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A 79-year-old man was scheduled for surgery for hepatocellular carcinoma(HCC)after transcatheter hepatic arterial embolization for rupture. Two weeks before surgery, the patient came to our hospital with a chief complaint of back pain. First, we performed biliary drainage, under the diagnosis of HCC with obstructive jaundice due to haemobilia. Hepatectomy was performed when the patient's condition stabilized. It should be kept in mind that haemobilia may occur after TAE for HCC with bile duct tumor thrombus, and appropriate treatment should be performed when bleeding occurs.

Deregulating fibroblast growth factor receptor (FGFR) signaling is a promising strategy for cancer therapy. Herein, we report the discovery of compound 5 (TAS-120, futibatinib), a potent and selective covalent inhibitor of FGFR1-4, starting from a unique dual inhibitor of mutant epidermal growth factor receptor and FGFR (compound 1 ). Compound 5 inhibited all four families of FGFRs in the single-digit nanomolar range and showed high selectivity for over 387 kinases. Binding site analysis revealed that compound 5 covalently bound to the cysteine 491 highly flexible glycine-rich loop region of the FGFR2 adenosine triphosphate pocket. Futibatinib is currently in Phase I-III trials for patients with oncogenically driven FGFR genomic aberrations. In September 2022, the U.S. Food & Drug Administration granted accelerated approval for futibatinib in the treatment of previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring an FGFR2 gene fusion or other rearrangement., Competing Interests: The authors declare the following competing financial interest(s): All authors are employees of Taiho Pharmaceutical Co. Ltd., (© 2023 American Chemical Society.)

FGFR signaling is deregulated in many human cancers, and FGFR is considered a valid target in FGFR-deregulated tumors. Here, we examine the preclinical profile of futibatinib (TAS-120; 1-[(3S)-[4-amino-3-[(3,5-dimethoxyphenyl)ethynyl]-1H-pyrazolo[3, 4-d] pyrimidin-1-yl]-1-pyrrolidinyl]-2-propen-1-one), a structurally novel, irreversible FGFR1-4 inhibitor. Among a panel of 296 human kinases, futibatinib selectively inhibited FGFR1-4 with IC 50 values of 1.4 to 3.7 nmol/L. Futibatinib covalently bound the FGFR kinase domain, inhibiting FGFR phosphorylation and, in turn, downstream signaling in FGFR-deregulated tumor cell lines. Futibatinib exhibited potent, selective growth inhibition of several tumor cell lines (gastric, lung, multiple myeloma, bladder, endometrial, and breast) harboring various FGFR genomic aberrations. Oral administration of futibatinib led to significant dose-dependent tumor reduction in various FGFR-driven human tumor xenograft models, and tumor reduction was associated with sustained FGFR inhibition, which was proportional to the administered dose. The frequency of appearance of drug-resistant clones was lower with futibatinib than a reversible ATP-competitive FGFR inhibitor, and futibatinib inhibited several drug-resistant FGFR2 mutants, including the FGFR2 V565I/L gatekeeper mutants, with greater potency than any reversible FGFR inhibitors tested (IC 50 , 1.3-50.6 nmol/L). These results indicate that futibatinib is a novel orally available, potent, selective, and irreversible inhibitor of FGFR1-4 with a broad spectrum of antitumor activity in cell lines and xenograft models. These findings provide a strong rationale for testing futibatinib in patients with tumors oncogenically driven by FGFR genomic aberrations, with phase I to III trials ongoing. SIGNIFICANCE: Preclinical characterization of futibatinib, an irreversible FGFR1-4 inhibitor, demonstrates selective and potent antitumor activity against FGFR-deregulated cancer cell lines and xenograft models, supporting clinical evaluation in patients with FGFR-driven tumors. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/22/4986/F1.large.jpg., (©2020 American Association for Cancer Research.)

Previously, we generated and screened a panel of monoclonal antibodies (mAbs) against methicillin-resistant Staphylococcus aureus (MRSA) to identify protective mAbs in mouse infection models. One of these mAbs, ZBIA3H, bound to lipoteichoic acid (LTA) and exerted protective effects in a mouse sepsis model. To reinforce the ability of the mAb to protect against infection, combination therapies with the mAb and antibiotics need to be examined. Therefore, herein, we studied the efficacy of ZBIA3H (in combination or alone) in a mouse sepsis model. ZBIA3H improved the survival rate in the mouse models of sepsis induced by highly virulent or refractory S. aureus (community-acquired MRSA strain MW2, vancomycin-intermediate S. aureus strain Mu3, or vancomycin-resistant S. aureus strain VRS1). Furthermore, ZBIA3H remarkably improved the survival rate in combination with antimicrobial agents (vancomycin, daptomycin, or linezolid) in mouse sepsis models. From these results we conclude that anti-LTA mAb ZBIA3H or its humanized form is a promising mAb individually, or in combination with antibiotics, against clinical refractory infection of S. aureus., Competing Interests: Declaration of Competing Interest HO and JE are employees of Zenyaku Kogyo. TB and KH have no conflicts of interest to declare., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective A positive correlation is observed between the progression of renal impairment and the increasing risk of cardiovascular disease. Our aim was to examine the relationship between the renal resistive index (RRI) assessed by duplex sonography and the extent of atherosclerosis in patients without renal impairment undergoing vascular imaging studies. Methods The RRI was evaluated pre-procedurally among 106 outpatients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 undergoing clinically-driven coronary computed tomography angiography (CCTA). In those subjects, a carotid artery ultrasound scan was also performed to evaluate carotid artery disease. We investigated the association between the RRI and the atherosclerotic extent, defined by the presence of coronary artery calcium (CAC) >0 and carotid intima-media thickness (cIMT) ≥1.0 mm. Results Multi-site atherosclerosis (CAC>0 and cIMT≥1.0 mm) was found in 31 patients. The RRI was significantly increased with an increasing number of atherosclerotic vessels (absence of atherosclerosis: 0.65±0.04 vs. single-site atherosclerosis: 0.67±0.06 vs. multi-site atherosclerosis: 0.71±0.05, p<0.001). A multivariate logistic regression analysis showed that RRI>0.70 [odds ratio (OR): 4.05, 95% confidence interval (CI), 1.37-12.0, p=0.01], cardio ankle vascular index (CAVI) ≥9.0 (OR: 8.18, 95% CI: 2.47-27.1, p<0.01), diabetes (OR: 4.34, 95% CI: 1.37-13.7, p=0.01) and an eGFR>90 mL/min/1.73 m 2 (OR: 5.89, 95% CI: 1.39-25.1, p=0.01) were associated with multi-site atherosclerosis. Conclusion The RRI, a sub-clinical renal parameter is an atherosclerotic marker in patients without renal impairment.

TAS-121 is a novel orally active selective covalent inhibitor of the mutant EGFR. We performed preclinical characterization of TAS-121 and compared its efficacy and selectivity for common EGFR mutations (Ex19del and L858R), first- and second- generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) resistance mutation (T790M), and uncommon mutations (G719X and L861Q) with those of other EGFR-TKIs. We also commenced investigation of the clinical benefits of TAS-121. The IC 50 for intracellular EGFR phosphorylation was determined by using Jump-In GripTite HEK293 cells transiently transfected with EGFR expression vectors. Mouse xenograft models were used to evaluate the antitumor activity of TAS-121. TAS-121 potently inhibited common activating and resistance EGFR mutations to the same extent as another third-generation EGFR-TKI (osimertinib). In addition, TAS-121 showed equivalent inhibitory activity against some uncommon mutations such as G719X and L861Q. Furthermore, TAS-121 demonstrated greater selectivity for mutant EGFRs versus the wild-type EGFR compared with other EGFR-TKIs. Moreover, TAS-121 displayed antitumor activity in SW48 ( EGFR G719S) and NCI-H1975 ( EGFR L858R/T790M) xenograft models, and achieved an objective response in patients with NSCLC with EGFR mutations including G719A mutation. In conclusion, TAS-121 is a novel third-generation EGFR-TKI and demonstrates antitumor activities in patients with NSCLC expressing either common or uncommon EGFR mutations., (©2019 American Association for Cancer Research.)

Activated HER2 is a promising therapeutic target for various cancers. Although several reports have described HER2 inhibitors in development, no covalent-binding inhibitor selective for HER2 has been reported. Here, we report a novel compound TAS0728 that covalently binds to HER2 at C805 and selectively inhibits its kinase activity. Once TAS0728 bound to HER2 kinase, the inhibitory activity was not affected by a high ATP concentration. A kinome-wide biochemical panel and cellular assays established that TAS0728 possesses high specificity for HER2 over wild-type EGFR. Cellular pharmacodynamics assays using MCF10A cells engineered to express various mutated HER2 genes revealed that TAS0728 potently inhibited the phosphorylation of mutated HER2 and wild-type HER2. Furthermore, TAS0728 exhibited robust and sustained inhibition of the phosphorylation of HER2, HER3, and downstream effectors, thereby inducing apoptosis of HER2-amplified breast cancer cells and in tumor tissues of a xenograft model. TAS0728 induced tumor regression in mouse xenograft models bearing HER2 signal-dependent tumors and exhibited a survival benefit without any evident toxicity in a peritoneal dissemination mouse model bearing HER2-driven cancer cells. Taken together, our results demonstrated that TAS0728 may offer a promising therapeutic option with improved efficacy as compared with current HER2 inhibitors for HER2-activated cancers. Assessment of TAS0728 in ongoing clinical trials is awaited (NCT03410927)., (©2019 American Association for Cancer Research.)

Several studies have reported the effects of vitamin C (L-ascorbic acid, AA) on ultraviolet B (UVB)-induced cell damage using cultured keratinocytes. However, the epidermis consists of multiple cell layers, and the effect of AA on UVB-induced damage to the human epidermis remains unclear. Therefore, we investigated the effect of AA on UVB-induced skin damage using reconstituted human epidermis. The reconstituted human epidermal surface was treated with 100 and 500 mM AA and cultured for 3 h before (pre-AA treatment) or after (post-AA treatment) 120 mJ/cm 2 UVB irradiation. Pre- and post-AA treatments of the epidermal surface suppressed UVB-induced cell death, apoptosis, DNA damage, reactive oxygen species (ROS) production, and the inflammatory response by downregulating tumour necrosis factor-α (TNF-α) expression and release. Moreover, the pre-AA treatment was more effective at preventing UVB-induced skin damage than the post-AA treatment. In summary, pre- and post-AA treatments of the epidermis prevent UVB-induced damage.

Activating mutations in the EGFR gene are important targets in cancer therapy because they are key drivers of non-small cell lung cancer (NSCLC). Although almost all common EGFR mutations, such as exon 19 deletions and the L858R point mutation in exon 21, are sensitive to EGFR-tyrosine kinase inhibitor (TKI) therapies, NSCLC driven by EGFR exon 20 insertion mutations is associated with poor clinical outcomes due to dose-limiting toxicity, demonstrating the need for a novel therapy. TAS6417 is a novel EGFR inhibitor that targets EGFR exon 20 insertion mutations while sparing wild-type (WT) EGFR. In cell viability assays using Ba/F3 cells engineered to express human EGFR, TAS6417 inhibited EGFR with various exon 20 insertion mutations more potently than it inhibited the WT. Western blot analysis revealed that TAS6417 inhibited EGFR phosphorylation and downstream molecules in NSCLC cell lines expressing EGFR exon 20 insertions, resulting in caspase activation. These characteristics led to marked tumor regression in vivo in both a genetically engineered model and in a patient-derived xenograft model. Furthermore, TAS6417 provided a survival benefit with good tolerability in a lung orthotopic implantation mouse model. These findings support the clinical evaluation of TAS6417 as an efficacious drug candidate for patients with NSCLC harboring EGFR exon 20 insertion mutations. Mol Cancer Ther; 17(8); 1648-58. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Recent clinical trials to develop anti-methicillin-resistant Staphylococcus aureus (MRSA) therapeutic antibodies have met unsuccessful sequels. To develop more effective antibodies against MRSA infection, a panel of mAbs against S. aureus cell wall was generated and then screened for the most protective mAb in mouse infection models. Twenty-two anti-S. aureus IgG mAbs were obtained from mice that had been immunized with alkali-processed, deacetylated cell walls of S. aureus. One of these mAbs, ZBIA5H, exhibited life-saving effects in mouse models of sepsis caused by community-acquired MRSA strain MW2 and vancomycin-resistant S. aureus strain VRS1. It also had a curative effect in a MW2-caused pneumonia model. Curiously, the target of ZBIA5H was considered to be a conformational epitope of either the 1,4-β-linkage between N-acetylmuramic acid and N-acetyl-D-glucosamine or the peptidoglycan per se. Reactivity of ZBIA5H to S. aureus whole cells or purified peptidoglycan was weaker than that of most of the other mAbs generated in this study. However, the latter mAbs did not have the protective activities against S. aureus that ZBIA5H did. These data indicate that the epitopes that trigger production of high-yield and/or high-affinity antibodies may not be the most suitable epitopes for developing anti-infective antibodies. ZBIA5H or its humanized form may find a future clinical application, and its target epitope may be used for the production of vaccines against S. aureus infection., (© 2015 The Authors. Microbiology and Immunology Published by The Societies and Wiley Publishing Asia Pty Ltd.)

We retrospectively evaluated the initial clinical experience of intraoperative cardiac output measurement by a new arterial pressure-based cardiac output (APCO:FloTrac/Vigileo) analysis in patients undergoing open heart surgery. Thirty-two patients (mean age 76.4, range 59 to 90)who underwent cardiac surgery under cardiopulmonary bypass( CPB) from July 2008 to September 2009 in our institute were enrolled in this study. There were 14 women and 18 men. The cardiac operations included 28 valve surgeries and 4 coronary artery bypass grafting. The APCO was introduced initially, then a continuous cardiac output (CCO:Swan-Ganz catheter) analysis system was established following the induction of anesthesia. The correlation of both cardiac output measurements was evaluated at 5 time points, T1:induction of anesthesia, T2:sternotomy, T3:after weaning from CPB, T4:closure of the chest, and T5:arrival at intensive care unit. There were no serious complications related to APCO and CCO. The correlation between APCO and CCO was evaluated by Bland-Altman plot analysis. The percentages of correlation between both groups were T1:81.2%, T2:78.1%, T3:59.4%, T4:62.5%, and T5:65.6%. A good correlation was shown in all 6 patients with atrial fibrillation at T1 and T2. No correlation was shown in the 3 patients with left ventricular( LV) dysfunction below LVEF 40%, 1 case at T3, all 3 cases at T4, and 2 cases at T5. Before the institution of CPB, 3 of the 6 at T1 and 3 of the 7 at T2 in whom no correlation was shown, had severe aortic valve insufficiency (AVI).From these results, APCO appears to be an acceptable device to evaluate the intraoperative cardiac output measurement compared with CCO, except in patients with LV dysfunction or AVI at some time points. Further studies will be necessary to elucidate the precise clinical evidence to assess the efficacy of this new analysis device.

Objectives: To determine whether any difference exists in responses to indirect moxibustion (IM) relative to thermal stimulation duration., Methods: In experiment 1, 9 subjects attended two experimental sessions consisting of single stimulation with IM or triple stimulation with IM, using a crossover design. A K-type thermocouple temperature probe was fixed on the skin surface at the GV14 acupuncture point. IM stimulation was administered to the top of the probe in order to measure the temperature curve. In addition, each subject evaluated his or her subjective feeling of heat on a visual analogue scale after each stimulation. Experiment 2 was conducted on 42 participants, divided into three groups according to the envelope allocation method: single stimulation with IM (n=20), triple stimulation with IM (n=11) and a control group (n=11). A thermograph was used to obtain the skin temperature on the posterior trunk of the participant. To analyse skin temperature, four arbitrary frames (the scapular, interscapular, lumbar and vertebral regions) were made on the posterior trunk., Result: In experiment 1, no significant difference in maximum temperature was found in IM and subjective feeling of heat intensity between single and triple stimulation with IM. In experiment 2, increases in skin temperature occurred on the posterior trunk, but no differences in skin temperature occurred between the groups receiving single and triple stimulation with IM., Conclusion: No difference exists in the skin temperature response to moxibustion between the single and triple stimulation with IM.

Pediatric patients with end-stage heart failure require mechanical circulatory support (MCS) just as adults do. In order to meet the special requirements for neonates' and infants' MCS, pediatric circulatory support devices must be compact with low priming volume, easily controllable with low flow, less traumatic for blood cells and tissues, and biocompatible with minimum anticoagulation. We have designed and developed a miniature rotary centrifugal blood pump, "TinyPump," with a priming volume of 5 mL, which has already demonstrated its controllable performance for low flow and durability in vitro. To evaluate the feasibility of the TinyPump as a left ventricular assist device (LVAD) suitable for neonates and infants, we have examined the biocompatibility and hemodynamic performance of the TinyPump in a pediatric animal model using Shiba goats. The TinyPump is a miniaturized centrifugal pump weighing 150 g comprising a disposable pump head with a 30-mm diameter impeller having six straight-vanes and a reusable motor driver. The impeller in the pump head is supported by a hydrodynamic bearing at its center and is driven by radial magnetic force coupled to the motor driver. TinyPump implantations were performed in 22 Shiba goats (17 female and 5 male), with body weights ranging from 8.4 to 27.2 kg. Under gas anesthesia, via left lateral thoracotomy, a 22 Fr inflow cannula was inserted through the left ventricular apex, while a 6-mm outflow graft was anastomosed to the descending aorta, which were then connected to a TinyPump mounted on the animal's back. Postoperative hemodynamic monitoring included heart rate, arterial and central venous pressure, pump flow, and rotation speed. Target pump flow in all animals was maintained at 0.9 ± 0.1 L/min, which is approximately half the normal pulmonary artery flow measured in control animals. Blood samples were collected to evaluate peripheral organ functions, hemolysis, and thrombosis. Goats were divided into three groups-acute phase (6 h; n = 4), subchronic phase (6 h 2 postoperative days [POD]; n = 11), and chronic phase (3 POD-16 POD; n = 8)-based on their survival duration. In the early experiments, hemolysis and thrombi formation at the impeller bearing resulted in termination of the study. Subsequent modifications of the bearing design, pump housing design, and magnetic coupling force helped to minimize the hemolysis and thrombi formation, prolonging the survival duration of the Shiba goats to 2 weeks with minimum adverse effects on the blood components and organ functions. With further experiments and improvements in pump durability and hemocompatibility, the TinyPump can serve as a suitable circulatory support device for neonates and infants bridging to heart transplantation as well as to heart recovery., (© 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Protein kinase C (PKC) plays an essential role in a wide range of cellular functions. Although crystal structures of the PKC-theta, PKC-iota and PKC-betaII kinase domains have previously been determined in complexes with small-molecule inhibitors, no structure of a PKC-substrate complex has been determined. In the previously determined PKC-iota complex, residues 533-551 in the C-terminal tail were disordered. In the present study, crystal structures of the PKC-iota kinase domain in its ATP-bound and apo forms were determined at 2.1 and 2.0 A resolution, respectively. In the ATP complex, the electron density of all of the C-terminal tail residues was well defined. In the structure, the side chain of Phe543 protrudes into the ATP-binding pocket to make van der Waals interactions with the adenine moiety of ATP; this is also observed in other AGC kinase structures such as binary and ternary substrate complexes of PKA and AKT. In addition to this interaction, the newly defined residues around the turn motif make multiple hydrogen bonds to glycine-rich-loop residues. These interactions reduce the flexibility of the glycine-rich loop, which is organized for ATP binding, and the resulting structure promotes an ATP conformation that is suitable for the subsequent phosphoryl transfer. In the case of the apo form, the structure and interaction mode of the C-terminal tail of PKC-iota are essentially identical to those of the ATP complex. These results indicate that the protein structure is pre-organized before substrate binding to PKC-iota, which is different from the case of the prototypical AGC-branch kinase PKA.

Moxibustion-like thermal stimulation (MTS) was applied to the gastrocnemius muscle to measure local muscle blood flow (MBF) in the stimulated region and the change in the MBF in the region, and its mechanism was examined. In the experiment, we used urethane-anesthetized rats under artificial respiration and observed the change caused by gastrocnemius MTS using a laser Doppler blood-flow meter. MTS applied to the gastrocnemius muscle caused a two-phase response in blood flow that showed a transient decrease followed by an increase without blood pressure change. It is suggested that the increase in response occurs because of an axon reflex that has a reflex arc below the spinal cord, and the decrease in response is caused by direct stimulation of postganglionic muscle sympathetic fibers.

We report a direct observation of the intrinsic magnetization behavior of Au in thiol-capped gold nanoparticles with permanent magnetism at room temperature. Two element specific techniques have been used for this purpose: X-ray magnetic circular dichroism on the L edges of the Au and 197Au Mössbauer spectroscopy. Besides, we show that silver and copper nanoparticles synthesized by the same chemical procedure also present room-temperature permanent magnetism. The observed permanent magnetism at room temperature in Ag and Cu dodecanethiol-capped nanoparticles proves that the physical mechanisms associated to this magnetization process can be extended to more elements, opening the way to new and still not-discovered applications and to new possibilities to research basic questions of magnetism.

The effects of acupuncture-like stimulation of a hind limb on heart rate were examined in anesthetized rats. An acupuncture needle, having a diameter of either 160 or 340 microm, was inserted into the skin and underlying muscles at a depth of about 5 mm and twisted right and left twice every second for 1 min. Stimulation by a needle with a diameter of either 160 or 340 microm produced a decrease in heart rate. Severance of the femoral and sciatic nerves ipsilateral to the hind-limb stimulation completely abolished the bradycardiac response. Also, heart rate was significantly decreased by acupuncture-like stimulation of the hind-limb muscles alone, but was not significantly influenced by the stimulation of the hind-limb skin alone. The bradycardiac response induced by acupuncture-like stimulation was not influenced by bilateral severance of the vagal nerves at the cervical level, but was abolished by bilateral stellectomy. Acupuncture-like stimulation of the hind limb induced a decrease in the activity of the cardiac sympathetic efferent nerve as well as a decrease in heart rate. These results indicate that the decrease in heart rate induced by acupuncture-like stimulation of a hind limb is a reflex response. The afferent pathway is composed of hind-limb muscle afferents, and the efferent pathway is composed of cardiac sympathetic nerves.

Purpose: When injured, the adult newt possesses the remarkable capability to regenerate tissues and organs with return of function and physiology. One example is the newt eye, in which regeneration can restore normal vision if the retina or lens has been removed. We wanted to examine how the retinotectal projections regenerate after removal of the brain's optic tectum and establish this animal as a model for retinal projection as well as a central nervous system regeneration model., Methods: A major portion of the left optic tectum was removed in several adult newts, and the animals were monitored postoperatively for eight months to observe regeneration and innervation. Cell proliferation was examined by histological methods and by BrdU incorporation., Results: We observed that adult newts have the capability to the excised optic tectum. As indicated by horseradish peroxidase staining, 80% of the retinotectal projection area was regenerated eight months after the operation, even though the wound closed much earlier. Our study provides the first quantitation of regeneration of the retinotectal projections. The ependymal cells that line the ventricle were the most likely source of the regenerated tectum. After removal, cell proliferation was detected only in the ependymal cells layer. Double staining of proliferating cells and neurons was limited, indicating that direct transition of ependymal cells is a possibility., Conclusions: The retinotectal projections after removal of the adult newt optic tectum can be readily re-established. Thus, this model can become indispensable for the study of vision restoration and neurogenesis.

Purpose: Some investigators suggest that hemodynamic outcomes may be superior with the stentless aortic bioprosthesis when compared with a mechanical valve. The goal of this study was to characterize outcomes and hemodynamic data associated with each type of valve., Subjects and Methods: Patient outcomes and echocardiographic data were compared between 25 patients with stentless valves and 59 patients with mechanical valves., Results: There were no significant differences in survival and freedom from cardiovascular adverse events between two groups. The duration of anticoagulation therapy was limited to 3 months in the stentless group. There was no significant difference in preoperative and postoperative New York Heart Association (NYHA) status when comparing the two groups, and NYHA status significantly improved in both groups (P<0.05). There was no significant difference in the echocardiographic data when comparing the two groups., Conclusion: Aortic valve replacement using the stentless valve and the mechanical valve provided good clinical and hemodynamic outcomes. There was no significant difference in these parameters when comparing the two groups. There may be advantages in the limited required duration of anticoagulation therapy of the stentless valve , especially in elderly patients. However, longer follow-up is required before definitive conclusions regarding the benefits of the stentless valve relative to the mechanical valve can be determined.

The localization of small lung masses at thoracoscopic operation is very difficult. A 67-year-old female with tiny pulmonary metastases of renal cell carcinoma primary was successfully treated by pulmonary thoracoscopic resection after transbronchial localization using a dye.

A 46-year-old male with asthma bronchiale and eosinophilia was admitted to our hospital because of continuous severe chest pain. Electrocardiography showed ST segment elevation in leads II, III and aVF during chest pain. Emergency coronary angiography showed a series of coronary arterial narrowings in segments 1 and 2. After injection of nitroglycerin 0.1 mg and nicorandil 2 mg into the right coronary artery, the coronary arterial narrowing was gradually relieved. The artery became completely normal after 10 min. Left coronary arterial angiography showed no abnormalities. The diagnosis was spontaneous coronary arterial spasm based on the coronary angiographic findings. The spasm occurred as multiple short narrow arterial segments. Normalization of the coronary artery took a long time. In a case like this, thrombus is easily formed that may cause acute myocardial infarction and unnecessary coronary angioplasty may be performed.

Objectives: To identify the relationship of risk factors for atherosclerosis with venous thromboembolism (VTE) and the utility of transthoracic echocardiography in acute pulmonary thromboembolism (APTE)., Methods: In 75 patients with VTE (VTE group), 101 patients with suspected VTE (N group), and 50 control subjects (control group), the frequency of atherosclerosis risk factors such as hyperlipidemia, obesity, hypertension, smoking, and diabetes mellitus and the number of risk factors were evaluated. Transthoracic echocardiographic findings such as tricuspid regurgitation, right ventricular dilation, pulmonary hypertension, and right ventricular dysfunction were evaluated in 15 patients with APTE (APTE group) and 38 patients in the N group (NC group)., Results: The incidence of hyperlipidemia in the VTE group was statistically higher than that in the control group (odds ratio 2.16, 95% confidence interval 1.43-3.08). Additionally, the incidence of obesity was higher in the VTE and N groups than in the control group (odds ratio was 2.76, 95% confidence interval 1.67-4.37). Risk factors other than obesity and hyperlipidemia and the number of risk factors were not significant. The incidence of tricuspid regurgitation, right ventricular dilation, and pulmonary hypertension in APTE was statistically greater than that in NC group. Right ventricular dilation and right ventricular dilation + tricuspid regurgitation are reliable findings in echocardiography. However, even combining with tricuspid regurgitation, right ventricular dilation is insufficient to identify or screen patients with APTE., Conclusions: Hyperlipidemia and obesity may be risk factors for VTE. However, obese patients can manifest similar findings to VTE. Although transthoracic echocardiograpghy is not recommended as a diagnostic or screening test in APTE, it should be used as an ancillary test.

Background/aims: CT has proven useful in diagnosing appendicitis, but it also has some disadvantages. In this study we investigated clinical factors influencing CT findings of acute appendicitis and identified the most appropriate patients for preoperative CT., Methodology: Enhanced helical CT scans were obtained preoperatively in 95 patients who underwent appendectomy. They were gangrenous in 52 (55%), phlegmonous in 38 (40%) and catarrhal in 5 (5%) and we usually indicated emergent surgery for phlegmonous or gangrenous appendicitis patients. 62 (69%) of 90 phlegmonous or gangrenous cases had both an enlarged appendix (> or = 6mm) and periappendiceal fat strand in CT, which strongly suggested the need for emergent operation (Positive group). We compared clinical factors in the positive group with those in the other 28 patients (Equivocal group)., Results: There was no significant difference between the positive and equivocal groups in age, gender, or white blood cell count. The depth of subcutaneous fat (SCF) at the umbilicus level in CT and the number of patients with gangrenous appendicitis were significantly increased in the positive group compared with the equivocal group by both univariate and multilogistic regression analysis., Conclusions: These indicated that the degree of inflammation and SCF were significantly associated with CT findings of appendicitis and CT should be routinely done in obese patients.

Background: Major pulmonary resection with systematic node dissection (SND) for early lung cancer by video-assisted thoracic surgery (VATS) is performed in many institutes, but the feasibility of SND for early lung cancer by VATS remains controversial. The aim of this study was to elucidate the feasibility and safety of SND by VATS., Methods: Three hundred fifty patients with clinical stage I lung cancer who underwent pulmonary major resection with SND between 1998 and 2003 were enrolled in this study. Of these patients, 191 (VATS group) underwent pulmonary resection with SND by VATS; 159 patients (open thoracotomy [OT] group) did so through anterolateral thoracotomy. The clinical and pathologic data, including the number of dissected nodes in each nodal station, of the 2 groups were compared to evaluate the feasibility of SND by VATS., Results: Pathologic data showed that, in the VATS group, more patients had adenocarcinoma (P = .0078) and fewer patients had advanced factors than the OT group. The greatest tumor diameter was 24.5 mm and 29.6 mm in the VATS group and OT group, respectively (P < .0001). The total number of mediastinal nodes dissected in right upper lobectomy plus right middle lobectomy (RUL+RML), right lower lobectomy (RLL), left upper lobectomy (LUL), and lower left lobectomy (LLL) also did not differ between the 2 groups. The total number of mediastinal nodes dissected in RUL+RML, RLL, LUL, and LLL was 19.7 in the VATS group versus 22.0 in the OT group (P = .122), 23.4 versus 21.0 (P = .241), 14.8 versus 17.5 (P = .123), and 18.8 versus 15.8 (P = .202), respectively. The number of dissected nodes in each nodal station in RUL+RML, RLL, LUL, and LLL was similar between the 2 groups. Operative mortality, morbidity, or recurrence did not differ between the 2 groups., Conclusions: With regard to the number of dissected nodes, SND by VATS was not inferior to that of OT. SND by VATS is technically feasible and safe, and seems acceptable for clinical stage I lung cancer.

Objectives: The cause of exercise-induced ST depression was studied by assessing left ventricular end-diastolic pressure (LVEDP)., Methods: This study included 28 patients with normal coronary artery, 24 patients with vasospastic angina pectoris and 28 patients with fixed organic lesion who underwent both treadmill exercise testing and selective coronary arteriography. Exercise-induced ST deviation was considered as maximal ST deviation during the exercise test and maximum LVEDP was considered as the pressure measured 1 min after left ventriculography., Results: The degree of exercise-induced ST depression in aVF showed no significant differences between the three groups. Exercise-induced ST elevation occurred in the intracardiac leads and exercise-induced ST depression occurred in the epicardial leads. These electrocardiographic changes were not contradictory to subendocardial ischemia. In addition, there was a good correlation (r = - 0.465, p < 0.01) between exercise-induced ST depression and maximum LVEDP elevation., Conclusions: Exercise-induced ST depression was caused by subendocardial ischemia due to increased LVEDP.

Objective: The feasibility of systematic node dissection (SND) for stage I primary lung cancer by video-assisted thoracic surgery (VATS) remains controversial. The aim of this study was to assess the feasibility of SND by VATS., Methods: Four hundred and eleven patients with clinical stage I primary lung cancer were enrolled in this study. Two hundred and twenty-one patients, VATS group, underwent a major pulmonary resection with SND by VATS through a minithoracotomy (30-70mm) and two access ports; 190 patients, open thoracotomy (OT) group, did so through anterolateral thoracotomy. The two groups were compared regarding clinical data including number of dissected nodes in each nodal station for evaluating the feasibility of SND by VATS., Results: In the right side, the total number (N) of nodes dissected (VATS 31 vs OT 31, P=0.899), N of mediastinal nodes dissected (20 vs 21, P=0.553), and N of dissected nodes in each nodal station were similar between the two groups. In the left side, total N of nodes dissected (28 vs 27, P=0.714), N of mediastinal nodes dissected (16 vs 17, P=0.333), and N of dissected nodes in each nodal station were similar between the two groups. There were three (1.4%) and five (2.6%) operation related deaths in the VATS group and OT group, respectively (P=0.48). Chest tube duration was shorter in the VATS group than the OT group (5.8 vs 7.6 days, P=0.001). The incidences of chylothorax, recurrent laryngeal nerve injury and pleural effusion requiring thoracentesis after surgery were similar between the two groups (3 vs 4, P=0.709; 5 vs 3, P=0.480, 3 vs 8, P=0.122). The 5-year actuarial recurrence-free survival rate and cumulative survival rate of pathological stage IA cases were similar between the two groups (88.6 vs 92.4%, P=0.698; 92.9 vs 86.5%, P=0.358)., Conclusions: The SND by VATS was as technically feasible as SND through OT regarding number of dissected nodes and morbidity. It seems acceptable as an oncological treatment for clinical stage I lung cancer.

In this report, we describe a new, easy method for putting "U" stitches inside the chest wall. The method does not require extension of the skin incision nor subcutaneous dissection and it minimizes chest wall injury. This method may also be applied to other surgical fields where needles can penetrate the wall of the cavity when it is difficult to stitch from the inside of the cavity.

We present an unusual case of a patient with a right pulmonary interlobar node metastasis from renal cell carcinoma following nephrectomy. She underwent interlobar node dissection (ND) by video-assisted thoracoscopic surgery (VATS). Interlobar ND without lobectomy by VATS has not been reported until now in English literature. The retraction of the right intermediate bronchus is a useful technique during this procedure.

Objectives: Indicators of ischemic heart disease were studied for the practice of preventive medicine., Methods: Intravascular ultrasonography was performed in 97 patients with no abnormalities by left anterior descending artery angiography. Coronary risk factors were evaluated based on the relationship between plaque formation and lipoprotein levels., Results: Plaque was observed in 81% of patients. The relationship between mean plaque area(%) and the low-density lipoprotein/high-density lipoprotein(LDL/HDL)ratio was examined. Mean plaque area(%) was significantly higher at LDL/HDL < or = 2.5 than at LDL/HDL > 2.5. The border of significant change level of mean plaque area(%)was LDL/HDL = 2.5. There was a good correlation between mean plaque area (%) and LDL/HDL (r = 0.65, p < 0.01). Mean plaque area (%) at LDL/HDL 2.5 was calculated at 15%. Patients with coronary risk factors had LDL/HDL lower than 2.5 at mean plaque area of 15%., Conclusions: Maintaining LDL/HDL at 2.5 is very important for preventive medicine. However, LDL/HDL should be managed at under 2.5 in patients with coronary risk factors.

Objectives: To examine the relationship between insulin resistance (IR) and the reduction of oxidative stress in vivo by the statin atorvastatin., Methods: This study included 40 patients with hypercholesterolemia without a history of diabetes mellitus (21 males, 19 females, mean age 62 +/- 11 years). Homeostasis assessment insulin resistance (HOMA-IR) was used as a marker for insulin resistance. The patients were divided into two groups [IR group (n = 24) and non-IR group (n = 16), using the cut off level of 1.73]. Urinary 8-iso-prostaglandin F2alpha (U-8-iso) excretion was used as an oxidative stress marker. The subjects were treated with atorvastatin (10 mg/day) for 12 weeks., Results: The IR group had significantly higher U-8-iso levels than the non-IR group before atorvastatin administration (211 +/- 112 vs 137 +/- 33 pg/mg Cr, p = 0.01). Low-density lipoprotein cholesterol, triglyceride, and 8-iso levels were significantly reduced in both groups after 12 weeks, U-8-iso levels were significantly higher in the IR group than the non-IR group (178 +/- 61 vs 110 +/- 38 pg/mg Cr, p = 0.003), and HOMA-IR showed no significant change. Multiple regression analysis after 12 weeks showed that HOMA-IR and triglyceride levels were independent variables for U-8-iso levels (standard regression coefficient = 0.60, 0.59, p < 0.0001, p = 0.0002)., Conclusions: Insulin resistance is important in the occurrence of oxidative stress in patients with hypercholesterolemia. Since atorvastatin does not reduce insulin resistance, further therapy to reduce insulin resistance is necessary for early prevention of cardiovascular events during atorvastatin treatment.

Objective: A chest tube is usually placed in the pleural cavity after wedge resection of the lung, even after thoracoscopic procedures. The aim of this study was to determine the validity and safety of postoperative management without chest tube placement for patients undergoing thoracoscopic wedge resection of the lung., Methods: Between 1998 and 2002, 93 patients underwent thoracoscopic wedge resection of the lung. In January 2000, we established the following criteria for avoiding chest tube placement: (1) absence of air leaks during intraoperative alternative sealing test, (2) absence of bullous or emphysematous changes on inspection, (3) absence of severe pleural adhesions, and (4) absence of prolonged pleural effusion requiring chest drainage preoperatively. Seventeen of 93 patients did not satisfy the criteria. The other 76 patients were divided into two groups: group 1 consisted of 34 patients who underwent thoracoscopic resection before 1999 and in whom a chest tube was routinely placed in spite of retrospectively meeting the criteria, group 2 consisted of 42 patients who underwent thoracoscopic resection after 2000 and in whom chest tube was not placed. The clinical data were evaluated and analyzed between the two groups., Results: Two patients in group 1 required new intervention after removal of a chest tube that had been inserted during the operation due to recurrence of a pneumothorax, so did two patients in group 2 after the operation. The rate of late pneumothorax requiring intervention is similar in groups 1 and 2. No differences were found between the two groups with regard to postoperative chest pain and hospital stay. No patients experienced a significant adverse outcome., Conclusions: Avoiding the chest tube placement did not increase postoperative morbidity if carefully selected criteria are met.

Background: This study attempted to investigate the influence of massage on the skin and the intramuscular circulatory changes associated with localized muscle fatigue., Material/methods: Twenty-nine healthy male subjects participated in two experimental sessions (massage and rest conditions). Subjects lay prone on the table and were instructed to extend their trunks until the inferior portion of their rib cage no longer rested on the table. Subjects held this position for 90 seconds (Load I). Subjects then either received massage on the lumbar region or rested for 5 minutes, then repeated the same load (Load II). Skin blood flow (SBF), muscle blood volume (MBV), skin temperature (ST), and subjects' subjective feelings of fatigue were evaluated using Visual Analogue Scale (VAS)., Results: An increase of MBV between pre- and post-load II periods was higher after massage than after rest (p<0.05). An increase of SBF at pre- and post-load II was observed only under massage condition. An increase of SBF between post-load I and pre-load II periods was higher after massage than after rest (p<0.05). An increase of ST between post-load I and post-load II periods was greater after massage than after rest (p<0.05). The VAS score was lower with massage than with rest in the post-treatment period (p<0.01)., Conclusions: A significant difference was observed between massage and rest condition on VAS for muscle fatigue. Lumbar massage administration also appeared to have some effect on increasing skin temperature and enhancement of blood flow in local regions.

Objective: The purpose of this study was to assess which clinical features of patients with myasthenia gravis predict postoperative respiratory problems due to myasthenic crisis after transsternal thymectomy., Methods: One hundred twenty-two patients who underwent transsternal thymectomy in our institute were analyzed retrospectively. Fourteen of those experienced myasthenic crisis and required prolonged (48 hours or more) postoperative mechanical ventilation. The following factors were evaluated: sex, age, body mass index, grade of symptom, disease interval, existence of thymoma, history of preoperative crisis, doses of anticholinesterase drugs, steroid use, pulmonary function, serum anti-acetylcholine receptor antibody, history of pulmonary disease, presence of other disease, operation time, and blood loss., Results: Univariate analysis revealed preoperative bulbar symptoms (odds ratio = 14.246, P =.001), history of preoperative myasthenic crisis (7.091,.018), and preoperative serum level of anti-acetylcholine receptor antibody > 100 nmol/L (4.098,.044) were prognostic factors for postoperative myasthenic crisis. On the other hand, multivariate logistic regression analysis revealed preoperative bulbar symptoms (33.333,.004), preoperative serum level of anti-acetylcholine receptor antibody > 100 nmol/L (7.874,.020), and intraoperative blood loss > 1000 mL (18.519,.048) were prognostic factors for postoperative myasthenic crisis., Conclusions: In this study, postoperative myasthenic crisis after transsternal thymectomy in 122 patients with myasthenia gravis was affected by the existence of preoperative bulbar symptoms, history of preoperative myasthenic crisis, preoperative serum level of anti-acetylcholine receptor antibody > 100 nmol/L, and intraoperative blood loss > 1000 mL. Meticulous preoperative and postoperative care should be carried out to prevent postoperative myasthenic crisis in patients with these prognostic factors.

Background: A lateral stabilizer has been used to prevent bar displacement during the Nuss procedure for pectus excavatum repair in pediatric patients. We experienced wound troubles in patients who had a stabilizer placed within them. The aim of this study was to examine the effect of a lateral stabilizer and other clinical factors on wound troubles after the Nuss procedure., Methods: 53 patients with pectus excavatum underwent repair by the Nuss procedure. Preoperative clinical data, operative data, and postoperative complications were examined in all patients., Results: A lateral stabilizer was placed in 29 of the 53 patients. Short-term results were excellent in 42 patients (79.2%). Postoperative complications involved pneumothorax requiring drainage in two patients, atelectasis in one patient, pleural effusion in three patients, deterioration of scoliosis in one patient, erythema in one patient, persistent pain in two patients, bar displacement in four patients, and local wound complications (Seroma with dermatitis due to pressure damage) in five patients. All seromas with dermatitis due to pressure damage were initially aseptic around lateral stabilizers and became infected in four patients after resection of the seroma or spontaneous perforation. Removal of both the pectus bar and lateral stabilizer was performed in two of those four patients and the lateral stabilizer was removed in the other two patients to prevent catastrophic infection such as empyema or mediastinitis. The use of a lateral stabilizer increases the incidence of wound trouble (p = 0.041)., Conclusions: Although the Nuss procedure has evolved into an effective method for pectus excavatum repair, the use of a lateral stabilizer increases the incidence of wound difficulties.

A 68-year-old male, who had suffered from pulmonary tuberculosis with cavities on the right upper lobe, developed breathlessness, bloody sputum, right chest pain and fever. His laboratory data on admission showed severe infection or sepsis (WBC 2,600/mL, CRP 40.2 mg/dL), and his respiratory condition rapidly worsened. In the intensive care unit (ICU) he was given continuous hemodiafiltration (CHDF), but his respiratory condition failed to improve and it was therefore decided to perform a right pneumonectomy. His severe hypoxemia was resolved but because high dose catecholamines medication was still required, polymyxin-B immobilized fiber (PMX) and CHDF were performed. The operation was successful and he was transferred from the ICU to a general ward seven days postoperatively. The vicious circle of septic shock presenting in this case was successfully broken by the pneumonectomy and subsequent treatment by PMX and CHDF, which eliminated the causative factors of sepsis. (Ann Thorac Cardiovasc Surg 2003; 9: 319-22)

The effects of foods on the pharmacokinetics and clinical efficacy of quazepam, a benzodiazepine derivative, in healthy persons were examined. Six healthy Japanese male subjects were randomly divided into three groups and each subject was treated with quazepam under the following three conditions by the crossover method. For the fasting state, subjects were administered 15 mg quazepam 11 hours after a meal. For the postprandial state, subjects were administered 15 mg or 30 mg quazepam 2 hours after a meal. Mean peak plasma concentration (Cmax) of quazepam was significantly higher [1.6-2.8 fold] with administration 2 hours after a meal than 11 hours after a meal. However, in regard to 15 mg of quazepam administration, the area under the curve (AUC) did not differ between administration 2 hours after a meal and 11 hours after a meal. In addition, differences were observed neither in other pharmacokinetic parameters or blood metabolite concentration under all of the study conditions, nor in clinical evaluation of subjective symptoms, complete blood count, or biochemical analyses between administrations 2 and 11 hrs after a meal. The present study showed that administration 2 hours after a meal did not affect subjective symptoms or physical functions so much; therefore it suggested favorable tolerance of this drug. However, it was also suggested that, in actual clinical use, it is important to evaluate the physical function including measurements of vital signs and hematological test results, carefully considering the effects of foods and daily life-style.

Objectives: The relationship between oxidative stress in vivo and insulin resistance was examined., Methods: This study included 87 patients, 46 males and 41 females (mean age 63 +/- 10 years), without coronary artery disease. The homeostasis assessment insulin resistance (HOMA-IR) (fasting blood sugar x fasting immunoreactive insulin/405), a marker for insulin resistance, was measured. The patients were divided into three groups: the noninsulin resistance group (N-IR group) without diabetes mellitus (DM) and with fasting blood glucose level of 126 mg/dl and HOMA-IR < or = 1.73 (n = 44), the insulin resistance group (IR group) without diabetes mellitus and with fasting blood glucose level of 126 mg/dl and HOMA-IR > 1.73 (n = 29), and the DM group (type 2 diabetes mellitus) (n = 14). Urinary 8-iso-prostaglandin F2 alpha (U-8-iso-PGF2 alpha) excretion was measured as a marker of in vivo oxidative stress., Results: There were significantly more obese patients in the IR group than in the N-IR group (62% vs 25%, p = 0.001), and the remnant-like particle cholesterol level was significantly higher in the IR group than in the N-IR group (7.6 +/- 5.2 vs 4.6 +/- 1.5 mg/dl, p < 0.01). Patients in the IR group had a significantly larger number of coronary risk factors. U-8-iso-PGF2 alpha excretion was significantly higher in the IR group and DM groups (201 +/- 86, 191 +/- 136 vs 129 +/- 50 pg/mg. Cr, p < 0.0001, p = 0.01), and there was a significantly positive correlation between the number of coronary risk factors, fasting blood sugar and U-8-iso-PGF2 alpha concentration (correlation coefficient = 0.32, 0.37, p = 0.002, p = 0.0003). Multiple regression analysis showed that remnant-like particle cholesterol, fasting blood sugar and insulin resistance were independent factors for U-8-iso-PGF2 alpha concentration (p < 0.0001, p = 0.0007, p = 0.02)., Conclusions: Insulin resistance, remnant lipoprotein and hyperglyceridemia are deeply involved in oxidative stress in vivo.

We describe here a case with a large bronchogenic cyst treated by surgical resection, who presented with evidence of left atrial overload on electrocardiogram (ECG). The 50-year-old male patient presented with the chief complaint of heaviness in the chest on exertion. An ECG revealed evidence of left atrial overload, and echocardiography and imaging revealed a mass having a maximum diameter of 9 cm on the cranial aspect of the left atrium, caudal to the tracheal bifurcation. The patient was treated by surgical resection of the cystic mass via right anterolateral thoracotomy. His postoperative course was satisfactory and the patient was relieved of his main symptom.

Objectives: The preventive effect of pemirolast against restenosis after coronary stent placement was evaluated., Methods: Eighty-four patients with 89 de novo lesions who underwent successful coronary stenting were assigned to the pemirolast group(40 patients, 45 lesions) and the control group(44 patients, 44 lesions). Administration of pemirolast(20 mg/day) was initiated from the next morning after stenting and continued for 6 months of follow-up. Quantitative coronary angiography was performed immediately after stenting and at follow-up. Angiographic restenosis was defined as diameter stenosis > or = 50% at follow-up. Intravascular ultrasound study conducted at follow-up angiography was used to measure vessel cross-sectional area(CSA), stent CSA, lumen CSA, neointima CSA(stent CSA--lumen CSA), and percentage neointima CSA(neointima CSA/stent CSA x 100%) at the minimal lumen site., Results: There were no significant differences in baseline characteristics between the two groups. Restenosis rate was significantly lower in the pemirolast group than in the control group(15.0% vs 34.1% of patients, 13.3% vs 34.1% of lesions, p < 0.05, respectively). The intravascular ultrasound study at follow-up(36 lesions in the pemirolast group, 33 in the control group) found no significant differences in vessel CSA and stent CSA between the two groups(17.3 +/- 2.2 vs 16.8 +/- 2.4 mm2, 8.6 +/- 1.9 vs 8.4 +/- 1.7 mm2, respectively). However, lumen CSA was significantly larger in the pemirolast group than in the control group(5.5 +/- 1.3 vs 4.4 +/- 1.1 mm2, p < 0.05). Moreover, neointima CSA and percentage neointima CSA were significantly smaller in the pemirolast group(3.1 +/- 1.1 vs 4.0 +/- 1.2 mm2, p < 0.05 and 36.2 +/- 15.9% vs 47.4 +/- 15.6%, p < 0.01)., Conclusions: Pemirolast has a preventive effect against restenosis after stent placement, possibly by inhibiting neointimal hyperplasia.

Based on long-term, although intermittent, observations (2 years 4 months of 14 years), we present data on birth seasonality, age at first birth, interbirth intervals, mortality rates, age at first emigration, and population change of a wild population of West African patas monkeys ( Etythrocebus patas patas) in northern Cameroon. Birth season was from the end of December until the middle of February, corresponding to the mid-dry season. In spite of large body size, the patas females had the earliest age at first birth (36.5 monthsold) and the shortest interbirth intervals (12 months) compared to the closely related wild forest guenons. Age at first emigration of the males was considered to occur between 2.5 and 4.5 years. The group size of the focal group drastically decreased between 1984 and 1987, and steadily increased until 1994, then decreased again in 1997. The neighboring group also showed a similar trend in group size. The population decreases were likely to be caused by drought over 3 years. Annual crude adult mortality rate was 4% during population increase periods (PIP) between 1987 and 1994. It rose to 22% during all the periods (AP), including drought over 3 years. Despite their smaller body size, the rate of the wild forest guenons ( Cercopithecus mitis) (4%) was the same and much lower than those of the patas during PIP and AP, respectively. The annual average juvenile mortality rate was 13% during PIP and it also rose to 37% during AP. That of wild forest guenons ( C. ascanius) (10-12%) was a little lower and much lower than those of the patas during PIP and AP, respectively. These findings were consistent with Charnov's theoretical model of mammalian life-history evolution in that patas with high adult and juvenile mortality showed early and frequent reproduction in spite of large body size. Charnov also considered high adult mortality as a selective force and high juvenile mortality as a density-dependent consequence of high fecundity. Our results support the former but not the latter research findings.

Data on social changes in patas monkey (Erythrocebus patas) groups were collected to clarify the general characteristics of male supplantation and to evaluate the overall role of supplanting in patas society. Seven patas groups were observed in Kala Maloue National Park, Northern Cameroon for 11 years. Analysis of this data revealed that social change, such as male supplanting, was restricted to the mating season. Male supplanting occurred in the course of outsider males seeking to gain access to estrous females within the heterosexual group and supplanting was inevitably followed by a multi-male situation arising in the group. Many cases of multi-male invasion were preceded by the supplanting of resident males and the multi-male situation arose due to a temporary absence of serious aggression towards invader males by the new resident males. Notably, an all-male group was found only once and it did not contribute to the supplanting of resident males in the one-male group.

The effect of electro-acupuncture stimulation (EAS) on duodenal motility was examined in anesthetized, artificially ventilated rats. EAS was applied to the abdominal area or to a hindpaw for 30 s at stimulus intensities of 0.1-10.0 mA with a stimulus frequency of 20 Hz. The duodenal motility was measured using the balloon method at a position about 1.5 cm caudal from the pylorus. Duodenal motility was inhibited by EAS at intensities of more than 5.0 mA (suprathreshold of group IV afferent excitation) when applied to the abdominal area. The duodenal inhibitory response existed after bilateral vagotomy or spinal transection, but was abolished by sectioning bilateral splanchnic nerves. Duodenal motility was facilitated by EAS at intensities of more than 2.0 mA (subthreshold of group IV, and suprathreshold for groups II+III afferent excitation) when applied to a hindpaw. The duodenal facilitatory response by EAS to a hindpaw existed after sectioning the splanchnic nerves, but disappeared after bilateral vagotomy or spinal transection. Furthermore, repetitive electrical stimulation of vagal efferent nerves enhanced duodenal motility, while repetitive electrical stimulation of the splanchnic efferent nerves inhibited the motility. It was concluded that the inhibitory response of duodenal motility elicited by EAS to the abdominal area is a spinal reflex response involving splanchnic inhibitory efferent nerves, and the enhanced response of duodenal motility by EAS to a hindpaw is a supraspinal reflex response involving vagal excitatory nerves.