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Biomedical subjects

K Kishikawa

Publications and source records attributed to K Kishikawa.

At least 37 records · Page 2Linked to original sources
PubMed1995

Partial hepatic grafting: porcine study on critical volume reduction.

BACKGROUND: The safe limit of volume reduction in partial hepatic transplantation, including extracorporeal hepatic resection, remains to be clarified. This study evaluated such a limit and pathologic features associated with transplantation of a less than critical volume. METHODS: Partial hepatic grafting was performed in a porcine orthotopic autotransplantation model. According to the remnant liver volume, animals were classified into three groups: group 1, 73.8% +/- 4.2% (SD); group 2, 52.6% +/- 6.7%; and group 3, 29.4% +/- 6.7% of the whole liver (n = 5 each). RESULTS: Three-day survival was achieved in five (100%), four (80%), and zero animals, respectively. All animals in group 3 died of graft nonfunction; their intraoperative clearance of the total bile acids was significantly worse than the other groups (p < 0.01). After operation the clearance of the total bile acids and hyaluronic acid, which is selectively cleared by hepatic endothelial cells, was significantly better in group 1 than group 2 (p < 0.01 and < 0.05, respectively). On histologic examination postperfusion biopsy specimens of group 3 exhibited severe ischemic changes and portosinusoidal hyperemia, whereas that of groups 1 and 2 exhibited only mild ischemic damages. CONCLUSIONS: Transplantation of less than 30% of expected full liver volume could lead to primary graft nonfunction after partial hepatic grafting.

Animals↗
PubMed1995

Visceral antinociceptive effects of spinal clonidine combined with morphine, [D-Pen2, D-Pen5] enkephalin, or U50,488H.

BACKGROUND: Visceral pain is an important component of many clinical pain states. The perispinal administration of drug combinations rather than a single agent may reduce side effects while maximizing analgesic effectiveness. The purpose of this study was to examine the nature of interactions between an alpha 2-adrenergic agonist (clonidine) and a mu-opioid agonist (morphine), a delta-opioid agonist ([D-Pen2, D-Pen5] enkephalin [DPDPE]), or a kappa-opioid agonist (U50,488H). METHODS: Colorectal distension was used to elicit a nociceptive visceromotor response (contraction of abdominal musculature) in rats. The ability of intrathecally administered clonidine alone or in combination with morphine, DPDPE, or U50,488H to alter thresholds for the production of the visceromotor response was examined. RESULTS: Clonidine produced dose-dependent reduction in threshold. U50,488H, at the doses tested, showed no synergistic interaction with clonidine. CONCLUSIONS: Spinal combinations of alpha 2-adrenergic and mu- or delta- but not kappa-opioid agonists may be beneficial in the control of visceral pain.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1995

Effect of propofol on spinal dorsal horn neurons. Comparison with lack of ketamine effects.

BACKGROUND: Pentobarbital reduces low-threshold receptive field (RF) size and enhances responses of some spinal dorsal horn neurons to noxious stimulation in cats. To better understand the effects of general anesthetics on spinal sensory processing, this study was designed to determine if intravenous propofol and ketamine have similar effects. METHODS: Spinal dorsal horn neuronal responses to RF stimulation were observed in physiologically intact, awake, drug-free cats. After baseline observations were made, the effects of propofol (7.5 or 10 mg/kg intravenous) or ketamine (10 mg/kg intravenous) on those neuronal responses were observed. RESULTS: Propofol is capable of producing a profound reduction in low-threshold RF size. Propofol also depressed neuronal responses to non-noxious and noxious RF stimulation in many of the neurons tested. Ketamine was not observed to produce any change in either RF size or neuronal response to non-noxious RF stimulation. CONCLUSIONS: General anesthetics that interact with gamma aminobutyric acid receptors may significantly depress low-threshold sensory information within the spinal dorsal horn. This may contribute to anesthetic-induced loss of sensation. Lack of a ketamine effect suggests an absence of n-methyl-d-aspartate receptor involvement in spinal dorsal horn processing of low threshold sensory information.

Action Potentials↗
PubMed1995

Low-threshold neuronal activity of spinal dorsal horn neurons increases during REM sleep in cats: comparison with effects of anesthesia.

1. Cats were prepared for chronic recordings from the lumbar enlargement of the spinal dorsal horn. At the beginning of each recording session, a tungsten microelectrode was advanced through the dura in a physiologically intact, awake, drug-free animal, until amplitude discrimination provided a single neuron with a receptive field on the hindquarters. 2. Extracellular recordings of activity of each neuron were made during receptive field stimulation with tactile and thermal nonnoxious and noxious stimuli. 3. Baseline responses obtained in the awake state were compared with responses of the same neurons during slow-wave or rapid-eye-movement (REM) sleep. In a subpopulation of neurons, the effects of anesthesia (propofol, 7.5 mg/kg iv) were observed after the completion of sleep studies. 4. The low-threshold receptive fields of the seven neurons studied during REM sleep were all increased in size when compared with the baseline value. The average increase was 52.6% (range 26.2-96.7%). 5. The low-threshold receptive fields of the seven neurons studied during REM sleep were reduced by propofol anesthesia by an average of 49.1% (range 29-74%). 6. Neuronal response to receptive field brushing was observed in 15 neurons during REM sleep. The effect of propofol on receptive field brushing was observed in 8 of those neurons. In only one of those eight neurons were the effects of REM sleep and anesthesia in the same direction. 7. Changes in neuronal responses were less consistent during slow-wave sleep but still differed from changes induced by propofol.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1995

Severe or multiple rejection episodes are associated with early recurrence of hepatitis C after orthotopic liver transplantation.

Recurrent hepatitis C causes significant morbidity after liver transplantation. Because immunosuppression is associated with enhanced viral replication, we postulated that clinical recurrence of the disease may be associated with augmented immunosuppression for rejection. In 96 patients with hepatitis C who received liver transplants, we recorded the interval from transplantation to recurrence, the episodes of steroid-resistant rejection (SRR) requiring OKT3, the number of rejection episodes, and the use of OKT3 induction. Recurrence was diagnosed based on elevated transaminases and characteristic histology. Hepatitis C recurred in 43 of 96 patients. Fifteen of 21 patients (71.4%) who previously had SRR had recurrence, versus 28 of 75 patients (37.3%) who either had no SRR (72 patients) or had it after recurrence was diagnosed (3 patients) (P < .01). Mean time to recurrence was 127 +/- 31 days in the 15 patients who had had SRR versus 246 +/- 42 days in the other 28 patients (P = .02). Recurrence and number of rejection episodes were clearly associated: 6 of 33 patients (18.2%) with no rejection had recurrence (P < .05), versus 11 of 26 patients (42.3%) with one rejection episode (P < .05) and 26 of 37 (70.2%) with more than 1 episode (P < .05). OKT3 induction was used in 15 patients; 9 of 15 patients had recurrence (ns) at 337 +/- 95 days. Of 72 patients who initially received triple immunosuppression, 30 patients had recurrence at 186 +/- 25 days (P = .05). Nine patients received primary FK506; 4 had recurrence at 68 +/- 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Resistance↗
PubMed1994

Beneficial effect of thromboxane A2 synthetase inhibitor on cold-stored rat liver.

Prostanoids such as prostacyclin and thromboxane A2 have recently been suggested to play important roles in cold ischemia/reperfusion injury. The purpose of this study was to investigate the effect of thromboxane A2 synthetase inhibitor (OKY-046) on cold-stored livers of the rat using an ex vivo perfusion system. Addition of OKY-046 to preservation solution and the perfusate of livers stored cold (4 degrees C) in lactated Ringer's solution resulted in significantly lower glutamic pyruvic transaminase release (3.01 +/- 0.86 IU/g liver vs. 1.79 +/- 1.08 IU/g liver at 120 min after perfusion; P < 0.05), reduced perfusate ammonia levels (8.51 +/- 2.51 micrograms/dl/g liver vs. 3.62 +/- 1.71 micrograms/dl/g liver at 60 min; P < 0.05 and thereafter), lower perfusate taurocholate levels (0.63 +/- 0.10 vs. 0.18 +/- 0.05 at 15 min; P < 0.01 and thereafter), perfusate hyaluronic acid clearance (0.934 +/- 0.132 vs. 0.76 +/- 0.127 at 30 min; P < 0.05 and thereafter), and a reduced number of trypan blue-positive sinusoidal lining cells (50.1 +/- 9.9%; vs. 17.4 +/- 7.0%; P < 0.01). Histologically, the liver preserved for 6 hr in simple cold lactated Ringer's solution exhibited interstitial edema, various degrees of hepatocyte swelling, and sinusoidal stenosis, as well as dilatation, while the livers treated with OKY-046 demonstrated much less hepatocyte swelling, and change in sinusoidal width was nearly absent. We conclude that OKY-046 reduces post-preservation reoxygenation injury by protecting sinusoidal endothelial cells and hepatocytes.

Alanine Transaminase↗
PubMed1994

Obviation of prereperfusion rinsing and decrease in preservation/reperfusion injury in liver transplantation by portal blood flushing.

Liver allografts are traditionally rinsed with cold lactated Ringer's (LR) prereperfusion to clear K(+)-rich preservation solution from the hepatic vasculature. LR has been shown, however, to be injurious to the graft. By restoring portal blood flow without rinsing and discarding the initial blood traversing the liver (PB flush), we sought to eliminate rinsing without inducing hyperkalemia. Between August 1988 and December 1992, 481 OLTx were performed in 412 pts. Four rinsing methods were used sequentially: group 1 (157 pts)--low-flow-rate cold LR rinse (500 ml, 100 ml/min via standard i.v. tubing at 100 cm H2O [LFLR]) during lower caval anastomosis; Group 2 (120 pts)--LFLR as in group 1, at reperfusion, 500 ml PB flush via IVC catheter; group 3 (66 pts)--high-flow-rate LR rinse (500 ml, 1 L/min using large-bore tubing with 100 cm H2O rinsing pressure [HFLR]), PB flush as in group 2; Group 4 (62 pts)--no LR rinse; PB flush as in groups 2 and 3. Poor early graft function (PEGF) was defined as peak ALT or AST > 2500 U or PT > 16 sec (on POD 2); PEGF causing re-OLTx or death within 14 days was called primary nonfunction (PNF). Group 1 and Group 3 had high PEGF rates. Group 4 had significantly less PEGF than Group 1, with a trend toward a significant difference from Group 3. In Group 1, 3 pts. had intraoperative hyperkalemic cardiac arrest; this did not occur when PB flush was performed. PB flush without prior rinsing optimizes graft function without risk of hyperkalemia. LR rinse, alone or followed by PB flush, is unnecessary and may be deleterious.

Adolescent↗
PubMed1994

Serum hyaluronic acid for the assessment of graft viability in porcine liver transplantation.

For the assessment of graft viability, serum hyaluronic acid (HA) levels during porcine orthotopic liver transplantation were measured in two groups: group 1 (viable: n = 5) in which allografts were transplanted following a minimal cold (4 degrees C) preservation, and group 2 (nonviable: n = 4) in which allografts were transplanted after cold static storage (4 degrees C) for 24 h in University of Wisconsin solution. The changes in the HA levels reached a significant difference between the two groups at 30 min after reperfusion (P < 0.02). In group 1, all animals survived for over 4 days, while all animals in group 2 died within 24 h. The serum HA also demonstrated a significant correlation with prothrombin time, beta-glucuronidase, and aspartate aminotransferase at 120 min after reperfusion. These results suggest that the measurement of serum HA is a potentially effective index for evaluating hepatic allograft viability.

Animals↗
PubMed1994

Effects of ONO-1078, a peptide leukotriene antagonist, on endotoxin-induced acute lung injury.

The role of lipoxygenase metabolites in the pathogenesis of endotoxin (LPS)-induced lung injury remains to be clarified. We investigated the contribution of peptide leukotrienes to LPS-induced acute lung injury using a potent antagonist, ONO-1078 (ONO). Experimental groups consisted of a saline group (n = 10), an LPS group (n = 9) injected intravenously with 2 mg E. coli LPS, an ONO group (n = 8) receiving 30 mg/kg of intraperitoneal ONO, and an LPS+ONO group (n = 6) receiving 30 mg/kg of ONO intraperitoneally 10 min before the LPS injection. The [125I]albumin lung plasma ratio, which is a parameter of acute lung injury, was significantly increased (p < 0.01) in the LPS group compared with the saline, ONO, and LPS+ONO groups. The [125I]albumin BAL fluid plasma ratio was also increased (p < 0.01) in the LPS group compared with the other groups. ONO pretreatment attenuated the LPS-induced increases in neutrophil counts in the BAL fluid. In vitro studies showed that ONO suppresses the neutrophil chemotaxis induced by LTB4, zymosan-activated serum, and FMLP. We conclude that (1) ONO-1078 attenuates LPS-induced acute lung injury; and (2) this effect appears mainly a result of its potent antagonistic actions against peptide leukotrienes and also, in part, the suppression of neutrophil chemotaxis.

Albumins↗
PubMed1994

[An adult case of basal encephalomeningocele with recurrent meningitis].

A 35-year-old man developed meningitis for the first time at the age of 23. Thereafter, he repeatedly suffered from meningitis for six times before he was admitted to our clinic. Each meningitis was preceded by upper respiratory infection. Chronic infection in the head and neck, fracture of the skull base, liquorrhea, Mollaret meningitis, and acquired immunodeficiency were all ruled out. Nasal fiberscope examination revealed a palpating white tumor in the left olfactory cleavage. Coronal CT scanning demonstrated encephalomeningocele at the left ethmoidal cavity. The encephalomeningocele was surgically repaired and the patient has been free from further meningitis. The causal relationship between the encephalomeningocele and recurrent meningitis was discussed.

Adult↗
PubMed1993

Prediction of hepatic graft viability before reperfusion: an analysis of effluent from porcine allografts.

Rapid and reliable assessment of hepatic graft viability is important for successful orthotopic liver transplantation (OLTx). OLTx was performed in 11 pairs of pigs via a venovenous bypass. Six of these grafts were transplanted immediately (group A), while the other five were preserved in University of Wisconsin (UW) solution for 24 h and then transplanted (group B). All grafts were flushed with 300 ml of chilled (4 degrees C) Ringer's lactate solution before reperfusion of the graft, when 20 ml of effluent from the graft was collected and the concentrations of ammonia, lactic acid, GOT, and LDH were measured. Four of the six pigs in group A survived longer than 3 days, while the other two pigs died of causes other than graft dysfunction. All five pigs in group B died either of hemoperitoneum or hemodynamic instability due to liver failure. The histology of postperfusion biopsies in group A showed minimal pathological changes, while the grafts in group B revealed moderate to severe ischemic injuries. Ammonia and lactic acid in the effluent of group B were significantly higher than those of group A (1511 +/- 216 vs 417 +/- 333 micrograms/dl and 114.1 +/- 12.2 vs 91.4 +/- 12.2 mg/dl, respectively; P < 0.05 in both cases). Before reperfusion, the rate of total adenine nucleotides in all of the substances in the graft, which were measured using high performance liquid chromatography (HPLC), inversely correlated with the ammonia levels in the effluent. We conclude that an analysis of the effluent, (i.e. the levels of ammonia and lactic acid), flushed from a hepatic graft before reperfusion could serve as a predictor of hepatic graft viability.

Adenine Nucleotides↗
PubMed1993

Prolonged preservation in University of Wisconsin solution associated with hepatic artery thrombosis after orthotopic liver transplantation.

Hepatic artery thrombosis (HAT) after liver transplantation (LTx) usually mandates retransplantation. Prolonged preservation with Eurocollins solution has been associated with HAT. We reviewed our experience with 359 LTx patients to identify risk factors for HAT. All grafts were preserved in University of Wisconsin solution. HAT developed in 12 patients (3%) within 50 days. Seven patients were asymptomatic; four presented with biliary sepsis and 1 with poor graft function. Two patients had suffered acute rejection; another 2 had severe preservation injury. Technical problems accounted for 4 cases; in the remaining 8, no etiology was found. Diagnosis was at a mean 14.7 days after LTx. One patient maintains normal graft function 3 years after LTx without intervention. Eight underwent re-LTx, 3 of whom died. Routine surveillance via duplex enabled early diagnosis and revascularization in 3 patients; in all 3, no biliary complications occurred between 6 and 20 months. Overall graft and patient survival after HAT were 33.3% and 75%, respectively. Cold ischemic time (CIT) averaged 813 min in patients with HAT and 669 min in those without HAT (P < .05). HAT occurred in 7/165 patients with CIT > 12 hr, and in 3/234 patients with CIT < 12 hr (P = 0.0699). By avoiding CIT > 12 hr, we have recently avoided HAT in 78 consecutive patients. We conclude that CIT > 12 hr may increase the risk of HAT. When HAT is diagnosed before biliary sepsis develops, flow can often be restored and retransplantation averted.

Adenosine↗
PubMed1993

Norepinephrine prolongs tetracaine spinal anesthesia in surgical patients: a preliminary study.

We conducted a double-blinded examination of the effects of norepinephrine as a vasoconstrictor on the onset and duration of tetracaine spinal anesthesia in 80 surgical patients. The patients were randomly allocated to four groups (n = 20 in each group). Each patient received 10 mg of tetracaine in a volume of 2.0 mL which contained either 0 micrograms/mL, 5 micrograms/mL, 10 micrograms/mL, or 15 micrograms/mL of norepinephrine. The onset of spinal anesthesia was determined by the time to reach Th-10 level as well as by the time required to obtain the highest level of sensory analgesia. The time for two-segment regression and full-motor recovery were defined as the duration of spinal anesthesia. The time to reach Th-10, the highest analgesia level, and the time to obtain the highest analgesia level did not differ among the groups. Two-segment regression was prolonged significantly by 175%, 103%, and 106% as compared with the plain tetracaine group, in 5 micrograms/mL, 10 micrograms/mL, and 15 micrograms/mL of norepinephrine groups, respectively. Motor recovery also was extended significantly by 111%, 152%, and 121% as compared with the plain tetracaine group, in 5 micrograms/mL, 10 micrograms/mL, and 15 micrograms/mL of norepinephrine groups, respectively. There were no differences in the changes of arterial blood pressure and heart rate associated with the addition of norepinephrine among the groups. We conclude that norepinephrine provides a clinically meaningful prolongation of the duration of tetracaine spinal anesthesia.

Abdomen↗
PubMed1993

Extracorporeal hepatic resection for previously unresectable neoplasms.

BACKGROUND: Some hepatic tumors are judged inoperable solely for anatomic reasons, such as the proximity of the tumor with the major vasculature. This is because of high mortality and morbidity rates, as well as a compromised surgical margin. METHODS: We successfully performed extracorporeal hepatic resections in two patients who were judged to have inoperable tumors by conventional means. RESULTS: Both patients had an uneventful postoperative course, and although one patient had intrahepatic recurrence 6 months after operation, the other patient shows no recurrence 10 months later. CONCLUSIONS: Advances in techniques for liver transplantation and organ preservation now allow resection of anatomically unresectable hepatic tumors that were deemed inoperable in the past.

Extracorporeal Circulation↗
PubMed1992

Ischemic injury in liver transplantation: difference in injury sites between warm and cold ischemia in rats.

Using liver allografts with warm or cold ischemia, we evaluated functional and morphological alterations in hepatocytes, sinusoidal endothelial cells and Kupffer cells in a rat transplantation model. All recipients of allografts with either 4 hr of cold or 30 min of warm ischemia lived more than 22 days and were judged viable. On the other hand, all recipients of grafts with 6 hr of cold or 60 min of warm ischemia died within 2 days and were therefore judged to be nonviable. With these viable and nonviable allograft models, hepatocyte function was evaluated by the bile output and serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase and serum lactate dehydrogenase levels; endothelial cell function was judged by the serum hyaluronic acid level, and Kupffer cell function was measured by an intravenous colloidal carbon clearance test. Hepatocyte injury was the prominent feature in warm ischemic grafts, especially in the nonviable ones. On the other hand, serum hyaluronic acid values were significantly higher in the nonviable cold ischemic group, compared with the viable counterpart, suggesting that the functional depression of endothelial cells was predominant in cold, nonviable livers. Histological examinations coincided with the above findings. The phagocytic activity of Kupffer cells was depressed by warm or cold ischemia, whereas the number of Kupffer cells was reduced in the warm ischemia group. We conclude that in liver allografts the main site of injury in warm ischemia is the hepatocytes and suggest that cold ischemia is associated with endothelial cell damage.

Animals↗
PubMed1992

ONO-4057, a novel, orally active leukotriene B4 antagonist: effects on LTB4-induced neutrophil functions.

ONO-4057(5-[2-(2-Carboxyethyl)-3-[6-(4-methoxyphenyl)-5E- hexenyl]oxyphenoxy]valeric acid), an orally active leukotriene B4(LTB4) antagonist, displaced the binding of [3H] LTB4 to the LTB4 receptor in human neutrophil (Ki = 3.7 +/- 0.9 nM). ONO-4057 inhibited the LTB4-induced rise in cytosolic free calcium (the concentration causing 50% inhibition (IC50) = 0.7 +/- 0.3 microM) and inhibited human neutrophil aggregation, chemotaxis or degranulation induced by LTB4 (IC50 = 3.0 +/- 0.1, 0.9 +/- 0.1 and 1.6 +/- 0.1 microM) without showing any agonist activity at concentration up to 30 microM. ONO-4057 did not inhibit fMLP or C5a-induced neutrophil activation at concentrations up to 30 microM. In the in vivo study, ONO-4057 given orally, prevented LTB4-induced transient neutropenia or intradermal neutrophil migration in guinea pig (the dose causing 50% efficacy (ED50) = 25.6mg/kg or 5.3mg/kg). Furthermore, ONO-4057 given topically, suppressed phorbol-12-myristate-13-acetate (PMA)-induced neutrophil infiltration in guinea pig ear (the effective dose = 1 mg/ear). These results indicate that ONO-4057 is a selective and orally active LTB4 antagonist and may be a potential candidate for the treatment of various inflammatory diseases.

Animals↗