of all critical events totally attributable to anesthesia were 4.92, 8.81, 14.74, 20.95, 4.34, 11.40, 15.80 and 22.67 in patients with ASA-PS of I, II, III, IV, I E, II E, III E, and IV E, respectively. The mortality rates after cardiac arrest totally attributable to anesthesia were 0.00, 0.00, 0.61 and 4.53 in patients with ASA-PS of I-IV, I E-II E, III E, and IV E, respectively. The overall mortality rates totally attributable to anesthesia were 0.00, 0.04, 0.18, 0.00, 0.00, 0.61 and 4.53 in patients classified to ASA-PS of I, II, III, IV, I E-II E, III E, and IV E, respectively. Only one death, due to overdose of anesthetics, was reported among patients with good physical status (ASA-PS of I, II, II E and II E). Anesthetic management was mainly responsible for critical events in patients with good physical status, while co-existing diseases were in those with poor physical status. The major co-existing diseases or conditions leading to critical events were heart diseases in elective anesthetics, and hemorrhagic shock in emergency anesthetics. We reconfirmed that ASA-PS is beneficial to predict perioperative mortality and morbidity. It also seems likely that we should make much more efforts to reduce anesthetic morbidity in patients with good physical status, and to improve preanesthetic assessment and preparation of cardiovascular conditions in those with poor physical status.

[Annual study of perioperative mortality and morbidity for the year of 1999 in Japan: the outlines--report of the Japan Society of Anesthesiologists Committee on Operating Room Safety].

Anesthetic mortality and morbidity in Japan Society of Anesthesiologists (JSA) Certified Training Hospitals (CTH) for the year 1999 were reported as continuation of annual studies started in 1993. The JSA Committee on Operating Room Safety (CORS) sent confidential questionnaires to 774 CTH and received valid responses from 60.3% of hospitals. A total number of 793,840 anesthetics were documented. The respondents were asked to report all cases of cardiac arrests and other critical incidents (serious hypotension, serious hypoxemia and others), and their outcomes (death in operating room, death within 7 days, transfer to vegetative state and rescue without sequelae) as well as one principal cause for each incident from list of 52 items. They were also requested to submit the tabulation of patients by ASA physical status, age distribution, surgery sites and anesthetic methods. Analysis was made by total incidents under anesthesia/surgery, and also by incidents totally attributable to anesthetic management (AM), due to preoperative complications (PC), due to intraoperative pathological events (IP) and due to surgery (SG), with special reference to each of four tabulation groups and the whole group of patients. This paper focused analysis on all patients, as analyses with special reference to ASA physical status, age distribution, surgery sites and anesthetic methods were previously reported. Total incidence of cardiac arrest under anesthesia/surgery was 6.53 per 10,000 anesthetics. PC, IP and SG represented principal causes in 42.9%, 22.0% and 21.4% causes of total cardiac arrest cases, respectively. AM was noted as the principal cause in 12.0% of cases, with an incidence rate of 0.78 per 10,000. In 52 more detailed classification of principal causes, the most frequent cause of cardiac arrest was preoperative hemorrhagic shock, 20.3% of all cardiac arrests. The second cause was massive hemorrhage and/or hypovolemia due to surgical procedures (13.1%), and the third was intraoperative myocardial infarction/coronary ischemia/coronary spasm (9.5%). Prognoses of cardiac arrest cases declined due to PC: 71.1% of cardiac arrests died in the operating room or within 7 days after surgery and only 19.8% survived without sequelae. The best prognoses were found in cardiac arrest cases due to AM: 69.4% survived without sequelae and 12.9% died. The mortality rate post-cardiac arrest was 3.44 per 10,000 anesthetics, of those 0.10 due to AM, 0.57 due to IP, 1.99 due to PC and 0.76 due to SG. The mortality rate after critical incidents other than cardiac arrest such as severe hypotension and severe hypoxemia was 3.75, of those 0.03 due to AM, 0.28 due to IP, 2.31 due to PC and 1.13 due to SG. The final mortality rate attributable to anesthesia/surgery including deaths post-cardiac arrest and after other critical incidents was 7.19 per 10,000 anesthetics and very close to 7.18 [6.22, 8.13], that of mean [95% C.I.] in 1994-1998. The final mortality rate totally attributable to anesthesia was 0.13 per 10,000 anesthetics, which was significantly improved from 0.21 [0.15, 0.27], that of mean [95% C.I.] in 1994-1998. IP, PC and SG showed the final mortality rate of 0.84, 4.30 and 1.89, respectively. Five major causes of all critical incidents were massive hemorrhage due to surgical procedures (20.8%), preoperative hemorrhagic shock (10.7%), surgical technique (8.0%), inappropriate airway management (5.2%) and intraoperative myocardial infarction and coronary ischemia (4.5%). Drug overdose or selection error (3.9%) and overdose of main anesthetic (2.9%) as a result of human error occupied the 7th and 10th places. As far as anesthetic management to reduce mortality and morbidity related to anesthesia is concerned, we should increase vigilance to avoid human errors in addition to improving preanesthetic preparations and assessment of cardiovascular status as well as intraoperative management of cardiovascular events.

Marked therapeutic effect of dimyristoylphosphatidylcholine liposomes on carcinoma mice model in vivo.

Significantly prolonged survival rate was obtained for the first time using carcinoma mice models after the administration of single-component liposomes of dimyristoylphosphatidylcholine (DMPC) without any drug. An increase in lymphocytes under optical microscope was observed without any increase in the neutrophils count, suggesting that the DMPC liposomes might inhibit the tumor growth as well as increase in lymphocytes in vivo.

Derivation of extracellular fluid volume fraction and equivalent dielectric constant of the cell membrane from dielectric properties of the human body. Part 1: Incorporation of fat tissue into cell suspension model in the arm.

The non-invasive characterisation of cell pathophysiology is clinically important. A cell suspension model is applied to derive the extracellular fluid (ECF) volume fraction and the equivalent dielectric constant of the cell membrane epsilon m from the dielectric properties of human arms. Frequency-dependent dielectric constants and electrical conductivities of arms are obtained from 35 surgical patients over a frequency range of 5-1000 kHz. The cell suspension model is applied to fit the data using a complex non-linear least-squares method. The arms show typical dielectric dispersions, although the cell suspension model yields a poor fitting in dielectric constants at lower frequencies and electrical conductivities at higher frequencies. In contrast, a new cell suspension model, taking into account the fat tissue component, remarkably improves the overall fitting performance, allowing estimation of the volume fractions of ECF (0.34 +/- 0.05) and fat tissue (0.16 +/- 0.04) and the equivalent epsilon m (23 +/- 9). The resulting estimates of the volume fraction of fat tissue are in good correlation with arm skinfold thickness (fat volume fraction of arm = 2.42 x 10(-3) x arm skinfold thickness (mm) + 0.099, R = 0.756, p < 0.0001). Therefore it is concluded that the newly derived cell suspension model is well suited for the description of the dielectric properties of human tissues and thus the derivation of the ECF volume fraction and equivalent epsilon m.

Derivation of extracellular fluid volume fraction and equivalent dielectric constant of the cell membrane from dielectric properties of the human body. Part 2: A preliminary study for tracking the progression of surgical tissue injury.

A study is conducted to determine whether the extracellular fluid (ECF) volume fraction and equivalent dielectric constant of the cell membrane epsilon m, derived from the dielectric properties of the human body can track the progression of surgical tissue injury. Frequency-dependent dielectric constants and electrical conductivities of body segments are obtained at surgical (trunk) and non-surgical sites (arm and leg) from five patients who have undergone oesophageal resections, before and at the end of surgery and on the day after the operation. The ECF volume fraction and the equivalent epsilon m of body segments are estimated by fitting the dielectric data for body segments to the cell suspension model incorporating fat tissue, and their time-course changes are compared between body segments. By the day after the operation, the estimated ECF volume fraction has increased in all body segments compared with that before surgery, by 0.13 in the arm, 0.16 in the trunk and 0.14 in the leg (p < 0.05), indicating postoperative fluid accumulation in the extracellular space. In contrast, the estimated equivalent epsilon m shows a different time course between body segments on the day after the operation, characterised by a higher change ratio of epsilon m of the trunk (1.34 +/- 0.66, p < 0.05), from that of the arm (0.66 +/- 0.34) and leg (0.61 +/- 0.11). The results suggest that the equivalent epsilon m of a body segment at a surgical site can track pathophysiological cell changes following surgical tissue injury.

Hemodynamic effects of milrinone during weaning from cardiopulmonary bypass: comparison of patients with a low and high prebypass cardiac index.

OBJECTIVE: To compare the hemodynamic effects of milrinone during weaning from cardiopulmonary bypass (CPB) in patients with a low pre-CPB cardiac index (CI) <2.5 L/min/m2) and in patients with a high pre-CPB CI (> or =2.5 L/min/m2). DESIGN: Prospective, randomized, double-blind study. SETTING: University hospital. PARTICIPANTS: Forty-eight patients scheduled for elective coronary artery bypass graft surgery. INTERVENTION: Patients were divided into 4 groups: (1) low pre-CPB CI/placebo, (2) low pre-CPB CI/milrinone, (3) high pre-CPB CI/placebo, and (4) high pre-CPB CI/milrinone. Patients received a loading dose of 20 microg/kg of milrinone followed by an infusion of 0.2 microg/kg/min or placebo 15 minutes before the anticipated weaning time. MEASUREMENTS AND MAIN RESULTS: In the low pre-CPB CI/ placebo group, low CIs and high systemic vascular resistances (SVRs) were observed after CPB. High doses of dopamine and dobutamine were needed, and infusion of epinephrine was used in 5 of the 12 patients for hemodynamic support. Milrinone improved CI and reduced SVR in the low pre-CPB CI/milrinone group. Norepinephrine was needed to maintain an adequate systemic blood pressure in 6 of the 12 patients, however. In the high pre-CPB CI/placebo group, satisfactory CIs and SVRs were observed during weaning from CPB with low doses of dopamine and dobutamine. Milrinone significantly increased CI and decreased SVR in the high pre-CPB CI/milrinone group: 10 of the 12 patients had CIs above the upper limit of normal, and 7 patients had SVRs below the lower limit of normal. CONCLUSION: Milrinone was effective during weaning from CPB in patients with a low pre-CPB CI. Milrinone in combination with norepinephrine was a good alternative to epinephrine for the treatment of myocardial dysfunction after CPB.

[Measurements of extracellular water volume by bioelectrical impedance analysis during perioperative period of esophageal resection].

Segmental bioelectrical impedance analysis (BIA) was conducted in five patients who underwent esophageal resections. Resistance values fitted at zero frequency (R0) in each body segment (arm, trunk and leg) were determined before the induction of anesthesia, at the end of surgery and on the second or third postoperative day. Extracellular water volume (ECW) in each body segment was estimated using the equation derived from the cell suspension theory. ECW in whole body was obtained from the sum of each body segment. R0 in trunk and leg significantly decreased at the end of surgery compared to the values before the induction of anesthesia (P < 0.05). The change ratio of R0 in trunk before the induction of anesthesia was significantly lower at the end of surgery than that in arm (P < 0.05), resulting from the most striking fluid accumulation in the trunk. Postoperatively, R0 in all body segments, however, appeared to decrease similarly compared to the values before the induction of anesthesia, suggesting the redistribution phenomena of extracellular water among body segments. The correlation (r = 0.90, P < 0.001) and good agreement [bias = 0.01 (L)] between net fluid balances and estimates of ECW changes in whole body suggest that BIA allows close monitoring of tissue hydration during perioperative period by providing estimates of ECW in body segments.

Chemotherapy with hybrid liposomes for melanomatosis.

The inhibitory effects of the hybrid liposomes on the growth of B-16 melanoma cells in vitro and in vivo were examined. The 50% inhibitory concentration of the hybrid liposomes composed of 90 mol% dimyristoylphosphatidylcholine (DMPC) and 10 mol% polyoxyethylenedodecyl ether (C12(EO)10) was one-twelfth of that of DMPC liposomes. It was noteworthy that for the first time significantly prolonged survival was obtained using a mouce model of carcinoma after the administration of the hybrid liposomes of 90 mol% DMPC/10 mol% C12(EO)n (n=10 or 23) without antitumor drugs.

Segmental bioelectrical impedance analysis improves the prediction for extracellular water volume changes during abdominal surgery.

OBJECTIVE: To determine whether the segmental multifrequency bioelectrical impedance analysis may improve the prediction for intraoperative changes in extracellular water volume (deltaECW) compared with whole body multifrequency bioelectrical impedance analysis in abdominal surgical patients. DESIGN: Prospective, consecutive sample. SETTING: Surgical operative patients in a university-affiliated city hospital. PATIENTS: Thirty patients who underwent elective gastrointestinal surgery. INTERVENTIONS: Multifrequency bioelectrical impedance analysis was conducted preoperatively (before the induction of anesthesia) and postoperatively (after recovery from anesthesia). Resistance values fitted at zero frequency (R0) in the whole body and in each body segment (arm, trunk, and leg) were determined by performing nonlinear curve-fitting and subsequent extrapolation. DeltaECW values were estimated from the whole body resistance between wrist and ankle using two different prediction formulas. In segmental multifrequency bioelectrical impedance analysis, however, ECW was obtained as the sum of each body segment (arms, trunk, and legs) using the equation newly derived from the cell suspension theory. DeltaECW estimated from both measurements were compared with net fluid balances during surgery. MEASUREMENTS AND MAIN RESULTS: R0 in whole body and all body segments significantly decreased after surgery (p < .0001). The most striking decrease in post/preoperative ratios was found in the R0 in the trunk. The post/preoperative ratio of the R0 value in the trunk was significantly lower than the post/preoperative ratio of the R0 value in the leg (p = .0007). DeltaECW from segmental multifrequency bioelectrical impedance analysis was similar to net fluid balance (r2 = .80, bias = -0.03 L), whereas whole body multifrequency bioelectrical impedance analysis resulted in considerable underestimations of deltaECW (r2 = .50, .51, bias = 0.95, 0.53 L). CONCLUSIONS: The difference in the prediction of deltaECW between whole body and segmental multifrequency bioelectrical impedance analysis may be explained by the significant decrease in the resistance of the trunk, which contributed only minimally to the whole body resistance. Segmental multifrequency bioelectrical impedance analysis provides a better approach to predict ECW changes in critically ill patients with nonuniform fluid distribution.

Processed electroencephalogram during combined extradural and general anaesthesia.

The processed electroencephalogram (pEEG) was monitored in eight patients undergoing gynaecological laparotomy under combined extradural and nitrous oxide-isoflurane anaesthesia. Pre-incisional mean spectral edge frequency 95 percentile (SEF95) and median frequency (MF) were 11.67 (SD 1.63) Hz and 3.74 (0.24) Hz, respectively. After skin incision, both SEF95 and MF decreased to 6.61 (2.04) Hz and 2.72 (0.32) Hz, respectively (P < 0.001). An increase in mean arterial pressure after incision suggested inadequate depth of anaesthesia. After introduction of extradural analgesia, these variables returned to pre-incisional values (SEF95 11.65 (1.73); MF 4.02 (0.41)). Reduction of end-tidal isoflurane from 1.0% to 0.5% after extradural analgesia did not cause significant pEEG changes. pEEG may assist anaesthetists to recognize adequacy of combined general-extradural anaesthesia.

Changes in regional lung mechanics and ventilation distribution after unilateral pulmonary artery occlusion.

Regional pneumoconstriction induced by alveolar hypocapnia is an important homeostatic mechanism for optimization of ventilation-perfusion matching. We used positron imaging of 13NN-equilibrated lungs to measure the distribution of regional tidal volume (VT), lung volume (VL), and lung impedance (Z) before and after left (L) pulmonary artery occlusion (PAO) in eight anesthetized, open-chest dogs. Measurements were made during eucapnic sinusoidal ventilation at 0.2 Hz with 4-cmH2O positive end expiratory pressure. Right (R) and L lung impedances (ZR and ZL) were determined from carinal pressure and positron imaging of dynamic regional VL. LPAO caused an increase in magnitude of ZL relative to magnitude of ZR, resulting in a shift in VT away from the PAO side, with a L/R magnitude of Z ratio changing from 1.20 +/- 0.07 (mean +/- SE) to 2.79 +/- 0.85 after LPAO (P < 0.05). Although mean L lung VL decreased slightly, the VL normalized parameters specific admittance and specific compliance both significantly decreased with PAO. Lung recoil pressure at 50% total lung capacity also increased after PAO. We conclude that PAO results in an increase in regional lung Z that shifts ventilation away from the affected area at normal breathing frequencies and that this effect is not due to a change in VL but reflects mechanical constriction at the tissue level.

An apnea monitor using a rapid-response hygrometer.

OBJECTIVE: The aim of this study was to detect cyclic changes in the relative humidity (RH) occurring with spontaneous respiration using a rapid-response hygrometer, and to evaluate its potential applicability as an apnea monitor in nonintubated subjects. METHODS: Respiratory monitoring using a rapid-response hygrometer was performed in spontaneously breathing, nonintubated subjects. Changes in RH during spontaneous breathing were measured in adult volunteers, breathing room air and nonintubated infants who underwent cardiac catheterization under intravenous anesthesia. The detection of apnea by the hygrometer was assessed in the adult patients during the induction of anesthesia and those undergoing minor gynecologic surgery under epidural anesthesia. The hygrometric sensor was positioned in front of the nostril; a simultaneous recording of CO2 was obtained from nasal cannulas by a sidestream capnograph. Each waveform was collected and acquired by a PC-based computer, and data were analyzed off-line. RESULTS: The hygrometer showed a rapid response to the cyclic changes in RH during spontaneous respiration and could identify respiratory phases of tachypnea as high as 60 breaths per minute in infants. RH rapidly increased to 80% with a plateau on expiration and decreased to 40% on inspiration. These phasic changes, consisting of three distinct phases, expiratory upstroke, plateau and inspiratory downslope, preceded the corresponding capnographic changes by nearly two seconds. Expiratory increase in RH appeared to be influenced by the respiratory flow rate as well as the response time of the equipment. As respiration was depressed due to airway obstruction, the magnitude of RH gradually decreased and then disappeared at the time of apnea. CONCLUSIONS: The hygrometer could detect cyclic changes in RH during spontaneous respiration. Apnea was immediately detected by the decreases in the magnitude of RH. The results demonstrate the potential usefulness of a rapid-response hygrometer for monitoring respiratory rate and early detection of apnea.