[Show abstract][Hide abstract] ABSTRACT: Singlet oxygen is a causal factor in light-induced skin photoaging and the cytotoxic process of tumor cells in photodynamic chemotherapy. To develop a better understanding of the functional consequences of protein modification by singlet oxygen, the effects of naphthalene endoperoxide on lysosomal protease, cathepsin, were examined. When the soluble fraction of normal human fetal skin fibroblast cells was treated with the endoperoxide, the activities of cysteine proteases, cathepsins B and L/S, were inhibited, but that of aspartate protease, cathepsin D/E, was not. The reduction of the endoperoxide-treated soluble fractions by treatment with dithiothreitol barely recovered the activities. Cathepsin B, purified from normal human liver, exhibited similar profiles to that in cytosol. These data suggest that singlet oxygen oxidatively modifies an amino acid residue essential for catalysis and consequently results in the irreversible inactivation of cysteine protease-type cathepsin.
Biochemical and Biophysical Research Communications 06/2005; 331(1):215-23. DOI:10.1016/j.bbrc.2005.03.146 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We tested a hypothesis that extended gynecological paraaortic lymph node dissection seriously impairs postoperative pancreatic function.
We studied 82 patients who underwent gynecologic surgery for malignancy from January, 2002 to October, 2003. After scheduled operation, we assigned them to one of two groups; patients who underwent extended gynecological paraaortic lymph node dissection (n=34) or those who did not (n=48). We measured plasma amylase levels in all patients before operation and 1, 3, 7 days after operation.
Preoperative amylase levels were the same in the two groups. Time-dependent increases in plasma amylase level were noted in both groups. From 1 to 3 days after operation, however, plasma amylase levels were significantly higher in patients who had undergone paraaortic lymph node dissection than in those who had not. Furthermore, lethal postoperative pancreatitis developed in one patient who showed marked high levels in plasma amylase level after paraaortic lymph node dissection.
Our results suggest that paraaortic lymph node dissection in gynecologic operations seriously impairs pancreatic function and that one should maintain a high suspicion of postoperative pancreatitis.
Masui. The Japanese journal of anesthesiology 05/2005; 54(4):393-6.
[Show abstract][Hide abstract] ABSTRACT: General anesthetics modulate autonomic nervous system function including thermoregulatory control, which resides in the preoptic area of the anterior hypothalamus. However, the mechanism by which anesthetics modulate hypothalamic function remains unknown. We hypothesized that isoflurane increases norepinephrine release in the preoptic area and in the posterior hypothalamus causing hypothermia during anesthesia. To test this hypothesis, we performed a series of in vivo and in vitro studies in rats. In vivo studies: 1) Norepinephrine release was measured by microdialysis in the preoptic area or the posterior hypothalamus (n=9 each) before, during (30 min), and after (50 min) rats were anesthetized with 2% isoflurane. 2) In five rats, blood gases and arterial pressure were measured. 3) Body temperature changes (n=6 each) were measured after prazosin (0, 0.05, 0.5 microg), norepinephrine (0, 0.1, 1.0 microg), or 0.5 microg prazosin with 1.0 microg norepinephrine injection into the preoptic area. In vitro study: Norepinephrine release was measured from anterior or posterior hypothalamic slices (n=10 each) incubated with 0, 1, 2, or 4% isoflurane in Ca2+-containing buffer or with 4% isoflurane (n=10) in Ca2+-free buffer. Data were analyzed with repeated measures or factorial ANOVA and Student-Newman-Keuls tests. P<0.05 was significant. During anesthesia, norepinephrine release in the preoptic area was increased approximately 270%, whereas the release in the posterior hypothalamus remained unchanged. During emergence, posterior hypothalamic norepinephrine release increased by approximately 250% (P<0.05). Rectal temperature changes correlated with norepinephrine release from the preoptic area. Norepinephrine in the preoptic area enhanced isoflurane-induced hypothermia, while prazosin reversed it. Norepinephrine release from anterior hypothalamic slices increased at all isoflurane concentrations, but only at the highest concentration in posterior hypothalamic slices. Under Ca2+-free conditions, 4% isoflurane increased norepinephrine from both regions. These results suggest that augmentation of norepinephrine release in the preoptic area is responsible for hypothermia during general anesthesia.
[Show abstract][Hide abstract] ABSTRACT: We tested a hypothesis that major gene variations of methicillin-resistant Staphylococcus aureus (MRSA) are detectable in a single patient.
We isolated 363 strains of MRSA in 192 patients diagnosed as having MRSA infection in Yamagata University Hospital. By an established pulsed-field gel electrophoresis method, all strains were analysed by Sma I macrorestriction patterns of genomic DNA.
A total of 54 different electrophoresis was observed, (8 major types each of which has 5-8 subtypes). Two or more strains could be isolated in 68 patients. Out of these patients 2-4 different gene variations were detected in a single patient.
Our results suggest that gene variations can be detectable in a single patient and that caution should be paid for diagnosis of MRSA cross infection.
Masui. The Japanese journal of anesthesiology 12/2004; 53(11):1243-8.
[Show abstract][Hide abstract] ABSTRACT: Other than age, the risk factors for postherpetic neuralgia are not well established. We studied whether the concentration of interleukin 8 in the cerebrospinal fluid is associated with the risk of postherpetic neuralgia.
We enrolled 170 patients more than 50 years old who had a typical painful and nontrigeminal herpetic rash. Patients were treated with acyclovir; no corticosteroids were given. Cerebrospinal fluid was taken for analysis of interleukin 8 during and at full crusting of the herpetic rash. Age, sex, comorbid conditions, prodromal pain, localization and severity of herpetic rash, number of skin lesions, and degree of pain were recorded. We used multivariate logistic regression modeling to identify significant predictive factors. Receiver operating characteristic (ROC) curves were evaluated to determine the contribution of each factor.
Six months after healing, 31 patients (18%) had postherpetic neuralgia; 27 patients still had it after 1 year. Only three variables-age (odds ratio [OR] = 2.7 per 10-year increase; 95% confidence interval [CI]: 1.2 to 6.2), acute pain (OR = 1.8 per unit increase in visual analog scale; 95% CI: 1.2 to 2.8), and interleukin 8 concentration in the cerebrospinal fluid at full crusting of the herpetic rash (OR = 1.6 per 20-microg/L increase; 95% CI: 1.3 to 2.0)-were significant predictors of postherpetic neuralgia at 1 year. Interleukin 8 concentration also had the highest area under the ROC curve at these evaluation points (P <0.001).
Our results suggest that interleukin 8 concentration in the cerebrospinal fluid at full crusting of herpetic rash may be useful for identifying patients who are likely to develop intractable postherpetic neuralgia.
The American Journal of Medicine 03/2004; 116(5):318-24. DOI:10.1016/j.amjmed.2003.10.027 · 5.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: During a period of five years from January 1996 through December 2000 total intravenous anesthesia with mainly propofol, fentanyl and ketamine was administered to 26,079 patients including cardiac and neurosurgical patients at the University of Hirosaki Hospital and five other affiliated hospitals. The patients studied ranged from 1 year 8 months to 93 years in age, 9.2 kg to 135.0 kg in body weight and from 18 min to 22 hours 50 min in anesthetic time. With adequate monitoring, fentanyl 1-2 micrograms.kg-1 was given at first, then total-dose of ketamine 1 mg.kg-1 and propofol 1-2 mg.kg-1 were administered for the induction of anesthesia in adult patients. A total dose of fentanyl 3-15 micrograms.kg-1 was given combined with propofol 5-10 mg.kg-1 and ketamine 0.3-1.0 mg.kg.h-1. In craniotomy patients, ketamine was excluded. For pediatric patients, sevoflurane anesthesia was employed to establish i.v. route, and intravenous agents were given almost same as in the same manner as in adult patients. None of them developed either cardiac arrest or severe cardiovascular insufficiencies due to anesthesia alone. Their postoperative hepatic and renal functions evaluated by various biochemical indices and urine output were adequately maintained during anesthesia and for a week postoperatively. They were followed up to 3 months postoperatively only to fail to detect any adverse events related directly to this method of anesthesia. These data suggest that total intravenous anesthesia with propofol, fentanyl and ketamine has a very wide margin of safety.
Masui. The Japanese journal of anesthesiology 01/2003; 51(12):1336-42.
[Show abstract][Hide abstract] ABSTRACT: A 49 year-old-woman was scheduled for resection of a huge hemangioma of the face and neck region. After the resection, severe edema developed on the tongue, larynx, and pharynx even leaving no space between the tracheal tube and these tissues. Prolonged respiratory management with endotracheal tube intubation was needed to maintain the upper airway for more than three weeks. Tracheostomy was performed 27 days after the operation. Two weeks later, the edema of the upper airway subsided. Thereafter her clinical course was uneventful, and she was discharged 22 days after the tracheostomy. Resection of a huge facial and neck hemangioma should be carefully managed as it can be followed by unexpected severe postoperative upper airway edema leading to suffocation.
Masui. The Japanese journal of anesthesiology 12/2001; 50(11):1253-6.
[Show abstract][Hide abstract] ABSTRACT: Conventional treatments are often ineffective for patients having painful abdominal scars. There are painful points in and around scar tissue. We tested the hypothesis that insertion of intradermal needles into these painful points reduces scar pain.
Patients with abdominal scar pain with painful points that is not relieved by conventional treatments were allocated to a treatment group (n = 23), a sham-treatment group (n = 23), or a control group (n = 24). In the treatment group, intradermal needles were inserted into painful points detected by a pressure threshold meter (pain < or = 2.5 kg/cm(2)). In the sham-treatment group, the same needles were inserted into nonpainful points. The needles were kept in place for 24 hours. This process was repeated 20 times over a 4-week period. Responses were evaluated before and at the end of treatment, and 4 and 26 weeks after the treatment. Continuous and lancinating pain was evaluated on a 10-cm visual analog scale. We measured the area of pain and the pressure required to initiate painful-point pain. All patients took diclofenac as needed and completed a diary of daily diclofenac consumption.
Patients in the treatment group showed a marked reduction in all pain parameters (>70%). In contrast, analgesia was minimal in the other groups. The decreases in the pain threshold pressure correlated with the decreases in continuous and lancinating pain (r =.57 and r =.63, respectively).
Our data suggest that insertion of intradermal needles into painful points is a remarkably effective treatment for intractable abdominal scar pain. Analgesia presumably results from inactivation of painful points, through a yet to be elucidated mechanism.
Regional Anesthesia and Pain Medicine 11/2001; 26(6):532-8. DOI:10.1053/rapm.2001.25897 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IMPLICATIONS: This report describes six patients who had marked hyperkalemia 60-150 min after cessation of intravenous ritodrine, which had been administered for management of preterm labor. Abnormal electrocardiographic findings are very important clues for a prompt diagnosis of hyperkalemia.
[Show abstract][Hide abstract] ABSTRACT: Objective: Anesthesia and surgery decrease antimicrobial and increase proinflammatory functions of alveolar immune cells. Thus, anti-inflammatory agents that do not further suppress antimicrobial functions are required. We tested the hypothesis that intraoperative prostaglandin E1 (PGE1) suppresses proinflammatory responses and prevents the reduction in antimicrobial responses of alveolar immune cells.
Design: Prospective, randomized, controlled, double-blind study.
Setting: University hospital.
Patients: A total of 40 patients undergoing elective orthopedic surgery under propofol/fentanyl anesthesia.
Intervention: In double-blind fashion, the patients received PGE1 from the beginning to the end of surgery (PGE1 group, n = 20) or nothing (control group, n = 20).
Methods and Main Results : Alveolar immune cells were harvested by bronchoalveolar lavage immediately after induction of anesthesia; 2, 4, and 6 hrs after induction of anesthesia; and at the end of surgery. We measured opsonized and nonopsonized phagocytosis. Microbicidal activity was evaluated to directly kill Listeria monocytogenes in alveolar macrophages. Finally, we determined the expression of proinflammatory cytokines including interleukin (IL)-1β, IL-8, interferon-γ, and tumor necrosis factor-α, and that of anti-inflammatory cytokines (IL-4 and IL-10) by semiquantitative polymerase chain reaction. Nonopsonized and opsonized phagocytosis and microbicidal activity of alveolar macrophages decreased and the expression of genes for all pro- and anti-inflammatory cytokines increased significantly over time in both groups. Starting 2–4 hrs after induction of anesthesia, the increases in gene expression of proinflammatory cytokines were 1.5–3 times smaller in the PGE1 than in the control group. Starting 6 hrs after anesthesia, the increase in gene expression of IL-10 was 1.5–3 times greater in the PGE1 than in the control group. Intraoperative decreases in phagocytic and microbial activities were the same in the two groups.
Conclusion: Intraoperative PGE1 not only suppressed proinflammatory responses, but also protected antimicrobial functions of alveolar macrophages, possibly because PGE1 is mostly inactivated in the pulmonary intravascular space. Our results suggest that intraoperative PGE1 protects the pulmonary immune defense in alveolar immune cells.
Critical Care Medicine 09/2001; 29(10):1943-1949. DOI:10.1097/00003246-200110000-00016 · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In a controlled and double-blind study, the authors tested the hypothesis that preoperative insertion of intradermal needles at acupoints 2.5 cm from the spinal vertebrae (bladder meridian) provide satisfactory postoperative analgesia.
The authors enrolled patients scheduled for elective upper and lower abdominal surgery. Before anesthesia, patients undergoing each type of surgery were randomly assigned to one of two groups: acupuncture (n = 50 and n = 39 for upper and lower abdominal surgery, respectively) or control (n = 48 and n = 38 for upper and lower abdominal surgery, respectively). In the acupuncture group, intradermal needles were inserted to the left and right of bladder meridian 18-24 and 20-26 in upper and lower abdominal surgery before induction of anesthesia, respectively. Postoperative analgesia was maintained with epidural morphine and bolus doses of intravenous morphine. Consumption of intravenous morphine was recorded. Incisional pain at rest and during coughing and deep visceral pain were recorded during recovery and for 4 days thereafter on a four-point verbal rating scale. We also evaluated time-dependent changes in plasma concentrations of cortisol and catecholamines.
Starting from the recovery room, intradermal acupuncture increased the fraction of patients with good pain relief as compared with the control (P < 0.05). Consumption of supplemental intravenous morphine was reduced 50%, and the incidence of postoperative nausea was reduced 20-30% in the acupuncture patients who had undergone either upper or lower abdominal surgery (P < 0.01). Plasma cortisol and epinephrine concentrations were reduced 30-50% in the acupuncture group during recovery and on the first postoperative day (P < 0.01).
Preoperative insertion of intradermal needles reduces postoperative pain, the analgesic requirement, and opioid-related side effects after both upper and lower abdominal surgery. Acupuncture analgesia also reduces the activation of the sympathoadrenal system that normally accompanies surgery.
[Show abstract][Hide abstract] ABSTRACT: Background: In a controlled and double-blind study, the authors tested the hypothesis that preoperative insertion of intradermal needles at acupoints 2.5 cm from the spinal vertebrae (bladder meridian) provide satisfactory postoperative analgesia.
[Show abstract][Hide abstract] ABSTRACT: Tobacco smoking inhibits alveolar macrophage function, but cessation of smoking markedly reduces the risk of postoperative pulmonary complications. The authors therefore evaluated the effect of nonsmoking duration on both antimicrobial and inflammatory functions of alveolar macrophages during anesthesia and surgery.
The authors studied 15 patients who had never smoked, 15 current smokers, and 41 former smokers, all of whom underwent general anesthesia. Former smokers were further allocated to one of three groups depending on their smoke-free periods: 2 months (n = 13), 3-5 months (n = 13), and 6-12 months (n = 15). Alveolar immune cells were collected by bronchoalveolar lavage immediately after induction of anesthesia, at 2 and 4 h after induction of anesthesia, and at the end of surgery. Opsonized and nonopsonized phagocytosis were measured. Microbicidal activity was determined as the ability of the macrophages to kill Listeria monocytogenes directly. Finally, we determined the expression of proinflammatory cytokines, including interleukin 1beta, interleukin 8, interferon gamma, and tumor necrosis factor alpha, and of antiinflammatory cytokines (interleukin 4 and 10) by semiquantitative polymerase chain reaction.
Nonopsonized and opsonized phagocytosis and microbicidal activity of alveolar macrophages (antimicrobial functions) decreased 20-50%, and the expression of genes for all proinflammatory and antiinflammatory cytokines increased 3-30-fold over time in all groups. Starting 4 h after induction of anesthesia, the decreases in antimicrobial functions were 1.5-3 times greater in current and former smokers (2 months' abstinence) than in patients who had never smoked. Starting 4 h after anesthesia, the increase in expression of all cytokines, except interleukin 8, was twofold to fivefold less in current and former smokers (2-6 months' abstinence) than in patients who had never smoked.
Our data suggest that former smokers may have a limited ability to mount effective pulmonary immune defenses for long as 6 months after stopping cigarette use.
[Show abstract][Hide abstract] ABSTRACT: There is no effective treatment for intractable postherpetic neuralgia. Because there is evidence that postherpetic neuralgia has an inflammatory component, we assessed treatment with intrathecally administered methylprednisolone to reduce pain in patients with this disorder.
We enrolled 277 patients who had had intractable postherpetic neuralgia for at least one year, 270 of whom were followed for two years. The patients were randomly assigned to receive intrathecal methylprednisolone and lidocaine (3 ml of 3 percent lidocaine with 60 mg of methylprednisolone acetate, 89 patients), lidocaine alone (3 ml of 3 percent lidocaine, 91 patients), or no treatment (90 patients) once per week for up to four weeks. Each weekly dose was injected into the lumbar intrathecal space. Pain was evaluated before randomization, at the end of the treatment period, and then four weeks, one year, and two years later. Samples of cerebrospinal fluid were obtained for measurement of interleukin-8 before and at the end of the treatment period.
There was minimal change in the degree of pain in the lidocaine-only and control groups during and after the treatment period. In the methylprednisolone-lidocaine group, the intensity and area of pain decreased, and the use of the nonsteroidal antiinflammatory drug diclofenac declined by more than 70 percent four weeks after the end of treatment. No complications related to intrathecal methylprednisolone were observed. Before treatment, the concentrations of interleukin-8 in the cerebrospinal fluid were inversely related to the duration of neuralgia in all the patients (r=-0.49, P<0.001). In the patients who received methylprednisolone, interleukin-8 concentrations decreased by 50 percent, and this decrease correlated with the duration of neuralgia and with the extent of global pain relief (P<0.001 for both comparisons).
The results of this trial indicate that the intrathecal administration of methylprednisolone is an effective treatment for postherpetic neuralgia.
New England Journal of Medicine 11/2000; 343(21):1514-9. DOI:10.1056/NEJM200011233432102 · 55.87 Impact Factor