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We applied a new implanting technique for an implantable cardioverter defibrillator (ICD) in a 4-month-old girl with repeated ventricular fibrillation (Vf) due to long QT syndrome. This technique consisted of placement of an oval patch lead on the outer surface of the pericardium in the left pleural cavity. This was useful in preventing the complications of the conventional epicardial patch leads (ie, crinkling of the lead and constrictive pericarditis). This patch should be contemplated as an alternative option for implanting ICD in infants.

We report a case of perforated Meckel's diverticulum with aseptic peritonitis in a 17-day-old neonate. The baby had been brought to the hospital with fever and abdominal distention. Abdominal computed tomography showed a 5-cm abscess in the lower abdomen, and emergency laparotomy was performed for suspected perforated appendicitis. However, we found a perforated Meckel's diverticulum. No bacteria were detected in the purulent ascites from the peritoneal cavity. We speculate that the narrow lumen between the small intestine and the diverticulum, accompanied by poor self-emptying had caused acute inflammation resulting in perforation of Meckel's diverticulum. The anatomic limitations in "walling off" the perforated Meckel's diverticulum by the surrounding loops of small intestine prevented the bowel contents from spreading within the peritoneal cavity.

A boy, prenatally diagnosed as hypoplastic left heart syndrome (HLHS) with intact atrial septum (IAS) was successfully treated by hybrid procedures. He underwent emergent catheter atrial septostomy and stent insertion in the atrial septum on Day 1 and then underwent bilateral pulmonary artery banding, ductal stent insertion, modified Norwood operation, bidirectional Glenn’s operation and finally Fontan type operation at 2 years of age. Considering the presence of decompression pathway from the left atrium in HLHS with IAS, we should organize a treatment team for collaborative work and plan an appropriate treatment strategy before delivery. Although his clinical course has been uneventful until now, closer medical observation is warranted because he may have coexisting pulmonary disease.

Video-assisted thoracoscopic surgery is a type of minimal-access surgery. The nature of the surgery means that there are limitations on the size of a tumor that can be removed through an access incision. Herein, we report our experience removing a giant teratoma (16 × 14 × 13 cm in size) from the anterior mediastinum of a young girl. We employed video-assisted thoracoscopic surgery to remove the teratoma through a mini-thoracotomy following the extraction of the cystic components.

We herein report the case of a splenic artery aneurysm with a hepatosplenomesenteric trunk that presented in a pregnant woman. Catheter embolization was not performed due to the wide neck of the aneurysm and its close location to the trunk indicates a high risk of mesenteric trunk thrombosis. We instead performed surgical resection of the aneurysm after successful delivery of the infant by Caesarian section. The splenic artery was reconstructed by side-to-end anastomosis with the common hepatic artery.

Aortoesophageal fistula occurring as a complication of a thoracic aortic aneurysm is difficult to repair because of the contaminated surgical field. We report the case of a 67-year-old man in whom an aortoesophageal fistula developed secondary to a dissecting thoracic aortic aneurysm. We performed in situ graft repair of the aneurysm, then covered the site with omentum and resected the esophagus to prevent graft infection. About 5 months later, the esophagus was reconstructed subcutaneously using an ascending colon pedicle. The patient recovered well and has resumed leading a normal life.

A cystic lesion between the left internal thoracic artery (LITA) graft and left anterior descending artery (LAD) flow was detected by routine transthoracic echocardiography in a patient after coronary artery bypass grafting. The cystic lesion communicated with the anastomotic site of the LITA graft to LAD, and it was diagnosed as a pseudoaneurysm of the LITA graft by transthoracic echocardiography.Because pseudoaneurysm of a coronary bypass graft is a potentially fatal complication after coronary artery bypass grafting, it is important to detect the LITA graft flow at the anastomotic site by transthoracic echocardiography in routine examination.

Controlled growth of titanium oxide films by sequential surface chemical reactions was studied using a novel vapor combination of tetrachlorotitanium (TiCl4) and hydrogen peroxide (H2O2). Optical constants and thicknesses of these films were investigated in terms of growth temperature and vapor pressures by using a variable-angle spectroscopic ellipsometer. Growth rates were almost constant at approximately 0.065 nm cycle−1 (= 0.65 nm min−1) for substrate temperatures from 340 °C to 490 °C. Indices of refraction were also constant at 2.6 in almost the same temperature range.

冠動脈病変を合併した大動脈瘤症例で, 大動脈瘤手術前にPTCAにより冠血行再建を行った5症例の動脈瘤手術成績を検討した. 1987年11月から1993年11月の期間の当科での真性大動脈瘤手術症例60例 (腹部大動脈瘤(AAA)45例, 胸部大動脈瘤(TAA)15例) 中, 待機手術をした46例全例に術前冠動脈造影を施行した. 23例 (AAA 19例, TAA 4例) に冠動脈病変合併を認め, 12例 (AAA 10例, TAA 2例) に冠血行再建を併せ行った. この12例中, 動脈瘤, 冠動脈病変の診断が同時期に得られた症例は9例で, 動脈瘤手術前にPTCAを行った5例 (AAA 3例, TAA 2例) を対象とした. 性別は男性4例, 女性1例, 年齢は63～76歳(平均68歳). PTCAを6病変に行い, 成功4病変, 不成功1病変, 失敗1病変 (緊急CABGとなった) であった. 動脈瘤手術近接期, 遠隔期の心筋梗塞発症例, 死亡例はなく, PTCAは冠血行再建手段として, とくに高齢者で有用であった.

The association between abdominal aortic aneurysm (AAA) and renal tumor is becoming more frequent, and the increasing incidence of this synchronous diseases raised questions about the procedures of treatment. In most of the previous cases, open nephrectomy and AAA surgery have been reported, however in high risk and elderly patients, the procedure is life threatening. We present a successful staged treatment of AAA and renal tumor using novel minimally invasive treatment with endovascular aneurysm repair and retroperitoneal laparoscopic radical nephrectomy in an elderly and high-risk case.

Thirteen patients with Dupuytren's contractures were treated surgically and the relationship between preoperative factors and results investigated.The mean postoperative follow-up period was 4 years 9 months, ranging from 7 months to 9 years. The surgical technique was limited fasciectomy in all hands.According to Tubiana's evaluation of postoperative results, 6 hands achieved excellent results, five were good 4 hands were fair, and results in one hand were judged to be poor.Results became worse as the grade according to Meyerding's classification, advanced.Dupuytren's contractures involving the small finger or the PIP joint had the worse prognosis.

Reconstructive surgery using bone cement in total knee arthroplasties (TKA) for severe bone defects of the medial tibial condyle in osteoarthritis was reviewed in three patients. The mean duration of follow-up was 6 years and 10 months.At the time of surgery, several techniques were added to the typical TKA. The postoperative femorotibial angle (FTA) was corrected to 170°, and tibial component was shifted laterally rotational position.The preoperative Japanese Orthopaedic Association score of Knee Arthrosis averaged 37 points. The postoperative score averaged 86 points.The bony support of the tibial component in anteroposterior roentgenogram was about 77% postoperatively.The radiolucent area averaged 1mm at 6 years and 10 months after surgery, and loosening did not occur in any cases.In cases with more than 75% tibial bony support, good results were achieved using our surgical methods.

脳虚血に伴う神経細胞障害と脳局所乳酸acidosisの関係を知る目的で, 細胞外乳酸acidosis時における培養神経細胞の変化を検討した.Wistar rat胎児の大脳皮質細胞を単離し, 4日間培養した後, 乳酸を用いてpHを11段階に調整した培地に置換し, それぞれの培地で3, 6, 24, 72時間培養した.更にこれらの細胞の細胞内ミトコンドリア機能 (MTT assayにより検討), 蛋白量 (SRB assayにより検討), 培養神経細胞の形態などの時間的変化を各pHにおいて観察した.ミトコンドリア機能は, いずれの培養時間でもpH5.75以下で急速な低下を認めた.蛋白量はこの培養時間内では, いずれの群でも有意な変化は認めなかった.光学顕微鏡による細胞の形態学的変化の観察では, 低pH培地で培養したものは細胞体の腫脹傾向を認めた.これらの結果より, 細胞周囲の乳酸acidosisは細胞内ミトコンドリア機能の低下をきたし, 細胞障害を惹起する原因の一つになることが示唆された.

There are no guidelines for the optimal therapeutic range of anticoagulant therapy in Japanese patients with mechanical heart valves. A total of 214 patients were followed retrospectively after mitral mechanical valve replacement (mean duration of follow-up, 4.8 years; total duration of follow-up, 1,027 patient-years). The target range of the international normalized ratio (INR) for oral anticoagulation was between 1.5 and 2.5. For all patients 10,416 measurements of the INR were obtained during the follow-up period and approximately 76% of the intensity measurements were within the target range. Thromboembolism occurred in 8 patients (0.8 per 100 patient-years) and major bleeding in 5 patients (0.5 per 100 patient-years). There was no correlation between the distribution of the INR and the occurrence of thromboembolic or bleeding complications. In the univariate analysis of the various risk factors, patients who had a tilting valve or did not receive antiplatelet therapy had an increased risk of thromboembolism. However, there were no risk factors with respect to bleeding complications. A target range of 1.5 to 2.5 INR appears to be the optimal range and is safe for thromboembolism or bleeding complications. Thromboembolism may be reduced by additional antiplatelet therapy, and a tilting valve needs more intense anticoagulation.

The synthesis of four vitamin D3 analogues, 1α,24(S)- and 1α,24(R)-dihydroxy-22-oxa-vitamin D3, (5) and (6), and their 26,27-diemethylated homologues, (7) and (8), and the preliminary evaluation of their differentiation-inducing activity in vitro are described.

Rupture of a chronic postinfarction aneurysm of the left ventricle is rare and usually fatal. A 63-year-old man with rupture of a true left ventricular aneurysm 67 days after myocardial infarction was treated successfully with resection of the aneurysm. The postoperative course was uneventful.

Four vitamin D3 analogues, 1α, 24(S)-and 1α, 24(R)-dihydroxy-22-oxavitamin D3 (5 and 6) and their 20(R)-epimers (7 and 8) were synthesized from the 20(S)-alcohol (10). In tests of activity to induce differentiation of human myeloid leukemia cells (HL-60) to macrophages, 5 showed comparable activity to 1α, 25-dihydroxy-22-oxavitamin D3 (OCT) (2), and the other three analogues (6, 7 and 8) were less active than OCT (2). The binding properties of these analogues to the chick embryonic intestinal 1α, 25-dihydroxyvitamin D3 (1) receptor were evaluated. Furthermore, 20(R)-OCT (9) was synthesized and its biological properties were compared with those of OCT (2) and the 20(R)-epimers (7 and 8).

Two cases of sacrococcygeal chordoma, were surgically treated in our hospital. One case was discovered after investigation of an episode of bruising on the hip, and the other case was diagnosed two years after the excision of rectal cancer that had no specific histological features.Both cases had partial destruction of sacral bone in the lateral plain X-ray film of the pelvis and a defined mass anterior to the lower sacrum was seen on MRI. We performed complete excision of tumor using the posterior approach and retained the unilateral S3 nerve. Postoperatively there was no neurological disturbance except the symptom of slight residual urine.

Milnacipran is a specific serotonin and norepinephrine reuptake inhibitor, which has been widely used against major depressive episodes. In this study, cardiovascular effects of milnacipran were assessed in comparison with those of a typical tricyclic antidepressant imipramine using the halothane-anesthetized dogs. Milnacipran (n = 6) or imipramine (n = 6) was intravenously administrated in three escalating doses of 0.1, 1 and 10 mg/kg over 10 min with a pause of 20 min between the doses. Clinically relevant plasma concentrations were obtained after 0.1–1 mg/kg of milnacipran in this study, whereas therapeutic dose and plasma concentration of imipramine were reported to be similar to those of milnacipran. The low and middle doses of milnacipran hardly affected cardiohemodynamic or electrophysiological variables except that they slightly increased vascular tone and ventricular contraction, whereas same doses of imipramine delayed repolarization process without affecting the other variables. The high dose of both milnacipran and imipramine induced similar extent of negative chronotropic, inotropic and dromotropic effects together with vasoconstriction and repolarization delay. Thus, the effects of milnacipran may be more selective for cardiohemodynamics than for repolarization delay, whereas reverse will be true for imipramine, supporting lack of clinical report of patients with milnacipran-induced long QT syndrome unlike imipramine.

The cytotoxicity of 1-β- d -arabinofuranosylcytosine (ara-C) in combination with hydroxyurea (HU) or 2′-deoxyguanosine (GdR) on human gastric carcinoma MK-1 cells and colon carcinoma HT-15 cells was studied. Synergistic interaction between ara-C and HU on MK-1 cells and HT-15 cells, or ara-C and GdR on MK-1 cells was shown using the combination index method. HU increased the accumulation of ara-C triphosphate (ara-CTP) in the acid-soluble pool and diminished the cellular deoxyCTP (dCTP) pool. HU had no effect on the incorporation of ara-C into DNA and RNA. These results indicate that HU-induced elevation in ara-CTP and decrease in dCTP are the basis for synergy among ara-C and HU in MK-1 cells. GdR diminished cellular dCTP slightly, but it decreased the accumulation of ara-CTP in the acid-soluble pool and did not increase the incorporation of ara-C into DNA. On the other hand, ara-C increased cellular deoxyGTP (dGTP) level in the presence of GdR. These results indicate that synergy between ara-C and GdR is mediated through increased cellular dGTP which might inhibit DNA synthesis directly.

Six analogues of 1 alpha,25-dihydroxy-22-oxavitamin D3 (OCT) (2), 26,27-dimethyl OCT (5), 26,27-diethyl OCT (6), 24-norOCT (7), 24-homoOCT (8), 24-dihomoOCT (9), and 24-trihomoOCT (10) were synthesized from the 20(S)-alcohol (11) as the common starting material. In the activity inducing differentiation of human myeloid leukemia cells (HL-60) into macrophages, 26,27-dimethyl OCT (5) and 24-homoOCT (8) showed the highest activities. The binding properties of these analogues to the chick embryonic intestinal 1 alpha,25-dihydroxyvitamin D3 (1) receptor are also described.

1 alpha,25-Dihydroxy-21-norvitamin D3 (3) was synthesized from 1 alpha-hydroxydehydroepiandrosterone (4). Certain biological properties of 3 were examined in comparison with those of 1 alpha,25-dihydroxyvitamin D3 (1) and 1 alpha,25-dihydroxy-21-nor-20-oxavitamin D3 (2) to evaluate the effect of the 21-methyl substituent on biological activities. The differentiation-inducing activity of 3 towards human myeloid leukemia cells was approximately one-fifth of that of 1, while in the binding affinity with chick intestinal cytosolic receptor, 3 was about one-tenth of that of 1. The rather weak effect of 3 on serum calcium levels in normal mice at a dosage of 500 micrograms/kg (intravenous administration) indicates that the essential importance of the 21-methyl moiety may lie in its effect on the regulation of calcium metabolism.

Aim: In 2003, the American Diabetes Association recommended that the threshold for diagnosing impaired fasting glucose (IFG) should be lowered from 6.1 mmol/L (110 mg/dL) to 5.6 mmol/L (100 mg/dL). To discuss the diagnostic threshold for IFG, the association between fasting plasma glucose (FPG) and the risk of future diabetes must be known; however, data regarding this relation in the Japanese population are scarce. The aim of this study was to determine the relation between FPG and the risk of future diabetes in the Japanese general population.Methods: A retrospective cohort study was conducted using data from annual health check-ups performed in Omiya city. A total of 11,369 subjects between the ages of 40-79 years who were not dia-betic at baseline were followed for seven years. Diabetes was defined as FPG ≥126 mg/dL or self-report.Results: The incidence of diabetes increased as the baseline FPG level increased and a similar pattern was observed irrespective of sex or age. The hazard ratios compared with subjects with FPG

A mass in the right atria was detected by computed tomography (CT) 2 years ago in a 61-year-old man with a medical history of hypertension and surgery for gall bladder carcinoma. The latest CT imaging indicated enlargement of the mass. Transthoracic echocardiography showed that a mobile mass in contact with the septum was present in the right atria, and a very bright region suggesting partial calcification was noted (Figure 1A and online-only Data Supplement). On nongated chest contrast CT, a low-intensity 26×20-mm region without enhancement and with partial calcification was present in the right atrium (Figure 1B and online-only Data Supplement); noncontrast MRI of the chest showed a round lesion with a diameter of approximately 26 mm and a clear boundary in contact with the septum. The inner region of the mass showed a slight high intensity on T1-weighted imaging (Figure 2A and online-only Data Supplement) and a low intensity …

We report a long-term survivor with Uhl's anomaly who underwent one and a half ventricle repair combined with a partial right ventriculectomy in infancy, followed by successful total cavopulmonary conversion with right ventricular exclusion 5 years later. The combination of total cavopulmonary connection and right ventricular exclusion could be the optimal surgical option for a critically ill infant with Uhl's anomaly.

A 72-year-old man with a history of old myocardial infarction was admitted to our hospital for surgical treatment of a ruptured abdominal aortic aneurysm. His hemodynamics was stable. He had left lumbar pain on moving his left leg and constipation for ten days without abdominal pain and high fever. Elevation of fat density around the aneurysm and ureter involvement were noted on the computed tomography. These characteristic image findings indicated inflammatory aortic aneurysm. During operation, an infrarenal abdominal aortic aneurysm with an 8 cm maximum diameter was noted. This aneurysm was firm and thick and adhered to some organs due to inflammation. An 5 × 5 cm punched-out defect was found on the lateral wall of the aneurysm. We replaced the ruptured aneurysm with a Dacron graft. Histological examination showed that the aneurysm wall had an infiltrate of inflammatory cells, lymphoid follicles and thickened adventitia. From these findings, the diagnosis was inflammatory aortic aneurysm.

A 69-year-old man with a medical history of neurofibromatosis was transferred to our hospital for the treatment of an aortic valve mass. His workup identified an aortic valve papillary fibroelastoma based on the absence of signs of infection, thrombus in the left atrium, and valvular destruction or abnormal valvular function. A tumor was excised under cardiopulmonary bypass. The pathology of the mass was a papillary fibroelastoma. Neurofibromatosis with cardiac tumor is extremely rare. This is the first report of a case of papillary fibroelastoma associated with neurofibromatosis.

We report a case of locally constrictive pericarditis and epicarditis, which did not indicate typical findings of CT and MRI, late after open-heart surgery. A 74-year-old man with a history of coronary artery bypass grafting was transferred to our hospital for treatment of heart failure. Transthoracic echocardiography, computed tomography (CT) and magnetic resonance imaging (MRI) showed a cystic lesion that compressed the right ventricle and main pulmonary artery without enhancement. However, the pericardial hypertrophy was not clear. We suggested a benign, cystic lesion based on these examinations and planned surgical removal of the mass to release the compression of the heart and to confirm the diagnosis of the capsulized mass. At surgery, cystic mass formation was covered by a thickened fibrous tissue, pericardium and epicardium and was filled with transparent yellowish fluid. We performed a waffle procedure without cardiopulmonary bypass. Histopathologic examination of the excised epicardium revealed neovascularization, minimal inflammation and thickened hyaline connective tissue and was diagnosed as constrictive percarditis and epicarditis.

A case of intraaortic balloon entrapment is reported. To our knowledge, this is the tenth case in the literature. We conclude that balloon entrapment can occur without any signs of rupture of the balloon and that the balloon should be removed surgically.

The effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) in enhancing antimicrobial chemotherapy was investigated. Combined treatments of rG-CSF with cefotaxime, cefazolin, fosfomycin, gentamicin or amphotericin B were evaluated in systemic infections with Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Staphylococcus aureus and Candida albicans in leucopenic mice induced by pretreatment with cyclophosphamide. Administration of appropriate antibiotics afforded a dose-related inhibition of death from infection in normal mice and mice treated with rG-CSF after cyclophosphamide injection. In cyclophosphamide-treated mice, even larger doses of the antibiotics failed to provide protection against infection with the same inoculum size. These results suggest the possibility that rG-CSF could be of help in treatments with antimicrobial agents against infections in leucopenic patients.

Circulatory distress can occur in the long term after the formation of a traumatic arteriovenous fistula (AVF), but cardiac failure rarely occurs in a patient with an AVF in the lower extremity. The present patient underwent surgery to treat a traumatic popliteal AVF 9 years after sustaining the injury. Although the patient was asymptomatic with regard to cardiac circulation, cardiomegaly was noted and it resolved promptly after the surgical treatment. Cardiac insufficiency should be borne in mind even when a patient is asymptomatic because young patients have a high tolerance for cardiac overload. (Circ J 2009; 73: 776 - 778)

The patient was a 76-year-old woman who underwent left atrial thrombectomy in November 2003 at our hospital. A mass adhered to the non-coronary aortic cusp was found during annual echocardiography, and the patient was admitted to our hospital. Transthoracic echocardiography detected two masses with pendulum-like movement: a 7-mm mass adhered to the non-coronary cusp and a 5-mm mass on the right coronary cusp. Papillary fibroelastoma was diagnosed based on the absence of inflammatory reactions or valvular destruction. Anticoagulant therapy was continued to prevent left atrial thrombus formation. At surgery, a 7-mm mass was adhered to the belly of the non-coronary cusp and a 5-mm pediculate mass was attached to a site near the nodule of Arantius of the right coronary cusp. Movable fibrous connective tissue 4 mm in length was present at two sites near the nodule of Arantius of the left coronary cusp, and these were also excised. All excised specimens, including those considered to be connective tissue, were found to be papillary fibroelastoma on pathological examination. Four papillary fibroelastomas that developed in all the cusps, including two small connective tissue-like morphologies and two sea anemone-like morphologies, indicated the process of papillary fibroelastoma growth and looked like 'a family'.

In the present study, we identified a gene termed Nbla10993 whose expression levels are higher in favorable neuroblastomas versus unfavorable ones. Structural analysis showed that Nbla10993 is a novel splicing variant of the ER-associated protein of 140 kDa (ERAP140), which lacks the central acidic as well as the COOH-terminal Cys/His-rich domain. Similarly, ERAP140 was preferentially expressed in favorable neuroblastomas relative to unfavorable ones. During the all-trans-retinoic acid (ATRA)-mediated neuronal differentiation in neuroblastoma-derived RTBM1 cells, the expression levels of ERAP140/Nbla10993 increased at the mRNA level. Consistent with these observations, the luciferase reporter analysis demonstrated that the ERAP140/Nbla10993 promoter responds to ATRA. In addition, the immunoprecipitation/immunoblotting experiments showed that ERAP140 forms a stable complex with RARalpha but not with RXRalpha in cells, suggesting that ERAP140 is involved in RAR-mediated transcriptional regulation. Furthermore, the quantitative real-time PCR analysis using 109 primary neuroblastoma samples demonstrated that the expression levels of ERAP140/Nbla10993 significantly correlate with a better clinical outcome of neuroblastomas. Taken together, our present findings indicate that ERAP140/Nbla10993 plays an important role in the regulation of ATRA-mediated neuronal differentiation, and is a novel member of prognostic indicators for neuroblastoma.

The effects of ribonucleotide reductase inhibitors on the growth of the human colon carcinoma cell line HT-29 were examined. Inhibitors were chosen for these studies that were specifically directed at each of the subunits of ribonucleotide reductase. The concentrations of drugs required to inhibit the growth of HT-29 cells by 50% (IC50) for hydroxyurea, 2,3-dihydro-lH-pyrazole-[2,3a]imidazole (IMPY), and 4-methyl-5-amino-l-formyl-isoquinoline thiosemicarbazone (MAIQ) were 206, 996, and 3.2 microM, respectively. Although the IC50 for deoxyadenosine alone was greater than 2,000 microM, in the presence of 5 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), which protects deoxyadenosine from deamination by adenosine deaminase, it was reduced to 112 microM. The IC50 for deoxyguanosine was 1,060 microM. The addition of 8-aminoguanosine to protect deoxyguanosine from phosphorolysis by purine nucleoside phosphorylase did not increase the toxicity of deoxyguanosine in HT-29 cells. The combination of MAIQ or IMPY and deoxyadenosine/EHNA gave strong synergistic inhibition of HT-29 cell growth. The results of these studies indicate that ribonucleotide reductase inhibitors effectively block the growth of human colon carcinoma HT-29 cells and that combinations of inhibitors directed at the individual subunits of reductase result in synergistic inhibition of HT-29 cell growth in culture.

Administration of 2,3-dihydro-1H-pyrazole[2,3a]imidazole (IMPY, 150 mg/kg) followed 8 hr later by injection of deoxyadenosine/erythro-9-(2-hydroxyl-3-nonyl)adenine (dAdo/EHNA, 175 mg/17.5 mg/kg) on days 2, 3, 6, and 7 increased the mean survival time of L1210 tumor bearing mice (210%). The sequential treatment was more efficacious than the simultaneous administration of these drugs. Administration of IMPY or dAdo/EHNA, alone, at the same doses as in the combination, did not prolong the life-span of tumor bearing mice. To determine the basis for the increased survival due to the sequential treatment with IMPY and dAdo/EHNA, cell cycle analysis and deoxyribonucleoside triphosphate concentrations were measured. Cytotoxicity of IMPY and dAdo/EHNA is known to be achieved through the inhibition of ribonucleotide reductase. IMPY is a specific inhibitor of the nonheme-iron subunit of ribonucleotide reductase, whereas deoxyadenosine in the presence of the adenosine deaminase inhibition, EHNA, is converted to deoxyadenosine 5'-triphosphate (dATP), which is a specific inhibitor of the effector-binding-subunit of ribonucleotide reductase. Our studies showed that L1210 cells accumulated in early S-phase, whereas intracellular dATP and deoxyguanosine triphosphate (dGTP) pools were depleted 8 hr after IMPY administration. dAdo/EHNA administration 8 hr after IMPY injection caused an increase in the intracellular concentration of dATP while maintaining the depletion of the dGTP pool and prolonged the S-phase as compared to the administration of IMPY alone.

In response to DNA damage, p53 and its homolog p73 have a function antagonistic to NF-kappaB in deciding cell fate. Here, we show for the first time that p73, but not p53, is stabilized by physical interaction with nuclear IkappaB kinase (IKK)-alpha to enhance cisplatin (CDDP)-induced apoptosis. CDDP caused a significant increase in the amounts of nuclear IKK-alpha and p73alpha in human osteosarcoma-derived U2OS cells. Ectopic expression of IKK-alpha prolonged the half-life of p73 by inhibiting its ubiquitination and thereby enhancing its transactivation and pro-apoptotic activities. Consistent with these results, small interfering RNA-mediated knockdown of endogenous IKK-alpha inhibited the CDDP-mediated accumulation of p73alpha. The kinase-deficient mutant form of IKK-alpha interacted with p73alpha, but failed to stabilize it. Furthermore, CDDP-mediated accumulation of endogenous p73alpha was not detected in mouse embryonic fibroblasts (MEFs) prepared from IKK-alpha-deficient mice, and CDDP sensitivity was significantly decreased in IKK-alpha-deficient MEFs compared with wild-type MEFs. Thus, our results strongly suggest that the nuclear IKK-alpha-mediated accumulation of p73alpha is one of the novel molecular mechanisms to induce apoptotic cell death in response to CDDP, which may be particularly important in killing tumor cells with p53 mutation.

Electropharmacological effects of chronically administered amiodarone and candesartan on atria that had been remodeled against congestive heart failure were assessed using dogs (about 10 kg in weight) with chronic atrioventricular block. Amiodarone was administered orally in a dose of 200 mg/body per day for the initial 7 days followed by 100 mg for the following 21 days (n = 7). Candesartan was administered in a dose of 12 mg/body per day for 28 days (n = 7). All animals survived the 4-week experimental period, indicating the lack of risks for inducing cardiohemodynamic collapse or torsade de pointes by these drugs. The plasma amiodarone concentration was 353 ng/ml at 4 weeks of treatment. Before candesartan treatment (control), intravenous administration of 30 ng/kg of angiotensin II increased the mean blood pressure by 18 mmHg, which was significantly decreased to 1 mmHg by 4 weeks of treatment. Amiodarone prolonged the atrial effective refractory period without affecting inter-atrial conduction time and decreased the duration of the burst pacing-induced atrial fibrillation, whereas candesartan hardly affected these variables. These results indicate that amiodarone should become a pragmatic pharmacological strategy against atrial fibrillation in patients with chronically compensated heart failure and suggest that a much higher dose of candesartan may be needed to exert its efficacy in this model. Keywords:: amiodarone, candesartan, atrial fibrillation, atrioventricular block

Retroperitoneal tumors and other abdominal malignancies invading the inferior vena cava can be treated surgically when no metastases are present. We resected four retroperitoneal tumors, two renal cell carcinomas, and one gastrointestinal stromal tumor with a concomitant caval resection. Although meticulous care is required when manipulating the major vessels, long-term survival with an improvement in the quality of life was achieved. These cases are described, with particular focus on the management of the major vessels.

We report a case of mediastinal liposarcoma, recurrent after 20 years. A 58-year-old man who presented with dyspnea on exertion was found to have a large mediastinal tumor in chest computed tomography (CT), and he was referred to our hospital. He had undergone an extirpation of a mediastinal liposarcoma about 20 years earlier, and we suspected its recurrence. Because the tumor was very large, it was removed in two stages. Histologically it was diagnosed as a recurrence of the previous well-differentiated liposarcoma. Although liposarcoma is one of the most common soft-tissue sarcomas in adults, a mediastinal liposarcoma is rare. Because the recurrence rate is very high, it is necessary to follow up carefully over a long term.

Objectives: We have assessed clinically systemic tissue oxygenation by monitoring mixed venous oxygen saturation (SvO2) in addition to hematocrit (Hct) during cardiopulmonary bypass. Based on results of experimental studies together with clinical experience, we previously defined the lower limits of the critical range as an Hct of 12% and an SvO2 of 46%. However, these values do not provide direct information about cerebral oxygenation. This study was performed to identify critical values for these variables that would be able to ensure sufficient jugular venous oxygen saturation (SjO2), which reflects global cerebral oxygenation. Methods: Normovolemic hemodilution was performed in ten rabbits. Hct, SvO2 and SjO2 were measured every 7 minutes. The safety limit for cerebral oxygenation was defined as an SjO2 of 50% based on studies of Croughwell et al. and Cook et al. The limit point was defined as 7 minutes before the time that the SjO2 decreased below 50% for the first time. Results: Minimal values for Hct and SvO2 to maintain SjO2 at 50% or more during normovolemic normothermic hemodilution, expressed as the 95% confidence interval, were Hct of 7.4% to 10.0% and SvO2 of 41.8% to 51.4%. Conclusion: Adopting the higher values of these pairs, safety limits for cerebral oxygenation would be an Hct of 10.0% and an SvO2 of 51.4%. In conclusion, our experiments in rabbits suggest new safety limits during normovolemic normothermic hemodilution of Hct of 12% and SvO2 of 52%, taking both whole-body and cerebral oxygenation into consideration.

AIMS In order to evaluate the prevalence of human papillomavirus (HPV) in the pregnant population in Japan. METHODS We examined cervical swabs of 1,183 pregnant women for HPV DNA using a PCR-RFLP method during October, 2000 and February, 2001. The overall prevalence of HPV in 1,183 pregnant women was analyzed and stratified by age. RESULTS The overall prevalence of HPV in pregnant women was 12.5% (148 of 1,183 cases). The prevalence in pregnant women younger than 25 years (22.6%, 28 of 124 cases) was significantly higher compared with that in pregnant women > or =25 years (11.3%, 120 of 1057 cases, P< 0.0005). CONCLUSIONS The data indicate a significantly higher prevalence of HPV infection in younger pregnant Japanese women.