Biomedical subjects

T Okutomi

Publications and source records attributed to T Okutomi.

At least 19 recordsLinked to original sources

PubMed2006

The effect of hydroxyethylstarch infusion on bupivacaine pharmacokinetics in rats.

BACKGROUND: Bupivacaine is the agent most often used for labor analgesia. However, the risk of accidental intravascular injection of this drug and consequent acute systemic toxicity is ever-present. Although hydroxyethylstarch (HES) is preferred over crystalloid for prevention of hypotension during regional anesthesia, the pharmacokinetics of bupivacaine during fluid preloading has not been studied. METHODS: Twenty-four awake Sprague-Dawley rats were randomly allocated to receive the continuous intravenous infusion of HES 70K, 200K or 400K, or normal saline (NS). After 1 hour of prehydration all animals received bupivacaine, 1mg kg(-1), bolus, followed by a continuous infusion, 0.4mg kg(-1) min(-1) for 15 minutes. After the completion of bupivacaine infusion serial arterial blood samples to determine the plasma bupivacaine concentration were obtained. The plasma concentration-time profile of bupivacaine was fitted to a two-compartment open model, and the estimated intercepts and slopes were used for calculation of standard pharmacokinetic parameters. RESULTS: The mean peak bupivacaine concentration during HES 400K infusion was significantly lower than during NS infusion (1488 +/- 302 ng ml(-1) vs 2388 +/- 582 ng ml(-1)). Mean volume of distribution in each of the three HES groups was greater than in NS group. Mean area under curves (AUC) during HES 200K and HES 400K infusions were significantly lower than during NS infusion (32534 +/- 4180 and 29619 +/- 4431 min ng ml(-1), respectively, vs 39802 +/- 6268 min ng ml(-1)). Mean total clearance of bupivacaine during HES 200K and HES 400K infusions was significantly higher than during NS infusion (115 +/- 14 and 132 +/- 15 ml min(-1) kg(-1), respectively, vs 92 +/- 14 ml min(-1) kg(-1)). CONCLUSION: Our results suggest that the increased volume of distribution during HES infusion could be counterbalanced by the increased total clearance, resulting in unchanged half-life or elimination rate constant of bupivacaine.

Anesthetics, Local↗

PubMed2005

Magnesium and bupivacaine-induced convulsions in awake pregnant rats.

BACKGROUND: Magnesium sulfate (MgSO(4)) is widely used for the treatment and prevention of convulsions associated with preeclampsia. The aim of this study was to determine whether it alters the dose of bupivacaine required to produce convulsions in awake pregnant rats. METHOD: Twelve pregnant rats were pretreated with an intravenous infusion of either MgSO(4) or saline. Following 2 h of the pretreatment, bupivacaine was concomitantly infused in all animals until the onset of convulsions. Mean arterial pressure (MAP) and heart rate (HR) were monitored throughout. Serial arterial samples were obtained during the infusion. At the onset of convulsions, fetuses were delivered and maternal and fetal blood, as well as various tissue samples, were obtained. All samples were assayed for bupivacaine and magnesium concentrations. RESULTS: Maternal MAP and HR decreased significantly shortly after the initiation of MgSO(4), while saline did not affect these measurements. Baseline concentrations of magnesium in plasma were similar in both MgSO(4) and saline groups; magnesium increased significantly during the infusion of MgSO(4). The dose (mean+/-SD) of bupivacaine required to produce convulsions in the animals receiving MgSO(4) was significantly larger (10.2+/-1.9 mg/kg) than that in the saline group (5.9+/-1.0 mg/kg) (P<0.05). As a consequence, bupivacaine concentrations in the brain and liver at the onset of convulsions were greater in animals receiving MgSO(4) (16.0+/-8.4 and 18.2+/-4.3 microg/g wet weight, respectively) than in those given saline (12.1+/-2.2 and 9.9+/-2.0 microg/g wet weight, respectively). Fetal bupivacaine concentrations at the onset of convulsions in the MgSO(4) group were also higher than those in saline group. However, the rate of placental transfer of this drug was similar between MgSO(4) and saline animals. CONCLUSION: This study demonstrates that the clinically used concentration of magnesium sulfate increased the threshold of bupivacaine-induced convulsions in awake rats.

Anesthetics, Local↗

PubMed2002

Intrathecal fentanyl/meperidine combined with low-dose epidural bupivacaine for Cesarean section in a patient with advanced Krukenberg tumors.

This case report demonstrates the anesthetic management of a 41-year-old primiparous parturient with massive ascites due to advanced Krukenberg tumors, undergoing Cesarean section. We chose a combined intrathecal-epidural technique, using intrathecal hypobaric fentanyl and hyperbaric meperidine, and a low dose of epidural bupivacaine in order to avoid hemodynamic instability in this critically ill patient. Surgery was carried out without difficulty under adequate regional anesthesia. The blood pressure was maintained with low doses of phenylephrine and dopamine. Opioid-related complications such as nausea-vomiting, pruritus, drowsiness, and respiratory depression were not observed in this patient. Therefore, intrathecal opioids combined with a low dose of epidural local anesthetics for Cesarean section is suitable for critically ill patients with malignant abdominal tumors, such as a Krukenberg tumor, complicated by massive ascites.

Adjuvants, Anesthesia↗

PubMed2002

Continuous spinal analgesia for labor and delivery in a parturient with hypertrophic obstructive cardiomyopathy.

Induction of labor under analgesia was planned for a 30-year-old-primiparous patient with hypertrophic obstructive cardiomyopathy (HOCM), as her fetal evaluation revealed intrauterine growth restriction at 38 weeks' gestation. However, regional analgesia during labor may present a potential risk for hemodynamic instability in patients with HOCM due to the possibility of a sympathetic block, as a result of vasodilation associated with the administration of local anesthesia. This case report demonstrates the successful management of the patient with analgesia provided by a continuous spinal catheter dosed with a continuous infusion of fentanyl and supplemental meperidine. Fetal surveillance monitoring included fetal pulse oximetry in addition to conventional cardiotocography, on the basis of which cesarean section was avoided.

Adult↗

PubMed2001

Modified labial tissue sliding flaps for repairing large lower lip defects.

PURPOSE: Common flap techniques for reconstructing large defects in the lower lip are often destructive and complex and result in unsatisfactory function and appearance. This article describes a modified technique that uses sliding labial tissue flaps to avoid these problems. PATIENTS AND METHODS: Eight patients with lower lip carcinomas had defects ranging from one third to four fifths of the length of the lower lip after tumor resection. The defects were closed with sliding labial tissue flaps, taking advantage of the elasticity of soft tissue to reduce the loss of normal tissue. Patients were followed for 2 to 12 years. RESULTS: The functional and cosmetic results were good, and there were no intra- or postoperative complications. Some patients experienced tightness of the lower lip that disappeared within 6 months. Carcinoma did not recur in any patient after a median follow-up period of more than 5 years. CONCLUSIONS: This modified labial tissue sliding flap technique is simple, safe, functionally and aesthetically satisfactory, sacrifices little healthy tissue, heals rapidly, and requires no further revision. The technique is effective for repairing defects covering one third to four fifths of the lower lip.

Aged↗

PubMed2000

[Clinical effects of adjuvant therapy using Z-100 (Ancer 20 injection) for oral cancer--prevention of stomatitis and hematopoietic impairment].

A combination of radiotherapy and chemotherapy is a usual treatment method for malignant head and neck tumors, however chemoradiotherapy is associated with hematopoietic impairment and serious stomatitis in patients. The clinical effects and evaluation of hematopoietic activity (e.g., leukocyte count) and the degree of stomatitis under adjuvant therapy using Z-100 (Ancer 20 injection) for oral cancer were investigated for preoperative cancer therapy. In order to evaluate the clinical effects of Ancer 20 injection with regard to hematopoietic activity and the degree of stomatitis, a clinical study was performed for 18 patients with oral cancer in our department. The 18 patients, who had oral squamous cell carcinomas (5 of the tongue, 4 of the mandibular gingiva, 3 of the maxillary gingiva, 1 of the floor of the mouth, 3 of the buccal mucosa, and 2 others), were treated with this combination of adjuvant therapy with Ancer 20 injection, from March, 1991 to March, 1997. They were injected with Ancer 20 (twice a week, 40 micrograms) during the cancer treatment period. We investigated hematopoietic activity, (e.g., leukocyte and platelet counts) and the degree of stomatitis periodically, before and after the combined radiotherapy and chemotherapy treatment period. It was found that in the patients who were treated with Ancer 20 injection, the decrease in leukocyte and platelet counts was prevented and the condition of stomatitis was improved. These results suggest that Ancer 20 injection may generally improve various dysfunctions due to hematopoietic impairment by radiotherapy combined with chemotherapy, and improve immunological factors. We conclude that Ancer 20 injection is a useful adjuvant treatment for oral cancer.

Antineoplastic Agents↗

PubMed1999

Saline volume and local anesthetic concentration modify the spread of epidural anesthesia.

PURPOSE: To examine the effects of the volume of saline and the concentration of local anesthetic on the quality of anesthetic level. METHODS: One hundred and fifty two patients received thoracic epidural anesthesia were allocated into two groups; mepivacaine 1% (75 patients) and 1.5% (77 patients). Each group was randomly divided into three subgroups depending on epidural saline volumes of 1 ml, 5 ml, or 10 ml. Fifteen minutes after the injection of 10 ml mepivacaine, the dermatome levels of hypesthesia to cold and pinprick were determined by an individual blinded to the saline volume. RESULTS: The number of spinal segments with hypesthesia to cold in the three subgroups in the mepivacaine 1% group were 12.5 [6-20], 13 [8.5-20.5] and 12.5 [6.5-22], respectively (median [range]). The segments in the mepivacaine 1.5% group were 12 [7-18.5], 14 [8.5-19]* and 15 [6-23]*, respectively (*P < 0.05 vs 1-ml group). The number of spinal segments with hypesthesia for pinprick in the three subgroups in the 1% mepivacaine group were 10.5 [2-22], 10.5 [4-17] and 11 [4-19], respectively. The segments in the mepivacaine 1.5% group were 12 [7.5-16], 12 [7.5-17] and 11.5 [5-22.5], respectively. Saline volume did not alter the anesthetic level of the mepivacaine 1%, although it did affect the anesthetic spread of the mepivacaine 1.5%. In both groups, a differential nerve block was elicited in the 5 ml and 10 ml saline subgroups. CONCLUSION: When a large volume of saline is administered prior to local anesthetic, more differential blockade and a greater extent of anesthesia may be elicited.

Aged↗

PubMed1999

Saline-anesthetic interval and the spread of epidural anesthesia.

PURPOSE: To examine the effect of modifying the interval between administration of saline used during the loss of resistance (LOR) method and local anesthetic on epidural anesthetic level and its quality. METHODS: Seventy-three patients who received thoracic epidural anesthesia were randomly allocated into three groups; the 2, 5 and 10 min groups, according to the interval between the administration of saline and 8 ml mepivacaine 1.5%. Fifteen minutes after the mepivacaine injection, the dermatome level of hypesthesia was determined by an individual blinded to the interval. RESULTS: When the saline-anesthetic interval was prolonged, the hypesthetic levels for coldness and pinprick were decreased. The number of spinal segments with hypesthesia for coldness were 15 [12-20]#, 12.5 [10.5-22.5]## and 10.5 [6.5-15.5]### in the 2, 5 and 10 min groups, respectively (median [range], # P < 0.05 vs the 5 min group, ## P < 0.05 vs the 10 min group, ### P < 0.05 vs the 2 min group). The number of spinal segments with hypesthesia for pinprick were 13.5 [11-18]#, 11 [7.5-20.5]## and 10 [5.5-13]### in the 2, 5 and 10 min groups, respectively. There were differences in all groups between the number of segments with hypesthesia for coldness and pinprick elicited. CONCLUSION: The interval between the administration of saline and local anesthetic alters the anesthetic level and quality of epidural analgesia.

Abdomen↗

PubMed1998

Enhanced anti-Candida activity of neutrophils and azole antifungal agents in the presence of lactoferrin-related compounds.

We investigated the effects of lactoferrin (Lf)-related compounds on growth inhibition of Candida albicans by neutrophils or antifungal agents in vitro. Human neutrophils partially inhibited the growth of C.albicans. The growth inhibition caused by human neutrophils was augmented by the addition of human Lf at concentrations which did not show any inhibitory effect in the absence of neutrophils. Similar observations were obtained also with the following combinations: human neutrophils + bovine Lf, murine neutrophils + bovine Lf, and murine neutrophils + iron saturated bovine Lf, but not in the case of murine neutrophils + human transferrin. The minimum inhibitory concentration (MIC) of azole antifungal agents, clotrimazole, ketoconazole, fluconazole, and itraconazole was reduced by 1/4 to 1/16 in the presence of a sub-MIC level of each of bovine Lf, bovine Lf pepsin hydrolysate, and the antimicrobial peptide "lactoferricin B" (Lfcin B). Other types of antifungal agents, amphotericin B, nystatin, and flucytosine did not show such combined effects with these Lf-related compounds. The anti-Candida activity of bovine Lf or Lfcin B in combination with clotrimazole was shown to be synergistic by checkerboard analysis. Clinically isolated azole-resistant C. albicans strains were more susceptible to bovine Lf or Lfcin B than azole-susceptible strains. Trailing growth of an azole-resistant strain in the presence of fluconazole was reduced by the addition of sub-MIC levels of bovine Lf or Lfcin B. These results suggest that Lf-related compounds even at relatively low concentrations may function as an antifungal effector in combination with neutrophils thereby modulating azole antifungal efficacies in vivo.

Animals↗

PubMed1998

Viscosity of diluent and sensory level of subarachnoid anaesthesia achieved with tetracaine.

PURPOSE: Our objective was to evaluate the effect of viscosity in determining the cephalad spread of tetracaine administered by the subarachnoid route. METHODS: We studied 42 patients that were randomly assigned to receive subarachnoid anaesthesia for arthroscope of the knee. They received 8 mg tetracaine dissolved in either glucose 10%, sodium chloride (NaCl) 5%, glucose 5%, or NaCl 2.5%. The specific gravity and viscosity of each solvent was also measured. Cephalad spread was defined as the level of sensory block achieved. RESULTS: The specific gravity of the glucose 5% and the NaCl 2.5% solutions were similar (1.0197 +/- 0.0001 vs 1.0177 +/- 0.0001 (mean +/- SD)). That was also true for the more concentrated pair of solutions (1.0385 +/- 0.0001 for glucose 10% vs 1.0353 +/- 0.0003 in NaCl 5%). However, the viscosities of the 10% and 5% solutions of glucose (0.01178 +/- 0.0002 and 0.01020 +/- 0.0002 (g.cm-1.sec-1)) were higher (P < 0.05) than that of the other two solutions, being 0.00955 +/- 0.0001 for NaCl 5% and 0.00934 +/- 0.0002 for NaCl 2.5%. The median maximal extent of sensory block achieved was significantly higher (P < 0.05) with a solution of tetracaine in glucose 10% injected into the subarachnoid space at the L3-4 interspace than that observed in the two groups administered tetracaine in NaCl. The level of sensory block 30 min after the injection of anaesthetic was; T3 [T1-6] (median [range]) with glucose 10%, T6 [T4-10] with NaCl 5%, T5 [T2-11] with glucose 5%, and T5.5 [T2-11] with NaCl 2.5%. CONCLUSION: Viscosity was shown to be one of determinants of the clinical extent of spread of a subarachnoid anaesthetic such as tetracaine.

Adolescent↗

PubMed1998

Epidural saline solution prior to local anaesthetic produces differential nerve block.

PURPOSE: The loss-of-resistance technique is generally used to identify the epidural space usually with normal saline. However, the effect of epidural saline on anaesthetic spread has not been demonstrated. The purpose of this study was to determine whether epidural saline affected the anaesthetic level and the quality of analgesia. METHODS: Seventy patients undergoing upper abdominal surgery received thoracic epidural anaesthesia combined with general anaesthesia. The patients were randomly allocated into three groups using epidural saline volumes of 1, 5, or 10 ml. Ten minutes after epidural injection of 12 ml mepivacaine 1%, the dermatome levels of hypaesthesia for cold and pinprick were determined by an individual blinded to the amount of saline administered. RESULTS: The levels of hypaesthesia for cold sensation were not different among the three groups (23 [14-44] total bilateral dermatomes blocked with 1 ml saline, 22 [16-41] dermatomes with 5 ml, and 24 [10-36] dermatomes with 10 ml (median [range])). However, the larger volume of saline produced decreased spread of hypaesthesia for pinprick (22 [4-41] dermatomes blocked bilaterally for 1 ml vs 16 [8-24] dermatomes for 10 ml group, P < 0.004). CONCLUSION: Our results suggest that a large volume of saline solution injected in the epidural space to elicit loss-of-resistance dilutes the local anaesthetic solution, resulting in reduced spread of the block to pinprick.

Abdomen↗

PubMed1998

Anti-Candida activity of calprotectin in combination with neutrophils or lactoferrin.

The effect of an anti-microbial protein, calprotectin, in combination with neutrophils on the growth of Candida albicans was investigated. The growth inhibition of C. albicans by murine neutrophils was augmented by the addition of a low concentration of calprotectin prepared from rat peritoneal exudate cells. The concentrations of calprotectin causing 50% inhibition of growth of C. albicans in the absence or presence of neutrophils at an effector-to-target (E/T) ratio of 30 and 60 were estimated to be 0.45, 0.34 and 0.28 U/ml, respectively. The anti-Candida activity of calprotectin was completely inhibited by 2 microM of zinc ion, while it only partially lowered the activity of the combination of calprotectin and neutrophils. Lactoferrin, which is an anti-microbial protein released from neutrophils, strongly inhibited the growth of C. albicans in combination with calprotectin. These results suggest that calprotectin and lactoferrin released from neutrophils may cooperate to inhibit the growth of C. albicans at a local lesion of the infection where there is an accumulation of neutrophils.

Animals↗

PubMed1998

[Inhibition of mycelial growth of Candida albicans by ascites fluid of tumor bearing mice].

The effects of ascites fluids and sera of tumor-bearing mice on the mycelial growth of Candida albicans were examined. When the ascites fluids or the sera obtained from mice inoculated with MM46 mammary carcinoma were added to the culture medium, mycelial growth of C. albicans was strongly inhibited. The molecular size of the growth inhibitory factor in the ascites fluids was estimated to be approximately 80 K dalton by gel-filtration chromatography. Ferric chloride (6 microM) neutralized the anti-Candida activity. On the basis of these results including morphological observation, a possible role of a transferrin-like molecule was discussed.

Animals↗

PubMed1998

[Cooperative inhibitory effects of cervical mucus and neutrophils on growth of Candida albicans].

Preparations of human cervical mucus were obtained from fifteen female volunteers with or without vaginal candidiasis. Their content of lactoferrin and inhibitory effects on the growth of Candida albicans were estimated. The concentration of lactoferrin in cervical mucus was measured by enzyme linked immunosorbent assay (ELISA). Lactoferrin concentration of the eleven preparations among them was more than 0.2 mg/ml. The effects of these cervical mucus preparations on Candida growth were examined in vitro. Candida growth was not inhibited by the addition of 1/200 diluted cervical mucus alone, however, anti-Candida activity of murine neutrophils was augmented by such an addition. These results suggest that the combination of neutrophils and cervical mucus may have an important role in defense against Candida infection in the vaginal mucosa.

Adult↗

PubMed1997

Augmentation of production of TNF-alpha and anti-tumour activity by an amphotericin B preparation for clinical use in mice.

Effects of amphotericin B on production of endogenous tumour necrosis factor alpha (TNF-alpha) and anti-tumour activity in mice was examined. Intravenous administration of Fungizone, an amphotericin B preparation complexed with deoxycholate, augmented the induction of endogenous TNF in response to a second stimulus with intravenous doses of FK23 (heat-killed Enterococcus faecalis). This augmentation was observed when more than 1.8 microg of Fungizone was injected intravenously before intravenous dosing of FK23. The time interval between priming injection of Fungizone and secondary injection of FK23 for the maximal effect was 3 h. Similar augmentation of TNF production was also observed in amphotericin B-primed and FK23-injected mice. Correspondingly, anti-tumour activity of the combined, intravenous injection of Fungizone and FK23 with a 3-h interval was examined. Growth of Meth A fibrosarcoma was clearly inhibited by this combination but not by administration of either one alone. These results suggest that amphotericin B is able to elicit anti-tumour activity, perhaps through activation of the immune system, and in particular augmentation of the induction of endogenous TNF.

Amphotericin B↗

PubMed1997

Augmented inhibition of growth of Candida albicans by neutrophils in the presence of lactoferrin.

The combined inhibitory effects of neutrophils and lactoferrins on the growth of Candida albicans were examined. Murine or human neutrophils partially inhibited growth of C. albicans when cultured with C. albicans in vitro. The growth inhibition was augmented by a combination of neutrophils and more than 30 microg/ml of bovine lactoferrin or 1 microg/ml of human lactoferrin, concentrations less than 1/10-1/200 their inhibiting concentrations when used alone. The inhibition of C. albicans was also enhanced by combination of neutrophils and bovine apolactoferrin or iron-bound holo-lactoferrin, but not by transferrin. Combination effects of neutrophils and lactoferrin were also observed in a condition where there was no contact between neutrophils and Candida cells. These results suggest that neutrophils inhibit the growth of C. albicans regardless of whether there is direct contact between them and Candida cells: neutrophil growth inhibition effects were augmented in the presence of a physiological concentration of lactoferrin, perhaps through some action of lactoferrin other than chelation of ferric ion.

Animals↗

PubMed1997

Nitric oxide metabolite in pregnant women before and after delivery.

BACKGROUND: During pregnancy, systemic vascular resistance as well as vascular sensitivity to vasoconstrictive agents decreases in pregnant women. METHODS AND MATERIALS: The vascular resistance of the fetus is also maintained in the presence of low blood pressure. We believe that the main factors in this phenomenon are nitric oxide (NO), along with prostaglandin. NO is an unstable compound with a short half-life;it is easily converted to nitrite (NO2) and nitrate (NO3). Since NO cannot be precisely quantified, we measured the NO2 concentration in maternal blood just before and after delivery and compared in with the values of non-pregnant women. RESULTS: NO2 concentrations in the 13 women who received cesarean deliveries under epidural anesthesia were not significantly changed by the anesthesia. Before anesthesia the NO2 concentration was 216 +/- 115 pmol/mg protein, and after the induction of anesthesia, but before surgery, it was 218 +/- 112 pmol/mg protein. The NO2 concentration then fell significantly after the surgery to 174 +/- 75 pmol/mg protein (p < 0.05). In addition, after vaginal delivery, in 17 other patients we observed marked decreases in NO2 concentration, falling from 160 +/- 82 to 125 +/- 61 pmol/mg protein (p < 0.05). These values were significantly higher than those of non-pregnant women (3.4 +/- 2.1 microM, 33 +/- 22 pmol/mg protein) (p < or = 0.0001). CONCLUSION: These results suggest that NO contributes to the low vascular resistance observed in the mother and fetus during pregnancy.

Adult↗

PubMed1997

[Fatal pulmonary embolism during knee surgery under epidural anesthesia].

A 36 year old male patient suddenly died of pulmonary embolism during the second application of a pneumatic tourniquet undergoing tibial fracture repair. Pulmonary artery angiography using Swan-Ganz catheter demonstrated that the left and right pulmonary arteries were occluded except the partial left upper lobe. PaO2 was below 7 mmHg, and cardiopulmonary resuscitation was not possible. Autopsy showed massive emboli completely blocking the both pulmonary arteries.

Adult↗